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Tumour infiltrating lymphocytes and stromal CD68 in early stage HER2 positive breast cancer
  1. Jacques Raphael1,2,
  2. IY Gong2,
  3. S Nofech-Mozes3,
  4. JMS Bartlett4,
  5. H Nafisi3,
  6. S Verma1,2
  1. 1 Medical Oncology Department, Sunnybrook Odette Cancer Centre, Toronto, Ontario, Canada
  2. 2 Faculty of Medicine, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
  3. 3 Pathology Department, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
  4. 4 Transformative Pathology, Ontario Institute for Cancer Research, Toronto, Ontario, Canada
  1. Correspondence to Dr Jacques Raphael, Medical Oncology Department, Breast Site, Sunnybrook Odette Cancer Centre, 2075 Bayview Avenue, Toronto, Ontario, Canada M4N3M5; raphaeljack13{at}

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High levels of tumour infiltrating lymphocytes (TILs) at diagnosis were shown to be associated with decreased distant recurrence rates in triple negative breast cancer (BC) and increased trastuzumab (T) benefit in HER2+ disease.1

However, conflicting data showed that HER2+ cases with high TILs might not benefit from the addition of T to chemotherapy.2 Moreover, emerging literature suggests association between high tumour-associated macrophages (TAMs) and poor prognosis in patients with BC.3

We conducted a retrospective study using the Sunnybrook Biomatrix database to quantify TILs and macrophages markers in an HER2+ BC population treated with neoadjuvant chemotherapy and explore their role in predicting the benefit from T.

Two independent pathologists with BC expertise reviewed all core biopsies to select the optimal slide for TILs assessment. Pathological complete response (pCR) was defined as no invasive residual in breast or nodes.

After using the self-training tutorial supplementing the published guideline recommendations,4 the two pathologists semiquantified stromal TILs using 4–5 µm thick H&E-stained slides. TILs were assessed as the percentage of tumour stroma containing infiltrating lymphocytes as a continuous scale. Cases with 60% TILs or more were categorised as lymphocyte-predominant BC (LPBC). CD68 Immunohistochemistry (IHC) was performed (prediluted KP-1; clone 790-2931; Ventana) on automated Benchmark Ultra platform in two runs using standard procedure. The proportion of CD68-positive stromal mononuclear cells of all TILs was evaluated using a double headed microscope and high CD68 ratio was defined as >60%. The inter-rater reliability was excellent (Cohen's κ 0.89).

Fifty-two patients were successfully assessed. Baseline characteristics are presented in table 1. In the neoadjuvant setting, 40 patients received chemotherapy and T (77%) and 12 patients had only chemotherapy (23%).

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Table 1

Baseline characteristics

The pCR rate was 41% in the whole cohort (21/51) and …

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  • Contributors Planning the study: JR and SV. Conducting: JR, SN-M, IYG, JMSB, HN and SV. Reporting: JR, SN-M, IYG and SV.

  • Competing interests SV: Advisory Board—Roche, EISAI, Amgen, Novartis, Astra Zeneca. JMSB: consulting or advisory role. Entity: Insight Genetics and BioNTech GmbH. Patents, royalties and other intellectual property. Entity: we have filed two patents relating to biomarkers in breast cancer.

  • Ethics approval The institutional review board approved this work. None of the guidelines supplied by the EQUATOR Network are appropriate for this study: retrospective pathological analysis and chart review.

  • Provenance and peer review Not commissioned; externally peer reviewed.