Breastfeeding and the Risk of Breast Cancer in BRCA1 and BRCA2 Mutation Carriers

Joanne Kotsopoulos; Jan Lubinski; Leonardo Salmena; Henry T Lynch; Charmaine Kim-Sing; William D Foulkes; Parviz Ghadirian; Susan L Neuhausen; Rochelle Demsky; Nadine Tung; Peter Ainsworth; Leigha Senter; Andrea Eisen; Charis Eng; Christian Singer; Ophira Ginsburg; Joanne Blum; Tomasz Huzarski; Aletta Poll; Ping Sun; Steven A Narod

Disclosures

Breast Cancer Res. 2012;14(2):R42 

In This Article

Abstract and Introduction

Abstract

Introduction: Breastfeeding has been inversely related to breast cancer risk in the general population. Clarifying the role of breastfeeding among women with a BRCA1 or BRCA2 mutation may be helpful for risk assessment and for recommendations regarding prevention. We present an updated analysis of breastfeeding and risk of breast cancer using a large matched sample of BRCA mutation carriers.
Methods: We conducted a case-control study of 1,665 pairs of women with a deleterious mutation in either BRCA1 (n = 1,243 pairs) or BRCA2 (n = 422 pairs). Breast cancer cases and unaffected controls were matched on year of birth, mutation status, country of residence and parity. Information about reproductive factors, including breastfeeding for each live birth, was collected from a routinely administered questionnaire. Conditional logistic regression was used to estimate the association between ever having breastfed, as well as total duration of breastfeeding, and the risk of breast cancer.
Results: Among BRCA1 mutation carriers, breastfeeding for at least one year was associated with a 32% reduction in risk (OR = 0.68; 95% CI 0.52 to 0.91; P = 0.008); breastfeeding for two or more years conferred a greater reduction in risk (OR = 0.51; 95% CI 0.35 to 0.74). Among BRCA2 mutation carriers, there was no significant association between breastfeeding for at least one year and breast cancer risk (OR = 0.83; 95% CI 0.53 to 1.31; P = 0.43).
Conclusions: These data extend our previous findings that breastfeeding protects against BRCA1-, but not BRCA2-associated breast cancer. BRCA mutation carriers should be advised of the benefit of breastfeeding in terms of reducing breast cancer risk.

Introduction

In the general population, reproductive factors, including late age at menarche, parity and breastfeeding, have been shown to protect against the development of breast cancer.[1–3] Various proposed mechanisms include reducing lifetime exposure to ovarian hormones, reducing the cumulative number of ovulatory cycles and differentiation of the breast lobules.[4,5] We and others have evaluated the impact of reproductive factors in the etiology of BRCA-associated breast cancer, although the results are conflicting and vary by BRCA1 or BRCA2 mutation.[6–8] With respect to breastfeeding and breast cancer risk in BRCA1 mutation carriers, two previous studies reported no relationship[9,10] and three studies reported a protective effect.[11,12] One case-control study of BRCA2 mutation carriers reported no association between breastfeeding and breast cancer risk.[8]

We have previously reported in a study of 965 matched pairs that the total duration of breastfeeding was associated with a significant reduction in breast cancer risk among BRCA1, but not among BRCA2, mutation carriers.[11] The association was particularly strong for breastfeeding for more than one year (OR = 0.55; 95% CI 0.38 to 0.80). No association was seen for BRCA2 mutation carriers (OR = 0.95; 95% CI 0.59 to 1.59). Here we update the analysis of total duration of breastfeeding and risk of breast cancer using a larger sample of BRCA mutation carriers with the addition of 700 matched pairs. Because childbirth and breastfeeding are strongly correlated, we restricted the present analysis to parous women and we matched on parity to eliminate any potential confounding effect of parity.

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