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

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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Journal
BMC Cancer
Published
2026-08-03
DOI
https://doi.org/10.1186/s12885-026-16667-y
Primary Topic
Breast Cancer Treatment Studies
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article
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article

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

Ugur Ozberk, Mesut Yılmaz, Lamia Şeker Can, Ece Baydar et al.
BMC Cancer
Breast Cancer Treatment Studies
article

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

Ugur Ozberk, Mesut Yılmaz, Lamia Şeker Can, Ece Baydar, Fatma Keskin Uzundere, Onur Yazdan Balçık, Nargız Majidova, Hasibe Bilge Gür, Kayhan Ertürk, İlhan Hacıbekiroğlu, Anıl Karakayalı, Guzin Demirağ, Akif DOĞAN, Ahmet Gülmez, Tuğba Akın Telli, Ayberk Bayramgil, Efnan Algın, İlker Ökten, Hasan Çağrı Yıldırım, Mustafa Seyyar, Erdem Göker, Onur Alkan, Rumeysa Çolak, Meltem Baykara, Yasemi̇n Kemal, Seval Akay, Tolga Köşeci, Çağlar Köseoğlu, Neslihan Özyurt, Cengiz Akosman, Kezban Nur Pilancı, Ali̇ Kalem, Yunus Emre Altıntaş, Sedat Biter, Salih Tünbekici, Yasemin Aydınalp Camadan, İlknur Deliktaş Onur, Okan Aydın, Ali Süner, Pınar Peker, İlkay Çıtakkul, Gamze Emin, Gökçe Gül GÜNEYSU, Emir Gökhan Kahraman, Pervin Can Sanci, Melih Akpunar, İsmail Nazlı, Elif Sahin, Merve Kuday Özkan, Ali Alkan, Mustafa Şahbazlar, Müge Sönmez, Tulay Kus, Musa Barış Aykan, Teyfik Demir, Mehmet Uzun, Umut Kefeli, Canan Çolak, Sinem Solmaz Karabel, Ülkü Yalçıntaş Arslan, Halil Göksel Güzel, Atila Yıldırım, Tugay Avcı, Zuhat Urakçı, Devrim Çabuk
article en

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.

BMC Cancer
Dicle University (TR), Izmir University (TR), Karadeniz Technical University (TR), Istanbul Bilim University (TR), Manisa Celal Bayar University (TR), Başkent University (TR), Ondokuz Mayıs University (TR), Bezmiâlem Vakıf Üniversitesi (TR), Ege University (TR), Konya Numune Hastanesi (TR), Gülhane Askerî Tıp Akademisi (TR), Adana Hospital (TR), Memorial Ankara Hospital (TR), Ankara Onkoloji Eğitim ve Araştırma Hastanesi (TR), Antalya Eğitim ve Araştırma Hastanesi (TR), Ümraniye Eğitim ve Araştırma Hastanesi (TR), Memorial Sisli Hospital (TR), Medical Park Gaziantep Hospital (TR), Sakarya Eğitim ve Araştırma Hastanesi (TR), Alanya University (TR), Bakırköy Dr.Sadi Konuk Eğitim ve Araştırma Hastanesi (TR), Education Training And Research (US), Şanlıurfa Mehmet Akif İnan Eğitim ve Araştırma Hastanesi (TR), Izmir Tepecik Eğitim ve Araştırma Hastanesi (TR), Istanbul Eye Hospital (TR), Department of Public Health (MM), Antalya IVF (TR), Afyonkarahisar Sağlık Bilimleri Üniversitesi, Maltepe University (TR), Kocaeli Üniversitesi (TR), Afyon Kocatepe University (TR), Cukurova University (TR), Istanbul Medeniyet University (TR), Gaziantep University (TR), Ordu University (TR), Istanbul University (TR), Muğla University (TR)
Good health and well-being
Openalex Percentile: Top 13%
Breast Cancer Treatment Studies
DOIOpen Access PDFOpenAlex
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