Reproductive factors and risk of breast cancer by tumor subtypes among Ghanaian women: A population-based case-control study

Abstract

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. We analyzed data from 1,126 cases (aged 18-74 years) with invasive breast cancer and 2,106 controls recruited from a population-based case-control study in Ghana. Odds ratios (OR) and 95% confidence intervals (CI) were estimated for menstrual and reproductive factors using polytomous logistic regression models adjusted for potential confounders. 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. <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 tumors (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. 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.

Keywords: breast cancer; racial disparities; reproductive risk factors; subtype heterogeneity.

Figure 1:

Details of cases and controls for analysis of reproductive factors and breast cancer risk by tumour characteristics in the Ghana Breast Health Study

Figure 2:. Temporal trends of menstrual and reproductive risk factors for cases and controls in the Ghana Breast Health Study by birth cohorts from 1945 to 1975

(A) Age at menarche, (B) parity, (C) age at first birth and (D) median breastfeeding months per pregnancy. The means and standard deviations plotted are the results of a 3-point running average. Grey indicates standard deviation.

Figure 3:. ORs and 95% CIs for joint effects of parity and breastfeeding (vs nulliparous) by ER status and age of onset

Polytomous logistic regression models were used to calculate ORs and 95% CI, adjusted for age, education, study site, body size, family history of breast cancer, age at menarche, age at first birth, menopausal status and age at menopause. Error bars indicate standard deviations = breastfeeding. ER = Oestrogen receptor.