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Background: The SINODAR-ONE trial is a prospective noninferiority multicenter randomized study aimed at assessing the role of axillary lymph node dissection (ALND) in patients undergoing either breast-conserving surgery or mastectomy for T1-2 breast cancer (BC) and presenting one or two macrometastatic sentinel lymph nodes (SLNs). The endpoints were to evaluate whether SLN biopsy (SLNB) only was associated with worsening of the prognosis compared with ALND in terms of overall survival (OS) and relapse., Methods: Patients were randomly assigned (1:1 ratio) to either removal of ≥ 10 axillary level I/II non-SLNs followed by adjuvant therapy (standard arm) or no further axillary treatment (experimental arm)., Results: The trial started in April 2015 and ceased in April 2020, involving 889 patients. Median follow-up was 34.0 months. There were eight deaths (ALND, 4; SNLB only, 4), with 5-year cumulative mortality of 5.8% and 2.1% in the standard and experimental arm, respectively (p = 0.984). There were 26 recurrences (ALND 11; SNLB only, 15), with 5-year cumulative incidence of recurrence of 6.9% and 3.3% in the standard and experimental arm, respectively (p = 0.444). Only one axillary lymph node recurrence was observed in each arm. The 5-year OS rates were 98.9% and 98.8%, in the ALND and SNLB-only arm, respectively (p = 0.936)., Conclusions: The 3-year survival and relapse rates of T1-2 BC patients with one or two macrometastatic SLNs treated with SLNB only, and adjuvant therapy, were not inferior to those of patients treated with ALND. These results do not support the use of routine ALND., (© 2022. Society of Surgical Oncology.)

Introduction: The optimal surgical management of BRCA-mutation carriers remains a subject of debate. To evaluate the appropriateness of breast cancer (BC) treatment, the oncological outcomes of BRCA-mutation carriers treated either with breast-conserving therapy (BCT) or mastectomy were compared. Additionally, the role of bilateral salpingo-oophorectomy (BSO) and potential independent predictive factors for BC treatment were analyzed., Materials and Methods: We retrospectively reviewed all the consecutive patients with a pathogenic germline mutation in the BRCA1/2 genes tested at our Institution between July 2008 and October 2018. Primary end-points were disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS)., Results: The characteristics and outcomes of 124 BRCA-associated BC patients were analyzed. Overall, 69 (55.7%) and 55 (44.3%) patients underwent BCT and mastectomy, respectively; 72 (58.1%) patients underwent BSO. After a median interval of 13.3 months, 24 patients underwent mastectomy after primary BCT. There was no significant difference in terms of DFS, DDFS, and OS between patients treated with BCT or mastectomy (p = 0.39,p = 0.27,p = 0.265, respectively). Patients treated with BSO had significantly better DDFS and OS compared to ovarian conservation (p = 0.033,p = 0.040, respectively). Three independent predictive factors for BCT were identified: age ≤41 years, genetic testing performed post-operatively, and breast tumors ≤21 mm., Conclusions: Our data suggest that BRCA-mutation carriers treated with BCT present similar oncological outcomes compared to mastectomy. Ovarian preservation decreases survival. Young BRCA-mutated patients with small BCs may not need up-front mastectomy, and BSO might be performed when ovarian cancer risk epidemiologically rises and potential reproductive desire is fulfilled., Competing Interests: Declaration of competing interest Santoro A: participation to Advisory Board and fees as speaker for Sandoz, Servier, EISAI, Roche, Novartis, Gilead, Pfizer, and BMS. The remaining authors declare no conflict of interest., (Copyright © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Luminal-like breast cancer (BC) constitutes the majority of BC subtypes, but, differently from highly aggressive triple negative BC, is poorly infiltrated by the immune system. The quality of the immune infiltrate in luminal-like BCs has been poorly studied, thereby limiting further investigation of immunotherapeutic strategies. By using high-dimensional single-cell technologies, we identify heterogeneous behavior within the tissue-resident memory CD8+ T (Trm) cells infiltrating luminal-like tumors. A subset of CD127- CD39 hi Trm cells, preferentially present in the tumor compared to the adjacent normal breast tissue or peripheral blood, retains enhanced degranulation capacity compared to the CD127+ CD39 lo Trm counterpart ex vivo, and is specifically associated with positive prognosis. Nevertheless, such prognostic benefit is lost in the presence of highly-suppressive CCR8 hi ICOS hi IRF4+ effector Tregs. Thus, combinatorial strategies aiming at boosting Trm function and infiltration while relieving from Treg-mediated immunosuppression should be investigated to achieve proper tumor control in luminal-like BCs., (© 2021. The Author(s).)

Mucinous carcinoma (MC) is a rare breast cancer characterized by the presence of large extracellular mucin amount. Two main subtypes can be distinguished: pure (PMC) and mixed (MMC). We conducted a retrospective MC analysis in our prospective maintained database, calculating disease-free survival (DFS) and 5-year overall survival (OS). We found a global 92.1% OS (higher in MMC group and statistically significative) and a DFS of 95.3% (higher in MMC group but not statistically significative)., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest in relation to this work., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Luminal B breast cancers (BC) have a more aggressive behavior associated with a higher rate of tumor relapse and worse prognosis compared to luminal A tumors. In this study, we evaluated the involvement of specific epithelial-to-mesenchymal transition- (EMT-) and immune-related pathways in the dissemination of luminal B BC cells. The expression of 42 EMT- and immune-related genes was evaluated in matched sentinel lymph nodes (SLNs) analyzed by the one-step nucleic acid amplification assay (OSNA) and primary tumors of 40 luminal B BC patients by gene array and immunohistochemistry. The results were validated in an independent group of 150 luminal B tumors by immunohistochemistry and immunofluorescence and using gene expression data from 315 luminal B BC patients included in the Metabric dataset. We found that the expression of CXCR4 ( p = 3.28 E - 02) and CD163 ( p = 6.92 E - 03) was significantly upregulated in SLNs of recurrent luminal B BC patients. Luminal B primary tumors overexpressing CXCR4 were characterized by an increased expression of vimentin and a high content of CD163-positive macrophages. Bioinformatics analysis confirmed the correlation of CXCR4 with CXCL12 , VIM , and CD163 expression and LN involvement. Our results suggest that the upregulation of the CXCR4/CXCL12 pathway and the presence of protumor macrophages in the primary tumor and SLNs sustain the aggressiveness of an important subgroup of luminal B BC.

Phyllodes tumor is an extremely rare tumor of the breast. It occurs in females in the third and fourth decades. The difficulty in distinguishing between phyllodes tumors and benign fibroadenoma may lead to misdiagnosis. Lymph node involvement is rarely described in phyllodes tumors; for this reason, sentinel node biopsy may be warranted. We present a case of a 33-year-old woman affected by huge tumor of the right breast with ulceration in the skin with a rapid tumor growth and with omolateral axillary metastasis.