SAN ANTONIO – Estrogen receptor status flip-flops in 1 in 3 breast cancer patients when the primary tumor progresses to recurrence or distant metastasis, and HER2 status changes in 1 in 10, according to a Swedish study.
Dr. Jonas Bergh
"Our data, together with other retrospective and prospective studies, really challenge the present management, which is to use primary tumor data for the management of metastatic disease," Dr. Jonas Bergh said in presenting the findings at the San Antonio Breast Cancer Symposium.
His argument that breast cancer relapses should be biopsied routinely for repeat hormone receptor and HER2 testing won widespread acceptance at the meeting.
"In the corridors around here the last couple of days this issue of primary tumor/metastasis heterogeneity has been the most discussed topic," Dr. Mitchell Dowsett noted in a conference-closing review highlighting the past year’s major developments in translational breast cancer research. He called the proportion of patients with marker changes in Dr. Bergh’s study "pretty startling."
"In 2010, I think the evidence supports rebiopsy if the result could affect management of the patient. And I do absolutely support this sort of analysis being mandatory in clinical trials of targeted therapy," said Dr. Dowsett, professor of translational research at Breakthrough Breast Cancer and of biochemical endocrinology at The Royal Marsden hospital, both in London.
Dr. Bergh presented a retrospective analysis that showed estrogen receptor status changed from positive in the primary to negative in the relapse specimen in 26% of 459 patients and from negative to positive in 7%.
"Hormone receptors are not stable during progression," concluded Dr. Bergh, professor of oncology at the Karolinska Institute, Stockholm.
The clinical relevance of this observation is underscored by the fact that patients who lost estrogen receptor positivity during tumor progression had a statistically significant 40% increase in the risk of dying compared with patients with stable estrogen receptor–positive disease, he added.
Moreover, among 118 patients whose HER2 status was known both in the primary tumor and the rebiopsied relapse, 7% lost their HER2 amplification and another 3% went from HER2-negative in the primary tumor to HER2-positive in the relapse.
Audience member Dr. Alastair M. Thompson rose to suggest that the time has come for biopsy of breast cancer recurrences or metastases to be considered the standard of care throughout the world. Dr. Thompson of Ninewells Hospital and Medical School, Dundee, Scotland, was lead author of the Breast Recurrence in Tissues Study (BRITS), a recent prospective 137-patient study showing that one in six women with relapse of breast cancer would have their treatment changed as a result of rebiopsy of their recurrent or metastatic disease (Breast Cancer Res. 2010;12:R92 [doi:10.1186/bcr2771]).
Dr. Lisa A. Carey, in a conference-closing summary of the past year’s progress in advanced breast cancer, noted that the 2010 ASCO meeting included three studies comprising roughly 520 patients, all showing "small but real changes" in hormone receptor and HER2 status between the primary tumor and metastatic disease.
"I think that rebiopsying at the time of relapse is a reasonable thing. The main reason to rebiopsy is to make sure you’re treating what you think you’re treating. I used to keep a list for my fellows of the psittacosis, nocardia, sarcoid, and other things that were masquerading as metastatic breast cancer," said Dr. Carey, medical director of the breast center at the University of North Carolina at Chapel Hill.
As for reanalyzing the hormone receptor and HER2 status, that is valuable, too, but with a caveat: "You have to be very cautious in using that information to guide therapy," she said. "For example, a hormone receptor–positive breast cancer that’s negative on rebiopsy may or may not reflect endocrine-insensitive disease. I think that’s a question that’s left outstanding."
Dr. Bergh disclosed that he receives honoraria for lectures from Amgen, AstraZeneca, Novartis, Pfizer, Roche, and Sanofi-Aventis.