De-escalating breast surgery: intraductal techniques and refining lumpectomy

Abstract

This thesis explores innovative approaches to improve the diagnosis and treatment of breast diseases, focusing on two areas: the management of pathological nipple discharge (PND) and the optimization of breast-conserving surgery (BCS) for breast cancer. In the case of PND, a condition characterized by spontaneous, unilateral discharge, current diagnostic techniques such as mammography and ultrasound often fail to provide conclusive results, leading to a high number of unnecessary surgeries. This thesis highlights that only 8.1% of patients with PND are diagnosed with malignancy after surgery. This means the majority of patients undergo invasive procedures for benign conditions, underscoring the need for improved diagnostic methods. Ductoscopy, a minimally invasive micro-endoscopic technique allows direct visualization and treatment of abnormalities within the milk ducts. Previous studies show that ductoscopy can prevent unnecessary surgery in approximately two-thirds of patients by accurately identifying and treating intraductal lesions. To enhance its diagnostic and therapeutic capabilities, UMC Utrecht, in collaboration with Delft University of Technology, developed new biopsy needles designed specifically for use during ductoscopy. These tools have shown potential in enabling more precise biopsies within the ducts, potentially improving diagnostic accuracy and reducing the need for exploratory surgeries. These newly designed biopsy tools were tested and patented. Another innovative intervention introduced is intraductal laser therapy, which enables the treatment of residual abnormalities within the ducts following a biopsy, offering a non-surgical treatment option. Additionally, this thesis investigated the role of microRNA expression in nipple fluid as a potential biomarker to differentiate between benign and malignant conditions. The results showed that miR-145-5p, upregulated in patients with intraductal papillomas, could serve as a useful diagnostic marker, offering a non-invasive alternative to current diagnostic methods. The introduction of these novel techniques has been impactful in the treatment of PND and have led to the inclusion of ductoscopy in the Dutch National Breast Cancer Guideline, with full reimbursement by health insurance companies in the Netherlands starting from January 2024. The second part of the thesis focused on optimizing BCS for breast cancer by identifying factors that influence lumpectomy size and positive margin rates to improve both cosmetic and oncological outcomes. This thesis presented several factors, such as BMI, breast size, and radiological tumor size, that affect lumpectomy size. It also demonstrated that postoperative lumpectomy sizes often exceed the commonly estimated 1-centimeter margin around the tumor. Based on these findings, a predictive tool and a web-based application were developed to help plastic surgeons better plan reconstructions more accurately, improving cosmetic outcomes and patient care. Factors associated with positive surgical margins, were also investigated. The study revealed that 8.0% of patients had positive margins after BCS, with factors such as invasive lobular carcinoma, larger tumors, smaller lumpectomy sizes, and treatment in lower-volume hospitals contributing to this risk. Understanding these predictors is crucial for improving both the cosmetic and oncological outcomes in BCS, with the goal of reducing reoperations and enhancing patient care.