New insights into the prognostic value of the tumor-stroma ratio in patients with breast cancer

In the last decade, the tumor microenvironment has shown to play an important role in tumor progression. Still, no markers concerning the microenvironment have been implemented in clinical decision making. The research presented in this thesis emphasizes the prognostic value of the tumor-stroma ratio (TSR), a method focusing on the tumor microenvironment. The TSR assessment is performed by the scoring method developed by Mesker et al. on routine hematoxylin and eosin (H&E) stained tissue slides of the primary tumor. Various validation studies demonstrated that the TSR is a reliable, simple, quick and inexpensive parameter with a good to a very good inter-observer agreement. The new insights presented in this thesis contribute to a better understanding of the role of the TSR on predicting clinical outcome in subgroups of breast cancer patients and in combination with other prognostic parameters. Furthermore, the described research is important for further research toward clinical implementation of the TSR and might finally be useful for decision-making regarding therapy. Moreover, molecular research of the stromal compartment in the near future is desirable for the development of new diagnostic, prognostic, monitoring and therapeutic markers. Printing of this thesis was financially supported by Uitgeverij Jaap, Erbe Nederland B.V., Norgine B.V., Pfizer B.V., Servier Nederland Farma B.V., Chipsoft B.V., Sysmex Nederland B.V. and Blaak&Partners. The research described in this thesis was financially supported by the Genootschap Keukenhof voor de vroege opsporing van kanker, Lisse, The Netherlands.LUMC / Geneeskund

Serum N-glycan profiles differ for various breast cancer subtypes

Breast cancer is the most prevalent cancer in women. Early detection of this disease improves survival and therefore population screenings, based on mammography, are performed. However, the sensitivity of this screening modality is not optimal and new screening methods, such as blood tests, are being explored. Most of the analyses that aim for early detection focus on proteins in the bloodstream. In this study, the biomarker potential of total serum N-glycosylation analysis was explored with regard to detection of breast cancer. In an age-matched case-control setup serum protein N-glycan profiles from 145 breast cancer patients were compared to those from 171 healthy individuals. N-glycans were enzymatically released, chemically derivatized to preserve linkage-specificity of sialic acids and characterized by high resolution mass spectrometry. Logistic regression analysis was used to evaluate associations of specific N-glycan structures as well as N-glycosylation traits with breast cancer. In a case-control comparison three associations were found, namely a lower level of a two triantennary glycans and a higher level of one tetraantennary glycan in cancer patients. Of note, various other N-glycomic signatures that had previously been reported were not replicated in the current cohort. It was further evaluated whether the lack of replication of breast cancer N-glycomic signatures could be partly explained by the heterogenous character of the disease since the studies performed so far were based on cohorts that included diverging subtypes in different numbers. It was found that serum N-glycan profiles differed for the various cancer subtypes that were analyzed in this study.Surgical oncolog

The intra-tumoural stroma in patients with breast cancer increases with age

PURPOSE: The tumour microenvironment in older patients is subject to changes. The tumour-stroma ratio (TSR) was evaluated in order to estimate the amount of intra-tumoural stroma and to evaluate the prognostic value of the TSR in older patients with breast cancer (≥ 70 years).METHODS: Two retrospective cohorts, the FOCUS study (N = 619) and the Nottingham Breast Cancer series (N = 1793), were used for assessment of the TSR on haematoxylin and eosin stained tissue slides.RESULTS: The intra-tumoural stroma increases with age in the FOCUS study and the Nottingham Breast Cancer series (B 0.031, 95% CI 0.006-0.057, p = 0.016 and B 0.034, 95% CI 0.015-0.054, p CONCLUSIONS: The intra-tumoural stroma increases with age. This might be the result of an activated tumour microenvironment. The TSR did not validate as an independent prognostic parameter in patients ≥ 70 years in contrast to young women with breast cancer as published previously.Surgical oncolog

New insights into the prognostic value of the tumor-stroma ratio in patients with breast cancer

In the last decade, the tumor microenvironment has shown to play an important role in tumor progression. Still, no markers concerning the microenvironment have been implemented in clinical decision making. The research presented in this thesis emphasizes the prognostic value of the tumor-stroma ratio (TSR), a method focusing on the tumor microenvironment. The TSR assessment is performed by the scoring method developed by Mesker et al. on routine hematoxylin and eosin (H&E) stained tissue slides of the primary tumor. Various validation studies demonstrated that the TSR is a reliable, simple, quick and inexpensive parameter with a good to a very good inter-observer agreement. The new insights presented in this thesis contribute to a better understanding of the role of the TSR on predicting clinical outcome in subgroups of breast cancer patients and in combination with other prognostic parameters. Furthermore, the described research is important for further research toward clinical implementation of the TSR and might finally be useful for decision-making regarding therapy. Moreover, molecular research of the stromal compartment in the near future is desirable for the development of new diagnostic, prognostic, monitoring and therapeutic markers. </p

The prognostic value of tumour-stroma ratio in primary breast cancer with special attention to triple-negative tumours: a review

Surgical oncolog

The prognostic value of tumor-stroma ratio in tumor-positive axillary lymph nodes of breast cancer patients

Surgical oncolog

Standardization of the tumor-stroma ratio scoring method for breast cancer research

Purpose The tumor-stroma ratio (TSR) has repeatedly proven to be correlated with patient outcomes in breast cancer using large retrospective cohorts. However, studies validating the TSR often show variability in methodology, thereby hampering comparisons and uniform outcomes. Method This paper provides a detailed description of a simple and uniform TSR scoring method using Hematoxylin and Eosin (H&E)-stained core biopsies and resection tissue, specifically focused on breast cancer. Possible histological challenges that can be encountered during scoring including suggestions to overcome them are reported. Moreover, the procedure for TSR estimation in lymph nodes, scoring on digital images and the automatic assessment of the TSR using artificial intelligence are described. Conclusion Digitized scoring of tumor biopsies and resection material offers interesting future perspectives to determine patient prognosis and response to therapy. The fact that the TSR method is relatively easy, quick, and cheap, offers great potential for its implementation in routine diagnostics, but this requires high quality validation studies

Standardization of the tumor-stroma ratio scoring method for breast cancer research

Purpose The tumor-stroma ratio (TSR) has repeatedly proven to be correlated with patient outcomes in breast cancer using large retrospective cohorts. However, studies validating the TSR often show variability in methodology, thereby hampering comparisons and uniform outcomes. Method This paper provides a detailed description of a simple and uniform TSR scoring method using Hematoxylin and Eosin (H&E)-stained core biopsies and resection tissue, specifically focused on breast cancer. Possible histological challenges that can be encountered during scoring including suggestions to overcome them are reported. Moreover, the procedure for TSR estimation in lymph nodes, scoring on digital images and the automatic assessment of the TSR using artificial intelligence are described. Conclusion Digitized scoring of tumor biopsies and resection material offers interesting future perspectives to determine patient prognosis and response to therapy. The fact that the TSR method is relatively easy, quick, and cheap, offers great potential for its implementation in routine diagnostics, but this requires high quality validation studies.Surgical oncolog

Prognostic value of tumor-stroma ratio combined with the immune status of tumors in invasive breast carcinoma

Surgical oncolog