@article{MTMT:33033281,
	title = {Assessment of Ki67 in Breast Cancer: Updated Recommendations From the International Ki67 in Breast Cancer Working Group},
	url = {https://m2.mtmt.hu/api/publication/33033281},
	author = {Nielsen, Torsten O. and Leung, Samuel C. Y. and Rimm, David L. and Dodson, Andrew and Ács, Balázs and Badve, Sunil and Denkert, Carsten and Ellis, Matthew J. and Fineberg, Susan and Flowers, Margaret and Kreipe, Hans H. and Laenkholm, Anne-Vibeke and Pan, Hongchao and Penault-Llorca, Friderique M. and Polley, Mei-Yin and Salgado, Roberto and Smith, Ian E. and Sugie, Tomoharu and Bartlett, John M. S. and McShane, Lisa M. and Dowsett, Mitch and Hayes, Daniel F.},
	doi = {10.1093/jnci/djaa201},
	journal-iso = {JNCI-J NATL CANCER I},
	journal = {JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE},
	volume = {113},
	unique-id = {33033281},
	issn = {0027-8874},
	abstract = {Ki67 immunohistochemistry (IHC), commonly used as a proliferation marker in breast cancer, has limited value for treatment decisions due to questionable analytical validity. The International Ki67 in Breast Cancer Working Group (IKWG) consensus meeting, held in October 2019, assessed the current evidence for Ki67 IHC analytical validity and clinical utility in breast cancer, including the series of scoring studies the IKWG conducted on centrally stained tissues. Consensus observations and recommendations are: 1) as for estrogen receptor and HER2 testing, preanalytical handling considerations are critical; 2) a standardized visual scoring method has been established and is recommended for adoption; 3) participation in and evaluation of quality assurance and quality control programs is recommended to maintain analytical validity; and 4) the IKWG accepted that Ki67 IHC as a prognostic marker in breast cancer has clinical validity but concluded that clinical utility is evident only for prognosis estimation in anatomically favorable estrogen receptor-positive and HER2-negative patients to identify those who do not need adjuvant chemotherapy. In this T1-2, N0-1 patient group, the IKWG consensus is that Ki675% or less, or 30% or more, can be used to estimate prognosis. In conclusion, analytical validity of Ki67 IHC can be reached with careful attention to preanalytical issues and calibrated standardized visual scoring. Currently, clinical utility of Ki67 IHC in breast cancer care remains limited to prognosis assessment in stage I or II breast cancer. Further development of automated scoring might help to overcome some current limitations.},
	keywords = {labeling index; ESTROGEN-RECEPTOR; PROGNOSTIC VALUE; ENDOCRINE THERAPY; CLINICAL-PRACTICE GUIDELINES; AMERICAN-SOCIETY; Adjuvant systemic therapy; PATIENT-LEVEL METAANALYSIS; STANDARDIZED SCORING PROTOCOL},
	year = {2021},
	eissn = {1460-2105},
	pages = {808-819},
	orcid-numbers = {Nielsen, Torsten O./0000-0003-3769-2517; Rimm, David L./0000-0001-5820-4397; Dodson, Andrew/0000-0002-7443-2362; Ács, Balázs/0000-0002-0972-4633; Badve, Sunil/0000-0001-8861-9980; Ellis, Matthew J./0000-0002-8467-8534; Fineberg, Susan/0000-0002-4769-7875; Laenkholm, Anne-Vibeke/0000-0003-2166-8686}
}

@article{MTMT:30658783,
	title = {Influence of mutagenic versus non-mutagenic pre-operative chemotherapy on the immune infiltration of residual breast cancer},
	url = {https://m2.mtmt.hu/api/publication/30658783},
	author = {Tőkés, Anna-Mária and Rusz, Orsolya and Cserni, Gábor and Tóth, Erika and Rubovszky, Gábor and Tőkés, Tímea and Vízkeleti, Laura and Reiniger, Lilla and Kószó, Renáta Lilla and Kahán, Zsuzsanna and Kulka, Janina and Donia, Marco and Vörös, András and Szállási, Zoltán},
	doi = {10.1080/0284186X.2019.1633015},
	journal-iso = {ACTA ONCOL},
	journal = {ACTA ONCOLOGICA},
	volume = {58},
	unique-id = {30658783},
	issn = {0284-186X},
	year = {2019},
	eissn = {1651-226X},
	pages = {1603-1611},
	orcid-numbers = {Tőkés, Anna-Mária/0000-0002-9581-7536; Rusz, Orsolya/0000-0001-5726-4072; Cserni, Gábor/0000-0003-1344-7744; Tóth, Erika/0000-0003-2054-8447; Rubovszky, Gábor/0000-0003-1723-5589; Tőkés, Tímea/0000-0002-5456-1706; Vízkeleti, Laura/0000-0001-6870-3499; Reiniger, Lilla/0000-0003-2248-4264; Kószó, Renáta Lilla/0000-0002-1958-7839; Kahán, Zsuzsanna/0000-0002-5021-8775; Kulka, Janina/0000-0001-6498-5943; Vörös, András/0000-0001-6837-0567; Szállási, Zoltán/0000-0001-5395-7509}
}

@article{MTMT:3376690,
	title = {Reproducibility and predictive value of scoring stromal tumour infiltrating lymphocytes in triple-negative breast cancer: a multi-institutional study},
	url = {https://m2.mtmt.hu/api/publication/3376690},
	author = {O'Loughlin, M and Andreu, X and Bianchi, S and Chemielik, E and Cordoba, A and Cserni, Gábor and Figueiredo, P and Floris, G and Foschini, MP and Heikkila, P and Kulka, Janina and Liepniece-Karele, I and Regitnig, P and Reiner, A and Ryska, A and Sapino, A and Shalaby, A and Stovgaard, ES and Quinn, C and Walsh, EM and Zolota, V and Glynn, SA and Callagy, G},
	doi = {10.1007/s10549-018-4825-8},
	journal-iso = {BREAST CANCER RES TR},
	journal = {BREAST CANCER RESEARCH AND TREATMENT},
	volume = {171},
	unique-id = {3376690},
	issn = {0167-6806},
	abstract = {BACKGROUND: Several studies have demonstrated a prognostic role for stromal tumour infiltrating lymphocytes (sTILs) in triple-negative breast cancer (TNBC). The reproducibility of scoring sTILs is variable with potentially excellent concordance being achievable using a software tool. We examined agreement between breast pathologists across Europe scoring sTILs on H&E-stained sections without software, an approach that is easily applied in clinical practice. The association between sTILs and response to anthracycline-taxane NACT was also examined. METHODOLOGY: Pathologists from the European Working Group for Breast Screening Pathology scored sTILs in 84 slides from 75 TNBCs using the immune-oncology biomarker working group guidance in two circulations. There were 16 participants in the first and 19 in the second circulation. RESULTS: Moderate agreement was achieved for absolute sTILs scores (intraclass correlation coefficient (ICC) = 0.683, 95% CI 0.601-0.767, p-value < 0.001). Agreement was less when a 25% threshold was used (ICC 0.509, 95% CI 0.416-0.614, p-value < 0.001) and for lymphocyte predominant breast cancer (LPBC) (ICC 0.504, 95% CI 0.412-0.610, p-value < 0.001). Intra-observer agreement was strong for absolute sTIL values (Spearman rho = 0.727); fair for sTILs >/= 25% (kappa = 0.53) and for LPBC (kappa = 0.49), but poor for sTILs as 10% increments (kappa = 0.24). Increasing sTILs was significantly associated with an increased likelihood of a pathological complete response (pCR) on multivariable analysis. CONCLUSION: Increasing sTILs in TNBCs improves the likelihood of a pCR. However, inter-observer agreement is such that H&E-based assessment is not sufficiently reproducible for clinical application. Other methodologies should be explored, but may be at the cost of ease of application.},
	year = {2018},
	eissn = {1573-7217},
	pages = {1-9},
	orcid-numbers = {Cserni, Gábor/0000-0003-1344-7744; Kulka, Janina/0000-0001-6498-5943}
}

@article{MTMT:3156141,
	title = {Tumor-infiltrating lymphocytes (TILs) are a powerful prognostic marker in patients with triple-negative breast cancer enrolled in the IBCSG phase III randomized clinical trial 22-00.},
	url = {https://m2.mtmt.hu/api/publication/3156141},
	author = {Pruneri, G and Gray, KP and Vingiani, A and Viale, G and Curigliano, G and Criscitiello, C and Láng, István and Ruhstaller, T and Gianni, L and Goldhirsch, A and Kammler, R and Price, KN and Cancello, G and Munzone, E and Gelber, RD and Regan, MM and Colleoni, M},
	doi = {10.1007/s10549-016-3863-3},
	journal-iso = {BREAST CANCER RES TR},
	journal = {BREAST CANCER RESEARCH AND TREATMENT},
	volume = {158},
	unique-id = {3156141},
	issn = {0167-6806},
	abstract = {The purpose of this study was to assess the prognostic and predictive value of tumor-infiltrating lymphocytes (TILs) in the triple-negative breast cancer (TNBC) cohort of the phase III IBCSG trial 22-00, comparing low-dose oral 'metronomic' cyclophosphamide-methotrexate maintenance chemotherapy (CM-maintenance) to no-CM-maintenance in early breast cancer. TILs were evaluated in full-face hematoxylin-and-eosin-stained sections of tumor samples confirmed centrally as TNBC (< 1 % of ER and PgR immunoreactivity and absence of HER2 overexpression or amplification). Mononuclear cells were evaluated in the stromal area within the borders of the invasive tumor. The primary endpoint was breast cancer-free interval (BCFI). Cox proportional hazards regression model assessed the association of BCFI and secondary endpoints with TILs score. In the 647 tumor samples, the median percentage of TILs was 18 % (IQR = 8-40 %), with 18 % having TILs >/= 50 % (lymphocyte-predominant breast cancer, LPBC). At a median follow-up of 6.9 years, TILs were associated with better prognosis. For every 10 % increase of TILs, BCFI risk reduction was 13 % (HR 0.87, 95 % CI 0.79-0.95,P = 0.003). DFS, DRFI, and OS risk reductions were 11 % (P = 0.005), 16 % (P = 0.003), and 17 % (P < 0.001), respectively. Multivariable analysis confirmed the independent prognostic value of TILs. No significant TILs-by-treatment interaction was observed (P = 0.39) for associations of TILs with BCFI, although patients with LPBC receiving CM-maintenance had a greater breast cancer risk reduction (HR 0.64,95 % CI 0.23-1.78) than those with non-LPBC (TILs < 50 %) (HR 0.96, 95 % CI 0.67-1.40). TILs score is a potent prognostic factor in patients with TNBC. Low-dose chemotherapy confers a greater (not statistically significant) clinical benefit in patients with LPBC.},
	year = {2016},
	eissn = {1573-7217},
	pages = {323-331}
}

@article{MTMT:2422053,
	title = {Prognostic and Predictive Value of Tumor-Infiltrating Lymphocytes in a Phase III Randomized Adjuvant Breast Cancer Trial in Node-Positive Breast Cancer Comparing the Addition of Docetaxel to Doxorubicin With Doxorubicin-Based Chemotherapy: BIG 02-98},
	url = {https://m2.mtmt.hu/api/publication/2422053},
	author = {Loi, S and Sirtaine, N and Piette, F and Salgado, R and Viale, G and Van, Eenoo F and Rouas, G and Francis, P and Crown, JPA and Hitre, Erika and de Azambuja, E and Quinaux, E and Di Leo, A and Michiels, S and Piccart, MJ and Sotiriou, C},
	doi = {10.1200/JCO.2011.41.0902},
	journal-iso = {J CLIN ONCOL},
	journal = {JOURNAL OF CLINICAL ONCOLOGY},
	volume = {31},
	unique-id = {2422053},
	issn = {0732-183X},
	abstract = {Purpose Previous preclinical and clinical data suggest that the immune system influences prognosis and response to chemotherapy (CT); however, clinical relevance has yet to be established in breast cancer (BC). We hypothesized that increased lymphocytic infiltration would be associated with good prognosis and benefit from immunogenic CT-in this case, anthracycline-only CT-in selected BC subtypes. Patients and Methods We investigated the relationship between quantity and location of lymphocytic infiltrate at diagnosis with clinical outcome in 2009 node-positive BC samples from the BIG 02-98 adjuvant phase III trial comparing anthracycline-only CT (doxorubicin followed by cyclophosphamide, methotrexate, and fluorouracil [CMF] or doxorubicin plus cyclophosphamide followed by CMF) versus CT combining doxorubicin and docetaxel (doxorubicin plus docetaxel followed by CMF or doxorubicin followed by docetaxel followed by CMF). Readings were independently performed by two pathologists. Disease-free survival (DFS), overall survival (OS), and interaction with type of CT associations were studied. Median follow-up was 8 years. Results There was no significant prognostic association in the global nor estrogen receptor (ER) - positive/human epidermal growth factor receptor 2 (HER2) -negative population. However, each 10% increase in intratumoral and stromal lymphocytic infiltrations was associated with 17% and 15% reduced risk of relapse (adjusted P = .1 and P = .025), respectively, and 27% and 17% reduced risk of death in ER-negative/HER2-negative BC regardless of CT type (adjusted P = .035 and P = .023), respectively. In HER2-positive BC, there was a significant interaction between increasing stromal lymphocytic infiltration (10% increments) and benefit with anthracycline-only CT (DFS, interaction P = .042; OS, P = .018). Conclusion In node-positive, ER-negative/HER2-negative BC, increasing lymphocytic infiltration was associated with excellent prognosis. Further validation of the clinical utility of tumor-infiltrating lymphocytes in this context is warranted. Our data also support the evaluation of immunotherapeutic approaches in selected BC subtypes. J Clin Oncol 31:860-867. (C) 2013 by American Society of Clinical Oncology},
	keywords = {Inflammation; EXPRESSION; SUBTYPES; ANTIBODY; Immunogenicity; anthracycline; ADAPTIVE IMMUNITY; ROLES; INVASIVE-CARCINOMA; ANTI-PD-1},
	year = {2013},
	eissn = {1527-7755},
	pages = {860-867}
}