Pregnancy after breast cancer ‘should not be discouraged’
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Breast cancer survivors of childbearing age appeared considerably less likely than women in the general population to become pregnant, according to study results presented at the virtual San Antonio Breast Cancer Symposium.
Survivors who conceived after completing treatment faced elevated risks for certain complications, including preterm birth. However, most survivors who became pregnant had healthy babies, with no increased risk for congenital abnormalities or adverse impact on long-term maternal survival.
“After adequate treatment and follow-up, pregnancy after breast cancer should not be discouraged,” Matteo Lambertini, MD, PhD, adjunct professor in medical oncology at University of Genova — IRCCS Policlinico San Martino Hospital in Genova, Italy, told Healio. “These findings are of paramount importance to raise awareness of the need to offer complete oncofertility counseling to all newly diagnosed young [women with breast cancer] in order to increase chances of future conception.”
Breast cancer is the most common malignancy among women of reproductive age, accounting for approximately 30% of new cancer diagnoses worldwide among those aged younger than 40 years.
The availability of more effective therapies has reduced breast cancer mortality over the past 2 decades. Consequently, there has been increased emphasis on survivorship and the potential long-term toxicities associated with treatment, including effects on fertility.
In addition, given the fact age of first pregnancy is on the rise, an increasing percentage of women are diagnosed with breast cancer prior to having children.
“Returning to a normal life after cancer diagnosis and treatment should be considered in the 21st century as a crucial ambition in cancer care,” Lambertini said. “[For] patients diagnosed during their reproductive years, this includes the possibility to complete their family planning.”
However, only a small number of women diagnosed with breast cancer during their reproductive years conceive following treatment.
Surveys show many women and their physicians have concerns about maternal and fetal safety after breast cancer diagnosis and treatment. These concerns include the potential that anticancer therapies may increase risk for congenital abnormalities or obstetric or birth complications, as well as the possibility that pregnancy may have a detrimental prognostic impact given many breast cancer subtypes are hormonally driven.
Consequently, it is crucial to provide updated evidence to guide women and their physicians during guideline-recommended oncofertility counseling, and to ensure women are not denied opportunities to complete family planning after treatment completion, Lambertini said.
Lambertini and colleagues conducted a systematic review and meta-analysis to assess pregnancy chances after breast cancer, as well as reproductive and disease outcomes, among women who completed breast cancer treatment.
The review encompassed 39 studies that identified women who became pregnant after breast cancer diagnosis. These studies included a combined 8.26 million women, 114,573 of whom had breast cancer and 57,739 of whom had malignancies other than breast cancer. Approximately 6.5% of those with breast cancer (n = 7,505) became pregnant after diagnosis.
Researchers determined breast cancer survivors who completed treatment were 60% less likely than women in the general population to become pregnant (RR = 0.4; 95% CI, 0.32-0.49). In the cohort of women who had malignancies other than breast cancer, only those with prior cervical cancer exhibited a lower pregnancy rate than that observed in the breast cancer subgroup (RR = 0.33; 95% CI, 0.31-0.35).
Breast cancer survivors who did conceive appeared more likely than those in the general population to require caesarean section (OR = 1.14; 95% CI, 1.04-1.25). They also exhibited elevated risks for certain complications, such low birth weight (OR = 1.5; 95% CI, 1.31-1.73), preterm delivery (OR = 1.45; 95% CI, 1.11-1.88) and having a baby small for gestational age (OR = 1.16; 95% CI, 1.01-1.33), although the latter two complications appeared restricted primarily to women who received chemotherapy.
Investigators reported no significant increased risk for congenital abnormalities (OR = 1.63; 95% CI, 0.89-2.98) or other pregnancy or delivery complications, such as gestosis, spontaneous or induced abortion, or postpartum hemorrhage.
Pregnancy after breast cancer did not appear to have a negative effect on maternal outcomes regardless of tumor characteristics, BRCA status, type of prior treatment or timing of pregnancy.
Those who became pregnant after breast cancer achieved longer OS (HR = 0.56; 95% CI, 0.46-0.67) and DFS (HR = 0.73; 95% CI, 0.56-0.94) than women who did not have a subsequent pregnancy. Studies that corrected for the potential “healthy mother effect” — which suggests women who have good prognoses and feel well are more likely to attempt to conceive — yielded similar results for OS (HR = 0.52; 95% CI, 0.42-0.65) and DFS (HR = 0.74; 95% CI, 0.58-0.96).
When researchers analyzed outcomes based on hormone receptor status, they determined pregnancy after breast cancer had no detrimental prognostic effect for women with hormone receptor-positive disease (HR for DFS = 1.1; 95% CI, 0.73-1.66). They observed better outcomes for those with hormone receptor-negative disease (HR for DFS = 0.72; 95% CI, 0.55-0.95).
“The higher risk [for] delivery and fetal complications — but not of congenital abnormalities — calls for ensuring a closer monitoring of these pregnancies,” Lambertini told Healio. “The lack of detrimental prognostic effect of pregnancy after breast cancer following appropriate treatment and follow-up strongly voices for the need for a deeper consideration of patients’ pregnancy desire as a crucial component of their survivorship care plan and wish to return to a normal life.”
The low rate of pregnancy among breast cancer survivors surprised investigators, but there are potential explanations, Lambertini said.
These include older age at diagnosis of breast cancer compared with other malignancies that occurred among women of reproductive age, the need to administer potentially gonadotoxic therapies — including cyclophosphamide-based chemotherapy regimens — and the 5- to 10-year duration of adjuvant endocrine treatment for women with hormone receptor-positive disease, during which pregnancy is contraindicated.
“Therefore, proper and timely referral of patients potentially interested in future conception to fertility units is crucial,” Lambertini told Healio. “Strengthening oncofertility programs and overcoming the barriers for their implementation — including financial burden — should be considered a priority to ultimately improve patients’ care in this setting.”
It also is possible that patients’ and physicians’ concerns that breast cancer diagnosis and treatment could have a negative impact on reproductive outcomes and maternal safety may have discouraged survivors from attempting pregnancy, Lambertini said.
“These highly relevant issues have been now strongly dispelled by the present meta-analysis,” he said.
Lambertini and colleagues acknowledged study limitations, including their inability to examine individual patient data and the fact most studies in their review were retrospective analyses.
In addition, most of the studies included in the analysis did not capture the number of women who tried to become pregnant after completing treatment. The studies that did include this information suggested more than half of women who attempted pregnancy were able to conceive without the need for assisted reproductive technology.
“Another crucial message from these studies is that some patients without pregnancy desire to conceive,” Lambertini said. “This highlights that oncofertility counseling should include not only information on fertility preservation and safety of pregnancy after breast cancer, but also information on adequate and safe contraception at diagnosis, as well as during treatment and follow-up.”
Perspective
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Amy Tiersten, MD
This is a very exciting and important study. It is very reassuring to see confirmation in a large study such as this one that pregnancy does not adversely affect long-term outcome for women who have had breast cancer across all subgroups the investigators studied. The information this study provides with regard to decreased chances of becoming pregnant and increased risk for delivery and fetal complications among breast cancer survivors also is very important and will allow us to counsel patients regarding these risks and follow them more closely during their pregnancies.
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Blondeaux E, et al. Abstract GS3-09. Presented at San Antonio Breast Cancer Symposium (virtual meeting); Dec. 8-11, 2020.
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