Cover Page The handle https://hdl.handle.net/1887/3142382

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Cover Page

The handle https://hdl.handle.net/1887/3142382 holds various files of this Leiden

University dissertation.

Author: Groen, E.J.

Title: The road towards conquering DCIS overtreatment

Issue Date:

2021-02-16

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551586-L-bw-Groen 551586-L-bw-Groen 551586-L-bw-Groen 551586-L-bw-Groen Processed on: 18-12-2020 Processed on: 18-12-2020 Processed on: 18-12-2020

Processed on: 18-12-2020 PDF page: 6PDF page: 6PDF page: 6PDF page: 6

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Thesis outline

The objectives of this thesis, aimed to reduce overtreatment of ductal carcinoma in situ (DCIS) of the breast, were: 1) to evaluate the risk of underestimation after a diagnosis of DCIS and the interrater reliability in the histopathological classification of DCIS, important conditions in order to safely adopt an active surveillance strategy for low-risk DCIS, 2) to investigate associations of clinicopathological factors with the risk of developing ipsilateral invasive breast cancer after treatment of DCIS and 3) to analyze the extent of response of DCIS, adjacent to HER2-positive breast cancer, to neoadjuvant systemic therapy and to investigate associations of clinicopathological and radiological factors with DCIS response.

In chapter 1 a review, summarizing our current knowledge on DCIS and the risks involved regarding

progression into invasive breast cancer, is presented. In addition, it highlights current knowledge gaps and provides recommendations on how to try and solve the dilemma of DCIS, preventing overtreatment in case of a harmless DCIS, but provide optimal treatment for potentially hazardous DCIS. In chapter 2 we provide a review on the DCIS dilemma for general clinicians, which focuses on

what DCIS is, and what a DCIS diagnosis and its associated knowledge gaps mean for their patients. In chapter 3 we performed a systematic literature review and a meta-analysis to identify the

most promising factors that are associated with the risk of subsequent invasive breast cancer after DCIS, that should be considered for validation, instrumental in the evaluation of their potential of being implemented in clinical practice. Also, we give an overview of frequently introduced biases in prognostic factor studies in DCIS.

Concerns exist regarding the safety of an active surveillance strategy for low-risk DCIS. Can we rely on a diagnosis of DCIS and its assigned grade, based on a preoperative biopsy, for safe selection of eligible patients? What is the risk of missing invasive breast cancer? In chapter 4, we have evaluated

the risk of underestimation after a diagnosis of DCIS based on a preoperative biopsy, both in terms of grade and stage. We studied the interrater reliability of grade and other histopathological DCIS features amongst a large group of European raters with varying expertise. Subsequently, using majority opinion-based scores for each feature, we assessed their association with the risk of invasive breast cancer (chapter 5).

In contrast to previous chapters describing pure DCIS, in chapter 6 the focus lies on DCIS that is

found adjacent to invasive breast cancer. In HER2-positive breast cancer a high rate of pathological complete response after neoadjuvant systemic treatment can be reached, allowing frequent conversion from ablative to breast-conserving surgery. However, the presence of adjacent DCIS and extensive calcifications on imaging before systemic treatment are often considered contra-indications for breast-conserving surgery, even in patients with radiological complete response of the tumor on MRI. We have estimated the response of DCIS, adjacent to HER2-positive breast cancer,

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9 to neoadjuvant systemic treatment including HER2-blockade and have assessed the associations of clinicopathological and radiological factors with DCIS response.

Lastly, in chapter 7, the main findings of this thesis are summarized and are put in perspective,