Radiotherapy After Primary CHEMotherapy for cT1-2cN1M0 Breast Cancer.: a Multicentre Prospective Registration Study.

Primary systemic treatment for breast cancer patients used to be given only to patients with locally advanced disease. Although until now no studies have been reported that primary systemic treatment leads to a superior survival compared to adjuvant chemotherapy [Mauri et al, 2005; Mieog et al, 2007], the last years have been showing an increase in the use of primary systemic treatment , also for patients with earlier stages of breast cancer. The suggested advantages of this policy are 1) that primary systemic treatment allows for monitoring of the response on the treatment, such that the type of chemotherapy can be changed in case of no response, and 2) that primary systemic treatment may shrink the tumour volume, allowing for a higher percentage of breast conserving therapy [Mieog et al, 2007]; and 3) the overall 40% chance of converting positive axillary nodes pre-PST to negative, questioning the need for an axillary dissection [Fontein et al, 2013; Kuehn et al, 2013]. A major disadvantage of primary systemic treatment is however, that the indications for post-operative radiotherapy are based upon studies where loco-regional recurrences were correlated to the pathological T and N stage in patients who had not been treated with chemotherapy before surgery. Since primary systemic treatment is affecting the pathological T and N stage, the indications for post-operative radiotherapy in these patients have become uncertain.

Objective: The primary aim of the study is to evaluate the 5 yr locoregional recurrence rate (LRR) in cT1-2cN0-1(cytology/histology and/or positive SN, excluding patients with > 3 pathologic axillary nodes on imaging) breast cancer patients, treated with neoadjuvant chemotherapy, breast surgery, and radiotherapy that is protocolized based on the pathology findings after chemotherapy and definitive surgery (ypTNM stage). The secondary aim is to develop a risk model based on risk factors, that can be used to predict which of the patients with a cT1-2cN0-1 breast carcinoma, treated with neoadjuvant chemotherapy and surgery, have a 5 yr LRR > 8 % if radiotherapy is withheld.

Study design: This study is a multicentre prospective cohort study. Study population: In total 710 patients with cT1-2pN0-1, excluding ≥cN2 and patients with > 3 pathologic axillary nodes on imaging, breast cancer, treated with at least three cycles of chemotherapy followed by breast and axillary surgery are eligible for the study.

During 5 years (2011-2015) patients diagnosed for primary breast cancer and eligible according to the criteria will be registered by the National Cancer Registry in this project.

Currently, three surgical strategies are being followed in cT1-2N0-1 patients, treated with primary systemic treatment :