Jan. 19, 2024 – A new study in the Journal of the American Medical Association presents hopeful findings about pregnancy among young breast cancer survivors whose genes not only carry a heightened cancer risk, but also risks of fertility problems. Among the nearly 5,000 women in the study, 22% became pregnant, most of them did so naturally, and for most, there was no evidence of an increased risk of breast cancer returning after pregnancy.
Researchers have sought to better evaluate the impact of pregnancy on breast cancer recurrence among carriers of BRCA gene mutations because reproductive counseling for the women can be complicated. The study authors noted that many women fear passing BRCA gene mutations to their children. The women’s genes can also impact reproductive factors like ovarian reserve, or the reproductive potential of their ovaries based on the quantity and quality of their eggs. Many affected women proactively have their ovaries and fallopian tubes removed due to a heightened risk of ovarian cancer, thus creating a narrow window of time to become pregnant between breast cancer treatment and preventive surgery.
Published last month, the findings showed a nearly identical risk of breast cancer recurrence among BRCA carriers who became pregnant, compared to those who did not. It’s the first large study to provide evidence of the safety of pregnancy among this group, said lead author Matteo Lambertini MD, PhD, noting that the only other study was a “very, very small” one from about 10 years ago.
The new analysis included 4,732 women age 40 or younger who had early-stage breast cancer and carried gene mutations known as BRCA1 or BRCA2, which are highly predictive of a woman developing breast cancer. During about an 8-year follow-up period, the researchers compared the breast cancer recurrence rate among the 659 women who became pregnant to that of the 4,073 who did not. The average age at diagnosis of breast cancer was 35 years old.
About 1 in 5 women in the study got pregnant within 10 years of diagnosis, although the pregnancy rate may not be an accurate measure of the odds of getting pregnant because it’s not known from the study how many were trying to do so. The women who got pregnant tended to be younger at cancer diagnosis, and the median age at delivery was just under 35. About 1 in 5 of the pregnancies involved assisted reproductive technology, such as in vitro fertilization, while the other 4 of 5 pregnancies occurred without medical assistance.
Among those who got pregnant, 45 had an induced abortion and 63 miscarried. The remaining 517 delivered at 37 weeks or later, and about 10% of the completed pregnancies were twins. The analysis showed the women had no increased risk of pregnancy complications, nor was there any increased risk for poor outcomes for the babies.
Nine out of 10 women in the study got chemotherapy as part of their cancer treatment, which is notable because of its link to infertility.
“Patients who had a pregnancy had significantly better breast cancer-specific survival and overall survival,” the authors wrote.
“Most of the time, patients with a pregnancy tend to have better outcomes,” said Lambertini, who is an associate professor of oncology at the University of Genova in Italy. “I don’t want to pass the message that the pregnancy is protective, but I’m saying that pregnancy for sure does not increase the risk of recurrence.”
Lambertini said the main message about this study’s findings should be about the safety of pregnancy because “there are many oncologists in the clinic who are still telling their patients not to have a pregnancy because of this concern that there may be an increased risk of recurrence, so the main message is that pregnancy does not increase the risk of recurrence.”
“Potentially, something we have discussed in the paper, is it could be that those patients with a better prognosis are those patients that will have a pregnancy later on, and those patients with worse prognosis may be the patients who have a relapse in the first few years after diagnosis so they will never be able to have a pregnancy,” Lambertini said.
Other possibilities for the improved survival data could be the details related to the type of cancer the pregnant women had, or possibly related to the women’s immune systems.
“We know that during pregnancy, there are a lot of immune system changes,” Lambertini said.
The BRCA gene mutations are linked to a much higher risk of getting breast cancer, particularly in both breasts. About 13% of women in the general population will have breast cancer at some point during their lives, but studies show that more than half of BRCA1 carriers and at least 45% of BRCA2 carriers will get breast cancer, according to the National Cancer Institute. The mutations also carry an increased risk of ovarian cancer and are linked to cancers occurring at younger ages.
About half of the women in the study got risk-reducing salpingo-oophorectomy, which is the removal of the ovaries and fallopian tubes. Among women with a pregnancy, 43% eventually had the procedure; among those without a pregnancy, 53 had the procedure.
The authors cautioned that the analysis did reveal some differences in risks based on whether a woman had the BRCA1 or BRCA2 gene mutation, which could be related to specific things about the type of breast cancer a woman had. The BRCA2 carriers tended to have a higher recurrence rate, and they also were more likely to have cancer sensitive to hormones like estrogen. But when researchers looked at all of the women in the study who had hormone-sensitive cancer, there was no overall increased risk of recurrence, ultimately suggesting that reproductive counseling for BRCA carriers should be individualized, based on the details of each person’s specific cancer diagnosis.
“Overall, I would say this study shows pregnancy is safe, but for patients with a BRCA2 mutation, I would be a bit more cautious,” Lambertini said, noting that he may advise his own BRCA2 patients who have hormone-sensitive cancer to first have 5 years of specialized hormone therapy to reduce the risk of recurrence, such as taking the drug tamoxifen, before deciding to try to get pregnant.
