Completion Rate and Positive Results Reporting Among Immunotherapy Trials in Breast Cancer, 2004-2023.

Importance: Clinical trials are the path to test and introduce new therapies in the clinic. Trials that are unable to produce results represent inefficiency in the system and may also undermine patient confidence in the new drug development process.

Objectives: To survey the immunotherapy clinical trial landscape of breast cancer between January 2004 and April 2023 and examine what fraction of trials with primary completion date up to November 30, 2022, failed to report outcome, assessing the proportion of trials that yielded positive results and describing trial features associated with these 2 outcomes.

Navigating practical challenges in immunotherapy for metastatic triple negative breast cancer.

Immunotherapy has revolutionized cancer therapy and now represents a standard of care for many tumor types, including triple-negative breast cancer. Despite the positive results that have led to the approval of immunotherapy in both early- and advanced-stage triple-negative breast cancer, pivotal clinical trials cannot address the myriad questions arising in everyday clinical practice, often falling short in delivering all the information that clinicians require. In this manuscript, we aim to address some of these practical questions, with the purpose of providing clinicians with a guide for optimizing the use of immune checkpoint inhibitors in the management of breast cancer patients and identifying opportunities for future research to clarify unresolved questions.

Management of Trastuzumab Deruxtecan-related nausea and vomiting in real-world practice.

Background: Nausea and vomiting are common side effects of Trastuzumab Deruxtecan (T-DXd), but guidelines for optimal management were not initially available. This retrospective single-center study aimed at evaluating the efficacy of two antiemetic regimens in patients receiving T-DXd.

Methods: Data from metastatic breast cancer patients receiving T-DXd were collected.

PARP Inhibitors for Breast Cancer Treatment: A Review.

Importance: Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors have revolutionized the treatment of patients with germline BRCA1/2-associated breast cancer, representing the first targeted therapy capable of improving outcomes in patients with hereditary tumors. However, resistance to PARP inhibitors occurs in almost all patients.

Observations: This narrative review summarizes the biological rationale behind the use of PARP inhibitors in breast cancer, as well as the available evidence, recent progress, and potential future applications of these agents.

Real-world use of multigene signatures in early breast cancer: differences to clinical trials.

Purpose: In Italy, Lombardy was the first region to reimburse multigene assays (MGAs) for patients otherwise candidates for chemotherapy. This is a real-world experience of MGAs usage in six referral cancer centers in Lombardy.

Methods: Among MGAs, Oncotype DX (RS) was used in 97% of cases.

Breast cancers with high proliferation and low ER-related signalling have poor prognosis and unique molecular features with implications for therapy.

Background: Luminal breast cancers with high proliferation (MKS) and low ER-related signalling (ERS) have a poor prognosis. We investigated treatment responses and molecular features of MKS/ERS tumours to inform potential therapies.

Methods: Gene expression data from patients who received neoadjuvant chemotherapy (NAC) without (MDACC, N = 199) or with pembrolizumab (I-SPY2, N = 40), or endocrine therapy (NET) without (POETIC, N = 172) or with palbociclib (NeoPalAna, N = 32) were analyzed to assess treatment response by MKS/ERS-subgroups.

Pan-cancer analysis of antibody-drug conjugate targets and putative predictors of treatment response.

Background: Antibody-drug conjugates (ADCs) are a rapidly expanding class of compounds in oncology. Our goal was to assess the expression of ADC targets and potential downstream determining factors of activity across pan-cancer and normal tissues.

Materials And Methods: ADCs in clinical trials (n = 121) were identified through ClinicalTrials.

Oncotype DX results increase concordance in adjuvant chemotherapy recommendations for early-stage breast cancer.

Adjuvant chemotherapy recommendations for ER+/HER2- early-stage breast cancers (eBC) involve integrating prognostic and predictive information which rely on physician judgment; this can lead to discordant recommendations. In this study we aim to evaluate whether Oncotype DX improves confidence and agreement among oncologists in adjuvant chemotherapy recommendations. We randomly select 30 patients with ER+/HER2- eBC and recurrence score (RS) available from an institutional database.

Tissue- and liquid biopsy-based biomarkers for immunotherapy in breast cancer.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy and now represent the mainstay of treatment for many tumor types, including triple-negative breast cancer and two agnostic registrations. However, despite impressive durable responses suggestive of an even curative potential in some cases, most patients receiving ICIs do not derive a substantial benefit, highlighting the need for more precise patient selection and stratification. The identification of predictive biomarkers of response to ICIs may play a pivotal role in optimizing the therapeutic use of such compounds.

Multigene signatures for early breast cancer in clinical practice: A report of the Lombardy genomic assays for breast cancer working group.

The increasing understanding of breast cancer biology has provided the basis for the development of multigene signatures aimed to improve the capability of clinicians to assess patients' prognostication and risk stratification. Incorporating these tools in clinical practice has profoundly impacted on the decision-making process for the adjuvant therapy of patients with ER+/HER2- early breast cancer and the results from prospective adjuvant trials have strengthened the clinical utility of multigene signatures in this setting. In July 2019, Lombardy was the first Region in Italy to reimburse genomic testing for patients with ER+/HER2- early breast cancer.

Treatment landscape of triple-negative breast cancer - expanded options, evolving needs.

Tumour heterogeneity and a long-standing paucity of effective therapies other than chemotherapy have contributed to triple-negative breast cancer (TNBC) being the subtype with the least favourable outcomes. In the past few years, advances in omics technologies have shed light on the relevance of the TNBC microenvironment heterogeneity, unveiling a close dynamic relationship with cancer cell features. An improved understanding of tumour-immune system co-evolution supports the need to adopt a more comprehensive view of TNBC as an ecosystem that encompasses the intrinsic and extrinsic features of cancer cells.

Personalized Risk-Benefit Ratio Adaptation of Breast Cancer Care at the Epicenter of COVID-19 Outbreak.

Northern Italy has been one of the European regions reporting the highest number of COVID-19 cases and deaths. The pandemic spread has challenged the National Health System, requiring reallocation of most of the available health care resources to treat COVID-19-positive patients, generating a competition with other health care needs, including cancer. Patients with cancer are at higher risk of developing critical illness after COVID-19 infection.

Patterns of treatment and outcome with 500-mg fulvestrant in postmenopausal women with hormone receptor-positive/HER2-negative metastatic breast cancer: a real-life multicenter Italian experience.

Background: Fulvestrant 500 mg (F500) is the most active endocrine single agent in hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer (MBC). Few data are available regarding the effectiveness of the drug in a real-world setting.

Patients And Methods: This prospective, multicenter cohort study aimed to describe the patterns of treatment and performance of F500 in a large population of unselected women with MBC, focusing on potential prognostic or predictive factors for disease outcome and response.

Vinflunine in Advanced Transitional Cell Cancer of the Urothelial Tract: A Potential Option for Maintenance Therapy? A Case Series.

Introduction: Vinflunine is a microtubule inhibitor approved in Europe as second-line treatment of advanced transitional cell cancer of the urothelium (TCCU). The inability to continue with a first-line platinum-based regimen beyond 6 cycles suggested investigating the use of vinflunine as switch maintenance therapy in patients with response or stable disease after first-line therapy.

Methods: Patients with advanced TCCU and documented disease control after 3-6 cycles of first-line platinum-based chemotherapy received vinflunine maintenance therapy within 6 weeks of the last cycle.