Neoadjuvant Chemotherapy +/- Bevacizumab Pharmacogenomics

Neoadjuvant chemotherapy (NAC) for breast cancer is widely employed. We performed genome-wide association studies (GWAS) to determine if germline genetic variability was associated with benefits, in terms of pathological complete response (pCR), disease-free survival (DFS), and overall survival (OS), in patients entered on the NSABP B-40 NAC (National Surgical Adjuvant Breast and Bowel Project, B-40, Neoadjuvant Chemotherapy) trial where some patients were randomized to receive bevacizumab, in addition to chemotherapy. ]]> Patients were randomized to one of three chemotherapy regimens, and one-half of the patients also randomized to receive bevacizumab, based on reports of efficacy in the advanced disease setting. The three regimens were four cycles of docetaxel followed by four cycles of doxorubicin plus cyclophosphamide, same as regimen 1, except for the addition of capecitabine to docetaxel, and same as regimen 1, except for the addition of gemcitabine to docetaxel. Patients were stratified according to age at entry (<49 or >50 years old), clinical tumor size (2.0 to 4 cm or >4.1 cm), and hormone receptor status (estrogen receptor [ER] positive, progesterone receptor [PgR] positive, or both vs. ER and PgR negative). Eligibility criteria for NSABP B-40 included primary operable breast cancer which was diagnosed with a core needle biopsy with a palpable primary tumor at least 2.0 cm in diameter, HER2-negative, and TMN stages T1c to T3, N0 to N2a, and M0. All patients on current study provided blood samples for DNA extraction and consent for genetic testing.]]>