Association of tumor-infiltrating lymphocytes with distant disease-free survival in the ShortHER randomized adjuvant trial for patients with early HER2+ breast cancer

M. V. Dieci, P. Conte, G. Bisagni, A. A. Brandes, A. Frassoldati, L. Cavanna, A. Musolino, F. Giotta, A. Rimanti, O. Garrone, E. Bertone, K. Cagossi, S. Sarti, A. Ferro, F. Piacentini, A. Maiorana, E. Orvieto, M. Sanders, F. Miglietta, S. Balduzzi & 2 others R. D'Amico, V. Guarneri

Research output: Contribution to journalArticle

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Abstract

Background There is the need to identify new prognostic markers to refine risk stratification for HER2-positive early breast cancer patients. The aim of this study was to evaluate the association of tumor-infiltrating lymphocytes (TILs) with distant disease-free survival (DDFS) in patients with HER2-positive early breast cancer enrolled in the ShortHER adjuvant trial which compared 9 weeks versus 1-year trastuzumab in addition to chemotherapy, and to test the interaction between TILs and treatment arm. Patients and methods Stromal TILs were assessed for 866 cases on centralized hematoxylin and eosin-stained tumor slides. The association of TILs as 10% increments with DDFS was assessed with Cox models. Kaplan-Meier curves were estimated for patients with TILs ≥20% and TILs <20%. Median follow-up was 6.1 years. Results Median TILs was 5% (Q1-Q3 1%-15%). Increased TILs were independently associated with better DDFS in multivariable model [hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.59-0.89, P = 0.006, for each 10% TILs increment]. Five years DDFS rates were 91.1% for patients with TILs <20% and 95.7% for patients with TILs ≥20% (P = 0.025). The association between 10% TILs increments and DDFS was significant for patients randomized to 9 weeks of trastuzumab (HR 0.60, 95% CI 0.41-0.88) but not for patients treated with 1 year of trastuzumab (HR 0.89, 95% CI 0.71-1.12; test for interaction P = 0.088). For patients with TILs <20%, the HR for the comparison between the short versus the long arm was 1.75 (95% CI 1.09-2.80, P=0.021); whereas, for patients with TILs ≥20% the HR for the comparison of short versus long arm was 0.23 (95% CI 0.05-1.09, P = 0.064), resulting in a significant interaction (P = 0.015). Conclusions TILs are an independent prognostic factor for HER2-positive early breast cancer patients treated with adjuvant chemotherapy and trastuzumab and may refine the ability to identify patients at low risk of relapse eligible for de-escalated adjuvant therapy.

Original languageEnglish
Pages (from-to)418-423
Number of pages6
JournalAnnals of Oncology
Volume30
Issue number3
DOIs
Publication statusPublished - Mar 1 2019

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Tumor-Infiltrating Lymphocytes
Disease-Free Survival
Breast Neoplasms
Confidence Intervals
Proportional Hazards Models
Hematoxylin
Adjuvant Chemotherapy
Eosine Yellowish-(YS)

Keywords

  • adjuvant
  • early breast cancer
  • HER2-positive breast cancer
  • trastuzumab
  • tumor-infiltrating lymphocytes

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

Association of tumor-infiltrating lymphocytes with distant disease-free survival in the ShortHER randomized adjuvant trial for patients with early HER2+ breast cancer. / Dieci, M. V.; Conte, P.; Bisagni, G.; Brandes, A. A.; Frassoldati, A.; Cavanna, L.; Musolino, A.; Giotta, F.; Rimanti, A.; Garrone, O.; Bertone, E.; Cagossi, K.; Sarti, S.; Ferro, A.; Piacentini, F.; Maiorana, A.; Orvieto, E.; Sanders, M.; Miglietta, F.; Balduzzi, S.; D'Amico, R.; Guarneri, V.

In: Annals of Oncology, Vol. 30, No. 3, 01.03.2019, p. 418-423.

Research output: Contribution to journalArticle

Dieci, MV, Conte, P, Bisagni, G, Brandes, AA, Frassoldati, A, Cavanna, L, Musolino, A, Giotta, F, Rimanti, A, Garrone, O, Bertone, E, Cagossi, K, Sarti, S, Ferro, A, Piacentini, F, Maiorana, A, Orvieto, E, Sanders, M, Miglietta, F, Balduzzi, S, D'Amico, R & Guarneri, V 2019, 'Association of tumor-infiltrating lymphocytes with distant disease-free survival in the ShortHER randomized adjuvant trial for patients with early HER2+ breast cancer', Annals of Oncology, vol. 30, no. 3, pp. 418-423. https://doi.org/10.1093/annonc/mdz007
Dieci, M. V. ; Conte, P. ; Bisagni, G. ; Brandes, A. A. ; Frassoldati, A. ; Cavanna, L. ; Musolino, A. ; Giotta, F. ; Rimanti, A. ; Garrone, O. ; Bertone, E. ; Cagossi, K. ; Sarti, S. ; Ferro, A. ; Piacentini, F. ; Maiorana, A. ; Orvieto, E. ; Sanders, M. ; Miglietta, F. ; Balduzzi, S. ; D'Amico, R. ; Guarneri, V. / Association of tumor-infiltrating lymphocytes with distant disease-free survival in the ShortHER randomized adjuvant trial for patients with early HER2+ breast cancer. In: Annals of Oncology. 2019 ; Vol. 30, No. 3. pp. 418-423.
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abstract = "Background There is the need to identify new prognostic markers to refine risk stratification for HER2-positive early breast cancer patients. The aim of this study was to evaluate the association of tumor-infiltrating lymphocytes (TILs) with distant disease-free survival (DDFS) in patients with HER2-positive early breast cancer enrolled in the ShortHER adjuvant trial which compared 9 weeks versus 1-year trastuzumab in addition to chemotherapy, and to test the interaction between TILs and treatment arm. Patients and methods Stromal TILs were assessed for 866 cases on centralized hematoxylin and eosin-stained tumor slides. The association of TILs as 10{\%} increments with DDFS was assessed with Cox models. Kaplan-Meier curves were estimated for patients with TILs ≥20{\%} and TILs <20{\%}. Median follow-up was 6.1 years. Results Median TILs was 5{\%} (Q1-Q3 1{\%}-15{\%}). Increased TILs were independently associated with better DDFS in multivariable model [hazard ratio (HR) 0.73, 95{\%} confidence interval (CI) 0.59-0.89, P = 0.006, for each 10{\%} TILs increment]. Five years DDFS rates were 91.1{\%} for patients with TILs <20{\%} and 95.7{\%} for patients with TILs ≥20{\%} (P = 0.025). The association between 10{\%} TILs increments and DDFS was significant for patients randomized to 9 weeks of trastuzumab (HR 0.60, 95{\%} CI 0.41-0.88) but not for patients treated with 1 year of trastuzumab (HR 0.89, 95{\%} CI 0.71-1.12; test for interaction P = 0.088). For patients with TILs <20{\%}, the HR for the comparison between the short versus the long arm was 1.75 (95{\%} CI 1.09-2.80, P=0.021); whereas, for patients with TILs ≥20{\%} the HR for the comparison of short versus long arm was 0.23 (95{\%} CI 0.05-1.09, P = 0.064), resulting in a significant interaction (P = 0.015). Conclusions TILs are an independent prognostic factor for HER2-positive early breast cancer patients treated with adjuvant chemotherapy and trastuzumab and may refine the ability to identify patients at low risk of relapse eligible for de-escalated adjuvant therapy.",
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TY - JOUR

T1 - Association of tumor-infiltrating lymphocytes with distant disease-free survival in the ShortHER randomized adjuvant trial for patients with early HER2+ breast cancer

AU - Dieci, M. V.

AU - Conte, P.

AU - Bisagni, G.

AU - Brandes, A. A.

AU - Frassoldati, A.

AU - Cavanna, L.

AU - Musolino, A.

AU - Giotta, F.

AU - Rimanti, A.

AU - Garrone, O.

AU - Bertone, E.

AU - Cagossi, K.

AU - Sarti, S.

AU - Ferro, A.

AU - Piacentini, F.

AU - Maiorana, A.

AU - Orvieto, E.

AU - Sanders, M.

AU - Miglietta, F.

AU - Balduzzi, S.

AU - D'Amico, R.

AU - Guarneri, V.

PY - 2019/3/1

Y1 - 2019/3/1

N2 - Background There is the need to identify new prognostic markers to refine risk stratification for HER2-positive early breast cancer patients. The aim of this study was to evaluate the association of tumor-infiltrating lymphocytes (TILs) with distant disease-free survival (DDFS) in patients with HER2-positive early breast cancer enrolled in the ShortHER adjuvant trial which compared 9 weeks versus 1-year trastuzumab in addition to chemotherapy, and to test the interaction between TILs and treatment arm. Patients and methods Stromal TILs were assessed for 866 cases on centralized hematoxylin and eosin-stained tumor slides. The association of TILs as 10% increments with DDFS was assessed with Cox models. Kaplan-Meier curves were estimated for patients with TILs ≥20% and TILs <20%. Median follow-up was 6.1 years. Results Median TILs was 5% (Q1-Q3 1%-15%). Increased TILs were independently associated with better DDFS in multivariable model [hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.59-0.89, P = 0.006, for each 10% TILs increment]. Five years DDFS rates were 91.1% for patients with TILs <20% and 95.7% for patients with TILs ≥20% (P = 0.025). The association between 10% TILs increments and DDFS was significant for patients randomized to 9 weeks of trastuzumab (HR 0.60, 95% CI 0.41-0.88) but not for patients treated with 1 year of trastuzumab (HR 0.89, 95% CI 0.71-1.12; test for interaction P = 0.088). For patients with TILs <20%, the HR for the comparison between the short versus the long arm was 1.75 (95% CI 1.09-2.80, P=0.021); whereas, for patients with TILs ≥20% the HR for the comparison of short versus long arm was 0.23 (95% CI 0.05-1.09, P = 0.064), resulting in a significant interaction (P = 0.015). Conclusions TILs are an independent prognostic factor for HER2-positive early breast cancer patients treated with adjuvant chemotherapy and trastuzumab and may refine the ability to identify patients at low risk of relapse eligible for de-escalated adjuvant therapy.

AB - Background There is the need to identify new prognostic markers to refine risk stratification for HER2-positive early breast cancer patients. The aim of this study was to evaluate the association of tumor-infiltrating lymphocytes (TILs) with distant disease-free survival (DDFS) in patients with HER2-positive early breast cancer enrolled in the ShortHER adjuvant trial which compared 9 weeks versus 1-year trastuzumab in addition to chemotherapy, and to test the interaction between TILs and treatment arm. Patients and methods Stromal TILs were assessed for 866 cases on centralized hematoxylin and eosin-stained tumor slides. The association of TILs as 10% increments with DDFS was assessed with Cox models. Kaplan-Meier curves were estimated for patients with TILs ≥20% and TILs <20%. Median follow-up was 6.1 years. Results Median TILs was 5% (Q1-Q3 1%-15%). Increased TILs were independently associated with better DDFS in multivariable model [hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.59-0.89, P = 0.006, for each 10% TILs increment]. Five years DDFS rates were 91.1% for patients with TILs <20% and 95.7% for patients with TILs ≥20% (P = 0.025). The association between 10% TILs increments and DDFS was significant for patients randomized to 9 weeks of trastuzumab (HR 0.60, 95% CI 0.41-0.88) but not for patients treated with 1 year of trastuzumab (HR 0.89, 95% CI 0.71-1.12; test for interaction P = 0.088). For patients with TILs <20%, the HR for the comparison between the short versus the long arm was 1.75 (95% CI 1.09-2.80, P=0.021); whereas, for patients with TILs ≥20% the HR for the comparison of short versus long arm was 0.23 (95% CI 0.05-1.09, P = 0.064), resulting in a significant interaction (P = 0.015). Conclusions TILs are an independent prognostic factor for HER2-positive early breast cancer patients treated with adjuvant chemotherapy and trastuzumab and may refine the ability to identify patients at low risk of relapse eligible for de-escalated adjuvant therapy.

KW - adjuvant

KW - early breast cancer

KW - HER2-positive breast cancer

KW - trastuzumab

KW - tumor-infiltrating lymphocytes

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U2 - 10.1093/annonc/mdz007

DO - 10.1093/annonc/mdz007

M3 - Article

VL - 30

SP - 418

EP - 423

JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

IS - 3

ER -