Positioning oral selective estrogen receptor degraders in patients with metastatic breast cancer.

Approximately 40 % of patients with estrogen receptor (ER)-positive, HER2-negative metastatic breast cancer (mBC) who receive first-line treatment with CDK4/6 inhibitors (CDK4/6i) and aromatase inhibitors (AIs) develop acquired ESR1 mutations, leading to ligand-independent ER activation and resistance to AIs. Fulvestrant, the first selective estrogen receptor degrader (SERD) approved for clinical use, was developed to address this resistance and has remained the standard second-line endocrine therapy. However, its clinical use is limited by intramuscular administration and low bioavailability.

Circulating tumor DNA: a biomarker for oncology drug development in phase I clinical trials?

Introduction: Circulating tumor DNA (ctDNA) is a noninvasive and promising biomarker for cancer diagnosis, prognosis, and therapeutic monitoring, offering significant potential for real-time insights into tumor dynamics when compared to traditional tissue-based biopsies. Phase I oncology clinical trials, which primarily focus on assessing the safety, pharmacodynamics, and early activity of novel cancer therapies, might find in the unique biological characteristics of ctDNA, a valuable biomarker to boost the efficiency of testing novel agents.

Areas Covered: This review explores the utility of ctDNA as a biomarker in phase I trials, discussing its biological and technical features, clinical relevance, current limitations, and future potential in advancing early clinical drug development.

The evolving landscape of hormone receptor-positive/HER2-negative metastatic breast cancer (EVOLVE): An Italian Delphi consensus report.

Background: The expanding treatment landscape for patients with hormone receptor-positive, HER2-negative (HR+/HER2-) metastatic breast cancer (mBC) has led to the emergence of new "grey areas" not covered by international guidelines, where treatment decision making is particularly challenging.

Methods: Sixteen relevant statements regarding the management of HR+ /HER2- mBC were formulated by an Executive Board and validated by a Scientific Board, composed by internationally recognized experts in the field of BC. Subsequently, 50 Italian oncologists were surveyed between May 2024 and June 2024 through the modified Delphi method, in order to capture their rate of agreement and disagreement on the proposed statements.

Bispecific Antibodies in Hematologic and Solid Tumors: Current Landscape and Therapeutic Advances.

Bispecific antibodies (bsAbs) have emerged as a novel class of therapeutics, offering a dual-targeting strategy to enhance the therapeutic efficacy of monoclonal antibodies, which is often limited by tumor heterogeneity and the occurrence of resistance mechanisms. By simultaneously engaging two distinct antigens or pathways, bsAbs disrupt multiple signaling cascades simultaneously, preventing escape mechanisms and offering a more durable response. Furthermore, they can optimize immune activation, improving immune cell recruitment strategies.

From Dose-Finding to Dose-Optimization in Early-Phase oncology clinical trials.

Dose optimization in Phase I oncology trials balances therapeutic efficacy and patient safety. Traditional dose-escalation methods, such as the 3 + 3 design, primarily focus on safety, often resulting in prolonged exposure to subtherapeutic or excessively toxic doses. Additionally, these methods may fail to account for modern therapies' complex pharmacokinetics and pharmacodynamics, including targeted agents and immunotherapies.

Rechallenge with platinum-based chemotherapy in patients with platinum-resistant ovarian carcinoma: A cohort study.

Background: According to the 2018 ESMO-ESGO consensus conference recommendations on ovarian cancer, platinum rechallenge could be considered in patients with platinum-resistant disease following a treatment with a non‑platinum regimen, if they had not progressed during prior platinum therapy. However, few data are available in this specific setting, especially after the incorporation of novel agents in the current treatment algorithm for ovarian cancer.

Methods: We conducted a single-center, retrospective, cohort study to evaluate the activity of platinum rechallenge in patients with high-grade ovarian cancer, progressing on at least one non‑platinum regimen for platinum-resistant disease, from January 2010 to June 2024, at the European Institute of Oncology (Italy).

The pathologic and genomic evolution of primary malignant phyllodes tumors of the breast: retrospective cohort study and case-control genomic analysis.

Background: In patients with phyllodes tumors of the breast, the presence of mediator of RNA polymerase II transcription subunit 12 homolog mutations (MED12m) and a history of previous fibroadenoma may predict better outcomes. To aid in the prognostication of malignant phyllodes tumors of the breast (B-MPT), we assessed the prognostic value of fibroadenoma-like areas (supposed to have stemmed from a pre-existing fibroadenoma) and MED12m, in patients with resected primary B-MPTs.

Methods: We conducted a single-center, retrospective, cohort study including all consecutive patients aged ≥18 years old, with non-metastatic B-MPT, who underwent surgery from January 2000 to December 2021.

Role of Social Media for Medical Oncologists and Medical Oncology Fellows (SMARTY): An Italian Cross-Sectional Study.

Purpose: The use of social media is transforming physician-patient communication, mainly in the field of medical oncology. The pattern of social media use by medical oncologists is poorly studied. Therefore, we developed a survey to understand the preferences, experiences, opinions, and expectations of Italian medical oncologists and oncology fellows regarding the use of social media in cancer medicine to identify the different profiles of social media users.

Awareness, Knowledge, and Treatment Patterns of Nonmetastatic Inflammatory Breast Cancer in Low- and Middle-Income Countries: The BRIDGES Study.

Purpose: Trimodal therapy (TMT) is the standard treatment for patients with nonmetastatic inflammatory breast cancer (IBC). TMT consists of neoadjuvant systemic therapy, modified radical mastectomy (MRM), and postmastectomy radiation therapy. Although broadly considered the best approach for IBC, in the United States, only a third of patients receive TMT.

Metastasis-directed stereotactic radiotherapy and systemic treatment continuation for patients with oligoprogressive metastatic breast cancer.

Background: About 15-20 % of patients with metastatic breast cancer (mBC) can experience oligoprogressive disease (OPD) in ≤ 5 sites of disease. Patients with OPD may benefit from metastasis-directed stereotactic radiotherapy (SBRT) to all sites of cancer progression while maintaining the same systemic treatment, aiming to prolong the time to next systemic treatment (NEST). This study aims to assess the outcomes provided by this multimodal strategy.

Germline BRCA pathogenic variants and hematologic adverse events in patients with ovarian carcinoma receiving PARP inhibitors: a retrospective cohort study.

Background: Patients with a germline BRCA pathogenic variant (gBRCA-PV) and advanced high grade ovarian carcinoma (aHGOC) experience higher hematologic adverse events (HAEs) when receiving platinum salts and ionizing radiations, compared to non-carriers, due to a possible higher susceptibility of the hemopoietic stem cells to DNA targeting agents. However, the incidence of PARP inhibitor (PARPi)-related HAEs according to the gBRCA-PV status is currently unknown.

Patients And Methods: We conducted a single-center retrospective cohort study to describe the occurrence of HAEs in patients with aHGOC receiving ≥8 weeks of maintenance PARPi in any line of therapy, comparing gBRCA-PVs carriers to non-carriers.

PARP inhibitor resistant BRCA-mutated advanced breast cancer: current landscape and emerging treatments.

Purpose Of Review: Patients with advanced breast cancer (aBC) treated with PARP inhibitors (PARPi) can eventually experience disease progression for emerging treatment resistance. This review aims to depict the treatment the molecular landscape, and the innovative therapies for patients with PARPi-resistant BRCA-mutated aBC.

Recent Findings: No specific therapy is specifically available in the setting post-PARPi-failure, with antibody-drug conjugates or nonplatinum-based chemotherapy (PBC) representing the best treatment options in this setting.

Circulating tumor DNA in patients with locally advanced rectal cancer treated with multimodal treatment.

Background: The management of locally advanced rectal cancer (LARC) relies on a multimodal approach. Neither instrumental work-up nor molecular biomarkers are currently available to identify a risk-adapted strategy.

Objectives: We aim to investigate the role of circulating tumor DNA (ctDNA) and its clearance at different timepoints during chemo-radiotherapy (CRT) and correlate them with clinical outcomes.

The evolving landscape of metastatic HER2-positive, hormone receptor-positive Breast Cancer.

Therapeutic agents targeting Human Epidermal Growth Factor Receptor 2 (HER2) demonstrated to positively impact the prognosis of HER2-positive breast cancer. HER2-positive breast cancer can present either as hormone receptor-negative or positive, defining Triple-positive breast cancer (TPBC). TPBC demonstrate unique gene expression profiles, showing reduced HER2-driven gene expression, as recapitulated by a higher proportion of Luminal-type intrinsic subtypes.

Optimizing Postneoadjuvant Treatment in Patients With Early Breast Cancer Achieving Pathologic Complete Response.

pCR should be integrated with other prognostic factors to optimize postneoadjuvant treatments in BC.

Biomarkers for Antibody-Drug Conjugates in Solid Tumors.

The clinical development and then the progressive entry in clinical practice of antibody-drug conjugates (ADC) have marked a transformative advancement in the overall cancer treatment. ADCs have been extensively tested for a large number of tumors, reporting heterogeneous clinical efficacy and safety results. In some diseases, the advent of ADCs has yielded significant changes in the prognostic trajectory, portending an improvement of the survival and/or quality of life.

New Concepts in Cardio-Oncology.

Cancer and cardiovascular disease are the two major causes of morbidity and mortality in worldwide. Discovering new therapeutic agents for the management of breast cancer (BC) has increased the numbers of cancer survivors but with the risk of cardiovascular adverse events (CV-AEs). All drugs can potentially damage the cardiovascular system, with different types of clinical manifestations from ischemic myocardial disease to vasculitis, thrombosis or pericarditis.

Targeting HER2 heterogeneity in breast and gastrointestinal cancers.

About 20% of breast and gastric cancers and 3% of colorectal carcinomas overexpress the human epidermal growth factor receptor 2 (HER2) and are sensitive to HER2-directed agents. The expression of HER2 may differ within the same tumoral lesion (spatial intralesional heterogeneity), from different tumor locations (spatial interlesional heterogeneity), and throughout treatments (temporal heterogeneity). Spatial and temporal heterogeneity may impact on response and resistance to HER2-targeting agents and its prevalence and predictive role changes across HER2-overexpressing solid tumors.

Primary malignant phyllodes tumors of the breast: A retrospective analysis from a referral center.

Background: The treatment for primary malignant phyllodes tumors of the breast (B-MPT) consists of wide local excision with negative margins (≥1 cm). However, because of their rarity, prognostic factors, type of surgery and adjuvant treatments are still a matter of debate.

Methods: We conducted a single-center retrospective study to describe outcomes and prognostic factors of patients with primary B-MPT, who underwent breast surgery from January 2000 to December 2021.

Treatment optimization in early triple negative breast cancer.

Introduction: The treatment of early-stage triple-negative breast cancer (TNBC) has radically changed in recent years. Response to neoadjuvant treatment has provided prognostic information, and the achievement of a pathological complete response (pCR) is associated with improved prognosis. An exact treatment algorithm that embraces the trade-off of efficacy and toxicity in a risk-adapted manner has, however, not been consolidated.