Introduction: Breast cancer (BC) is the most common cancer among women in South Africa (SA), with an age-standardised incidence rate of 52.6 and an age-standardised mortality rate of 16.0 per 100,000 population. There is a paucity of evidence on the risk factors for BC among women of all races in SA. Given the rising prevalence of BC in SA, literature-based evidence is critical for the appropriate dissemination of preventative measures. This study aimed to identify the risk factors associated with the development of BC among women in Ekhuruleni Metropolitan Municipality.

Methods: An unmatched case-control study was conducted from 1 January 2017 to 31 December 2020 using secondary data extracted from the Ekurhuleni Population-Based Cancer Registry. Unconditional multivariable logistic regression analysis was carried out using the adjusted odds ratio (aOR). The variables race, employment, human immunodeficiency virus (HIV), smoking and alcohol status were included in the multivariable logistic regression model while the model was adjusted for age.

Results: A total of 2,217 cases and 851 controls were enrolled in the study. The mean age (±SD) in years was 55.7 (±15.2). The White population group, being self-employed and being HIV positive was significantly associated with reduced odds of BC development. HIV-positive women were 61% less likely to have BC than women who were HIV-negative (aOR 0.39; 95% confidence interval (CI): 0.27‒0.57). White women were 65% less likely to have BC than women of other races (aOR 0.35; 95% CI: 0.29‒0.43). Self-employed women were 59% less likely to have BC than women who were formally employed (aOR 0.41; 95% CI: 0.18‒0.97). No evidence of association was observed between tobacco smoking and BC as well as alcohol consumption and BC.

Conclusion: There was a 65% reduction in BC risk among White women compared to other races. HIV-positive women demonstrated a 61% lower likelihood of BC while self-employed women showed a 59% reduced risk of developing BC. These findings suggest that being White, self-employed or HIV-positive may provide some protection against BC. However, additional research is needed to validate these results and establish the underlying reasons behind these associations.