Tumour-infiltrating lymphocytes as a prognostic and tamoxifen predictive marker in premenopausal breast cancer: data from a randomised trial with long-term follow-up
Autor: | Maria Ekholm, Carina Forsare, Lisa Rydén, Pär-Ola Bendahl, Christine Lundgren, Bo Nordenskjöld, Olle Stål, Mårten Fernö, Ute Krüger |
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Rok vydání: | 2020 |
Předmět: |
Oncology
Breast cancer TILs Prognosis Tamoxifen Premenopausal Predictive Biomarker Receptor ErbB-2 0302 clinical medicine Surgical oncology Cumulative incidence Breast Prospective Studies skin and connective tissue diseases Mastectomy 0303 health sciences Predictive marker Middle Aged lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Immunohistochemistry Receptors Estrogen Chemotherapy Adjuvant 030220 oncology & carcinogenesis Female medicine.drug Research Article Adult medicine.medical_specialty Breast Neoplasms lcsh:RC254-282 Disease-Free Survival 03 medical and health sciences Lymphocytes Tumor-Infiltrating Internal medicine medicine Biomarkers Tumor Humans Clinical significance 030304 developmental biology Aged Neoplasm Staging Retrospective Studies Cancer och onkologi business.industry Proportional hazards model medicine.disease Premenopause Drug Resistance Neoplasm Cancer and Oncology Neoplasm Recurrence Local business Follow-Up Studies |
Zdroj: | Breast Cancer Research : BCR Breast Cancer Research, Vol 22, Iss 1, Pp 1-14 (2020) |
ISSN: | 1465-542X |
Popis: | Background Tumour-infiltrating lymphocytes (TILs) are of important prognostic and predictive value in human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) and triple-negative breast cancer (TNBC), but their clinical relevance in oestrogen receptor-positive/HER2-negative (ER+/HER2−) remains unknown. The primary study aim was to analyse the prognostic effect of TILs on the BC-free interval (BCFi) in premenopausal patients stratified by BC subtypes. The secondary aim was to investigate if TILs are predictive of tamoxifen (TAM) benefit. Methods Archival tissues from primary breast tumours were collected from patients from the SBII:2pre trial, in which 564 premenopausal women were randomised to 2 years of adjuvant TAM or no systemic treatment, regardless of hormone receptor status. TILs were scored on whole tissue sections from 447 patients with available ER status. Tumours were divided into ER+/HER2−, HER2+ and TNBC subtypes by immunohistochemistry and in situ hybridisation. The prognostic value of TILs was analysed in systemically untreated patients (n = 221); the predictive information was investigated in the ER+ subgroup (n = 321) by cumulative incidence curves and Cox regression analyses. The median follow-up was 28 years. Results High (≥ 50%) infiltration of TILs was a favourable prognostic factor in terms of BCFi (univariable analysis: hazard ratioBCFi (HRBCFi) 0.40; 95% confidence interval (CI) 0.22–0.71; P = 0.002). Similar effects were observed across all BC subtypes. The effect of adjuvant TAM was stronger in patients with ER+ tumours and TILs BCFi 0.63; 95% CI 0.47–0.84; P = 0.002) than in patients with high immune infiltration (≥ 50%) (HRBCFi 0.84; 95% CI (0.24–2.86); P = 0.77). However, evidence for differential effects of TAM in categories of TILs, i.e. interaction, was weak. Conclusions We demonstrate a long-term favourable prognostic value of high infiltration of TILs in a cohort of premenopausal BC patients and the positive prognostic effect was extended to the ER+/HER2− subgroup. A beneficial effect of TAM in ER+ patients was observed in patients with tumours of low TIL infiltration, but evidence for a treatment predictive effect was weak. Trial registration This trial is registered in the ISRCTN database, trial ID: ISRCTN12474687. |
Databáze: | OpenAIRE |
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