The studies in this thesis contribute to more accurate risk assessment and prognosis prediction for DCIS and to better response evaluation of IBC treatment.For the Ductal Carcinoma In Situ (DCIS)... Show moreThe studies in this thesis contribute to more accurate risk assessment and prognosis prediction for DCIS and to better response evaluation of IBC treatment.For the Ductal Carcinoma In Situ (DCIS) studies, unbiased cohorts were used within the international Grand Challenge PRECISION consortium, funded by Cancer Research UK and KWF Dutch Cancer Society. DCIS is graded as low-, intermediate-, or high-grade depending on how abnormal the DCIS-cells look like. However, we showed that pathologists often disagree on grade. To overcome this limitation, we found that almost all DCIS scored as non-high-grade by the majority of pathologists express the estrogen receptor (ER) and are negative for the growth factor receptor HER2, whereas high-grade DCIS is mixed in expression for ER and HER2. We also provided insights in the recurrence risks of DCIS after treatment. See also https://cancergrandchallenges.org/teams/precision.The studies on Invasive Breast Cancer (IBC) were performed on a hospital-based cohort. We found for example substantial variation in tumour response evaluation for HER2-positive IBC after pre-operative chemotherapy due to different guidelines used. For accurate outcome analysis, reducing such variation is mandatory. Therefore, we are working on reaching international consensus of response evaluation. Show less
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... Show morePurpose 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 < 0.001, respectively). Fifty-one per cent of the patients from the Nottingham Breast Cancer series < 40 years had a stroma-high tumour compared to 73% of the patients of >= 90 years from the FOCUS study. The TSR did not validate as an independent prognostic parameter in patients >= 70 years. 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. Show less
Prognostic factors are used for making treatment decisions regarding adjuvant systemic therapy. The major prognostic variables that are used in clinical practice are the number of positive axillary... Show morePrognostic factors are used for making treatment decisions regarding adjuvant systemic therapy. The major prognostic variables that are used in clinical practice are the number of positive axillary lymph nodes and tumour size. A number of other variables are associated with disease recurrence and survival as well. In particular UPA and PAI-1 appear to be strong prognostic variables. No differences in prognostic value of oestrogen receptor and progesterone receptor detected by immunocytochemical assay or enzyme immuno assay were found. In the study presented no significant association between mitotic counts and disease recurrence or survival was found, which was explained by the favourable tumour characteristics of the group of patients and the associated low number of events. Several tools have been developed to make individualised estimates of baseline prognosis and absolute survival benefit of adjuvant systemic therapy. Two of these tools, Adjuvant! and Numeracy, were compared. Adjuvant! was the preferred prognostic model. The administration of adjuvant chemotherapy concurrently with radiotherapy appeared too toxic. As anthracyclin-containing regimens have become standard for adjuvant chemotherapy in early breast cancer which are considered more toxic than the regimens studied the concurrent administration of adjuvant chemotherapy and radiotherapy is dissuaded. Show less
