Is Pregnancy Safe Following Breast Cancer for Patients With a BRCA Mutation?

Pregnancy following breast cancer appears to be safe for women with BRCA mutations, according to the results of a large international study (abstract 11506) presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.

“We know that family planning is a priority area of concern for many young women with newly diagnosed breast cancer,” said Matteo Lambertini, MD, PhD, of Policlinico San Martino Hospital at the University of Genova, who presented the results. “Prior work from our group and others have shown that pregnancy after breast cancer is safe, even among women with hormone receptor–positive disease. However, additional challenges exist for patient care with a germline BRCA mutation.”

Lambertini and colleagues conducted an international, multicenter, hospital-based, retrospective cohort study that included consecutive patients with invasive early breast cancer (stages I–III). Patients were ≤ 40 years of age at diagnosis and positive for known deleterious germline BRCA mutations. The primary endpoints were pregnancy rate and disease-free survival. The secondary endpoints were overall survival, as well as pregnancy, fetal, and obstetrical outcomes. 

“They also may have a reduced ovarian reserve and fertility potential even before starting anticancer therapies. So, their window for fertility and pregnancy can be particularly narrow,” said Lambertini.

A total of 1,252 women with breast cancer and a BRCA mutation were included in the study (BRCA1, 811 patients; BRCA2, 430; both, 11). At a median of 4.5 years (range, 3.1–6.7 years) after breast cancer diagnosis, the pregnancy rate was 16% (195/1,252; 95% CI, 14%–18%). Abortion rates were 8.2% (16/195) and 10.3% (20/195) for induced and spontaneous abortions, respectively. Thus, 150 women conceived (170 babies).

The investigators conducted two different survival analyses to account for guarantee-time bias. According to the study protocol, the first was a case-control comparison matching (1:3) pregnant and non-pregnant patients for prognostic factors: disease-free interval, year of diagnosis, nodal status, hormone receptor status, and type of BRCA mutation. The second was an extended Cox model with occurrence of pregnancy as a time-varying covariate that included all patients. 

After a median follow-up of 8.3 years (range, 8.1–8.7 years), patients who were pregnant had better disease-free survival (hazard ratio [HR], 0.71; 95% CI, 0.51–0.99; P = .045) compared with the controls; however, patient baseline characteristics showed that these patients were younger at the time of diagnosis, had more BRCA1 than BRCA2 mutations, had smaller tumors, had more hormone receptor–negative tumors, and more node-negative disease than patients in the non-pregnancy cohort.

The majority of patients in both cohorts received chemotherapy (both about 95%). Patients in the pregnancy cohort were less likely to receive tamoxifen alone (28.8% vs 45.4%; P = .002), more likely to receive tamoxifen plus an LHRH agonist (55.9% vs 30.2%; P = .002), and received a shorter duration of adjuvant endocrine therapy (median, 50 months vs 60 months; P < .001) compared with patients in the non-pregnancy cohort.

The median age at the time of pregnancy was 35.7 years (interquartile range, 32.9–38.6). Patients who were hormone receptor positive had a significant delay in the time from diagnosis to pregnancy (6.3 years vs 4.0 years; P < .001) compared with those who had hormone receptor–negative disease.

“It is possible that a large number of the women who intended to become pregnant had expressed that wish to their oncologist and then were subsequently screened for occult metastases, and if those women then decided not to become pregnant, that would greatly bias the results in favor of the pregnancy subgroup,” said Ellen Warner, MD, of Odette Cancer Center at Sunnybrook Health Sciences Center in Toronto, who was the discussant for the study.

In the pregnancy cohort, pregnancy complications and congenital anomalies occurred in 11.6% and 1.8% of cases, respectively, all of which, including the spontaneous abortion rate, are similar to the numbers expected for the general population, explained Lambertini.

There was no difference in overall survival between the two groups (HR, 0.86; 95% CI, 0.44–1.67; P = .65) in the case-control analysis. However, a subgroup analysis revealed that the improved disease-free survival rate was limited to the patients who had BRCA1 mutations (P-interaction < .01). The second analysis yielded similar results.

“It’s our duty in the oncology community to not only extend the length of life of our breast cancer patients but also to optimize their quality of life, and we can do this by avoiding overtreatment, minimizing acute and long-term toxicities of our treatments, and doing our utmost to enable these women to achieve their prediagnoisis goals and dreams safely,” concluded Warner.