Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i): Mechanisms of resistance and where to find them.

CDK4/6 inhibitors (CDK4/6i) have significantly impacted on the treatment of HR + HER2 negative (HER2-) metastatic breast cancer (BC) when combined with endocrine therapy. Nonetheless, despite significant research efforts, the mechanisms of de novo and acquired resistance to CDK4/6i have not yet been fully elucidated, highlighting the need for a deeper understanding of these process. Additionally, the importance of dissecting CDK4/6i resistance from endocrine resistance for personalized treatment is increasingly recognized.

Radiomic features of primary retroperitoneal sarcomas: a prognostic study.

Background: Risk-stratification of patients with retroperitoneal sarcomas (RPS) relies on validated nomograms, such as Sarculator. This retrospective study investigated whether radiomic features extracted from computed tomography (CT) imaging could i) enhance the performance of Sarculator and ii) identify G3 dedifferentiated liposarcoma (DDLPS) or leiomyosarcoma (LMS), which are currently consider in a randomized clinical trial testing neoadjuvant chemotherapy.

Methods: Patients with primary localized RPS treated with curative-intent surgery (2011-2015) and available pre-operative CT imaging were included.

Unsupervised clustering analysis-based characterization of spatial profiles of inaccuracy in apparent diffusion coefficient values with varying acquisition plan orientation and diffusion weighting gradient direction - a large multicenter phantom study.

This large multicenter study of 37 magnetic resonance imaging scanners aimed at characterizing, for the first time, spatial profiles of inaccuracy (namely, Δ-profiles) in apparent diffusion coefficient (ADC) values with varying acquisition plan orientation and diffusion weighting gradient direction, using a statistical approach exploiting unsupervised clustering analysis. A diffusion-weighted imaging (DWI) protocol (b-value: 0-200-400-600-800-1000 s mm) with different combinations of acquisition plan orientation (axial/sagittal/coronal) and diffusion weighting gradient direction (anterior-posterior/left-right/feet-head) was acquired on a standard water phantom. For each acquisition setup, Δ-profiles along the 3 main orthogonal directions were characterized by fitting data with a second order polynomial function ().

Prospective study on Oncotype DX® assay to assess recurrence risk in early ER-positive HER2-negative breast cancer patients with uncertain biological behavior by standard parameters and its impact on treatment recommendation: The POST trial.

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.

Proximal and Classic Epithelioid Sarcomas are Distinct Molecular Entities Defined by MYC/GATA3 and SOX17/Endothelial Markers, Respectively.

Epithelioid sarcoma (ES) is a rare tumor hallmarked by the loss of INI1/SMARCB1 expression. Apart from this alteration, little is known about the biology of ES. Despite recent advances in treatment, the prognosis of ES remains unsatisfactory.

Second Primary Cancer Risks After Breast Cancer in and Pathogenic Variant Carriers.

Purpose: Second primary cancer (SPC) risks after breast cancer (BC) in pathogenic variant (PV) carriers are uncertain. We estimated relative and absolute risks using a novel linkage of genetic testing data to population-scale National Disease Registration Service and Hospital Episode Statistics electronic health records.

Methods: We followed 25,811 females and 480 males diagnosed with BC and tested for germline PVs in NHS Clinical Genetics centers in England between 1995 and 2019 until SPC diagnosis, death, migration, contralateral breast/ovarian surgery plus 1 year, or the 31st of December 2020.

International Multicenter Retrospective Study From the Ultra-rare Sarcoma Working Group on Low-grade Fibromyxoid Sarcoma, Sclerosing Epithelioid Fibrosarcoma, and Hybrid Forms: Outcome of Primary Localized Disease.

The aim of the study was to report the outcome of primary localized low-grade fibromyxoid sarcoma (LGFMS), sclerosing epithelioid fibrosarcoma (SEF), and hybrid LGFMS/SEF (H-LGFMS/SEF). Patients with primary localized LGFMS, SEF, or H-LGFMS/SEF, surgically treated with curative intent from January 2000 to September 2022, were enrolled from 14 countries and 27 institutions. Pathologic inclusion criteria were predefined by expert pathologists.

Follow-up of early breast cancer in a public health system: A 2024 AIGOM consensus project.

Breast cancer stands as the most frequently diagnosed cancer and the primary cause of cancer-related mortality among women worldwide, including Italy. With the increasing number of survivors, many are enrolled in regular follow-up programs. However, adherence to recommendations from scientific societies (such as ASCO, ESMO, AIOM) for breast cancer follow-up management varies in daily clinical practice across different cancer centers, potentially resulting in unequal management and escalating costs.

Adequate assessment yields appropriate care-the role of geriatric assessment and management in older adults with cancer: a position paper from the ESMO/SIOG Cancer in the Elderly Working Group.

With the aging population, older adults constitute a growing proportion of the new cancer cases. Given the heterogeneous health status among older adults and their susceptibility to aging-related vulnerabilities, understanding their diversity and its implications becomes increasingly crucial for prognostication and guiding diagnostics, treatment decisions, and follow-up, as well as informing supportive care interventions. Geriatric assessment and management (GAM) refers to the comprehensive evaluation of an older individual's health status with subsequent management plans focusing on both oncologic and non-oncologic interventions.

TRAbectedin in adVanced rEtroperitoneal well differentiated/dedifferentiated Liposarcoma and Leiomyosarcoma (TRAVELL): results of a phase II study from the Italian Sarcoma Group.

Background: This is a multicentre, single-arm, phase II study aimed at further exploring the activity of trabectedin as second-/further-line treatment in retroperitoneal leiomyosarcoma (LMS) and well-differentiated/dedifferentiated liposarcoma (LPS).

Materials And Methods: The primary endpoint was the growth modulation index (GMI) defined as the ratio between PFS under trabectedin (PFS) and during previous chemotherapy treatment: time to progression (TTP-1). Secondary endpoints were objective response rate (ORR) and PFS.

Adjuvant endocrine therapy choices in premenopausal patients with hormone receptor-positive early breast cancer: Insights from the prospective GIM23-POSTER study.

Background: Most premenopausal patients with early breast cancer (eBC) are diagnosed with hormone receptor-positive disease and therefore candidate for adjuvant endocrine therapy (ET).

Patients And Methods: The Gruppo Italiano Mammella (GIM) 23-POSTER (GIM23) is a multicenter, prospective, observational study conducted in 26 Italian institutions, aiming to evaluate ET choices for premenopausal patients affected by hormone receptor-positive eBC in a real-world setting. Here we report also the results in terms of type of ET prescribed according to the definition of high-risk patients by monarchE and NATALEE trials.

6th and 7th International consensus guidelines for the management of advanced breast cancer (ABC guidelines 6 and 7).

This manuscript describes the Advanced Breast Cancer (ABC) international consensus guidelines updated at the last two ABC international consensus conferences (ABC 6 in 2021, virtual, and ABC 7 in 2023, in Lisbon, Portugal), organized by the ABC Global Alliance. It provides the main recommendations on how to best manage patients with advanced breast cancer (inoperable locally advanced or metastatic), of all breast cancer subtypes, as well as palliative and supportive care. These guidelines are based on available evidence or on expert opinion when a higher level of evidence is lacking.

First-Line Treatments and Management of Metastatic Renal Cell Carcinoma Patients: An Italian Interdisciplinary Uro-Oncologic Group Algorithm.

The treatment landscape for metastatic renal cell carcinoma (mRCC) has undergone significant transformations in recent years. The introduction of novel combination therapies involving tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors has resulted in improved oncological outcomes compared to traditional TKI monotherapy. In this evolving paradigm, the pivotal role of the multidisciplinary tumor board is underscored, particularly in shaping the therapeutic trajectory for patients eligible for locoregional interventions like cytoreductive nephrectomy and metastasectomy.

Clinical trials in older patients with cancer - typical challenges, possible solutions, and a paradigm of study design in breast cancer.

Background And Purpose: While the prevalence of older breast cancer patients is rapidly increasing, these patients are greatly underrepresented in clinical trials. We discuss barriers to recruitment of older patients to clinical trials and propose solutions on how to mitigate these challenges and design optimal clinical trials through the paradigm of IMPORTANT trial.

Patients And Methods: This is a narrative review of the current literature evaluating barriers to including older breast cancer patients in clinical trials and how mitigating strategies can be implemented in a pragmatic clinical trial.

Outcome improvement with chemotherapy and radiotherapy in primary, localized, radiation-associated angiosarcoma of the breast region: a retrospective case series analysis.

Background: We report on a series of consecutive patients with localized radiation-associated angiosarcoma (RAAS) of the breast region (BR) treated at two Italian sarcoma reference centers.

Materials And Methods: We retrospectively reviewed all cases of primary, localized, resectable RAAS of the BR, treated at one of the two participating institutions from 2000 to 2019. Relapse-free survival (RFS) and overall survival (OS) were calculated.

Front-Line Therapeutic Strategy in Metastatic Hormone Sensitive Prostate Cancer: An Updated Therapeutic Algorithm.

Prostate carcinoma (PC), the second most diagnosed cancer globally, saw approximately 1,414,000 new cases in 2020, with 17% being de novo metastatic. In these cases, the 5-year relative survival rate is 32%. Metastatic hormone-sensitive prostate cancer (mHSPC) includes those with metastatic disease at initial diagnosis or after initial therapy without long-term androgen deprivation therapy (ADT), eventually progressing to castration-resistant prostate cancer (CRPC).

The patient perspective on sirolimus for epithelioid hemangioendothelioma (EHE): results of a community survey highlighting the importance of equitable access to treatments.

Background: Epithelioid hemangioendothelioma (EHE) is an ultra-rare, vascular sarcoma with clinical presentation ranging from an indolent to an aggressive form. Over 50% of patients present with metastatic disease, requiring systemic therapy, although no systemic therapies are specifically approved for EHE. Retrospective evidence supports the activity of mTOR inhibitors (e.

Mutational Analysis of Circulating Tumor DNA in Patients With Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer Receiving Palbociclib: Results From the TREnd Trial.

Purpose: To identify prognostic circulating biomarkers to cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i), we performed a mutational analysis on circulating tumor DNA (ctDNA) samples from patients included in the TREnd trial, which randomly assigned patients to receive the CDK4/6i palbociclib alone or with the endocrine treatment (ET) to which they had progressed.

Methods: Forty-six patients were enrolled in this substudy. Plasma was collected before treatment (T0), after the first cycle of therapy (T1), and at the time of progression (T2).

Acetyl-CoA carboxylase 1 controls a lipid droplet-peroxisome axis and is a vulnerability of endocrine-resistant ER breast cancer.

Targeting aromatase deprives ER breast cancers of estrogens and is an effective therapeutic approach for these tumors. However, drug resistance is an unmet clinical need. Lipidomic analysis of long-term estrogen-deprived (LTED) ER breast cancer cells, a model of aromatase inhibitor resistance, revealed enhanced intracellular lipid storage.

Selective CDK7 Inhibition Suppresses Cell Cycle Progression and MYC Signaling While Enhancing Apoptosis in Therapy-resistant Estrogen Receptor-positive Breast Cancer.

Purpose: Resistance to endocrine therapy (ET) and CDK4/6 inhibitors (CDK4/6i) is a clinical challenge in estrogen receptor (ER)-positive (ER+) breast cancer. Cyclin-dependent kinase 7 (CDK7) is a candidate target in endocrine-resistant ER+ breast cancer models and selective CDK7 inhibitors (CDK7i) are in clinical development for the treatment of ER+ breast cancer. Nonetheless, the precise mechanisms responsible for the activity of CDK7i in ER+ breast cancer remain elusive.