Reproductive Factors and Risk of Breast Cancer by Tumor Subtypes among Ghanaian Women: A Population-based Case-control Study

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Abstract
Background: Higher proportions of early-onset and estrogen receptor (ER) negative cancers are observed in women of African ancestry than in women of European ancestry. Differences in risk factor distributions and associations by age at diagnosis and ER status may explain this disparity. Methods: We analyzed data from 1,126 women (aged 18–74 years) with invasive breast cancer and 2,106 population controls recruited from three hospitals in Ghana from 2013 to 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. Results: Among controls, 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. P -heterogeneity by ER = 0.02), which was offset by extended breastfeeding. Similar associations were observed by intrinsic-like subtypes. Less consistent relationships were observed with ages at menarche and first birth. Conclusion: Reproductive risk factor distributions are different from European populations but exhibited etiologic 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. Key Messages: Distribution of intrinsic-like breast cancer subtypes among Ghanaian women are distinct compared to European ancestry populations, with a higher proportion of ER-negative subtypes at younger ages. Increasing number of births and extended breastfeeding were associated with reduced risk for both ER-positive and ER-negative subtypes among later-onset breast cancer cases (women age ≥50 years). Extended breastfeeding offset a direct association that we observed of multiparity with early-onset (women age <50 years) ER-negative breast cancers. Number of births and breastfeeding duration are much higher in Ghanaian women compared to women of European ancestry and African Americans, however the relationships with risk are consistent when assessed by molecular subtype.
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