Adjuvant ovarian function suppression and aromatase inhibitors in premenopausal patients with hormone receptor and HER2 positive breast cancer, by timing of chemotherapy and trastuzumab and response to neoadjuvant therapy
Year: 2025
Type: article
Study design: Observational Study
Abstract: BACKGROUND: The benefit of adjuvant ovarian function suppression (OFS) and aromatase inhibitors (AI) in premenopausal patients with hormone receptor positive, HER2 positive (HR+/HER2+) breast cancer (BC) is unclear. We aimed to investigate this question in a retrospective cohort, stratified by timing (adjuvant or neoadjuvant) of chemotherapy and trastuzumab and by response to neoadjuvant therapy. METHODS: Patients aged <45Y at diagnosis, with stage I-III HR + HER2+ BC, treated with (neo)adjuvant chemotherapy and trastuzumab ( ± pertuzumab) and endocrine therapy were included. LHRH-agonists and oophorectomy were considered OFS. We compared distant disease-free survival (DDFS) with tamoxifen, OFS + tamoxifen and OFS + AI in three cohorts: neoadjuvant-pathologic complete response (pCR), neoadjuvant-residual disease (RD) and adjuvant. Endocrine therapy (ET) was modeled as a time dependent covariate in cox logistic regression analyses. RESULTS: The study included 1124 patients with median follow-up of 72.6 months (range:0-205 months). DDFS rates at 5 years were 83.9 %, 86.8 % and 92.1 % with tamoxifen, OFS + tamoxifen and OFS + AI respectively in the RD group, 94.3 %, 97.6 % and 96.5 % in the pCR group, and 94.3 %, 93.4 % and 98.6 % in the adjuvant group. OFS + AI was associated with better DDFS compared to tamoxifen in the RD group (n = 366) (multivariable weighted HR 0.28. 95 % CI 0.11-.069, p = 0.006), but associations of ET with DDFS in the pCR (n = 307, p = 0.59) and adjuvant (n = 451, p = 0.18) cohorts were not detected. Stage III was associated with worse DDFS in all groups. CONCLUSION: OFS + AI were associated with better DDFS in patients with RD after neoadjuvant therapy. Our findings can assist shared decision-making on adjuvant endocrine therapy of these patients.
Source: The Breast
Authors: Ayelet Shai, Hans Wildiers, Claudio Venieri, Katarzyna Pogoda, Barbro Linderholm, Matteo Lambertini, Leonor Matos, Eleonora De Maio D'Esposito, Nawale Hajjaji, Erika Matos, Lucía González Cortijo, Giuseppe Fotia, Ana Fortuna, Tal Sella, Helena Gouveia, Laurent Rosset, Anastasia Constantinidou, Eurydice Angeli, Irfan Cicin, Vivianne Tjan-Heijnen, Natacha Ruyssers, Sofie Demasure, Areen Abu Remilah, Greet Huygh, Shani Paluch-Shimon, Edoardo Chiappe, Natali Shirron, Patrick Neven, Mehmet Artac, Bilgesah Kilictas, Jalal Baranseh, Elena Vicente-Rubio, Mustafa Atci, Ottavia Amato, Frederieke van Duijnhoven
Institutions: Technion – Israel Institute of Technology, Rambam Health Care Campus, Universitair Ziekenhuis Leuven, University of Milan, Fondazione IRCCS Istituto Nazionale dei Tumori, The Maria Sklodowska-Curie National Research Institute of Oncology, Sahlgrenska University Hospital, Ospedale Policlinico San Martino, University of Genoa, Champalimaud Foundation, Centro Champalimaud, Institut universitaire du cancer de Toulouse Oncopole, Centre Oscar Lambret, Institute of Oncology Ljubljana, Hospital Universitario Quirónsalud Madrid, Unidade Local de Saúde do Algarve, Sheba Medical Center, Bank of Cyprus Oncology Center, Hôpital Avicenne, Istinye University, Maastricht University Medical Centre, AZ Turnhout, AZ Groeninge, Shaare Zedek Medical Center, Bikur Cholim Hospital, Hebrew University of Jerusalem, Hadassah Medical Center, Necmettin Erbakan University, Luigi Sacco Hospital, ASST Fatebenefratelli Sacco, The Netherlands Cancer Institute
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,200
OpenAlex ID: W4417080343