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Background: Patients with hormone receptor-positive (HR+)/HER2- metastatic breast cancer (mBC) generally receive hormonal therapy (HT) combined with CDK4/6 inhibitors (CDK4/6i). Despite this treatment, resistance mechanisms to CDK4/6i emerge and the majority of these patients experience disease progression (PD). This highlight the necessity to uncover the resistance mechanism to CDK4/6i through the identification of specific biomarkers. The primary objective is to assess the accuracy and feasibility of a novel multi-gene target panel NGS assay on circulating tumor DNA (ctDNA) to detect molecular alterations of AKT1, ERBB2, ESR1, KRAS, PIK3CA, and TP53 genes in women with BC undergoing HT plus CDK4/6i treatment. Secondarily, the study aims to explore the relationship between genomic profiling and clinical outcomes. Materials and Methods: Plasma samples were collected from 16 patients diagnosed with advanced/locally advanced HR+/HER2- BC at 2 time points: T0 (baseline) and at T1 (3 months after CDK4/6i treatment). Starting from 2 mL of plasma, ctDNA was isolated and libraries were set up using the Plasma-SeqSensei (PQS)® Breast Cancer IVD Kit, sequenced on Nextseq 550 and analyzed using the Plasma-SeqSensei™ IVD Software®. Results: Among the five patients who presented PD, three had PIK3CA mutations and, of these, two showed a higher mutant allele frequency (MAF) at T1. In three patients with stable disease and in eight patients with partial response, the MAF of the detected alterations decreased dramatically or disappeared during CDK4/6i treatment. Conclusions: Based on our findings, the liquid biopsy analysis using the PQS panel seems to be both feasible and accurate, demonstrating a strong sensitivity in detecting mutations. This exploratory analysis of the clinical outcome associated to the mutational status of patients highlights the potential of molecular analysis on liquid biopsy for disease monitoring, although further validation with a larger patient cohort is necessary to confirm these preliminary observations. [ABSTRACT FROM AUTHOR]

Simple Summary: Advancements in molecular technologies have extended the potential role of circulating biomarkers in diagnosis, disease monitoring, and outcome prediction. Research is working towards personalized treatment in early breast cancer patients, and tools for intensification/de-intensification strategies are needed to guide clinicians' choices. In this review, we explore the current developments of promising biomarkers in early breast cancer for cancer detection and tailoring neoadjuvant therapies. The research on non-invasive circulating biomarkers to guide clinical decision is in wide expansion, including the earliest disease settings. Several new intensification/de-intensification strategies are approaching clinical practice, personalizing the treatment for each patient. Moreover, liquid biopsy is revealing its potential with multiple techniques and studies available on circulating biomarkers in the preoperative phase. Inflammatory circulating cells, circulating tumor cells (CTCs), cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), and other biological biomarkers are improving the armamentarium for treatment selection. Defining the escalation and de-escalation of treatments is a mainstay of personalized medicine in early breast cancer. In this review, we delineate the studies investigating the possible application of these non-invasive tools to give a more enlightened approach to escalating/de-escalating strategies in early breast cancer. [ABSTRACT FROM AUTHOR]

Objective: The coronavirus disease 2019 (COVID‐19) outbreak has been declared a global pandemic of unprecedented proportions. Italy is a country which has been heavily affected. Cancer patients are at a higher risk owing to their intrinsic fragility related to their underlying disease and oncologic treatment. Against this backdrop, we conducted a survey to investigate how patients perceived their condition, clinical management and availability of information during the pandemic. Methods: Between 15 April and 1 May 2020 a survey was submitted to cancer patients at oncology departments in the Marche region. Questions regarding the perception of personal safety, continuity of cancer care, information quality and psychological distress. Results: Seven hundred patients participated in the survey; 59% were female and 40% were aged between 46 and 65. The majority of the participants perceived compliance with appropriate safety standards by cancer care providers and 80% were reassured about their concerns during the medical interview. 40% were worried of being at a higher risk of infection and 71% felt they were at a greater risk because of chemotherapy. 55% felt that postponing cancer treatment could reduce its efficacy, however 76% declared they did not feel abandoned at the time of treatment postponement. Patients between 46 and 65 years declared a significant reduction in sleep (p < 0.01) and in concentration (p = 0.03). Conclusions: The emergency care offered to cancer patients has been deemed satisfactory in terms of both safety standards and care management. However, the majority of participants perceived the mutual negative influence between their oncologic disease and the risk of infection highlighting the need for special measures to ensure safe continuity of care. [ABSTRACT FROM AUTHOR]

Since the introduction of targeted therapies, prognosis in human epidermal growth factor receptor (HER) 2-positive metastatic breast cancer (MBC) has radically changed. The addition of Pertuzumab to Trastuzumab and standard chemotherapy has further increased patients' overall survival (OS). However, there is no agreement regarding the optimal duration of trastuzumab therapy in selected patients achieving long-term complete remission. In addition, no potential factors of long-term benefit have been identified yet. In the present study, we report the case of a MBC woman who was successfully treated with trastuzumab for over 10 years. At the time of diagnosis (February 2005), she revealed lung, nodal and bone metastases. Therefore, a first-line chemotherapy with Epirubicine and Docetaxel was administered for 6 cycles and then the patient started Trastuzumab plus hormonal therapy until reaching a sensible reduction of mammary lump and disappearance of distant metastases. Following a multidisciplinary evaluation, in November 2006, the patient underwent radical mastectomy and axillary dissection, achieving a complete remission. She continued Trastuzumab until September 2015 (for a total of 156 cycles) when a pleural diffusion was demonstrated. Long-term survival during anti-HER2 treatment remains a rare and optimal situation. Currently, no data exist to support trastuzumab interruption in this setting and collaborative efforts to better analyze the characteristics of long-responder patients are needed. Data regarding prognostic factors in this setting are relatively confusing. Our review reveals that hormonal receptor (HR)-positive disease is associated with a better prognosis, whereas the role of visceral spread differs by single or dual target anti HER2-inhibition. The introduction of Pertuzumab is raising concerns in terms of toxicity and its cost effectiveness. While waiting for novel molecular data and randomized trials, available evidence advocates continuous use of anti-HER2 therapies until disease progression or development of side effects. [ABSTRACT FROM AUTHOR]