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Background <p>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.</p> Methods <p>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 (<i>n</i> = 474) and postmenopausal (<i>n</i> = 570) patients.</p> Results <p>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 (&lt; 50%; HR 2.202; <i>p</i> = 0.003) and stage III disease (HR 2.722; <i>p</i> &lt; 0.001) were independent adverse prognostic factors. Endocrine therapy type was associated with DFS on unadjusted analysis (log-rank <i>p</i> = 0.021) but was not significant after multivariable adjustment (adjusted overall <i>p</i> = 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; <i>p</i> = 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; <i>p</i> = 0.003), and endocrine therapy type was not associated with DFS (log-rank <i>p</i> = 0.751; adjusted overall <i>p</i> = 0.614).</p> Conclusions <p>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.</p>

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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

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  • 发表日期：

    2026年8月3日

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  • Mustafa Seyyar,
  • Pervin Can Şancı,
  • Akif Doğan,
  • Sedat Biter,
  • Tolga Köşeci,
  • Onur Yazdan Balçık,
  • Sinem Solmaz Karabel,
  • Ali Kalem,
  • Cengiz Akosman,
  • Kezban Nur Pilancı,
  • İlknur Deliktaş Onur,
  • Ülkü Yalçıntaş Arslan,
  • Yasemin Kemal,
  • Tugay Avcı,
  • Mustafa Şahbazlar,
  • Seval Akay,
  • Emir Gökhan Kahraman,
  • Ayberk Bayramgil,
  • Yunus Emre Altıntaş,
  • Salih Tünbekici,
  • Erdem Göker,
  • Canan Çolak,
  • Teyfik Demir,
  • Güzin Demirağ,
  • Gökçe Gül Güneysu,
  • Musa Barış Aykan,
  • İsmail Nazlı,
  • Onur Alkan,
  • İlker Nihat Ökten,
  • Rumeysa Çolak,
  • Mesut Yılmaz,
  • Hasibe Bilge Gür,
  • İlhan Hacıbekiroğlu,
  • Müge Sönmez,
  • Neslihan Özyurt,
  • Okan Aydın,
  • Kayhan Ertürk,
  • Elif Şahin,
  • Anıl Karakayalı,
  • Ece Baydar,
  • İlkay Çıtakkul,
  • Gamze Emin,
  • Atila Yıldırım,
  • Ahmet Gülmez,
  • Uğur Özberk,
  • 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,
  • Nargiz Majidova,
  • Mehmet Uzun,
  • Merve Kuday Özkan,
  • Meltem Baykara,
  • Halil Göksel Güzel,
  • Hasan Çağrı Yıldırım,
  • Umut Kefeli,
  • Devrim Çabuk,
  • Tulay Kus

摘要

Background

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.

Methods

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.

Results

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).

Conclusions

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.