Association of reproductive and menstrual factors with the risk of breast cancer in women: a population-based study.

BACKGROUND: Reproductive factors significantly impact the incidence of breast cancer (BC), a concerning trend. This study aims to reassess this association and provide recommendations for fertility policies to delay the onset of BC. METHODS: Utilizing data from a national survey, we applied weighted Cox and restricted cubic spline (RCS) methods to evaluate the impact of various modifiable and non-modifiable reproductive factors on breast cancer (BC) incidence. Interaction and subgroup analyses were conducted to investigate favorable fertility combinations and identify target populations. RESULTS: Our analysis included 15,938 cases, representing 63,247,160 women in the United States, with 4.06% diagnosed as BC survivors. Multiple models consistently demonstrated that a later age at menarche (AM), higher parities, and an earlier age at first birth (AFB) were associated with a delayed BC onset. Specifically, women with four or more parities experienced a 32% reduction in BC risk (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.48-0.95), while those with an AFB of 25 years or older faced a 51% increased risk (HR 1.51, 95% CI 1.17-1.94). Women with an AM of 13 years or older had a 26% decreased risk in multivariate Cox analysis. Restricted cubic spline (RCS) analysis revealed a negative linear relationship between parities and BC risk. However, interaction and subgroup analyses indicated that these factors were less impactful than an earlier AFB, particularly in the high-risk group, including individuals with early AM or long-term survivors, where no significant differences were observed. CONCLUSION: Among reproductive factors, both modifiable factors such as increased parity and earlier AFB, as well as the non-modifiable factor of later AM, delay the onset of BC. The effect of an earlier AFB in postponing BC onset are notably more pronounced compared to having more children, especially within specific high-risk cohorts.