Meeting NewsPerspective

Pregnancy after breast cancer feasible, safe for BRCA carriers

CHICAGO — Pregnancy after invasive early breast cancer appeared safe among women with BRCA mutations, according to results of an international cohort study presented at ASCO Annual Meeting.

“We know that family planning is a priority of concern for many young women with newly diagnosed breast cancer, and many prior studies from our group and others have shown that pregnancy after breast cancer is safe, including in women with hormone receptor-positive disease,” Matteo Lambertini, MD, adjunct professor at IRCCS Ospedale Policlinico San Martino in Genova, Italy, said during a presentation. “However, additional challenges exist for patients carrying the germline BRCA mutation. In fact, these patients are candidates to undergo prophylactic risk-reducing salpingo-oophorectomy at a young age due to an increased risk [for] ovarian cancer. In addition, importantly, to date we have very limited data on reproductive outcomes and safety of pregnancy following breast cancer in [women with BRCA mutations].”

In the international, multicenter, hospital-based, retrospective cohort study, Lambertini and colleagues evaluated 1,252 consecutive women aged 40 years and younger diagnosed between 2000 and 2012 with stage I to stage III BRCA-mutated breast cancer (BRCA1, n = 811; BRCA2, n = 430; BRCA1 and BRCA2, n = 11).

Pregnancy rate and DFS served as the primary endpoints, with OS and pregnancy outcomes as secondary endpoints.

Among these women, 195 became pregnant (pregnancy rate, 16%; 95% CI, 14-18) at a median of 4.5 years (interquartile range [IQR], 3.1-6.7) after breast cancer diagnosis. Median age at time of pregnancy was 35.7 years (IQR = 32.9 -38.6).

Women who had a pregnancy following breast cancer were significantly more likely to be younger and have ER-negative tumors. Sixteen patients (8.2%) had induced abortions and 20 (10.3%) had spontaneous abortions.

Of the 150 women (76.9%) who completed pregnancy, 13 (11.6%) experienced delivery complications, with congenital abnormalities reported in two cases (1.8%).
Researchers conducted two survival analyses to account for guarantee-time bias. One used a case-control approach matching pregnant and nonpregnant women in a 1:3 ratio according to standard prognostic factors, including disease-free interval, nodal and hormone receptor status, year at diagnosis and type of BRCA mutation. The second included all patients and used an extended Cox model with time-varying covariates.

At a median follow-up of 8.3 years (range, 8.1-8.7) for the case-control analysis, pregnant women had longer DFS (HR = 0.71; 95% CI, 0.51-0.99) and no difference in OS (HR = 0.86; 95% CI, 0.44-1.67) compared with nonpregnant women. In a subgroup analysis, the researchers found that this superior DFS was limited to pregnant patients with BRCA1 mutations (HR = 0.53; 95% CI, 0.35- 0.81). The extended Cox model with pregnancy occurrence as a time-varying covariate showed similar results for DFS (adjusted HR = 0.87; 95% CI, 0.61-1.23) and OS (adjusted HR = 0.88; 95% CI, 0.5-1.56).

“In our large, unique cohort of young BRCA-mutated patients, 16% of women had a pregnancy following breast cancer,” Lambertini said during the presentation. “It was a higher rate than expected and previously described in the overall breast cancer population, which probably reflected the very young age at the time of diagnosis for [women with BRCA mutations]. We believe that our findings provide reassurance for counseling young [patients with] BRCA-mutated breast cancer inquiring about the feasibility and safety of future conception.” – by Jennifer Byrne

Reference:

Lambertini M, et al. Abstract 11506. Presented at: ASCO Annual Meeting; May 31-June 4, 2019; Chicago.

Disclosures: Lambertini reports a consultant/advisory role with Teva Pharmaceuticals. Please see the abstract for all other authors’ relevant financial disclosures.

CHICAGO — Pregnancy after invasive early breast cancer appeared safe among women with BRCA mutations, according to results of an international cohort study presented at ASCO Annual Meeting.

“We know that family planning is a priority of concern for many young women with newly diagnosed breast cancer, and many prior studies from our group and others have shown that pregnancy after breast cancer is safe, including in women with hormone receptor-positive disease,” Matteo Lambertini, MD, adjunct professor at IRCCS Ospedale Policlinico San Martino in Genova, Italy, said during a presentation. “However, additional challenges exist for patients carrying the germline BRCA mutation. In fact, these patients are candidates to undergo prophylactic risk-reducing salpingo-oophorectomy at a young age due to an increased risk [for] ovarian cancer. In addition, importantly, to date we have very limited data on reproductive outcomes and safety of pregnancy following breast cancer in [women with BRCA mutations].”

In the international, multicenter, hospital-based, retrospective cohort study, Lambertini and colleagues evaluated 1,252 consecutive women aged 40 years and younger diagnosed between 2000 and 2012 with stage I to stage III BRCA-mutated breast cancer (BRCA1, n = 811; BRCA2, n = 430; BRCA1 and BRCA2, n = 11).

Pregnancy rate and DFS served as the primary endpoints, with OS and pregnancy outcomes as secondary endpoints.

Among these women, 195 became pregnant (pregnancy rate, 16%; 95% CI, 14-18) at a median of 4.5 years (interquartile range [IQR], 3.1-6.7) after breast cancer diagnosis. Median age at time of pregnancy was 35.7 years (IQR = 32.9 -38.6).

Women who had a pregnancy following breast cancer were significantly more likely to be younger and have ER-negative tumors. Sixteen patients (8.2%) had induced abortions and 20 (10.3%) had spontaneous abortions.

Of the 150 women (76.9%) who completed pregnancy, 13 (11.6%) experienced delivery complications, with congenital abnormalities reported in two cases (1.8%).
Researchers conducted two survival analyses to account for guarantee-time bias. One used a case-control approach matching pregnant and nonpregnant women in a 1:3 ratio according to standard prognostic factors, including disease-free interval, nodal and hormone receptor status, year at diagnosis and type of BRCA mutation. The second included all patients and used an extended Cox model with time-varying covariates.

At a median follow-up of 8.3 years (range, 8.1-8.7) for the case-control analysis, pregnant women had longer DFS (HR = 0.71; 95% CI, 0.51-0.99) and no difference in OS (HR = 0.86; 95% CI, 0.44-1.67) compared with nonpregnant women. In a subgroup analysis, the researchers found that this superior DFS was limited to pregnant patients with BRCA1 mutations (HR = 0.53; 95% CI, 0.35- 0.81). The extended Cox model with pregnancy occurrence as a time-varying covariate showed similar results for DFS (adjusted HR = 0.87; 95% CI, 0.61-1.23) and OS (adjusted HR = 0.88; 95% CI, 0.5-1.56).

“In our large, unique cohort of young BRCA-mutated patients, 16% of women had a pregnancy following breast cancer,” Lambertini said during the presentation. “It was a higher rate than expected and previously described in the overall breast cancer population, which probably reflected the very young age at the time of diagnosis for [women with BRCA mutations]. We believe that our findings provide reassurance for counseling young [patients with] BRCA-mutated breast cancer inquiring about the feasibility and safety of future conception.” – by Jennifer Byrne

Reference:

Lambertini M, et al. Abstract 11506. Presented at: ASCO Annual Meeting; May 31-June 4, 2019; Chicago.

Disclosures: Lambertini reports a consultant/advisory role with Teva Pharmaceuticals. Please see the abstract for all other authors’ relevant financial disclosures.

    Perspective

    Pregnancy following cancer has been a topic of substantial interest in recent years, and there is meaningful evidence to support the safety of pregnancy following early breast cancer. However, there has been little information in women who carry BRCA mutations who desire pregnancy following breast cancer. This is important because, frequently, these patients are young and are counseled to undergo risk-reducing salpingo-oophorectomy, and yet there’s been little information for clinicians to use to guide individual patients.

    This study specifically focuses on young women who carry BRCA mutations and become pregnant following an early breast cancer. It provides information indicating that it is safe and that the pregnancy does not appear to increase the risk for breast cancer recurrence in these patients. The bulk of the data comes from BRCA1 carriers. The security of the information on BRCA2 carriers is not quite as good, because there were relatively few BRCA2 carriers in this cohort.

    The study also demonstrated that despite the fact that many of these women had had standard treatment for their breast cancer, including chemotherapy, the outcomes of the pregnancy, including obstetrical complications and fetal or birth defects, don’t appear any different than in the general population. For clinicians who are guiding patients with early breast cancer who are genetically predisposed because they carry BRCA mutations, this is very helpful in assisting patients in thinking through this complex problem.

    • Darcy Spicer, MD
    • Keck School of Medicine of USC

    Disclosures: Spicer reports no relevant disclosures.

    See more from ASCO Annual Meeting