Top

Published in:

Open Access 16-05-2024 | Cytostatic Therapy | Research

Alteration of PD-L1 (SP142) status after neoadjuvant chemotherapy and its clinical significance in triple-negative breast cancer

Authors: Ji Won Woo, Eun Kyung Han, Koung Jin Suh, Se Hyun Kim, Jee Hyun Kim, So Yeon Park

Published in: Breast Cancer Research and Treatment | Issue 2/2024

Abstract

Purpose

The tumor immune microenvironment can change after neoadjuvant chemotherapy (NAC) for triple-negative breast cancer (TNBC). We aimed to investigate the effects of NAC on PD-L1 (SP142) status and its clinical significance in TNBC.

Methods

Paired samples of biopsy and resection specimens were collected from 182 patients with TNBC before and after NAC. PD-L1 (SP142) expression in immune cells in pre- and post-NAC breast cancer samples and the changes between them were analyzed, along with their relationships with the clinicopathological features and clinical outcomes of the patients.

Results

Of the 182 patients, 61 (33.5%) achieved pathologic complete response (pCR) after NAC. PD-L1 (SP142) positivity, defined as immune cell staining in ≥ 1% of tumor area, was a predictor for pCR. PD-L1-positive immune cells significantly increased after NAC (2.8% to 5.2% on average) in 109 patients with measurable residual disease. Alteration of PD-L1 status was observed in 24 (22.0%) of the 109 patients with measurable residual tumors after NAC, and all PD-L1 status-converted patients, except one, revealed negative-to-positive conversion. Regarding chemotherapeutic agents, the use of platinum agents was associated with a significant increase in PD-L1-positive immune cells after NAC. In survival analyses, a positive PD-L1 status after NAC and increase of PD-L1-positive immune cells after NAC were associated with better recurrence-free survival of the patients.

Conclusion

PD-L1 (SP142) status changes after NAC, mostly as a positive conversion. As PD-L1 (SP142) status can convey prognostic and predictive information, it needs to be tested before and after NAC.

Available only for authorised users

Bauer KR, Brown M, Cress RD, Parise CA, Caggiano V (2007) Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry. Cancer 109:1721–1728. https://doi.org/10.1002/cncr.22618CrossRefPubMed

Vagia E, Mahalingam D, Cristofanilli M (2020) The landscape of targeted therapies in TNBC. Cancers (Basel). https://doi.org/10.3390/cancers12040916CrossRefPubMed

Schmid P, Adams S, Rugo HS et al (2018) Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med 379:2108–2121. https://doi.org/10.1056/NEJMoa1809615CrossRefPubMed

Miles D, Gligorov J, Andre F et al (2021) Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer. Ann Oncol 32:994–1004. https://doi.org/10.1016/j.annonc.2021.05.801CrossRefPubMed

Cortes J, Cescon DW, Rugo HS et al (2020) Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet 396:1817–1828. https://doi.org/10.1016/S0140-6736(20)32531-9CrossRefPubMed

Schmid P, Cortes J, Pusztai L et al (2020) Pembrolizumab for early triple-negative breast cancer. N Engl J Med 382:810–821. https://doi.org/10.1056/NEJMoa1910549CrossRefPubMed

Ventana R PD-L1 (SP142) Assay Interpretation Guide for Triple-Negative Breast Carcinoma (TNBC). Last revised July 29, 2020

Agilent Technologies. PD-L1 IHC 22C3 pharmDx Interpretation Manual –Triple-Negative Breast Cancer (TNBC). Last revised Nov 16, 2020

Thompson AM, Moulder-Thompson SL (2012) Neoadjuvant treatment of breast cancer. Ann Oncol 23(Suppl 10):x231–x236. https://doi.org/10.1093/annonc/mds324CrossRefPubMedPubMedCentral

10.

Merlano MC, Denaro N, Galizia D et al (2022) How chemotherapy affects the tumor immune microenvironment: a narrative review. Biomedicines. https://doi.org/10.3390/biomedicines10081822CrossRefPubMedPubMedCentral

11.

Axelrod ML, Nixon MJ, Gonzalez-Ericsson PI et al (2020) Changes in peripheral and local tumor immunity after neoadjuvant chemotherapy reshape clinical outcomes in patients with breast cancer. Clin Cancer Res 26:5668–5681. https://doi.org/10.1158/1078-0432.CCR-19-3685CrossRefPubMedPubMedCentral

12.

van den Ende T, van den Boorn HG, Hoonhout NM et al (2020) Priming the tumor immune microenvironment with chemo(radio)therapy: A systematic review across tumor types. Biochim Biophys Acta Rev Cancer 1874:188386. https://doi.org/10.1016/j.bbcan.2020.188386CrossRefPubMed

13.

Alhesa A, Awad H, Bloukh S, Al-Balas M, El-Sadoni M, Qattan D, Azab B, Saleh T (2022) PD-L1 expression in breast invasive ductal carcinoma with incomplete pathological response to neoadjuvant chemotherapy. Int J Immunopathol Pharmacol 36:3946320221078433. https://doi.org/10.1177/03946320221078433CrossRefPubMed

14.

Hoffmann LG, Sarian LO, Vassallo J et al (2021) Evaluation of PD-L1 and tumor infiltrating lymphocytes in paired pretreatment biopsies and post neoadjuvant chemotherapy surgical specimens of breast carcinoma. Sci Rep 11:22478. https://doi.org/10.1038/s41598-021-00944-wCrossRefPubMedPubMedCentral

15.

Lee J, Kim DM, Lee A (2019) prognostic role and clinical association of tumor-infiltrating lymphocyte, programmed death ligand-1 expression with neutrophil-lymphocyte ratio in locally advanced triple-negative breast cancer. Cancer Res Treat 51:649–663. https://doi.org/10.4143/crt.2018.270CrossRefPubMed

16.

Pelekanou V, Carvajal-Hausdorf DE, Altan M 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 19:91. https://doi.org/10.1186/s13058-017-0884-8CrossRefPubMedPubMedCentral

17.

Tomioka N, Azuma M, Ikarashi M, Yamamoto M, Sato M, Watanabe KI, Yamashiro K, Takahashi M (2018) The therapeutic candidate for immune checkpoint inhibitors elucidated by the status of tumor-infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) expression in triple negative breast cancer (TNBC). Breast Cancer 25:34–42. https://doi.org/10.1007/s12282-017-0781-0CrossRefPubMed

18.

Denkert C, Loibl S, Noske A et al (2010) Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer. J Clin Oncol 28:105–113. https://doi.org/10.1200/JCO.2009.23.7370CrossRefPubMed

19.

Mao Y, Qu Q, Zhang Y, Liu J, Chen X, Shen K (2014) The value of tumor infiltrating lymphocytes (TILs) for predicting response to neoadjuvant chemotherapy in breast cancer: a systematic review and meta-analysis. PLoS ONE 9:e115103. https://doi.org/10.1371/journal.pone.0115103CrossRefPubMedPubMedCentral

20.

Dieci MV, Criscitiello C, Goubar A 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 25:611–618. https://doi.org/10.1093/annonc/mdt556CrossRefPubMedPubMedCentral

21.

Luen SJ, Salgado R, Dieci MV 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 30:236–242. https://doi.org/10.1093/annonc/mdy547CrossRefPubMed

22.

Allison KH, Hammond MEH, Dowsett M et al (2020) Estrogen and progesterone receptor testing in breast cancer: ASCO/CAP guideline update. J Clin Oncol 38:1346–1366. https://doi.org/10.1200/JCO.19.02309CrossRefPubMed

23.

Wolff AC, Hammond MEH, Allison KH et al (2018) Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. Arch Pathol Lab Med 142:1364–1382. https://doi.org/10.5858/arpa.2018-0902-SACrossRefPubMed

24.

Symmans WF, Peintinger F, Hatzis C et al (2007) Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol 25:4414–4422. https://doi.org/10.1200/JCO.2007.10.6823CrossRefPubMed

25.

Kuerer HM, Newman LA, Smith TL et al (1999) Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol 17:460–469. https://doi.org/10.1200/JCO.1999.17.2.460CrossRefPubMed

26.

Salgado R, Denkert C, Demaria S et al (2015) The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann Oncol 26:259–271. https://doi.org/10.1093/annonc/mdu450CrossRefPubMed

27.

Dieci MV, Radosevic-Robin N, Fineberg S 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 52:16–25. https://doi.org/10.1016/j.semcancer.2017.10.003CrossRefPubMed

28.

Stanowska O, Kuczkiewicz-Siemion O, Debowska M, Olszewski WP, Jagiello-Gruszfeld A, Tysarowski A, Prochorec-Sobieszek M (2022) PD-L1-positive high-grade triple-negative breast cancer patients respond better to standard neoadjuvant treatment-A retrospective study of PD-L1 expression in relation to different clinicopathological parameters. J Clin Med. https://doi.org/10.3390/jcm11195524CrossRefPubMedPubMedCentral

29.

Wimberly H, Brown JR, Schalper K et al (2015) PD-L1 expression correlates with tumor-infiltrating lymphocytes and response to neoadjuvant chemotherapy in breast cancer. Cancer Immunol Res 3:326–332. https://doi.org/10.1158/2326-6066.CIR-14-0133CrossRefPubMed

30.

Shin J, Chung JH, Kim SH et al (2019) Effect of platinum-based chemotherapy on PD-L1 expression on tumor cells in non-small cell lung cancer. Cancer Res Treat 51:1086–1097. https://doi.org/10.4143/crt.2018.537CrossRefPubMed

31.

Yi M, Zheng X, Niu M, Zhu S, Ge H, Wu K (2022) Combination strategies with PD-1/PD-L1 blockade: current advances and future directions. Mol Cancer 21:28. https://doi.org/10.1186/s12943-021-01489-2CrossRefPubMedPubMedCentral

Title: Alteration of PD-L1 (SP142) status after neoadjuvant chemotherapy and its clinical significance in triple-negative breast cancer
Authors: Ji Won Woo
Eun Kyung Han
Koung Jin Suh
Se Hyun Kim
Jee Hyun Kim
So Yeon Park
Publication date: 16-05-2024
Publisher: Springer US
Keywords: Cytostatic Therapy
Breast Cancer
Breast Cancer
Published in: Breast Cancer Research and Treatment / Issue 2/2024
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-024-07359-x

2024 ESC Congress

Springer Medicine

Alteration of PD-L1 (SP142) status after neoadjuvant chemotherapy and its clinical significance in triple-negative breast cancer

Abstract

Purpose

Methods

Results

Conclusion

2024 ESC Congress

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 2/2024

Correction to: Ethnic inequities in use of breast conserving surgery and radiation therapy in Aotearoa/New Zealand: which factors contribute?

UM171 suppresses breast cancer progression by inducing KLF2

Combination of monensin and erlotinib synergistically inhibited the growth and cancer stem cell properties of triple-negative breast cancer by simultaneously inhibiting EGFR and PI3K signaling pathways

Development and application of a weighted change score to evaluate interventions for vasomotor symptoms in patients with breast cancer using regression trees: a cohort study

The REMAR (Rhein-Main-Registry) real-world study: prospective evaluation of the 21-gene breast recurrence score® assay in addition to Ki-67 for adjuvant treatment decisions in early-stage breast cancer

A correlation study of adhesion G protein-coupled receptors as potential therapeutic targets for breast cancer