What have we achieved for women with breast cancer so far?

IBCSG has focused on clinical trials designed to tailor treatments to breast cancer patient populations to improve prognosis, minimize morbidity, and enhance quality of life. Some selected examples are cited below:

• Key Achievements of the POSITIVE Trial Since 2014, the ETOP IBCSG Partners Foundation, together with BIG and the Alliance for Clinical Trials in Oncology in North America, has been conducting the POSITIVE study (Pregnancy Outcome and Safety of Interrupting Therapy for women with endocrine responsIVE breast cancer). The trial investigates whether young women with hormone-sensitive breast cancer can safely interrupt endocrine therapy to pursue pregnancy. A total of 518 women aged 42 or younger enrolled. The first results, published in the New England Journal of Medicine in May 2023, showed that pausing endocrine therapy for up to two years to attempt pregnancy did not increase short-term breast cancer recurrence. https://www.nejm.org/doi/full/10.1056/NEJMoa2212856?query=featured_home With about six years of follow-up now available, updated data presented at the 2025 ESMO Congress confirm that these results remain consistent. Recurrence rates among women who paused therapy (12.3%) were comparable to those in similar cohorts who did not interrupt treatment (13.2%). In total, 76% of participants became pregnant, and 440 babies were born, including 18 sets of twins. Long-term follow-up through 2029 is essential to fully understand recurrence risks over time. Beyond these main outcomes, the POSITIVE trial has also offered a unique opportunity to study key aspects of fertility, pregnancy, breastfeeding, and tumor biology in young women with hormone-sensitive breast cancer, as well as insights into their psychological well-being.
  • Fertility preservation & assisted reproductive technologies (ART): A secondary analysis presented at the 2023 San Antonio Breast Cancer Symposium (SABCS) and published in the Journal of Clinical Oncology (2024) showed that fertility preservation and ART are effective and do not increase three-year recurrence risk. https://ascopubs.org/doi/10.1200/JCO.23.02292
  • Breastfeeding: Another analysis presented at the 2024 ESMO Congress and published in Journal of Clinical Oncology (2025) confirmed that breastfeeding after hormone-sensitive early breast cancer is feasible and does not increase short-term recurrence risk. https://ascopubs.org/doi/10.1200/JCO-24-02697
  • Hormonal factors predictive of fertility: Results presented at the 2025 ESMO Breast and published in The Breast (2025) highlighted the relevance of hormonal factors when counselling patients who interrupt endocrine therapy to pursue pregnancy. Hormonal factors predictive of fertility in patients with breast cancer interrupting adjuvant endocrine therapy to attempt pregnancy in POSITIVE trial - The Breast Taken together, the achievements of the POSITIVE trial represent significant progress for young breast cancer survivors navigating treatment decisions while planning a family. These findings provide reassuring, evidence-based guidance that supports informed care.
• The group pioneered research demonstrating the role of accurately-determined steroid hormone receptor status (estrogen and/or progesterone receptor) of the tumor and menopausal status of the patient as critical features that impact treatment selection. Early studies demonstrated the importance of hormonal therapy against disease expressing hormone receptors, the hormonal effects of chemotherapy for biologically-defined premenopausal women, and the importance of chemotherapy against disease that does not express hormone receptors.
• IBCSG conducted the BIG 1-98 study, which enrolled over 8000 women and demonstrated improved outcomes with the aromatase inhibitor, letrozole, compared with tamoxifen for postmenopausal women with hormone receptor positive disease.
• IBCSG 23-01 showed that axillary dissection did not improve disease control compared with no axillary dissection for patients with micrometastases in sentinel lymph nodes, thus avoiding adverse side effects of the more extensive surgery for many women.
• The SOLE (Study of Letrozole Extension) trial demonstrated that for postmenopausal women with node-positive disease who had completed 4-6 years of prior post-surgical hormonal therapy, using up to 5 more years of intermittent letrozole therapy (with 3 months of planned treatment interruption) had similar disease control with less toxicity compared with continuous letrozole administration.
• The CALOR (Chemotherapy Adjuvant for Local Or Regional recurrence) trial showed that using chemotherapy after resecting loco-regional recurrences improved disease control for recurrences that were hormone receptor negative, but not for those that were hormone receptor positive  
• The PANACEA study provided proof-of principle evidence that immunotherapy, specifically PD-1 inhibition like pembrolizumab, can help overcome trastuzumab resistance that is seen in patients with metastatic HER2-positive breast cancer.
  In addition, quantification of tumor infiltrating lymphocytes (TILs) seems to be a meaningful way for us to identify those who would benefit most from an immunotherapeutic approach.
• The SOFT (Suppression of Ovarian Function Trial) and TEXT (Tamoxifen and Exemestane Trial) studies established new standards of care for premenopausal women with higher-risk hormone responsive disease, demonstrating improved control of disease recurrence with ovarian function suppression plus the aromatase inhibitor, exemestane, compared with either tamoxifen alone, or tamoxifen plus ovarian function suppression.
• SOFT and TEXT also demonstrated that patients with lower-risk disease achieved excellent disease control with tamoxifen alone.