Background: Breast cancer incidence is much higher in Western than Eastern populations, with rates in the UK nearly three times those in China. Studies among Western populations have shown that lower parity, later age at childbearing and use of oral contraceptives were associated with a higher breast cancer risk, while limited prospective evidence is available from Chinese women who have different reproductive profiles.

Objectives: This study compares parity, age at childbearing, and use of oral contraceptives between Chinese and UK women and examines their associations with breast cancer risk.

Methods: We analyzed data from three prospective cohort studies: the China Kadoorie Biobank (CKB, 300,824 women aged 30–79, recruited between 2004 and 2008 from 10 regions in China), the Million Women Study (MWS, 1.3 million women aged 50-64, recruited between 1996 and 2001 through invitations for routine breast screening in the UK), and the UK Biobank (UKB, 273,402 women aged 40–69, recruited between 2006 and 2010 from 22 centers in the UK). Cox proportional hazard models were used to calculate hazard ratios (HRs) for parity, age at first birth, time since last birth, use of oral contraceptives, and duration of use, adjusted for socio-demographic and anthropometric characteristics, lifestyles, family history of cancer, and other reproductive factors. Meta-analysis was used to pool HRs across cohorts, and heterogeneity was assessed using Cochran’s Q test. Subgroup analyses were further conducted by menopausal status.

Results: Three cohorts included ~1.8 million women and ~100,000 incident breast cancer cases over 31.6 million person-years of follow-up. Almost all women in CKB were parous (98.72%), a proportion higher than MWS (89.31%) and UKB (81.41%). On average, women in CKB had a younger age at first birth (23.38 [3.19]) and at last birth (27.31 [4.20]) compared with those in UKB (25.93 [5.15] and 30.09 [5.19]) and MWS (23.80 [4.28] and 28.48 [4.76]). Women in CKB also had a lower prevalence of oral contraceptive use history (9.63%) and a shorter duration of usage (3.54 [4.64] years on average) than women in UKB (81.34%, 10.69 [7.99] years) and MWS (58.82%, 6.84 [5.71] years). A higher parity was associated with a lower breast cancer risk in all cohorts, with CKB women having a greater magnitude (HR 0.85 [0.79-0.93] per birth) than UKB (HR 95 [0.92-0.98] per birth) and MWS (HR 0.95 [0.94-0.96] per birth). Higher age at first birth was associated with a higher breast cancer risk (pooled HR 1.06 [1.05-1.07] per 5 years), and longer time since last birth was associated with a lower risk (pooled HR 0.95 [0.94-0.96] per 5 years) in all cohorts without significant heterogeneity. A longer duration of oral contraceptive use was associated with a higher breast cancer risk in CKB (HR 1.02 [1.00-1.04] per year), and in UKB for only pre-menopausal breast cancer (HR 1.03 [1.02-1.05] per year).

Conclusions: The differences in distributions of childbearing and use of oral contraceptives, and their associations with breast cancer risk between UK and Chinese women, may help explain the disparities in breast cancer incidence between the two populations.

Association between childbearing factors and breast cancer risk in 3 cohorts and meta-analysis