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Study Identifies Modifiers of Breast and Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

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Key Points

  • Risk of breast cancer was reduced by later age at first live birth in BRCA1 mutation carriers and increased by smoking in BRCA2 mutation carriers.
  • Risk of ovarian cancer was reduced by breast-feeding and tubal ligation in BRCA1 mutation carriers and by oral contraceptive use in BRCA1/2 mutation carriers.

In a systematic review and meta-analysis reported in the Journal of the National Cancer Institute, Friebel et al attempted to identify factors that appear to modulate risk of breast and ovarian cancer in women who have inherited BRCA1 or BRCA2 mutations. Although the ability to perform meta-analysis was limited by small sample sizes for many potential factors, many of which had data available from only single studies, the findings indicated potential effects of age at first live birth and smoking for breast cancer and of breastfeeding, tubal ligation, and oral contraceptive use for ovarian cancer.

Study Details

The analysis included 44 studies that met predefined quality criteria, including case-control studies and prospective and retrospective cohort studies. When sufficient data were available for potential modifying factors, fixed effects meta-analyses were performed using hazard ratios or odds ratios (ORs) to estimate pooled effect estimates (ES) and 95% confidence intervals (CIs).

Breast Cancer Risk

Later age at first live birth was associated with reduced risk of breast cancer in BRCA1 mutation carriers, with women aged ≥ 30 years having reduced risk vs younger women (ES = 0.65, 95% CI = 0.42–0.99) and women aged 25 to 29 years having reduced risk vs younger women (ES = 0.69, 95% CI = 0.48–0.99). In BRCA2 carriers, a pooled estimate showed an increased risk of breast cancer for > 4 years vs never-smokers (ES = 1.97, 95% CI = 1.43–2.72), although an ever- vs never-smoker meta-analysis showed no increased risk (ES = 0.94, 95% CI = 0.74–1.19).

Ovarian Cancer Risk

Although meta-analyses could not be performed due to insufficient data, available evidence suggested reduced risk of ovarian cancer in BRCA1 carriers for ever vs never breastfeeding (OR = 0.74,  95% CI = 0.56–0.97)  and for > 1 year vs never breastfeeding (OR = 0.64, 95% CI = 0.47–0.91). Similarly, although meta-analysis could not be performed due to differences in study design, three studies showed significant 20% to 61% reductions in risk of ovarian cancer in BRCA1 carriers by who had tubal ligation.

Although meta-analysis could not be performed, studies consistently showed significantly reduced risk of ovarian cancer in BRCA1 carriers (33%–80% reduction with use > 1 year) and BRCA2 carriers (58%–63% reduction with ever use) with oral contraceptive use.

The investigators concluded, “Data assessing many potential risk modifiers are inadequate, and many have not been externally validated. Although additional studies are required to confirm some associations, sufficient information is available for some risk factors to be used in risk counseling or lifestyle modification to minimize cancer risk in BRCA1/2 mutation carriers.”

Timothy Rebbeck, PhD, of University of Pennsylvania School of Medicine, is the corresponding author for the Journal of the National Cancer Institute article.

The study was supported by grants from the Basser Center, University of Pennsylvania School of Medicine.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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