Standardized assessment of tumor-infiltrating lymphocytes in breast cancer: an evaluation of inter-observer agreement between pathologists

<p><b>Introduction:</b> In breast cancer, there is a growing body of evidence that tumor-infiltrating lymphocytes (TILs) may have clinical utility and may be able to direct clinical decisions for subgroups of patients. Clinical utility is, however, not sufficient for warranting the implementation of a new biomarker in the routine practice, and evaluation of the analytical validity is needed, including testing the reproducibility of decentralized assessment of TILs. The aim of this study was to evaluate the inter-observer agreement of TILs assessment using a standardized method, as proposed by the International TILs Working Group 2014, applied to a cohort of breast cancers reflecting an average breast cancer population.</p> <p><b>Material and methods:</b> Stromal TILs were assessed using full slide sections from 124 breast cancers with varying histology, malignancy grade and ER- and HER2 status. TILs were estimated by nine dedicated breast pathologists using scanned hematoxylin–eosin stainings. TILs results were categorized using various cutoffs, and the inter-observer agreement was evaluated using the intraclass coefficient (ICC), Kappa statistics as well as individual overall agreements with the median value of TILs.</p> <p><b>Results:</b> Evaluation of TILs led to an ICC of 0.71 (95% CI: 0.65–0.77) corresponding to an acceptable agreement. Kappa values were in the range of 0.38–0.46 corresponding to a fair to moderate agreement. The individual agreements increased, when using only two categories (‘high’ vs. ‘low’ TILs) and a cutoff of 50–60%.</p> <p><b>Discussion:</b> The results of the present study are in accordance with previous studies, and shows that the proposed methodology for standardized evaluation of TILs renders an acceptable inter-observer agreement. The findings, however, indicate that assessment of TILs needs further refinement, and is in support of the latest St. Gallen Consensus, that routine reporting of TILs for early breast cancer is not ready for implementation in a clinical setting.</p

Male breast cancer: a nation-wide population-based comparison with female breast cancer

<p><b>Objective:</b> Describe prognostic parameters of Danish male breast cancer patients (MBCP) diagnosed from 1980–2009. Determine all-cause mortality compared to the general male population and analyze survival/mortality compared with Danish female breast cancer patients (FBCP) in the same period.</p> <p><b>Material and methods:</b> The MBCP cohort was defined from three national registers. Data was extracted from medical journals. Data for FBCP is from the DBCG database. Overall survival (OS) was quantified by Kaplan–Meier estimates. Standardized mortality ratios (SMRs) were calculated based on mortality rate among patients relative to the mortality rate in the general population. The association between SMR and risk factors were analyzed in univariate and multivariable Poisson regression models. Separate models for each gender were used for the analyses.</p> <p><b>Results:</b> We found a marked difference in OS for the two genders. For the total population of MBCP, 5- and 10-year survivals were 55.1% and 31.7%, respectively. For FBCP, the corresponding figures were 76.8% and 59.3%. Median age at diagnosis for FBCP was 61 years and 70 years for MBCP. By applying SMR, the difference in mortality between genders equalized and showed pronounced age-dependency. For males <40 years, SMR was 9.43 and for females 19.56 compared to SMR for males 80 + years (0.95) and females 80 + years (0.89). During the period 1980–2009, the risk of dying gradually decreased for FBCP (<i>p</i> < .0001). The risk 1980–1984 was 35% higher than 2005–2009 (RR 1.35). Although the risk of dying for MBCP was also lowest in 2005–2009, there was no clear tendency (<i>p</i> = .1439). The risk was highest in 1990–1994 (RR =2.48).</p> <p><b>Conclusion:</b> We found better OS for FBCP than for MBCP. But SMR showed similar mortality rate for the two genders, except for very young FBCP, who had higher SMR. Furthermore, significantly improved survival over time for FBCP was observed, with no clear tendency for MBCP.</p

Male breast cancer: a nation-wide population-based comparison with female breast cancer

Objective: Describe prognostic parameters of Danish male breast cancer patients (MBCP) diagnosed from 1980–2009. Determine all-cause mortality compared to the general male population and analyze survival/mortality compared with Danish female breast cancer patients (FBCP) in the same period. Material and methods: The MBCP cohort was defined from three national registers. Data was extracted from medical journals. Data for FBCP is from the DBCG database. Overall survival (OS) was quantified by Kaplan–Meier estimates. Standardized mortality ratios (SMRs) were calculated based on mortality rate among patients relative to the mortality rate in the general population. The association between SMR and risk factors were analyzed in univariate and multivariable Poisson regression models. Separate models for each gender were used for the analyses. Results: We found a marked difference in OS for the two genders. For the total population of MBCP, 5- and 10-year survivals were 55.1% and 31.7%, respectively. For FBCP, the corresponding figures were 76.8% and 59.3%. Median age at diagnosis for FBCP was 61 years and 70 years for MBCP. By applying SMR, the difference in mortality between genders equalized and showed pronounced age-dependency. For male

Male breast cancer: a nation-wide population-based comparison with female breast cancer

Objective: Describe prognostic parameters of Danish male breast cancer patients (MBCP) diagnosed from 1980–2009. Determine all-cause mortality compared to the general male population and analyze survival/mortality compared with Danish female breast cancer patients (FBCP) in the same period. Material and methods: The MBCP cohort was defined from three national registers. Data was extracted from medical journals. Data for FBCP is from the DBCG database. Overall survival (OS) was quantified by Kaplan–Meier estimates. Standardized mortality ratios (SMRs) were calculated based on mortality rate among patients relative to the mortality rate in the general population. The association between SMR and risk factors were analyzed in univariate and multivariable Poisson regression models. Separate models for each gender were used for the analyses. Results: We found a marked difference in OS for the two genders. For the total population of MBCP, 5- and 10-year survivals were 55.1% and 31.7%, respectively. For FBCP, the corresponding figures were 76.8% and 59.3%. Median age at diagnosis for FBCP was 61 years and 70 years for MBCP. By applying SMR, the difference in mortality between genders equalized and showed pronounced age-dependency. For male