Although early-stage disease is highly curable, most ovarian cancers are diagnosed at later stages due to a lack of effective screening. As a result, less than 50% of women survive beyond 5 years. Improving prevention by identifying modifiable risk factors could dramatically change the outcome of this disease. Epidemiologic studies have shown that parity, oral contraceptive use, and tubal ligation can alter the risk of ovarian cancer.
Breastfeeding has been suggested as another potentially modifiable risk factor for ovarian cancer; however, the literature on this association has been uneven and is limited by small sample sizes and the heterogeneity of ovarian cancer subtypes. Indirect support for the association of breastfeeding and ovarian cancer is the observation that ovarian cancer incidence rates have declined over the past 4 decades, coincident with the increasing use of oral contraceptives and breastfeeding.1
“Public health efforts to overcome barriers to breastfeeding could provide a significant contribution to the prevention of ovarian cancer.”— Mary B. Daly, MD, PhD
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Data Support Breastfeeding in Preventing Ovarian Cancer
The work of Babic et al,2 recently published in JAMA Oncology and reviewed in this issue of The ASCO Post, used a pooled analysis of 9,973 cases and 13,848 controls from 13 case-control studies participating in the Ovarian Cancer Association Consortium to evaluate the association between breastfeeding and ovarian cancer. They found breastfeeding was associated with an overall 24% lower risk of ovarian cancer, adjusting for oral contraceptive use and independent of parity. The association was seen both for invasive and borderline tumors. The reduction in risk was seen with as few as 1 to 3 months of breastfeeding and increased with the duration of breastfeeding. The reduction in risk was greatest for more recent breastfeeding, but the effect persisted for decades.
This finding is consistent with two recent meta-analyses.3,4 Although these studies suffer from heterogeneity of design and the biases inherent in retrospective data, two factors support the assumption that the association between breastfeeding and ovarian cancer is plausible. The extent of risk reduction, the dose-response relationship, and the long duration of protection observed are all consistent across these studies. In addition, the extent of risk reduction afforded by breastfeeding is similar to that attributed to parity and use of oral contraceptives, suggesting a similar underlying biologic mechanism. Together, they support breastfeeding as an important public health strategy to reduce the risk of ovarian cancer.
Questions Remain, Answers Needed
However, some questions remain. Despite decades of epidemiologic studies examining the association between breastfeeding and ovarian cancer, the underlying physiologic mechanisms to explain the effect are not known. The fact that just 3 months of breastfeeding can have a significant and long-lasting impact on ovarian cancer risk suggests a powerful mechanism that permanently alters the ovarian milieu.
A leading theory has long been the “incessant ovulation” hypothesis, whereby continued ovulation causes rupture and trauma to the surface epithelium of the ovaries, stimulating cell proliferation and malignant transformation. Any interruption of ovulation, such as induced by breastfeeding, pregnancy, or oral contraceptive use, could lower the risk of ovarian cancer.5 Other potential mechanisms invoked are the suppression of gonadotropins; alteration of reproductive hormones; and modulation of inflammatory, immune, or other metabolic pathways.2,6 Further research is needed to elucidate the mechanism(s) involved in reducing the risk of ovarian cancer by breastfeeding. This could potentially provide alternative interventions to breastfeeding for women who cannot or will not breastfeed or even for nulliparous women.
Now Another Reason to Encourage Breastfeeding
Breastfeeding has many positive health benefits for both mother and child and, from a public health perspective, may offer an opportunity to prevent a highly fatal disease. Breastfeeding rates in the United States decreased in the 20th century due to the widespread introduction of and heavy marketing strategies for baby formula as a more convenient alternative. However, this trend began to reverse around 1970, with the appreciation of the health hazards of formula feeding, such as childhood obesity and diabetes.7
The American Academy of Pediatrics recommends exclusive breastfeeding for 6 months and continued breastfeeding for at least 12 months. However, currently, less than 50% of infants are breastfed for 6 months, and less than 27% are breastfed for 12 months.6 Working mothers face particular challenges to breastfeeding. They include short or nonexistent paid maternity leave; lack of sufficient facilities for breastfeeding or pumping milk; and lack of support from workplace supervisors and co-workers.8
There will never be a prospective randomized clinical trial to measure the effect of breastfeeding on ovarian cancer incidence. As a modifiable risk factor, breastfeeding has few adverse effects and many beneficial effects for mothers and infants. Given the lack of effective screening for ovarian cancer and its high case-fatality rate, public health efforts to overcome barriers to breastfeeding could provide a significant contribution to the prevention of ovarian cancer. It may be time for health-care providers and proponents of breastfeeding to add the potential to reduce ovarian cancer to their advice to new mothers.
Dr. Daly works in the Department of Clinical Genetics and serves as Director of the Risk Assessment Program at Fox Chase Cancer Center, Philadelphia.
DISCLOSURE: Dr. Daly reported no conflicts of interest.
REFERENCES
1. Torre LA, Trabert B, DeSantis CE, et al: Ovarian cancer statistics, 2018. CA Cancer J Clin 68:284-296, 2018.
2. Babic A, Sasamoto N, Rosner BA, et al: Association between breastfeeding and ovarian cancer risk. JAMA Oncol. April 2, 2020 (early release online).
3. Sung HK, Ma SH, Choi JY, et al: The effect of breastfeeding duration and parity on the risk of epithelial ovarian cancer: A systematic review and meta-analysis. J Prev Med Public Health 49:349-366, 2016.
4. Li DP, Du C, Zhang ZM, et al: Breastfeeding and ovarian cancer risk: A systematic review and meta-analysis of 40 epidemiological studies. Asian Pac J Cancer Prev 15:4829-4837, 2014.
5. Fathalla MF: Incessant ovulation: A factor in ovarian neoplasia? Lancet 2:163, 1971.
6. Modugno F, Goughnour SL, Wallack D, et al: Breastfeeding factors and risk of epithelial ovarian cancer. Gynecol Oncol 153:116-122, 2019.
7. Stevens EE, Patrick TE, Pickler RP: A history of infant feeding. J Perinat Educ 18:32-39, 2009.
8. Johnston ML, Esposito N: Barriers and facilitators for breastfeeding among working women in the United States. J Obstet Gynecol Neonatal Nurs 36:9-20, 2007.
