Breast conservation and axillary management after primary systemic therapy in patients with early-stage breast cancer: the Lucerne toolbox

Breast conservation and axillary management after primary systemic therapy in patients with early-stage breast cancer: the Lucerne toolbox

Breast conservation and axillary management after primary systemic therapy in patients with early-stage breast cancer: the Lucerne toolbox

Peter Dubsky*, Katja Pinker*, Fatima Cardoso, Giacomo Montagna, Mathilde Ritter,Carsten Denkert, Isabel T Rubio, Evandro de Azambuja,
Giuseppe Curigliano, Oreste Gentilini, Michael Gnant, Andreas Günthert, Nik Hauser, Joerg Heil, Michael Knauer, Mona Knotek-Roggenbauerc,
Susan Knox, Tibor Kovacs, Henry M Kuerer, Sibylle Loibl, Meinrad Mannhart, Icro Meattini, Frederique Penault-Llorca, Nina Radosevic-Robin,
Patrizia Sager, Tanja Španić, Petra Steyerova, Christoph Tausch, Marie-Jeanne T F D Vrancken Peeters, Walter P Weber, Maria J Cardoso†,
Philip Poortmans†

Primary systemic therapy is increasingly used in the treatment of patients with early-stage breast cancer, but few guidelines specifically address optimal locoregional therapies. Therefore, we established an international consortium to discuss clinical evidence and to provide expert advice on technical management of patients with early-stage breast cancer. The steering committee prepared six working packages to address all major clinical questions from diagnosis to surgery. During a consensus meeting that included members from European scientific oncology societies, clinical trial groups, and patient advocates, statements were discussed and voted on. A consensus was reached in 42% of statements, a majority in 38%, and no decision in 21%. Based on these findings, the panel developed clinical guidance recommendations and a toolbox to overcome many clinical and technical requirements associated with the diagnosis, response assessment, surgical planning, and surgery of patients with early-stage breast cancer. This guidance could convince clinicians and patients of the major clinical advancements purported by primary systemic therapy, the use of less extensive and more targeted surgery to improve the lives of patients with breast cancer.

Introduction
Primary (or preoperative) systemic therapy (PST) is the standard of care for patients with locally advanced and large, resectable breast cancer.1 PST should also be considered for patients with a smaller tumour burden but with a clear chemotherapy indication at diagnosis, especially patients with triple-negative or HER2-positive breast cancer.1,2 One aim of PST is to reduce the extent of surgery, including the possibility of mastectomy3–5 or axillary lymph node dissection.5–7
Patients who respond to PST and have a pathological complete response show improved survival, particularly patients with aggressive tumour subtypes (eg, those with triple-negative or HER2-positive breast cancer).8 Improved outcomes have also been shown after PST escalation in patients with aggressive subtypes who do not have a pathological complete response.9,10 Ongoing trials are testing whether this approach is also beneficial in patients with luminal B-like tumours (NCT01864746) and in patients with triple-negative breast cancer who have a high residual disease burden (NCT02954874). In addition to tumour stage and biology, response to PST has become a third factor in tailoring systemic treatment and postoperative radiotherapy.11
Although previous trials have shown important improvements in the number of patients who have had a pathological complete response to PST, these results are often not consistent with breast-conserving surgery rates.12–15 This finding was confirmed in a meta-analysis,16 which showed that actual breast-conserving surgery rates were moderate, even in patients who were clinically eligible for breast conservation.17,18 Possibly, these moderate results are related to the absence of breast conserving surgery as a surrogate endpoint along with the primary endpoint of pathological complete response.
A large meta-analysis from the Early Breast Cancer Trialist’s Collaborative Group, which included 4756 patients from ten PST trials, indicated a significant increase in local cancer recurrences after PST.3 Although these data should be interpreted with caution (eg, patients who did not have surgery were included in the data set, the timeframe of the included trials ranged from 1983 to 2002, the options for systemic therapy and surgery are now outdated, and experience with PST was inconsistent among clinicians), these findings indicate the possibility of excessive de-escalation of local treatment for some patients who were scheduled for PST, a scenario which should be avoided. In addition to local treatment of the breast, delivering appropriate regional treatment to the lymph nodes after PST is a clinical challenge. In women presenting with clinically node-negative (cN0) breast cancer diagnosis, strong evidence suggests that sentinel lymph node biopsy after PST is feasible and safe.2,19–21 More controversy exists with  regard to women with initially limited nodal involvement (cN1) who downstage to cN0 after PST; prospective non-randomised trials have shown that, in this setting, false negative rates of sentinel lymph node biopsy are higher than in the primary surgery setting.19,22–24 Several new strategies for axillary staging after PST have been proposed.25–27 Although PST can reduce the extent of surgery, clinical trial data suggest that there is only moderate success in breast or breast tissue conservation16 and in de-escalating axillary treatment.21 Thus, an interdisciplinary consensus panel was  convened to specifically focus on challenging cases for upfront breast or axillary conservation, or both, after patients with early-stage breast cancer responded well to PST. Panellists aimed to address relevant questions, from diagnostic procedures to surgical planning and pathology assessment, based on available evidence and the clinical expertise of panellists. We report on the panel discussion and the voting and formulated a toolbox to implement strategies in the daily clinic. Based on current available evidence and panel expertise, this Policy Review provides a practical working toolbox for the optimum pathway for surgical treatment for patients with early-stage breast cancer after PST based on
chemotherapy. The toolbox consists of a comprehensive set of recommendations for the management of PST
across the multidisciplinary team, with the intention of supporting physicians in optimising the pathway towards
breast conservation and ultimately improving outcomes. The scope of this toolbox applies to resectable, early-stage breast cancer and is intended for use in daily clinical practice, especially for individuals who have a tumour volume exceeding 20–30% of the total breast volume.
Additionally, the consensus serves as a reference tool for clinical trials that aim to address PST for early-stage breast cancer.

 

Read the full article here: Lucerne toolbox-Lancet January 2021