CME Author: Vicki Brower
Study Authors: Hazel B. Nichols, Minouk Scheomaker, et al.
Target Audience and Goal Statement:
Obstetricians/gynecologists, mammographers, internal medicine physicians
The goal is to describe breast cancer risk in relation to childbirth, comparing that risk in women who have never had children with the risk in women who have given birth.
Study Synopsis and Perspective:
Generally, parity has been viewed as being protective against breast cancer, but this phenomenon may only pertain to the peak ages of breast cancer incidence — after age 60, post-menopause — and may not apply to younger women. Previous studies have demonstrated that recent childbirth gives women a short-term increase in breast cancer risk that may last for a decade or more, and which may be pronounced in those who give birth the first time at a later age. Evidence for this increased risk comes from a number of national registry-linkage studies in Scandinavian countries.
In the current study, researchers combined data from 15 prospective cohort studies of 890,000 women ages <55, which were part of the Premenopausal Breast Cancer Collaborative Group. Studies were conducted on women who did not have breast cancer at enrollment and were followed through direct contact or linkage with cancer registries.
They found that 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.
Specifically, when comparing nulliparous women to parous women, the 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.
Nichols and colleagues noted that parity is generally recognized as a protective factor for breast cancer, but also observed that “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.” Peak HRs for breast cancer associated with recent childbirth seemed to be higher with increasing age at first birth, and women in the youngest group at first birth (age <25) did not have an increased risk of breast cancer compared with women who had never given birth.
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.
Nichols and colleagues found approximately 18,800 cases of breast cancer were 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.
They also discovered that the association between time since most recent birth and breast cancer risk was modified by a family history of breast cancer (P=0.044). Researchers 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, researchers found that the association between time since most recent birth and breast cancer risk differed by ER status, and noted that 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.”
Annals of Internal Medicine Dec. 10,2018; DOI:10.7326/M18-1323
Study Highlights: Explanation of Findings
In this new study, women had a increased risk of breast cancer for 20 years after giving birth, peaking about 5 years post-partum, in comparison with women who did not have children.
In an accompanying editorial, Katrina Armstrong, MD, of Massachusetts General Hospital in Boston, acknowledged that the relationship between parity and breast cancer risk is “complex,” and that proving causality in an observational study “remains challenging.”
The fact that breast cancer is relatively rare in younger women and that a familial link is often present in younger women with breast cancer contributes to the complexity. “Increasing parity is understood to be protective for breast cancer,” she wrote, and added that while this study suggests that the relationship between childbirth and risk of breast cancer varies by time since birth, “they do not change the current consensus that parity is associated with lower risk for breast cancer, particularly after a decade or so since last childbirth.”
She summarized the study’s findings: “Overall the study estimated that 3 in 100 women will develop breast cancer between ages 41 and 50 years, a number that decreases to 2.8 for nulliparous women and increases to 3.1 for those who had a child 3 to 7 years earlier.”
She also described the clinical implications of these findings as “limited,” and wrote 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.”
The researchers found that risks for both ER-positive and ER-negative breast cancers were higher for 2 decades after the most recent birth in childbearing versus nulliparous women, regardless of their breastfeeding status. “With longer follow-up the expected inverse association between childbirth and breast cancer became apparent for ER-positive breast cancer, but risk remained elevated for ER-negative disease,” they stated.
The authors noted that these findings are consistent with a sustained increase in risk for ER-negative breast cancer for at least 25 years after birth in parous compared with nulliparous women, as reported in a pooled analysis of 4 U.S. studies that enrolled African-American women. “But the new study’s findings do not agree with that study’s report of no increase in ER-positive breast cancer in the first 15 years after last birth,” they wrote.
As familial breast cancer often occurs at a younger age, family history might modify associations between recent childbirth and breast cancer risk, they noted. Indeed, in their study, women who had a family history of breast cancer, and who had recently given birth, had a 3.5-fold increase in breast cancer risk in comparison with women with neither characteristic.
Study limitations included the fact that the calendar month was not available for all ages at childbirth and breast cancer diagnosis, so the authors 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.
Original story for MedPage Today by Molly Walker