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Pregnancy deemed safe in BRCA-mutated breast cancer survivors



– Pregnancy after breast cancer is safe in BRCA-mutated patients, according to a retrospective study.

Pregnancy did not affect disease-free or overall survival in a cohort of BRCA-mutated breast cancer patients. Additionally, fetal and pregnancy complications in this cohort were similar to complications observed in the general population.

“We believe that our findings provide reassurance for counseling young BRCA-mutated breast cancer patients inquiring about the feasibility and safety of future conception,” said Matteo Lambertini, MD, PhD, of Policlinico San Martino Hospital in Genova, Italy.

Dr. Lambertini presented the findings at the annual meeting of the American Society of Clinical Oncology.

He and his colleagues conducted an international, multicenter, retrospective cohort study of 1,252 patients. The patients had been diagnosed with stage I-III breast cancer between January 2000 and December 2012 at age 40 years or younger. All patients had BRCA mutations – 811 with BRCA1 alone, 430 with BRCA2 alone, and 11 with both.

Pregnant versus nonpregnant patients

At a median of 4.5 years after diagnosis, 195 patients (16%) had experienced a pregnancy.

Compared with the nonpregnant women, pregnant patients were younger (P less than .001), more likely to have a BRCA1 mutation (P = .01), have smaller tumors (P = .04), have node-negative disease (P = .003), and have hormone receptor–negative tumors (P = .002). Roughly 95% of patients in both cohorts had received chemotherapy, and the most common regimens were anthracycline or taxane based.

Compared with patients in the nonpregnancy cohort, those in the pregnancy cohort were less likely to receive tamoxifen alone as endocrine therapy (P = .002), were more likely to have a shorter duration of endocrine therapy (P less than .001), and were less likely to undergo salpingo-oophorectomy (P less than .001).

Pregnancy outcomes

“In terms of pregnancy, fetal, and obstetrical outcomes, no alarming signals were observed,” Dr. Lambertini said.

Most pregnant patients had a spontaneous pregnancy (82.1%), completed the pregnancy (76.9%), delivered at term (90.8%), and had no complications (86.6%). However, 10.3% of patients had a spontaneous abortion, 9.2% of pregnancies were pre term, and 1.8% of babies had congenital abnormalities.

“All these rates were highly comparable to rates that are expected in the general healthy population,” Dr. Lambertini said.

Survival analyses

The researchers performed two survival analyses. The first was a case-control approach in which they matched each pregnant patient with three controls (patients without pregnancy) according to the following:

  • Disease-free interval from breast cancer diagnosis (equal to or longer than that of pregnant patients).
  • Year at diagnosis (plus or minus 2.5 years).
  • Nodal status (negative vs. positive).
  • Hormone receptor status (positive vs. negative).
  • Type of BRCA mutation (BRCA1 vs. BRCA2).

The second survival analysis was an extended Cox model with pregnancy as a time-varying covariate.

Survival outcomes

At a median follow-up of 8.3 years, pregnant patients had better disease-free survival than nonpregnant patients in the case-control analysis, with a hazard ratio of 0.71 (P = .045). With the extended Cox model, the adjusted HR was 0.87 (P = .41). The analysis was adjusted for age, tumor size, nodal status, type of endocrine therapy, hormone receptor status, breast surgery, and BRCA mutation.

There was a significant interaction between type of BRCA mutation and pregnancy, with better disease-free survival observed in the BRCA1-mutated cohort. The HR was 0.53 in the BRCA1 cohort and 1.60 in the BRCA2 cohort (P less than .01). However, as Dr. Lambertini pointed out, only 44 pregnant patients had a BRCA1 mutation.

There was no significant interaction between hormone receptor status and pregnancy (P = .28).

Furthermore, there was no significant difference in overall survival between the pregnant and nonpregnant cohorts. In the case-control analysis, the HR was 0.86 (P = .65). In the extended Cox model, the adjusted HR was 0.88 (P = .66).

Dr. Lambertini disclosed a relationship with Teva.

SOURCE: Lambertini M et al. ASCO 2019, Abstract 11506.

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