Arimidex® Appears Superior to Continued Tamoxifen in Postmenopausal Women According to results presented at the 2003 San Antonio Breast Cancer Symposium, switching treatment to Arimidex® (anastrozole) after 2 years of tamoxifen (Nolvadex®) versus continued tamoxifen appears to significantly reduce recurrences in postmenopausal women with estrogen receptor (ER) positive breast cancer. With the recent rapid emergence of aromatase agents into the clinical setting, questions surrounding optimal timing and sequencing of these agents when used as hormone therapy continue to be evaluated. To date, several clinical trials have directly compared specific aromatase agents to tamoxifen in various clinical settings. Although tamoxifen is typically administered for 5 years in responding patients, researchers from Italy compared switching treatment to Arimidex® or continued tamoxifen in patients already receiving tamoxifen for two years.This trial included over 400 postmenopausal women with estrogen receptor (ER) positive, node-positive breast cancer. Patients had received at least 2 years of adjuvant tamoxifen and were randomly allocated to either continued tamoxifen for up to 5 years, or switching to Arimidex® for a comparable time duration. At a median of 24 months, recurrence rates were reduced by over 60% in the Arimidex® arm, compared to those were continued with tamoxifen. These results indicate that treatment with Arimidex® after being treated with tamoxifen for at least 2 years significantly reduces the risk of relapse, as opposed to continued tamoxifen in patients with postmenopausal, ER-positive, node-positive breast cancer. However, the authors caution that further trials are necessary in order to advise this strategy as a standard treatment approach. Reference: Boccardo F, Rubagotti A, Amoroso D, et al. Anastrozole appears to be superior to tamoxifen in women already receiving adjuvant tamoxifen treatment. Proceedings from the 2003 San Antonio Breast Cancer Symposium. December 2003. Abstract #3.

Selection Criteria for Breast Conserving Therapy (12/23/2003)
According to results presented at the 2003 San Antonio Breast Cancer Symposium, certain disease characteristics in patients with stages I-III breast cancer treated with neoadjuvant chemotherapy and breast-conserving therapy predict for a worse outcome, indicating a need for possible revision in eligibility criteria in patient selection considered for this treatment option.

Genetic Test Helps Predict Risk of Recurrence in Node-Negative Breast Cancer (12/23/2003)
According to results recently presented at the 2003 San Antonio Breast Cancer Symposium, a novel 21-gene assay provides accurate identification of node-negative, estrogen receptor (ER) positive breast cancer patients at a high, intermediate or low risk of recurrence. Ultimately, this diagnostic test, which is scheduled to be commercially available early 2004, could aid physicians in determining which of their patients are offered adjuvant chemotherapy.

Presence of Micrometastasis in the Bone Marrow Predicts for a Poor Outcome in Early Breast Cancer (12/23/2003)
According to results presented at the 2003 San Antonio Breast Cancer Symposium, the presence of bone marrow micrometastasis is a single, predictive indicator for poor outcomes in patients with early breast cancer.

Wide Excision Alone may Not Provide Optimal Outcomes for Ductal Carcinoma in Situ of the Breast (12/23/2003)
According to results presented at the 2003 San Antonio Breast Cancer Symposium, wide excision alone may not be the optimal treatment strategy for ductal carcinoma in situ of the breast.

Long-term Follow-Up Confirms Superiority of TAC in Early Breast Cancer (12/22/2003)
According to results recently presented at the 2003 San Antonio Breast Cancer Symposium, long-term follow-up of nearly 5 years provides evidence of long-term superiority of TAC (Taxotere®, Adriamycin®, cyclophosphamide) versus FAC (fluorouracil, Adriamycin®, cyclophosphamide) in terms of cancer-free and overall survival in early breast cancer.

Abraxane" More Effective than Taxol® in Metastatic Breast Cancer (12/22/2003)
According to results presented at the 2003 San Antonio Breast Cancer Symposium, the investigational agent Abraxane™ (ABI-007) produced higher response rates and improved time to cancer progression compared to Taxol® in metastatic breast cancer.

Neoadjuvant Taxotere® and Doxorubicin Evaluated for Operable Breast Cancer (11/20/2003)
Researchers in France have reported that the combination of docetaxel (Taxotere®) and doxorubicin is “an effective and well-tolerated combination in the neoadjuvant therapy of breast cancer.” The details of this phase II clinical trial were reported in the November 2003 issue of The Annals of Oncology. ¹

Screening Mammography Beyond Age 65 is Cost Effective (11/19/2003)
Based on a systematic review of 10 studies, researchers affiliated with the Cost Work Group of the U.S. Preventative Task Force have concluded that screening mammography every two years beyond age 65 years in women without significant co-morbid conditions is effective. They reported the results of their literature review in the November 18, 2003 issue of The Annals of Internal Medicine.

The Addition of Taxotere® to AC Regimen Improves Breast Cancer Responses (11/18/2003)
Researchers affiliated with the National Surgical Adjuvant Breast and Bowel Project Protocol B-27 have reported that adding docetaxel ( Taxotere®) to conventional neoadjuvant doxorubicin-cyclophosphamide regimen improves clinical and pathologic responses of women with stage I-III breast cancer. The results of this trial appeared in the November 15, 2003 issue of the Journal of Clinical Oncology.

Femara® Produces Higher Responses than Arimidex® but Does Not Prolong Responses or Improve Survival in Advanced Breast Cancer (11/13/2003)
A multicenter clinical trial sponsored by Novartis Pharma AG produced results indicating that advanced breast cancer is more responsive to letrozole (Femara®, Novartis) than anastrozole (Arimidex®, Zeneca Farma) as second-line therapy. These results were published in the November 2003 issue of the European Journal of Cancer.

Chemotherapy Mitigates Adverse Effects of BRCA1 Mutation (11/5/2003)
Researchers from Memorial Sloan-Kettering Cancer Center and McGill University have reported that “the poor prognosis associated with germline BRCA1 mutations is mitigated by adjuvant chemotherapy.” The results of this study were published in the October issue of Breast Cancer Research.

Herceptin® Every Three Weeks may be Preferable Schedule for Breast Cancer (10/31/2003)
Researchers from Canada have reported that Herceptin® can be given on an every three week schedule rather than the standard weekly schedule without an apparent loss in efficacy. The results of this study were published in the November 1, 2003 issue of the Journal of Clinical Oncology. ¹ An accompanying editorial suggests that this schedule of administration would save over $10,000 per year per patient if confirmed to be equally efficacious. ²

Women with Lobular Carcinoma of the Breast Have Better Survival (10/29/2003)
Researchers from the Fred Hutchinson Cancer Research Center have confirmed that women with invasive lobular carcinoma (ILC) of the breast have a better survival than women with invasive ductal carcinoma (IDC). The results of this study appeared in the October 13, 2003 issue of the Archives of Internal Medicine. ¹

8 Gy in One Fraction Equivalent to 30 Gy in 10 Fractions for Palliation of Bone Metastasis (10/23/2003)
Researchers affiliated with the Radiation Treatment Oncology Group (RTOG) have reported preliminary data suggesting equivalency of palliation of painful bone metastasis with 8 Gy of radiation in a single fraction compared to the standard approach of 30 Gy in 10 fractions. If confirmed with longer follow-up this could represent significant cost savings as well as being more convenient for patients. The results of this randomized trial were presented at the 45th annual meeting of the American Society for Therapeutic Radiology and Oncology on October 20, 2003 in Salt Lake City.

Surgical Decompression Plus Radiation Superior to Radiation Alone for Spinal Cord Metastasis (10/23/2003)
Researchers from the University of Maryland, University of Kentucky, Memorial Sloan Kettering Cancer Center, Neurosurgery Associates of Providence RI and the University of Kentucky have reported outcomes of a randomized trial of immediate surgical decompression followed by radiation therapy to that of radiation therapy alone. This trial showed clear benefits for the group receiving immediate surgical decompression. These results were presented at the 45th annual meeting of the American Society of Therapeutic Radiology and Oncology (ASTRO) on October 20, 2003 in Salt Lake City.

Women with Lobular Carcinoma of the Breast Have Better Survival (10/22/2003)
Researchers from the Fred Hutchinson Cancer Research Center have confirmed that women with invasive lobular carcinoma (ILC) of the breast have a better survival than women with invasive ductal carcinoma (IDC). The results of this study appeared in the October, 2003 issue of the Archives of Internal Medicine. ¹

Sentinal Node Biopsy Accepted As Standard Approach in Academic Cancer Centers for Managing Localized Breast Cancer (10/16/2003)
Researchers from 5 major academic centers have reported widespread non-clinical trial use of sentinel node biopsy (SNB) by oncologists in their centers. They suggest that “oncologists at cancer centers in our study have accepted SNB as standard-of-care for the treatment of breast cancer.” They also suggest that this “may affect accrual and generalizability of ongoing clinical trials of SNB.” This report appeared in the October 15, 2003 issue of the Journal of the National Cancer Institute.

Letrozole After Tamoxifen Decreases Breast Cancer Recurrences (10/10/2003)
An international multi-center trial has determined that letrozole, an aromatase inhibitor, decreases recurrences in post-menopausal women with hormone responsive localized breast cancer who have received 5 years of tamoxifen. The results of this trial appeared as an early online report in the October 9, 2003 issue of the New England Journal of Medicine. ¹

Are Women Aged 80 Years or Older with Breast Cancer Undertreated? (10/7/2003)
Researchers from Geneve, Switzerland reported in the October 1, 2003 issue of the Journal of Clinical Oncology that “half of elderly patients with breast cancer are undertreated, with strongly decreased specific survival as a consequence." ¹

Phase III Results Demonstrate Activity of Taxotere® and Adriamycin® in Metastatic Breast Cancer (10/2/2003)
In a phase III study presented at the 12th European Conference on Clinical Oncology (ECCO), the combination of Adriamycin® and Taxotere® (AT) produced a significantly longer mean progression free survival than 5-FU, Adriamycin®, and cyclophosphamide (FAC) in the treatment of metastatic breast cancer.

Randomized, Phase III Trial Shows Taxotere® to be Superior to Paclitaxel in Metastatic Breast Cancer (9/30/2003)
In the first trial directly comparing Taxotere® to paclitaxel, Taxotere® demonstrated a higher response rate and longer time to progression and median overall survival. These results were reported at the 12th European Conference on Clinical Oncology (ECCO), held Sept 21-25, 2003 in Copenhagen, Denmark.

Addition of Herceptin® to Taxotere® in Metastatic Breast Cancer Nearly Doubles Survival (9/30/2003)
Results from a randomized phase II trial indicated that patients with HER2-positive metastatic breast cancer who received Herceptin® and Taxotere® had a significantly higher response rate, significantly longer time to disease progression, and lived significantly longer compared to patients who received Taxotere® alone. These results were presented at the 12th European Conference on Clinical Oncology (ECCO) held in Copenhagen, Denmark, September 21-25, 2003.

Gemzar® and Taxotere®: An Active and Well-Tolerated Regimen for First-Line Treatment of Metastatic Breast Cancer (9/25/2003)
A phase II trial recently reported that the combination of Gemzar® and Taxotere® was active in the treatment of patients with metastatic breast cancer. This trial was presented at the 12th European Conference on Clinical Oncology (ECCO) held in Copenhagen, Sept 21-25, 2003.

Tumor Cells in Bone Marrow Predict Outcome of Patients with Localized Breast Cancer (9/19/2003)
Researchers from Norway reported that the presence or absence of tumor cells in the bone marrow is predictive of outcomes for women with localized breast cancer. Tumor cells in the bone marrow combined with other risk factors allows physicians to “classify subgroups of patients into excellent and high-risk prognostic groups.” These results were published in the September 15, 2003 issue of the Journal of Clinical Oncology.

Older Women with Localized Breast Cancer Less Likely to Receive Adjuvant Chemotherapy than Younger Women (9/11/2003)
Researchers from Ohio State University have reported that “based on older age alone, women are less likely to receive adjuvant chemotherapy.” They also suggest that “age bias may contribute to under treatment and lack of accrual of older women into clinical trials.” The results of this analysis were reported in the September 15, 2003 issue of Cancer.

Moderate Physical Activity Lowers Incidence of Breast Cancer (9/10/2003)
Researchers affiliated with The Women’s Health Initiative Cohort Study have reported that “increased physical activity is associated with reduced risk for breast cancer in postmenopausal women.” Longer duration provides most benefit, but the activity need not be strenuous. The results of this analysis were published in the September 10, 2003 issue of JAMA. ¹ Another study on this subject from Finland, published in the November 1, 2003 issue of the International Journal of Cancer suggest that “life-long physical activity may reduce the risk of breast cancer”. ²

Doxil® and Gemzar®: A Promising Regimen for Initial Treatment of Metastatic Breast Cancer (9/9/2003)
Reearchers from MD Anderson reported the results of a phase II study in the September 2, 2003 issue of the Journal of Clinical Oncology that indicates a regimen of Doxil® and Gemzar® “is active and well tolerated in patients with metastatic breast cancer.” ¹

Zoledronic Acid Reduces Angiogenic Factors in Blood (9/5/2003)
Researchers from Italy reported in the August 2003 issue of Clinical Cancer Research that zolenronic acid (Zometa®) reduces circulating blood levels of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) in patients with cancer.

Systematic Review Supports Use of Bisphosphonates for Metastatic Osteolytic Cancers (8/29/2003)
Based on a meta-analysis of 30 randomized studies that evaluated bisphosphonates in patients with bone metastasis, researchers from the UK concluded that bisphosphonates decrease skeletal morbidity in patients with bone metastasis but without an improvement in survival. These results were published in the August 30, 2003 issue of the British Medical Journal.

Further Evidence that Brachytherapy Can Replace External Beam Radiation for Localized Breast Cancer (8/27/2003)
Based on 5-year follow-up data, researchers from William Beaumont Hospital concluded that limited-field radiation therapy delivered to the tumor bed was as effective as whole breast radiation therapy for prevention of recurrences in women with early stage breast cancer. These results were published in the August 20, 2003 issue of the Journal of the National Cancer Institute.

The Million Women Study Documents Risks of Death From Breast Cancer Following Hormone Replacement (8/11/2003)
Researchers in the United Kingdom have documented an increased incidence of breast cancer in women taking hormone replacement therapy (HRT), especially with combined estrogen and progestin. For the first time a 22% increased death rate from breast cancer has also been documented in women on HRT. These results were published in the August 9, 2003 issue of the Lancet.

The Million Women Study Documents Risks of Death From Breast Cancer Following Hormone Replacement (8/11/2003)
Researchers in the United Kingdom have documented an increased incidence of breast cancer in women taking hormone replacement therapy (HRT), especially with combined estrogen and progestin. For the first time a 22% increased death rate from breast cancer has also been documented in women on HRT. These results were published in the August 9, 2003 issue of the Lancet.

Sentinel Node Biopsy As Effective as Axillary Lymph Node Dissection (8/8/2003)
Researchers from Italy reported in the August 7, 2003 issue of the New England Journal of Medicine that sentinel node biopsy is as effective as axillary lymph node dissection in determining spread of breast cancer and is associated with less morbidity.

Sentinel Node Biopsy As Effective as Axillary Lymph Node Dissection (8/8/2003)
Researchers from Italy reported in the August 7, 2003 issue of the New England Journal of Medicine that sentinel node biopsy is as effective as axillary lymph node dissection in determining spread of breast cancer and is associated with less morbidity.

Eighteen Year Follow-Up Confirms Effectiveness of Breast Conservation Therapy (8/6/2003)
With a median follow-up of over 18 years, the results of a National Cancer Institute (NCI) randomized trial still show no differences in disease-free survival or overall survival between patients treated with mastectomy or breast conservation therapy for localized breast cancer. These results were published in the August 15, 2003 issue of Cancer.

Eighteen Year Follow-Up Confirms Effectiveness of Breast Conservation Therapy (8/6/2003)
With a median follow-up of over 18 years, the results of a National Cancer Institute (NCI) randomized trial still show no differences in disease-free survival or overall survival between patients treated with mastectomy or breast conservation therapy for localized breast cancer. These results were published in the August 15, 2003 issue of Cancer.

Oral Xeloda® Provides Significant Palliation for Patients with Refractory Breast Cancer (7/31/2003)
Researchers from several cancer centers in Germany have confirmed the palliative effects of oral Xeloda® in women with breast cancer who have failed prior taxane treatment. These results appeared in the August 2003 issue of the Annals of Oncology.

Herceptin® and Navelbine® Effective for HER-2 Positive Breast Cancer (7/31/2003)
Researchers from 17 US cancer centers have reported that the combination of Herceptin® and Navelbine® is well tolerated and active for the initial treatment of women with stage IV HER-2 positive breast cancer. This report appeared in the August 1 issue of the Journal of Clinical Oncology.

Preoperative MRI Helps in Determining Extent of Surgery for Breast Cancer (7/22/2003)
Researchers from the University of Pennsylvania and the Mayo clinic reported that preoperative MRI changes the type of surgery needed in 20% of patients with breast cancer. These results were published in the July 15, 2003 issue of Cancer.

HER-2 and Cell Proliferation Identify High Risk Node Negative Breast Cancer (7/22/2003)
Italian researchers have reported that combining thymidine labeling with HER-2 analysis can assist in assigning risk of relapse to patients with node-negative breast cancer receiving loco-regional treatment only. This report appeared in the July 15, 2003 issue of the Journal of Clinical Oncology.

High Animal Fat Diet in Premenopausal Period Increases Incidence of Breast Cancer (7/18/2003)
Researchers from Harvard University reported in the July 2003 issue of The Journal of the National Cancer Institute that women who have a high dietary intake of animal fat have a significantly increased incidence of breast cancer.

Screening Mammography Lowers the Incidence of Advanced Breast Cancer and Reduces Mortality (7/15/2003)
English researchers report yet another study documenting the efficacy of routine screening mammography to detect early breast cancer and lower the incidence of advanced disease and possibly decrease mortality from breast cancer. These findings were reported in the July issue of the British Journal of Cancer.

Radiotherapy Prevents Recurrences of Ductal Carcinoma in Situ of the Breast Following Breast Conserving Surgery (7/15/2003)
Researchers in the United Kingdom, Australia, and New Zealand have reported that local radiation following breast conserving surgery decreases same breast recurrences in women with ductal carcinoma in situ (DCIS) of the breast. This same study failed to find a benefit for the use of prophylactic tamoxifen. These results appeared in the July 12, 22003 issue of The Lancet.

Role of Adjuvant Autologous Stem Cell Transplantion for Breast Cancer Still Controversial (7/8/2003)
In the July 3, 2003 issue of The New England Journal of Medicine three trials reported conflicting results regarding the role of high-dose chemotherapy and adjuvant autologous stem cell transplantation. The results of a large randomized clinical trial performed in Holland suggest that women with localized breast cancer with 10 or more positive nodes have a 10% improvement in progression-free survival when treated with high-dose chemotherapy (cyclophosphamide, thiotepa and carboplatin) with autologous stem cell support. Also, patients with HER-2 neu negative tumors had 34% reduction in recurrences and a better survival following high-dose therapy. In a companion paper researchers affiliated with the Eastern Cooperative Oncology Group (ECOG) reported that a high-dose regimen of cyclophosphamide and thiotepa did not improve outcomes compared to conventional CAF adjuvant therapy.

Breast Cancer Risks of Hormone Replacement Therapy Defined (6/30/2003)
Researchers involved with the Women’s Health Care Initiative have reported that relatively short term hormone replacement therapy (HRT) with estrogen and progestin increases the incidence of breast cancer and makes the diagnosis more difficult by creating abnormal mammograms. (1) In a second report, researchers from the Fred Hutchinson Cancer Center also demonstrated an increase in breast cancer in women on chronic HRT. (2) Both of these reports appeared in the June 25, 2003 issue of the Journal of the American Medical Association.

Doxil®, Taxotere® and Herceptin® Not Associated with Excessive Cardiac Toxicity in Patients with Breast Cancer (6/19/2003)
Researchers affiliated with ECOG presented data suggesting that a regimen of Doxil®, Taxotere®, and Herceptin® was not associated with excessive cardiac toxicity. (1) These data were presented in a poster session of the 39th meeting of the American Society of Clinical Oncology in June 2003.

Herceptin® Treatment Associated with High Frequency of CNS Metastasis due to Breast Cancer (6/17/2003)
Researchers from the Dana Farber Cancer Center reported that CNS metastasis occurred in over a third of women treated with Herceptin® for metastatic breast cancer. (1) In a separate study presented at the 39th meeting of the American Society of Clinical Oncology, researchers from the University of Pittsburgh reported that half of the relapses occurring in patients receiving Taxotere®, Paraplatin®, and Herceptin® as first-line chemotherapy in HER-2 positive metastatic breast cancer were in the CNS. (2)

Gemzar® and Taxol® Superior to Taxol® Alone After Failure of Anthracycline Based Adjuvant Therapy (6/16/2003)
The combination of Gemzar® and Taxol® appears to produce a higher response rate and a prolonged time to treatment failure in women with breast cancer who have received prior anthracycline treatment. These results were reported in an oral session on metastatic breast cancer at the 39th meeting of the American Society of Clinical Oncology held in Chicago in June 2003.

Celebrex® Enhances Effects of Aromasin® in Women with Breast Cancer (6/11/2003)
European researchers reported that Celebrex®, a COX-2 inhibitior, enhances the effects of Aromasin® in women with breast cancer who had failed tamoxifen. This study was presented at the 39th annual meeting of the American Society of Clinical Oncology.

A Randomized Trial of Direct Decompressive Surgical Resection in the Treatment of Spinal Cord Compression Caused by Metastasis (6/5/2003)
A multicenter trial, directed by Dr. Patchell from the University of Kentucky, has determined that patients with non-hematologic metastatic tumors causing spinal cord compression have better outcomes with immediate surgery than with radiation therapy. They reported these findings at a plenary session of the 39th annual meeting of the American Society of Oncology in Chicago in June of 2003.

German Researchers Suggest MRI to Replace Screening Mammography for Familial Breast Cancer (6/4/2003)
German researchers recently documented the ability of Magnetic Resonance Imaging (MRI) to detect breast cancers not detected by mammography or ultrasound in women at high risk for breast cancer. They reported these findings in a plenary lecture of the 39th annual meeting of the American Society of Clinical Oncology in Chicago in June of 2003.

Adjuvant High-Dose Chemotherapy May Benefit Subsets of Women with Localized High-Risk Breast Cancer (6/3/2003)
At the 2003 American Society of Clinical Oncology annual meeting, three scientific trials of increasing doses of chemotherapy for adjuvant treatment of localized breast cancer were presented. (1-3) There were significant differences in the high-dose regimens used. One study did not show a decrease in recurrences in the entire population or in subsets of the women studied. However, the other two trials showed a trend for decreasing the rate of recurrences that was statistically significant for some subsets of the population.

Estrogen and Progestin Associated with Adverse CNS Outcomes in Postmenopausal Women (5/30/2003)
Three articles that appeared in the May 28, 3003 issue of the Journal of the American Medical Society indicate that hormone replacement therapy with estrogen and progestin had an adverse effect on dementia, cognitive function, and stroke. (1-3) These articles were associated with the Women’s Health Initiative clinical trials program.

Femara® (letrozole) Superior to Tamoxifen for Treatment of Postmenopausal Hormone Receptor Positive Breast Cancer (5/29/2003)
The June 1, 2003 issue of the Journal of Clinical Oncology published long-term results of a multinational clinical trial indicate that Femara®, an aromitase inhibitor, is superior to standard tamoxifen as first-line endocrine therapy in postmenopausal women with hormone receptor positive advanced breast cancer. (1)

Neurontin® (gabapentin), an Anticonvulsant, May Suppress Chemotherapy Induced Nausea (5/19/2003)
Researchers from the University of Rochester in NY reported that the anticonvulsant Neurontin® appears to be effective in suppression of chemotherapy induced nausea. These findings were published in the May 17, 2003 issue of the Lancet.

Axillary Node Dissection Not Necessary in Women with Breast Cancer with Negative Sentinal Node (5/14/2003)
Researchers from the Mayo Clinic have reported that axillary lymph node dissection is not necessary in women with localized breast cancer who have a negative sentinel node removed. (1) They reported their findings in the May 2003 issue of the Archives of Surgery.

Estrogen Plus Progesterone Has No Effect on Quality of Life of Post-Menopausal Women (5/8/2003)
Researchers affiliated with the Women’s Health Initiative reported the results of a large clinical trial of estrogen plus progesterone in post-menopausal women in the May 8, 2003 issue of the New England Journal of Medicine. They concluded that estrogen and progesterone were no better than placebo for improving quality of life (QOL).

Estrogen Plus Progesterone Has No Effect on Quality of Life of Post-Menopausal Women (5/8/2003)
Researchers affiliated with the Women’s Health Initiative reported the results of a large clinical trial of estrogen plus progesterone in post-menopausal women in the May 8, 2003 issue of the New England Journal of Medicine. They concluded that estrogen and progesterone were no better than placebo for improving quality of life (QOL).

More Evidence That Mammography Screening Prevents Breast Cancer Deaths (4/30/2003)
Since 1990, the death rate from breast cancer has been decreasing. The exact reasons for this are not quite clear but some researchers think that screening mammography has played a major role. However, in 2000 two studies questioned the effectiveness of mammography in decreasing deaths from breast cancer. This has led to a series of analyses and re-analyses to determine the true effectiveness or lack of effectiveness of screening mammography.

More Evidence That Mammography Screening Prevents Breast Cancer Deaths (4/30/2003)
Since 1990, the death rate from breast cancer has been decreasing. The exact reasons for this are not quite clear but some researchers think that screening mammography has played a major role. However, in 2000 two studies questioned the effectiveness of mammography in decreasing deaths from breast cancer. This has led to a series of analyses and re-analyses to determine the true effectiveness or lack of effectiveness of screening mammography.

Further Evidence that the Dose of Adjuvant Chemotherapy for Breast Cancer is Related to the Incidence of Second Cancers (4/29/2003)
In the April 1, 2003 issue of the Journal of Clinical Oncology, researchers affiliated with the National Surgical Adjuvant Breast and Bowel Project reported a high incidence of secondary acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) in women receiving adjuvant chemotherapy treatment with the combination of doxorubicin and cyclophosphamide (AC). These researchers found that the incidence of AML/MDS was related to the intensity of the adjuvant regimen.

Further Evidence that the Dose of Adjuvant Chemotherapy for Breast Cancer is Related to the Incidence of Second Cancers (4/29/2003)
In the April 1, 2003 issue of the Journal of Clinical Oncology, researchers affiliated with the National Surgical Adjuvant Breast and Bowel Project reported a high incidence of secondary acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) in women receiving adjuvant chemotherapy treatment with the combination of doxorubicin and cyclophosphamide (AC). These researchers found that the incidence of AML/MDS was related to the intensity of the adjuvant regimen.

Alendronate (Fosamax®) Prevents Bone Loss in Women Who Stop Taking Hormone Replacement Therapy (4/15/2003)
In the April 14, 2003 issue of the Archives of Internal Medicine researchers from several centers around the world reported that alendronate can prevent bone loss in women who have discontinued taking HRT. Alendronate is an orally administered bisphosphonate that acts as a specific inhibitor of osteoclast-mediated bone resorption. Alendronate has been found to prevent loss of bone density in several malignant and non-malignant situations.

Alendronate (Fosamax®) Prevents Bone Loss in Women Who Stop Taking Hormone Replacement Therapy (4/15/2003)
In the April 14, 2003 issue of the Archives of Internal Medicine researchers from several centers around the world reported that alendronate can prevent bone loss in women who have discontinued taking HRT. Alendronate is an orally administered bisphosphonate that acts as a specific inhibitor of osteoclast-mediated bone resorption. Alendronate has been found to prevent loss of bone density in several malignant and non-malignant situations.

High Incidence of AML and MDS after Adjuvant Chemotherapy for Breast Cancer (4/10/2003)
In the April 1, 2003 issue of the Journal of Clinical Oncology, researchers affiliated with the National Surgical Adjuvant Breast and Bowel Project reported a high incidence of secondary AML and MDS in women receiving adjuvant chemotherapy treatment with the combination of doxorubicin and cyclophosphamide (AC).

High Incidence of AML and MDS after Adjuvant Chemotherapy for Breast Cancer (4/10/2003)
In the April 1, 2003 issue of the Journal of Clinical Oncology, researchers affiliated with the National Surgical Adjuvant Breast and Bowel Project reported a high incidence of secondary AML and MDS in women receiving adjuvant chemotherapy treatment with the combination of doxorubicin and cyclophosphamide (AC).

Difficult to Determine Which Women Should Receive Tamoxifen Prophylaxis for Breast Cancer Prevention (4/7/2003)
The gains that have been made in improving survival in women with breast cancer are due predominantly to earlier diagnosis and adjuvant therapy with Nolvadex® (tamoxifen) or other antiestrogens and chemotherapy. It is well documented that Nolvadex®, raloxifene, and anastrozole can prevent breast cancer recurrences in women with hormone receptor-positive breast cancer. These observations have led to several large trials of chemoprevention with Nolvadex® or raloxifene in women at higher than usual risk of breast cancer. However, the definition of who is at high risk is problematic and differs from trial to trial. Generally, high risk includes women with a family history of breast cancer, early menarche, later or no childbirth, or previous breast biopsy, even if negative.

Difficult to Determine Which Women Should Receive Tamoxifen Prophylaxis for Breast Cancer Prevention (4/7/2003)
The gains that have been made in improving survival in women with breast cancer are due predominantly to earlier diagnosis and adjuvant therapy with Nolvadex® (tamoxifen) or other antiestrogens and chemotherapy. It is well documented that Nolvadex®, raloxifene, and anastrozole can prevent breast cancer recurrences in women with hormone receptor-positive breast cancer. These observations have led to several large trials of chemoprevention with Nolvadex® or raloxifene in women at higher than usual risk of breast cancer. However, the definition of who is at high risk is problematic and differs from trial to trial. Generally, high risk includes women with a family history of breast cancer, early menarche, later or no childbirth, or previous breast biopsy, even if negative.

Herceptin® and Taxotere® A Well Tolerated Regimen for Breast Cancer Overexpressing HER2 (3/28/2003)
Women who have breast cancer that over expresses HER2 have a worse prognosis than women who do not have cancer that over expresses this oncogene. Herceptin® is a monoclonal antibody which has significant but palliative effects on HER2 positive breast cancer. In order to improve the efficacy of Herceptin®, other drugs have been administered with Herceptin®. When anthracyclines are administered with Herceptin® there is an increased response rate but there is also an increase in the incidence and severity of cardiac toxicities. Now, researchers in Italy have reported that the combination of Taxotere® and Herceptin® is well tolerated without significant cardiac toxicity. They reported their results in the March 2003 issue of the American Journal of Clinical Oncology:

Breast Implants Do Not Delay Diagnosis of Breast Cancer (3/20/2003)
The general consensus of most studies is that breast implants are not associated with an increased incidence of breast cancer compared to the normal population. (1) However, there has been concern that breast implants could interfere with the early diagnosis of breast cancer resulting in a decrease in survival from breast cancer. In the March 24, 2003 issue of the British Journal of Cancer, Danish researchers report no apparent delay in the diagnosis of breast cancer in women with implants.

Taxotere®-Doxorubicin Regimen Has Advantages Over Doxorubicin-Cyclophosphamide for Initial Treatment of Metastatic Breast Cancer (3/19/2003)
A study published in the March 2003 issue of the Journal of Clinical Oncology indicates that the combination of Taxotere® and doxorubicin is associated with a higher response rate and a longer time to treatment failure than the combination of doxorubicin and cyclophosphamide in women with metastatic breast cancer. However, there were no differences in survival between the two regimens.

Taxotere®-Doxorubicin Regimen Has Advantages Over Doxorubicin-Cyclophosphamide for Initial Treatment of Metastatic Breast Cancer (3/19/2003)
A study published in the March 2003 issue of the Journal of Clinical Oncology indicates that the combination of Taxotere® and doxorubicin is associated with a higher response rate and a longer time to treatment failure than the combination of doxorubicin and cyclophosphamide in women with metastatic breast cancer. However, there were no differences in survival between the two regimens.

Adjuvant Paclitaxel Decreases Recurrences and Improves Survival in Node Positive Localized Breast Cancer (3/17/2003)
Adjuvant chemotherapy decreases recurrences in women with lymph node positive breast cancer. Despite adjuvant chemotherapy, significant numbers of women will still have recurrences. Thus, the optimal adjuvant chemotherapy regimen has yet to be defined. There is increasing evidence that taxanes, paclitaxel and Taxotere®, improve outcomes of women with localized breast cancer when added to doxorubicin based chemotherapy. In the March 15, 2003 issue of The Journal of Clinical Oncology, researchers affiliated with the Cancer and Leukemia Group B (CALGB) reported the results of a relatively large study showed that escalating doses of doxorubicin did not decrease recurrences, but the addition of paclitaxel administered after doxorubicin decreased recurrences and improved survival. Though previously presented in abstract form, the current report represents the definitive analysis of this study which began in 1994 and completed patient accrual in 1999.

Adjuvant Paclitaxel Decreases Recurrences and Improves Survival in Node Positive Localized Breast Cancer (3/17/2003)
Adjuvant chemotherapy decreases recurrences in women with lymph node positive breast cancer. Despite adjuvant chemotherapy, significant numbers of women will still have recurrences. Thus, the optimal adjuvant chemotherapy regimen has yet to be defined. There is increasing evidence that taxanes, paclitaxel and Taxotere®, improve outcomes of women with localized breast cancer when added to doxorubicin based chemotherapy. In the March 15, 2003 issue of The Journal of Clinical Oncology, researchers affiliated with the Cancer and Leukemia Group B (CALGB) reported the results of a relatively large study showed that escalating doses of doxorubicin did not decrease recurrences, but the addition of paclitaxel administered after doxorubicin decreased recurrences and improved survival. Though previously presented in abstract form, the current report represents the definitive analysis of this study which began in 1994 and completed patient accrual in 1999.

Folate and B6 May Help Prevent Breast Cancer (3/12/2003)
The causes of breast cancer are probably multi-factorial with the primary causes remaining obscure. However, there are known factors that can lower or increase the risk of developing breast cancer. There is reasonably good information that high fruit and vegetable consumption can lower the risk for developing breast cancer. This may be due to the protective effects of antioxidants such as carotenoids, folic acid, vitamin C, flavonoids, phytoestrogens and isothiocyanates. Other factors, such as a high alcohol intake, obesity and smoking can increase the risk of developing breast cancer. Most of the studies that have generated the information on antioxidant vitamin intake have come from dietary histories with very little, if any, information on blood levels of specific vitamins. Researchers from Harvard Medical School have evaluated plasma levels of folate, vitamin B6, vitamin B12 and homocysteine in women with and without breast cancer. They found that higher plasma levels of folate and possibly vitamin B6 were associated with a lower incidence of breast cancer and they suggest that these vitamins are especially important in women who drink alcohol. They published their findings in the March 5, 2003 issue of the Journal of the National Cancer Institute.

Taxotere®-Based Salvage Regimen Highly Active As Initial Treatment of Breast Cancer (2/27/2003)
Patients with locally advanced or metastatic breast cancer have a poor prognosis following treatment with existing chemotherapy combinations. This has led to the development of a variety of treatment regimens in order to improve the complete response rate, which is one of the most important treatment parameters. Italian researchers have determined the optimal doses of Xeloda®, Taxotere® and Ellence® (TEX) in a phase I clinical trial involving women with metastatic breast cancer. ¹ They reported that the major toxicity of this regimen was febrile neutropenia. These same researchers have now reported promising results with this regimen in previously untreated women with locally advanced or metastatic breast cancer. The reported findings are in the February 2003 issue of the journal Cancer. ²

Her2 Status May Not Affect Response to Hormone Therapy in Breast Cancer (2/10/2003)
Approximately 25% to 30% of patients with breast cancer have overexpression of the human epidermal growth factor receptor 2 protein Her2-neu (HER2). The binding action of HER2 facilitates growth of cancer cells, conferring a worse prognosis when compared to HER2-negative breast cancers. There has been conflicting information about the benefit of hormonal therapy for the prevention of recurrences in women with HER2-positive localized breast cancer.

Radiotherapy Prevents Local Recurrences After Lumpectomy in Women Over the Age of 80 Years with Breast Cancer (2/10/2003)
Older women with breast cancer are less likely to receive aggressive treatments than younger women, although all published studies suggest that the same benefit is achieved regardless of age. The main reason for this is fear that age or co-morbidities would increase the complications associated with breast cancer treatments. In the December 2002 issue of the American Journal of Clinical Oncology, researchers from the University of Pittsburgh Medical Center reported the results of adjuvant radiation therapy for the treatment of 47 women ages 80-89. These women were treated over a 15-year period. Thirty-one of these women were treated with lumpectomy alone and 17 were treated with lumpectomy plus axillary node dissection. All received post-operative radiation therapy. All but 5 women with ductal carcinoma in situ had invasive carcinoma. Most women had breast radiation to 5,000 cGy with an additional boost to the operative area. Thirty-four women received adjuvant Nolvadex®. There are no patients with known local or regional recurrences and only 2 with distant metastasis. After an average follow-up of 43 months, over half the patients were alive with 12 being alive more than 5 years from treatment but only one patient died of breast cancer. The researchers reported that “Radiotherapy was well tolerated in all patients, and the majority had a good to excellent cosmetic result. Age alone is not a contraindication to the administration of post lumpectomy breast irradiation”.

Adjuvant Doxorubicin-Containing Regimens Benefit Women with HER2-Positive Breast Cancer (2/3/2003)
Approximately 25% to 30% of patients with breast cancer have overexpression of the human epidermal growth factor receptor 2 protein, Her2-neu (HER2). The binding action of HER2 facilitates growth of cancer cells, conferring a worse prognosis when compared to HER2-negative breast cancers. There has been conflicting information about the benefit of different adjuvant chemotherapy regimens for the prevention of recurrences in women with HER2-positive localized breast cancer. One of the most frequently used regimens is cyclophosphamide, methotrexate and 5-FU (CMF). There has been conflicting information about whether or not the addition of doxorubicin (Adriamycin®) or other anthracycline-containing regimens adds to the benefits of CMF in preventing recurrences. A recent analysis of adjuvant therapy from Italy suggests that the addition of doxorubicin to CMF benefits women with HER2-positive breast cancers but does not improve outcomes of women with HER2-negative breast cancers. This report appeared in the February 1, 2003 issue of the Journal of Clinical Oncology.

New Study Finds Abortions Do Not Increase Incidence of Breast Cancer (1/27/2003)
Researchers continue to study the potential association between induced abortion and breast cancer. This has become a political and possibly legal issue over the past decade. “Pro-choice” groups have recently accused the Bush Administration of removing information from Government Web sites stating that there is no conclusive evidence that abortions cause breast cancer. On the other side of the issue, there have been legal challenges to consent forms which do not include an increased risk of breast cancer as a consequence of induced abortion based on the argument that “the current level of scientific evidence linking induced abortion with increased breast cancer risk is sufficient to support an ethical and legal duty to disclose fully the risk to women who are considering induced abortion.” ¹

New Analysis Suggests Women at High-Risk of Breast Cancer Who Benefit from Prophylactic Nolvadex® (1/22/2003)
Nolvadex® (tamoxifen) is commonly used to treat or prevent recurrences in some women with breast cancer. This prompted the evaluation of Nolvadex® as a preventative drug in women at high risk of developing breast cancer. There have been 4 randomized controlled trials of Nolvadex® in women at risk for breast cancer. These trials have all shown a reduction in the risk of estrogen-positive breast cancer. Nolvadex® reduced the risk by 30-50% in these trials with the main side effects being thromboembolic phenomena and uterine cancer. Based on these data, Nolvadex® is not recommended for prevention of breast cancer in average-risk women. However, researchers continue to look for subgroups of women who may benefit more than others from Nolvadex® prophylaxis. In the January issue of the Journal of the National Cancer Institute, Italian researchers reported that women with early menarche, no pregnancies, late age at first birth and increased body mass appeared to benefit from Nolvadex® prophylaxis, but other subgroups did not.

Axillary Node Dissection May Not be Necessary for All Women with Positive Sentinel Node Biopsy (1/21/2003)
Axillary lymph node dissection is the traditional method for staging women with clinically localized breast cancer. Unfortunately, the removal of axillary lymph nodes (approximately 25 nodes) is associated with chronic side effects including pain, infection, limited shoulder motion, numbness and lymphedema (swelling of the arm due to an accumulation of lymph fluid). Since these complications can become debilitating, sentinel node biopsy has emerged as an alternative method of staging and is currently being evaluated and refined in clinical trials. There is also emerging evidence that women who have positive lymph nodes and receive adjuvant chemotherapy and/or adjuvant hormonal therapy may not benefit from removal of affected nodes. When performed appropriately, there is a 95% correlation between the results of sentinel node biopsy and lymph node dissection. At the present time, one approach is to perform a sentinel node biopsy and if negative, go no further. If positive, many women will receive a lymph node dissection to confirm these findings and to remove positive nodes as a form of therapy. The outcomes of women with a positive sentinel node biopsy and no lymph node dissection have not been extensively reported.

Ethnicity May Affect Breast Cancer Outcome (1/15/2003)
It has been known for quite some time that different racial, ethnic and socio-economic groups have different presentations and usually worse outcomes from breast cancer. Many studies have suggested that African American and Hispanic women present with a more advanced form of breast cancer and have worse outcomes than white women. It has not been clear from these studies whether or not there was a biologic difference between African Americans and Hispanics and whites or whether these differences were due to better screening and better treatments in white women. However, the lack of screening may not entirely account for the poorer outcome of African American and Hispanic women with breast cancer, as it has also been shown that Mexican women have breast cancer at an earlier age than white women.

Long-term Follow-ups Confirm Benefit of Intensive Combination Adjuvant Chemotherapy for Localized Breast Cancer (1/15/2003)
Adjuvant combination chemotherapy has been standard treatment for women with localized breast cancer for over 2 decades. However, the optimal drugs, doses and schedules of treatment remain to be determined. Most, but not all studies, have shown that combinations of agents given on an intensive dose-schedule are the most effective. However, most of these conclusions are based on limited follow-up. Two studies of adjuvant chemotherapy have recently been published with a 20 year and a 10 year follow-up.

Further Evidence That Screening Mammography Detects Early Breast Cancers (1/10/2003)
There has been considerable recent controversy over the benefits of screening mammography for the detection of early stage breast cancer. The most recent information suggests that annual or every other year mammography after age 40 does not significantly improve survival of women with breast cancer. This is despite the fact that all studies have shown that screening detects more early-stage breast cancers, especially carcinoma in situ, than unscreened populations of women. It is suggested that many of these early-stage detected cancers were not destined to cause death. It has also been suggested that screening mammography leads to an excess number of biopsies for benign disease and causes distress in women. One problem with most studies is that the length of follow-up is not enough to be sure of the survival benefits, as most studies limit their study circumscribed period of time, when what is needed for definitive conclusions is a screened and a control group studied for life. Nevertheless, despite these controversies, annual screening mammography is recommended by the American Cancer Society and every one to two years is recommended by the U.S. Preventive Services Task Force. Since survival is a difficult endpoint to evaluate because of the time factor, other benefits of screening mammography have been evaluated. Researchers at Kaiser Permanente in Colorado have compared the stage of breast cancer at diagnosis in women undergoing screening versus those not undergoing screening. They reported their results in the January 2003 issue of Cancer. These researchers concluded that women who had undergone mammography screening within 2 years of the diagnosis of breast cancer had earlier stage disease than women who had not undergone screening.

Iressa®, An Anti-Epithelial Growth Factor Receptor Inhibitor, Produces Responses in Women with Breast Cancer (1/3/2003)
Many breast cancers are hormonally dependent and can be treated with anti-estrogens. However, most hormonally dependent breast cancers become resistant to hormonal therapies. Activation of the epidermal growth factor receptor pathway through the ligand epidermal growth factor (EGF), transforming growth factor alpha (TGF-±) or insulin-like growth factor can promote anti-hormone treatment failure. In the laboratory, this is manifest by a doubling in the basal growth rate and a four-fold increase in invasiveness. It is now clear that formation of cell surface EGF receptor heterodimers, including EGFR/HER-2, activate two critical enzymatic pathways, the MAP kinase pathway responsible for proliferation and the AKT/p13K pathway necessary for survival signals (anti-apoptosis). Downstream events include phosphorylation of the estrogen receptor which results in tamoxifen behaving as an agonist in an endocrine resistant, EGFR-enhanced cell line. An autocrine simulating pathway drives increased EGF/TGF-alpha binding to receptors. Eventually, extreme priming of growth factor signaling pathways promotes complete endocrine resistance. In pre-clinical models, it is possible to mitigate these effects by adding Iressa® (imatinib), an epidermal growth factor receptor inhibitor. This agent causes decreased activation of MAP K, diminished phosphorylation of the estrogen receptor and restores hormone sensitivity. While neither Iressa® nor Nolvadex® alone can fully prevent the development of the resistant phenotype, the two agents together can block the development of Nolvadex®-resistance and lead to complete tumor regression in xenograft models.

Neoadjuvant Herceptin® and Paclitaxel, a Promising Neoadjuvant Regimen for Stage II-III Breast Cancer (1/2/2003)
Approximately 25% to 30% of women have breast cancer that over-expresses the epidermal growth factor, Her2-neu (HER2). Although many factors determine outcomes of women with localized breast cancer, those with HER2-positive breast cancers have a worse prognosis than those with HER2-negative cancers. Herceptin® is the first monoclonal antibody directed against HER2 that has been approved by the FDA for the treatment of breast cancer. Herceptin® is currently used in combination with a taxane such as paclitaxel or Taxotere®, or Gemzar® for the treatment of metastatic breast cancer and few studies in women with localized breast cancer have been performed. In the U.S., the approval by the FDA is currently limited to the treatment of women with metastatic breast cancer that is HER2-positive.

Hormonal Therapy Equivalent or Superior to Standard Chemotherapy for Adjuvant Treatment of Premenopausal Localized Breast Cancer (12/20/2002)
Chemotherapy is the current standard adjuvant therapy for localized breast cancer in pre-menopausal women. For patients who have hormone responsive disease, Nolvadex® is often added following completion of adjuvant chemotherapy. There is evidence that some of the effects of adjuvant chemotherapy are not due entirely to cytotoxic anti-tumor effects but to the production of ovarian failure. Pre-menopausal women who stop menstruating after chemotherapy have been shown to have a better outcome than those who continue menstruating. Luteinizing hormone-releasing hormone (LHRH) analogs, such as goserelin, offer an alternative form of ovarian estrogen suppression for pre-menopausal women and are being extensively studied in clinical trials. Two randomized clinical trials have addressed the issue of whether ovarian ablation is comparable to adjuvant chemotherapy for the prevention of recurrences in women with localized stage I-II breast cancer. Both clinical trials, published in the December 17, 2002 issue of the Journal of Clinical Oncology, concluded that combined adjuvant therapy with goserelin and Nolvadex® was superior or at least equivalent to standard adjuvant combination chemotherapy.

Genetic Microarray Analysis Predicts Outcomes of Women with Stage I-II Breast Cancer (12/20/2002)
Most women with stage I-II breast cancer receive adjuvant treatment with chemotherapy or hormonal therapy or both. However, not all women with localized breast cancer are destined to relapse if they don’t receive adjuvant treatment. Unfortunately, current risk factors such as age, size of tumor, number of lymph nodes involved and the histology of the tumor are less than precise in predicting failure of local therapy. Researchers from the Netherlands have reported a new test which may help predict patients with less aggressive disease who may not need aggressive adjuvant treatment. They reported their findings in the December 19, 2002 issue of The New England Journal of Medicine.

Dose-Dense Sequential Administration of Adjuvant Therapy for Localized Breast Cancer Decreases Recurrences (12/17/2002)
The usual method of administering adjuvant chemotherapy for primary breast cancer is to administer combinations such as FAC (5-FU, Adriamycin® (doxorubicin) and cyclophosphamide) or AC (Adriamycin® and cyclophosphamide) every three weeks for 6 cycles of therapy. An alternative method of administering such drugs is to give them sequentially, rather than in combination every three weeks for a total of 6 cycles. When single drugs are administered sequentially every 2 weeks, this is referred to as dose-dense sequential therapy. When combinations of drugs are administered, this is referred to as dose-dense combination chemotherapy.

Combined Hormone Replacement Increases the Incidence of Lobular Breast Cancers (12/9/2002)
Over the past two decades, there has been an increase in the incidence of breast cancer of the lobular histologic type. This type of breast cancer appears to be less aggressive than the more common ductal type and researchers have suspected that the increasing incidence was due to the increased use of hormone replacement therapy (HRT). As a generality, women with breast cancer that contains the lobular type have a better survival than women with the ductal type which may explain why the incidence of breast cancer can be high without a corresponding decrease in survival rates. However, the exact relationship between the type of hormone replacement therapy and increased breast cancer is not clear. The major finding to date is that the increased incidence of breast cancer is associated predominately with the use of combined estrogen and progestin and not estrogen alone. A recent study published in the December 3, 2002 issue of Cancer helps clarify these issues.

Axillary Lymph Node Dissection Leads to Significant Morbidity in Older Women (12/6/2002)
It has been known for a long time that women with breast cancer who undergo axillary lymph node dissection for staging purposes have significant morbidity, but this has not been quantified in older women. Furthermore, in recent years sentinel node biopsy and more aggressive adjuvant treatment strategies have brought into question the necessity of performing axillary node dissection in all women with early stage breast cancer. Researchers at the Lombardi Cancer Center have recently determined the morbidity of lymph node dissection in older women and reported their findings in the December 3, 2002 issue of Cancer.

Asian Women Not Receiving Optimal Treatment for Early Stage Breast Cancer (11/27/2002)
In the U.S., individuals in disadvantaged social and economic groups often receive less than optimal medical care. This is often due to lack of education, money and/or adequate health insurance. However, there may be cultural factors that affect treatment choices that are independent of social and economic factors. Researchers in the San Francisco Bay area have recently determined that Asian and Pacific Islander women receive less than optimal treatment for early-stage breast cancer. They concluded that this was not due to economics or lack of health insurance, however, they had no adequate explanation for this observation. They reported these results in the November 20, 2002 issue of the journal Cancer.

Alcohol and Hormone Replacement Therapy Can Double The Risk of Breast Cancer (11/22/2002)
It is reasonably well known that both alcohol and hormone replacement therapy (HRT) increase the risk of breast cancer in postmenopausal women. Estrogen is the cause of the increased risk of breast cancer in women taking HRT but the mechanism by which alcohol causes breast cancer is poorly understood. There has been some suggestion that alcohol stimulates the production of estrogen. Researchers from the Brigham and Women's Hospital, Harvard Medical School and Dana Farber Cancer Institute have evaluated the combined effects of estrogen and alcohol on the incidence of breast cancer and these results were published in the November 19, 2002 issue of the Annals of Internal Medicine.

Screening Mammography May Detect Smaller Cancers in Older Women (11/22/2002)
Screening mammography has not been clearly associated with a significant improvement in survival of women with breast cancer. However, survival benefit is a difficult end point to determine without the benefit of extremely large randomized trials with very long follow-ups. In the absence of such studies, researchers continue to search for surrogate markers for benefit of screening mammography. In the November 20, 2002 issue of the Annals of Internal Medicine, researchers from the University of Texas, Galveston reported potential benefits of screening mammography in women 75 years or older.

Taxotere® is Less Toxic and As Effective as 5-FU and Navelbine® For Salvage Treatment of Metastatic Breast Cancer (11/20/2002)
Less than 5% of women with metastatic breast cancer become long-term survivors following anthracycline-based chemotherapy. Women with the best outcomes have hormone receptor positive cancer, bone only disease, local-regional recurrences only and lack of liver and lung involvement. Thus, for the majority of women, chemotherapy is palliative especially after failure of initial therapy. There are many active agents for treatment of women who have failed anthracycline-based induction or adjuvant therapy. Some of the newer agents include the taxanes ( Taxotere® and paclitaxel), Navelbine®, Gemzar® and capecitabine. Many studies have been performed with single and multiple agents in the salvage setting. Most studies have failed to show a significant survival benefit and more toxicity from combination chemotherapy when compared to single agent chemotherapy. This trend was born out in a recent French randomized trial which compared Taxotere® to the combination of 5-FU and Navelbine®. The researchers concluded that single agent Taxotere® was less toxic and as effective as 5-FU plus Navelbine® in women with metastatic breast cancer who had failed anthracycline-based therapy. The results of this trial were published in the November 25, 2002 issue of the British Journal of Cancer.

Researchers Suggest that 4% of Breast Cancers are Related to Alcohol Consumption (11/19/2002)
Epidemiological studies have consistently shown an increase in the incidence of breast cancer in women who consume alcohol compared to those who do not. Epidemiological studies concerning tobacco use and breast cancer have been conflicting. Recently, it has been shown that direct and indirect exposure to tobacco smoke in young women increases the risk of breast cancer. In another study, it was suggested that tobacco increases the incidence of hormone receptor negative breast cancer in young women. Other studies have failed to show a correlation between smoking and breast cancer. One of the major problems with determining the effects of smoking and drinking on breast cancer is that these two factors are often linked and it is difficult to sort out cause and effect. However, researchers affiliated with the Collaborative Group on Hormonal Factors in Breast Cancer have presented data which suggests that alcohol is the culprit and tobacco can be exonerated. They published their findings in the November 15, 2002 issue of the British Journal of Cancer.

New Test, Cyclin E, May Predict Outcomes of Early-Stage Breast Cancer (11/18/2002)
Prognosis of disease-free survival of women with early-stage non-metastatic breast cancer is determined by tumor size, stage of disease as determined by lymph node involvement, hormone receptor status, presence of Her2-Neu gene abnormalities, and age. Despite the predictive ability of these factors, some women with negative risk factors will have disease recurrence and other women with positive risk factors will not have disease recurrence. Researchers have investigated other risk factors that might be more predictive of disease recurrence without remarkable success. This is an important area of research because many women are receiving adjuvant chemotherapy they do not need and some women are not receiving adjuvant chemotherapy they do need. Researchers from MD Anderson Cancer Center have now reported that high levels of a protein called cyclin E is correlated with survival of women with early stage but not metastatic breast cancer. Cyclin E is a gene product which regulates cell division and high levels of this protein accelerates cell division. These results were reported in the November 15 issue of The New England Journal of Medicine.

False Negative Sentinel Node Biopsies May Not Adversely Affect Treatment Options (11/11/2002)
Sentinel node biopsy is currently being evaluated as an alternative to axillary lymph node dissection for staging of women with localized breast cancer. The main advantage of performing a sentinel node biopsy is the avoidance of complications of lymph node dissection which include pain, infection, limited shoulder motion, numbness and lymphedema. Since these complications can become debilitating, reliance on sentinel node biopsy is very attractive. If the sentinel node biopsy is positive, there are no problems with this approach. However, there will inevitably be a number of false negative sentinel node biopsies and the consequences of this are still being investigated. The main concern is that women with a false negative sentinel node biopsy will be denied adjuvant chemotherapy which could prevent recurrences.

Increasing Cycles of Neoadjuvant Doxorubicin/Paclitaxel More Effective for Locally Advanced Breast Cancer. (11/7/2002)
Large primary breast cancers, including some stage II, IIIA or IIIB cancers, are collectively referred to as locally advanced breast cancer and are not typically treated with breast-conserving surgery because of their size. However, over the past decade it has become more common to administer neoadjuvant chemotherapy to shrink the primary breast cancer thereby allowing the patient to be treated with breast-conserving surgery and radiation. Currently, there is no evidence that neoadjuvant therapy improves survival compared to extensive surgery followed by adjuvant chemotherapy.

Anthracycline-Based Adjuvant Therapy Improves Outcomes of Postmenopausal Women with Localized Breast Cancer (11/6/2002)
It has been well documented that postmenopausal women who have estrogen/progesterone receptor positive localized breast cancer benefit from anti-estrogen therapy with Nolvadex® (tamoxifen). It has also been shown that the addition of adjuvant radiation therapy decreases the frequency of local-regional recurrences. However, the added benefit of chemotherapy to Nolvadex® and radiation therapy in this group of women has not been well documented.

Antiperspirant Use Does Not Increase the Risk of Breast Cancer (11/5/2002)
Recent undocumented news reports have suggested that the use of underarm deodorants and antiperspirants increase the risk of breast cancer. Although there has been no scientific study of this question, this association was apparently reported throughout the Internet. This prompted researchers at the Fred Hutchinson Cancer Research Center to include information on antiperspirant use in an epidemiological study they were conducting in western Washington state.

Italian Researchers Suggest that Initial Treatment of Metastatic Breast Cancer with Taxanes Improves Survival (11/1/2002)
The introduction of taxanes over a decade ago for the treatment of metastatic breast cancer has been hailed as a major achievement. However, the exact contribution of taxanes to survival of women with breast cancer has not been clear. There is no convincing evidence that the fraction of women with metastatic breast cancer that are cured with chemotherapy has increased with the introduction of taxanes and this fraction remains at less than 5%. All of the measurements of improved efficacy of taxanes relate to response rates, time to progression and survival. Thus, the question is how to use taxanes in the most effective palliative manner. Taxanes, paclitaxel and especially Taxotere®, are clearly the treatment of choice for women who have failed anthracycline-based therapy. However, the use of taxanes as initial therapy remains controversial. Thus, the current question is whether it is better to administer taxanes in initial treatment or reserve taxanes for use when patients fail first-line therapy with anthracycline based therapies. Italian Researchers have addressed this issue and concluded that it is better to administer paclitaxel as initial therapy rather than as second-line therapy. They presented their findings at the 27th meeting of the European Society of Clinical Oncology in October of 2002.

Estrogen Replacement Therapy May Not Increase Recurrences in Hormone Receptor Negative Breast Cancer (10/30/2002)
Hormone replacement therapy (HRT) for menopausal women has become a very contentious issue. Recent studies suggest that HRT with estrogen and progesterone may lead to more detriments than benefits. However, according to a recent governmental report, no definite conclusions can currently be reached about the benefits of estrogen replacement (ERT). For women with breast cancer, HRT of any kind is usually avoided because of fear of causing recurrences. Women with early stage breast cancer often suffer from premature menopause due to adjuvant chemotherapy. Thus, there is a large group of women who suffer from premature menopause and prolonged estrogen deficiency. Current data suggests that ERT increases the recurrence rate in women who have hormone receptor positive cancers but these cancers are usually curable with current treatment leading to no survival disadvantage. Nevertheless, most women with hormone receptor positive breast cancers choose not to take HRT. For women with hormone receptor negative breast cancers there may be no increase in recurrence rates with the use of ERT. Researchers at the MD Anderson Cancer Center have studied this question prospectively and concluded that ERT poses no increased risk of recurrences in women with hormone receptor negative or hormone receptor unknown breast cancers. They reported their findings in the November 1, 2002 issue of Cancer.

Age Not Found To Predict Outcome for Women with Ductal Carcinoma in Situ (10/28/2002)
Ductal carcinoma in situ (DCIS) is the earliest possible clinical diagnosis of breast cancer and is frequently diagnosed with screening mammography that has detected small areas of calcification in the breast. Currently, approximately 20% of all breast cancers detected by mammography are DCIS. Patients rarely suspect that they have breast cancer with this stage cancer.

Neoadjuvant Chemotherapy May Improve Survival in Women with Locally Advanced Breast Cancer (10/24/2002)
Patients with large primary cancers (stage IIIA-B) are often classified as having locally advanced breast cancer (LABC). These cancers are difficult to completely remove surgically and breast conserving surgery is not routinely performed. Over the past decade, the standard treatment has been to administer neoadjuvant chemotherapy before attempting surgical removal in order to make surgery less extensive and easier to perform. Clinical studies comparing neoadjuvant chemotherapy to mastectomy followed by adjuvant chemotherapy have demonstrated that the number of patients eligible for treatment with breast-conserving strategies can be increased following neoadjuvant chemotherapy. However, there is currently no evidence that survival is improved with neoadjuvant versus adjuvant chemotherapy in women with locally advanced breast cancer.

U.S. Preventive Services Task Force Issues Recommendations for Hormone Replacement Therapy (10/23/2002)
On October 15, the U.S. Preventive Services Task Force (USPSTF) issued guidelines for hormone replacement therapy. This document was prepared after the recent publications which cast doubt on the benefits of women taking hormonal therapy after menopause. These recommendations can be reviewed in total at http://www.preventiveservices.ahrq.gov and http://www.guideline.gov. This is the first update since 1996.

Twenty Year Follow-Up Confirms That Breast Conserving Surgery Does Not Jeopardize Survival of Women with Early Stage Breast Cancer (10/22/2002)
Over the past two decades, breast conserving surgery (lumpectomy or quadrantectomy) has emerged as the treatment of choice for many women with early-stage breast cancer. Lumpectomy and other breast conserving techniques not only preserve normal breast tissue but prevent many of the complications associated with radical and simple mastectomy. Despite all the evidence of equivalency of outcome of less versus more surgery in the U.S., it is estimated that less than 50% of women eligible for lumpectomy for breast cancer actually receive it. Instead, they generally receive simple mastectomy, which is clearly preferable to radical mastectomy which is rarely performed today. One of the reservations some physicians have about performing breast conserving surgery is that breast cancer can recur after years and that the follow-up of most studies comparing mastectomy to lumpectomy lack sufficient follow-up to be convincing.

Post-Mastectomy Radiation Therapy Decreases Local-Regional Recurrences After Mastectomy (10/18/2002)
The role of chest wall and axillary node radiation therapy in women with breast cancer undergoing mastectomy followed by adjuvant chemotherapy has been unclear. In many multicenter prospective clinical trials evaluating adjuvant chemotherapy, the decision to add radiation therapy is often left to the individual center. Now, researchers from MD Anderson Cancer Center have compared outcomes of women who were electively treated with adjuvant radiation therapy with those who were not. They reported their findings at the 44th annual meeting of the American Society of Therapeutic Radiation Oncology.

Increasing Use of Brachytherapy Alone As Adjuvant Radiation Therapy for Localized Breast Cancer (10/16/2002)
Patients with small localized breast cancers are usually treated with lumpectomy and radiation therapy to the whole breast. Recently there have been efforts to administer more precise radiation therapy through the use of radioactive implants (brachytherapy). In general there is less radiation delivered to skin, surrounding tissue and lung with brachytherapy than with external beam radiation therapy. The most common implant is Iridium-192. The potential advantages of this approach are more selective delivery of radiation and decreased visits needed to accomplish therapy. Brachytherapy can be delivered over several days versus the several weeks required for external beam radiation therapy. At the 44th annual meeting of the American Society of Therapeutic Radiation Oncology, 3 oral presentations revealed data on outcomes of women with primary breast cancer treated with lumpectomy and brachytherapy.

Breast Cancer in Men Reviewed in the Annals of Internal Medicine (10/16/2002)
Researchers at MD Anderson have reviewed the literature and summarized current knowledge about breast cancer in men. They report that 1,500 new cases of breast cancer are diagnosed in the United States each year with approximately 400 deaths per year. Breast cancer in men is usually treated in the same manner as breast cancer in women. These researchers point out that the rarity of this cancer precludes large randomized trials to determine optimal therapy. The researchers report that the risk factors for developing male breast cancer include: testicular disease, benign breast conditions, Jewish ancestry, family history and Klinefelter syndrome. BRCA2 mutations are apparently present in 4-14% of all cases of male breast cancer while BRCA1 is not frequent, as in women with breast cancer. The majority of cancers are estrogen receptor-positive and possibly more hormonally responsive than breast cancer in women. Gynecomastia was not associated with an increased risk for breast cancer in men. There is generally a greater delay in the diagnosis of breast cancer in men than in women, possibly due to lack of awareness. The researchers recommend the same adjuvant hormonal therapy and chemotherapy used in female breast cancer.

Radiation Therapy and Nolvadex® Prevent Local Recurrences in Breast Cancer Patients Undergoing Lumpectomy (10/14/2002)
Patients with localized breast cancer are often treated with lumpectomy, Nolvadex® and radiation therapy with or without adjuvant chemotherapy. However, the optimal treatment strategy for women with small breast cancers (one centimeter or less) and negative axillary lymph nodes has been questioned. In 1989, researchers affiliated with the National Surgical Adjuvant Breast and Bowel Project (NSABP) initiated a three-armed randomized trial to determine the effects of Nolvadex® alone, breast radiation therapy alone, or breast radiation therapy plus Nolvadex® in women undergoing lumpectomy for small breast cancers which had not spread to axillary lymph nodes. They concluded that there was enough reduction in the incidence of local-regional recurrences to warrant adjuvant radiation therapy and Nolvadex® in this group of women. The results of this trial were reported in the October 15, 2002 issue of the Journal of Clinical Oncology.

Motexafin Gadolinium (Xcytrin®) Improves Results of Whole Brain Radiation Therapy in Patients with Cancer Metastatic to Brain (10/14/2002)
Cancers often consist of areas of low oxygen concentration which complicates treatment. Hypoxic cells are more resistant to the effects of radiation than well-oxygenated tissues and there have been many candidate drugs for increasing oxygenation of cancers (radiosensitizers), none of which have been very successful. Xcytrin® (motexafin gadolinium) is a new type of radiation sensitizer that sensitizes both oxygenated and hypoxic cells to the effects of radiation. Xcytrin® also localizes selectively in tumors and this can be detected by magnetic resonance imaging (MRI). Laboratory and preclinical studies suggested that Xcytrin® could potentiate the effects of radiation for the treatment of cancers. In 1999, researchers at the University of Pennsylvania determined the optimal dose of Xcytrin® that could be given to patients with a variety of cancers receiving radiation therapy in a phase I trial. ¹

Temodol® Improves the Response Rate to Radiation Therapy for Cancer Metastatic to Brain (10/11/2002)
Temozolomide (Temodol®) is an analog of the alkylating agent procarbazine which has been approved by the U.S. Food and Drug Administration for the treatment of recurrent brain tumors. Current research with this drug primarily involves treatment of newly diagnosed brain tumors. However, researchers in Greece have evaluated the effectiveness of Temodol® for the treatment of cancer metastatic to brain. At the 2002 meeting of the American Society for Therapeutic Radiology and Oncology, the researchers reported that the addition of Temodol® to whole-brain radiation therapy resulted in significantly higher response rates of brain metastases compared to whole brain radiation alone.

Annual Screening Mammography After Age 40 Years Results in Fewer Mastectomies Than in Unscreened Women (10/9/2002)
There has been considerable recent controversy over the benefits of screening mammography for the detection of early stage breast cancer. The most recent information suggests that annual or every other year mammography after age 40 does not significantly improve survival of women with breast cancer. This is despite the fact that all studies have shown that screening detects more early-stage breast cancers, especially carcinoma in situ, than unscreened populations of women. It is suggested that many of these early-stage detected cancers were not destined to cause death. It has also been suggested that screening mammography leads to an excess number of biopsies for benign disease and causes distress in women. One problem with most studies is that the length of follow-up is not enough to be sure of the survival benefits, as most studies limit their study circumscribed period of time, when what is needed for definitive conclusions is a screened and a control group studied for life. Nevertheless, despite these controversies, annual screening mammography is recommended by the American Cancer Society and every one to two years is recommended by the U.S. Preventive Services Task Force. Since survival is a difficult endpoint to evaluate because of the time factor, other benefits of screening mammography have been evaluated. Researchers at Fox Chase Cancer Center have now reported that women who undergo regular screening mammography are more likely to undergo breast conserving lumpectomy than mastectomy, which for most women is a major benefit.

Stereotactic Radiosurgery Following Whole Brain Radiation Therapy Improves Palliation of Patients with Cancer Metastatic to Brain (10/8/2002)
Whole brain radiation therapy (WBRT) is the most frequent palliative modality for patients with cancer metastatic to the brain. Stereotactic radiosurgery (SRS), also called gamma knife therapy or 3-dimensional radiation therapy, can deliver precise doses of radiation to tumor sites while sparing normal tissue. Stereotactic techniques are used to treat a variety of cancers and are widely accepted as superior to non-precise radiation techniques. Since 1996, researchers from 34 medical institutions affiliated with the Radiation Therapy Oncology Group have been carrying out a study to document the benefits of SRS in individuals with cancers that are metastatic to the brain. They have concluded from this study that SRS adds significantly to the palliation achieved with WBRT alone. They reported these results at a plenary session of the annual meeting of the American Society of Therapeutic Radiology and Oncology in October of 2002.

Smoking Increases the Incidence of Breast Cancer (10/7/2002)
There has been inconsistent evidence that cigarette smoking increases the incidence of breast cancer. However, two recent reports strongly suggest a relationship between smoking and breast cancer. In the October 2002 issue of the American Journal of Epidemiology, German researchers evaluated the effect of active and passive smoking on the incidence of breast cancer. They collected data on lifetime active and passive smoking from 468 predominantly premenopausal breast cancer patients diagnosed by age 50 years and 1,093 controls. Former smokers had a 20% increased incidence of breast cancer and current smokers had a 50% increase. The risk of breast cancer increased with duration of smoking and decreased after quitting. Among women who had never smoked, passive smoking increased the odds of breast cancer by 60%. Exposure to environmental tobacco smoke during childhood or before the first pregnancy did not appear to increase breast cancer risk. At greatest risk were women who had a high level of exposure to both passive and active smoking, with an 80% increase in the incidence of breast cancer. Thus, this study strongly supports a relationship between active and passive smoke exposures and breast cancer risk.

Efficacy of Breast Self Examination Challenged by New Study (10/3/2002)
Both cornerstones of early detection of breast cancer, breast self examination (BSE) and mammography, have recently been challenged. Recent reports have suggested that routine mammography results in little, if any survival advantage over women who do not have routine mammography performed. Now, a very large study from China suggests that the routine practice of BSE also does not contribute to survival in women who develop breast cancer. Researchers from the Fred Hutchinson Cancer Research Center and physicians in Shanghai, China have reported that training of women to perform BSE does not improve the survival from breast cancer when compared to women who are not trained. They reported their results in the October 2 2002 issue of the Journal of the National Cancer Institute.

Image-Guided Large-Core Needle Biopsy of Non-Palpable Mammogram Detected Breast Masses Has Low False Negative Rate (10/2/2002)
Mammography detects breast masses before they become palpable by the patient or her physician. Image-guided large-core needle biopsy is a non-invasive method of evaluating non-palpable breast masses. If cancer is detected through this method, then it is usually at an early stage. However, the majority of biopsies are negative for cancer and it is not clear from the available information how often breast cancers are missed or how often biopsy negative patients go on to develop breast cancer. Researchers at the Northwest Hospital in Seattle have reported that the frequency of false negative image-guided large-core needle biopsies is very low. They reported their results in the October 2002 issue of the Journal of the American College of Surgeons.

Intraspinal Implantable Drug System Effective in Controlling Pain Due to Metastatic Cancer (10/1/2002)
The management of pain is an important component for the treatment of most patients with metastatic cancer. It is estimated that 5-15% of patients with metastatic cancer have pain that is refractory to oral and i.v. narcotics. Intraspinal implantable drug delivery systems (IDDSs) deliver small doses of morphine directly to the spinal fluid, theoretically requiring smaller doses of narcotics. Although this system is known to be effective, there have been no randomized controlled trials. Researchers in the U.S. and Europe affiliated with the Implantable Drug Delivery Systems Study Group have determined that IDDSs are better than conventional pain management techniques. They reported these results in the October 2002 issue of the Journal of Clinical Oncology.

Breast Cancer Patients with a Family History of Breast Cancer are at High Risk for Developing Ovarian Cancer (9/23/2002)
Women who carry the BRCA1 and BRCA2 genes have a high incidence of breast and ovarian cancer. However, these genes account for a relatively small number of the total cases of breast and ovarian cancer. It is thought that other unidentified genes may play a role in causing breast and ovarian cancer. Swedish researchers have evaluated the association of early onset breast cancer, before the age of 40, with the subsequent development of ovarian cancer. They found a very high incidence of ovarian cancer in young women with breast cancer who had a family history of breast or ovarian cancer. They reported their results in the September 2002 issue of The Lancet.

Hormone Replacement Therapy is Associated with Early Detection and Better Survival From Breast Cancer (9/19/2002)
An increased incidence of breast cancer has been associated with the use of long-term hormone replacement therapy (HRT) in many studies. However, the general consensus of opinion is that breast cancers which occur in women receiving HRT are detected early and survival is relatively favorable. These impressions were further substantiated by a recent analysis conducted by researchers affiliated with the Oregon Health Sciences University. They reported their results in the September 2002 issue of the A rchives of Surgery. These researchers evaluated 292 postmenopausal women with breast cancer to determine the method of cancer detection and outcomes. There were 144 women who had received HRT and 148 who had not received HRT.

Intraoperative Radiation Therapy May Prevent Local Recurrences After Breast Conserving Surgery for Localized Breast Cancer (9/19/2002)
Over the past 20 years, women with localized breast cancer have been treated more frequently with lumpectomy followed by radiation therapy to the breast rather than mastectomy. In addition to radiation to the whole breast, a boost of radiation is often delivered to the local tumor bed either by external beam radiation or by brachytherapy. Using these techniques, the local recurrence rates are usually 5%-15% following breast conserving surgery and radiation therapy. Researchers in Austria have recently reported a third method of delivering radiation to the tumor bed - intraoperative radiation therapy. Intraoperative radiation therapy has the advantage of delivering a very accurate boost to the tumor bed as the area to be irradiated is exposed by the surgeon. The researchers have reported their findings in the August 2002 issue of the European Journal of Cancer.

New Study Finds Tamoxifen Decreases Breast Cancer in High Risk Women But May be Associated with Increased Deaths (9/16/2002)
The antiestrogens, tamoxifen (Nolvadex®) and raloxifene (Evista®) have the potential for reducing estrogen-positive breast cancers in high-risk women. Randomized trials to define the role of tamoxifen in the prevention of breast cancer have generally been positive when the follow-up was sufficiently long. The randomized studies of raloxifene are too immature at this time. It is important to perform randomized trials because of the potential side effects of anti-estrogen therapy which include thromboembolic phenomenon, hot flushes and an increased incidence of uterine cancer.

Canadian Study Finds No Benefit of Annual Mammography For Women Between the Ages of 40 and 49 (9/4/2002)
The hypothesis that performing annual mammograms to detect early breast cancers would lead to more women being cured has recently been questioned. Several analyses have failed to show a survival benefit for women who underwent routine screening mammograms compared to women who had a mammogram performed only when a lump appeared. It has also been suggested that routine mammograms lead to over-diagnosis and over treatment. This can only be true if many cases of in situ breast cancers are not destined to grow and cause invasive cancers. It is also postulated that early detection by mammograms does not improve survival because the detected tumors would have been as curable later when detected clinically. At the present time it is safe to say that there is confusion about the cost-effectiveness and survival benefits of screening mammography compared to physical screening. Even if screening mammography is of benefit, it is not clear at what age women at average risk should start screening and for older women it is not clear what the screening intervals should be. A new study by Canadian researchers sheds some light on these question and their study suggests that there is no survival benefit of screening mammography in women between the ages of 40 and 49 years. They published their results in the September 3, 2002 issue of the Annals of Internal Medicine.

U.S. Preventive Services Task Force (USPSTF) Publishes Guidelines for Screening for Breast Cancer (9/4/2002)
The U.S. Preventive Services Task Force (USPSTF) published recommendations on screening for breast cancer and the supporting scientific evidence in the September 3, 2002 issue of the Annals of Internal Medicine. This information is available on the USPSTF Web site (www.preventiveservices.ahrq.gov), the National Guideline Clearinghouse (www.guideline.gov), and in print through the Agency for Healthcare Research and Quality Publications Clearinghouse (telephone, 800-358-9295; e-mail, ahrqpubs@ahrq.gov).

Screening Mammography Does Not Increase Number of Mastectomies (8/28/2002)
This past year has seen a major controversy arise over the benefit of screening mammograms. Critics say that there is no proven survival benefit from screening mammography and that screening leads to over-diagnosis and an increased number of mastectomies. In the August 23, 2002 issue of the British Medical Journal, Italian researchers reported that screening mammography does not increase the number of mastectomies performed, and in fact leads to a decrease in the number of mastectomies due to earlier diagnosis and treatment with less drastic surgery.

Twenty-Five Year Follow-Up Confirms Lack of Benefit From Lymph Node Removal or Radiation Therapy For Women With Primary Breast Cancer (8/26/2002)
Current management of women with primary breast cancer includes lumpectomy, staging with lymph node dissection or sentinal node biopsy and adjuvant chemotherapy with or without radiation therapy to breast and axilla. The effectiveness of lumpectomy and radiation therapy for small tumors compared to mastectomy has been well documented. There has also been data suggesting that removal of positive or negative lymph nodes has no impact on recurrences. The impact of radiation therapy to the axilla has been controversial, with conflicting results. For these reasons, it was deemed helpful to publish a 25-year follow-up that addresses some of these issues. Researchers affiliated with the National Surgical Adjuvant Breast and Bowel Project (NSABP) published a 25-year follow-up of a study begun in 1971.

Patients with Primary Breast Cancer That Over-Expresses p53 and Her2/neu May Not Have Improved Survival with High-Dose Chemotherapy with Autologous Stem Cell Support (8/13/2002)
The role of high-dose chemotherapy for the treatment of poor-risk patients with operable breast cancer is controversial. There are several ongoing randomized studies currently maturing that are designed to determine the ultimate impact of high-dose chemotherapy with autologous stem cell support compared to relatively high doses of chemotherapy without stem cell support. Patients in these trials have multiple positive lymph nodes and a high probability of relapse with standard dose adjuvant therapy. One of the hopes for high-dose chemotherapy was that it might overcome the added adverse effects of other poor-risk factors, such as over-expression of p53 and/or Her2/neu. When p53 and Her2/neu are over-expressed there is generally a higher chance of the disease recurring.

Radiation Over 22 Days as Effective as 35-Day Schedule Following Lumpectomy for Primary Breast Cancer (8/12/2002)
The current treatment of primary breast cancer in women with negative lymph nodes is lumpectomy followed by radiation therapy. Radiation therapy decreases the incidence of local recurrences following lumpectomy, but each center has essentially a different way of administering radiation therapy. One such approach is to deliver a total of 50 Gy in 2 Gy fractions on a Monday through Friday schedule, for a total treatment time of 35 days. An alternative approach uses larger fractions of radiation, lower total doses of radiation and a shorter time of treatment. A shorter time of treatment would be more convenient and more cost effective if it was not accompanied by an increase in recurrences or untoward side effects. Researchers in Canada published the results of a randomized comparison of a shorter treatment schedule compared to a more conventional treatment schedule. Their results appeared in the August 7, 2002, issue of the Journal of the National Cancer Institute. They concluded that a 22-day fractionated regimen was equivalent in results to a 35-day schedule.

Women with Primary Breast Cancer May Benefit From Long-Term Oral Biphosphonate (Clodronate) Therapy (8/1/2002)
Biphosphonates have been beneficial for the treatment of patients with bone lesions due to multiple myeloma. Biphosphonates significantly reduce the osteolytic complications of hypercalcemia, fractures, and pain associated with established bone metastases in patients with breast cancer. Biphosphonates may also decrease metastasis to bone in women with metastatic disease to other sites. Biphosphonates may also prevent metastatic spread to bone marrow. However, the exact role in preventing metastatic bone disease in primary breast cancer is unknown. In the August issue of the Journal of Clinical Oncology, English researches have reported the outcome of a randomized trial of two years of oral clodronate in women with operable primary breast cancer.

Breast Feeding Protects Women Against Breast Cancer (7/25/2002)
It has been thought for a long time that the earlier women had children and the more children they had, the lower the incidence of breast cancer. This observation has been used to explain the difference in breast cancer rates between developed countries, such as the U.S. and developing countries, where birth occurs early and multiple children are common. In the July 19 issue of the medical journal The Lancet, researchers affiliated with Collaborative Group on Hormonal Factors in Breast Cancer reported that breastfeeding also protects women from breast cancer.

Post-Menopausal Women With Negative Lymph Nodes Who Have Hormone Responsive Breast Cancer do not Benefit from Adjuvant Chemotherapy (7/22/2002)
The role of chemotherapy in preventing recurrences in older women with estrogen receptor-positive (ER-positive) breast cancer has been controversial. It has become relatively common to use adjuvant chemotherapy to treat most women with localized breast cancer. However, there have been doubts that chemotherapy adds much in women with hormonally responsive disease treated with 5 years of tamoxifen. The results of a recent randomized trial were published in the July 17 issue to the Journal of the National Cancer Institute and help clarify this issue. Researchers affiliated with the International Breast Cancer Study Group (IBCSG) present data that show that post-menopausal women with ER-positive breast cancer with negative axillary lymph nodes do not benefit from adding chemotherapy to tamoxifen.

Increased Use of Alternative Treatments, Especially Soy Products, for Treatment of Menopausal Women with Breast Cancer (7/17/2002)
Women who have had breast cancer are aware of the association of hormone replacement therapy (HRT) and the increased incidence of breast cancer recurrence and uterine cancer. Physicians are also reluctant to prescribe HRT for menopausal symptoms for the same reason. Thus, women with menopausal symptoms are often left on their own to try and control these symptoms.

Black Women Have Worse Outcome From Breast Cancer Than White Women (7/11/2002)
Black women have a worse outcome from breast cancer than white women. This is often attributed to a lower rate of self examination and mammography screening than among white women. Researchers at the University of Colorado examined the effect of routine screening on breast cancer staging by race and ethnicity. They found that women participating in routine screenings had earlier-stage disease by 5 to 13 percentage points, irrespective of race or ethnic group. In this study, white women were more likely to have early-stage disease compared with black and hispanic women. From this study, these researchers concluded that lack of screening coverage in black and hispanic populations did not completely explain the high stage of presentation of breast cancer in black and hispanic women.

Lack of Benefit and Potential Harm Halts Clinical Trial of Hormone Replacement for Post-Menopausal Women (7/10/2002)
Hormone replacement with estrogen plus progestin is often used to treat menopausal symptoms and to prevent osteoporosis and subsequent bone fractures. There has also been conflicting evidence that hormone replacement prevents heart disease. The association of hormone replacement with breast and uterine cancer has been well known, but usually these cancers present in early stages and do not affect survival. Estrogen and progestin are usually given together for women who have an intact uterus in order to prevent uterine cancer. Women who have had a hysterectomy usually are given estrogen alone. Researchers affiliated with the Women's Health Initiative have now reported that hormone replacement is not associated with prevention of heart disease, although overall survival was not affected one way or the other. Their results were published in the July 17 issue of the Journal of the American Medical Association.

Screening for Breast and Cervical Cancer in Rural Areas Lags Behind Urban Areas (7/10/2002)
Cancer screening programs have saved countless lives and are extremely cost effective. However, such programs are not equally available throughout the United States. There are still underserved areas in the U.S. where it is necessary to increase the fraction of women who are screened for breast and cervical cancer. Researchers from the Centers for Disease Control and Prevention have reported in a recent issue of the journal Cancer the differences between urban and rural screening for breast and cervical cancer.

Women at High Risk of Breast Cancer Should Consider Chemoprevention with Nolvadex® or Raloxifene (7/8/2002)
The gains that have been made in improving survival in women with breast cancer are due predominantly to earlier diagnosis and adjuvant therapy with Nolvadex® (tamoxifen) or other antiestrogens and chemotherapy. It is well documented that Nolvadex®, raloxifene and anastrozole can prevent breast cancer recurrences in women with hormone receptor-positive breast cancer. These observations have led to several large trials of chemoprevention with Nolvadex® or raloxifene in women at higher than usual risk of breast cancer. However, the definition of who is at high risk is problematic and differs from trial to trial, but generally includes women with a family history of breast cancer, early menarche, later or no childbirth, or previous breast biopsy, even if negative. The largest tamoxifen study, involved more than 13,000 U.S. women with an estimated five-year breast cancer risk of at least 1.66%. This 1.66% incidence of breast cancer means that large numbers of patients will need to be studied to determine if there is any effect of prophylactic treatment. It also means that large numbers of women will receive treatment they do not need because they are not destined to have breast cancer. Since there are side effects of Nolvadex® and other antiestrogens, each woman has to weigh the risks of taking a drug for a minimum of 5 years to prevent breast cancer versus the side effects of the treatment.

Oral Contraceptive Use is not Associated with a Significant Increase in Breast Cancer (6/28/2002)
There is suggestive information that oral contraceptive use is associated with an increased incidence of breast cancer. In the June 26 issue of The New England Journal of Medicine, researchers from the Division of Reproductive Health and Prevention, other governmental health agencies and several U.S. universities have reported that oral contraceptive use is not associated with an increased incidence of breast cancer.

Published Study Defines Benefit of Arimidex® Over Nolvadex® For Adjuvant Treatment of Primary Breast Cancer in Postmenopausal Women (6/26/2002)
For many years, Nolvadex® (tamoxifen) has been the standard adjuvant drug for the prevention of breast cancer in hormone response primary breast cancer in postmenopausal women. Five years of Nolvadex® in this group of women decreases the recurrence rate by 47% and reduces mortality by 26%. However, approximately one-third of women taking Nolvadex® have hot flashes, vaginal discharge or vaginal bleeding. Nolvadex® is also associated with an increase in the incidence of endometrial cancer and thromboembolic complications, although these risks are still very small. Arimidex® (anastrozole) is a third generation non-steroidal aromatase inhibitor that reduces estrogen concentrations in postmenopausal women and is currently emerging as a superior option for adjuvant treatment of breast cancer. The results of a large clinical trial comparing Arimidex®, to Nolvadex® and the combination of Arimidex® plus Nolvadex® were published in the June 22 issue of The Lancet.

Women with Breast Cancer who have “Stressful” Life Experiences do not have an Increase in Recurrences (6/25/2002)
Some studies have suggested that women with breast cancer who have stressful life experiences have a greater chance of cancer recurrence than women with less stressful lives. This is a difficult observation to confirm since having cancer is a stress by itself. However, some studies imply that women with breast cancer who apparently handle stress better than others have a better survival.

New Drug Combination (Eniluracil, 5-FU and Taxotere®) is Effective in Women with Metastatic Breast Cancer (6/18/2002)
Eniluracil is a new oral chemotherapy drug that has activity in patients with breast and colon cancer. Recent efforts have been made to incorporate eniluracil into combination chemotherapy regimens. Researchers from MD Anderson Cancer Center have reported in a recent issue of the journal Cancer that the combination of eniluracil, 5-fluorouracil (5-FU) and Taxotere® has significant activity in women with metastatic breast cancer.

Progress Being Made to Develop a Breast Cancer Vaccine (6/6/2002)
A lot of effort has been expended over the past 3 decades or more to develop effective immune therapies for cancer prevention or treatment. The development of effective vaccines has proven to be difficult, since essentially one is trying to elicit a response to “self” antigens. However, according to a report in the June issue of the Journal of Clinical Oncology, there does appear to be real progress in obtaining immune responses to the Her-2neu tumor antigen. Researchers at the University of Washington have demonstrated immune responses to a vaccine that may be ready for testing in women with breast cancer or in other Her-2neu positive cancers.

Xeloda® is as Active as Paclitaxel for the Treatment of Women with Breast Cancer who have Received Anthracyclines (6/3/2002)
Xeloda® is an anti-cancer agent that generates 5-fluorouracil preferentially at the site of cancers and has significant activity for patients with breast cancer. Researchers from several cancer centers in Europe and the U.S. have compared the effectiveness of Xeloda® with the more commonly used drug paclitaxel. They concluded that Xeloda® was at least as effective as paclitaxel for the treatment of women with breast cancer who had failed anthracyclines. They reported their results in a recent issue of the British Journal of Cancer.

Novel Combination Therapy Significantly Reduces Tumors in Women With Breast Cancer When Given Before Surgery (5/31/2002)
University of Miami/Sylvester Comprehensive Cancer Center

Docetaxel Improves Survival and Reduces Risk of Relapse In Women With Node-Positive Early-Stage Breast Cancer (5/31/2002)
ASCO abstract # 141: The first results of docetaxel as an adjuvant treatment show a large early benefit over a standard chemotherapy.

Outcomes of High-Dose Chemotherapy with Autologous Stem Cell Support for HER2 Positive Breast Cancer May Be Improved with Concurrent Herceptin® (5/30/2002)
According to results recently presented at the 38th Annual Meeting of the American Society of Clinical Oncology, the addition of Herceptin® to a high-dose treatment regimen for women with HER2-positive breast cancer may improve outcomes.

Bilateral Oophorectomy Reduces the Risk of Ovarian and Breast Cancer in Women who are Carriers of a BRCA1 or BRCA2 Mutation (5/23/2002)
Women with germ-line BRCA1 or BRCA2 mutations have an increased risk of breast and ovarian cancer as compared with the general population. These women often undergo bilateral prophylactic oophorectomy to reduce the risk of ovarian cancer. However, the magnitude of the risk reduction is not clear. Papillary serous peritoneal cancers have been reported in women who have undergone prophylactic oophorectomy, but this risk has also not been clearly defined. In addition, prophylactic oophorectomy reduces the risk of breast cancer by about 50 percent in both carriers of BRCA1 mutations and genetically uncharacterized women. Two recent studies have focused on the magnitude of cancer prevention achieved by prophylactic oophorectomy in women at high risk of ovarian and breast cancer.

Ethyol® May Prevent Granulocytopenia in Children Being Treated for Osteosarcoma (5/22/2002)
According to results recently published in the Journal of Pediatric Hematology-Oncology, Ethyol® (amifostine) decreases the incidence of granulocytopenia in patients undergoing treatment for osteogenic sarcoma.

Large Study Defines Results of Gleevec® in Patients with Chronic Myeloid Leukemia in Myeloid Blast Crisis (5/22/2002)
According to results recently published in Blood, Gleevec® used as a single agent induces responses in patients with CML in blast crisis (BC).

Component of Red Wine Has Potential Anti-cancer Properties (5/20/2002)
According to results recently published in the British Journal of Cancer, the cancer preventive agent resveratrol metabolizes into the anti-leukemic agent piceatannol, which may provide a novel explanation for the cancer preventive properties of resveratrol.

Chemotherapy after Complete Eradication of Local Recurrence of Breast Cancer Decreases the Incidence of Subsequent Recurrences (5/13/2002)
According to results recently published in the Breast Journal, the administration of chemotherapy in women with stage IV breast cancer with no evidence of disease appears to reduce the incidence of recurrences, compared to local therapy alone.

Young Women with Primary Breast Cancer Who Are Carriers Of BRCA1/2 Mutations Are At Increased Risk Of Second Breast Cancers Following Lumpectomy (5/10/2002)
According to results recently published in The Lancet, the risk of developing late ipsilateral and contralateral second primary tumors is higher in women with germline mutations in BRCA1/2 who have had conservative treatment than in women with sporadic breast cancer.

Prozac™ Improves Hot Flashes in Women With Risk of Breast Cancer (4/19/2002)
Researchers from the Mayo clinic have determined that Prosac™ (fluoxetine) can alleviate the symptoms of hot flashes in women. Their results were published in the March 15 issue of the Journal of Clinical Oncology.

Taxotere® and Herceptin® Effective for HER-2–Overexpressing Metastatic Breast Cancer (4/8/2002)
Researchers from the Anderson Cancer Center have demonstrated the effectiveness of Taxotere® and Herceptin® for the treatment of women with metastatic breast cancer. Their results were published in the April 1 issue of the Journal of Clinical Oncology.

High Dose Chemotherapy (HDC) with Autologous Stem Cell Support May Improve Long-Term Survival (4/4/2002)
Investigators associated with Cancer and Leukemia Group B (CALGB) trials and the Autologous Blood and Marrow Transplant Registry (ABMTR) have reported that women receiving HDC versus standard dose therapy (SDC) for metastatic breast cancer have a similar short-term probability of survival, and might have a modestly higher long-term probability of survival. These results were published in the February 1 issue of the Journal of Clinical Oncology.

Recent Update on Long-term Effects of Mammography Screening Show Unequivocal Benefit (3/25/2002)
Randomized trials recent re-analyses of the effects of mammography screening on survival have suggested no benefit on survival. Because of this controversy, researchers have updated the Swedish randomized controlled trials on mammography screening up to and including 1996.

Soy Phytoestrogens Do Not Alleviate Hot Flashes in Postmenopausal Women With Breast Cancer (3/21/2002)
Researchers from Canada evaluated the acceptability and effectiveness of a soy beverage containing phytoestrogens as a treatment for hot flashes in postmenopausal women with breast cancer. They concluded that the soy product tested was no more effective than placebo and these results were published in a recent issue of the Journal of Clinical Oncology.

Addition of Taxotere® Enhances the Neoadjuvant Effect of Anthracycline Based Chemotherapy in Breast Cancer (3/18/2002)
Researchers in England have determined that the sequential use of neoadjuvant Taxotere® after initial cyclophosphamide, Oncovin®, doxorubicin and prednisone (CVAP) chemotherapy in patients with anthracycline-refractory cancers resulted in enhanced clinical response. They reported their results in a recent edition of the Journal of Clinical Oncology.

Whole-Body Positron Emission Tomography (PET) is Superior to Conventional Imaging (CI) for Predicting Outcome in Previously Treated Breast Cancer Patients (3/13/2002)
Researchers in Sacramento determined the ability of whole body PET and CI to predict the outcomes in recently treated breast cancer patients. They demonstrated that one-time, whole body PET was significantly more predictive of breast cancer outcome than multiple conventional images. Their results were recently published in the Journal of Nuclear Medicine.

The Volume of Mammograms Read per Radiologist Affects Accuracy of Interpretation (3/11/2002)
The accuracy of mammograms is determined by specificity and sensitivity. Specificity requires a low percentage of false positive interpretations and sensitivity demands a high percentage of true positive interpretations. Researchers at the University of California at San Francisco; the Scottish Breast Screening Programme, South-East Scotland Division, Edinburgh; and the University of Iowa recently evaluated the impact of high-volume per radiologist on accuracy of mammogram interpretation. This study was recently reported in the Journal of the National Cancer Institute and suggests that reading a higher volume of mammograms is associated with increased diagnostic accuracy among radiologists.

High-Dose Chemotherapy with Autologous Stem Cell Rescue Does Not Overcome Inherent Poor Outcome of HER-2/neu Positive Breast Cancer Patients (3/6/2002)
Researchers at the University of Texas, M. D. Anderson Cancer Center, have compared the outcomes of autologous stem cell transplantation in patients with HER-2/neu positive and HER-2/neu negative metastatic breast cancer. They treated 236 patients with standard-dose induction chemotherapy followed by stem cell collection and high-dose chemotherapy with cyclophosphamide, Thioplex® and carmustine followed by autologous stem cell infusion.

Long-Term Use of Hormone Replacement Therapy Increases Risk of Breast Cancer (3/5/2002)
According to results recently published in the Journal of the American Medical Association, recent use of long-term hormone replacement therapy is associated with increased risk of breast cancer, particularly lobular breast cancer.

Clodronate Slows Bone Loss in Pre-Menopausal Breast Cancer Patients Receiving Adjuvant Chemotherapy (3/4/2002)
Researchers from Helsinki University Central Hospital in Finland have reported long term results of adjuvant clodronate in pre-menopausal women with primary breast cancer receiving cyclophosphamide, methotrexate, 5-FU (CMF) chemotherapy. These results were published in a recent issue of the European Journal of Cancer. They presented the 5-year results of the effect of adjuvant chemotherapy on bone mineral density and the efficacy of clodronate in the prevention of bone loss in 73 pre-menopausal women with primary breast cancer. All patients were treated with CMF chemotherapy.

The FDA Approves Zometa® for the Treatment of Bone Metastases Associated with a Broad Range of Tumor Types (2/26/2002)
Zometa® (zoledronic acid) is a new generation bisphosphonate that inhibits osteoclast bone resorption. A recent study compared Zometa® to Aredia® for the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of multiple myeloma.

Measurement of Estradiol in Postmenopausal Women Identifies Those at High Risk of Breast Cancer Who May Benefit Most From Raloxifene (2/12/2002)
High levels of estradiol are associated with a high incidence of breast cancer in post-menopausal women. The anti-estrogen drug, raloxifene, competes with endogenous estrogen for binding to estrogen receptors in breast tissue. The level of estradiol could have an impact on the anti-cancer preventative effects of raloxifene. Researchers at the University of California, San Francisco, coordinated a multi-center trial testing the hypothesis that raloxifene reduces breast cancer risk more in women with relatively high estradiol levels than in women with very low estradiol levels. If the hypothesis were correct, patients likely to benefit could be identified prospectively by measuring estradiol in the blood. They performed a randomized, double-blind, placebo-controlled trial between 1994 and 1999. This study involved 180 community settings and medical practices in 25 countries including the United States. A total of 7290 postmenopausal women aged 80 years or younger with osteoporosis who had baseline serum estradiol concentrations measured were randomized. Women with a history of breast cancer or estrogen use were excluded. Participants were randomly assigned to receive 60 mg/d or 120 mg/d of raloxifene (n = 4843) or matching placebo (n = 2447) for 4 years. In the placebo group, women with estradiol levels greater than 10 pmol/L (2.7 pg/mL) had a 3.0% incidence of breast cancer which was a 6.8-fold higher rate than that of women with undetectable estradiol levels who had an incidence of 0.6% per 4 years. Women with estradiol levels greater than 10 pmol/L in the raloxifene group had a rate of breast cancer that was 76% lower than that of women with estradiol levels greater than 10 pmol/L in the placebo group. This was an absolute reduction of 2.2%. In contrast, women with undetectable estradiol levels had similar breast cancer risk whether or not they were treated with. It was concluded that treating women with estradiol levels greater than 10 pmol/L with raloxifene for 4 years would have avoided 47% of breast cancer cases. They suggest that measurement of estradiol level by sensitive assay in postmenopausal women identifies those at high risk of breast cancer who may benefit most from raloxifene. If confirmed, this suggests that measuring estradiol and treating women with high estradiol levels could substantially reduce the rate of breast cancer among postmenopausal women.

Randomized Trial Involving More Than 5,000 Women With Stage I-II Breast Cancer Confirms Benefit of Local Boost of Radiation to Tumor Bed (2/12/2002)
Lumpectomy and radiation therapy is the current preferred treatment for stage I-II breast cancer. Multiple randomized trials have conclusively demonstrated that breast irradiation markedly reduces the rate of local recurrence after conservation surgery for breast cancer, but these studies did not deal with the dose or fractionation of radiation. The decision to deliver an additional localized dose of irradiation is based on the fact that most local recurrences occur within the vicinity of the primary tumor. For this reason, additional treatment was prescribed in all but one of the randomized trials that established the equivalence of breast-conserving and radical surgical therapy. However, the National Surgical Adjuvant Breast and Bowel Project trials limited the dose of radiation to 50 Gy when the excised tumor had microscopically negative margins, a practice that has been adopted as standard therapy in published guidelines.