March 25, 2019
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Breast cancer risk among BRCA carriers influenced by timing, number of pregnancies

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The timing and number of full-term pregnancies appeared to influence the risk for breast cancer among women with BRCA1 or BRCA2 mutations, according to study results published in Journal of the National Cancer Institute Cancer Spectrum.

BRCA1 carriers who had only one full-term pregnancy and BRCA2 carriers who had fewer than four pregnancies demonstrated higher risk for breast cancer, results showed. However, risk among BRCA1 carriers appeared to decrease with longer durations of breastfeeding.

“What we have learned is that timing really matters for many risk factors, and the dual effect of pregnancy we see in nonmutation carriers with a long-term protection but short- term increase following a pregnancy may not extend to all women with BRCA1 and BRCA2 mutations, as the short-term increase and long-term protection may relate much more to the timing of these pregnancies,” Mary Beth Terry, PhD, professor of epidemiology and environmental health sciences at Mailman School of Public Health at Columbia University and Herbert Irving Comprehensive Cancer Center, said in a press release.

Terry and colleagues used weighted and time-varying Cox proportional hazards models to assess the impact of reproductive events on breast cancer risk among BRCA1 and BRCA2 mutation carriers. In separate and combined analyses, researchers evaluated a retrospective cohort that included 5,707 BRCA1 carriers and 3,525 BRCA2 carriers, and a prospective cohort of 2,276 BRCA1 and 1,610 BRCA2 carriers.

Among BRCA1 carriers, results showed no overall correlation of parity vs. nulliparity in terms of breast cancer risk (combined hazard ratio [HRc] = 0.99; 95% CI, 0.83-1.18).

However, compared with uniparity, risk appeared lower among women with multiple full-term pregnancies, including two (HRc = 0.79; 95% CI, 0.69-0.9), three (HRc = 0.7; 95% CI, 0.59-0.82), or four or more (HRc = 0.5; 95% CI, 0.4-0.63) pregnancies (P < .0001 for trend).

Longer duration of breastfeeding also was linked to decreased risk for breast cancer among BRCA1 carriers (combined cohort, P = .0003 for trend).

Researchers observed increased breast cancer risk from uniparity among BRCA1 carriers only in the prospective analysis (prospective HR =1.69; 95% CI, 1.09-2.62).

Among BRCA2 carriers, parity appeared associated with a 33% increase in breast cancer risk (HRc = 1.33; 95% CI, 1.05-1.69). Multiparity appeared associated with lower risk only among BRCA2 carriers who had at least four full-term pregnancies vs. one full-term pregnancy (HRc = 0.72; 95% CI, 0.54-0.98).

Advancing age at full-term pregnancy was associated with reduced breast cancer risk among BRCA1 carriers in the retrospective analysis only. BRCA2 carriers showed an increased risk for breast cancer with later age at first full-term pregnancy.

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The researchers noted limitations to their study, including being restricted to addressing only known risk factors that had been ascertained across all analyses.

“The hormonal upheaval that occurs during the first pregnancy may have a more or less important impact on the risk [for] breast cancer, depending on whether the first pregnancy occurs during periods of life at higher risk [for] developing a breast cancer or at a less high risk — periods shifted by about 10 years between BRCA2 and BRCA1 mutation carriers, with a later peak for BRCA2 mutation carriers,” senior author Nadine Andrieu, PhD, director of research at Institut National de la Santé et de la Recherche Médicale and at Institut Curie in Paris, said in the release. – by Jennifer Byrne

Disclosures: Terry and Andrieu report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.