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The standard care for metastatic breast cancer (MBC) is systemic therapies with imbrication of focal treatment for symptoms. Recently, thanks to implementation of radiological and metabolic exams and development of new target therapies, oligometastatic and oligoprogressive settings are even more common—paving the way to a paradigm change of focal treatments role. In fact, according to immunophenotype, radiotherapy can be considered with radical intent in these settings of patients. The aim of this literature review is to analyze available clinical data on prognosis of bone metastases from breast cancer and benefits of available treatments for developing a practical guide for clinicians.

Women with sporadic breast cancer should consider unilateral surgery as first choice for local treatment. Contralateral prophylactic mastectomy should be offered to patients with BRCA mutation.

[...]while performing the extreme oncoplastic breast conserving surgery, the modern oncoplastic surgeon should always follow some specific and crucial steps, such as careful local staging of the disease with ultrasonography, mammography, and magnetic resonance before surgery; adequate radiological preoperative study with localization of tumor and/or calcifications; multidisciplinary discussion, in a dedicated “surgery board”, to choose an oncoplastic technique tailored to patient; intraoperative ultrasound to guide the resection; intraoperative radiological and pathological evaluation of the specimen for definition of lesion and margins of resection; frozen sections should be obtained from a portion of all six faces of the resected specimen; systematic circumferential tumor cavity shaving to have a backup to lumpectomy margins; placement of clips within the excision cavity as a “landmark” to define the tumor bed and guide adjuvant breast radiotherapy; accurate pathological assessment of the specimen using macrosections. Blohmer, J. Hoffmann, C. Solbach, C. Heitmann, B. Gerber, M. Haug, C. Kurzeder, \"First international consensus conference on standardization of oncoplastic breast conserving surgery,\" Breast Cancer Research and Treatment, vol. 165 no. 1, pp. 139-149, DOI: 10.1007/s10549-017-4314-5, 2017. [8] M. C. Strach, T. Prasanna, Y. M. Kirova, S. Alran, S. O’Toole, J. M. Beith, P. Poortmans, C. M. McNeil, S. Carroll, \"Optimise not compromise: the importance of a multidisciplinary breast cancer patient pathway in the era of oncoplastic and reconstructive surgery,\" Critical Review in Oncology/Hematology, vol. 134, pp. 10-21, DOI: 10.1016/j.critrevonc.2018.11.007, 2019.

Triple-negative breast cancer (TNBC) is characterized by the absence of hormone receptor and HER2 expression, and therefore a lack of therapeutic targets. Anthracyclines and taxane-based neoadjuvant chemotherapy have historically been the cornerstone of treatment of early TNBC. However, genomic and transcriptomic analyses have suggested that TNBCs include various subtypes, characterized by peculiar genomic drivers and potential therapeutic targets. Therefore, several efforts have been made to expand the therapeutic landscape of early TNBC, leading to the introduction of platinum and immunomodulatory agents into the neoadjuvant setting. This review provides a comprehensive overview of the currently available evidence regarding platinum agents and immune-checkpoint-inhibitors for the neoadjuvant treatment of TNBC, as well as the novel target therapies that are currently being evaluated in this setting. Taking into account the economic issues and the side effects of the expanding therapeutic options, we focus on the potential efficacy biomarkers of the emerging therapies, in order to select the best therapeutic strategy for each specific patient.

Oncoplastic level II breast-conserving surgery (OPS2) allows for wider excisions than standard breast-conserving surgery, but the literature on this technique in the treatment of DCIS is scarce. This study compares OPS2 to conservative mastectomy (CM) in patients undergoing surgery for large DCIS. The clinical, radiological, surgical, and post-operative data of 147 patients who underwent either CM or OPS2 for large DCIS between 2007 and 2021 were retrospectively reviewed. The surgical, oncological, and patient-reported outcomes (PRO) were analyzed and compared between the two groups. The surgical outcomes were similar, in terms of margin involvement (p = 0.211), complication rate (p = 0.827), and re-excision rate (p = 1). The rate of additional surgery for cosmetic optimization was significantly lower in the OPS2 group: only 1 (1.8%) patient required surgical adjustments versus 24 (26.4%) patients in the CM group (p < 0.001). The mean hospital stay was lower in the OPS2 group (p < 0.001). The oncological outcomes did not differ between the two groups (p = 0.662). The PRO analysis showed better outcomes in the OPS2 group, which achieved statistical significance in the sexual well-being module (p = 0.015). Skin sensitivity loss was also significantly lower in the OPS2 group (p < 0.001). When feasible, OPS2 should be considered in the treatment of large DCIS, as it is safe and shows high levels of patient satisfaction.

Triple-negative breast cancer (TNBC) is characterized by earlier recurrence and shorter survival compared with other types of breast cancer. Moreover, approximately 15 to 25% of all TNBC patients harbor germline BRCA (gBRCA) 1/2 mutations, which confer a more aggressive phenotype. However, TNBC seems to be particularly sensitive to chemotherapy, the so-called ‘triple negative paradox’. Therefore, Neoadjuvant chemotherapy (NACT) is currently considered the preferred approach for early-stage TNBC. BRCA status has also been studied as a predictive biomarker of response to platinum compounds. Although several randomized trials investigated the addition of carboplatin to standard NACT in early-stage TNBC, the role of BRCA status remains unclear. In this retrospective analysis, we evaluated data from 136 consecutive patients with Stage I-III TNBC who received standard NACT with or without the addition of carboplatin, in order to define clinical features and outcomes in BRCA 1/2 mutation carriers and non-carrier controls. Between January 2013 and February 2021, 67 (51.3%) out of 136 patients received a standard anthracyclines/taxane regimen and 69 (50.7%) patients received a platinum-containing chemotherapy regimen. Deleterious germline BRCA1 or BRCA2 mutations were identified in 39 (28.7%) patients. Overall, patients with deleterious gBRCA1/2 mutation have significantly higher pCR rate than non-carrier patients (23 [59%] of 39 vs. 33 [34%] of 97; p = 0.008). The benefit of harboring a gBRCA mutation was confirmed only in the subset of patients who received a platinum-based NACT (17 [65.4%] of 26 vs. 13 [30.2%] of 43; p = 0.005) while no differences were found in the platinum-free subgroup. Patients who achieved pCR after NACT had significantly better EFS (OR 4.5; 95% CI 1.9–10.7; p = 0.001) and OS (OR 3.3; 95% CI 1.3–8.9; p = 0.01) than patients who did not, regardless of BRCA1/2 mutation status and type of NACT received. Our results based on real-world evidence show that TNBC patients with the gBRCA1/2 mutation who received platinum-based NACT have a higher pCR rate than non-carrier patients, supporting the use of this chemotherapy regimen in this patient population. Long-term follow-up analyses are needed to further define the role of gBRCA mutation status on clinical outcomes in patients with early-TNBC.

Interactions occurring between malignant cells and the stromal microenvironment heavily influence tumor progression. We investigated whether this cross-talk affects some molecular and functional aspects specifically correlated with the invasive phenotype of breast tumor cells (i.e. adhesion molecule expression, membrane fluidity, migration) by co-culturing mammary cancer cells exhibiting different degrees of metastatic potential (MDA-MB-231>MCF-7) with fibroblasts isolated from breast healthy skin (normal fibroblasts, NFs) or from breast tumor stroma (cancer-associated fibroblasts, CAFs) in 2D or 3D (nodules) cultures. Confocal immunofluorescence analysis of the epithelial adhesion molecule E-cadherin on frozen nodule sections demonstrated that NFs and CAFs, respectively, induced or inhibited its expression in MCF-7 cells. An increase in the mesenchymal adhesion protein N-cadherin was observed in CAFs, but not in NFs, as a result of the interaction with both kinds of cancer cells. CAFs, in turn, promoted N-cadherin up-regulation in MDA-MB-231 cells and its de novo expression in MCF-7 cells. Beyond promotion of \"cadherin switching\", another sign of the CAF-triggered epithelial-mesenchymal transition (EMT) was the induction of vimentin expression in MCF-7 cells. Plasma membrane labeling of monolayer cultures with the fluorescent probe Laurdan showed an enhancement of the membrane fluidity in cancer cells co-cultured with NFs or CAFs. An increase in lipid packing density of fibroblast membranes was promoted by MCF-7 cells. Time-lapsed cell tracking analysis of mammary cancer cells co-cultured with NFs or CAFs revealed an enhancement of tumor cell migration velocity, even with a marked increase in the directness induced by CAFs.Our results demonstrate a reciprocal influence of mammary cancer and fibroblasts on various adhesiveness/invasiveness features. Notably, CAFs' ability to promote EMT, reduction of cell adhesion, increase in membrane fluidity, and migration velocity and directness in mammary cancer cells can be viewed as an overall progression- and invasion-promoting effect.