# Reclassifying Menopausal Breast Cancer and Assessing Non-Genetic Risk Factors in Ghanaian Women: Insights from a Cohort Study

## TL;DR

This study reclassifies breast cancer in Ghanaian women based on local menopausal age and finds reproductive factors like early childbirth are linked to lower risk.

## Contribution

The study redefines premenopausal/postmenopausal breast cancer classifications for Ghanaian women using a local menopausal age of 48 instead of the global standard of 50.

## Key findings

- Nulliparity increased the odds of early-onset breast cancer by 13.5-fold.
- First birth after age 23 doubled the odds of premenopausal breast cancer.
- Reproductive and lifestyle factors like menarche, alcohol, and breastfeeding were not associated with premenopausal breast cancer in this cohort.

## Abstract

Breast cancer is a multifactorial disease, with racial variations often observed in its presentation. These variations are influenced by population-specific risk factors and reproductive health characteristics. Menopausal age is used as a basis for classifying breast cancer, with most studies using 50 years as a proxy for the global menopausal age. However, menopause tends to occur relatively earlier in Indigenous African populations. Considering the younger age structure and menopausal age in Ghanaian women, this study reclassified premenopausal and postmenopausal breast cancer within a cohort, using the average menopausal age of 48 years observed in Ghanaian women. We then compared the disease presentation between both classifications and evaluated the association between modifiable and nonmodifiable risk factors and premenopausal breast cancer. This study emphasises the potential of public education in reducing advanced breast cancer presentation in Ghanaian women and highlights the need to profile the genetic risk factors to understand its molecular basis in this population.

Background/Objectives: Breast cancer incidence is increasing in younger Ghanaian women. However, few epidemiological studies have evaluated the modifiable risk factors in this population. Additionally, these studies have classified breast cancer in Ghanaian women based on the global menopausal case classification. This study reclassified premenopausal and postmenopausal breast cancer in a Ghanaian cohort, assessing the risk factors using the observed menopausal age in Ghanaian women of 48 years, rather than the global standard of 50 years. Methods: Women diagnosed with breast cancer and scheduled for surgery from December 2018 to March 2023 were recruited across four hospitals in Ghana for the Ghana Breast Cancer Omics Project (BCOPGh), and data were collected using a questionnaire. Cross-tabulation and linear regression were used to evaluate the relationships between categorical variables and age at diagnosis. Results: Out of a total of 262 women recruited, 34.4% were classified as having premenopausal breast cancer, while early-onset breast cancer (EOBC) accounted for 14.9% of all cases. The molecular subtypes were predominantly hormone receptor (HR)-positive (61%) while triple-negative breast cancer (TNBC) accounted for 16%. The tumours were predominantly at stage II (62%) and grade 2 (51%), with invasive carcinoma NST (56%) being the most common subtype. Within this cohort, nulliparity increased the odds of EOBC by 13.5-fold, while having a first birth after the age of 23 doubled the odds of premenopausal breast cancer. Reproductive factors (menarche and menopause) and lifestyle (alcohol intake, smoking, contraceptive use, and breastfeeding duration) were not associated with premenopausal breast cancer in this cohort. About 13% of participants reported a family history of breast cancer, and 79% had prior knowledge of the disease. Conclusion: This study supports previous reports of the relatively higher incidence of aggressive disease in young Ghanaian women and the protective effect of early age at first birth. It further underscores the need to investigate its genetic underpinnings, whilst highlighting the importance of public education on self-examination techniques to reduce advanced disease presentation in Ghanaian women.