TAKE A BIOPSY FROM METASTASES

Discordance Between Primary and Metastatic Tumors Seen in Breast Cancer

March 24, 2009 — There appears to be a substantial rate of discordance in pathology and molecular markers between primary and suspected metastatic lesions in women with breast cancer. This discordance is prevalent enough to alter treatment decisions in 20% of cases, according to a report published online March 18 in the Annals of Oncology.

These changes in molecular markers between primary lesions and metastatic disease are increasingly important because of the growing use of targeted therapies, the researchers note, and confirmation of tissue should be considered the standard of care in patients with clinical and/or radiologic suspicion of metastatic recurrence and lesions amenable to biopsy.

"It is not standard of care anywhere, but I think it is being increasingly done, given the results of retrospective and now this prospective trial," lead investigator Mark Clemons, MD, head of the Breast Medical Oncology Group at Princess Margaret Hospital, in Toronto, Ontario, told Medscape Oncology. "I think it would be prudent to talk about it with a patient."

But Dr. Clemons added that it is difficult to imagine that this will ever be a standard of care, because doing biopsies requires incredible interdisciplinary support. "We could not have done this study without our colleagues in interventional radiology and pathology," he said, adding that they had funding support as well.

Other studies have suggested that there can be changes in molecular phenotype between the primary and relapsed breast cancer, which can significantly alter response to treatment. As reported by Medscape Oncology at that time, a study presented at the 2008 annual meeting of the American Society of Clinical Oncology found that 28% of relapsed tumors had changes in either estrogen-receptor (ER)/progesterone-receptor (PR) or HER2-receptor status, and suggested that biopsies of relapsed sites should routinely be performed to determine optimal treatment options.

In the current study, Dr. Clemons and colleagues prospectively examined concordance in receptor status between primary tumor and distant metastases, and then evaluated the impact of discordance on treatment decisions.

Management Changes Needed in 20% of Cohort

Of 40 breast cancer patients enrolled in the study, 35 underwent biopsies of their metastatic lesions, from which 29 analyzable samples were obtained. Within this group, 61% had received adjuvant chemotherapy, 53% had received endocrine therapy, 2% had received trastuzumab, and 26% were still receiving endocrine therapy when metastases were diagnosed. The median time between the diagnosis of the primary breast cancer and metastasis was 2.4 years.

Upon analysis, 3 biopsy samples were diagnosed with benign disease and 1 sample was diagnosed as low-grade follicular lymphoma. The remaining 25 specimens confirmed the presence of metastatic breast cancer.

The original biopsy results from the primary tumor showed that 16 of 25 patients were ER-positive, 9 were PR-positive, and 4 were HER2-positive. The researchers noted that when these 25 samples from primary and metastatic lesions were paired together, 10 were discordant for ER/PR status, and 2 showed discordance for HER2, with a complete change in receptor status. The result was an overall discordance rate for ER and PR status of 40%, and an 8% discordance rate for HER2.

The results of the second biopsy resulted in a complete change in management in 6 (20%) of the 29 patients. The treatment plan changed for the 4 patients who showed no evidence of metastatic disease, as did their prognosis. The remaining 2 patients experienced a gain in HER2 overexpression, which now qualified them for either treatment with trastuzumab or entry into a clinical trial.

Although this study only included breast cancer patients, it is possible that discordance between primary lesions and metastatic disease exists in other types of tumors. "I see no reason at all why it would not be applicable for other cancers," said Dr. Clemons. "However, breast cancer is unique in that many years can pass between diagnosis and development of metastatic disease."

The researchers conclude that this study also "has implications for the design of clinical trials that evaluate targeted therapies."

"Mandating a biopsy of metastases at study entry would ensure that the target is expressed and would allow for a more efficient study to be carried out," they write.