International collaborations
The international POSITIVE study brings hope for young women with hormone receptor-positive breast cancer who wish to have children. The study, which is also being conducted in Austria with the participation of the ABCSG, investigates whether it is possible to safely interrupt endocrine therapy without compromising the recovery process in breast cancer patients. Led by the International Breast Cancer Study Group (ETOP IBCSG Partners Foundation), the study involves 20 countries, with ABCSG participating through centers in Graz, Salzburg, Vienna, and Innsbruck.
Hormone receptor-positive breast cancer is typically treated with endocrine therapy to inhibit tumor cell growth. However, this therapy presents a challenge for women who wish to conceive, as interrupting treatment may increase the risk of recurrence. The POSITIVE study is the first to systematically examine, in a controlled clinical trial setting, whether a temporary break in treatment is safe to enable pregnancy. A total of 518 patients who interrupted their endocrine therapy for up to two years in order to pursue pregnancy participated in the study. During this time, they were closely monitored to assess the risk of relapse and to track the course of their pregnancies.
The initial results of the study are highly promising. The rate of breast cancer recurrence was comparable to that of women who did not interrupt their treatment. Furthermore, the number of pregnancies and births was remarkably high: 368 women became pregnant, resulting in the birth of 365 children. These figures fall within the normal range or even above the average for the general population, underscoring the safety and feasibility of the procedure.
The POSITIVE trial thus provides the first evidence-based data on the possibility of pregnancy during treatment for hormone receptor-positive breast cancer. The results were prominently published in the New England Journal of Medicine in May 2023 (DOI: https://doi.org/10.1056/NEJMoa2212856). A follow-up publication, evaluating secondary endpoints, was published in The Journal of Clinical Oncology in May 2024 (DOI: https://doi.org/10.1200/JCO.23.02292).
The planned long-term follow-up aims to gain further insights into long-term safety, providing crucial data to improve the quality of life for affected women and help them make informed decisions. The ABCSG is proud to be part of this international project, contributing to the advancement of knowledge about breast cancer treatment options and pregnancy.
Adjuvant olaparib improves 3-year survival in patients with BRCA1– or BRCA2-mutated breast cancer.
The ABCSG 41 / BIG 6-13 / OlympiA trial is an international project investigating the efficacy and safety of olaparib in HER2-negative high-risk breast cancer patients with BRCA 1/2 germline mutations who have completed definitive local and neoadjuvant or adjuvant treatment. This Phase 3 trial began enrollment on May 28, 2019 and included 1,836 patients from 23 countries who were at high risk of disease recurrence after having received standard treatment such as chemotherapy, surgery and radiation.
The primary objective of the OlympiA trial was to determine invasive disease-free survival (iDFS). The highly positive results, prominently published in the New England Journal of Medicine in June 2021 under the title “Adjuvant Olaparib for Patients with BRCA1 or BRCA2 Mutated Breast Cancer,” demonstrated that the iDFS rate at three years was significantly higher in patients who received olaparib (85.9%) compared to those in the placebo group (77.1%). Additionally, the study showed significant improvements in distant disease-free survival (DDFS), with minimal impact on patient-reported quality of life.
These groundbreaking results represent a major milestone in the treatment of BRCA-associated early breast cancer, offering new therapeutic pathways for a patient group facing very specific challenges. This study is particularly significant as it marks the first time that a PARP inhibitor has been shown to reduce the risk of recurrence in high-risk patients with BRCA mutations when used in adjuvant therapy. As a result, olaparib has been approved by the U.S. Food and Drug Administration (FDA) for the adjuvant treatment of BRCA-mutated, HER2-negative early breast cancer.
The study’s findings also highlight the crucial role of genetic testing in identifying patients who may benefit from such therapies—a practice that we hope will soon become widely accessible and routinely implemented.
The ABCSG is proud to contribute to this important international project, which deepens our understanding of treatment options for HER2-negative, high-risk breast cancer patients with BRCA1/2 germline mutations. Further insights into long-term safety are expected from the ongoing long-term observation, which will continue until 2028.
New England Journal of Medicine, June 3, 2021;
DOI: 10.1056/NEJMoa2105215
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