Pregnancy after cancer: is it safe?
Fedro A. Peccatori, European Institute of Oncology, Milan, Italy
While there is increasing evidence from studies supporting pregnancy after cancer treatment, gaps in the data remain, especially regarding the impact of new therapies on fertility.
As a result of improvements in cancer prognosis, fertility preservation has become an increasingly important consideration in supporting women who aspire to have a child after cancer treatment. However, pregnancy rates are lower compared to the general population ( J Clin Oncol . 2021;39:3293–3305; Hum Reprod . 2018;33:1281–1290), and this may be due to several factors, including concerns about possible pregnancy complications and the risk of cancer recurrence during or after pregnancy.
For women who undergo fertility-preserving surgery for early-stage cervical cancer , there is an increased risk of preterm birth ( Obstet Gynecol . 2021;138:565–573; Int J Environ Res Public Health . 2020; 17:7103). The most challenging situation is for women who have undergone pelvic radiation . In this case, the uterus may suffer irreversible damage, especially if the treatment is administered before puberty.
Among women who became pregnant after treatment for breast cancer , an increased risk of complications during pregnancy was seen, including a 1.5 times increased risk of low birth weight, a 1.5 times increased risk of preterm birth and a 1.2-fold increased risk of a small-for-gestational-age newborn ( J Clin Oncol . 2021;39:3293–3305). Reassuringly, a significantly increased risk of congenital anomalies or other reproductive complications was not observed in this cohort.
The POSITIVE study provides more information on different specific indicators related to fertility, pregnancy and the biology of breast cancer in young women, investigating whether temporary interruption of endocrine therapy, with the aim of allowing pregnancy, is associated with an increased risk of breast cancer recurrence. ( NCT02308085 ).
Prospective data from this trial did not indicate increased risks of fetal malformations or other major pregnancy complications in women who discontinued endocrine therapy to try to become pregnant after breast cancer ( N Engl J Med . 2023;388:1645–1656) .
Cancer relapse during pregnancy is a concern, especially in women with hormone-sensitive breast cancer. However, retrospective data collected so far do not support an increased risk of relapse as a result of pregnancy in these patients.
Additionally, there was no increased risk of breast cancer events in women with hormone receptor-positive breast cancer compared with control patients over 41 months in the POSITIVE trial: 3-year incidence 8.9% (confidence interval [ 95% CI: 6.3–11.6) versus 9.2% (95% CI: 7.6–10.8), respectively ( N Engl J Med . 2023;388:1645–1656).
A landmark analysis of the 18-month breast cancer-free interval in patients who became pregnant during the POSITIVE trial demonstrated a pregnancy hazard ratio of 0.55 (95% CI, 0.28 to 1.06) in a univariate time-dependent Cox model. Data from this study will continue to be collected for up to 10 years, providing information about the long-term risks of pregnancy for women with breast cancer. For patients who relapse or develop metastatic disease during pregnancy, treatment can be challenging due to the reduction in the number of available options.
Medical evaluation and advice is recommended for all women who wish to become pregnant after cancer treatment.
This is crucial to ensure both good general health and awareness of potential risks.
Patients with chemotherapy-induced cardiomyopathy will require careful management during pregnancy to avoid complications. Additionally, it is essential to re-stage cancer before conception, as some tests are restricted during pregnancy. For example, CT scans of the pelvis and MRI of the breast with gadolinium should be avoided throughout pregnancy.
Although experience in managing pregnancy in patients after cancer treatment is increasing, gaps in data remain.
For example, the ovarian toxicity of some of the newer agents, such as poly ADP ribose polymerase (PARP) inhibitors and cyclin-dependent kinase (CDK) 4/6 inhibitors, has not yet been established . Furthermore, there is currently no registry of pregnancy outcomes for patients who received pelvic radiation therapy as young adults. In the future, multidisciplinary collaborations will be necessary to address these issues.
