Abstract OT3-20-03: Refusal of Breast Surgery in Breast Cancer Patients With cCR After Neoadjuvant Systemic Therapy and Vacuum-assisted Biopsy (VAB) and SLNB Confirmed pCR. An interim report of the prospective non-randomized trial. NCT04293796
Authors: Krivorotko Petr , Yerechshenko Sergey , Emelyanov Alexander , Busko Ekaterina , Tabagua Tengiz , Mortada Viktoria , Zernov Konstantin , Komyakhov Alexander , Nikolaev Kirill , Zhiltsova Elena , Gigolaeva Larisa , Pesotsky Roman , Enaldieva Diana , Bondarchuk Yana , Amirov Nikolay , Channov Valentin , Novikov Sergey , Bryantseva Zhanna , Artemyeva Anna , Smirnova Viktoriya , Semiglazova Tatiana , Belyaev Alexey , Semiglazov Vladimir 
Published: March 2023

Abstract
Introduction The aim of the study was to prove efficacy and safety of de-escalation of traditional breast surgery in BC patients who develop cCR after neoadjuvant systemic therapy. Refusal of surgery was offered to exceptional responders after vacuum-assisted tumor bed biopsy and sentinel lymph node biopsy confirmed absence of residual disease (pCR). Materials and methods A single-center prospective study was run in the NMRC n.a. N.N. Petrov. Starting from August of 2020, 35 patients with early сT1-2N0-1M0 (stage Ia-IIb) triple-negative and HER2-positive (both ER+ and ER-) unifocal tumours without DCIS in core-biopsy specimen enrolled in the study. Primary lesions were marked with a single clip in the centre. In cases with nodal involvement (cN1) the affected lymph nodes were also clipped. Patients with triple-negative breast cancer received 4 cycles of AC q21d followed by 12 cycles of weekly paclitaxel and carboplatin AUC 2.0. HER2-positive patients received 4 cycles of AC followed by 4 cycles of docetaxel combined with trastuzumab and pertuzumab q21d. Breast US, mammography and SPECT were used at baseline and at response evaluation. Vacuum-assisted biopsy was performed with 7G needle and US-guidance in the OR simultaneously with the SLNB. VAB protocol included retrieval of the tumor clip as first stage. Subsequently surrounding tissues were sampled, and markers were placed to guide radiotherapy. In case residual tumor was found patients received standard breast-conserving surgery. In case the sentinel lymph nodes were found to be positive, standard level II axillary clearance was performed. HER2-positive patients with pCR confirmed by VAB and SLNB received adjuvant trastuzumab up to one year. HER2-positive patients with residual breast or nodal involvement received trastuzumab emtansine up to one year. In case ER+, all patients received appropriate endocrine-therapy. In case of residual in-breast or nodal involvement patients with triple-negative breast cancer received standart capecitabine. Results The interim analysis included 25 patients in both groups. The median follow-up of disease-free survival for patients is 12 months. In the triple-negative group 12 patients achieved cCR. All patients went on to receive VAB and SLNB. After VAB and SLNB pCR was confirmed 11 patients (91.7%). 1 patient had invasive residual tumor with less than 5% cellularity. FNR in this group was 8.3% (1/12). Patient with invasive residual tumor received standard breast-conserving surgery. All the patients in the TNBC group were also found to be (sn)ypN0. In the HER2-positive group cCR was achieved 13 patients. All patients went on to receive VAB and SLNB. After VAB and SLNB pCR was confirmed 10 patients (77%). 3 patients had invasive residual tumor with less than 5% cellularity. FNR in this group was 23% (3/13). Patients with invasive residual tumor received standard breast-conserving surgery. All HER2-positive patients were found to be (sn)ypN0. One patient with HER2-positive subtype experienced a local reccurence in the postoperative zone 16 months after surgery. Initially, this patient achieved cCR and undergone VAB with SLNB. On final pathomorphologic examination isolated focuses of DCIS were found (ypTisN0). Standard breast-conserving surgery was performed and histologically only DCIS was found. This patient recieved 1-year of Trastuzumab and standard radiotherapy with boost. After the histologic confirmation of local reccurence patient underwent nipple-sparring mastectomy with reconstruction and nowadays she is recieveing therapy with trastuzumab emtansine (T-DM1). Conclusion All visualization modalities fail to provide reliable information on the true rate of pCR. Contemporary systemic therapy regimens after accurate selection of patients, following the inclusion criteria, allows to achieve pCR in 75-90%, thereby reducing the risk of FNR after VAB. The trial continues to enroll patients and further follow-up is needed.
Citation Format: Petr Krivorotko, Sergey Yerechshenko, Alexander Emelyanov, Ekaterina Busko, Tengiz Tabagua, Viktoria Mortada, Konstantin Zernov, Alexander Komyakhov, Kirill Nikolaev, Elena Zhiltsova, Larisa Gigolaeva, Roman Pesotsky, Diana Enaldieva, Yana Bondarchuk, Nikolay Amirov, Valentin Channov, Sergey Novikov, Zhanna Bryantseva, Anna Artemyeva, Viktoriya Smirnova, Tatiana Semiglazova, Alexey Belyaev, Vladimir Semiglazov. Refusal of Breast Surgery in Breast Cancer Patients With cCR After Neoadjuvant Systemic Therapy and Vacuum-assisted Biopsy (VAB) and SLNB Confirmed pCR. An interim report of the prospective non-randomized trial. NCT04293796. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT3-20-03.