Breast Cancer Risk Tied to Pregnancy History

Women's risk of breast cancer was highest about 5 years after childbirth, and lasted more than 20 years, compared with women who have never given birth, and breastfeeding did not appear to attenuate the risk, a large pooled analysis found.

When comparing nulliparous women to parous women, an increased risk of breast cancer peaked at about 5 years after giving birth (HR 1.80, 95% CI 1.63-1.99) and lasted around 20 years, reported Hazel B. Nichols, PhD, of the University of North Carolina Gillings School of Global Public Health in Chapel Hill, and colleagues.

Moreover, this association was not modified by breastfeeding, and varied according to estrogen receptor (ER) expression, age at first birth, parity, and family history, the authors wrote in the Annals of Internal Medicine.

They noted that parity is recognized as a protective factor for breast cancer, but "this may largely apply to the peak ages of incidence (after age 60)" and not younger women. The authors cited prior studies that found recent childbirth "confers a short-term increase in breast cancer risk" that may last ≥10 years, and "may be amplified in women who are older at first birth."

Researchers combined data from 15 cohort studies, which were part of the Premenopausal Breast Cancer Collaborative Group. Studies were conducted on women ages <55 who did not have breast cancer at enrollment and were followed through direct contact or linkage with cancer registries.

All 15 studies included attained age, age at first and most recent births, and parity at study enrollment, while 12 assessed pregnancy history after enrollment, and 12 had breastfeeding status available. Thirteen studies apiece had information on family history, reported breast cancer stage, and ER status.

There were around 18,800 cases of breast cancer diagnosed before age 55 among about 890,000 women. About 720,000 women were parous at enrollment, and about 72,000 contributed ≥1 birth during follow-up. Mean age at study entry was around 42, and last update of pregnancy information occurred at a mean age of 50.

Overall, when compared with nulliparous women, the highest risk of breast cancer peaked at 4.6 years after birth, and decreased to its lowest point (HR 0.77, 95% CI 0.67-0.88) at around 35 years after birth. They noted that the crossover in risk occurred about 24 years after birth.

However, the authors found an association between time since most recent birth and breast cancer risk was modified by family history of breast cancer. They also noted "significant heterogeneity in the association between time since most recent birth and breast cancer risk according to age at first birth... and parity... but not breastfeeding."

In addition, the association between time since most recent birth and breast cancer risk differed by ER status, the authors said, noting risk for ER-negative breast cancer was highest about 2 years after birth (HR 1.77, 95% CI 1.34-2.33), declining at about 34 years after birth (HR 1.38, 95% CI 101-1.88), "but did not cross over to a protective association," they noted. The authors also said that ER-positive breast cancer accounted for 76% of breast cancer cases and the pattern "was similar to the overall results."

In an accompanying editorial, Katrina Armstrong, MD, of Massachusetts General Hospital in Boston, described the clinical implications of these findings as "limited," and that it could help "identify the mechanisms linking this risk to reproductive history," which would hopefully lead to identify "novel targets for risk reduction."

Armstrong further commented that in general, this does not mean patients who recently had a child "should make different decisions about breast cancer diagnosis, screening, or prevention," except perhaps in the cases of when women in their 40s should begin mammography screening.

"A multiparous woman who did not have a child before age 25 years and had a child in her late 30s might choose to begin screening at age 40 years instead of waiting until age 50 years," she wrote. "Eventually, time since last childbirth may be included in risk prediction models for breast cancer, thereby enabling a robust evaluation of whether the additional information increases the ability of the models to discriminate between women at clinically meaningful risk thresholds."

Study limitations included the fact that calendar month was not available for all ages at childbirth and breast cancer diagnosis, so they could not distinguish cases of breast cancer diagnosed during pregnancy from those diagnosed in the months immediately postpartum. They also noted that breastfeeding information was not specific to each birth, so there was the potential for misclassification of the most recent birth if women breastfed some children, but not others.