Among women with relapsed or metastatic breast cancer, the sites of cancer recurrence might have an estrogen-receptor (ER)/progesterone-receptor (PR) and/or HER2 status that is different than the primary tumor. Researchers here at the American Society of Clinical Oncology 44th Annual Meeting reported that a significant proportion (28%) of relapsed tumors had changes in either ER/PR or HER2-receptor status, and suggested that biopsies of relapsed sites should routinely be performed to determine optimal treatment options.
It has been assumed that sites of relapse are the same phenotypes as the primary tumor in breast cancer, explained Robyn MacFarlane, MD, a resident in the department of medicine at the University of British Columbia, in Vancouver.
“Most patients do not have additional biopsies performed,” she said. “If there are differences in the phenotypes, we may need to make changes in treatment.”
Recent small studies have suggested that, in some breast cancer patients, the HER2- and hormone-receptor status of the relapsed tumor can be different than the status of the original lesion. In those cases, treatment options that were effective in the primary cancer might no longer be optimal for the relapsed/metastatic disease.
In this study, Dr. MacFarlane and colleagues compared the ER/PR and HER2-receptor status of relapsed/metastatic breast cancer tumors with the status of the original tumor, using a large population-based database and tissue microarray (TMA) cohort. The researchers identified women from the British Columbia Cancer Agency Breast Cancer Outcomes Unit (BCOU) database who experienced biopsy-proven relapses between 1986 and 1992.
The women identified from the database were associated with a current large TMA series (n = 4444) of primary breast cancers. After conducting a chart review, the researchers requested available tissue blocks of the relapsed/metastatic cancers. A secondary TMA series was created from the relapsed/metastatic tumors.
From the BCOU database, 281 cases were linked to the TMA series; of these, 184 tissue blocks were available. All patients had experienced a local, regional, or distant relapse of their breast cancer and, of the 184 samples, 160 were adequate for analysis of HER2 and PR/ER status of both the primary and relapsed tumors.
In all, 115 of the 160 samples (72%) showed no change in either hormone-receptor or HER2 status. However, the remaining 45 tumor samples (11%) did exhibit changes in receptor status. Eleven (7%) of these were local recurrences and 34 (21%) were regional or distant relapses.
“We saw changes in ER status from positive to negative and from negative to positive, and we also saw the same shift for HER2,” said Dr. MacFarlane.
Among the 34 regional/distant relapses:
11 changed from ER/PR positive to ER/PR negative
14 changed from ER/PR negative to ER/PR positive
3 changed from HER2 negative to HER2 positive
6 changed from HER2 positive to HER2 negative.
“This is one of the largest known studies to assess changes in molecular phenotype between the primary and relapsed breast cancer,” concluded Dr. MacFarlane. “And the results suggest that biopsies of relapsed/metastatic breast cancers should be performed routinely.”
Obtaining biopsies of recurrent sites could be an important factor in optimizing treatment, she added, and further study of this issue is warranted.
“This study address 3 of the biomarkers used in the clinic, which currently guide our choice of treatment,” said Paul E. Goss, MD, PhD, director of Breast Cancer Research at Massachusetts General Hospital, in Boston, in a discussion of the study. “The question put before us is whether there is biologic evolution from the primary tumor to relapse. If so, should these changes guide the treatment?”
Dr. Goss explained that although there are limitations to this study, we should view this as the beginning of the debate and not the end. “The study was retrospective and the sample size was small, and that makes it difficult to draw conclusions,” he said. “There is also the issue of sampling errors.”
Another factor to consider is the site of the sample; the different sites of metastases could show variations in status. Also, the data were restricted to ER, PR, and HER2, and no other pathways were analyzed. Finally, a critical issue is that the samples were taken after multiple adjuvant therapy.
However, this study has highlighted the importance of evaluating changes between primary and metastatic tumors. “We need to optimize the technologies available to verify these changes, and we need to prospectively correlate any biologic findings with subsequent response to treatment,” he said.
American Society of Clinical Oncology (ASCO) 44th Annual Meeting: Abstract 1000. Presented June 2, 2008.
Reviewed by Ramaz Mitaishvili, MD
