Pregnancy after breast cancer appears to be safe in patients with germline BRCA mutations—and particularly among those with BRCA1 mutations—according to new research.

Limited data are available on the safety of pregnancy and reproductive outcomes in patients with breast cancer and BRCA mutations, but an international cohort study conducted in Europe showed no decrements in disease-free or overall survival in a large cohort of women aged 40 years or younger with BRCA mutations who became pregnant after completing primary treatment for their breast cancer. In this cohort, 15.6% of women became pregnant following breast cancer treatment; maternal and fetal outcomes were similar to those observed in the general population.

Matteo Lambertini, MD, PhD

These findings were originally presented at the 2019 ASCO Annual Meeting by Matteo Lambertini, MD, PhD, of the University of Genova and IRCCS Policlinico San Martino Hospital, Italy, and colleagues.¹ The study was later discussed at Best of ASCO Austin by Elizabeth Wulff-Burchfield, MD, Assistant Professor in the Divisions of Medical Oncology and Palliative Medicine at the University of Kansas Medical Center, Kansas City,² along with other top selected abstracts in symptoms and survivorship.

The investigators maintain that these results are of paramount importance for fertility counseling in young patients with BRCA-mutated breast cancer. According to Dr. Wulff-Burchfield, they findings can impact clinical practice by enhancing patient conversations, but significant knowledge gaps remain, and they must still be disclosed and addressed with patients.

“Childbearing is extremely important to many of our young patients, both male and female,” she said. “But for women who have been treated for breast cancer and have a germline BRCA mutation, there are concerns that have not been previously addressed—specifically the idea that many of these women are candidates to undergoing risk-reducing surgery by the time they are still in childbearing years, and there is some suggestion in the literature that they may have a decreased ovarian reserve or fertility potential.”

Survival in Pregnant vs Nonpregnant Patients

This international, multicenter, retrospective cohort study included 1,252 women with invasive early-stage breast cancer with a BRCA1 and/or BRCA2 mutation (811 BRCA1, 430 BRCA2, 11 BRCA1 and BRCA2). BRCA healthy carriers, patients with metastatic disease and those with germline BRCA variants of unknown significance were excluded. The primary endpoints were disease-free survival and pregnancy rate. Secondary endpoints were overall survival, fetal and obstetric outcomes.

The median follow-up was 8.3 years. After a median of 4.5 years following diagnosis, 195 patients became pregnant.

“What is most noteworthy here is that there was not a statistically significant impact on disease-free survival in women who did become pregnant after completing primary breast cancer therapy,” said Dr. Wulff-Burchfield.

Patients who became pregnant and had a BRCA2 mutation had worse outcomes, but there were far fewer of these patients. “So it’s a little hard to draw conclusions,” she noted. Additionally, patients who became pregnant and had hormone receptor–positive cancer appeared to have slightly lower survival, though this did not reach statistical significance. In terms of overall survival, there was no clinical or statistical significance between the two cohorts, “which is excellent,” she noted.

Maternal and fetal outcomes were similar to the population at large. “But one thing I do think is important to note is that only 17.9% of these patients used assisted reproductive technology,” she said. “With that being a minority of the population, it’s difficult to conclude the extent to which that is safe in this BRCA-positive population.”

Study strengths include the large cohort, as well as a case-control design that was able to account for a number of possible confounding factors, Dr. Wulff-Burchfield said. “However, these data are observational, and I do think the follow-up is short for these young women who have hormone receptor–positive cancers,” she noted, adding that it is difficult to draw conclusions about outcomes in patients with BRCA2 mutations, and that “the jury is still out” regarding assistive reproductive technologies.

Are These Findings Practice-Changing?

According to Dr. Wulff-Burchfield, the clinical implications of these findings are limited. She maintains that the data have value in enriching the discussions physicians have with their younger patients, but because of the significant knowledge gaps, the findings “probably will not result in most of us proclaiming from the rooftops that pregnancy is perfectly safe and they can put their fears to rest.”

However, the data provide a good baseline from which to start a conversation about the safety of pregnancy in this specific population. “As long as we disclose the limitations in these data, I think we should be sharing them with our patients,” she said. ■

DISCLOSURE: Dr. Lambertini reported speaker’s honoraria from Theramex and Takeda. Dr. Wulff-Burchfield reported no conflicts of interest.

REFERENCES

1. Lambertini M, Ameye L, Hamy A-S, et al: Safety of pregnancy following breast cancer in patients carrying a BRCA mutation: Results of an international cohort study. 2019 ASCO Annual Meeting. Abstract 11506. Presented June 3, 2019.

2. Wulff-Burchfield EM: Symptoms and survivorship, including clinical applications for immune checkpoint inhibitor toxicities. 2019 Best of ASCO Austin. Presented July 27, 2019.