Publications by authors named "Marzia Locatelli"

Background: Elderly patients are underrepresented in clinical trials, particularly in early-phase studies. Our study assessed the safety and efficacy of novel anti-cancer treatments investigated in early-phase clinical trials, comparing outcomes between younger and elderly patients.

Methods: This retrospective study analyzed data from patients enrolled in phase I/II trials at our center between January 2014 and April 2021.

View Article and Find Full Text PDF

Cyclin-Dependent Kinase 4/6 inhibitors (CDK4/6is) in combination with Endocrine Therapy (ET) represent the standard frontline therapy for patients with Hormone Receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic Breast Cancer (mBC). Clinical activity and efficacy of CDK4/6is-based therapies have been proven both in the endocrine sensitive and resistant settings. Therapy resistance eventually underpins clinical progression to any CDK4/6is-based therapies, yet there is a lack of validated molecular biomarkers predictive of either intrinsic or acquired resistance to CDK4/6is in clinical practice.

View Article and Find Full Text PDF

Background: Immune-related adverse events (IRAE) pose a significant diagnostic and therapeutic challenge in patients treated with immune-oncology (IO) drugs. IRAEs have been suggested to correlate with better outcome, but studies are conflicting. Estimating the true incidence of IRAEs is particularly difficult in the early phase I/II trial setting.

View Article and Find Full Text PDF

Background: Baseline tumor size (BTS) has been associated with outcomes in patients with cancer treated with immunotherapy. However, the prognostic impact of BTS on patients receiving targeted therapies (TTs) remains undetermined.

Methods: We reviewed data of patients with advanced solid tumors consecutively treated within early-phase clinical trials at our institution from 01/2014 to 04/2021.

View Article and Find Full Text PDF

Pivotal trials of COVID-19 vaccines did not include cancer patients, with questions remaining about their safety and efficacy in this population. Patients enrolled in early-phase clinical trials receive novel treatments with unknown efficacy and safety profiles. Studies on the safety of COVID-19 vaccines in these patients are urgently required.

View Article and Find Full Text PDF

Background: Baseline tumour burden is a prognostic factor for patients with melanoma and non-small-cell lung cancer treated with immunotherapy. However, no data are available on its role in other solid tumours, nor for treatment with next-generation immunoncology agents (NGIOs).

Methods: We reviewed data of patients with any solid tumour consecutively treated at our institution from August 2014 to March 2019, who received ≥1 dose of immune checkpoint inhibitor and/or NGIO within phase 1 trials.

View Article and Find Full Text PDF

Breast cancer (BC) remains the most frequently diagnosed cancer and the most common cause of cancer death among women of all races worldwide. Over 80% of BC cases are hormone receptor (HR)-positive, comprised of luminal A and luminal B per molecular subtypes, imposing an urgent need to fully understand the mechanisms behind progression. Ribociclib is a selective cycline-dependent kinase 4 and 6 inhibitor.

View Article and Find Full Text PDF

Purpose Of Review: Notch signaling is a highly evolutionarily conserved cell-to-cell communication system that is involved in a number of pivotal cellular processes, such as development, stem cell maintenance, cell fate specification, differentiation, proliferation, and death. Much progress has been made in understanding Notch signaling. This review will focus on the role of canonical Notch signaling pathway in breast cancer cause and progressing.

View Article and Find Full Text PDF

Triple-negative breast cancer (TNBC) represents a heterogeneous breast cancer subtype with a poor prognosis. The optimal adjuvant chemotherapy regimen is still unknown. Although numerous large randomized trials have established the benefit of adjuvant anthracyclines and/or taxanes in TNBC, there is no preferred regimen for these patients.

View Article and Find Full Text PDF

Breast cancer accounts for 29% of malignant tumors. It is an heterogenous disease covering a spectrum of different molecular subtypes. Epigenetic aberrations may affect gene expression through DNA and histone proteins modifications thus promoting tumor progression and resistance to anti- tumor treatment.

View Article and Find Full Text PDF
Article Synopsis
  • The study investigated PF-03084014, a selective gamma-secretase inhibitor, in combination with docetaxel for treating advanced triple-negative breast cancer, focusing on dosage and safety outcomes.* -
  • A total of 29 patients were treated, determining the maximum tolerated dose to be PF-03084014 100 mg twice daily with docetaxel 75 mg/m², which was generally well-tolerated with manageable side effects.* -
  • Results showed a 16% response rate with four patients achieving a confirmed partial response, while the median progression-free survival was 4.1 months, indicating limited efficacy but significant safety.*
View Article and Find Full Text PDF

Is breast cancer (BC) immunogenic? Many data suggest that it is. Many observations demonstrated the prognostic role of tumor-infiltrating lymphocytes (TILs) in triple negative (TN) and human epidermal growth factor receptor 2 (HER-2)-positive BC. TNBCs are poorly differentiated tumors with high genetic instability and very high heterogeneity.

View Article and Find Full Text PDF

In the era of personalized medicine detection of the molecular drivers of tumors and of specific DNA mutations predicting response or resistance to targeted agents has become routine practice in clinical oncology. The tumor biopsy depicts only a single timeframe from a single site, and might be inadequate to characterize a tumor because of intratumoral and intermetastatic heterogeneity. Circulating tumor DNA offers a "real time" tool for serially monitoring tumor genomes in a non-invasive manner providing accessible genetic biomarkers for cancer diagnosis, prognosis, and response to therapy.

View Article and Find Full Text PDF

Cancer cachexia is a multi-organ, multifactorial and often irreversible syndrome affecting many patients with cancer. Cancer cachexia is invariably associated with weight loss, mainly from loss of skeletal muscle and body fat, conditioning a reduced quality of life due to asthenia, anorexia, anaemia and fatigue. Treatment options for treating cancer cachexia are limited.

View Article and Find Full Text PDF

Background: The long-term prognostic relevance of immediate breast reconstruction (IBR) for patients with estrogen receptor (ER)-negative breast cancer (BC) has not been fully elucidated.

Patients And Methods: The study population included 444 patients with ER-negative BC who underwent total mastectomy with complete axillary dissection between 1995 and 2006, 339 patients with and 105 patients without IBR. The median follow-up was 8.

View Article and Find Full Text PDF

Objectives: To assess efficacy of bevacizumab in combination with oral chemotherapy in patients with breast cancer with lymphangitic spread to the chest wall (LBC). To identify surrogate biomarkers of response to bevacizumab.

Patients And Methods: We randomly assigned patients to receive bevacizumab plus either sequential or concurrent oral vinorelbine and capecitabine every 3 weeks.

View Article and Find Full Text PDF

Background/aim: In breast cancer (BC) patients, breast surgery followed by immediate breast reconstruction (IBR) might favour recurrences and metastases due to extensive surgical manipulation. We retrospectively investigated whether IBR after mastectomy and neoadjuvant chemotherapy (NT) influenced the outcome in patients with early and locally advanced oestrogen receptor (ER)-negative BC.

Patients And Methods: Between 1995 and 2006, 133 BC patients received NT followed by total mastectomy, 59 of whom underwent IBR.

View Article and Find Full Text PDF

Determination of hormone receptor (estrogen receptor and progesterone receptor) and human epidermal growth factor receptor 2 status in the primary tumor is clinically relevant to define breast cancer subtypes, clinical outcome,and the choice of therapy. Retrospective and prospective studies suggest that there is substantial discordance in receptor status between primary and recurrent breast cancer. Despite this evidence and current recommendations,the acquisition of tissue from metastatic deposits is not routine practice.

View Article and Find Full Text PDF

In anticancer drug development, there has been increasing consideration for the potential of a compound to cause adverse electrocardiographic changes, especially QT interval prolongation, which can be associated with risk of torsades de pointes and sudden death. Irrespective of overt clinical toxicities, QTc assessment can influence decision making during the conduct of clinical studies, including eligibility for protocol therapy, dose delivery or discontinuation, and analyses of optimal dose for subsequent development. Efforts are needed to refine strategies for risk management, avoiding unintended consequences that negatively affect patient access and clinical development of promising new cancer treatments.

View Article and Find Full Text PDF

Recent evidence suggests that the immune system is involved in the carcinogenesis process and the antitumor immune responses impact the clinical outcome, thus emphasizing the concept of cancer immune surveillance. In this context, dendritic cells (DCs) seem to play a crucial role, as they are the most potent antigen-presenting cells (APCs) and are able to stimulate naive T lymphocytes and to generate memory T lymphocytes. Immunotherapy with DC-based vaccines is a very attractive approach to treat cancer, offering the potential for high tumor-specific cytotoxicity.

View Article and Find Full Text PDF

Immunotherapy for the treatment of breast cancer can be categorized as either (a) specific stimulation of the immune system by active immunization, with cancer vaccines, or (b) passive immunization, such as tumor-specific antibodies (including immune modulators) or adoptive cell therapy that inhibit the function of, or directly kill, tumor cells. We will present the current information and the future perspectives of immunotherapy in patients with breast cancer, including the prognostic role of tumor infiltrating lymphocytes, immune signatures, targeted therapies modulating the immune system, and tumor antigen cancer vaccines. Active immunotherapy in breast cancer and its implementation into clinical trials have been largely a frustrating experience in the last decades.

View Article and Find Full Text PDF

Background: The indication of adjuvant chemotherapy for patients with highly proliferative estrogen receptor-positive breast cancer is controversial. We analyzed the predictive value of Ki67 for the efficacy of adjuvant chemotherapy in patients with estrogen receptor-positive, node-positive breast cancer.

Patients And Methods: We identified 1241 patients with Luminal B early stage breast cancer with 1-3 axillary positive nodes who underwent surgery between 1995 and 2005 at the European Institute of Oncology and received adjuvant hormonotherapy and/or chemotherapy.

View Article and Find Full Text PDF

We present a rare case of lung metastasis from a malignant adenomyoepithelioma of the breast. A 44-year-old woman was surgically treated in 2008 for a malignant adenomyoepithelioma of the breast. Shortly after, two lung nodules were detected through a CT scan, and a diagnosis of malignant adenomyoepithelioma was rendered.

View Article and Find Full Text PDF

Circulating cell-free DNA represents a non-invasive biomarker, as it can be isolated from human plasma, serum and other body fluids. Circulating tumor DNA shed from primary and metastatic cancers may allow the non-invasive analysis of the evolution of tumor genomes during treatment and disease progression through 'liquid biopsies'. The serial monitoring of tumor genotypes, which are instable and prone to changes under selection pressure, is becoming increasingly possible.

View Article and Find Full Text PDF

Introduction: Evading immune destruction is an emerging hallmark of cancer. Immunotherapy of cancer is categorized as either specific stimulation of the immune system by active immunization, with cancer vaccines, or passive transfer of humor or cellular materials, such as, tumor specific antibodies (including immunomodulators) or adoptive cell therapy that inhibit the function of- or directly kill tumor cells. Modulation of immune response in cancer patients is the result of a balanced activity of T regulators and T effector cells.

View Article and Find Full Text PDF