In a pooled analysis reported in JAMA Oncology,¹ Naoko Sasamoto, MD, MPH, of the Obstetrics and Gynecology Epidemiology Center, Brigham and Women’s Hospital, Boston, and colleagues found that breastfeeding, even for durations of 1 to 3 months per birth, was associated with a significant reduction in the risk for epithelial invasive ovarian cancers, including high-grade serous disease. As stated by the investigators, the study is, to their knowledge, the largest such analysis reported to date.

“Breastfeeding is a potentially modifiable factor that may lower risk of ovarian cancer independent of pregnancy alone….”

— Naoko Sasamoto, MD, MPH, and colleagues

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Study Details

The study was a pooled analysis of data from 9,973 parous women with ovarian cancer and 13,843 parous controls from 13 Ovarian Cancer Association Consortium case-control studies, with initial data collection at consortium sites occurring between November 1989 and December 2009. A single breastfeeding episode was defined as breastfeeding offspring from a given pregnancy. At the time of analysis, mean ages were 57.4 years for women with ovarian cancer and 56.4 years for controls. Overall, 89% of participants identified as white. Ever breastfeeding was reported by 5,981 cases (60%) and 9,417 controls (68%).

Key Findings

On multivariate analysis, ever breastfeeding vs no breastfeeding was associated with a significantly reduced risk of invasive ovarian cancer (odds ratio [OR] = 0.76), as well as a decreased risk of borderline tumors (OR = 0.72).

• For invasive tumors, the association was significant for high-grade serous (OR = 0.75), endometrioid (OR = 0.73), and clear cell tumors (OR = 0.78). A similar but not statistically significant risk reduction was observed for low-grade serous tumors. No significant association was observed for mucinous tumors. For borderline tumors, significant reductions in risk were observed for mucinous (OR = 0.68 and serous tumors (OR = 0.77).
• In stratified analyses, no significant effect modification was observed according to age, body mass index at young adulthood, history of endometriosis, or family history of ovarian cancer. Risk reduction for invasive cancer was significant among white women (OR = 0.73) but not among black (OR = 0.92) or Asian women (OR = 0.81; P for interaction = .01), who comprised a small minority of the study population.
• Compared with no breastfeeding, longer mean duration of breastfeeding per episode was inversely associated with invasive ovarian cancer risk. For a single breastfeeding episode, significant reductions in risk were observed for mean breastfeeding durations of 1 to 3 months (OR = 0.82), 3 to < 6 months (OR = 0.75), 6 to < 9 months (OR  = 0.69), 9 to < 12 months (OR = 0.66), and ≥ 12 months (OR = 0.66; P for trend = .001). Respective odds ratios (all statistically significant) for high-grade serous disease were 0.79, 0.76, 0.68, 0.68, and 0.66 (P for trend = .01).
• Among primiparous women, ever breastfeeding was associated with significantly reduced risk of all invasive disease (OR = 0.86) and high-grade serous disease (OR = 0.84). Similar associations were observed for all invasive disease and high-grade serous tumors among multiparous women.
• Compared with no breastfeeding, more recent breastfeeding was associated with a significant reduction in risk for invasive disease (OR = 0.56, for time since last breastfeeding of < 10 years). The magnitude of risk reduction was reduced over time but remained significant with the time since last breastfeeding of ≤ 30 years (OR = 0.83; P for trend = .02).
• Among women who breastfed, older age at first breastfeeding (OR = 0.90, per 5-year increase in age; P for trend = .001) and at last breastfeeding episode (OR = 0.94, per 5-year increase in age; P for trend = .02) was associated with a lower risk of invasive disease.
• Analysis in the five studies with data on exclusive breastfeeding showed significant reductions in the risk of invasive disease for both women who breastfed exclusively for ≥ 3 months (OR = 0.81) and those who breastfed but not exclusively for ≥ 3 months (OR = 0.70), compared with no breastfeeding.

With regard to the potential mechanisms involved in the association between breastfeeding and reduced ovarian cancer risk, the investigators observed: “To date, the leading hypothesis has been that ovulation suppression during breastfeeding inhibits epithelial cell division and proliferation, thereby reducing the opportunity to initiate or promote carcinogenesis. This may especially be pertinent in the first few months postpartum, when immune function and tumor surveillance mechanisms remain suppressed…. However, we observed a stronger inverse association with longer breastfeeding duration. Several lines of evidence suggest that breastfeeding may also be associated with long-term modulation of inflammatory, immune, or metabolic pathways, which could influence ovarian cancer risk.”

The investigators concluded: “Breastfeeding is associated with a significant decrease in risk of ovarian cancer overall and for the high-grade serous subtype. The findings suggest that breastfeeding is a potentially modifiable factor that may lower risk of ovarian cancer independent of pregnancy alone…. The World Health Organization recommends exclusive breastfeeding for at least 6 months and continued breastfeeding with complementary foods for 2 or more years…. Our results support these recommendations, while noting that breastfeeding fewer than 3 months per child is still associated with significant ovarian cancer risk reduction.” 

DISCLOSURE: The study was funded by the National Cancer Institute. For full disclosures of the study authors, visit jamanetwork.com.

REFERENCE

1. Babic A, Sasamoto N, Rosner BA, et al: Association between breastfeeding and ovarian cancer risk. JAMA Oncol. April 2, 2020 (early release online).