Researchers from the M. D. Anderson Cancer Center and the University of Milan, Italy, have reported that women with Stage T1a,b, N0M0 HER2-positive breast cancers have a have a high recurrence rate without the administration of adjuvant chemotherapy or Herceptin® (trastuzumab). These data suggest that these women should be treated with Herceptin®-based adjuvant chemotherapy. The details of these two studies appeared in early online publications on November 2, 2009 in the Journal of Clinical Oncology.

Twenty to 25 percent of breast cancers overexpress HER2, which leads to increased growth of cancer cells and a worse prognosis. Fortunately, the development of drugs that specifically target HER2-positive cells has improved prognosis for women with HER2-positive breast cancer.

A question that remains uncertain is the need for HER2-targeted therapy among women with small (1 centimeter or less) HER2-positive breast cancers. To explore the behavior of these small cancers, researchers in the United States and Italy conducted studies of women with HER2-positive and HER2-negative breast cancers.

The U.S. study evaluated the records of 965 women with small cancers that had not been treated with HER2-targeted therapy or chemotherapy.[1] Ten percent of patients in this study had HER2-positive tumors. By the end of five years, 6% of women with HER2-negative breast cancer had a recurrence compared with 23% of women with HER2-positive breast cancer. The risk of recurrence for HER-2 positive tumors was five times that of HER-2 negative tumors, and the risk for distant recurrence was increased by almost eightfold.

The Italian study evaluated 150 women with small HER2-positive breast cancers and 229 women with small HER2-negative breast cancers.[2] None of the women had been treated with Herceptin.

• In patients who were hormone receptor-positive and HER-2 negative, the five-year disease-free survival was 99%.
• In patients who were hormone receptor positive and HER-2 positive, the five-year disease-free survival was 91%.
• In patients who were hormone receptor negative and HER-2 negative, the five-year disease-free survival was 92%.
• In patients who were hormone receptor negative and HER-2 positive, the five-year disease-free survival was 91%.

These authors concluded: “Patients with node-negative, HER2 positive, pT1a-b breast cancer have a low risk of recurrence at 5 years of follow-up. In patients with hormone receptor-positive disease and pT1a-b,NO tumors, HER2 overexpression was associated with a worse PFS.”

Comments: The results of these two studies suggest that even small HER2-positive breast cancers have an increased risk of recurrence. Consideration of adjuvant treatment with HER2-targeted therapy may be important for most women with HER2-positive breast cancer regardless of the size of the cancer. It should be noted, however, that these studies did not directly assess the effectiveness of HER2-targeted therapy in women with small cancers.

An accompanying editorial cautions that HER2-targeted therapy still may not be warranted in women with very small cancers (T1a or microinvasive; 0.5 cm or smaller).[3] The authors of the editorial state: “We suggest that consideration of trastuzumab plus chemotherapy generally be limited to patients with T1b or larger cancers, and we believe that among patients with small T1a or microinvasive cancers, it is less likely that the tradeoffs of risk and benefit warrant chemotherapy plus trastuzumab.”

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