Using Scottish cancer registry data linked to maternity health records, we show that parity, number of births and time since last birth to diagnosis of breast cancer differ by IHC-defined molecular subtypes of breast cancer among women ≤ 50 years of age at diagnosis of breast cancer. Breast cancer aetiology in younger women is not fully understood as few risk factors have been identified. Furthermore, few opportunities for early detection of breast cancer are available for younger women beyond genetic counselling for high-risk families.

Multiple reports and pooled analyses have recently evaluated IHC and mRNA expression profiling defined molecular subtypes of breast cancer and consistently show a positive association with parity for triple-negative or basal-like breast tumours [15,16,17,18,19,20]. Interestingly, significant differences in the incidence of breast cancer exist for different ethnic and racial groups that also frequently have different reproductive histories [21]. Consistent with these data, we also found evidence of heterogeneity in reproductive history across IHC-defined molecular subtypes of breast cancer in this Scottish cohort. Women with ER- tumours (HER2-overexpressed and TNBC) were more likely to have a higher number of births compared to women with luminal A-like subtype. Unlike ER- cancers, we did not observe heterogeneity in number of births between luminal B-like (HER2+) and luminal A-like, which concurs with other reports [22,23,24,25]. Time since last birth showed differential associations by subtype, where women with TNBC or luminal B-like (HER2+) were less likely than women with luminal A-like tumours to have a longer time between their most recent birth and diagnosis of breast cancer. Findings for TNBC correspond well with the existing studies [26, 27].

Parity confers a dual effect on the risk of breast cancer with an augmented risk observed in the initial years following pregnancy (3–5 years, or even up to 10–15 years) [28,29,30], possibly by stimulating the growth of cells that have undergone initial stages of malignant change and also due to the immunosuppressive effects of pregnancy [28, 31]. It is only subsequent to this phase that the protective effect of parity sets in [32, 33] owing to the differentiation of normal breast cells that have the potential to undergo malignant transformation. While this has been observed for ER+ breast cancers (luminal A-like) [8, 22, 34], an increased risk of ER- breast cancer continues to persist even in the longer term [25, 27, 35]. Our results did not observe significant differences across subtypes for age at first birth. However, TNBC cases were more likely to have a younger age at first birth when compared to luminal A-like cases (approximately 16% versus 12.5% patients for age at first birth < 20 years). A similar, statistically significant association has been reported by other studies [22, 23, 35,36,37]. Luminal B-like (HER2−) cases showed no statistically significant difference from luminal A-like for either of the three risk factors of interest even though studies have reported an inverse association with number of births and a positive association with age at first birth for this subtype [38, 39].

ER- breast cancers are less likely than ER+ breast cancers to be detected through screening [40], and predictive modelling of breast cancer risk has been proposed as possible solution for personalised medicine and risk stratified screening [41,42,43]. Modelling studies using UK data suggest such risk stratified screening approaches could reduce overdiagnosis, improve cost-effectiveness, while maintaining the benefits of screening [44].

The key strengths of our study are the high-quality longitudinal data collected within the Scottish Cancer Registry for the entire population, and the availability and high level of completeness of molecular marker and tumour grade data (≤ 10% missing data). Another strength of the study is the inclusion of women diagnosed at age 50 years or below. Although breast cancer is less common within this age range, the tumours are more aggressive with poor prognosis making it important to identify and implement effective approaches to prevention amongst this age group [45]. Moreover, breast cancer incidence appears to be increasing in younger age groups in recent years in Scotland [11] and other populations such as the United States [46].

Although this is one of the largest studies of breast cancer among young women, a limitation is the modest number of cases for rarer tumour subtypes, especially HER2-overexpressed (5% of all cases), potentially reducing the statistical power of analyses for these tumour subtypes. Our study did not assess incidence or risk of breast cancer, which would require comparisons to controls/general population. In addition, we cannot exclude some residual confounding by age at diagnosis since we did observe some association with age and missing subtype data. Future work including a comparison cohort of women not diagnosed with breast cancer would add further updated information about the role of reproductive history as a risk factor for breast cancer, including, in due course for whose breast cancer is diagnosed at older ages. Other limitations of our study were the potential for incomplete maternity records for women whose children were born outside Scotland, lack of availability of data for other factors such as breastfeeding as well as for a more detailed mRNA expression or mutation profiling of the cancers.

In conclusion, our data highlight the value of integrating molecular data from tumours with routinely collected health records data for understanding cancer epidemiology. There is scope for future analysis using the cancer registry linked to other datasets, including community prescription records, and primary care records, to provide more detailed information on the role and patterns of key risk factors and possible new aetiologic or prognostic factors for subtypes of breast and other cancers.