May 11, 2011
Genetics May Help Breast Cancer Survival
(Ivanhoe Newswire) -- Development of a predictive test that included genomic signatures that indicated chemoresistance, chemosensitivity and endocrine sensitivity for women with newly diagnosed breast cancer identified patients with an increased likelihood of survival following chemotherapy.
Identification of patients with high likelihood of survival following a standard chemotherapy regimen would reaffirm a treatment decision 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 in the article.Christos Hatzis, Ph.D., of Nuvera Biosciences Inc., Woburn, Mass., and colleagues conducted a study to develop a predictor of response and survival from chemotherapy for patients with invasive breast cancer. Different predictive signatures for resistance and response to preoperative chemotherapy were developed from gene expression microarrays (special type of testing) of newly diagnosed breast cancer. Breast cancer treatment sensitivity was predicted using the combination of signatures for sensitivity to endocrine therapy, chemoresistance, and chemosensitivity, with independent validation and comparison with other reported genomic predictors of chemotherapy response.
The researchers found that the chemopredictive test algorithm had a positive predictive value (PPV) of 56 percent for prediction of pathologic response after excluding patients with predicted endocrine sensitivity. In 28 percent of patients predicted to be treatment sensitive, the 3-year distant relapse-free survival (DRFS) was 92 percent, and there was an absolute risk reduction (ARR) of 18 percent. Patients predicted to be treatment sensitive had a 5-fold reduction in the risk of distant relapse. "Overall, there was a significant association between predicted sensitivity to treatment and improved DRFS," the authors write.
"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," the authors write.
The researchers add that a predictive test with this performance could potentially assist medical decision-making as it could identify patients with stage II-III, ER-positive and ERBB2-negative breast cancer with excellent 3-year and 5-year DRFS (97 percent) following a standard treatment.
SOURCE: JAMA, published online May 11, 2011