Royal College of Surgeons in Ireland
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The role of infiltrating lymphocytes in the neo-adjuvant treatment of women with HER2-positive breast cancer

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posted on 2023-01-10, 17:04 authored by AJ Eustace, Stephen MaddenStephen Madden, Joanna FayJoanna Fay, DM Collins, Elaine KayElaine Kay, Katherine SheehanKatherine Sheehan, Simon FurneySimon Furney, B Moran, A Fagan, PG Morris, A Teiserskiene, Arnold HillArnold Hill, Liam GroganLiam Grogan, JM Walshe, Oscar BreathnachOscar Breathnach, Colm PowerColm Power, Deirdre DukeDeirdre Duke, K Egan, WM Gallagher, N O’Donovan, J Crown, Sinead ToomeySinead Toomey, Bryan HennessyBryan Hennessy

Background: Pre-treatment tumour-associated lymphocytes (TILs) and stromal lymphocytes (SLs) are independent predictive markers of future pathological complete response (pCR) in HER2-positive breast cancer. Whilst studies have correlated baseline lymphocyte levels with subsequent pCR, few have studied the impact of neoadjuvant therapy on the immune environment.

Methods: We performed TIL analysis and T-cell analysis by IHC on the pretreatment and 'On-treatment' samples from patients recruited on the Phase-II TCHL (NCT01485926) clinical trial. Data were analysed using the Wilcoxon signed-rank test and the Spearman rank correlation.

Results: In our sample cohort (n = 66), patients who achieved a pCR at surgery, post-chemotherapy, had significantly higher counts of TILs (p = 0.05) but not SLs (p = 0.08) in their pre-treatment tumour samples. Patients who achieved a subsequent pCR after completing neo-adjuvant chemotherapy had significantly higher SLs (p = 9.09 × 10-3) but not TILs (p = 0.1) in their 'On-treatment' tumour biopsies. In a small cohort of samples (n = 16), infiltrating lymphocyte counts increased after 1 cycle of neo-adjuvant chemotherapy only in those tumours of patients who did not achieve a subsequent pCR. Finally, reduced CD3 + (p = 0.04, rho = 0.60) and CD4 + (p = 0.01, rho = 0.72) T-cell counts in 'On-treatment' biopsies were associated with decreased residual tumour content post-1 cycle of treatment; the latter being significantly associated with increased likelihood of subsequent pCR (p < 0.01).

Conclusions: The immune system may be 'primed' prior to neoadjuvant treatment in those patients who subsequently achieve a pCR. In those patients who achieve a pCR, their immune response may return to baseline after only 1 cycle of treatment. However, in those who did not achieve a pCR, neo-adjuvant treatment may stimulate lymphocyte influx into the tumour.


IReL Consortium

Irish Cancer Society’s research Centre BreastPredict (CCRC13GAL)

NECRET – the Northeast Cancer Research and Education Trust



The original article is available at

Published Citation

Eustace AJ. et al. The role of infiltrating lymphocytes in the neo-adjuvant treatment of women with HER2-positive breast cancer. Breast Cancer Res Treat. 2021;187(3):635-645

Publication Date

13 May 2021

PubMed ID



  • Beaumont Hospital
  • Data Science Centre
  • Molecular Medicine
  • Pathology
  • Physiology and Medical Physics
  • Radiology
  • Surgery

Research Area

  • Cancer
  • Neurological and Psychiatric Disorders
  • Surgical Science and Practice
  • Gynaecology, Obstetrics and Perinatal Health


Kluwer Academic


  • Published Version (Version of Record)