Skip to main content
Top

Open Access 04-05-2024 | Breast Cancer | Clinical trial

Tumor-infiltrating lymphocytes as a predictor of axillary and primary tumor pathological response after neoadjuvant chemotherapy in patients with breast cancer: a retrospective cohort study

Authors: Kian Chin, Amalia H. Landén, Anikó Kovács, Fredrik Wärnberg, Maria Ekholm, Per Karlsson, Roger Olofsson Bagge

Published in: Breast Cancer Research and Treatment

Login to get access

Abstract

Purpose

Tumor-infiltrating lymphocytes (TILs) can predict complete pathological response (pCR) of tumor in the breast but not so well-defined in the axilla after neoadjuvant chemotherapy. Since axillary surgery is being increasingly de-escalated after NACT, we aimed to investigate the relationship between TILs and pCR in the axilla and breast, as well as survival amongst NACT patients.

Methods

Clinicopathological data on patients who underwent NACT between 2013 and 2020 were retrospectively examined. Specifically, pre-TILs (before NACT), post-TILs (after NACT) and ΔTIL (changes in TILs) were assessed. Primary endpoint was pCR and secondary endpoints were breast cancer-free interval (BCFI) and overall survival (OS).

Results

Two hundred and twenty patients with nodal metastases were included. Overall axillary and breast pCR rates were 42.7% (94/220) and 39.1% (86/220), respectively, whereas the combined pCR rate was 32.7% (72/220). High pre-TILs (OR 2.03, 95% CI 1.02–4.05; p = 0.04) predicted axillary pCR whereas, high post-TILs (OR 0.33, 95% CI 0.14–0.76; p = 0.009) and increased ΔTILs (OR 0.25, 95% CI 0.08–0.79; p = 0.02) predicted non-axillary pCR. TILs were not a significant predictor for BCFI and OS.

Conclusions

This study supports the potential use of pre-TILs to select initially node-positive patients for axillary surgical de-escalation after NACT.
Literature
2.
go back to reference Hennigs A et al (2016) Changes in chemotherapy usage and outcome of early breast cancer patients in the last decade. Breast Cancer Res Treat 160(3):491–499CrossRefPubMedPubMedCentral Hennigs A et al (2016) Changes in chemotherapy usage and outcome of early breast cancer patients in the last decade. Breast Cancer Res Treat 160(3):491–499CrossRefPubMedPubMedCentral
3.
go back to reference Schneeweiss A et al (2013) Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol 24(9):2278–2284CrossRefPubMed Schneeweiss A et al (2013) Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol 24(9):2278–2284CrossRefPubMed
5.
go back to reference Boughey JC et al (2013) Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial. JAMA 310(14):1455–1461CrossRefPubMedPubMedCentral Boughey JC et al (2013) Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial. JAMA 310(14):1455–1461CrossRefPubMedPubMedCentral
6.
go back to reference Kuehn T et al (2013) Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy (SENTINA): a prospective, multicentre cohort study. Lancet Oncol 14(7):609–618CrossRefPubMed Kuehn T et al (2013) Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy (SENTINA): a prospective, multicentre cohort study. Lancet Oncol 14(7):609–618CrossRefPubMed
7.
go back to reference Boileau JF et al (2015) Sentinel node biopsy after neoadjuvant chemotherapy in biopsy-proven node-positive breast cancer: the SN FNAC study. J Clin Oncol 33(3):258–264CrossRefPubMed Boileau JF et al (2015) Sentinel node biopsy after neoadjuvant chemotherapy in biopsy-proven node-positive breast cancer: the SN FNAC study. J Clin Oncol 33(3):258–264CrossRefPubMed
8.
go back to reference Zetterlund LH et al (2017) Swedish prospective multicenter trial evaluating sentinel lymph node biopsy after neoadjuvant systemic therapy in clinically node-positive breast cancer. Breast Cancer Res Treat 163(1):103–110CrossRefPubMedPubMedCentral Zetterlund LH et al (2017) Swedish prospective multicenter trial evaluating sentinel lymph node biopsy after neoadjuvant systemic therapy in clinically node-positive breast cancer. Breast Cancer Res Treat 163(1):103–110CrossRefPubMedPubMedCentral
9.
go back to reference Bruni D, Angell HK, Galon J (2020) The immune contexture and Immunoscore in cancer prognosis and therapeutic efficacy. Nat Rev Cancer 20(11):662–680CrossRefPubMed Bruni D, Angell HK, Galon J (2020) The immune contexture and Immunoscore in cancer prognosis and therapeutic efficacy. Nat Rev Cancer 20(11):662–680CrossRefPubMed
10.
go back to reference Manuel M et al (2012) Lymphopenia combined with low TCR diversity (divpenia) predicts poor overall survival in metastatic breast cancer patients. Oncoimmunology 1(4):432–440CrossRefPubMedPubMedCentral Manuel M et al (2012) Lymphopenia combined with low TCR diversity (divpenia) predicts poor overall survival in metastatic breast cancer patients. Oncoimmunology 1(4):432–440CrossRefPubMedPubMedCentral
12.
go back to reference Denkert C et al (2018) Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol 19(1):40–50CrossRefPubMed Denkert C et al (2018) Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol 19(1):40–50CrossRefPubMed
13.
14.
go back to reference Li S et al (2022) Predictive and prognostic values of tumor infiltrating lymphocytes in breast cancers treated with neoadjuvant chemotherapy: A meta-analysis. Breast 66:97–109CrossRefPubMedPubMedCentral Li S et al (2022) Predictive and prognostic values of tumor infiltrating lymphocytes in breast cancers treated with neoadjuvant chemotherapy: A meta-analysis. Breast 66:97–109CrossRefPubMedPubMedCentral
15.
go back to reference Dieci MV et al (2018) Update on tumor-infiltrating lymphocytes (TILs) in breast cancer, including recommendations to assess TILs in residual disease after neoadjuvant therapy and in carcinoma in situ: a report of the international immuno-oncology biomarker working group on breast cancer. Semin Cancer Biol 52(Pt 2):16–25CrossRefPubMed Dieci MV et al (2018) Update on tumor-infiltrating lymphocytes (TILs) in breast cancer, including recommendations to assess TILs in residual disease after neoadjuvant therapy and in carcinoma in situ: a report of the international immuno-oncology biomarker working group on breast cancer. Semin Cancer Biol 52(Pt 2):16–25CrossRefPubMed
16.
go back to reference Kovács A et al (2019) Effect of radiotherapy after breast-conserving surgery depending on the presence of tumor-infiltrating lymphocytes: a long-term follow-up of the SweBCG91RT randomized trial. J Clin Oncol 37(14):1179–1187CrossRefPubMed Kovács A et al (2019) Effect of radiotherapy after breast-conserving surgery depending on the presence of tumor-infiltrating lymphocytes: a long-term follow-up of the SweBCG91RT randomized trial. J Clin Oncol 37(14):1179–1187CrossRefPubMed
19.
go back to reference Ogston KN et al (2003) A new histological grading system to assess response of breast cancers to primary chemotherapy: prognostic significance and survival. Breast 12(5):320–327CrossRefPubMed Ogston KN et al (2003) A new histological grading system to assess response of breast cancers to primary chemotherapy: prognostic significance and survival. Breast 12(5):320–327CrossRefPubMed
20.
go back to reference Tolaney SM et al (2021) Updated standardized definitions for efficacy end points (STEEP) in adjuvant breast cancer clinical trials: STEEP version 2.0. J Clin Oncol 39(24):2720–2731CrossRefPubMedPubMedCentral Tolaney SM et al (2021) Updated standardized definitions for efficacy end points (STEEP) in adjuvant breast cancer clinical trials: STEEP version 2.0. J Clin Oncol 39(24):2720–2731CrossRefPubMedPubMedCentral
21.
go back to reference (www.swebcg.se) (2020) S.B.C.G. Nationell Bröstcancer Vårdprogram (National Treatment Guidelines for Breast Cancer). Online publication. (www.​swebcg.​se) (2020) S.B.C.G. Nationell Bröstcancer Vårdprogram (National Treatment Guidelines for Breast Cancer). Online publication.
22.
go back to reference Paijens ST et al (2021) Tumor-infiltrating lymphocytes in the immunotherapy era. Cell Mol Immunol 18(4):842–859CrossRefPubMed Paijens ST et al (2021) Tumor-infiltrating lymphocytes in the immunotherapy era. Cell Mol Immunol 18(4):842–859CrossRefPubMed
23.
go back to reference Pelekanou V et al (2017) Effect of neoadjuvant chemotherapy on tumor-infiltrating lymphocytes and PD-L1 expression in breast cancer and its clinical significance. Breast Cancer Res 19(1):91CrossRefPubMedPubMedCentral Pelekanou V et al (2017) Effect of neoadjuvant chemotherapy on tumor-infiltrating lymphocytes and PD-L1 expression in breast cancer and its clinical significance. Breast Cancer Res 19(1):91CrossRefPubMedPubMedCentral
24.
go back to reference Criscitiello C et al (2018) A gene signature to predict high tumor-infiltrating lymphocytes after neoadjuvant chemotherapy and outcome in patients with triple-negative breast cancer. Ann Oncol 29(1):162–169CrossRefPubMed Criscitiello C et al (2018) A gene signature to predict high tumor-infiltrating lymphocytes after neoadjuvant chemotherapy and outcome in patients with triple-negative breast cancer. Ann Oncol 29(1):162–169CrossRefPubMed
25.
go back to reference Lee H et al (2020) Changes in tumor-infiltrating lymphocytes after neoadjuvant chemotherapy and clinical significance in triple negative breast cancer. Anticancer Res 40(4):1883–1890CrossRefPubMed Lee H et al (2020) Changes in tumor-infiltrating lymphocytes after neoadjuvant chemotherapy and clinical significance in triple negative breast cancer. Anticancer Res 40(4):1883–1890CrossRefPubMed
26.
go back to reference Llano-León M et al (2023) Effect of neoadjuvant chemotherapy on tumor immune infiltration in breast cancer patients: systematic review and meta-analysis. PLoS ONE 18(4):e0277714CrossRefPubMedPubMedCentral Llano-León M et al (2023) Effect of neoadjuvant chemotherapy on tumor immune infiltration in breast cancer patients: systematic review and meta-analysis. PLoS ONE 18(4):e0277714CrossRefPubMedPubMedCentral
27.
go back to reference Pelekanou V et al (2018) Tumor-infiltrating lymphocytes and PD-L1 expression in pre- and posttreatment breast cancers in the SWOG S0800 phase II neoadjuvant chemotherapy trial. Mol Cancer Ther 17(6):1324–1331CrossRefPubMedPubMedCentral Pelekanou V et al (2018) Tumor-infiltrating lymphocytes and PD-L1 expression in pre- and posttreatment breast cancers in the SWOG S0800 phase II neoadjuvant chemotherapy trial. Mol Cancer Ther 17(6):1324–1331CrossRefPubMedPubMedCentral
28.
go back to reference Dieci MV et al (2014) Prognostic value of tumor-infiltrating lymphocytes on residual disease after primary chemotherapy for triple-negative breast cancer: a retrospective multicenter study. Ann Oncol 25(3):611–618CrossRefPubMedPubMedCentral Dieci MV et al (2014) Prognostic value of tumor-infiltrating lymphocytes on residual disease after primary chemotherapy for triple-negative breast cancer: a retrospective multicenter study. Ann Oncol 25(3):611–618CrossRefPubMedPubMedCentral
29.
go back to reference Miyashita M et al (2015) Prognostic significance of tumor-infiltrating CD8+ and FOXP3+ lymphocytes in residual tumors and alterations in these parameters after neoadjuvant chemotherapy in triple-negative breast cancer: a retrospective multicenter study. Breast Cancer Res 17(1):124CrossRefPubMedPubMedCentral Miyashita M et al (2015) Prognostic significance of tumor-infiltrating CD8+ and FOXP3+ lymphocytes in residual tumors and alterations in these parameters after neoadjuvant chemotherapy in triple-negative breast cancer: a retrospective multicenter study. Breast Cancer Res 17(1):124CrossRefPubMedPubMedCentral
30.
go back to reference Wang K et al (2017) The CD4/CD8 ratio of tumor-infiltrating lymphocytes at the tumor-host interface has prognostic value in triple-negative breast cancer. Hum Pathol 69:110–117CrossRefPubMed Wang K et al (2017) The CD4/CD8 ratio of tumor-infiltrating lymphocytes at the tumor-host interface has prognostic value in triple-negative breast cancer. Hum Pathol 69:110–117CrossRefPubMed
31.
go back to reference Stenmark Tullberg A et al (2021) Immune infiltrate in the primary tumor predicts effect of adjuvant radiotherapy in breast cancer; results from the randomized SweBCG91RT trial. Clin Cancer Res 27(3):749–758CrossRefPubMed Stenmark Tullberg A et al (2021) Immune infiltrate in the primary tumor predicts effect of adjuvant radiotherapy in breast cancer; results from the randomized SweBCG91RT trial. Clin Cancer Res 27(3):749–758CrossRefPubMed
33.
go back to reference Asano Y et al (2017) Prediction of survival after neoadjuvant chemotherapy for breast cancer by evaluation of tumor-infiltrating lymphocytes and residual cancer burden. BMC Cancer 17(1):888CrossRefPubMedPubMedCentral Asano Y et al (2017) Prediction of survival after neoadjuvant chemotherapy for breast cancer by evaluation of tumor-infiltrating lymphocytes and residual cancer burden. BMC Cancer 17(1):888CrossRefPubMedPubMedCentral
34.
go back to reference Luen SJ et al (2019) Prognostic implications of residual disease tumor-infiltrating lymphocytes and residual cancer burden in triple-negative breast cancer patients after neoadjuvant chemotherapy. Ann Oncol 30(2):236–242CrossRefPubMed Luen SJ et al (2019) Prognostic implications of residual disease tumor-infiltrating lymphocytes and residual cancer burden in triple-negative breast cancer patients after neoadjuvant chemotherapy. Ann Oncol 30(2):236–242CrossRefPubMed
35.
go back to reference Mamtani A et al (2022) Is local recurrence higher among patients who downstage to breast conservation after neoadjuvant chemotherapy? Cancer 128(3):471–478CrossRefPubMed Mamtani A et al (2022) Is local recurrence higher among patients who downstage to breast conservation after neoadjuvant chemotherapy? Cancer 128(3):471–478CrossRefPubMed
37.
go back to reference Amgad M et al (2020) Report on computational assessment of tumor infiltrating lymphocytes from the international immuno-oncology biomarker working group. NPJ Breast Cancer 6:16CrossRefPubMedPubMedCentral Amgad M et al (2020) Report on computational assessment of tumor infiltrating lymphocytes from the international immuno-oncology biomarker working group. NPJ Breast Cancer 6:16CrossRefPubMedPubMedCentral
38.
go back to reference Baker JL et al (2022) Association between physical activity and neoadjuvant chemotherapy completion and pathologic complete response in primary breast cancer: the CANTO study. Br J Cancer 127(5):886–891CrossRefPubMedPubMedCentral Baker JL et al (2022) Association between physical activity and neoadjuvant chemotherapy completion and pathologic complete response in primary breast cancer: the CANTO study. Br J Cancer 127(5):886–891CrossRefPubMedPubMedCentral
Metadata
Title
Tumor-infiltrating lymphocytes as a predictor of axillary and primary tumor pathological response after neoadjuvant chemotherapy in patients with breast cancer: a retrospective cohort study
Authors
Kian Chin
Amalia H. Landén
Anikó Kovács
Fredrik Wärnberg
Maria Ekholm
Per Karlsson
Roger Olofsson Bagge
Publication date
04-05-2024
Publisher
Springer US
Published in
Breast Cancer Research and Treatment
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-024-07334-6
Live Webinar | 01-10-2024 | 12:30 (CEST)

Recent advances in the use of CAR T-cell therapies in relapsed/refractory diffuse large B-cell lymphoma and follicular lymphoma

Live: Tuesday 1st October 2024, 12:30-14:00 (CEST)

In this live webinar, Professor Martin Dreyling and an esteemed, international panel of CAR-T experts will discuss the very latest data on the safety, efficacy and clinical impact of CAR T-cell therapies in the treatment of r/r DLBCL and r/r FL, as presented at ASH 2023, EU CAR-T 2024, and EHA 2024. 

Please note, this webinar is not intended for healthcare professionals based in the US and UK.

Sponsored by: Novartis Pharma AG

Chaired by: Prof. Martin Dreyling
Developed by: Springer Healthcare