SUMMARY: Breast cancer is the most common cancer among women in the US and about 1 in 8 women (12%) will develop invasive breast cancer during their lifetime. It is estimated that in the US, approximately 310,720 new cases of female breast cancer will be diagnosed in 2024, and about 42,250 individuals will die of the disease, largely due to metastatic recurrence.
The median age at the time of breast cancer diagnosis in the US is 62 years. However approximately 5% of new diagnoses each year occur in those who are under 40 years. These young patients with Hormone Receptor (HR)-positive breast cancer receiving modern adjuvant endocrine therapy have excellent long-term outcomes. Nonetheless, 40-60% of patients who are diagnosed with breast cancer at age 40 or younger are concerned about their future fertility and pregnancy, as many have not completed their family planning at diagnosis due to delay in childbearing. The POSITIVE (Pregnancy Outcome and Safety of Interrupting Therapy for Women with Endocrine Responsive Breast Cancer) trial designed to evaluate whether temporary interruption of adjuvant endocrine therapy to attempt pregnancy was associated with a higher risk of breast cancer recurrence, did indeed suggest that women with a history of HR-positive breast cancer could safely pause hormonal therapy to have a child. (N Engl J Med 2023; 388:1645-1656)
Young women diagnosed with breast cancer, especially those harboring a BRCA mutation, often desire to conceive post-treatment. However, concerns loomed over the safety of pregnancy following a breast cancer diagnosis. Previous studies provided limited data, necessitating further exploration to guide patients and physicians adequately.
This international Hospital-Based Cohort Study was conducted to investigate if pregnancy after breast cancer among women carrying germline BRCA pathogenic variants was associated with adverse maternal or fetal outcomes. The study encompassed a vast cohort comprising 4,732 women with a BRCA mutation, all diagnosed with invasive breast cancer at the age of 40 or younger, between January 2000 and December 2020. This extensive retrospective cohort study spanned numerous international hospital centers, ensuring a diverse and comprehensive representation of patients. The Primary end points of this study were cumulative incidence of pregnancy after breast cancer and Disease Free Survival (DFS). Secondary end points included Breast Cancer–Specific Survival, Overall Survival, pregnancy, fetal and obstetric outcomes. The median follow up was 7.8 years.
Out of the entire cohort of 4,732 women with a BRCA mutation, 659 patients had at least 1 pregnancy after their breast cancer diagnosis. The cumulative pregnancy incidence at 10 years after diagnosis was 22%. The median time from breast cancer diagnosis to conception was 3.5 years, and 28% of pregnancies occurred after 5 years. Compared with women who did not get pregnant, women who became pregnant were more likely to have a BRCA1 mutation alone (73% versus 63%), be younger at breast cancer diagnosis (median age 30 yrs versus 35 yrs), have node-negative disease (62.5% versus 52%), and have HR-negative disease (68% versus 52%).
The cumulative incidence of pregnancy at 10 years was 18% in patients with HR-positive disease and 26% in patients with HR-negative disease (P<0.001) and the median time from diagnosis to conception was 4.3 years and 3.2 years, respectively (P<0.001). The proportion of pregnancies occurring after 5 years was 40% and 22%, respectively.
Overall, the median age at pregnancy was 35 years, 79% of patients had a spontaneous pregnancy without the use of any assisted reproductive technology, and 80% delivered a child. Of all pregnancies, 8% had an induced abortion and 10% had a miscarriage, and majority of patients (86%) did not experience pregnancy complications. There was no significant difference in Disease Free Survival observed between patients with or without a pregnancy after breast cancer, and patients who had a pregnancy had significantly better Breast Cancer–Specific Survival and Overall Survival.
The authors from this study concluded that 1 in 5 young BRCA carriers conceived within 10 years after breast cancer diagnosis. They added that pregnancy following breast cancer in BRCA carriers was not associated with decreased Disease Free Survival and conceiving after proper treatment and follow up for breast cancer should not be contraindicated anymore in young BRCA carriers. Coupled with the analysis from the POSITIVE trial, which suggests that fertility preservation and assisted reproductive technologies do not heighten the risk of recurrence, these results alleviate many concerns surrounding post-breast cancer pregnancy.
This international, large-scale study offers critical insights into the safety and feasibility of pregnancy post-breast cancer diagnosis, for women with BRCA mutations. The findings provide valuable guidance for patients and healthcare providers, potentially reshaping clinical practices and decision-making processes. In essence, this pioneering research represents a pivotal milestone in the field of breast cancer management, offering hope, reassurance, and clarity to countless young women navigating the intersection of cancer treatment and fertility preservation.
Pregnancy After Breast Cancer in Young BRCA Carriers. Lambertini M, Blondeaux E, Agostinetto E, et al. JAMA. 2024;331:49-59.
