Treatment Changes in Breast Cancer Management and De-Escalation of Breast Surgery

Abstract

A better understanding of tumor biology and new drugs have led to significant changes in the management of breast cancer (BC). Radical mastectomy, which had been the treatment for BC for more than a century, was based on the hypothesis that BC is a local-regional disease. In the 1970s, Fisher's studies showed that cancer cells could reach the systemic circulation without passage through the regional lymphatic system. Multidisciplinary treatment of BC, which was now considered a systemic disease, was started and radical mastectomy was replaced by breast-conserving surgery (BCS)+, axillary dissection (AD), systemic chemotherapy, hormonotherapy, and radiotherapy in early-stage BC. Modified radical mastectomy, chemotherapy, and radiotherapy were applied as a treatment for locally advanced BC. However, later clinical studies demonstrated that the breast can be preserved in those who respond well to neo-adjuvant chemotherapy (NAC). In the early 1990s, sentinel lymph node biopsy (SLNB) in early-stage BC (cN0) was performed using blue dye and radioisotope markers. It was shown that AD may be avoided in SLN-negative patients, and SLNB has been a standard intervention in cN0 patients. In this way, the very serious complications of AD, especially lymphedema, were avoided. BC has been shown to be a heterogeneous disease and the tumor may be divided into four different molecular subtypes. Thus, optimal treatment differed from patient to patient (one size fits all was inappropriate), individualized treatments have emerged and over-treatment was avoided. The prolongation of life expectancy and the decrease in recurrence led to an increase in the rate of BCS, an acceptable cosmetic result with oncoplastic surgery, and a better quality of life. The increase in the rate of complete response to NAC with new and targeted agents and especially in human epidermal growth factor receptor-2+ and triple-negative patients with a poor prognosis has led to the use of NAC regardless of cN0. The complete disappearance of the tumor after NAC has been reported by some studies, suggesting that breast surgery may not be needed. However, other studies have shown that vacuum biopsies performed on the tumor bed have a high rate of false negativity. Therefore, it is difficult to suggest that there is no need for lumpectomy, which is cheaper and safer today. The false negativity rate of SLNB is high in patients with cN1 at the time of diagnosis and cN0 after NAC (approximately 13%). In order to reduce this rate to ≤5%, clinical studies have recommended the use of the dual method, marking the positive lymph node before chemotherapy and removing 3-4 nodules with SLN. In summary, a better understanding of tumor biology and new drugs have changed the management of BC and de-escalate the role of surgical treatment.

Keywords: Breast cancer management; chemotherapy; molecular subtypes; sentinel lymph node biopsy; surgery.