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Background: Data published in 2015 showed that patients with early breast cancer (EBC) and a low-risk (LR) Recurrence Score® (RS) result by the 21-gene Oncotype DX® assay ("the test") did not derive benefit from adding chemotherapy (CT) to endocrine therapy (HT), while those with a high-risk (HR) RS result did. However, the role of CT remained uncertain in patients with intermediate-risk (IR) cancers. We designed a study to assess the test's ability to categorize patients with EBC with uncertain biological behavior into the groups (LR and HR) for which the value of additional chemotherapy was defined., Methods: The POST trial was a multicenter, prospective cohort study conducted in 14 Breast Centers of the Tuscany region of Italy. Consecutive patients with pT1-2 pN0-N1mi hormone receptor-positive/HER2-negative EBC and uncertain biological behavior based on standard parameters were enrolled. Patients were categorized based on RS results into LR, IR, and HR groups if RS result was < 11, 11-25, and > 25, respectively. Treatment recommendations by multidisciplinary meeting assessed before and after RS results were available., Results: Of 246 tested samples, 78 were classified as LR or HR, with most of the patients (65.4 %) being at IR. Following test results, the recommendation changed in 15.9 % of cases. Among patients initially recommended for CT or for discussion about the role of CT, respectively 64.3 % and 75.9 % ultimately received recommendation for HT alone., Conclusions: Our study suggests that RS results can refine treatment decisions for patients with EBC exhibiting uncertain biological behavior initially recommended or considered for CT. (250/250)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Serum biomarkers have been investigated as predictive risk factors for cancer-related cardiovascular (CV) risk, but their analysis is limited to their baseline level rather than their overtime change. Besides historically validated causal factors, inflammatory and oxidative stress (OS) related markers seem to be correlated to CV events but this association needs to be further explored. We conducted an observational study to determine the predictive role of the longitudinal changes of commonly used and OS-related biomarkers during the cancer treatment period., Methods: Patients undergoing anticancer therapies, either aged 75+ years old or younger with an increased CV risk according to European Society of Cardiology guidelines, were enrolled. We assessed the predictive value of biomarkers for the onset of CV events at baseline and during therapy using Cox model, Subpopulation Treatment-Effect Pattern Plot (STEPP) method and repeated measures analysis of longitudinal data., Results: From April 2018 to August 2021, 182 subjects were enrolled, of whom 168 were evaluable. Twenty-eight CV events were recorded after a median follow up of 9.2 months (Interquartile range, IQR: 5.1-14.7). Fibrinogen and troponin levels were independent risk factors for CV events. Specifically, patients with higher than the median levels of fibrinogen and troponin at baseline had higher risk compared with patients with values below the medians, hazard ratio (HR) = 3.95, 95% CI, 1.25-12.45 and HR = 2.48, 0.67-9.25, respectively. STEPP analysis applied to Cox model showed that cumulative event-free survival at 18 and 24 months worsened almost linearly as median values of fibrinogen increased. Repeated measure analysis showed an increase over time of D-Dimer ( p -interaction event*time = 0.08), systolic ( p = 0.07) and diastolic ( p = 0.05) blood pressure and a decrease of left ventricular ejection fraction ( p = 0.15) for subjects who experienced a CV event., Conclusions: Higher levels of fibrinogen and troponin at baseline and an increase over time of D-Dimer and blood pressure are associated to a higher risk of CV events in patients undergoing anticancer therapies. The role of OS in fibrinogen increase and the longitudinal monitoring of D-dimer and blood pressure levels should be further assessed., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 The Author(s). Published by IMR Press.)

Purpose: Data from recently trials have provided practice-changing recommendations in management of the axilla in early breast cancer (eBC). However, further controversies have been raised, resulting in heterogeneous diffusion of these recommendations. Our purpose was to obtain a better homogeneity., Material and Methods: In 2021, the Tuscan Breast Network (TBN) established a consensus with the aim to update recommendations in this area. We performed a literature review on axillary management in eBC patients which led to an expert Delphi consensus aiming to explore the gray areas, build consensus and propose evidence-based suggestions for an appropriate management. Thereafter, we investigate their implementation in clinical practice., Results: (1) DCIS patients should have SLN biopsy only in case of mastectomy or in conservative surgery if tumor is in a location that would preclude future nodal sampling or in case of a mass; (2) ALND may be omitted for 1-2 positive SLN patients undergoing BCS in T1-2 tumors with 1-2 SLN positive, eligible for whole-breast irradiation and adjuvant systemic therapies; (3) consider the option of RNI in patients with 1-3 positive lymph nodes and one or more high-risk characteristics; (4) the population identified in 2) should NOT undergo lymph node irradiation as an alternative to axillary surgery and (5) patients with clinically (pre-operatively) positive axilla, or undergoing primary systemic therapy, or outside the criteria reported in 2) must receive additional ALND and/or RT as per local policy., Conclusion: This consensus provided a practical tool to stimulate local and national breast surgical and radiotherapy protocols., (© 2024. Italian Society of Medical Radiology.)

The therapeutic landscape of estrogen receptor (ER)-positive breast cancer includes endocrine treatments with aromatase inhibitors (AIs), selective estrogen receptor modulators (SERMs), and selective estrogen receptor degraders (SERDs). Fulvestrant is the first approved SERD with proven efficacy and good tolerability in clinical practice. However, drug resistance, low receptor affinity, and parental administration stimulated the search for new oral SERDs opening a new therapeutic era in ER + breast cancer. Elacestrant is an orally bioavailable SERD that has been recently approved by the FDA for postmenopausal women with ER+, human epidermal growth factor receptor 2-negative (HER2-), estrogen receptor 1 (ESR1)-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy. Other molecules of the same class currently tested in clinical trials are amcenestrant, giredestrant, camizestrant, and imlunestrant. The current review article offers a detailed pharmacological perspective of this emerging drug class, which may help with their possible future clinical applications., Competing Interests: Declaration of competing interest Giorgio Guglielmi: none; Marzia Del Re: Ipsen, Novartis, Pfizer, Sanofi Genzyme, AstraZeneca, Pierre-Fabre, Janssen (scientific advisory board, consulting relationship), Ipsen, AstraZeneca, Sanofi Genzyme (travel, accommodation, expenses); Leila Sadeghi Gol: none; Carmelo Bengala: Astra Zeneca, Pfizer, Daiichi-Sankyo, Novartis, Gilead, Pierre Fabre, Roche, GSK (scientific advisory boards, travel, accommodation); Romano Danesi: Roche, Ipsen, Novartis, Pfizer, Sanofi Genzyme, AstraZeneca, Janssen, Gilead, Lilly, Gilead, EUSA Pharma (scientific advisory board, consulting relationship), Ipsen, Sanofi Genzyme (travel, accommodation, expenses). Stefano Fogli: Pfizer, Novartis, Roche, BMS, Lilly, Teva, Janssen, Celgene (scientific advisory board, consulting relationship, travel expenses)., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Recurrent gynecological tumors (e.g., endometrial, and ovarian cancers) are incurable diseases; therefore, new treatment options are urgently needed. The PTEN-AKT-PI3K pathway is frequently altered in these tumors, representing a potential treatment target. Alpelisib is an α-specific PI3K inhibitor approved in PIK3CA-mutated advanced breast cancer. We report outcomes from a large series of patients with PIK3CA-mutated gynecological cancers prospectively treated with alpelisib within a controlled program., Methods: From April 2021 to December 2022, 36 patients with PIK3CA-mutated advanced gynecological cancers received alpelisib 300 mg orally once daily. Objective response (ORR) and disease control (DCR) rates provided measure of the antitumor activity of alpelisib, the primary objective of the study., Results: Included patients had endometrial (17/36 [47%]), ovarian (10/36 [28%]), or other gynecological cancers (9/36 [25%]). Most patients had received 2-3 prior systemic treatments (endometrial, 47·2%; ovarian, 60%; other, 56%), and presented with visceral metastases at baseline (82%, 70%, and 56%, respectively). Overall, 17 different PIK3CA mutations were found, including 53% in the kinase domain (most commonly H1047R) and 36% in the helical domain (most commonly E545K). Overall, the ORR was 28% and DCR was 61%, with the greatest benefit observed in patients with endometrial cancer (35% and 71%, respectively)., Conclusion: Alpelisib represents an active treatment option in patients with recurrent gynecological cancers harboring a PIK3CA mutation. These findings support the need of biomarker-driven randomized trials of PI3K inhibitors in gynecological cancers., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)