Impact of adjuvant endocrine therapy on disease-free survival in early triple-positive breast cancer: a multicenter retrospective cohort study of the Turkish oncology group
Abstract
Triple-positive breast cancer (TPBC), characterized by concurrent ER, PR, and HER2 positivity, poses unique therapeutic challenges due to ER–HER2 crosstalk. The optimal adjuvant endocrine therapy in TPBC patients receiving anti-HER2 regimens remains poorly defined. This multicenter retrospective cohort study included 1044 early-stage TPBC patients (stage II–III) treated with neoadjuvant chemotherapy and HER2-targeted therapy between 2007 and 2024. Disease-free survival (DFS) was analyzed using Kaplan–Meier estimates and Cox regression models, with separate multivariate analyses for premenopausal ( n = 474) and postmenopausal ( n = 570) patients. At a median follow-up of 52 months, the 5-year DFS was 88.2% and the pCR rate was 44.3%. Residual disease was the strongest prognostic factor in both menopausal groups. In premenopausal patients, low ER expression (< 50%; HR 2.202; p = 0.003) and stage III disease (HR 2.722; p < 0.001) were independent adverse prognostic factors. Endocrine therapy type was associated with DFS on unadjusted analysis (log-rank p = 0.021) but was not significant after multivariable adjustment (adjusted overall p = 0.069). Although tamoxifen plus LHRH agonist showed a numerically higher recurrence risk than tamoxifen alone in exploratory subgroup comparison (HR 2.124; 95% CI 1.093–4.129; p = 0.026), this finding should be interpreted with caution given the non-significant overall association. In postmenopausal patients, stage III disease was the only independent adverse factor among baseline clinicopathological variables (HR 2.225; p = 0.003), and endocrine therapy type was not associated with DFS (log-rank p = 0.751; adjusted overall p = 0.614). In this large real-world TPBC cohort, residual disease was the dominant prognostic factor regardless of menopausal status. Endocrine therapy type was not independently associated with DFS after multivariable adjustment in either menopausal group. These findings are hypothesis-generating and should not guide endocrine therapy selection; prospective studies are warranted in premenopausal TPBC.
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Authors: Mustafa Seyyar, Pervin Can Sanci, Akif DOĞAN, Sedat Biter, Tolga Köşeci, Onur Yazdan Balçık, Sinem Solmaz Karabel, Ali̇ Kalem, Cengiz Akosman, Kezban Nur Pilancı, İlknur Deliktaş Onur, Ülkü Yalçıntaş Arslan, Yasemi̇n Kemal, Tugay Avcı, Mustafa Şahbazlar, Seval Akay, Emir Gökhan Kahraman, Ayberk Bayramgil, Yunus Emre Altıntaş, Salih Tünbekici, Erdem Göker, Canan Çolak, Teyfik Demir, Guzin Demirağ, Gökçe Gül GÜNEYSU, Musa Barış Aykan, İsmail Nazlı, Onur Alkan, İlker Ökten, Rumeysa Çolak, Mesut Yılmaz, Hasibe Bilge Gür, İlhan Hacıbekiroğlu, Müge Sönmez, Neslihan Özyurt, Okan Aydın, Kayhan Ertürk, Elif Sahin, Anıl Karakayalı, Ece Baydar, İlkay Çıtakkul, Gamze Emin, Atila Yıldırım, Ahmet Gülmez, Ugur Ozberk, Efnan Algın, Çağlar Köseoğlu, Fatma Keskin Uzundere, Zuhat Urakçı, Melih Akpunar, Ali Alkan, Ali Süner, Pınar Peker, Yasemin Aydınalp Camadan, Lamia Şeker Can, Tuğba Akın Telli, Nargız Majidova, Mehmet Uzun, Merve Kuday Özkan, Meltem Baykara, Halil Göksel Güzel, Hasan Çağrı Yıldırım, Umut Kefeli, Devrim Çabuk, Tulay Kus
Institutions: Memorial Ankara Hospital, Ondokuz Mayıs University, Kocaeli Üniversitesi, Education Training And Research, Gaziantep University, Ege University, Medical Park Gaziantep Hospital, Istanbul University, Antalya Eğitim ve Araştırma Hastanesi, Karadeniz Technical University, Bezmiâlem Vakıf Üniversitesi, Ordu University, Istanbul Medeniyet University, Muğla University, Manisa Celal Bayar University, Afyon Kocatepe University, Cukurova University, Izmir University, Alanya University, Department of Public Health, Memorial Sisli Hospital, Ankara Onkoloji Eğitim ve Araştırma Hastanesi, Ümraniye Eğitim ve Araştırma Hastanesi, Gülhane Askerî Tıp Akademisi, Bakırköy Dr.Sadi Konuk Eğitim ve Araştırma Hastanesi, Sakarya Eğitim ve Araştırma Hastanesi, Istanbul Eye Hospital, Başkent University, Adana Hospital, Dicle University, Konya Numune Hastanesi, Şanlıurfa Mehmet Akif İnan Eğitim ve Araştırma Hastanesi, Istanbul Bilim University, Maltepe University, Izmir Tepecik Eğitim ve Araştırma Hastanesi, Afyonkarahisar Sağlık Bilimleri Üniversitesi, Antalya IVF