Following Neoadjuvant Chemotherapy, Biomarkers Change in 41% of Breast Cancer Patients


Key Points

  • Following neoadjuvant chemotherapy, 41% of patients with early breast cancer experienced a change in estrogen receptor, progesterone receptor, or HER2 status in a study from MD Anderson Cancer Center.
  • A change in receptor status was associated with improved recurrence-free survival but not overall survival.

After neoadjuvant chemotherapy, 41% of early breast cancer patients experienced a change in status for the estrogen receptor, progesterone receptor, or HER2 oncogene, researchers from The University of Texas MD Anderson Cancer Center reported at the 2013 Breast Cancer Symposium in San Francisco (Abstract 48).

“Discordance in breast cancer biomarker status has been reported, but reports of an association between discordance and outcome have shown inconsistent results,” said Napa Parinyanitikul, MD, who presented the findings.

Study Details

The study evaluated the changes in receptor status between the primary tumor and residual disease after neoadjuvant chemotherapy and its association with clinical outcomes for 398 patients in the MD Anderson Breast Cancer Management System Database. Patients received neoadjuvant chemotherapy with an anthracycline-based, taxane-based, or anthracycline/taxane-based regimen; 88% of patients with hormone-positive disease received adjuvant endocrine therapy.

The researchers observed that 40.7% had a change in at least one biomarker. Regarding the estrogen receptor, 11% changed from estrogen receptor–positive to estrogen receptor–negative and 21% changed from estrogen receptor–negative to estrogen receptor–positive. Progesterone receptor status changed from positive to negative in 35% and from progesterone receptor–negative to progesterone receptor–positive in 12%. Of the 72 HER2-positive tumors, 40% changed to HER2-negative, whereas only 3% of HER2-negative tumors changed to positive. Among the 35 HER2-positive patients who received trastuzumab (Herceptin), 46% became HER2-negative, Dr. Parinyanitikul reported.

By breast cancer subtype, 20% changed from hormone receptor–positive to HER2-positive or triple-negative; 12.5% changed from HER2-positive to triple-negative; and 2% changed from triple-negative to HER2-positive. All these changes were statistically significant.

Relationship of Biomarker Changes to Outcomes

“In our study, a change in any of the tumor biomarkers was independently associated with improved recurrence-free survival (hazard ratio [HR] = .63) but had no statistical impact in overall survival (HR = .78), she reported.  

At a median follow-up of 40 months, 5-year overall survival was 73% for patients with any change in receptor status and 63% for those without a change (P = .07); 5-year recurrence-free survival was 63% and 48%, respectively (P = .003).    

“It is still uncertain if mechanisms for tumor discordance—such as tumor heterogeneity, clonal selection, genetic switch and differential treatment response—would be the main explanations for the lack of stability in the tumor biomarkers,” she commented.

Caution Advised When Dealing With Discordant Results

Lajos Pusztai, MD, PhD, of Yale Cancer Center in New Haven, Connecticut, offered commentary on the findings during a panel discussion at the meeting. He pointed out that while much is made of tumor heterogeneity, it may be overstated as a means for explaining changes in receptor status.“Tumor heterogeneity is a popular explanation, but the bulk of clinical data does not support it as a major influence,” Dr. Pusztai noted.

He also maintained that the neoadjuvant treatment may not be responsible, either. “Receptor status changes 23% of the time when we mail tumor blocks from local sites to central labs [in previous studies],” he said. “Are we to conclude that the airplane flight changed them? We cannot, and we also cannot conclude it was the chemotherapy that changed the receptor status…. There is always ‘noise,’ and about 20% of tumors will have discordant results when we repeat the test.”

It is possible that discordant results are due to “technical artifacts” of the assays, he said, and he would not recommend altering treatment based on a change in status. “It would be dangerous to actually withhold endocrine therapy or anti-HER2 therapy when tumors turn negative on a second assay,” he emphasized. “You don’t know which assay may be wrong. Be very careful in making decisions based on conflicting results.”

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.