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 Apr 18;10(1):29.
doi: 10.1038/s41523-024-00636-4.

Tumor-infiltrating lymphocytes in HER2-positive breast cancer treated with neoadjuvant chemotherapy and dual HER2-blockade

M C Liefaard  1   2 , A van der Voort  2 , M van Seijen  1 , B Thijssen  3   4 , J Sanders  5 , S Vonk  1   6 , L Mittempergher  7 , R Bhaskaran  7 , L de Munck  8 , A E van Leeuwen-Stok  9 , R Salgado  10 , H M Horlings  5 , E H Lips  1 , G S Sonke  11
Affiliations

Tumor-infiltrating lymphocytes in HER2-positive breast cancer treated with neoadjuvant chemotherapy and dual HER2-blockade

M C Liefaard et al. NPJ Breast Cancer. .

Abstract

Tumor-infiltrating lymphocytes (TILs) have been associated with outcomes in HER2-positive breast cancer patients treated with neoadjuvant chemotherapy and trastuzumab. However, it remains unclear if TILs could be a prognostic and/or predictive biomarker in the context of dual HER2-targeting treatment. In this study, we evaluated the association between TILs and pathological response (pCR) and invasive-disease free survival (IDFS) in 389 patients with stage II-III HER2 positive breast cancer who received neoadjuvant anthracycline-containing or anthracycline-free chemotherapy combined with trastuzumab and pertuzumab in the TRAIN-2 trial. Although no significant association was seen between TILs and pCR, patients with TIL scores ≥60% demonstrated an excellent 3-year IDFS of 100% (95% CI 100-100), regardless of hormone receptor status, nodal stage and attainment of pCR. Additionally, in patients with hormone receptor positive disease, TILs as a continuous variable showed a trend to a positive association with pCR (adjusted Odds Ratio per 10% increase in TILs 1.15, 95% CI 0.99-1.34, p = 0.070) and IDFS (adjusted Hazard Ratio per 10% increase in TILs 0.71, 95% CI 0.50-1.01, p = 0.058). We found no interactions between TILs and anthracycline treatment. Our results suggest that high TIL scores might be able to identify stage II-III HER2-positive breast cancer patients with a favorable prognosis.

PubMed Disclaimer

Conflict of interest statement

G.S.S. reports institutional research support from Agendia, AstraZeneca, Merck, Novartis, Roche and Seagen and consultancy fees paid to the institute from Biovica and Seagen. H.M.H. reports institutional research support from Roche. A.E.v.L. reports institutional research support from Agendia, AstraZeneca, Daiichi, Lilly, Novartis and Roche. L.M and R.B. were employees of Agendia NV at the time of analysis. The remaining authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Pathological complete response rate according to TIL scores and treatment.
a Pathological complete response rate according to treatment arm and TIL score with a 14% cut-off. b Pathological complete response rate according to treatment arm and TIL score categorized as low (≤10%), intermediate (11–59%) and high (≥60%). FEC-T 5-Fluoruracil, Epirubicin, Cyclophosphamide, Trastuzumab, Pertuzumab, PTC Paclitaxel, Trastuzumab, Carboplatin, Pertuzumab, TILs tumor-infiltrating lymphocytes.
Fig. 2
Fig. 2. Survival curves according to TILs ≥ 60% and clinical variables.
a Kaplan–Meier curve for TILs <60% vs. TILs ≥60% at diagnosis. b Kaplan–Meier curve for the combination of TILs (60% cut-off) and pCR after neoadjuvant treatment. c Kaplan–Meier curve for the combination of TILs (60% cut-off) and nodal stage at diagnosis. d Kaplan–Meier curve for the combination of TILs (60% cut-off) and hormone receptor status. All presented p-values are from global log-rank tests. TIL tumor infiltrating lymphocytes, IDFS invasive disease free survival, pCR pathological complete response, cN0 node-negative, cN+ node-positive, HR neg hormone receptor negative, HR pos hormone receptor positive.
See this image and copyright information in PMC

References

    1. Cardoso F, et al. Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2019;30:1674. doi: 10.1093/annonc/mdz189. - DOI - PubMed
    1. Korde LA, et al. Neoadjuvant Chemotherapy, Endocrine Therapy, and Targeted Therapy for Breast Cancer: ASCO Guideline. J. Clin. Oncol. 2021;39:1485–1505. doi: 10.1200/JCO.20.03399. - DOI - PMC - PubMed
    1. van Ramshorst MS, et al. Neoadjuvant chemotherapy with or without anthracyclines in the presence of dual HER2 blockade for HER2-positive breast cancer (TRAIN-2): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2018;19:1630–1640. doi: 10.1016/S1470-2045(18)30570-9. - DOI - PubMed
    1. van der Voort A, et al. Efficacy of neoadjuvant treatment with or without pertuzumab in patients with stage II and III HER2-positive breast cancer: a nationwide cohort analysis of pathologic response and 5-year survival. Breast. 2022;65:110–115. doi: 10.1016/j.breast.2022.07.005. - DOI - PMC - PubMed
    1. Schneeweiss A, et al. 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. 2013;24:2278–2284. doi: 10.1093/annonc/mdt182. - DOI - PubMed