Distinct molecular subtypes of breast cancer among Indian women exhibit heterogeneous risk profiles shaped by reproductive, lifestyle, and psychosocial factors, which underscores the need for targeted public health strategies focusing on modifiable risk factors.
Women with estrogen receptor negative (ER-) contralateral breast cancer (CBC) are 50% more likely to die of CBC compared to women with estrogen receptor positive (ER+) CBC. We comprehensively investigated risk factors for ER subtype-specific CBC using the Women’s Environmental Cancer and Radiation Epidemiology Study, a population-based, case-control study of 1521 CBC cases under age 55 years and 2212 individually matched unilateral breast cancer controls. Information about breast cancer risk factors and ER status was obtained by interview and medical record abstraction and common genetic variants with GWAS. Multivariable rate ratios and 95% confidence intervals were estimated using conditional logistic regression models, adjusting for known and suspected risk factors. Among 2800 women where the matched case had known ER CBC status, chemotherapy, hormone therapy, and increasing number of full-term pregnancies were associated with decreased ER+ CBC risk. Drinking, smoking, first breast cancer lobular histology, first-degree breast cancer family history, a polygenic risk score (PRS) of 313 common variants, and an ER+ subtype-specific PRS were associated with increased ER+ CBC risk. More than 2 years of breastfeeding was associated with decreased ER- CBC risk. While none of the PRSs were associated with ER- CBC risk, first- and second-degree family history of breast cancer and second-degree family history of ovarian cancer were associated with increased ER- CBC risk. We identified differential risk factors for ER subtype-specific CBC which can inform individualized risk prediction models for future clinical impact. There remains an unexplained genetic component of ER- CBC.
Anne S. Reiner, K. Malone, Charles F. Lynch et al.· International Journal of Can...· 0 citations
Several reproductive factors are significantly associated with breast cancer risk among women in Central India and promotion of breastfeeding and identification of women with adverse reproductive profiles may facilitate early screening and risk reduction strategies.
Sriyansh Jain, R. Arjariya, Sunil Kumar Saxena et al.· Indian Journal of Pharmaceut...· 0 citations
Early menarche and low parity were more frequently associated with aggressive non-Luminal A molecular subtypes, highlighting the importance of reproductive history in breast cancer risk assessment and individualized management.
Resti Arania, Amirah Zhafira Rizqiyanda, Zaleha Ulfa et al.· THE JOURNAL OF Mother and Ch...· 0 citations
This pooled analysis of 15,731 cases showed that nulliparity, age at menopause, MHT, and BMI have independent, dose-response associations with ER, PR, and grade, clarifying patterns of etiologic heterogeneity.
Daniel Adams, Amber N. Hurson, T. Ahearn et al.· Journal of the National Canc...· 0 citations
To examine the associations between reproductive factors — parity, lactation duration, and menopausal age — and tumour characteristics, molecular subtype, and PC-RISK-5 prognostic scores in women with breast cancer from a tertiary centre in Kerala, India.
This retrospective cohort study included 221 women with invasive breast carcinoma diagnosed between January 2015 and June 2016 at a tertiary centre in Kerala, India. Molecular subtyping followed the St Gallen 2013 framework (Luminal A defined as Ki-67 <20%; HER2 3+ only). The PC-RISK-5 score assigned one point each for age >60 years, Ki-67 >30%, histological grade ≥II, lymph node positivity, and HER2 (IHC 2+/3+). Patients were stratified into three age bands (≤39, 40–65, >65 years). Associations were assessed using chi-squared, Kruskal–Wallis, and Mann–Whitney tests. Overall survival was analysed using Kaplan–Meier estimates with log-rank comparison. A two-sided
p
< 0.05 was considered statistically significant.
Among 221 women (mean age 55.7 years), invasive ductal carcinoma predominated (93.7%). Later menopausal age was associated with higher PC-RISK-5 scores (mean 2.27, 2.86, and 3.00 across <42, 42–50, and >50 years;
p =
0.028) and with greater nodal positivity (19%, 46%, and 57%;
p =
0.041). PC-RISK-5 scores differed significantly across molecular subtypes (
p =
0.0003), being highest in HER2-driven tumours. Lactation duration showed a non-significant trend toward lower triple-negative proportion with longer duration (25.9% to 14.9%;
p =
0.32). Parity, age at first childbirth, and reproductive factors overall showed no significant association with molecular subtype, grade, or survival.
In this Kerala cohort, most reproductive factors were not significantly associated with tumour biology or outcome. Later menopausal age was the notable exception, associated with higher prognostic risk and nodal involvement, consistent with prolonged oestrogen exposure. PC-RISK-5 scores varied with molecular subtype, although this partly reflects shared components.
Parvathy Chandra Kollamparambil, D. Ramakrishnan· South Asian Journal of Cance...· 0 citations
A meta-analysis of the existing literature was conducted to quantify breast cancer risk according to histologic subtype of benign breast disease (BBD) among women of diverse racial and ethnic backgrounds worldwide. PubMed (Medline), EMBASE (Emtree), and other relevant biomedical databases were searched through February 2026 to identify studies reporting the development of subsequent breast cancer in women diagnosed with either nonproliferative disease (NP), proliferative disease without atypia (PDWA), or atypical hyperplasia (AH). Seven studies met the eligibility criteria. Women of Asian ancestry with PDWA or AH had a substantially higher risk of breast cancer than those with NP. Among Black women, breast cancer risk associated with BBD subtypes was comparable to historically reported risks among White women, whereas associations among Hispanic women were less clear due to greater data limitations. The variable BBD-associated breast cancer risk across racial groups warrants confirmation and underscores the need for further investigation of the mechanisms underlying these differences.
A. Koric, Nusrat Preema, A. Anandarajah et al.· Research Square· 0 citations
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