- Published in The New England Journal of Medicine (1), first results of the international POSITIVE study co-authored by VHIO’s Cristina Saura show that the temporary interruption of endocrine therapy in select women aged 42 or younger with previous hormone receptor-positive early breast cancer attempting pregnancy did not increase the short-term risk of disease recurrence.
- Enrolling 516 women across sites in 20 countries this multicenter study was designed to evaluate if treatment interruption increased the risk of breast cancer recurrence in these patients who had received between 18 to 30 months of prior adjuvant endocrine therapy.
- After a median follow-up of 41 months data showed that the relapse rate in those women who temporarily stopped treatment was 8.9% versus 9.2% in those who received continued, uninterrupted therapy.
- Among the 497 women who were followed for pregnancy status, 368 had at least one pregnancy and 317 had at least one live birth. In total, 365 babies were born.
Adjuvant endocrine therapy is the cornerstone of systemic treatment of patients with hormone receptor-positive (HR+) breast cancer. For young women desiring pregnancy after HR+ breast cancer, 5-10 years of subsequent endocrine therapy may substantially reduce the chance of conception. Furthermore, exposure to this therapy can increase the risk of fetal malformation and patients are discouraged from becoming pregnant while receiving this treatment. In addition, HR+ tumors associate with an increased risk of disease recurrence due to higher estrogen levels during pregnancy.
Between 40 and 60% of breast cancer patients aged 40 or younger are concerned about their future fertility, especially if they are diagnosed before they have decided if they would like to have children. Aimed at addressing this preoccupation, the multicenter and international POSITIVE study is the first prospective study to evaluate pregnancy outcomes and the safety of interrupting endocrine therapy in women who are diagnosed with breast cancer at an early age, for whom treatment is recommended for at least 5 years.
First results of this pioneering study, coordinated in Spain by the SOLTI Breast Cancer Research Group and GEICAM Spanish Breast Cancer Group and led by Cristina Saura —Principal Investigator of the Vall d’Hebron Institute of Oncology’s (VHIO) Breast Cancer Group and Head of the Vall d’Hebron University Hospital’s (HUVH) Breast Cancer Unit — recently published as an Original Article in The New England Journal of Medicine (1), and carried an accompanying editorial (2).
Data show that among select young women under the age of 42 with previous hormone-receptor (HR)-positive early breast cancer, temporary interruption of adjuvant endocrine therapy to attempt pregnancy —under close medical surveillance and during a period of no more than two years— did not confer a greater short-term risk of disease recurrence, than that in the external control cohort of patients who continued to receive uninterrupted therapy.
Led by Olivia Pagani, study Chair on behalf the International Breast Cancer Study Group (IBCSG), the POSITIVE investigators observed that the risk of disease recurrence in the treatment-interruption group was 8.9% versus 9.2% in those patients who would have met the entry criteria for this present study, and who received uninterrupted endocrine therapy.
“Results of this pioneering study, that were previously selected to first outing at last December’s San Antonio Breast Cancer Symposium, reinforce the suitability of fertility preservation prior to starting treatment and allow for the possibility of a safe pregnancy for those patients with hormone receptor-positive breast cancer who desire pregnancy once they have completed at least 18 months of adjuvant endocrine therapy,” says Cristina Saura, co-author of this present study and member of SOLTI’s Board of Directors.
Up until now, the recommendation for these patients has been to start attempting pregnancy having survived breast cancer for at least 5 years, free of disease recurrence. This time frame is usually longer and can therefore complicate family planning. POSITIVE results could lead to a change in the current clinical guidelines, reducing the time from diagnosis until the recommended time for these patients to start attempting pregnancy.
“While our initial results are reassuring, long-term follow-up of these patients will be essential to corroborate our data. It is also important to add that any treatment decision must naturally be discussed and taken by the multidisciplinary team of healthcare professionals, and hand in hand with each individual patient,” adds Saura.
“The POSITIVE study yields hopeful results for those young women diagnosed with hormone receptor-positive breast cancer who want to become mothers, and provides deeper scientific insights into the relationship between this tumor subtype and pregnancy, which could lead to a paradigm shift in the management of this disease in patients who desire pregnancy,” observes Manuel Ruiz Borrego, Head of the Breast Cancer Unit at the Virgen del Rocio University Hospital in Seville, co-coordinator of POSITIVE in Spain, and a member of GEICAM’s Board of Directors.
“We know that breast cancer is increasingly common in young women. Diagnosis therefore coincides with the desire of many of these patients to be mothers. For this reason, fertility and pregnancy are important issues for cancer patients as well as investigators, who seek to identify new avenues for the optimal management of these cases,” concludes Borrego.
Advancing insights into pregnancy and breast cancer Another ongoing academic, cooperative study is currently exploring whether there is a causal relationship between pregnancy and breast cancer occurrence. Led by GEICAM, the pregnancy and breast cancer EMBARCAM study has been designed to advance insights into breast cancer diagnosed during pregnancy or in the first postpartum year or any time during lactation —known as gestational breast cancer— to help predict disease occurrence and develop strategies aimed at achieving safe pregnancies. Research pioneered by Cristina Saura is also investigating breast milk for the early detection of breast cancer. Having analyzed specific cases, initial results suggest that breast milk could potentially be used to detect cancer mutations earlier than through blood, since the concentration of DNA is much higher in breast milk. To confirm these data, the investigators plan to launch the international MMaterna study to analyze women who become pregnant at over 40 years of age or are healthy carriers of a genetic mutation that increases their risk of breast cancer. MMaterna aims to establish if breast cancer can be diagnosed earlier on in the postpartum period using breast milk versus blood samples or conventional radiological studies.
Spanish participation in POSITIVE
Patients from 116 sites spanning 20 countries participated in this study; 23% from North America, 16% from Asia/Pacific and the Middle East, and 61% from Europe, of whom 72 were enrolled from 18 Spanish hospitals and recruited through the SOLTI and GEICAM breast cancer research groups.
To assess the risk of disease recurrence over time, the POSITIVE investigators continue to follow-up the study participants. Given that recurrent hormone receptor-positive breast cancer can occur years after initial diagnosis, the authors acknowledge that the short follow-up of 3 years and six months to date is a limitation of this study. The investigators will therefore continue to follow-up study participants for 10 years in order to corroborate the first results of this present study.
The study is promoted and led worldwide by the International Breast Cancer Study Group (IBCSG), a division of the ETOP-IBCSG Partners Foundation, and the Alliance for Clinical Trials in Oncology in North America, in collaboration with the Breast International Group (BIG) through its member groups SOLTI and GEICAM in Spain.
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References:
- Partridge AH, Niman SM, Ruggeri M, Peccatori FA, Azim HA Jr, Colleoni M, Saura C, Shimizu C, Sætersdal AB, Kroep JR, Mailliez A, Warner E, Borges VF, Amant F, Gombos A, Kataoka A, Rousset-Jablonski C, Borstnar S, Takei J, Lee JE, Walshe JM, Ruíz-Borrego M, Moore HCF, Saunders C, Bjelic-Radisic V, Susnjar S, Cardoso F, Smith KL, Ferreiro T, Ribi K, Ruddy K, Kammler R, El-Abed S, Viale G, Piccart M, Korde LA, Goldhirsch A, Gelber RD, Pagani O; International Breast Cancer Study Group; POSITIVE Trial Collaborators. Interrupting Endocrine Therapy to Attempt Pregnancy after Breast Cancer. N Engl J Med. 2023 May 4;388(18):1645-1656.
- Giordano SH. POSITIVE Results for Breast Cancer Survivors Who Desire Pregnancy. N Engl J Med. 2023 May 4;388(18):1709-1710.
