Chemopredictive test may identify women most likely to survive newly diagnosed breast cancer

Women with a high probability of survival after chemotherapy for newly diagnosed breast cancer may now be easily identified with the use of a predictive test that indicates chemoresistance, chemosensitivity and endocrine sensitivity. According to researchers, identifying these patients would reaffirm treatment decisions regarding the use of chemotherapy.

“Conversely, identification of those with significant risk of relapse despite standard chemotherapy could be used to advise participation in an appropriate clinical trial of potentially more effective treatment,” according to background information cited in the article.

From June 2000 to March 2010, researchers conducted a study to develop a predictor of response and survival to chemotherapy for patients with newly diagnosed ERBB2 (HER-2 or HER-2/neu)–negative breast cancer treated with chemotherapy containing sequential taxane and anthracycline-based regimens. Using gene expression microarrays, predictive signatures for resistance and response to preoperative chemotherapy were developed. According to a press release, breast cancer treatment sensitivity was predicted using a combination of signatures for sensitivity to endocrine therapy, chemoresistance and chemosensitivity, with independent validation among 198 patients, and comparison with other reported genomic predictors of chemotherapy response.

The chemopredictive test algorithm had a positive predictive value of 56% for the prediction of pathologic response after excluding patients with predicted endocrine sensitivity. The 3-year distant relapse-free survival (DRFS) rate among 28% of patients predicted to be treatment sensitive was 92%; the absolute risk reduction among these patients was 18%. These patients had a fivefold reduction in the risk for distant relapse.

“Overall, there was a significant association between predicted sensitivity to treatment and improved DRFS,” the researchers wrote.

Thirty percent of patients in the ER-positive phenotypic subgroup and 26% of those in the ER-negative subgroup were determined to be treatment sensitive. Patients in the ER-positive subgroup had a DRFS of 97% and an absolute risk reduction of 11% at 3-year follow-up. Patients with ER-negative disease had a DRFS of 83% and an absolute risk reduction of 26% at 3 years. The positive predictive value of pathologic response among these patients was 83%.

Other genomic predictors showed worse survival for patients predicted to be responsive to chemotherapy, according to the researchers.

“Any test based on predicted sensitivity, resistance or both to guide the selection of a standard adjuvant treatment regimen should predict a high probability of survival for patients predicted to be treatment sensitive (negative predictive value, no relapse if predicted to be treatment sensitive) and a clinically meaningful survival difference between patients predicted to be treatment sensitive and insensitive (ARR), as well as improve on predictions using existing clinical-pathological information. The performance of our predictive test meets these criteria in an independent validation cohort,” they wrote.

A test with this performance could possibly help medical decision-making by identifying those with stage II to III, ER-positive and ERBB2-negative disease who have excellent 3- and 5-year DRFS after a standard adjuvant treatment, the researchers said.

“[It is] imperative to continue to evaluate the predictive accuracy of this test in additional validation studies,” they wrote.

For more information:

Hatzis C. JAMA. 2011;305:1873-1881.

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