Reproductive Factors and Risk of Breast Cancer by Tumour Subtypes Among Ghanaian Women: A Population-Based Case-Control Study

Abstract

Background: Women of African ancestry have a higher proportion of early-onset and oestrogen receptor (ER) negative cancers compared to women of European ancestry. Differences in risk factor distributions and associations by age at diagnosis and ER status might explain this disparity. Methods: We analysed data from 1,126 women with invasive breast cancer and 2,106 population controls aged 18-74 years recruited from three hospitals in Ghana from 2013-2015. Odds ratios (OR) and 95% confidence intervals (CI) were estimated for menstrual and reproductive factors using polytomous logistic regression models adjusted for potential confounders. Findings: Among controls, the medians for age at menarche, parity, age at first birth and breastfeeding/pregnancy were 15 years, 4 births, 20 years, and 18 months, respectively. For women >50 years, parity and extended breastfeeding were associated with decreased risks: >5 births vs. nulliparous, OR 0·40 (95% CI 0·20-0·83), and 0·71 (95% CI 0·51-0·98) for >19 vs. <13 breastfeeding months/pregnancy, which did not differ by ER. In contrast, for earlier onset cases (<50 years) parity was associated with increased risk for ER-negative tumours (p-heterogeneity by ER=0·02), which was offset by extended breastfeeding. Similar associations were observed by intrinsic-like subtypes. Less consistent relations were observed with ages at menarche and first birth. Interpretation: Reproductive risk factor distributions were different from European populations, but exhibited aetiologic heterogeneity by age at diagnosis and ER status similar to other populations. Differences in reproductive patterns and subtype heterogeneity are consistent with racial disparities in subtype distributions. Funding: Intramural program of the National Cancer Institute. Declaration of Interest: Authors have no conflicts of interest to declare. Ethical Approval: The study was approved by the Special Studies Institutional Review Board of the National Cancer Institute (Rockville, MD, USA), the Ghana Heath Service Ethical Review Committee and institutional review boards at the Noguchi Memorial Institute for Medical Research (Accra, Ghana), the Kwame Nkrumah University of Science and Technology (Kumasi, Ghana), the School of Medical Sciences at Komfo Anokye Teaching Hospital (Kumasi, Ghana), and Westat (Rockville, MD, USA). All participants provided written informed consent.