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Background: Few data are available about real-life cardiotoxicity associated with s.c. versus i.v. trastuzumab treatment of early-stage, HER2-positive breast cancer, and little is known about its predisposing factors., Patients and Methods: We retrospectively reviewed data of 363 adult patients treated with adjuvant trastuzumab for HER2-positive breast cancer. Univariate statistical analysis was performed, and a multivariable logistic model was developed to identify independent risk factors of cardiac toxicity., Results: Within 5 years, the overall incidence of events meeting our criteria was 11.8%, and an early discontinuation of trastuzumab was recorded in 20 patients (5.5%). No cases of congestive heart failure occurred, neither multiple events per patient were observed. A total of 184 patients received i.v. and 179 received s.c. trastuzumab. Compared with the s.c. formulation, a higher cardiotoxicity rate for the i.v. administration (15.2% vs 8.4%) was found, and particularly in those patients with cardiovascular risk factors (19.3% vs 8.7%), at the univariate and multivariate analyses. Although more patients with prior anthracycline-based chemotherapy experienced cardiac events, the association of this therapy with cardiac events was not significant. The incidence of cardiac events was not influenced by anthropometric data (e.g. body mass index) or a diagnosis of diabetes mellitus. 5-year event-free survival was 91.7% in the overall population; event-free survival rates were similar between the s.c. and the i.v. groups., Conclusion: Our study shows a more favorable safety profile of s.c. versus i.v trastuzumab administration. The use of s.c. trastuzumab could be advisable in at-risk patients., Competing Interests: Declaration of competing interest Armando Santoro has received honoraria from BMS, AstraZeneca, MSD, Lilly, Bayer, Takeda, Roche, Mundipharma, Novartis, Servier, Amgen, ArQule, Celgene, Incyte, AbbVie, Gilead, Pfizer, Daiichi, Sandoz, and Sanofi. Rita De Sanctis has received honoraria form EISAI, Kyowa Kirin and Novartis. The other authors have no funding and conflicts of interests to disclose., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: To evaluate acute toxicity and cosmetic outcomes of hypofractionated simultaneous integrated boost (SIB) as adjuvant treatment after breast-conserving surgery and adjuvant chemotherapy and to review the association of chemotherapy and short fractionation with boost., Materials and Methods: Patients presenting early-stage breast cancer were enrolled in a phase II trial. All patients received VMAT-SIB technique to the whole breast and tumor bed in 15 fractions, for a total dose of 40.5 and 48 Gy. Acute and late skin toxicities and breast pain were recorded. Cosmetic outcomes were also assessed as excellent/good or fair/poor., Results: Between August 2010 and December 2015, 787 consecutive patients were treated and had at least 2 year follow-up. A subset of 175 patients underwent adjuvant chemotherapy (median age of 55 years) and was analysed. The median follow up was 39 months (range 24-80). At the end of RT treatment, skin toxicity was G1 in 51.1% of patients, G2 in 9.7%. At 2 years of follow up, it was G1 in 13.5% of patients, no cases ≥ G2; cosmetic outcome was excellent in 63.5% and good in 36.5% of the patients. No significant difference compared to the patients without systemic therapy was observed., Conclusion: Hypofractionated VMAT-SIB in patients who had undergone adjuvant systemic therapy was safe and well tolerated in terms of acute and early late settings and cosmesis. Our data confirmed the results of other studies published on the association of hypofractionation and chemotherapy or concomitant boost., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Multidisciplinary management of oligometastatic breast cancer with local therapy could improve disease control. The aim of our study is the assessment of safety and efficacy of Stereotactic Body Radiation Therapy (SBRT) in selected subset of patients., Patients and Methods: Oligometastastic patients from breast cancer were treated with SBRT for 1-3 lung and liver lesions, in an observational study. Inclusion criteria were: age >18 years, ECOG 0-2, diagnosis of breast cancer, no extrapulmonary and/or extrahepatic disease, other metastatic sites stable or responding after chemotherapy were allowed, no life threatening conditions, less than 5 lung and liver lesions (with maximum diameter <5 cm), chemotherapy completed at least 3 weeks before treatment, written informed consent. Prescription dose ranged between 48 and 75 Gy in 3 or 4 consecutive fractions. Primary end-point was local control (LC). Secondary end-points were toxicity, overall survival (OS) and progression-free survival (PFS)., Results: From April 2010 to June 2014, 33 patients for a total number of 43 lesions were irradiated. Median follow up was 24 months (range 3-59). Actuarial LC rates were 98% at 1 year and 90% at 2 and 3 years. Complete response, partial response and progressive disease were detected in 25 (53.2%), 16 (34%), and 6 (12.8%) lesions, respectively. Median OS was 48 months. Actuarial OS rates at 1 and 2 years were 93% and 66% respectively. Median PFS was 11 months, with a PFS rate at 1 and 2 years of 48% and 27%, respectively. At univariate analysis DFI >12 months, hormonal receptor positivity, medical therapies after SBRT showed a significant impact on OS. Treatment was well tolerated, with no G3-4 toxicities., Conclusions: SBRT is a safe and feasible alternative treatment of liver and lung oligometastases from breast cancer, in selected patients not amenable to surgery, with good local control and survival rate., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Purpose: We investigated in a single institution series of 124 women with operable breast cancer whether tumor clinicopathological features could predict the 70-gene signature (Mammaprint, MP) results, and whether MP results could help to make decisions for the use of chemotherapy (CT) in patients (pts) with ER positive breast cancer beyond recommendations of international guidelines., Results: Among the 68 ER/PgR positive, HER2 negative tumors, Ki-67 ≥ 20% was the only significant predictor of a high risk-MP among standard clinicopathological features. In candidates for endocrine therapy with undetermined benefit from CT according to international guidelines, MP results would have led to different treatment decisions in 13/46 (28%) and in 20/68 (29%) pts according to NCCN and St. Gallen recommendations, respectively., Conclusions: Ki-67 independently predicted high risk-MP in ER/PgR positive, HER2 negative tumors. MP results would have led to discordant treatment recommendations in about 30% of cases, generally increasing indication rate for CT. The results of large randomized trials are warranted in order to understand whether we should rely on multigene assays rather than on standard clinicopathological features for treatment decisions., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: The level of HER2/neu amplification may vary widely in breast cancers with HER2/neu alteration. The clinical significance of this phenomenon is still unclear. This study was aimed to explore the level of HER2/neu amplification in primary tumours and metastases in HER2-positive metastatic breast cancer (MBC) and its potential impact on survival after a trastuzumab-containing therapy., Methods: We retrospectively identified MBC patients treated with a trastuzumab-containing therapy and performed dual-colour FISH on tumour samples from either primary tumour and/or metastasis in a central laboratory., Results: We retrieved 110 tumour samples from 91 patients and included 79 tumour samples (primary = 56; metastasis = 23) from 63 patients in the final analysis. We found higher level of HER2/neu amplification in the metastases than in the primary tumours (median HER2/CEP17 ratio: 10.5 vs. 7.0, respectively). In 69% of patients (n = 16) with two tumour samples, the level of HER2/neu amplification was higher in the metastasis than in the paired primary tumour (median HER2/CEP17 ratio: 10.9 vs. 8.3, respectively, p = 0.004). The incremental gain in level of HER2/neu amplification was associated with significantly shorter OS after trastuzumab-containing therapy (p = 0.023, HR 1.014, CI95%: 1.002-1.025)., Conclusions: The level of HER2/neu amplification tends to increase from the primary tumour to the paired metastases in a significant proportion of patients with HER2-positive MBC. This phenomenon, although still not completely understood, could lead to a shorter OS after trastuzumab therapy., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

T1N0M0 (stage I) breast cancer (BC) has been increasing in recent decades but the optimal adjuvant approach remains controversial. To assess the outcome of BC patients stratified and treated with multimodal therapies according to St. Gallen consensus meeting recommendations, we retrospectively evaluated an unselected cohort of T1N0M0 BC patients, with respect to the St. Gallen criteria. At a median follow-up of 5 years, the recurrence rate, recurrence-free survival and overall survival were 7%, 94% and 96% respectively, and 60% of relapses were locoregional. No statistically significant difference was observed between T1a,b/T1c groups, or among risk categories (high/intermediate/low). The very low rate of distant recurrences even in patients with unfavorable prognostic factors seems to support the use of adjuvant systemic therapies but better prognostic and predictive factors are strongly needed for this subset of patients.