(CSPOT35) Live birth rate in female breast cancer survivors compared with the general population: matched cohort study using linked UK electronic health records

Background: With improving survival rates from cancer, as well as delayed childbearing, the number of women considering pregnancy after cancer is increasing. There are few population-based studies investigating the live birth rate in breast cancer survivors.

Objectives: To compare the live birth rate between breast cancer survivors and women with no history of cancer and explore the role of chemotherapy and stage at diagnosis, using electronic health data from England.

Methods: We undertook a matched cohort study using prospective primary care data from the UK Clinical Practice Research Datalink database and linked hospital, death and cancer registry data from 2012-2018. Those with first diagnosis of breast cancer aged 18 to 44 years were matched on age, sex, GP postcode and calendar time, with up to ten comparators never diagnosed with cancer. Follow-up began at cancer diagnosis, or matched date for comparators. Live birth was defined using medical codes in primary or secondary care. The effect of history of cancer was assessed using Cox regression, stratified by matched set, and adjusted for parity, socioeconomic status and smoking, problematic alcohol use. We classified cancer survivors according to receipt of chemotherapy and stage at diagnosis, then assessed the risk of live birth in the cancer groups compared to cancer-free comparators.

Results: There were 12663 breast cancer survivors matched to 106,774 women without a history of cancer. The median age at breast cancer diagnosis was 39.8 years (IQR 36.5 to 42.1). Cancer survivors were followed up for a median of 7.4 years. In women with breast cancer, the rate of live births was 3.6 per 1000, compared to 6.1 per 1000 in women without a history of cancer; after adjustment, having a history of breast cancer was associated with a reduced chance of live birth (HR 0.55, 95%CI 0.49-0.62). The reduced chance of live birth was seen in those who received (HR 0.30, 95%CI 0.16-0.57) as well as those who did not receive chemotherapy (HR 0.63, 95%CI 0.51-0.77), compared to cancer-free comparators. Lower live birth rates were observed with increasing stage at diagnosis (stage I breast cancer HR 0.64, 95%CI 0.48-0.84 and Stage IV HR 0.07, 95%CI 0.01-0.52).

Conclusions: A history of breast cancer was associated with a greatly reduced chance of subsequent live birth and chance reduced with increasing stage at diagnosis. Both women receiving and not receiving chemotherapy had a reduced chance of live birth, compared to women without a history of cancer. Further studies investigating the role of specific treatments (including hormone therapy) versus the role fertility choices will help explain these associations.