Trastuzumab plus lapatinib or chemotherapy in patients with HER2-overexpressed advanced breast cancer: a randomized, phase II trial (GIM12-TYPHER).

Background: Trastuzumab combined with chemotherapy is a standard treatment for human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer in later lines. Lapatinib and trastuzumab have also demonstrated efficacy. This study assessed the efficacy, toxicity, and quality of life (QoL) of trastuzumab plus lapatinib (with endocrine therapy for hormone receptor-positive cases) versus trastuzumab with physician-selected chemotherapy in patients previously treated with at least 2 anti-HER2 regimens.

Comparative analysis of Denosumab and Zoledronic acid in advanced breast cancer patients receiving CDK4/6 inhibitors.

A comparative analysis of Denosumab (DMAB) and Zoledronic Acid (ZA) was conducted in a real-world cohort of 864 patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer with bone metastases, who were undergoing CDK4/6 inhibitors plus endocrine therapy. We evaluated the time to first skeletal-related events (SREs), progression-free survival (PFS), and overall survival (OS). To adjust for confounding variables, we utilized propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) methodologies.

Multidisciplinary discussion on phenotypical characterization of metastatic breast cancer and patient pathway optimization from an expert panel across South Italian regions.

Breast cancer (BC) might change its receptor status during malignant progression, resulting in challenging clinical care. The project, developed during two residential meetings by expert Italian oncologists and pathologists, was aimed at optimizing metastatic BC management. A 17-point survey was administered to healthcare workers in centers of three regions, essentially to assess the perception of metastasis biopsy on treatment choice in different BC molecular subtypes, the appropriate timing for performing tissue and liquid biopsy in metastatic BC, the selection of target genes and the use of multidisciplinary approaches in tumour management.

Insights on the association of anthropometric and metabolic variables with tumor features and genomic risk in luminal early breast cancer: Results of a multicentric prospective study.

Background: Hormone receptor-positive (HR+)/HER2-negative (HER2-) early-stage breast cancers (EBC) are treated with adjuvant endocrine therapy (ET), with chemotherapy (CT) reserved for high-risk cases. Obesity is linked to increased recurrence risk. The Oncotype DX® assay predicts prognosis and CT benefit.

Survival Following CDK4/6 Inhibitor Therapy for Hormone Receptor-Positive, ERBB2-Negative Metastatic Breast Cancer.

Importance: Endocrine therapy (ET) combined with cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) agents is the standard first-line treatment for patients with hormone receptor-positive, ERBB2 (formerly HER2 or HER2/neu)-negative metastatic breast cancer. However, optimal therapy after tumor progression to ET plus CDK4/6i remains unclear.

Objective: To evaluate progression-free survival (PFS) and overall survival (OS) in the clinical practice setting in patients with hormone receptor-positive, ERBB2-negative metastatic breast cancer following progression with ET plus CDK4/6i.

Prognostic implications of risk definitions from the monarchE and NATALEE trials.

Background: The monarchE and NATALEE trials employed different high-risk inclusion criteria. The main objective is to assess prognostic differences based on their inclusion criteria.

Methods: Patients with hormone receptor-positive/HER2-negative early breast cancer enrolled in the phase III Mammella InterGruppo (MIG) 1, Gruppo Italiano Mammella (GIM) 2, and GIM3 trials were categorized as high-risk cohort (HRC) and low-risk cohort (LRC) according to the inclusion criteria of monarchE and NATALEE trials.

Real life outcome analysis of breast cancer brain metastases treated with Trastuzumab Deruxtecan.

Tumor dissemination to the central nervous system (CNS) is almost a rule in the treatment journey of advanced HER2+ breast cancer (BC). Recent results demonstrated high intracranial efficacy with Trastuzumab Deruxtecan (T-DXd). However, a real-world evidence is lacking in literature.

CAR-T cell therapy for breast cancer: Current status and future perspective.

Within the expanding therapeutic landscape for breast cancer (BC), metastatic breast cancer (MBC) remains virtually incurable and tend to develop resistance to conventional treatments ultimately leading to metastatic progression and death. Cellular immunotherapy (CI), particularly chimeric antigen receptor-engineered T (CAR-T) cells, has emerged as a promising approach for addressing this challenge. In the wake of their striking efficacy against hematological cancers, CAR-T cells have also been used where the clinical need is greatest - in patients with aggressive BCs.

Clinical impact of drug-drug interactions on abemaciclib in the real-world experience of AB-ITALY study.

Abemaciclib demonstrated clinical benefit in women affected by HR+/HER2- advanced breast cancer (aBC). Drug-drug interactions (DDIs) can lead to reduced treatment efficacy or increased toxicity. This retro-prospective study aimed to evaluate outcomes, DDIs' impact, and toxicities of abemaciclib combined with endocrine therapy in a real-world setting.

Intermediate clinical endpoints in early-stage breast cancer: an analysis of individual patient data from the Gruppo Italiano Mammella and Mammella Intergruppo trials.

Background: Intermediate clinical endpoints (ICEs) are frequently used as primary endpoint in randomised trials (RCTs). We aim to assess whether changes in different ICEs can be used to predict changes in overall survival (OS) in adjuvant breast cancer trials.

Methods: Individual patient level data from adjuvant phase III RCTs conducted by the Gruppo Italiano Mammella (GIM) and Mammella Intergruppo (MIG) study groups were used.

Sacituzumab Govitecan for the treatment of advanced triple negative breast cancer patients: a multi-center real-world analysis.

Objective: The objective of this multicenter, observational, retrospective analysis was to evaluate the safety and efficacy of sacituzumab govitecan in metastatic triple-negative breast cancer (mTNBC) patients managed according to common clinical practice in Italy.

Methods: Data were retrieved by 7 sites. Triple-negative BC was defined by the lack of expression of estrogen receptor (ER <1%), progesterone receptor (PgR <1%) and human-epidermal growth factor receptor-2 (HER2 0, 1+, 2+ ISH-not amplified) according to standard ASCO-CAP criteria.

Central obesity, body mass index, metabolic syndrome and mortality in Mediterranean breast cancer patients.

Obesity and metabolic disorders have been associated with poor outcomes in non-Mediterranean breast cancer (BC) patients. The purpose of this study was to investigate the prognostic potential of anthropometric variables in patients with early BC living in Southern Mediterranean region of Italy. We enrolled 955 consecutive early BC patients treated in hospitals in Naples between 2009 and 2013 (median follow-up 11.

Neratinib as adjuvant therapy in patients with HER2 positive breast cancer: expert opinion.

Neratinib is a tyrosine kinase receptor inhibitor used in the extended adjuvant therapy of early-stage breast cancer. After adjuvant trastuzumab therapy, neratinib reduces the risk of recurrence and, if taken within 1 year from trastuzumab, significantly improves the invasive disease-free survival of patients with early-stage human epidermal growth factor receptor-2 positive (HER2+) breast cancer with no increased risk of long-term toxicity. Diarrhea, the most common adverse event associated with neratinib use, deters some clinicians from prescribing this drug.

Long-term complete response with third-line PARP inhibitor after immunotherapy in a patient with triple-negative breast cancer: a case report.

While standard treatment has shown efficacy in patients with breast cancer gene () mutations, recurrence rates are high and additional effective therapies are needed. Olaparib, a poly adenosine diphosphate-ribose polymerase (PARP) inhibitor, approved for the treatment of metastatic germline / breast cancer (BC), has demonstrated evidence of a progression-free survival (PFS) benefit, good safety profile, and improved quality of life compared with standard chemotherapy. We here describe the case of a patient with mutated advanced BC and a long history of response to chemotherapy and immunotherapy who received systemic treatment with olaparib.

Toxicity profile of antibody-drug conjugates in breast cancer: practical considerations.

Antibody-drug conjugates (ADCs) represent a novel and evolving class of antineoplastic agents, constituted by monoclonal antibody linked to biologically active drugs, delivering cytotoxic compounds at the tumor site, reducing the likelihood of systemic exposure and toxicity. They are generally well tolerated, nevertheless some predictable adverse reactions need careful monitoring and timely approach. These include neutropenia, nausea and vomiting, alopecia, diarrhea, left ventricular dysfunction, ILD/pneumonitis.

Prognostic and clinical impact of the endocrine resistance/sensitivity classification according to international consensus guidelines for advanced breast cancer: an individual patient-level analysis from the Mammella InterGruppo (MIG) and Gruppo Italiano Mammella (GIM) studies.

Background: Prior exposure to adjuvant endocrine therapy (ET) and timing to recurrence are crucial factors for first-line treatment choices in patients with hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer (BC) and in clinical trial eligibility, classifying metastatic HR+/HER2- BC as endocrine sensitive (ES) or primary (1ER)/secondary (2ER) resistant. However, this classification is largely based on expert opinion and no proper evidence exists to date to support its possible prognostic and clinical impact.

Methods: This analysis included individual patient-level data from 4 adjuvant phase III randomized trials by the Mammella InterGruppo (MIG) and Gruppo Italiano Mammella (GIM) study groups.

Serum thymidine kinase activity in patients with HR-positive/HER2-negative advanced breast cancer treated with ribociclib plus letrozole: Results from the prospective BioItaLEE trial.

Background: Thymidine kinase 1 (TK1) is an enzyme downstream of the CDK4/6 pathway, with a critical role in DNA synthesis; serum TK1 activity (sTKa) is a novel liquid biopsy biomarker of tumour cell proliferation.

Methods: The phase IIIb, BioItaLEE trial (NCT03439046) collected sera from postmenopausal patients with hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer (ABC) treated with first-line ribociclib plus letrozole at baseline, day 15 of cycle 1 (C1D15), day 1 of cycle 2 (C2D1), and at first imaging. Associations between sTKa assessed at different time points or sTKa dynamic patterns, and progression-free survival (PFS) were evaluated using multivariate Cox models.

Ribociclib Plus Letrozole in Italian Male Patients with Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Case Studies of Phase 3b CompLEEment-1 Trial.

Abstract: Male breast cancer (BC) is rare, globally constituting only 0.5-1% of all patients with BC. In Italy, more than 2000 new male BC cases were registered between 2000 and 2014.

Safety and Efficacy of Ribociclib in Combination with Letrozole in Patients with HR+, HER2- Advanced Breast Cancer: Results from the Italian Subpopulation of Phase 3b CompLEEment-1 Study.

Background: Ribociclib plus letrozole demonstrated manageable safety and efficacy profiles in hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) advanced breast cancer (ABC) in the Phase 3b CompLEEment-1 trial.

Objective: To evaluate the safety and efficacy of ribociclib plus letrozole in the Italian subpopulation with HR+, HER2- ABC from the CompLEEment-1 trial.

Patients And Methods: Patients with HR+, HER2- ABC received ribociclib (600 mg/day, 3 weeks on/1 week off) plus letrozole (2.

Inhibition of autophagy by chloroquine prevents resistance to PI3K/AKT inhibitors and potentiates their antitumor effect in combination with paclitaxel in triple negative breast cancer models.

Background: Triple negative breast cancer (TNBC) is an aggressive disease characterized by high risk of relapse and development of resistance to different chemotherapy agents. Several targeted therapies have been investigated in TNBC with modest results in clinical trials. Among these, PI3K/AKT inhibitors have been evaluated in addition to standard therapies, yielding conflicting results and making attempts on elucidating inherent mechanisms of resistance of great interest.

Targeting Autophagy in Breast Cancer.

Breast cancer is a heterogeneous disease consisting of different biological subtypes, with differences in terms of incidence, response to diverse treatments, risk of disease progression, and sites of metastases. In the last years, several molecular targets have emerged and new drugs, targeting PI3K/Akt/mTOR and cyclinD/CDK/pRb pathways and tumor microenvironment have been integrated into clinical practice. However, it is clear now that breast cancer is able to develop resistance to these drugs and the identification of the underlying molecular mechanisms is paramount to drive further drug development.