Omission of SLNB in Triple-negative and HER2-positive Breast Cancer Patients With rCR and pCR in the Breast After NAST
Omission of SLNB in Triple-negative and HER2-positive Breast Cancer Patients With rCR and pCR in the Breast After NAST
Currently, axillary surgery for breast cancer is considered as staging procedure that does
 not seem to influence breast cancer mortality, since the risk of developing metastasis
 depends mainly on the biological behaviour of the primary (seed-and-soil model). Based on
 this, the postsurgical therapy should be considered on the basis of biologic tumor
 characteristics rather than nodal involvement.

 Improvements in systemic treatments for breast cancer have increased the rates of pathologic
 complete response (pCR) in patients receiving neoadjuvant systemic therapy (NAST), offering
 the opportunity to decrease, and perhaps eliminate, surgery in patients who have a pCR.

 The investigators designed a clinical trial in which only patients with the highest
 likelihood of having a pCR after NAST (triple-negative or HER2-positive breast cancer) will
 be included and type of surgery will be defined according to the response to NAST rather than
 on the classical T and N status at presentation. In the planned trial, axillary surgery will
 be eliminated completely (no axillary sentinel lymph node biopsy [SLNB]) for initially cN0
 patients with radiologic complete remission (rCR) and a breast pCR as determined in the
 lumpectomy specimen.

 The trial design is a multicenter single-arm study with a limited number of patients (N=267)
 which might give practice-changing results in a short period of time, sparing the time and
 the costs of a randomized comparison. Patients will be recruited in European countries
 (Austria, Germany, Italy, Spain and Sweden) over a period of 24 months.
EUBREAST-01 is a prospective non-randomized, single-arm surgical trial. Included patients
 will be recruited for the experimental arm (no axillary SLNB in cases with breast pCR after
 NAST) exclusively. EUBREAST-01 is an international multicentric trial and designed by
 European Breast Cancer Research Association of Surgical Trialists (EUBREAST). The University
 Medicine Rostock (Germany) will overtake the sponsorship for the trial.

 Duration of recruitment is 2 years among 30 German, 10-15 Italian, 3 Spanish, 3 Swedish, and
 3 Austrian study centres. The total number of patients to be recruited into the trial will be
 267. All participating centres are experienced in conduction of clinical trials and stated at
 least a rate of 50 primary breast cancer diagnosis per year. At least 30% of all primary
 breast cancer are TNBC or HER2-positive tumors. The great majority of these cases will be
 diagnosed in tumor stage T1c-T3 (>1cm). The NAST with chemotherapy (plus anti-HER2 therapy if
 HER2-positive) is standard for this cohort in Germany, Austria, Italy, Spain and Sweden. If
 each study center will recruit 3 cases per year, the planned recruitment of 267 patients
 (per-protocol analysis) will be reached in 2 years.

 Efficacy analyses will be conducted after a follow-up of 3 years for each patient regarding
 the primary outcome and after 5 years follow-up for the secondary outcomes. No interim
 analysis is planned. Patients will be assessed for disease recurrence according to standard
 national clinical practice over a period of at least 5 years. Longest follow-up is 7 years.
 History and physical examination will be performed every 6 months for the first 36 months and
 yearly thereafter. Annual mammography and sonography will be required; other testing will be
 based on symptoms and investigator preference.
Inclusion Criteria:

 -  Written informed consent prior to breast-conserving surgery, including expected
 cooperation of the patients for follow-up, must be obtained and documented according
 to the European regulatory requirements

 -  Histologically confirmed unilateral primary invasive carcinoma of the breast (core
 biopsy). Multifocal or multicentric tumors are allowed if breast-conserving surgery is
 planned.

 -  Age at diagnosis at least 18 years

 -  imaging techniques with estimated tumor stage between cT1c-T3 prior to NAST

 -  triple-negative or HER2-positive invasive breast cancer

 -  clinically and sonographically tumor-free axilla prior to core biopsy (cN0/iN0)

 -  in cases with cN0 and iN+, a negative core biopsy or fine needle aspiration (FNA)
 biopsy of the sonographically suspected lymph node is required

 -  no evidence for distant metastasis (M0)

 -  standard NAST with radiologic complete response (rCR)

 -  planned breast-conserving surgery with postoperative external whole-breast irradiation
 (conventional fractionation or hypofractionation)

 Exclusion Criteria:

 -  History of malignancy within last 5 years, except curatively treated basalioma of the
 skin and carcinoma in situ of the cervix

 -  Time since last cycle of NAST >3 months (optimal <1 month)

 -  histologically non-invasive breast carcinoma

 -  ER-positive/HER2-negative disease (triple-positive tumors are allowed)

 -  cT4 or iT4 tumors

 -  pregnant or lactating patients

 -  no radiologic complete response at the end of NAST

 -  planned total mastectomy after NAST

 -  planned intraoperative radiotherapy (e.g. Intrabeam) or postoperative partial breast
 irradiation (e.g. multicatheter technique) alone; both procedures are allowed as boost
 techniques

 -  male patients