Study: Is it safe for BRCA mutation carriers to become pregnant following breast cancer?

IN-DEPTH REVIEW OF RESEARCH
Study background:

Several misconceptions concerning fertility preservation and pregnancy-related issues in breast cancer patients with BRCA mutations persist, even among health care providers who provide breast cancer care. For example, a study of physicians’ knowledge and practices towards fertility and pregnancy-related issues in young breast cancer patients showed that 45% of physicians did not believe pregnancy after breast cancer was safe for patients with a BRCA mutation. 

Following a breast cancer diagnosis, BRCA mutation carriers have a narrow window for pregnancy—this is often when they are considering risk-reducing salpingo oophorectomy and may also face a decreased ovarian reserve.  Focused research efforts can help in two areas: first, to address these patient issues and second, to improve physicians’ knowledge about post-treatment pregnancy for BRCA carriers and improve their awareness of available guidelines.

Researchers of this study wanted to know:

About the safety of pregnancy and reproductive outcomes for patients with a BRCA mutation with prior breast cancer history. 

Population(s) looked at in the study:

This study enrolled patients with early-stage, invasive breast cancer (stages, I, II or III) between January 2000 and December 2012. All patients were ≤40 years old and had a germline (inherited) BRCA mutation.

Of the 1,252 study participants, 811 had a BRCA1 germline mutation, 430 had a mutation in BRCA2, and 11 had a germline mutation in both BRCA1 and BRCA2. Most patients (95%) were treated wtih chemotherapy that consisted of anthracycline- and/or taxane-based regimens.

Study design:

This was a retrospective, hospital-based study. Primary endpoints in this study were pregnancy rate and disease-free survival; secondary endpoints included overall survival and pregnancy outcomes.

Study findings:  

Following a breast cancer diagnosis, 195 (16%) patients in this study became pregnant. Of these, 16 (8.2%) had an induced abortion and 20 (10.3%) had a spontaneous abortion. 

Pregnant patients were younger and had more ER-negative tumors.

• Among the 150 (76.9%) patients who conceived and completed pregnancy, 170 babies were born (7 pregnancies were ongoing at the time of the study and the outcomes of 2 pregnancies were unknown).
• For the 112 patients with pregnancy outcome data
  • Pregnancy complications were described for 13 (11.6%) patients.
  • Congenital anomalies were reported for 2 (1.8%) children (median follow-up was 8.3 years).
  • Pregnant patients had better disease-free survival compared to matched non-pregnant study participants.
  • No difference was observed in overall survival between pregnant and non-pregnant patients.
  • Pregnant patients with a BRCA1 mutation had better outcomes than patients with a mutation in BRCA2 or both BRCA1/2.

Of note, the rate of pregnancy and fetal complications observed in this study are similar to those observed for the general population.

Limitations:

Limitations of this study include:

• A limited median follow-up of disease-free and overall survival: just 8.3 years. At this time, long-term outcomes for these patients are unknown.
• All participating patients were followed at major medical centers where they likely received high-quality maternal and fetal care. Whether these results are applicable to patients who may not have a similar quality of care remains unknown.
• These results are specific to women who have a BRCA1 or BRCA2 mutation. It is unknown if they are also applicable for women with germline mutations in other high-risk breast cancer genes.

Conclusions:

This is the largest study to look at the safety of pregnancy and reproductive outcomes for breast cancer patients with a BRCA mutation. For these patients, pregnancy following breast cancer is safe, particularly for patients with a BRCA1 mutation.  Pregnancy does not appear to worsen fetal outcomes or maternal prognosis.  This study provides reassurance to breast cancer patients who have a BRCA mutation and are interested in future family planning.