麻豆传媒

One in five young women with germline BRCA pathogenic variants were able to conceive within 10 years of invasive breast cancer diagnosis, and their pregnancies were not associated with adverse maternal prognosis or fetal outcomes, an international retrospective cohort study suggested.

In the cohort of over 4,700 women, the cumulative incidence of pregnancy at 10 years was 22%, with a median time from breast cancer diagnosis to conception of 3.5 years (interquartile range 2.2-5.3 years), reported Matteo Lambertini, MD, of the University of Genova-IRCCS Ospedale Policlinico in Genova, Italy, and colleagues.

There was no significant difference in disease-free survival between patients with or without a pregnancy after breast cancer (adjusted HR 0.99, 95% CI 0.81-1.20), they noted in .

Moreover, pregnancy in BRCA carriers was associated with a lower rate of breast cancer-specific survival events (adjusted HR 0.60, 95% CI 0.40-0.88, P=0.009), and the occurrence of pregnancy was associated with a lower rate of death due to any cause (adjusted HR 0.58, 95% CI 0.40-0.85, P=0.005).

"Our results can inform counseling of young BRCA carriers interested in conceiving following breast cancer diagnosis," Lambertini and team wrote.

More than 12% of young newly diagnosed patients carry pathogenic BRCA1 or BRCA2 variants, but data on the feasibility and safety of pregnancy in this population have been limited. Lambertini and colleagues previously reported on 1,252 BRCA carriers from 30 centers showing no negative consequences in maternal or fetal outcomes.

These positive results suggest that all women diagnosed with cancer during the reproductive years should be offered fertility preservation strategies before anticancer therapy, the authors noted.

Erica Mayer, MD, MPH, of Dana-Farber Cancer Institute in Boston, told 麻豆传媒 that "the findings reinforce for us as oncologists that these young women want to get pregnant, so we need appropriate data to guide our counseling regarding the feasibility and safety of pregnancy."

Calling the study "an important organization of a large cohort of patients," Mayer, who was not involved in the study, added, "the data are very impactful for clinical practice because they allow us to counsel our youngest patients that pregnancy may be a safe option after initial diagnosis and treatment."

The interval from breast cancer diagnosis to conception was significantly longer in patients with hormone-receptor (HR)-positive cancer: 4.3 years, with 39.8% of pregnancies occurring after 5 years. Reassuringly, the prospective POSITIVE study showed that HR-positive women who wish to conceive can pause endocrine therapy for as long as 2 years without risk of cancer recurrence.

This study cohort consisted of 4,732 patients diagnosed with invasive breast cancer at age 40 or younger from January 2000 to December 2020. All had germline pathogenic variants in BRCA1 and/or BRCA2. Patients came from 78 treatment centers across Southern, Northern, and Eastern Europe, as well as North and Latin America, Asia, and Australia/Oceania. The largest regional group (44%) came from Southern Europe. Median follow-up was 7.8 years.

Median age at breast cancer diagnosis was 35 years, and 659 patients had at least one pregnancy after diagnosis, a higher incidence than previously reported in young breast cancer survivors, the authors noted.

Of the pregnancies, 79.2% occurred spontaneously, despite previous chemotherapy in more than 90% of the cohort.

Among the patients with pregnancy, 6.9% and 9.7% had an induced abortion or a miscarriage, respectively. Of the 79.7% with a completed pregnancy, 91% delivered at term (≥37 weeks) and 10.4% had twins. Among 470 infants, only four had documented congenital anomalies.

Among the study's limitations were its retrospective observational design and its reliance on data from oncology medical records not formulated for the study's outcomes, thereby posing a risk of under-reporting. Moreover, data came from disparate healthcare systems across the globe treating patients for two decades, during which time therapies have improved.

In addition, patients diagnosed toward the study's end had less time to conceive and be evaluated for outcomes. Finally, those at higher risk of recurrence may have received different fertility counseling, and healthier, lower-risk women may have conceived more readily.

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