Premenopausal Breast Cancer Risk Factors and Associations with Molecular Subtypes: A Case-Control Study

Abstract

Background. Breast cancer (BC) is the most prevalent cancer in women and the leading cause of women’s cancer-related deaths and morbidity worldwide. In Rwanda, BC incidence is increasing with an unacceptably high mortality rate in premenopausal women. Objectives. The purpose was to identify modifiable BC risk factors and assess associations between common breast cancer risks factors and molecular subtypes in premenopausal women in Rwanda. Methods. This was a case-control study. Premenopausal women with histological confirmation of BC and frequency-matched for age controls were recruited. A preestablished questionnaire was administered to both cases and controls for sociodemographics, BC probable risk factors, and clinical and pathological characteristics. BC was classified into luminal A, luminal B, HER2-type, basal-like (triple negative), and unclassified molecular subtypes by immunohistochemistry (IHC). Odds ratio (OR) and 95% confidence interval (CI) were estimated using multivariate logistic regression analysis. Results. 340 participants were recruited into the study (170 cases vs. 170 controls). The median age was 39 years. The majority of cases presented at advanced stages of the disease (51.2% in stages III and IV) and had invasive ductal carcinoma (98.2%). 60.6% had subtypes of poor prognosis (HER2 enriched 14.7%, triple negative 12.9%, and unclassified 32.9%). Alcohol intake $\left(\text{AOR}=3.73,95\%CI2.19-6.32,p<0.001\right)$ , obesity/overweight in adolescence or early adulthood $\left(\text{AOR}=10.86,95\%CI4.82-24.4,p<0.001\right)$ , history of primary infertility $\left(\text{AOR}=33.8,95\%CI3.5-321.5,p=0.002\right)$ , nulliparity $\left(\text{AOR}=3.75,95\%CI1.61-8.75,p=0.002\right)$ , and a history of benign breast disease $\left(\text{AOR}=6.06,95\%CI1.19-30.73,p=0.03\right)$ were associated with the occurrence of premenopausal breast cancer. There was no significant difference between risk factor stratification per molecular subtype. Conclusion. Several reproductive, environmental, and lifestyle risk factors have been identified to be associated with premenopausal BC. Among them, alcohol intake and obesity/overweight during adolescence/early adulthood can be modified. Interventions targeting alcohol consumption and obesity/overweight in adolescents and young adults may decrease the incidence of premenopausal breast cancer.