Breast cancer heterogeneity
Authors: Ntirenganya Faustin , Twagirumukiza Jean Damascene , Bucyibaruta Georges , Rugwizangoga Belson , Rulisa Stephen 
Published: November 2022

Background:Breast cancer (BC) is the most prevalent cancer in women and the leading cause of women's cancer-related deaths and morbidity worldwide. Conventionally considered as a single disease, recent advances suggest that BC is rather a heterogeneous disease with different molecular subtypes exhibiting distinct clinical presentation, anatomo-pathological features, response to treatment and survival outcomes. The purpose of this study was to compare tumor characteristics and epidemiologic risk factors associated with premenopausal versus postmenopausal BC and to assess heterogeneity by menopausal status.Methods:This was a comparative cross-sectional study. A total of 340 patients were included in the study (170 premenopausal vs. 170 postmenopausal BC). Patients' and tumor characteristics were compared in both populations. Percentages and means have been used for descriptive statistics. For categorical variables with comparison groups not exceeding 2, Fischer's exact test was used, otherwise, Chi-square test was used. For continuous variables, Mann–WhitneyU-test has been used to compare the numerical ranked variables. A value ofP= 0.05 or less was considered statistically significant. Odds ratio (OR) and 95% confidence interval (CI) was estimated using logistic regression analysis.Results:The median age of patients was 49 years (range: 18–89 years), with premenopausal median age of 41 years (range 18–50 years) and postmenopausal median age of 58 years (range 48–89 years). Factors associated more with the occurrence of premenopausal BC than postmenopausal BC were obesity/overweight in adolescence/early adulthood (OR = 0.29 95% CI 0.18–0.49,P< 0.001) and history of benign breast disease (OR 0.34 95% CI 0.14–0.83,P= 0.014), while factors associated more with postmenopausal than premenopausal BC included alcohol intake (OR = 2.47 95% CI 1.54–3.98,P< 0.001), history of breastfeeding (OR = 2.75 1.12–6.78,P= 0.036). However, sports activities (OR = 0.33 95% CI 0.16–0.65,P= 0.0015) and contraceptive use (OR = 0.19 95% CI 0.12–0.32,P< 0.001) seem to be protective for postmenopausal BC. In premenopausal period, patients presented more at advanced stages (Stage III and IV) (51.2% of premenopausal vs. 44.7% for postmenopausal,P= 0.0246), reported more intermediate-to-rapid disease progression (92% in premenopausal vs. 81.1% in postmenopausal (P< 0.001), had more invasive ductal carcinoma (98% in premenopausal vs. 93.5% in postmenopausal (P= 0.053) and had more poorly differentiated tumors (72% compared to 19.4% of postmenopausal BC patients (P< 0.0001). There was no statistically difference in molecular subtypes distribution between premenopausal and postmenopausal women (P= 0.062). However, progesterone receptor (PR) positivity was more associated with postmenopausal BC (P= 0.0165).Conclusion:BC is a heterogeneous disease. Premenopausal BC seems to be more aggressive than postmenopausal BC, with a relatively high prevalence of poorly differentiated and high-grade tumors with rapid progression. However, pre- and postmenopausal BC have similar molecular subtypes with different PR expression but similar ER and human epidermal growth factor receptor 2/Neu oncogene expression.