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CC BY-NC-ND 4.0 · Ann Natl Acad Med Sci 2019; 55(01): 034-047
DOI: 10.1055/s-0039-1694085
Original Article
National Academy of Medical Sciences (India)

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

Sunita Saxena
1   National Institute of Pathology, VMMC and Safdarjung Hospital, New Delhi, India
,
Anurupa Chakraborty
1   National Institute of Pathology, VMMC and Safdarjung Hospital, New Delhi, India
,
Mishi Kaushal
1   National Institute of Pathology, VMMC and Safdarjung Hospital, New Delhi, India
,
R. S. Mohil
2   Department of Surgery, VMMC and Safdarjung Hospital, New Delhi, India
,
A. K. Mishra
1   National Institute of Pathology, VMMC and Safdarjung Hospital, New Delhi, India
,
L. C. Singh
1   National Institute of Pathology, VMMC and Safdarjung Hospital, New Delhi, India
,
Jaganath Sharma
3   Dr. B. Borooah Cancer Institute, Guwahati, India
,
Anju Bansal
1   National Institute of Pathology, VMMC and Safdarjung Hospital, New Delhi, India
,
Usha Agrawal
1   National Institute of Pathology, VMMC and Safdarjung Hospital, New Delhi, India
,
Jatin Mehta
1   National Institute of Pathology, VMMC and Safdarjung Hospital, New Delhi, India
,
Shailendra Asthana
1   National Institute of Pathology, VMMC and Safdarjung Hospital, New Delhi, India
,
Amal Chand Kataki
3   Dr. B. Borooah Cancer Institute, Guwahati, India
,
Sujala Kapur
1   National Institute of Pathology, VMMC and Safdarjung Hospital, New Delhi, India
,
Chintamani,
Dinesh Bhatnagar
2   Department of Surgery, VMMC and Safdarjung Hospital, New Delhi, India
› Author Affiliations Funding The authors acknowledge support from the following projects: research grant on “Genetics of Breast Cancer in Indian Women” by Indo-French Centre for Promotion of Advanced Research; research grant on “Role of tobacco use in causation of cancer in Northeast India”—Indian Council of Medical Research Task Force project; ICMR PDF grant to Dr. Jatin Mehta “Study on Androgen Signaling in Breast Cancer.”
Further Information

Publication History

Publication Date:
03 October 2019 (online)

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Abstract

Breast 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.

Keywords

breast cancer - genetic risk factors - predictive biomarkers
 

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