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

Abstract & Commentary

Synopsis: The influence of breast feeding upon breast cancer development was examined in women who carry deleterious mutations of the BRCA gene. They found that one or more years of breast feeding in women with deleterious BRCA1 gene mutations was associated with a reduction in breast cancer risk of 45%, an effect that is much greater than that observed in the general population.

Source: Jernstrom H, et al. J Natl Cancer Inst. 2004; 96:1094-1098.

Breast cancer risk, in general, decreases with increasing duration of breast feeding. In the current report, the influence of breast feeding duration upon cancer development in women with BRCA1 or BRCA2 mutations was examined. For this, a case-control method was used. From an international registry of women with such BRCA mutations, breast cancer patients were compared with appropriately matched controls (women with BRCA mutations but without cancer). The study involved 965 cases and 965 paired controls. Among women with BRCA1 mutations, the mean total duration of breast feeding was significantly shorter for case subjects (breast cancer patients) than controls (6.0 vs 8.7 months, respectively; mean difference = 2.7 months; 95% confidence interval [CI] = 1.4-4.0; P < 0.001). The total duration of breast-feeding was associated with a reduced risk of breast cancer (for each month of breast feeding, odds ratio [OR] = 0.98; 95% CI = 0.97-0.99; P < 0.001). Women with BRCA1 mutations who breast-fed for more than 1 year were less likely to have breast cancer than those who never breast-fed (OR = 0.55; 95% CI = 0.38-0.80; P = 0.001). The number of cases/controls with BRCA2 mutations was less and no association between breast feeding duration and breast cancer development was demonstrable for this group.

Comment by William B. Ershler, MD

Jernstrom and colleagues observed that women carrying deleterious BRCA1 mutations had a reduced risk of breast cancer if they breast fed for 1 year or more. Unfortunately, in this study, the reasons for not starting, or for stopping breast feeding were not ascertained. Thus, as the authors speculate, it is possible that women who have trouble with breast feeding are particularly susceptible to breast cancer. Indeed, one study1 of women with nonhereditary breast cancer found that the risk of breast cancer was increased among women who tried to breast feed, but could not.

The data from this report support the conjecture, that breast cancer occurring in women with deleterious BRCA1 mutations are under the same, or similar, hormonal and reproductive influences as the occurrence of breast cancer in the general population. In fact, it was found that 1 or more years of breast feeding was associated with a reduction in breast cancer risk of 45%, an effect that is much larger than seen in the general population.2,3

The influence of breast feeding on breast cancer development remains incompletely explained, but certainly it may relate to changes in mammary gland differentiation or to effects on breast estrogen levels. There are a number of changes within the breast that occur during pregnancy, including the development of more well-differentiated alveolar lobules.4 It is known that BRCA1 is critical to both appropriate proliferation and differentiation within the mammary gland5 and it is possible that women with low levels of normal BRCA1 have increased breast epithelial cell proliferation in response to the increased estrogen of pregnancy.

Of course, this is an epidemiological finding from which clinical recommendations should be drawn with caution. However, a prospective, randomized trial of breast feeding duration in BRCA1 carriers would be logistically and ethically problematic. Thus, common sense will have to suffice. The data from this report are consistent with current understanding of breast cancer in general, and it is conceivable that the high risk of breast cancer development in BRCA1 mutation carriers may be reduced by successful breast feeding of one year or more. Furthermore, BRCA1 carriers who find that they are unable to breast feed may be at a particularly higher risk of cancer development. This latter concern may well be addressed by additional epidemiological investigation.

References

1. Yang CP. Am J Epidemiol. 1993;138:1050-1056.

2. Collaborative Group on Hormonal Factors in Breast Cancer. Lancet. 2002;360:197-195.

3. Narod SA. Nat Rev Cancer. 2002;2:113-123.

4. Russo J, et al. Breast J. 2001;7:278-291.

5. Marquis ST, et al. Nat Genet. 1995;11:17-26.

William B. Ershler, MD INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC is Editor of Clinical Oncology Alert.