De-escalation of breast & axillary surgery in early-stage breast cancer patients

Over the past decade, the incidence of breast cancer worldwide has been steadily increasing, while the overall 10-year breast cancer recurrence- and mortality rates have decreased. This can partly be attributed to the earlier detection of breast cancer by improved imaging techniques. The greatest impact, however, is caused by more effective targeted and systemic therapies (chemo- and immunotherapy) which are increasingly tailored to tumor biology. Today, in early-stage breast cancer patients, systemic therapies are more often applied prior to surgery (i.e, neoadjuvant systemic therapy). Major advantages of neoadjuvant versus adjuvant systemic therapy are in vivo response monitoring and tumor downsizing, enabling less invasive surgery in patients with good response. In this thesis, we investigated several different approaches and conditions for optimal locoregional breast cancer staging in early-stage breast cancer patients, aiming to identify patients who are eligible for safe de-escalation of treatment. This is important because, since breast cancer survival has greatly improved over the past decades, the long-term side-effects of locoregional treatment are becoming increasingly apparent and can have a major impact on quality of life. This thesis discusses the following three questions: 1). Can we identify exceptional responders with a pathological complete response of the breast after neoadjuvant systemic treatment without invasive surgery, in whom surgery may be omitted? 2). Can we safely select patients who have an increased risk of tumor-positive resection margins for breast conserving surgery, without compromising surgical and oncological outcomes? 3). Can we identify patients in which de-escalated locoregional treatment of the lymph nodes is safe, even in case of multiple involved nodes prior to systemic therapy?