Abstract
BackgroundFew studies have investigated risk factor heterogeneity by molecular subtypes in indigenous African populations where prevalence of traditional breast cancer (BC) risk factors, genetic background, and environmental exposures show marked differences compared to European ancestry populations.MethodsWe conducted a case-only analysis of 838 pathologically confirmed BC cases recruited from 5 groups of public, faith-based, and private institutions across Kenya between March 2012 to May 2015. Centralized pathology review and immunohistochemistry (IHC) for key markers (ER, PR, HER2, EGFR, CK5-6, and Ki67) was performed to define subtypes. Risk factor data was collected at time of diagnosis through a questionnaire. Multivariable polytomous logistic regression models were used to determine associations between BC risk factors and tumor molecular subtypes, adjusted for clinical characteristics and risk factors.ResultsThe median age at menarche and first pregnancy were 14 and 21 years, median number of children was 3, and breastfeeding duration was 62 months per child. Distribution of molecular subtypes for luminal A, luminal B, HER2-enriched, and triple negative (TN) breast cancers was 34.8%, 35.8%, 10.7%, and 18.6%, respectively. After adjusting for covariates, compared to patients with ER-positive tumors, ER-negative patients were more likely to have higher parity (OR = 2.03, 95% CI = (1.11, 3.72), p = 0.021, comparing ≥ 5 to ≤ 2 children). Compared to patients with luminal A tumors, luminal B patients were more likely to have lower parity (OR = 0.45, 95% CI = 0.23, 0.87, p = 0.018, comparing ≥ 5 to ≤ 2 children); HER2-enriched patients were less likely to be obese (OR = 0.36, 95% CI = 0.16, 0.81, p = 0.013) or older age at menopause (OR = 0.38, 95% CI = 0.15, 0.997, p = 0.049). Body mass index (BMI), either overall or by menopausal status, did not vary significantly by ER status. Overall, cumulative or average breastfeeding duration did not vary significantly across subtypes.ConclusionsIn Kenya, we found associations between parity-related risk factors and ER status consistent with observations in European ancestry populations, but differing associations with BMI and breastfeeding. Inclusion of diverse populations in cancer etiology studies is needed to develop population and subtype-specific risk prediction/prevention strategies.
Highlights
Few studies have investigated risk factor heterogeneity by molecular subtypes in indigenous African populations where prevalence of traditional breast cancer (BC) risk factors, genetic background, and environmental exposures show marked differences compared to European ancestry populations
Fifty-four percent of patients were diagnosed under 50 years of age, 69% had Body mass index (BMI) ≥ 25 kg/m2 at diagnosis and 61% lived in rural areas
Compared to patients admitted to the other 4 hospital groups, Aga Khan University (AKU) patients were more likely to be overweight or obese (79%), have tertiary education level (45%), start the first pregnancy ≥ 25 years (35%), have < 3 children (39%), and have shorter breastfeeding duration per child, which is as expected given that AKU is a private health facility, and compared to the others, patients are generally from a higher socioeconomic status
Summary
Few studies have investigated risk factor heterogeneity by molecular subtypes in indigenous African populations where prevalence of traditional breast cancer (BC) risk factors, genetic background, and environmental exposures show marked differences compared to European ancestry populations. There is variation in the relative survival (RS) from BC by stage and country-level human development index (HDI) in sub-Saharan Africa (SSA) with the 5-year RS after breast cancer diagnosis in Mauritius at 83.2% and the lowest in Uganda at 12.1%, while it ranges between 40.1 and 64% in Kenya as per data abstracted from the Eldoret and Nairobi Cancer Registries, respectively [2]. Survival differences in SSA remain for any given breast cancer stage with the lowest 3-year breast cancer-specific survival observed in Nigeria at 38% compared with 68% in Black women from Namibia, underlying as yet unexplained risks with survival [3]. Advanced stage at presentation, lack of awareness about BC and limited access to available screening and treatment options [5] are contributing factors to disparate mortality rates, whether incidence for more aggressive breast cancers are higher in African women remains controversial. Women of African descent present with BCs a decade earlier than their Caucasian counterparts [6, 3], and despite correcting for risk factor distribution, their tumors still tend to be estrogen receptor (ER) negative [7], suggesting the interplay of other biologic and genetic differences that remain largely unexplored
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