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. We 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. The 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. In 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.

中文翻译：

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与肯尼亚乳腺癌患者分子亚型相关的乳腺癌危险因素

很少有研究通过分子亚型调查非洲土著人群的风险因素异质性，其中传统乳腺癌 (BC) 风险因素的患病率、遗传背景和环境暴露与欧洲血统人群相比有显着差异。我们对 2012 年 3 月至 2015 年 5 月期间从肯尼亚的 5 组公共、宗教和私人机构招募的 838 例病理确诊 BC 病例进行了仅病例分析。关键标志物（ER、 PR、HER2、EGFR、CK5-6 和 Ki67) 用于定义亚型。在诊断时通过问卷收集危险因素数据。多变量多分逻辑回归模型用于确定 BC 危险因素与肿瘤分子亚型之间的关联，根据临床特征和危险因素进行调整。初潮和第一次怀孕的中位年龄分别为 14 岁和 21 岁，孩子的中位数为 3 岁，母乳喂养时间为每个孩子 62 个月。管腔 A、管腔 B、富含 HER2 和三阴性 (TN) 乳腺癌的分子亚型分布分别为 34.8%、35.8%、10.7% 和 18.6%。调整协变量后，与 ER 阳性肿瘤患者相比，ER 阴性患者更有可能具有更高的胎次（OR = 2.03，95% CI = (1.11, 3.72)，p = 0.021，比较≥ 5 至≤ 2孩子们）。与管腔 A 肿瘤患者相比，管腔 B 患者更可能具有较低的胎次（OR = 0.45，95% CI = 0.23, 0.87，p = 0.018，比较≥ 5 至≤ 2 个儿童）；富含 HER2 的患者不太可能肥胖（OR = 0.36, 95% CI = 0.16, 0.81, p = 0.013) 或更年期（OR = 0.38, 95% CI = 0.15, 0.997, p = 0.049）。身体质量指数 (BMI)，无论是整体还是绝经状态，都没有因 ER 状态而显着变化。总体而言，不同亚型的累积或平均母乳喂养持续时间没有显着差异。在肯尼亚，我们发现胎次相关风险因素和 ER 状态之间的关联与在欧洲血统人群中的观察结果一致，但与 BMI 和母乳喂养的关联不同。需要在癌症病因学研究中纳入不同的人群，以制定特定人群和亚型的风险预测/预防策略。不同亚型的累积或平均母乳喂养持续时间没有显着差异。在肯尼亚，我们发现胎次相关风险因素和 ER 状态之间的关联与在欧洲血统人群中的观察结果一致，但与 BMI 和母乳喂养的关联不同。需要在癌症病因学研究中纳入不同的人群，以制定特定人群和亚型的风险预测/预防策略。不同亚型的累积或平均母乳喂养持续时间没有显着差异。在肯尼亚，我们发现胎次相关风险因素和 ER 状态之间的关联与在欧洲血统人群中的观察结果一致，但与 BMI 和母乳喂养的关联不同。需要在癌症病因学研究中纳入不同的人群，以制定特定人群和亚型的风险预测/预防策略。