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... Show moreThis 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. Show less
The objective of the work presented in this thesis is to assess information provision about adjuvant systemic therapy during consultations between early-stage breast cancer patients and medical... Show moreThe objective of the work presented in this thesis is to assess information provision about adjuvant systemic therapy during consultations between early-stage breast cancer patients and medical oncologists in general. In this era of personalized medicine, prediction tools (e.g., Adjuvant!) are becoming an integral part of information provision during patient consultations. However, evidence is lacking about a) how prevalent the use of such tools is during patient consultations, and b) whether and how the use of such tools influences information provision. Therefore, this thesis in addition to assessing the availability and the quality of prediction tools for the early-stage breast cancer setting, also zooms in on the use of such tools during patient consultations and their impact on the content of consultations. Show less
Upon activation by estrogen, the Estrogen Receptor binds the chromatin and influences gene transcription. This ultimately leads to cell proliferation. About 75% of breast cancer patients... Show moreUpon activation by estrogen, the Estrogen Receptor binds the chromatin and influences gene transcription. This ultimately leads to cell proliferation. About 75% of breast cancer patients express this hormonal receptor. These patients are often treated with tamoxifen, which competitively inhibits the proliferative effects of estrogen in breast cancer cells. While tamoxifen inhibits the tumor growth of breast cancer, its effects in other Estrogen Receptor-positive tissues vary, as reviewed in chapter 1. Its most adverse side-effect is that it increases the risk for endometrial cancer. Chapters 2 and 3 describe the effects of tamoxifen on the DNA binding sites of the Estrogen Receptor in tamoxifen-associated endometrial cancer, and the similarities of these binding sites with those found in breast cancer. Unfortunately, there are Estrogen Receptor-positive breast cancer patients who do not respond to hormonal treatment. Chapter 4 reveals a key-role for activating transcription factor 2 on tamoxifen’s inhibitory response on cell proliferation. Chapter 5 discusses components of the Estrogen Receptor pathway and highlights their potential as biomarkers in hormonal response therapy. Finally, chapter 6 provides new questions invoked by this thesis, and discusses the importance of unraveling the Estrogen Receptor pathway in multiple tissues in order to develop tailor-made treatments. Show less
