The Cost of Simplicity for Early-stage Breast Cancer Treatment

INTRODUCTION In radiation oncology, the most challenging clinical task is defining the clinical target volume, which is a margin for the radiation field that includes microscopic extension beyond the bulk of cancer seen on imaging.1 Should this encompass any single possible cell, including those filtered in the regional lymph nodes or in transit to the nodes? Or should one assume that this microscopic disease may not significantly impact the overall survival or locoregional recurrence? For early-stage breast cancers, the simplest approach is to include all the breast tissue into the clinical target volume, limited to the fascia pectoralis and 5 mm below the skin.2 Standard treatment for early breast cancers includes limited surgery followed by whole breast radiotherapy, which is equivalent to mastectomy in terms of cancer control but better in terms of cosmesis and quality of life.3–5 To de-escalate further, the concept of partial breast radiotherapy (PBI) has evolved for >30 years. It enables accelerated treatment because radiating a smaller volume allows delivering larger doses per fraction, and treatment spans over a single week instead of 3 to 6.6 In contrast, it requires robust data that it does not lead to increased local or distant recurrence. In 1991, Bethune7 questioned the logic of whole breast radiotherapy. He argued that in patients treated with partial mastectomy and radiation most of the early recurrences, within 2 years, tended to occur at the site of the primary lesion, while later recurrences tended to occur elsewhere in the breast. After 10 years, most patients have ∼5% risk of contralateral breast cancer, and hence a rate similar to the rate of recurrence far from the surgical bed. So, treating the whole breast to prevent recurrences far from the surgical bed may as well justify treating both breasts. The William Beaumont team was one of the first groups to explore the clinical evaluation of PBI, proposing many technical solutions, ranging from multicatheter brachytherapy, device-based brachytherapy, and finally conformal external radiotherapy.8,9 Eventually this led to the US NSABP/RTOG B-39 phase III trial comparing standard whole breast radiotherapy in 25 fractions plus a boost to PBI in 10 fractions over 5 days using either conformal external beam radiotherapy or brachytherapy.10 Since the publication of the US phase III trial, an additional 7 prospective randomized trials enrolling well over 10,000 patients with follow ranging from 5 to 20 years have been published. All studies show no or a minimal difference in local control, no difference in disease-free survival or overall survival, equivalent cosmesis in the majority of studies, and improved quality of life. Currently, trials have focused on improving PBI techniques and further de-escalating treatment. To that end, on June 22, 2022, experts in the field of PBI gathered in Florence, Italy to present the current and future status of PBI. This section of the American Journal of Clinical Oncology compiles the discussions and agreements from this group of experts with guidelines and recommendations for the optimal application of PBI and future trends.