Risk factors associated with molecular subtypes of breast cancer among indian women: a multicentre matched...

Breast cancer is a biologically diverse disease with distinct molecular subtypes, each linked to specific risks and outcomes. However, subtype-specific risk factors remain insufficiently explored, particularly in diverse populations such as Indian women. This study examined the associations of reproductive, lifestyle, and psychosocial factors with the risk of developing breast cancer subtypes defined by hormone receptor (HR) and human epidermal growth factor receptor-2 (HER2) status.

We conducted a multicentric matched case-control study among Indian women at three tertiary cancer centres. Pathologically confirmed breast cancer cases and age-matched controls were recruited, and detailed information on socio-demographic, reproductive, lifestyle, and psychosocial characteristics was collected through structured interviews. Breast cancer cases were classified into four molecular subtypes (HR+HER2-, HR+HER2+, HR-HER2+, and HR-HER2-). Multivariable conditional logistic regression models were used to estimate subtype-specific odds ratios and 95% confidence intervals.

HR+HER2 - was the most prevalent subtype. Increased risks for this subtype were observed among women with later age at marriage, artificial menopause, prolonged breastfeeding, unmarried status, obesity in midlife, frequent fried-food consumption, benign breast disease, and higher psychological stress. HR+HER2 + breast cancer was strongly associated with artificial menopause and low physical activity. HR-HER2 - breast cancer was linked to artificial menopause, family history of ovarian cancer, passive smoking, limited physical activity, and psychosocial stress.

Distinct molecular subtypes of breast cancer among Indian women exhibit heterogeneous risk profiles shaped by reproductive, lifestyle, and psychosocial factors. This underscores the need for targeted public health strategies focusing on modifiable risk factors such as promoting breastfeeding, maintaining healthy body weight, increasing physical activity, and improving dietary habits. Enhancing psychosocial well-being, awareness of family history, community education, and early screening programmes may help reduce the breast cancer burden in India.