Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 May 15;30(10):2160-2169.
doi: 10.1158/1078-0432.CCR-24-0106.

Tumor-Infiltrating Lymphocytes Refine Outcomes in Triple-Negative Breast Cancer Treated with Anthracycline-Free Neoadjuvant Chemotherapy

Miguel Martín #  1   2   3   4   5 , Rachel Yoder  6 , Roberto Salgado  7 , María Del Monte-Millán  1   2   3 , Enrique L Álvarez  1   2 , Isabel Echavarría  1   2   3 , Joshua M Staley  6 , Anne P O'Dea  8 , Lauren E Nye  8 , Shane R Stecklein  9 , Coralia Bueno  10 , Yolanda Jerez  1   2   3 , María Cebollero  1   2 , Oscar Bueno  1   2 , José Ángel García Saenz  11 , Fernando Moreno  1   4 , Uriel Bohn  12 , Henry Gómez  13 , Tatiana Massarrah  1   2   3 , Qamar J Khan  8 , Andrew K Godwin  9 , Sara López-Tarruella  1   2   3   4   5 , Priyanka Sharma #  8
Affiliations

Tumor-Infiltrating Lymphocytes Refine Outcomes in Triple-Negative Breast Cancer Treated with Anthracycline-Free Neoadjuvant Chemotherapy

Miguel Martín et al. Clin Cancer Res. .

Abstract

Purpose: Stromal tumor-infiltrating lymphocytes (sTIL) are associated with pathologic complete response (pCR) and long-term outcomes for triple-negative breast cancer (TNBC) in the setting of anthracycline-based chemotherapy. The impact of sTILs on refining outcomes beyond prognostic information provided by pCR in anthracycline-free neoadjuvant chemotherapy (NAC) is not known.

Experimental design: This is a pooled analysis of two studies where patients with stage I (T>1 cm)-III TNBC received carboplatin (AUC 6) plus docetaxel (75 mg/m2; CbD) NAC. sTILs were evaluated centrally on pre-treatment hematoxylin and eosin slides using standard criteria. Cox regression analysis was used to examine the effect of variables on event-free survival (EFS) and overall survival (OS).

Results: Among 474 patients, 44% had node-positive disease. Median sTILs were 5% (range, 1%-95%), and 32% of patients had ≥30% sTILs. pCR rate was 51%. On multivariable analysis, T stage (OR, 2.08; P = 0.007), nodal status (OR, 1.64; P = 0.035), and sTILs (OR, 1.10; P = 0.011) were associated with pCR. On multivariate analysis, nodal status (HR, 0.46; P = 0.008), pCR (HR, 0.20; P < 0.001), and sTILs (HR, 0.95; P = 0.049) were associated with OS. At 30% cut-point, sTILs stratified outcomes in stage III disease, with 5-year OS 86% versus 57% in ≥30% versus <30% sTILs (HR, 0.29; P = 0.014), and numeric trend in stage II, with 5-year OS 93% versus 89% in ≥30% versus <30% sTILs (HR, 0.55; P = 0.179). Among stage II-III patients with pCR, EFS was better in those with ≥30% sTILs (HR, 0.16; P, 0.047).

Conclusions: sTILs density was an independent predictor of OS beyond clinicopathologic features and pathologic response in patients with TNBC treated with anthracycline-free CbD chemotherapy. Notably, sTILs density stratified outcomes beyond tumor-node-metastasis (TNM) stage and pathologic response. These findings highlight the role of sTILs in patient selection and stratification for neo/adjuvant escalation and de-escalation strategies.

PubMed Disclaimer

Conflict of interest statement

Potential conflicts of interest: MM reports research funding from PUMA; consulting/advisory fees from Roche, Novartis, AstraZeneca, Daiichi-Sankyo, Seagen, Lilly, and Sanofi; speaker’s honoraria from Seagen, Lilly, AstraZeneca, Pfizer, Daiichi-Sankyo, and Roche; role as chairman for GEICAM; and member of the Board of Directors for TRIO. RS reports research funding from Roche, Puma, Merck, and BMS; consulting or advisory role for BMS, Roche, Owkin, AstraZeneca, Daiichi Sankyo, and Case45; and travel and conferences fees from Roche, Merck, BMS, Daiichii Sankyo, and AstraZeneca. IE reports speakers’ fees from Roche, Teva, Novartis, Pfizer, and Lilly; and advisory role for Lilly and AstraZeneca. APO reports honoraria, consulting/advisory role, and travel fees from AstraZeneca, Daiichi Sankyo, Novartis, Pfizer, Puma Biotechnology, Seattle Genetics, and Stemline. LEN reports advisory role for Myriad. CB reports speaker’s honoraria from Roche, Novartis, Lilly, MSD, AstraZeneca, Daiichi Sankyo, and GSK; and travel grants from Roche, Novartis, and Pfizer. YJ reports consultant/advisory role fees from Novartis, Pfizer, Roche, and AstraZeneca; speaker’s honoraria from Roche, Novartis, Lilly, and AstraZeneca; and travel and training grants from Roche, Novartis, Pfizer, and Lilly. JAGS reports consulting/advisory role for Lilly, Novartis, AstraZeneca, Daiichi Sankyo, Stemline Menarini, Pierre Fabre, Seagen, Gilead, Adium, and Exact Sciences. FM reports research funding from Pfizer; consulting/advisory role for Pfizer, Novartis, Seagen, AstraZeneca, Daiichi Sankyo, Gilead, Roche, and Exact Sciences; and travel expenses from Pfizer and Pierre Fabre. TM reports consulting/advisory board fees from AstraZeneca, Novartis, Roche, and GSK; and travel grants from Novartis and AstraZeneca. AKG reports research funding to the institution from VITRAC Therapeutics and Predicine; consulting/advisory role for Sinochips Diagnostics; honoraria from Biovica; and stock options for Clara Biotech and EXOKĒRYX. SLT reports speaker’s bureau fees from Lilly; and consulting/advisory role fees from AstraZeneca, Novartis, Roche, Pfizer, Pierre Fabre, Lilly, Seagen, Daiichi Sankyo Europe GmbH, Gilead Sciences, MDS, GSK, and Veracyte. PS reports research funding to the institution from Novartis, Bristol Myers Squibb, Merck, and Gilead; consulting/advisory board participation for Merck, Pfizer, Gilead, GSK, Sanofi, Exact Life sciences, SeaGen, Novartis, and AstraZeneca; stock ownership in Amgen, Johnson & Johnson/Janssen, and Sanofi; and royalties from UpToDate. All remaining authors declare no potential conflicts of interest.

Figures

Figure 1:
Figure 1:
Survival by sTILs. (A) Event-free survival in all stages. (B) Overall survival in all stages. (C) Event-free survival in TNM stage I. (D) Overall survival in TNM stage I. (E) Event-free survival in TNM stage II. (F) Overall survival in TNM stage II. (G) Event-free survival in TNM stage III. (H) Overall survival in TNM stage III.
Figure 2:
Figure 2:
Survival by sTILs and pathologic response in TNM stage II-III. (A) Event-free survival in patients with pathologic complete response. (B) Overall survival in patients with pathologic complete response. (C) Event-free survival in patients with residual disease. (D) Overall survival in patients with residual disease.
See this image and copyright information in PMC

References

    1. Dent R, Trudeau M, Pritchard KI, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. Aug 1 2007;13(15 Pt 1):4429–34. doi:10.1158/1078-0432.ccr-06-3045 - DOI - PubMed
    1. Liedtke C, Mazouni C, Hess KR, et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol. Mar 10 2008;26(8):1275–81. doi:10.1200/jco.2007.14.4147 - DOI - PubMed
    1. Cardoso F, Kyriakides S, Ohno S, et al. Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. Oct 1 2019;30(10):1674. doi:10.1093/annonc/mdz189 - DOI - PubMed
    1. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer. Version 4.2023. 2023. March 23, 2023. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf - PubMed
    1. Wolff AC, Blackford AL, Visvanathan K, et al. Risk of marrow neoplasms after adjuvant breast cancer therapy: the national comprehensive cancer network experience. J Clin Oncol. Feb 1 2015;33(4):340–8. doi:10.1200/jco.2013.54.6119 - DOI - PMC - PubMed

MeSH terms

LinkOut - more resources