22 research outputs found
Optimizing breast cancer survival models based on conventional biomarkers and stromal parameters
This thesis deals with multiple aspects of breast cancer
risk stratification after locoregional treatment.
The first part of the thesis deals with the reproducibility of established
pathological parameters that currently stratify breast cancer patients to
low- or high risk, on the basis of which systemic therapies are considered.
The reproducibility of estrogen receptor, progesterone receptor and HER2 is
investigated. Additionally, prognostic implication of lymph vascular space
invasion is assessed as well as its interobserver reproduciblity. Lastly, the
reproducibility of Ki67 assays are determined.
The second part of the thesis concerns investigations into the prognostic
aspects of the tumor-associated stromal tissues. These tissues might be used
to further improve breast cancer risk stratifications as well as help
determine tumor susceptibility to systemic treatments. The prognostic
implications of the tumor-stroma ratio is investigated. Proteomic studies
into the tumor-associated stroma is described as well as a work-flow for
investigating metabolic interactions between the tumor epithelium and tumor
stroma. The prognostic significance of TGF-beta signaling is also
investigated.
LUMC / Geneeskund
Tumor-stroma ratio is associated with Miller-Payne score and pathological response to neoadjuvant chemotherapy in HER2-negative early breast cancer
The tumor-stroma ratio (TSR) has proven to be a strong prognostic factor in breast cancer, demonstrating better survival for patients with stroma-low tumors. Since the role of the TSR as a predictive marker for neoadjuvant chemotherapy outcome is yet unknown, this association was evaluated for HER2-negative breast cancer in the prospective DIRECT and NEOZOTAC trials. The TSR was assessed on 375 hematoxylin and eosin-stained sections of pre-treatment biopsies. Associations between the TSR and chemotherapy response according to the Miller-Payne (MP) grading system, and between the TSR and pathological response were examined using Pearson's chi-square, Cochran-Armitage test for trend and regression analyses. A stroma-low tumor prior to neoadjuvant chemotherapy was significantly associated with a higher MP score (P = .005). This relationship remained significant in the estrogen receptor (ER)-negative subgroup (P = .047). The univariable odds ratio (OR) of a stroma-low tumor on pathological complete response (pCR) was 2.46 (95% CI 1.34-4.51, P = .004), which attenuated to 1.90 (95% CI 0.85-4.25, P = .119) after adjustment for relevant prognostic factors. Subgroup analyses revealed an OR of 5.91 in univariable analyses for ER-negativity (95% CI 1.19-29.48, P = .030) and 1.48 for ER-positivity (95% CI 0.73-3.01, P = .281). In conclusion, a low amount of stroma on pre-treatment biopsies is associated with a higher MP score and pCR rate. Therefore, the TSR is a promising biomarker in predicting neoadjuvant treatment outcome. Incorporating this parameter in routine pathological diagnostics could be worthwhile to prevent overtreatment and undertreatment.Surgical oncolog
Quality assessment of estrogen receptor and progesterone receptor testing in breast cancer using a tissue microarray-based approach
Assessing hormone receptor status is an essential part of the breast cancer diagnosis, as this biomarker greatly predicts response to hormonal treatment strategies. As such, hormone receptor testing laboratories are strongly encouraged to participate in external quality control schemes to achieve optimization of their immunohistochemical assays. Nine Dutch pathology departments provided tissue blocks containing invasive breast cancers which were all previously tested for estrogen receptor and/or progesterone receptor expression during routine practice. From these tissue blocks
Optimizing breast cancer survival models based on conventional biomarkers and stromal parameters
This thesis deals with multiple aspects of breast cancer
risk stratification after locoregional treatment.
The first part of the thesis deals with the reproducibility of established
pathological parameters that currently stratify breast cancer patients to
low- or high risk, on the basis of which systemic therapies are considered.
The reproducibility of estrogen receptor, progesterone receptor and HER2 is
investigated. Additionally, prognostic implication of lymph vascular space
invasion is assessed as well as its interobserver reproduciblity. Lastly, the
reproducibility of Ki67 assays are determined.
The second part of the thesis concerns investigations into the prognostic
aspects of the tumor-associated stromal tissues. These tissues might be used
to further improve breast cancer risk stratifications as well as help
determine tumor susceptibility to systemic treatments. The prognostic
implications of the tumor-stroma ratio is investigated. Proteomic studies
into the tumor-associated stroma is described as well as a work-flow for
investigating metabolic interactions between the tumor epithelium and tumor
stroma. The prognostic significance of TGF-beta signaling is also
investigated.
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Discordances in ER, PR and HER2 receptors after neoadjuvant chemotherapy in breast cancer
Neoadjuvant chemotherapy (NAC) for breast cancer is evolving and subsequent adjuvant systemic treatment is mainly based on the presence of the Estrogen (ER) receptor, Progesterone (PR) receptor and Human Epidermal growth factor Receptor 2 (HER2) status on the core needle biopsy prior to treatment. It is not well known whether these biomarkers change after NAC, requiring a change in further adjuvant systemic treatment. A review of the literature (PubMed search) revealed 32 relevant studies that investigated the concordance of the hormone receptors (ER and/or PR) and HER2 after NAC with or without trastuzumab. Discordance of the hormone receptor status was reported in four out of eight studies in 8-33% of the patients. About half of the studies that tested the ER and PR receptor status separately reported discordances of 2.5-17% and 5.9-51.7% respectively. Studies that concluded that ER and/or PR receptor remained stable after NAC were performed with evidently lower number of patients compared to studies that reported a change. Good concordance of the HER2 amplification tested with FISH was reported, although the HER2 expression measured with immunohistochemistry was more discordant. A switch to a negative HER2 receptor in up to 43% of the patients was reported when NAC was combined with trastuzumab. Until more comparable studies are being published, retesting the receptor status of the residual tumor after NAC should be considered in order to improve future tailored adjuvant therapies.Clinical OncologyOV
The prognostic value of tumour-stroma ratio in primary breast cancer with special attention to triple-negative tumours: a review
Surgical oncolog
Comment on: The prognostic significance of tumour-stroma ratio in oestrogen receptor-positive breast cancer
Immunology and molecular genetics of gynecological cancer
The prognostic value of the tumour-stroma ratio in primary operable invasive cancer of the breast: a validation study
Surgical oncolog
The prognostic value of tumor-stroma ratio in tumor-positive axillary lymph nodes of breast cancer patients
Surgical oncolog