Need to Biopsy at Metastatic Breast Cancer Relapse?

Assumptions Can Be Wrong

Nick Mulcahy

February 09, 2012

February 9, 2012 — Taking a biopsy of metastatic cancer that has spread beyond the breast can lead to a change in systemic therapy, and thus management, in some patients, according to a prospective study published online November 28, 2011, in the Journal of Clinical Oncology.

Canadian researchers biopsied metastases to see if the receptor status was "discordant" with the original status of the primary breast tumor.

Specifically, the status of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth-factor receptor 2 (HER2) were determined in both the breast tumor and a metastatic site in 121 women.

The discordance in ER, PR, and HER2 between the primary tumor and the metastasis was 16%, 40%, and 10%, respectively, write the study authors, led by Eitan Amir, MD, from the University of Toronto in Ontario, Canada.

Biopsy led to a reported change of management in 14% of women (95% confidence interval, 8.4% to 21.5%).

Dr. Amir described one such a change in management.

A postmenopausal patient in the study, who had an initial breast tumor that was ER-positive, PR-positive, and HER2-negative, was diagnosed with a liver metastasis 18 months later. "The rebiopsy showed ER-positive, PR-positive, and HER2-positive disease. Therefore, the planned treatment was changed from letrozole to paclitaxel and trastuzumab," he told Medscape Medical News in an email.

Rebiopsies of metastases represent a substantial change in practice, Dr. Amir and colleagues suggest.

"The receptor status of metastatic disease is usually assumed to be the same as that of the primary tumor," they write, adding that the primary tumor's receptor status dictates the choice of systemic therapy.

This study challenges those assumptions and dictates and suggests that biopsy of metastases, which the researchers call "technically feasible," be performed in this setting.

"Tissue confirmation should be considered in women with breast cancer and suspected metastatic recurrence," the researchers conclude.

The call to biopsy breast cancer metastases has been made by other investigators, as has been previously reported by Medscape Medical News.

Need Proof of Benefit, Says Expert

But an expert not involved with the study expressed skepticism about such testing.

In an editorial related to the study, published online January 30, Stephen Chia, MD, from the British Columbia Cancer Agency in Vancouver, Canada, writes that various retrospective studies have repeatedly demonstrated that discordance is a fairly common phenomenon — occurring in 20% to 30% of breast cancer metastases.

However, Dr. Chia emphasizes that prospective studies are needed to demonstrate that any changes in treatment based on biopsies actually result in improved outcomes.

He points out that, in retrospective studies, the majority of the discordance seen was in a loss of receptor expression. In practice, this means that clinicians will "struggle with whether to withhold the associated targeted therapy." Such drugs have the potential for "significant efficacy," he writes.

Dr. Chia also says there is another reason that clinicians should be cautious about the idea of routinely biopsying metastases: the results are not entirely reliable. In other words, different labs and techniques come up with different results sometimes.

A recent round-robin review of HER2 testing in 3 central laboratories involved in large adjuvant trials demonstrated that 8% of HER2 immunohistochemistry and fluorescent in situ hybridization test results differed, Dr. Chia explains. This highlights the role that testing variables "may play in the observed discordance in biomarker testing."

Another Study in HER2-Positive Disease

Another study, also published online November 28, 2012, in the Journal of Clinical Oncology, suggests that a discordant metastasis influences prognosis — for the worse.

Having a discordant metastasis was associated with worse survival in 182 women with HER2-positive primary breast cancers, according to a single-center study conducted at the University of Texas M.D. Anderson Cancer Center in Houston.

The investigators, led by Naoki Niikura, MD, retrospectively found that 24% of the women (n = 43) had a HER2-negative metastatic lesion on review. The team demonstrated that the patients with a discordant HER2 result (HER2-positive primary disease but HER2-negative metastases) had worse survival than patients with a concordant HER2 result (hazard ratio, 0.43; P = .003).

Dr. Chia explains that the survival difference presumably occurred because the patients with HER2-positive metastases benefited from anti-HER2 therapy, whereas those without this receptor expression did not.

The researchers and Dr. Chia have disclosed no relevant financial relationships.

J Clin Oncol. Published online November 28, 2011, and January 30, 2012. Abstract, Abstract, Editorial

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