Breast cancer survivors of child-bearing age appear to have a more difficult time becoming pregnant than the general population, and when they do become pregnant, they have a higher risk of preterm labor and need for cesarean section. Fortunately, most women deliver healthy babies, but they are more likely to be low birth weight or small for gestational age compared with newborns in the general population, especially if the mothers were exposed to chemotherapy during breast cancer treatment. Breast cancer survivors who became pregnant did not have compromised disease-free survival or overall survival compared to breast cancer survivors without subsequent pregnancy.
These findings of a large systematic review and meta-analysis were presented at the 2020 San Antonio Breast Cancer Symposium by the study’s first author, Eva Blondeaux, MD, of IRCCS Policlinico San Martino Hospital, Genoa, Italy.1 “Results of this meta-analysis provide reassuring evidence on the feasibility and safety of conceiving in women with a history of breast cancer,” she said.
Eva Blondeaux, MD
Although the data are reassuring, “the reduced chance of future conception among breast cancer survivors raises awareness of offering complete oncofertility counseling at diagnosis to all young women,” Dr. Blondeaux said. She noted that current guidelines do include recommendations for complete oncofertility counseling in patients with breast cancer who are of child-bearing age, and they do not discourage women from becoming pregnant after completing breast cancer treatment.
The aim of the study was to assess the chances of pregnancy in breast cancer survivors compared with the general population and survivors of other cancers; the reproductive outcomes in this population, including complications, delivery outcomes, and fetal outcomes; and to report maternal safety (ie, disease-free survival and overall survival). The meta-analysis included 39 studies with no language restrictions with a total of 114,573 patients with breast cancer and 8,093,401 women from the general population. The meta-analysis included retrospective and prospective case-control and cohort studies that included women undergoing pregnancy after breast cancer. Of the 114,573 patients with breast cancer, 7,505 had a pregnancy after diagnosis and 107,068 did not.
Looking at the chances of pregnancy among breast cancer survivors, the investigators compared data from 48,513 breast cancer survivors with data from 3,289,113 women from the general population. A pooled analysis found that patients with breast cancers were 60% less likely to become pregnant (P < .001). Compared with other cancer survivors, only those with cervical cancers were less likely to become pregnant than breast cancer survivors. Overall, cancer survivors were less likely to become pregnant compared to the general population.
Reproductive outcomes were compared among 3,240 patients with breast cancer and 4,814,452 women from the general population. No differences were found in spontaneous and induced abortion or pregnancy complications. Breast cancer survivors were at a 14% increased risk for cesarean section (P = .007). However, offspring of breast cancer survivors were at a 50% increased risk for having low birth weight (P < .001), a 45% increased risk for preterm birth (P = .006), and a 16% increased risk for being small for gestational age (P = .039).
Fortunately, offspring of breast cancer survivors were not at increased risk for congenital defects, and breast cancer survivors who were pregnant did not have an increased risk of pregnancy complications, including spontaneous or induced abortion, gestosis, antepartum or postpartum hemorrhage, compared with the general population.
In a separate analysis of the three fetal outcomes by receipt or nonreceipt of chemotherapy, all three fetal outcomes were increased in women exposed to chemotherapy, while no major impact was found for those not treated with chemotherapy. The risk of low birth weight was increased by 62%, and the risk of small for gestational age by 51% if breast cancer survivors were exposed to chemotherapy during treatment.
Maternal Safety Outcomes
When maternal safety was evaluated by comparing 2003 breast cancer survivors who were pregnant with 37,779 breast cancer survivors who did not become pregnant after treatment, no detrimental effect of pregnancy was found. Disease-free survival was 27% better in patients with breast cancer who became pregnant than in those who did not.
For the overall survival analysis, 3,261 patients with breast cancer with posttreatment pregnancy were compared with 58,238 patients with breast cancer who did not become pregnant after treatment. Overall survival was improved by 44% when pregnant survivors were compared with nonpregnant breast cancer survivors (P < .001).
Pregnancy had no detrimental effect on disease-free survival and overall survival in a subgroup analysis that included BRCA status and nodal status.
Dr. Blondeaux noted that, although the data support the feasibility and safety of pregnancy in breast cancer survivors, the higher risk of fetal complications indicate that close monitoring is needed for breast cancer survivors who become pregnant, especially those exposed to chemotherapy.
Comment on Study
Ian E. Krop, MD, PhD
Session moderator, Ian E. Krop, MD, PhD, Associate Professor, Harvard Medical School; Associate Chief, Division of Breast Oncology, Susan F. Smith Center for Women’s Cancers; and Clinical Research Director, Breast Oncology Center, Dana-Farber Cancer Institute, Boston, was concerned about the fetal outcomes affected by chemotherapy, according to the findings of this study.
“I was struck by the fact that all three fetal outcomes were affected by chemotherapy—low birth weight, preterm birth, and small for gestational age. Even congenital outcomes appeared to trend toward worse outcomes for patients with breast cancer with a postterm pregnancy. Most of the studies included in this analysis trended in the same direction,” Dr. Krop said.
“I have always told my patients with breast cancer that if they get pregnant, they will be fine. I guess this question needs to be revisited for patients treated with chemotherapy,” he noted.
DISCLOSURE: Dr. Blondeaux reported no conflicts of interest. Dr. Krop has served as an advisor or consultant for Context Therapeutics, Daiichi Sankyo, Genentech/Roche, Macrogeneics, Merck & Co, Novartis Pharmaceuticals, and Taiho Pharmaceutical and has received grants for clinical research from Daiichi Sankyo, Genentech/Roche, Pfizer, and Taiho Pharmaceutical.
1. Blondeaux E, Perachino M, Bruzzone M, et al: Chances of pregnancy after breast cancer, reproductive and disease outcomes. 2020 San Antonio Breast Cancer Symposium. Abstract GS3-09. Presented December 11, 2020.