Abstract

BackgroundBecause birth size appears to be positively associated with breast cancer risk, we have studied whether this risk may differ according to molecular breast cancer subtypes.MethodsA cohort of 22,931 women born 1920–1966 were followed up for breast cancer occurrence from 1961 to 2012, and 870 were diagnosed during follow-up. Archival diagnostic material from 537 patients was available to determine molecular breast cancer subtype, specified as Luminal A, Luminal B (human epidermal growth factor receptor 2 (HER2)-), Luminal B (HER2+), HER2 type, and Triple negative (TN) breast cancer. Information on the women’s birth weight, birth length and head circumference at birth was used to estimate hazard ratios (HR) with 95% confidence intervals (CI) for each molecular subtype, applying Cox regression, and stratified by maternal height.ResultsBirth length (per 2 cm increments) was positively associated with Luminal A (HR = 1.2, 95% CI, 1.0–1.3), Luminal B (HER2+) (HR = 1.3, 95% CI, 1.0–1.7), and TN breast cancer (HR = 1.4, 95% CI, 1.0–1.9). No clear association was found for birth weight and head circumference. The positive associations of birth length were restricted to women whose mothers were relatively tall (above population median).ConclusionWe found a positive association of birth length with risk of Luminal A, Luminal B (HER2+) and TN breast cancer that appears to be restricted to women whose mothers were relatively tall. This may support the hypothesis that breast cancer risk is influenced by determinants of longitudinal growth and that this finding deserves further scrutiny.

Highlights

  • Because birth size appears to be positively associated with breast cancer risk, we have studied whether this risk may differ according to molecular breast cancer subtypes

  • Birth length was positively associated with risk of Luminal A breast cancer (HR = 1.2, 95% confidence intervals (CI), 1.0–1.3), Luminal B (HER2+) breast cancer (HR = 1.3, 95% CI, 1.0–1.7), and Triple negative (TN) breast cancer (HR = 1.4, 95% CI, 1.0–1.9), but there were no clear associations with Luminal B (HER2-) and Human epidermal growth factor receptor 2 (HER2) type (p for heterogeneity 0.8)

  • The results restricted to the subset of women with information on maternal height and the adult risk factors age at first birth and parity were similar to the main results, for some categories, the number of participants was low in the subset analysis

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Summary

Introduction

Because birth size appears to be positively associated with breast cancer risk, we have studied whether this risk may differ according to molecular breast cancer subtypes. The hypothesis that breast cancer may originate in utero is based on the fact that the mammary gland, which is not fully developed at birth, is exposed to high levels of intrauterine mammotropic hormones [11, 12]. This may increase the mammary gland-specific stem cell pool and eventually, the likelihood for cancer initiation later in life [13]. Birth size may be positively associated with breast cancer risk later in life [17]

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