Francesca Carlino - Academia.edu (original) (raw)

Papers by Francesca Carlino

Research paper thumbnail of Editorial: Heterogeneity in breast cancer: clinical and therapeutic implications

Frontiers in oncology, Feb 26, 2024

Research paper thumbnail of Prognostic significance of progesterone receptor levels in luminal-like Her2- early breast cancer patients. A retrospective single cancer center analysis

Annals of Oncology, Oct 1, 2019

Background The prognostic role of Progesterone receptor (PR) expression in early invasive breast ... more Background The prognostic role of Progesterone receptor (PR) expression in early invasive breast cancer (BC) remains controversial. The aim of this retrospective analysis was to investigate the impact of PR expression levels on outcome of patients with luminal-like Her2 negative early BC. Methods A population cohort of 441 primary invasive ER+/Her2- early BC patients from a single cancer center underwent surgery and received adjuvant endocrine therapy from 2000 to 2017 was retrieved. To assess the impact of the different PR levels on the prognosis, we calculated the Distant Free Survival (DFS) and the Breast Cancer Specific Survival (BCSS) according to 4 subtypes established on the basis of Ki67 value and PR expression rate (Subtype 1: PR ≥ 20%/Ki67<20%; Subtype 2: PR ≥ 20%/Ki67≥20%; Subtype 3: PR

Research paper thumbnail of Abstract LB241: FateAI: Analysis of circulating DNA fragmentomics with an artificial intelligence model for cancer screening

Cancer research, Apr 5, 2024

Research paper thumbnail of HER2-Low Status Does Not Affect Survival Outcomes of Patients with Metastatic Breast Cancer (MBC) Undergoing First-Line Treatment with Endocrine Therapy plus Palbociclib: Results of a Multicenter, Retrospective Cohort Study

Cancers, Oct 11, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of Prognostic Relevance of Progesterone Receptor Levels in Early Luminal-Like HER2 Negative Breast Cancer Subtypes: A Retrospective Analysis

Frontiers in Oncology, Mar 28, 2022

In luminal-like early breast cancer (BC), the lack of Progesterone Receptor (PR) expression gener... more In luminal-like early breast cancer (BC), the lack of Progesterone Receptor (PR) expression generally correlates with more aggressive behavior but the clinical validity of low PR levels remains a debated issue. Methods: The main aim of this retrospective analysis was to assess the survival outcome (Breast cancer specific survival, BCSS) in a cohort of 687 luminal-like HER2 negative early BC patients treated at our Institutions from January 2000 to December 2018, using a subclassification of tumors in subgroup 1 (PR high/Ki67 low), subgroup 2 (PR high/Ki67 high), subgroup 3 (PR low/Ki67 low), subgroup 4 (PR low/Ki67 high) according to PR and Ki67 values. Results: At a median follow-up of 7 years, BCSS rates were 96.3%, 89%, 86.8% and 85% in the subgroup 1, 2, 3, 4 respectively. Overall, a statistically significant difference in BCSS rates was observed among the 4 subgroups (p=0.0036). On univariate analysis, post-menopause, older age (≥ 50 years), low PR and high Ki67 expression, poorly differentiated grade and size ≥ 2 cm as well as luminal B-like tumors (subgroups 2, 3, 4) were significantly associated with a worse BCSS. Multivariate analysis identified grade, size and subgroup classification of BC as independent prognostic markers of poorer outcome. In particular, subgroups 4, 3 and 2 displayed a significantly higher risk of BCrelated death (HR=4.11; p=0.008; HR=3.43; p=0-007; HR=2.57; p=0.020, respectively) when compared to subgroup 1. Conclusions: Our results support the usefulness of PR and Ki67 levels as prognostic markers, corroborating their crucial role in the decision-making process of patients with

Research paper thumbnail of 183P Prognostic value of high mesenchymal-epithelial transition factor gene (MET) expression in patients with estrogen receptor positive (ER+), human epidermal growth factor receptor negative (HER2-) early breast cancer

Research paper thumbnail of Expression of c-MET in Estrogen Receptor Positive and HER2 Negative Resected Breast Cancer Correlated with a Poor Prognosis

Journal of Clinical Medicine

Introduction: The mesenchymal-epithelial transition factor (c-MET) receptor is overexpressed in a... more Introduction: The mesenchymal-epithelial transition factor (c-MET) receptor is overexpressed in about 14–54% of invasive breast cancers, but its prognostic value in clinical practice is still unclear. Methods: In order to investigate the relationship between c-MET expression levels and prognosis, we retrospectively reviewed the clinical features and outcomes of 105 women with estrogen receptor positive HER2 negative (ER+/HER2-) resected breast cancer. We used the Kaplan Meier method to estimate Disease Free Survival (DFS) and Breast Cancer Specific Survival (BCSS) in the subgroups of patients with high (≥50%) and low (<50%) c-MET expression. Univariate and multivariate Cox proportional regression models were performed to assess the prognostic impact of clinicopathological parameters for DFS an BCSS. Results: High c-MET values significantly correlated with tumor size, high Ki67 and low (<20%) progesterone receptor expression. At a median follow up of 60 months, patients with hi...

Research paper thumbnail of Prognostic Significance of Progesterone Receptor Immunohistochemistry for Lymph Node Metastases in Endometrial Carcinoma

Gynecologic Oncology, 1999

Objective.The aim of this study was to determine whether progesterone receptor (PR), estrogen rec... more Objective.The aim of this study was to determine whether progesterone receptor (PR), estrogen receptor (ER), p53 protein, and proliferating cell nuclear antigen (PCNA) expression constitute independent prognostic factors for lymph node metastases in endometrial carcinoma using immunohistochemical techniques on hysterectomy and biopsy specimens.Methods.We evaluated the correlation between lymph node metastases and PR/ER immunohistochemistry, p53/PCNA expression, age, tumor grade, myometrial tumor

Research paper thumbnail of Immune-Based Therapy in Triple-Negative Breast Cancer: From Molecular Biology to Clinical Practice

Cancers

Triple-negative breast cancer (TNBC) has been considered for many years an orphan disease in term... more Triple-negative breast cancer (TNBC) has been considered for many years an orphan disease in terms of therapeutic options, with conventional chemotherapy (CT) still representing the mainstay of treatment in the majority of patients. Although breast cancer (BC) has been historically considered a “cold tumor”, exciting progress in the genomic field leading to the characterization of the molecular portrait and the immune profile of TNBC has opened the door to novel therapeutic strategies, including Immune Checkpoint Inhibitors (ICIs), Poly ADP-Ribose Polymerase (PARP) inhibitors and Antibody Drug Conjugates (ADCs). In particular, compared to standard CT, the immune-based approach has been demonstrated to improve progression-free survival (PFS) and overall survival (OS) in metastatic PD-L1-positive TNBC and the pathological complete response rate in the early setting, regardless of PD-L1 expression. To date, PD-L1 has been widely used as a predictor of the response to ICIs; however, man...

Research paper thumbnail of Metachronous Gastrointestinal Stromal Tumors (GISTS) or Relapse of the Primary Tumor? A Challenging Case of Multiple GISTS in an Elderly Patient

Background: Gastrointestinal Stromal Tumors (GISTs) are the most common mesenchymal cancers of th... more Background: Gastrointestinal Stromal Tumors (GISTs) are the most common mesenchymal cancers of the gastrointestinal tract and the majority of them carries pathogenic mutations of KIT and PDGFRA genes. Sporadic Multiple Primary GISTs (MPGs) are a rare entity that could occur in adult patients characterized by multiple synchronous lesions generally located in the same organ and even more rarely by metachronous neoplasms. The differential diagnosis among MPGs and disseminated disease or recurrent primary GIST is critical as it affects clinical management. Case report: Here, we present a case of an 86-year-old female who underwent emergency surgery in June 2016 for a giant GIST of the stomach occupying most of the left side of the abdomen. After two years, during adjuvant imatinib 400 mg daily, emergency sigmoid resection was performed due to subacute obstruction and a colonic GIST carrying the same KIT mutation (deletion 557-558 at exon 11) of the previous gastric neoplasm was detected...

Research paper thumbnail of 302P Clinical implication of tissue re-biopsy in metastatic breast cancer (MBC) patients: A single centre retrospective analysis

Research paper thumbnail of 173P Prognostic impact of progesterone receptor levels in luminal-like Her2- early breast cancer patients: A retrospective analysis

Research paper thumbnail of 3O Efficacy of the triple combination of Estrogen Receptor, CDK4/6 and PI3K pathway inhibitors in ex-vivo models of breast cancer

Research paper thumbnail of Feasibility of next-generation sequencing in clinical practice: results of a pilot study in the Department of Precision Medicine at the University of Campania ‘Luigi Vanvitelli’

ESMO Open, 2020

BackgroundThe emerging role of next-generation sequencing (NGS) targeted panels is revolutionisin... more BackgroundThe emerging role of next-generation sequencing (NGS) targeted panels is revolutionising our approach to cancer patients, providing information on gene alterations helpful for diagnosis and clinical decision, in a short time and with acceptable costs.Materials and methodsIn this work, we evaluated the clinical application of FoundationOne CDx test, a hybrid capture-based NGS. This test identifies alterations in 324 genes, tumour mutational burden and genomic signatures as microsatellite instability. The decision to obtain the NGS assay for a particular patient was done according to investigator’s choice.ResultsOverall, 122 tumour specimens were analysed, of which 84 (68.85%) succeeded. The success rate was influenced by type of specimen formalin-fixed paraffin embedded (FFPE block vs FFPE slides), by origin of the sample (surgery vs biopsy) and by time of fixation (<5 years vs ≥5 years). The most frequent subgroups of effective reports derived from colorectal cancer (25...

Research paper thumbnail of Early Triple Negative Breast Cancer: Conventional Treatment and Emerging Therapeutic Landscapes

Cancers, 2020

Triple negative breast cancers (TNBCs) are characterized by worse prognosis, higher propensity to... more Triple negative breast cancers (TNBCs) are characterized by worse prognosis, higher propensity to earlier metastases, and shorter survival after recurrence compared with other breast cancer subtypes. Anthracycline- and taxane-based chemotherapy is still the mainstay of treatment in early stages, although several escalation approaches have been evaluated to improve survival outcomes. The addition of platinum salts to standard neoadjuvant chemotherapy (NACT) remains controversial due to the lack of clear survival advantage, and the use of adjuvant capecitabine represents a valid treatment option in TNBC patients with residual disease after NACT. Recently, several clinical trials showed promising results through the use of poly ADP-ribose polymerase (PARP) inhibitors and by incorporating immunotherapy with chemotherapy, enriching treatment options beyond conventional cytotoxic agents. In this review, we provided an overview on the current standard of care and a comprehensive update of ...

Research paper thumbnail of PARP inhibitors in ovarian cancer

Cancer Treatment Reviews, 2018

Research paper thumbnail of Cancer Treatment–Induced Bone Loss (CTIBL): State of the Art and Proper Management in Breast Cancer Patients on Endocrine Therapy

Current Treatment Options in Oncology, 2021

Opinion statementAbout 70–80% of early breast cancer (BC) patients receive adjuvant endocrine the... more Opinion statementAbout 70–80% of early breast cancer (BC) patients receive adjuvant endocrine therapy (ET) for at least 5 years. ET includes in the majority of cases the use of aromatase inhibitors, as upfront or switch strategy, that lead to impaired bone health. Given the high incidence and also the high prevalence of BC, cancer treatment–induced bone loss (CTIBL) represents the most common long-term adverse event experimented by patients with hormone receptor positive tumours. CTIBL is responsible for osteoporosis occurrence and, as a consequence, fragility fractures that may negatively affect quality of life and survival expectancy. As recommended by main international guidelines, BC women on aromatase inhibitors should be carefully assessed for their fracture risk at baseline and periodically reassessed during adjuvant ET in order to early detect significant worsening in terms of bone health. Antiresorptive agents, together with adequate intake of calcium and vitamin D, should ...

Research paper thumbnail of Genomic Profile and BRCA-1 Promoter Methylation Status in BRCA Mutated Ovarian Cancer: New Insights in Predictive Biomarkers of Olaparib Response

Frontiers in Oncology

We assessed the genomic profile of four representative BRCA-mutated ovarian cancer (OC) patients ... more We assessed the genomic profile of four representative BRCA-mutated ovarian cancer (OC) patients treated with olaparib to investigate the relationship between intratumor heterogeneity and response to olaparib treatment. The main aim is to identify possible predictive biomarkers of response to olaparib through the analysis of HRD or not HRD genes and the definition of BRCA1 promoter methylation status. Methods: DNA, isolated from formalin-fixed, paraffin-embedded (FFPE) diagnostic OC tissues, was analyzed by FoundationOneCDx TM. This assay detects alterations in a total panel of 324 genes, using the Illumina ® HiSeq 4000 platform. Methylation analysis of the BRCA gene promoter was carried out by pyrosequencing with PyroMark Q24 platform (Qiagen), an in vitro nucleic acid sequence-based detection test based on pyrosequencing technology for quantitative measurements of methylation status. Results: Case #1 and #2 were defined Long-term responders since they received olaparib for 27 and 36 months, respectively. These remarkable results could be explained, at least in part, by the presence of somatic IDH1 mutation in case #1 and PI3K and SOX2 amplification in the case #2. In case #3, the somatic NF1 mutation appeared to be related to the short duration of response. In the case #4, in which the patients is on olaparib from 1 year achieving a stable disease, a somatic mutation of BRCA1 was recorded. Moreover, in all cases, levels of BRCA1 promoter were strictly related to olaparib response. Conclusions: Based on our experience, genomic analysis of tumor tissue at diagnosis might help to determine the future response to olaparib in advanced OC setting, revealing predictive biomarkers beyond BRCA 1-2 and HRD status.

Research paper thumbnail of Triple-Negative Breast Cancers: Systematic Review of the Literature on Molecular and Clinical Features with a Focus on Treatment with Innovative Drugs

Current oncology reports, Jan 20, 2018

Triple-negative breast cancer (TNBC) accounts for 15-20% of diagnosed breast tumours, with higher... more Triple-negative breast cancer (TNBC) accounts for 15-20% of diagnosed breast tumours, with higher incidence in young and African-American women, and it is frequently associated with BRCA germline mutations. Chemotherapy is the only well-established therapeutic option in both early- and advanced-stages of the disease. TNBC tumours relapse earlier after standard anthracycline- and/or taxane-based chemotherapy treatments, generally within 1-3 years after the diagnosis, and often develop visceral metastases, representing the subtype with a worse prognosis among all breast cancers. In the present review, we will provide an updated overview of the available results of recent clinical trials for this disease and we will describe the implications of the known molecular pathways representing novel targets for development of future therapies for TNBC patients. Over the past decade, the advent of gene expression micro-array technology has led to the identification of different actionable targe...

Research paper thumbnail of Editorial: Heterogeneity in breast cancer: clinical and therapeutic implications

Frontiers in oncology, Feb 26, 2024

Research paper thumbnail of Prognostic significance of progesterone receptor levels in luminal-like Her2- early breast cancer patients. A retrospective single cancer center analysis

Annals of Oncology, Oct 1, 2019

Background The prognostic role of Progesterone receptor (PR) expression in early invasive breast ... more Background The prognostic role of Progesterone receptor (PR) expression in early invasive breast cancer (BC) remains controversial. The aim of this retrospective analysis was to investigate the impact of PR expression levels on outcome of patients with luminal-like Her2 negative early BC. Methods A population cohort of 441 primary invasive ER+/Her2- early BC patients from a single cancer center underwent surgery and received adjuvant endocrine therapy from 2000 to 2017 was retrieved. To assess the impact of the different PR levels on the prognosis, we calculated the Distant Free Survival (DFS) and the Breast Cancer Specific Survival (BCSS) according to 4 subtypes established on the basis of Ki67 value and PR expression rate (Subtype 1: PR ≥ 20%/Ki67&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;20%; Subtype 2: PR ≥ 20%/Ki67≥20%; Subtype 3: PR

Research paper thumbnail of Abstract LB241: FateAI: Analysis of circulating DNA fragmentomics with an artificial intelligence model for cancer screening

Cancer research, Apr 5, 2024

Research paper thumbnail of HER2-Low Status Does Not Affect Survival Outcomes of Patients with Metastatic Breast Cancer (MBC) Undergoing First-Line Treatment with Endocrine Therapy plus Palbociclib: Results of a Multicenter, Retrospective Cohort Study

Cancers, Oct 11, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of Prognostic Relevance of Progesterone Receptor Levels in Early Luminal-Like HER2 Negative Breast Cancer Subtypes: A Retrospective Analysis

Frontiers in Oncology, Mar 28, 2022

In luminal-like early breast cancer (BC), the lack of Progesterone Receptor (PR) expression gener... more In luminal-like early breast cancer (BC), the lack of Progesterone Receptor (PR) expression generally correlates with more aggressive behavior but the clinical validity of low PR levels remains a debated issue. Methods: The main aim of this retrospective analysis was to assess the survival outcome (Breast cancer specific survival, BCSS) in a cohort of 687 luminal-like HER2 negative early BC patients treated at our Institutions from January 2000 to December 2018, using a subclassification of tumors in subgroup 1 (PR high/Ki67 low), subgroup 2 (PR high/Ki67 high), subgroup 3 (PR low/Ki67 low), subgroup 4 (PR low/Ki67 high) according to PR and Ki67 values. Results: At a median follow-up of 7 years, BCSS rates were 96.3%, 89%, 86.8% and 85% in the subgroup 1, 2, 3, 4 respectively. Overall, a statistically significant difference in BCSS rates was observed among the 4 subgroups (p=0.0036). On univariate analysis, post-menopause, older age (≥ 50 years), low PR and high Ki67 expression, poorly differentiated grade and size ≥ 2 cm as well as luminal B-like tumors (subgroups 2, 3, 4) were significantly associated with a worse BCSS. Multivariate analysis identified grade, size and subgroup classification of BC as independent prognostic markers of poorer outcome. In particular, subgroups 4, 3 and 2 displayed a significantly higher risk of BCrelated death (HR=4.11; p=0.008; HR=3.43; p=0-007; HR=2.57; p=0.020, respectively) when compared to subgroup 1. Conclusions: Our results support the usefulness of PR and Ki67 levels as prognostic markers, corroborating their crucial role in the decision-making process of patients with

Research paper thumbnail of 183P Prognostic value of high mesenchymal-epithelial transition factor gene (MET) expression in patients with estrogen receptor positive (ER+), human epidermal growth factor receptor negative (HER2-) early breast cancer

Research paper thumbnail of Expression of c-MET in Estrogen Receptor Positive and HER2 Negative Resected Breast Cancer Correlated with a Poor Prognosis

Journal of Clinical Medicine

Introduction: The mesenchymal-epithelial transition factor (c-MET) receptor is overexpressed in a... more Introduction: The mesenchymal-epithelial transition factor (c-MET) receptor is overexpressed in about 14–54% of invasive breast cancers, but its prognostic value in clinical practice is still unclear. Methods: In order to investigate the relationship between c-MET expression levels and prognosis, we retrospectively reviewed the clinical features and outcomes of 105 women with estrogen receptor positive HER2 negative (ER+/HER2-) resected breast cancer. We used the Kaplan Meier method to estimate Disease Free Survival (DFS) and Breast Cancer Specific Survival (BCSS) in the subgroups of patients with high (≥50%) and low (<50%) c-MET expression. Univariate and multivariate Cox proportional regression models were performed to assess the prognostic impact of clinicopathological parameters for DFS an BCSS. Results: High c-MET values significantly correlated with tumor size, high Ki67 and low (<20%) progesterone receptor expression. At a median follow up of 60 months, patients with hi...

Research paper thumbnail of Prognostic Significance of Progesterone Receptor Immunohistochemistry for Lymph Node Metastases in Endometrial Carcinoma

Gynecologic Oncology, 1999

Objective.The aim of this study was to determine whether progesterone receptor (PR), estrogen rec... more Objective.The aim of this study was to determine whether progesterone receptor (PR), estrogen receptor (ER), p53 protein, and proliferating cell nuclear antigen (PCNA) expression constitute independent prognostic factors for lymph node metastases in endometrial carcinoma using immunohistochemical techniques on hysterectomy and biopsy specimens.Methods.We evaluated the correlation between lymph node metastases and PR/ER immunohistochemistry, p53/PCNA expression, age, tumor grade, myometrial tumor

Research paper thumbnail of Immune-Based Therapy in Triple-Negative Breast Cancer: From Molecular Biology to Clinical Practice

Cancers

Triple-negative breast cancer (TNBC) has been considered for many years an orphan disease in term... more Triple-negative breast cancer (TNBC) has been considered for many years an orphan disease in terms of therapeutic options, with conventional chemotherapy (CT) still representing the mainstay of treatment in the majority of patients. Although breast cancer (BC) has been historically considered a “cold tumor”, exciting progress in the genomic field leading to the characterization of the molecular portrait and the immune profile of TNBC has opened the door to novel therapeutic strategies, including Immune Checkpoint Inhibitors (ICIs), Poly ADP-Ribose Polymerase (PARP) inhibitors and Antibody Drug Conjugates (ADCs). In particular, compared to standard CT, the immune-based approach has been demonstrated to improve progression-free survival (PFS) and overall survival (OS) in metastatic PD-L1-positive TNBC and the pathological complete response rate in the early setting, regardless of PD-L1 expression. To date, PD-L1 has been widely used as a predictor of the response to ICIs; however, man...

Research paper thumbnail of Metachronous Gastrointestinal Stromal Tumors (GISTS) or Relapse of the Primary Tumor? A Challenging Case of Multiple GISTS in an Elderly Patient

Background: Gastrointestinal Stromal Tumors (GISTs) are the most common mesenchymal cancers of th... more Background: Gastrointestinal Stromal Tumors (GISTs) are the most common mesenchymal cancers of the gastrointestinal tract and the majority of them carries pathogenic mutations of KIT and PDGFRA genes. Sporadic Multiple Primary GISTs (MPGs) are a rare entity that could occur in adult patients characterized by multiple synchronous lesions generally located in the same organ and even more rarely by metachronous neoplasms. The differential diagnosis among MPGs and disseminated disease or recurrent primary GIST is critical as it affects clinical management. Case report: Here, we present a case of an 86-year-old female who underwent emergency surgery in June 2016 for a giant GIST of the stomach occupying most of the left side of the abdomen. After two years, during adjuvant imatinib 400 mg daily, emergency sigmoid resection was performed due to subacute obstruction and a colonic GIST carrying the same KIT mutation (deletion 557-558 at exon 11) of the previous gastric neoplasm was detected...

Research paper thumbnail of 302P Clinical implication of tissue re-biopsy in metastatic breast cancer (MBC) patients: A single centre retrospective analysis

Research paper thumbnail of 173P Prognostic impact of progesterone receptor levels in luminal-like Her2- early breast cancer patients: A retrospective analysis

Research paper thumbnail of 3O Efficacy of the triple combination of Estrogen Receptor, CDK4/6 and PI3K pathway inhibitors in ex-vivo models of breast cancer

Research paper thumbnail of Feasibility of next-generation sequencing in clinical practice: results of a pilot study in the Department of Precision Medicine at the University of Campania ‘Luigi Vanvitelli’

ESMO Open, 2020

BackgroundThe emerging role of next-generation sequencing (NGS) targeted panels is revolutionisin... more BackgroundThe emerging role of next-generation sequencing (NGS) targeted panels is revolutionising our approach to cancer patients, providing information on gene alterations helpful for diagnosis and clinical decision, in a short time and with acceptable costs.Materials and methodsIn this work, we evaluated the clinical application of FoundationOne CDx test, a hybrid capture-based NGS. This test identifies alterations in 324 genes, tumour mutational burden and genomic signatures as microsatellite instability. The decision to obtain the NGS assay for a particular patient was done according to investigator’s choice.ResultsOverall, 122 tumour specimens were analysed, of which 84 (68.85%) succeeded. The success rate was influenced by type of specimen formalin-fixed paraffin embedded (FFPE block vs FFPE slides), by origin of the sample (surgery vs biopsy) and by time of fixation (<5 years vs ≥5 years). The most frequent subgroups of effective reports derived from colorectal cancer (25...

Research paper thumbnail of Early Triple Negative Breast Cancer: Conventional Treatment and Emerging Therapeutic Landscapes

Cancers, 2020

Triple negative breast cancers (TNBCs) are characterized by worse prognosis, higher propensity to... more Triple negative breast cancers (TNBCs) are characterized by worse prognosis, higher propensity to earlier metastases, and shorter survival after recurrence compared with other breast cancer subtypes. Anthracycline- and taxane-based chemotherapy is still the mainstay of treatment in early stages, although several escalation approaches have been evaluated to improve survival outcomes. The addition of platinum salts to standard neoadjuvant chemotherapy (NACT) remains controversial due to the lack of clear survival advantage, and the use of adjuvant capecitabine represents a valid treatment option in TNBC patients with residual disease after NACT. Recently, several clinical trials showed promising results through the use of poly ADP-ribose polymerase (PARP) inhibitors and by incorporating immunotherapy with chemotherapy, enriching treatment options beyond conventional cytotoxic agents. In this review, we provided an overview on the current standard of care and a comprehensive update of ...

Research paper thumbnail of PARP inhibitors in ovarian cancer

Cancer Treatment Reviews, 2018

Research paper thumbnail of Cancer Treatment–Induced Bone Loss (CTIBL): State of the Art and Proper Management in Breast Cancer Patients on Endocrine Therapy

Current Treatment Options in Oncology, 2021

Opinion statementAbout 70–80% of early breast cancer (BC) patients receive adjuvant endocrine the... more Opinion statementAbout 70–80% of early breast cancer (BC) patients receive adjuvant endocrine therapy (ET) for at least 5 years. ET includes in the majority of cases the use of aromatase inhibitors, as upfront or switch strategy, that lead to impaired bone health. Given the high incidence and also the high prevalence of BC, cancer treatment–induced bone loss (CTIBL) represents the most common long-term adverse event experimented by patients with hormone receptor positive tumours. CTIBL is responsible for osteoporosis occurrence and, as a consequence, fragility fractures that may negatively affect quality of life and survival expectancy. As recommended by main international guidelines, BC women on aromatase inhibitors should be carefully assessed for their fracture risk at baseline and periodically reassessed during adjuvant ET in order to early detect significant worsening in terms of bone health. Antiresorptive agents, together with adequate intake of calcium and vitamin D, should ...

Research paper thumbnail of Genomic Profile and BRCA-1 Promoter Methylation Status in BRCA Mutated Ovarian Cancer: New Insights in Predictive Biomarkers of Olaparib Response

Frontiers in Oncology

We assessed the genomic profile of four representative BRCA-mutated ovarian cancer (OC) patients ... more We assessed the genomic profile of four representative BRCA-mutated ovarian cancer (OC) patients treated with olaparib to investigate the relationship between intratumor heterogeneity and response to olaparib treatment. The main aim is to identify possible predictive biomarkers of response to olaparib through the analysis of HRD or not HRD genes and the definition of BRCA1 promoter methylation status. Methods: DNA, isolated from formalin-fixed, paraffin-embedded (FFPE) diagnostic OC tissues, was analyzed by FoundationOneCDx TM. This assay detects alterations in a total panel of 324 genes, using the Illumina ® HiSeq 4000 platform. Methylation analysis of the BRCA gene promoter was carried out by pyrosequencing with PyroMark Q24 platform (Qiagen), an in vitro nucleic acid sequence-based detection test based on pyrosequencing technology for quantitative measurements of methylation status. Results: Case #1 and #2 were defined Long-term responders since they received olaparib for 27 and 36 months, respectively. These remarkable results could be explained, at least in part, by the presence of somatic IDH1 mutation in case #1 and PI3K and SOX2 amplification in the case #2. In case #3, the somatic NF1 mutation appeared to be related to the short duration of response. In the case #4, in which the patients is on olaparib from 1 year achieving a stable disease, a somatic mutation of BRCA1 was recorded. Moreover, in all cases, levels of BRCA1 promoter were strictly related to olaparib response. Conclusions: Based on our experience, genomic analysis of tumor tissue at diagnosis might help to determine the future response to olaparib in advanced OC setting, revealing predictive biomarkers beyond BRCA 1-2 and HRD status.

Research paper thumbnail of Triple-Negative Breast Cancers: Systematic Review of the Literature on Molecular and Clinical Features with a Focus on Treatment with Innovative Drugs

Current oncology reports, Jan 20, 2018

Triple-negative breast cancer (TNBC) accounts for 15-20% of diagnosed breast tumours, with higher... more Triple-negative breast cancer (TNBC) accounts for 15-20% of diagnosed breast tumours, with higher incidence in young and African-American women, and it is frequently associated with BRCA germline mutations. Chemotherapy is the only well-established therapeutic option in both early- and advanced-stages of the disease. TNBC tumours relapse earlier after standard anthracycline- and/or taxane-based chemotherapy treatments, generally within 1-3 years after the diagnosis, and often develop visceral metastases, representing the subtype with a worse prognosis among all breast cancers. In the present review, we will provide an updated overview of the available results of recent clinical trials for this disease and we will describe the implications of the known molecular pathways representing novel targets for development of future therapies for TNBC patients. Over the past decade, the advent of gene expression micro-array technology has led to the identification of different actionable targe...