Computational pathology of pre-treatment biopsies identifies lymphocyte density as a predictor of response to neoadjuvant chemotherapy in breast cancer
| العنوان: | Computational pathology of pre-treatment biopsies identifies lymphocyte density as a predictor of response to neoadjuvant chemotherapy in breast cancer |
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| المؤلفون: | Ali, H. Raza, Dariush, Aliakbar, Provenzano, Elena, Bardwell, Helen, Abraham, Jean E., Iddawela, Mahesh, Vallier, Anne-Laure, Hiller, Louise, Dunn, Janet. A., Bowden, Sarah J., Hickish, Tamas, McAdam, Karen, Houston, Stephen, Irwin, Mike J., Pharoah, Paul D. P., Brenton, James D., Walton, Nicholas A., Earl, Helena M., Caldas, Carlos |
| المساهمون: | Ali, Raza [0000-0001-7587-0906], Abraham, Jean [0000-0003-0688-4807], Irwin, Mike [0000-0002-2191-9038], Pharoah, Paul [0000-0001-8494-732X], Brenton, James [0000-0002-5738-6683], Walton, Nicholas [0000-0003-3983-8778], Earl, Helena [0000-0003-1549-8094], Caldas, Carlos [0000-0003-3547-1489], Apollo - University of Cambridge Repository |
| المصدر: | Breast Cancer Research : BCR |
| بيانات النشر: | BioMed Central Ltd., 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Adult, PROGNOSIS, PROTEIN EXPRESSION, AUTOMATED-ANALYSIS, Receptor, ErbB-2, Biopsy, Immunology, Breast Neoplasms, Treatment resistance, SYSTEMS PATHOLOGY, RC0254, Breast cancer, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, Humans, TUMOR-INFILTRATING LYMPHOCYTES, Oncology & Carcinogenesis, Lymphocytes, ANTHRACYCLINE CHEMOTHERAPY, Aged, Epirubicin, Medicine(all), Science & Technology, ASSOCIATION, Middle Aged, Computational pathology, Neoadjuvant Therapy, QR, Oncology, MPDL3280A, Chemotherapy, Adjuvant, NEO-TANGO, TRIAL, Female, Taxoids, Neoadjuvant, Life Sciences & Biomedicine, 1112 Oncology And Carcinogenesis, Research Article |
| الوصف: | Background There is a need to improve prediction of response to chemotherapy in breast cancer in order to improve clinical management and this may be achieved by harnessing computational metrics of tissue pathology. We investigated the association between quantitative image metrics derived from computational analysis of digital pathology slides and response to chemotherapy in women with breast cancer who received neoadjuvant chemotherapy. Methods We digitised tissue sections of both diagnostic and surgical samples of breast tumours from 768 patients enrolled in the Neo-tAnGo randomized controlled trial. We subjected digital images to systematic analysis optimised for detection of single cells. Machine-learning methods were used to classify cells as cancer, stromal or lymphocyte and we computed estimates of absolute numbers, relative fractions and cell densities using these data. Pathological complete response (pCR), a histological indicator of chemotherapy response, was the primary endpoint. Fifteen image metrics were tested for their association with pCR using univariate and multivariate logistic regression. Results Median lymphocyte density proved most strongly associated with pCR on univariate analysis (OR 4.46, 95 % CI 2.34-8.50, p < 0.0001; observations = 614) and on multivariate analysis (OR 2.42, 95 % CI 1.08-5.40, p = 0.03; observations = 406) after adjustment for clinical factors. Further exploratory analyses revealed that in approximately one quarter of cases there was an increase in lymphocyte density in the tumour removed at surgery compared to diagnostic biopsies. A reduction in lymphocyte density at surgery was strongly associated with pCR (OR 0.28, 95 % CI 0.17-0.47, p < 0.0001; observations = 553). Conclusions A data-driven analysis of computational pathology reveals lymphocyte density as an independent predictor of pCR. Paradoxically an increase in lymphocyte density, following exposure to chemotherapy, is associated with a lack of pCR. Computational pathology can provide objective, quantitative and reproducible tissue metrics and represents a viable means of outcome prediction in breast cancer. Trial registration ClinicalTrials.gov NCT00070278; 03/10/2003 Electronic supplementary material The online version of this article (doi:10.1186/s13058-016-0682-8) contains supplementary material, which is available to authorized users. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1465-542X 1465-5411 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::8fcf24df1dcbb7bf1c385b8feb48f5faTest http://wrap.warwick.ac.uk/85329/1/WRAP_art%3A10.1186%2Fs13058-016-0682-8.pdfTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.pmid.dedup....8fcf24df1dcbb7bf1c385b8feb48f5fa |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1465542X 14655411 |
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