Breastfeeding and the Risk of Ovarian Cancer Among Women with BRCA Mutations

CQ #210 – November 9, 2020

by Anne Eglash MD, IBCLC, FABM

#LACTFACT

Breastfeeding is associated with a decreased risk of ovarian cancer among women with the BRCA1 or BRCA2 mutation.

Breastfeeding and the risk of epithelial ovarian cancer among women with a BRCA1 or BRCA2 Mutation

Gynecologic Oncology online Sept 30th 2020

Do women with the BRCA1 or BRCA2 gene mutations have a lower risk of ovarian cancer if they breastfeed?

Several well-designed studies, including at least 1 meta-analysis have concluded that breastfeeding is associated with a decreased risk of ovarian cancer. I reviewed a large meta-analysis on this topic in a CQW published in June 2019.

The question is whether breastfeeding also reduces the risk of ovarian cancer among women with the Breast Cancer Genes, AKA BRCA1 and BRCA2.

The recent article for this week’s CQW is an international study that included women with known BRCA1 or BRCA2 mutation, from 61 participating centers in 15 countries. These women sought genetic testing due to a family history of breast and/or ovarian cancer, or a personal history of breast cancer. Data collected included history of pregnancies/birthing, ever vs never breastfed, number of months they had breastfed, and contraception use. Approximately 2000 control subjects with BRCA1 or BRCA2 were matched with 1650 case subjects who developed ovarian cancer. The average age at time of diagnosis was 52 years.

The researchers found that the control group had significantly higher cumulative duration of breastfeeding (14.5 months) as compared to the women who developed ovarian cancer (13 months).

What do you think are other accurate statements regarding the association of ovarian cancer and breastfeeding among subjects with the BRCA1 and BRCA2 mutations, based on this data? Choose 1 or more:

Subjects who developed ovarian cancer were less likely to ever breastfeed.
Ever-breastfeeding was associated with a 23% reduction in the risk of ovarian cancer.
The longer a subject breastfed, the lower her risk of ovarian cancer, up until 7 months. Breastfeeding beyond 7 months did not add further protection.
Breastfeeding was associated with a greater risk reduction of ovarian cancer for women who completed childbearing under age 35 vs women who gave birth to an infant at age 35 or older.
Women who had a history of both breastfeeding and oral contraceptive use had the lowest risk for ovarian cancer.

See the Answer

Correct Answers: All except D

Breastfeeding and the risk of epithelial ovarian cancer among women with a BRCA1 or BRCA2 Mutation

Gynecologic Oncology online Sept 30th 2020

Joanne Kotsopoulos, Jacek Gronwald, Jeanna M. McCuaig, Beth Y. Karlan, Andrea Eisen, Nadine Tung, Louise Bordeleau, Leigha Senter, Charis Eng, Fergus Couch, Robert Fruscio, Jeffrey N. Weitzel, Olufunmilayo Olopade, Christian F. Singer, Tuya Pal, William D. Foulkes, Susan L. Neuhausen, Ping Sun, Jan Lubinski, Steven A. Narod, the Hereditary Ovarian Cancer Clinical Study Group

Abstract

Objective

BRCA mutation carriers face a high lifetime risk of developing ovarian cancer. The strong inverse association between breastfeeding and the risk of ovarian cancer is established in the general population but is less well studied among women with a germline BRCA1 or BRCA2 mutation.

Method

Thus, we conducted a matched case-control analysis to evaluate the association between breastfeeding history and the risk of developing ovarian cancer. After matching for year of birth, country of residence, BRCA gene and personal history of breast cancer, a total of 1650 cases and 2702 controls were included in the analysis. Conditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence intervals (CI) associated with various breastfeeding exposures.

Results

A history of ever-breastfeeding was associated with a 23% reduction in risk (OR = 0.77; 95%CI 0.66–0.90; P = 0.001). The protective effect increased with breastfeeding from one month to seven months after which the association was relatively stable. Compared to women who never breastfed, breastfeeding for seven or more months was associated with a 32% reduction in risk (OR = 0.68; 95%CI 0.57–0.81; P < 0.0001) and did not vary by BRCA gene or age at diagnosis. The combination of breastfeeding and oral contraceptive use was strongly protective (0.47; 95%CI 0.37–0.58; P < 0.0001).

Conclusions

These findings support a protective effect of breastfeeding for at least seven months among women with a BRCA1 or BRCA2 mutation, that is independent of oral contraceptive use.

IABLE Comment by Anne Eglash MD, IBCLC, FABM

Women in this study who had a child after age 35 benefited from a greater protective effect from breastfeeding than those who finished childbearing under age 35, 40% reduced risk vs 19%, respectively!

The finding that older women who breastfed had more protection from ovarian cancer vs women who were younger, was also found in a large collaborative analysis from 13 case-control studies.

The authors state that the common theory of fewer ovulatory cycles protecting from ovarian cancer may not fully explain these findings, and that maybe hormonal changes during breastfeeding play an additional role in the prevention of ovarian cancer.

In their discussion, the authors explain that as women age, premalignant cells accumulate in the ovary, due to the inflammation and genetic mutations that occur from cyclical ovulation. Some of these premalignant cells go on to become cancer. There is a lack of research exploring the effect of hormone changes during lactation on the propensity of these cells becoming cancerous.

An additional theory is that cells in the fallopian tube are a source of the most common type of ovarian cancer, which is why many women have their fallopian tubes removed rather than ligated for permanent contraception. A study that looked at the fallopian tubes of women who underwent routine ovarian and fallopian tube removal for cancer prevention found more precancerous changes in the fallopian tubes of women who had shorter breastfeeding (7.4 months) vs longer breastfeeding (14.5 months).

Given how we have no good means of screening for ovarian cancer, the importance of lactation ought to be stressed to all people who give birth as a powerful means of preventing ovarian cancer!