Livebirth among 5940 Danish women diagnosed with breast cancer at age 18–40 years between 1968 and 2016: a register-based cohort study

STUDY QUESTION Does livebirth probability differ between women diagnosed with breast cancer and unaffected women and is it impacted by age at diagnosis, time trends, parity, partnership status, and the presence of lymph node metastases and distant metastases? SUMMARY ANSWER Livebirth probability was significantly reduced in 5940 women diagnosed with breast cancer aged 18–40 years during 1968–2016 compared to 1 126 478 age-matched unaffected women, particularly among women with higher diagnosis age, parity ≥ 1, marriage, and the presence of nodal involvement and distant metastases. WHAT IS KNOWN ALREADY The survival rate for women diagnosed with breast cancer has increased over the recent decades, and in Denmark, the 5-year survival rate for women diagnosed <50 years of age was 92.2% in 2022. Chemotherapy can damage the ovarian reserve, resulting in premature ovarian insufficiency and infertility. The age of first-time mothers is increasing, and many women have not yet completed family building at the time of diagnosis. Consequently, greater focus is now placed on quality-of-life following breast cancer, including the possibility of survivors to have children. Studies have shown a decreased fertility rate in women diagnosed with cancer during their reproductive lifespan, however, studies specifically focusing on the probability of livebirth in women previously diagnosed with breast cancer are scarce. STUDY DESIGN, SIZE, DURATION This is a national, register-based cohort study including women diagnosed with breast cancer from the Danish Cancer Register between 1968 and 2016, aged 18–40 years at time of diagnosis (n = 5940). Each woman was randomly matched with ∼190 unaffected women from the background population according to the age at diagnosis (n = 1 126 478). The women were followed in medical and sociodemographic national population registers until childbirth, death, immigration, or end of study (31 December 2018). PARTICIPANTS/MATERIALS, SETTING, METHODS In all analyses, we compared the probability of livebirth between women diagnosed with breast cancer and the age-matched comparison group. Analyses were stratified by parity- and partnership status at diagnosis, age-group at diagnosis, and year of diagnosis. Stratified analyses on the probability of livebirth were conducted for women with lymph-node metastases and distant metastases at the time of diagnosis. Analyses were adjusted for age, year of diagnosis, parity, educational level, and migration status. MAIN RESULTS AND THE ROLE OF CHANCE The study population consisted of 5940 women aged 18–40 years at diagnosis of breast cancer between 1968 and 2016 and 1 126 478 women in the age-matched comparison group. Breast cancer survivors had a significantly lower probability of livebirth than the age-matched comparison group (aHR 0.38 [95% CI 0.35–0.41]); negatively impacted by increasing age at diagnosis (35–40 years: aHR 0.34 [95% CI 0.28–0.40], 18–24 years: 0.66 [95% CI 0.46–0.95]), parity ≥1 (parous: aHR 0.31 [95% CI 0.27–0.35], nulliparous: 0.51 [95% CI 0.45–0.59]), and marriage (married: aHR 0.31 [95% CI 0.27–0.36], single 0.53 [95% CI 0.45–0.63]). Being diagnosed in recent decades increased the probability of livebirth in nulliparous women; however, the same association was not found for parous women. Among women with nodal involvement (48%) and distant metastases (3%), the probability of livebirth compared to unaffected women was aHR 0.30 [95% CI 0.26–0.35] and 0.18 [95% CI 0.08–0.42], respectively. LIMITATIONS, REASONS FOR CAUTION We did not have information on whether the women desired children or whether they underwent fertility preservation (FP) prior to receiving gonadotoxic treatment. For women diagnosed in the most recent decades, the follow-up time was limited. Information on tamoxifen treatment for estrogen receptor-positive tumors could have been relevant, as it likely delays pregnancy and consequently reduces conception probability. WIDER IMPLICATIONS OF THE FINDINGS Our results highlight the continued importance of onco-fertility counseling and FP in young women diagnosed with breast cancer, particularly among women diagnosed toward the end of their reproductive lifespan and those with the presence of lymph node metastases and distant metastases. STUDY FUNDING/COMPETING INTEREST(S) The study is funded by the Independent Research Fund Denmark (Grant ID 10.46540/4308-00130B). Anja Pinborg has received grants (payment to institution) and consultancy fees from Gedeon Richter, Ferring Pharmaceuticals, Merck A/S, and Cryos; honoraria from Gedeon Richter, Ferring Pharmaceuticals, Merck A/S, and Organon; and support for attending meetings and/or travel (payment to institution) from Gideon Richter. These companies had no role in the study. The remaining authors have no conflicts or interests to declare. TRIAL REGISTRATION NUMBER N/A.