Researchers from Canada reported that sites of relapse may have different molecular phentoypes than the primary tumor in breast cancer, and thus may require individual biopsies. However, further testing is necessary as the results presented were from a retrospective analysis of tumor samples. These results were recently reported at the 2008 annual meeting of the American Society of Clinical Oncology (ASCO).

Biopsies for breast cancer involve information including molecular phenotypes such as the human epidermal growth factor receptor 2 (HER2) status and hormone receptor status, to name a few. It has been assumed that sites of relapse possess the same molecular distinctions as primary tumors in breast cancer, and treatment options are derived under this consideration without biopsy of sites of relapse. However, a couple of small studies have indicated that in some patients, sites of relapse may actually display phenotypic molecular markers that differ from the primary tumor. As a result these sites of relapse may potentially benefit from different treatment than what is considered for the primary tumor.

A retrospective, nonrandomized histologic analysis was undertaken that included patients diagnosed with primary breast cancer who were linked to a tissue microarray analysis (TMA) series. Patients were identified by the British Columbia Cancer Agency Breast Cancer Outcomes Unit (BCCA BCOU) and had experienced a local, regional, or distant relapse. One hundred and sixty tumor blocks were identified that could be analyzed for hormone receptor and HER2 status of both the primary and relapsed tumors through immunohistochemistry. New primary cancers in the contralateral breast were not included in the analysis.

• 28% of tumors had changes in either estrogen receptor, progesterone receptor, and/or HER2 receptor status between the primary and relapsed sites of cancer.
• Both gain and loss of receptors were noted between primary and relapsed tumor sites; these gains and losses occurred among individuals who had received prior systemic chemotherapy, hormone therapy, or both.

Comments: The researchers concluded that with nearly 30% of tumors with changes in hormone and HER2-receptor status between the primary and relapsed sites of tumor among breast cancer patients, biopsies of relapsed sites may make sense to determine optimal treatment options. However, this was a retrospective analysis, warranting caution of interpretation of results. Further study regarding this issue is warranted to determine potential antigen loss through archiving as well as heterogeneity within a single tumor site.

Reference: MacFarlane R, Speers C, Masoudi H, and Chia S. Molecular changes in the primary breast cancer versus the relapsed/metastatic lesion from a large populations-based database and tissue microarray series. Program and abstracts of the 44th American Society of Clinical Oncology Annual Meeting; May 30 - June 3, 2008; Chicago, Illinois. Abstract 1000.