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 AOR = 3.73 , 95 % C I 2.19 − 6.32 , p < 0.001 , obesity/overweight in adolescence or early adulthood AOR = 10.86 , 95 % C I 4.82 − 24.4 , p < 0.001 , history of primary infertility AOR = 33.8 , 95 % C I 3.5 − 321.5 , p = 0.002 , nulliparity AOR = 3.75 , 95 % C I 1.61 − 8.75 , p = 0.002 , and a history of benign breast disease AOR = 6.06 , 95 % C I 1.19 − 30.73 , p = 0.03 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.

Delineation of Pathogenomic Insights of Breast Cancer in Young Women

“…The results indicated that the ratios of BC subtypes did not differ significantly between the three age groups ( Figure 6 a). This observation is not in line with previous data that showed a high prevalence of TNBC/basal-like cancer in BCYW [ 12 ], presumably due to the use of a minimum log 2-fold change in computing our findings in the present study. Figure 6 b demonstrates the numbers of upregulated and downregulated genes in each of four intrinsic breast tumor subtypes and gene overlaps among the three age groups.…”

“…Studies have shown that BCYW is generally more aggressive with a poorer prognosis than BC in older patients [ 16 , 17 , 18 ]. A high prevalence of TNBC, basal-like tumors, and luminal B exists in BCYW [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. However, the effect of cancer subtypes on the genome of women with BC aged ≤40 years remains poorly studied.…”

“…The range of clinical characteristics exhibited in BCYW is distinct from that exhibited in older premenopausal and postmenopausal women with BC; thus, BCYW could be considered a subset of premenopausal diseases. BCYW exhibits more aggressive cancer subtypes (such as TNBC/basal, HER2-positive, and luminal B) than BC in older patients [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. The prognosis of BCYW is generally worse than that of BC in older patients, presumably due to its aggressive subtypes, detection at an advanced stage, and a high recurrence rate [ 1 , 6 , 15 , 16 , 17 , 18 , 19 ].…”

Diagnostic efficacy of physical examination and radiological findings in palpable breast masses

“…Breast cancer is associated with various risk factors such as aging, family history, early menarche, late menopause, late age at first pregnancy, and nulliparity. Moreover, excessive alcohol consumption increases dietary fat intake, and a sedentary lifestyle can increase the risk of breast cancer [9]. Aging is one of the most relevant risk factors for the occurrence of breast cancer.…”

Accuracy and Utility of Preoperative Ultrasound-Guided Axillary Lymph Node Biopsy for Invasive Breast Cancer: A Systematic Review and Meta-Analysis

“…At present, no clear therapeutic factors for breast cancer have been found. It is generally believed that pathogenic factors are family history and genetics [ 18 ], endogenous estrogen, exogenous estrogen, radiation exposure, benign breast disease and breast cancer in situ, alcohol intake, caffeine intake through coffee and tea [ 3 ], weight gain or overweight, sedentary, diet dominated by meat and sweets, and insufficient vitamin intake [ 19 , 20 ]. Early detection and treatment are very important [ 21 ].…”