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
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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