Reproductive history differs by molecular subtypes of breast cancer among women aged ≤50 years in Scotland in 2009-16: A population-based retrospective cohort study

Abstract

Background The aetiology of breast cancers diagnosed ≤ 50 years of age remains unclear. We aimed to compare reproductive risk factors between molecular subtypes of breast cancer thereby suggesting possible aetiologic clues, using routinely collected cancer registry and maternity data in Scotland. Methods We conducted a population-based retrospective cohort study of 4,108 women aged ≤ 50 years with primary breast cancer diagnosed between 2009–2016 linked to maternity data. Molecular subtypes of breast cancer were defined using immunohistochemistry (IHC) tumour markers, oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), and tumour grade. Age-adjusted logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association of number of births, age at first birth and time since last birth with IHC-defined breast cancer subtypes: luminal A-like, luminal B-like (HER2-), luminal B-like (HER2+), HER2-overexpressed and triple negative breast cancer (TNBC). Results Mean (SD) for number of births, age at first birth and time since last birth was 1.4 (1.2) births, 27.2 (6.1) years and 11.0 (6.8) years, respectively. Luminal A-like was the most common subtype (40%), while HER2-overexpressed and TNBC represented 5% and 15% of cases, respectively. Larger numbers of births were recorded among women with TNBC (p-trend = 0.05) and HER2-overexpressed (p-trend = 0.03) compared with luminal A-like tumours. Women with their most recent birth > 10 years prior to being diagnosed were less likely to have TNBC or luminal B-like (HER2+) tumours compared to luminal A-like (p-trend = 6X10− 6 and 0.01, respectively. We found limited evidence for differences by subtype with age at first birth. Conclusion Number of births and time since last birth differed by subtypes of breast cancer among women aged ≤ 50 years. Analyses using linked routine electronic medical records by molecularly defined tumour pathology data can be used to investigate the aetiology and prognosis of cancer.