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

被引：69

作者：

Dieci, M. V. ^{[1
,2
]}

Conte, P. ^{[1
,2
]}

Bisagni, G. ^{[3
]}

Brandes, A. A. ^{[4
]}

Frassoldati, A. ^{[5
]}

Cavanna, L. ^{[6
]}

Musolino, A. ^{[7
]}

Giotta, F. ^{[8
]}

Rimanti, A. ^{[9
]}

Garrone, O. ^{[10
]}

Bertone, E. ^{[11
]}

Cagossi, K. ^{[12
]}

Sarti, S. ^{[13
]}

Ferro, A. ^{[14
]}

Piacentini, F. ^{[15
,16
]}

Maiorana, A. ^{[17
]}

Orvieto, E. ^{[18
]}

Sanders, M. ^{[19
]}

Miglietta, F. ^{[1
]}

Balduzzi, S. ^{[20
]}

D'Amico, R. ^{[20
]}

Guarneri, V. ^{[1
,2
]}

机构：

[1] Univ Padua, Dept Surg Oncol & Gastroenterol, Padua, Italy

[2] Ist Oncol Veneto IRCCS, Med Oncol 2, Padua, Italy

[3] Azienda USL IRCCS, Oncol Unit, Dept Oncol & Adv Technol, Reggio Emilia, Italy

[4] IRCCS Ist Sci Neurol, Med Oncol, Azienda Unita Sanit Locale Bologna, Bologna, Italy

[5] S Anna Univ Hosp, Clin Oncol, Dept Morphol Surg & Expt Med, Ferrara, Italy

[6] Guglielmo da Saliceto Hosp, Dept Oncol Hematol, Piacenza, Italy

[7] Univ Hosp Parma, Med Oncol Unit, Piacenza, Italy

[8] Ist Tumori Giovanni Paolo II, Div Med Oncol, IRCCS, Bari, Italy

[9] Azienda Osped Mantova, Med Oncol, Mantua, Italy

[10] AOS Croce & Carle Teaching Hosp, Med Oncol, Cuneo, Italy

[11] St Anna Hosp, Med Oncol, Turin, Italy

[12] Ramazzini Hosp, Breast Unit Ausl Modena, Carpi, Italy

[13] IRCCS, Ist Sci Romagnolo Studio & Cura Tumori IRST, Meldola, Italy

[14] Rete Clin Senol Oncol Med S Chiara, Trento, Italy

[15] Univ Hosp Modena, Div Med Oncol, Dept Med & Surg Sci Children & Adults, Modena, Italy

[16] Azienda Osped Univ Modena, Modena, Italy

[17] Univ Hosp Modena, Dept Diagnost Clin Med & Publ Hlth, Modena, Italy

[18] Ulss 5 Polesana, Pathol Unit, Rovigo, Italy

[19] Vanderbilt Univ, Med Ctr, Pathol Microbiol & Immunol, Nashville, TN USA

[20] Univ Hosp Modena, Dept Med & Surg Sci Children & Adults, Modena, Italy

来源：

ANNALS OF ONCOLOGY | 2019年 / 30卷 / 03期

关键词：

early breast cancer; tumor-infiltrating lymphocytes; HER2-positive breast cancer; trastuzumab; adjuvant; HER2-POSITIVE BREAST-CANCER; TRASTUZUMAB; SUBTYPES; CHEMOTHERAPY; WOMEN;

D O I：

10.1093/annonc/mdz007

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 TILs20% and TILs<20%. Median follow-up was 6.1years. 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 TILs20% (P=0.025). The association between 10% TILs increments and DDFS was significant for patients randomized to 9weeks of trastuzumab (HR 0.60, 95% CI 0.41-0.88) but not for patients treated with 1year 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 TILs20% 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.

引用

页码：418 / 423

页数：6

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