Breast Cancer in Indian Women: Genetic Risk Factors and Predictive Biomarkers

AbstractBreast cancer is the most common cancer among Indian women with a significant increase in incidence in young women. To identify risk factors for breast cancer in young women, study of BRCA1 and BRCA2 germ line mutations was done in a cohort of 204 Indian breast cancer patients. The study showed a total of 18 mutations in 2.94% of the tested patients, 44% BRCA1 and 78% BRCA2 mutations were found unique to the Indian population. Association of low penetrance genes mainly CYP17, VDR gene and AR-CAG repeat polymorphisms with breast cancer risk showed CYP17 A2 and VDR Poly-A L as high risk alleles, the risk of developing breast cancer among women carrying three high-risk alleles is 4.68 (95% confidence interval [CI]: 0.77–28.0; p for trend = 0.10) compared with women carrying none. CYP17 A2 allele was also found associated with development of breast cancer at young age and can also serve as a target for therapy. Betel quid chewing has been found as a significant and independent risk factor for developing breast cancer in North East Indian women which induces genetic alterations leading to breast carcinogenesis. Studies to assess the predictive role of various tumor markers showed that expression of p-glycoprotein in pretreatment biopsy predicts a poor clinical response to neoadjuvant chemotherapy (NACT) in patients having locally advanced breast cancer. The chemotherapy-induced toxicity (vomiting and alopecia) correlated significantly with clinical and immunohistochemical response (reduction in bcl2/bax ratio) and were found to be a cost-effective and reliable predictor of response to NACT. Androgen receptor (AR) has been identified as independent predictive marker for response to NACT in locally advanced breast cancer cases and can serve as novel therapeutic target for triple negative breast cancers.