A prognostic model based on combining estrogen receptor expression and Ki-67 value after neoadjuvant chemotherapy predicts clinical outcome in locally advanced breast cancer: Extension and analysis of a previously reported cohort of patients

Miglietta, Loredana; Morabito, Fortunato; Provinciali, Nicoletta; Canobbio, Luciano; Meszaros, Paolo; Naso, C.; Murialdo, Roberto; Boitano, Monica; Salvi, Sandra; Ferrarini, Manlio

doi:10.1016/j.ejso.2013.06.024

Cited by 24 publications

(20 citation statements)

References 21 publications

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“…22,23 Regardless, Ki67 is usually interpreted in the context of other clinicopathological parameters, such as tumor size, lymph node status and grade, or biomarkers, such as ER, PR and HER2 status. In this regard, Denkert et al noted that treatment decisions for individual patients should not be made based on small differences of Ki67 around a given cutpoint.…”

Section: Discussionmentioning

confidence: 99%

Analytical validation of a standardized scoring protocol for Ki67: phase 3 of an international multicenter collaboration

et al. 2016

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Pathological analysis of the nuclear proliferation biomarker Ki67 has multiple potential roles in breast and other cancers. However, clinical utility of the immunohistochemical (IHC) assay for Ki67 immunohistochemistry has been hampered by unacceptable between-laboratory analytical variability. The International Ki67 Working Group has conducted a series of studies aiming to decrease this variability and improve the evaluation of Ki67. This study tries to assess whether acceptable performance can be achieved on prestained core-cut biopsies using a standardized scoring method. Sections from 30 primary ER+ breast cancer core biopsies were centrally stained for Ki67 and circulated among 22 laboratories in 11 countries. Each laboratory scored Ki67 using three methods: (1) global (4 fields of 100 cells each); (2) weighted global (same as global but weighted by estimated percentages of total area); and (3) hot-spot (single field of 500 cells). The intraclass correlation coefficient (ICC), a measure of interlaboratory agreement, for the unweighted global method (0.87; 95% credible interval (CI): 0.81–0.93) met the prespecified success criterion for scoring reproducibility, whereas that for the weighted global (0.87; 95% CI: 0.7999–0.93) and hot-spot methods (0.84; 95% CI: 0.77–0.92) marginally failed to do so. The unweighted global assessment of Ki67 IHC analysis on core biopsies met the prespecified criterion of success for scoring reproducibility. A few cases still showed large scoring discrepancies. Establishment of external quality assessment schemes is likely to improve the agreement between laboratories further. Additional evaluations are needed to assess staining variability and clinical validity in appropriate cohorts of samples.

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Section: Discussionmentioning

confidence: 99%

Analytical validation of a standardized scoring protocol for Ki67: phase 3 of an international multicenter collaboration

et al. 2016

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“…[1][2][3][4] However, the considerable variation in clinical outcome of ER-negative patients has fuelled the quest for additional markers to better stratify this disease subset and eventually provide more effective personalized treatment. 5 Tumor infiltration by various cells of the immune system has been associated with a favorable clinical outcome in ER-negative breast cancer.…”

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confidence: 99%

Beyond immune density: critical role of spatial heterogeneity in estrogen receptor-negative breast cancer

et al. 2015

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The abundance of tumor-infiltrating lymphocytes has been associated with a favorable prognosis in estrogen receptor-negative breast cancer. However, a high degree of spatial heterogeneity in lymphocytic infiltration is often observed and its clinical implication remains unclear. Here we combine automated histological image processing with methods of spatial statistics used in ecological data analysis to quantify spatial heterogeneity in the distribution patterns of tumor-infiltrating lymphocytes. Hematoxylin and eosin-stained sections from two cohorts of estrogen receptor-negative breast cancer patients (discovery: n = 120; validation: n = 125) were processed with our automated cell classification algorithm to identify the location of lymphocytes and cancer cells. Subsequently, hotspot analysis (Getis-Ord Gi*) was applied to identify statistically significant hotspots of cancer and immune cells, defined as tumor regions with a significantly high number of cancer cells or immune cells, respectively. We found that the amount of co-localized cancer and immune hotspots weighted by tumor area, rather than number of cancer or immune hotspots, correlates with a better prognosis in estrogen receptornegative breast cancer in univariate and multivariate analysis. Moreover, co-localization of cancer and immune hotspots further stratified patients with immune cell-rich tumors. Our study demonstrates the importance of quantifying not only the abundance of lymphocytes but also their spatial variation in the tumor specimen for which methods from other disciplines such as spatial statistics can be successfully applied.

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“…These inconsistent results may be due to the use of different detection platforms. Mego [36]. Unlike the prognostic model in our earlier study, the chemotherapy response fold increased metastatic potential compared to single CTCs [42].…”

Section: Discussionmentioning

confidence: 75%

Circulating Tumor Cell Subtypes may Predict Responses to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer

Wang

et al. 2020

Preprint

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Background: Neoadjuvant chemotherapy (NCT) is the standard treatment for patients with locally advanced breast cancer (LABC). However, the predictive value of circulating tumor cells (CTCs) with different molecular subtypes in NCT response has not yet been determined, which was, therefore, the aim of this study. Methods: All patients were staged as LABC and received an EC×4 –T×4 NCT regimen. Blood samples were collected from patients at the time of biopsy, and after the first and eighth NCT courses. Patients were divided into High responders (High-R) and Low responders (Low-R) according to Miller-Payne system and changes in Ki-67 levels after NCT treatment. A novel SE-i•FISH strategy was applied to detect CTCs. Subtypes were successfully analyzed in LABC patients undergoing NCT, for the first time. Results: Total CTCs increased continuously and were higher for Low-R patients; while in the High-R group, total CTCs increased slightly during NCT before returning to baseline levels. Triploid and tetraploid chromosome 8 as well as the proportion of each, increased for Low-R but not High-R patients. The number of small CTCs in the Low-R group increased significantly until the last sample, however, remained constant in the High-R group. The patients with more CTCs had shorter PFS and OS than those with less CTCs after the 8th course of NCT. Conclusions: Total CTCs as well as individual subtypes within peripheral blood following NCT were predictive of patient responses to NCT. More detailed characterization of CTC blood profiles may improve predictive capacity and lead to improved LABC treatments.

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A prognostic model based on combining estrogen receptor expression and Ki-67 value after neoadjuvant chemotherapy predicts clinical outcome in locally advanced breast cancer: Extension and analysis of a previously reported cohort of patients

Cited by 24 publications

References 21 publications

Analytical validation of a standardized scoring protocol for Ki67: phase 3 of an international multicenter collaboration

Analytical validation of a standardized scoring protocol for Ki67: phase 3 of an international multicenter collaboration

Beyond immune density: critical role of spatial heterogeneity in estrogen receptor-negative breast cancer

Circulating Tumor Cell Subtypes may Predict Responses to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer

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