Brigida Stanzione - Academia.edu (original) (raw)

Papers by Brigida Stanzione

International Journal of Molecular Sciences

The therapeutic landscape in patients with advanced non-small-cell lung cancer harboring oncogeni... more The therapeutic landscape in patients with advanced non-small-cell lung cancer harboring oncogenic biomarkers has radically changed with the development of targeted therapies. Although lung cancers are known to frequently metastasize to the brain, oncogene-driven non-small-cell lung cancer patients show a higher incidence of both brain metastases at baseline and a further risk of central nervous system progression/relapse. Recently, a new generation of targeted agents, highly active in the central nervous system, has improved the control of intracranial disease. The intracranial activity of these drugs poses a crucial issue in determining the optimal management sequence in oncogene-addicted non-small-cell lung cancer patients with brain metastases, with a potential change of paradigm from primary brain irradiation to central nervous system penetrating targeted inhibitors.

International Journal of Molecular Sciences

The severe prognosis linked with a lung cancer diagnosis has changed with the discovery of oncoge... more The severe prognosis linked with a lung cancer diagnosis has changed with the discovery of oncogenic molecularly driven subgroups and the use of tailored treatment. ALK-translocated advanced lung cancer is the most interesting model, having achieved the longest overall survival. Here, we report the most important paradigmatic shifts in the prognosis and treatment for this subgroup population occurred among lung cancer.

International Journal of Molecular Sciences

Osimertinib is currently the preferred first-line therapy in patients with non-small cell lung ca... more Osimertinib is currently the preferred first-line therapy in patients with non-small cell lung cancer (NSCLC) with common epidermal growth factor receptor (EGFR) mutation and the standard second-line therapy in T790M-positive patients in progression to previous EGFR tyrosine kinase inhibitor. Osimertinib is a highly effective treatment that shows a high response rate and long-lasting disease control. However, a resistance to the treatment inevitably develops among patients. Understanding the secondary mechanisms of resistance and the possible therapeutic options available is crucial to define the best management of patients in progression to osimertinib. We provide a comprehensive review of the emerging molecular resistance mechanism in EGFR-mutated NSCLC pre-treated with osimertinib and its future treatment applications.

International Journal of Molecular Sciences

Patients with non-small cell lung cancer (NSCLC) develop bone metastasis (BoM) in more than 50% o... more Patients with non-small cell lung cancer (NSCLC) develop bone metastasis (BoM) in more than 50% of cases during the course of the disease. This metastatic site can lead to the development of skeletal related events (SREs), such as severe pain, pathological fractures, spinal compression, and hypercalcemia, which reduce the patient’s quality of life. Recently, the treatment of advanced NSCLC has radically changed due to the advent of immunotherapy. Immune checkpoint inhibitors (ICI) alone or in combination with chemotherapy have become the main therapeutic strategy for advanced or metastatic NSCLC without driver gene mutations. Since survival has increased, it has become even more important to treat bone metastasis to prevent SRE. We know that the presence of bone metastasis is a negative prognostic factor. The lower efficacy of immunotherapy treatments in BoM+ patients could be induced by the presence of a particular immunosuppressive tumor and bone microenvironment. This article rev...

This concise and handy manual provides straightforward, up-to-date guidance for cardiologists and... more This concise and handy manual provides straightforward, up-to-date guidance for cardiologists and other practitioners on the management of cancer patients with cardiac problems, whether they be due to the cancer itself or to antineoplastic treatment. Detailed attention is devoted to the various forms of cardiotoxicity associated with chemotherapy and radiotherapy. The drugs commonly responsible for each toxicity are identified and clear advice is offered on monitoring techniques and treatment approaches. In addition, the issue of cardiotoxicity due to cancer treatment in particular patient groups \u2013 children, the elderly, and those with pre-existing cardiac disease \u2013 is addressed separately, with guidance on when and how antineoplastic (and/or cardiological) treatments should be modified. Further sections describe the correct responses to cardiac problems secondary to the cancer itself, including thromboembolic disorders and electrolyte imbalances, and the diagnosis, treatm...

The incidence and the prevalence of both cardiovascular and the neoplastic diseases are increasin... more The incidence and the prevalence of both cardiovascular and the neoplastic diseases are increasing, as are the therapeutic possibilities and survival. Thus, identifying the best cardiovascular care in a patient ready to start an antineoplastic treatment is becoming a rather common problem.

Journal of Clinical Oncology, 2013

e11528 Background: Hormone therapy (HT) is limited by the onset of resistance. Preclinical studie... more e11528 Background: Hormone therapy (HT) is limited by the onset of resistance. Preclinical studies suggest that complete blockade of the estrogen receptor (ER) with the ER antagonist Fulvestrant (F) can overcome this resistance. The aim of this study was to evaluate the efficacy and tolerability of F in postmenopausal women with hormone-responsive (HR) metastatic breast cancer (MBC) previously treated with Tamoxifen (T) or Aromatase Inhibitors (AI). Methods: From May 2006 to July 2008 83 patients with HR MBC progressing after T or AI for adjuvant or metastatic disease receiving F 250 mg/month were identified. Median time to progression (TTP), overall survival (OS), clinical benefit rate (CBR) defined as the proportion of partial or complete responses (CR, PR) or stable disease (SD) lasting ‡6 months were analyzed. Results: Six, 32, 33 and 12 patients received F as 1st, 2nd, 3rd and 4thline of HT for MBC, respectively. Fulvestrant resulted in an overall CBR of 38.6% (32/83) with 0% C...

Journal of Clinical Oncology, 2010

e11025 Background: Taxane-based adjuvant chemotherapy regimens for EBC yield on average an improv... more e11025 Background: Taxane-based adjuvant chemotherapy regimens for EBC yield on average an improvement of disease-free-survival (DFS) and overall survival (OS) as compared to anthracycline-based regimens (De Laurentiis et al., JCO 2008). It has been questioned, however, that this average benefit may results from a markedly improved outcome for some subsets of patients, with others not receiving any advantage. To check this hypothesis, we performed a meta-analysis of the predictive effects both of HER2 and of ER status by pooling subsets data of the available randomized trials (RTs). The efficacy of taxane-based regimens in the subgroup of triple-negative (TN) pts was also evaluated. Methods: We searched the Pubmed database to identify randomized trials that compared taxane-based with non-taxane-based adjuvant chemotherapy regimens for EBC and reported efficacy data according to: HER2 or ER or the combination HER2/ER or the TN status. We also searched the proceedings of major international conferences to i...

Current Cancer Drug Targets, 2018

Over the last 15 years, we have seen a huge expansion of the development of drugs directed agains... more Over the last 15 years, we have seen a huge expansion of the development of drugs directed against biomolecular targets within breast cancer cells. The over-expression of certain receptors (ER, PgR, HER-2, VEGF-R), as well as alteration of several intracellular signal transduction pathways (the PI3K-AKT-mTOR pathway, MEK-MAPK pathway, loss of PTEN, etc ...) has a great impact on the likelihood of recurrence and progression of the disease, influencing the natural history of breast cancer. The recent biomolecular classification of breast cancer (Luminal A / B, HER2- driven, Basal Like) allowed finally to identify specific treatments against molecular target to associate or not to traditional chemotherapy, and to use in relation to the prognosis of the disease. In the following paragraphs, we will set out the major targeted drug that have received indications in breast cancer, both in the localized and in advanced disease, referring to the specific target (hormonal receptors, HER2, VEG...

The Breast, 2017

Background: According to current guidelines, endocrine therapy (ET) is recommended as first-line ... more Background: According to current guidelines, endocrine therapy (ET) is recommended as first-line treatment of luminal-like metastatic breast cancer (MBC), whereas chemotherapy (CT) should be considered in presence of life-threatening disease. In daily practice, CT is often used outside of this clinical circumstance. Factors influencing first-line choice and the relative impact on outcome are unknown. Methods: A consecutive series of luminal-like HER2-negative MBC patients treated from 2004 to 2014 was analyzed to test the association of disease-and patient-related factors with the choice of first-line treatment (ET vs. CT). A propensity score method was used to estimate impact of first-line strategy on outcome. Results: Of 604 consecutive luminal-like MBC patients identified, 158 cases were excluded due to unknown or positive HER2-status. Among 446 HER2-negative cases, 171 (38%) received first-line CT. On multivariate analysis, the only factors significantly associated with lower CT use were old age (OR 0.25, 95%C.I. 0.13e0.49) or presence of bone metastases only (OR 0.26, 95%C.I. 0.13e0.53). In propensity score matched population, no differences were observed between CT and ET as first-line treatment either in terms of overall survival (37.5 months and 33.4 months respectively, log-rank test, P ¼ 0.62) or progression-free survival (13.3 months and 9.9 months respectively, log-rank test, P ¼ 0.92). Conclusions: High percentage of patients with luminal-like MBC received CT as first-line therapy in reallife. The choice was mainly driven by age and site of metastases. With the limitations of a nonrandomized comparison, no differences on patients' outcome were observed depending on the firstline strategy.

Expert Opinion on Pharmacotherapy, 2016

The introduction of Highly Active Antiretroviral Therapy (HAART) into clinical practice has drama... more The introduction of Highly Active Antiretroviral Therapy (HAART) into clinical practice has dramatically changed the outcome of HIV-infected patients by prolonging their survival. The increase in life expectancy has led to an increased risk of non-AIDS-related mortality and morbidity, including cardiovascular diseases, neurocognitive diseases, neuroendocrine dysfunctions and cancer.

Combination Products in Therapy, 2013

In the last few decades the approach to metastatic breast cancer (MBC) treatment using chemothera... more In the last few decades the approach to metastatic breast cancer (MBC) treatment using chemotherapy, either as single or combination agents, has been largely studied and a wide spectrum of therapeutic options is now available. Anthracyclines and taxanes remain the cornerstone of treatment in this setting. The choice of combination chemotherapy versus monochemotherapy is still open to debate since results from clinical trials are, unfortunately, conflicting. Despite improvements in response and disease-free survival rates, there has been no overall survival benefit reported although toxicity is increased. Therefore, based on available data, clinical decision-making for a busy practitioner should consider not only patient/tumor characteristics and the potential benefits of treatments, but also their toxicity profiles and patient preferences. Novel cytotoxic compounds have been approved for clinical use and combination regimens incorporating these agents may bring new treatment opportunities for MBC patients. In this review, we summarize the main achievements and the currently available and future combinations of cytotoxic drugs for patients with HER2-negative MBC.

Cancer Treatment Reviews, 2010

Breast cancer is not considered anymore a unique disease. Microarray gene expression analysis led... more Breast cancer is not considered anymore a unique disease. Microarray gene expression analysis led to the identification of 4 major breast cancer "intrinsic" subtypes, including hormone receptor (HR)-positive luminal A and B, human epidermal growth receptor 2 (HER2)-positive and basallike breast cancer (BLBC). These subtypes have distinct phenotypes, molecular profiles, clinical behaviour and response to therapy, with the BLBC carrying the worst outcome. Microarray analysis is not feasible in routine practice and therefore oncologists rely on a simpler immunohistochemical (IHC) classification to identify relevant breast cancer subtypes. Triple negative breast cancer (TNBC) is defined by the absence of oestrogen receptor, progesterone receptor and HER2 expression at IHC analysis. TNBC is strictly related to BLBC and, given the lack of common therapeutic targets, represent a major challenge for breast oncologist. In this review we will summarize the updated knowledge on TNBC, with emphasis on its current treatment and on the new therapeutic options under development.

International Journal of Molecular Sciences

ROS proto-oncogene 1 (ROS1) rearrangements occur in 0.9–2.6% of patients with non small cell lung... more ROS proto-oncogene 1 (ROS1) rearrangements occur in 0.9–2.6% of patients with non small cell lung cancer (NSCLC), conferring sensitivity to treatment with specific tyrosine-kinase inhibitors (TKI). Crizotinib, a first-generation TKI, was the first target-therapy approved for the first-line treatment of ROS1-positive NSCLC. Recently, entrectinib, a multitarget inhibitor with an anti-ROS1 activity 40 times more potent than crizotinib and better activity on the central nervous system (CNS), received approval for treatment-naive patients. After a median time-to-progression of 5.5–20 months, resistance mechanisms can occur, leading to tumor progression. Therefore, newer generation TKI with greater potency and brain penetration have been developed and are currently under investigation. This review summarizes the current knowledge on clinicopathological characteristics of ROS1-positive NSCLC and its therapeutic options.

Journal of Thoracic Oncology

In Vivo, 2021

Background: Osimertinib is a third-generation EGFR-tyrosine kinase inhibitor approved for the tre... more Background: Osimertinib is a third-generation EGFR-tyrosine kinase inhibitor approved for the treatment of T790M-positive non-small-cell lung cancer. More recently, osimertinib demonstrated improved disease control compared to other EGFR-TKIs. Multiple mechanisms of resistance have been described in T790M-positive patients who experienced treatment failure with osimertinib. Case Report: We report the case of a 78-year-old non-smoker woman with stage IV EGFR L858R-positive lung adenocarcinoma presented with T790M mutation after five years of treatment with gefitinib. The patient was started on osimertinib, but after two and a half years of treatment experienced disease progression. The analyses of circulating tumor DNA using next-generation sequencing showed, together with the pre-existing T790M and exon 21 L858R, the presence of the EGFR C797G resistance mutation. Conclusion: Our case report revealed a rare EGFRdependent acquired resistance mutation to osimertinib in circulating tumor DNA. Liquid biopsy appears to be a promising resource to understand the biology of osimertinib resistance by clonal evolution monitoring and the identification of novel resistance mechanisms.

BMC cancer, Feb 6, 2018

Metastases to the thyroid gland are more frequent than previously thought, although most of them ... more Metastases to the thyroid gland are more frequent than previously thought, although most of them are occult or not clinically relevant. Overall, only 42 cases of metastases to thyroid from breast cancer have been reported thus far. Here we report the case of a patient with breast cancer metastatic to the thyroid. We also review the 42 previously reported cases (published between 1962 and 2012). This is the first review about metastases to thyroid gland from breast cancer. A 64-year-old woman of Caucasian origin was diagnosed with a lobular invasive carcinoma of the breast (luminal A, stage II). She received adjuvant chemotherapy, followed by endocrine therapy. During follow-up, fine-needle cytology of a thyroid nodule revealed malignant cells that were estrogen-positive, which suggested a diagnosis of metastases to the thyroid. Imaging did not reveal any other metastatic site and showed only enlargement of the left thyroid lobe and an inhomogeneous pattern of colloid and cystic dege...

Oncotarget, 2017

HCC represents the sixth most common cancer worldwide and the second leading cause of cancer-rela... more HCC represents the sixth most common cancer worldwide and the second leading cause of cancer-related death. Despite the high incidence, treatment options for advanced HCC remain limited and unsuccessful, resulting in a poor prognosis. Despite the major advances achieved in the diagnostic management of HCC, only one third of the newly diagnosed patients are presently eligible for curative treatments. Advances in technology and an increased understanding of HCC biology have led to the discovery of novel biomarkers. Improving our knowledge about serum and tissutal markers could ultimately lead to an early diagnosis and better and early treatment strategies for this deadly disease. Serum biomarkers are striking potential tools for surveillance and early diagnosis of HCC thanks to the non-invasive, objective, and reproducible assessments they potentially enable. To date, many biomarkers have been proposed in the diagnosis of HCC. Cholangiocarcinoma (CCA) is an aggressive malignancy, characterized by early lymph node involvement and distant metastasis, with 5-year survival rates of 5%-10%. The identification of new biomarkers with diagnostic, prognostic or predictive value is especially important as resection (by surgery or combined with a liver transplant) has shown promising results and novel therapies are emerging. However, the relatively low incidence of CCA, high frequency of co-existing cholestasis or cholangitis (primary sclerosing cholangitis-PSC-above all), and difficulties with obtaining adequate samples, despite advances in sampling techniques and in endoscopic visualization of the bile ducts, have complicated the search for accurate biomarkers. In this review, we attempt to analyze the existing literature on this argument. HEPATOCELLULAR CARCINOMA

European review for medical and pharmacological sciences, 2015

To study the expression of programmed death-ligand1 (PD-L1) in hepatocellular carcinoma and its r... more To study the expression of programmed death-ligand1 (PD-L1) in hepatocellular carcinoma and its relationship with clinicopathological characteristics and, prognosis of hepatocellular carcinoma and APE1, P53 protein expression levels. A total of 128 patients with hepatocellular carcinoma were enrolled in this study. The expression of PD-L1, APE1 and P53 were detected by immunohistochemistry.Use immunohistochemical ABC staining method to detect the expression levels of PD-L1, APE1 and P53 protein in the hepatocellular carcinoma of 128 cases. Positive The positive expression rates levels of PD-L1, APE1, and P53 protein in hepatocellular carcinoma tissues are were 82.03%, 92.19%, and 60.94%. PD-L1 positive expression were significantly associated with clinical stage, The PD-L1 protein has a high expression in patients with I ~ II stage liver cancerHBV infection positive and nonportal vein thrombosis (p=0.041; p=0.030; p=0.014). It is inversely correlated with P53 and PD-L1 expression (c...

International Journal of Molecular Sciences

The therapeutic landscape in patients with advanced non-small-cell lung cancer harboring oncogeni... more The therapeutic landscape in patients with advanced non-small-cell lung cancer harboring oncogenic biomarkers has radically changed with the development of targeted therapies. Although lung cancers are known to frequently metastasize to the brain, oncogene-driven non-small-cell lung cancer patients show a higher incidence of both brain metastases at baseline and a further risk of central nervous system progression/relapse. Recently, a new generation of targeted agents, highly active in the central nervous system, has improved the control of intracranial disease. The intracranial activity of these drugs poses a crucial issue in determining the optimal management sequence in oncogene-addicted non-small-cell lung cancer patients with brain metastases, with a potential change of paradigm from primary brain irradiation to central nervous system penetrating targeted inhibitors.

International Journal of Molecular Sciences

The severe prognosis linked with a lung cancer diagnosis has changed with the discovery of oncoge... more The severe prognosis linked with a lung cancer diagnosis has changed with the discovery of oncogenic molecularly driven subgroups and the use of tailored treatment. ALK-translocated advanced lung cancer is the most interesting model, having achieved the longest overall survival. Here, we report the most important paradigmatic shifts in the prognosis and treatment for this subgroup population occurred among lung cancer.

International Journal of Molecular Sciences

Osimertinib is currently the preferred first-line therapy in patients with non-small cell lung ca... more Osimertinib is currently the preferred first-line therapy in patients with non-small cell lung cancer (NSCLC) with common epidermal growth factor receptor (EGFR) mutation and the standard second-line therapy in T790M-positive patients in progression to previous EGFR tyrosine kinase inhibitor. Osimertinib is a highly effective treatment that shows a high response rate and long-lasting disease control. However, a resistance to the treatment inevitably develops among patients. Understanding the secondary mechanisms of resistance and the possible therapeutic options available is crucial to define the best management of patients in progression to osimertinib. We provide a comprehensive review of the emerging molecular resistance mechanism in EGFR-mutated NSCLC pre-treated with osimertinib and its future treatment applications.

International Journal of Molecular Sciences

Patients with non-small cell lung cancer (NSCLC) develop bone metastasis (BoM) in more than 50% o... more Patients with non-small cell lung cancer (NSCLC) develop bone metastasis (BoM) in more than 50% of cases during the course of the disease. This metastatic site can lead to the development of skeletal related events (SREs), such as severe pain, pathological fractures, spinal compression, and hypercalcemia, which reduce the patient’s quality of life. Recently, the treatment of advanced NSCLC has radically changed due to the advent of immunotherapy. Immune checkpoint inhibitors (ICI) alone or in combination with chemotherapy have become the main therapeutic strategy for advanced or metastatic NSCLC without driver gene mutations. Since survival has increased, it has become even more important to treat bone metastasis to prevent SRE. We know that the presence of bone metastasis is a negative prognostic factor. The lower efficacy of immunotherapy treatments in BoM+ patients could be induced by the presence of a particular immunosuppressive tumor and bone microenvironment. This article rev...

This concise and handy manual provides straightforward, up-to-date guidance for cardiologists and... more This concise and handy manual provides straightforward, up-to-date guidance for cardiologists and other practitioners on the management of cancer patients with cardiac problems, whether they be due to the cancer itself or to antineoplastic treatment. Detailed attention is devoted to the various forms of cardiotoxicity associated with chemotherapy and radiotherapy. The drugs commonly responsible for each toxicity are identified and clear advice is offered on monitoring techniques and treatment approaches. In addition, the issue of cardiotoxicity due to cancer treatment in particular patient groups \u2013 children, the elderly, and those with pre-existing cardiac disease \u2013 is addressed separately, with guidance on when and how antineoplastic (and/or cardiological) treatments should be modified. Further sections describe the correct responses to cardiac problems secondary to the cancer itself, including thromboembolic disorders and electrolyte imbalances, and the diagnosis, treatm...

The incidence and the prevalence of both cardiovascular and the neoplastic diseases are increasin... more The incidence and the prevalence of both cardiovascular and the neoplastic diseases are increasing, as are the therapeutic possibilities and survival. Thus, identifying the best cardiovascular care in a patient ready to start an antineoplastic treatment is becoming a rather common problem.

Journal of Clinical Oncology, 2013

e11528 Background: Hormone therapy (HT) is limited by the onset of resistance. Preclinical studie... more e11528 Background: Hormone therapy (HT) is limited by the onset of resistance. Preclinical studies suggest that complete blockade of the estrogen receptor (ER) with the ER antagonist Fulvestrant (F) can overcome this resistance. The aim of this study was to evaluate the efficacy and tolerability of F in postmenopausal women with hormone-responsive (HR) metastatic breast cancer (MBC) previously treated with Tamoxifen (T) or Aromatase Inhibitors (AI). Methods: From May 2006 to July 2008 83 patients with HR MBC progressing after T or AI for adjuvant or metastatic disease receiving F 250 mg/month were identified. Median time to progression (TTP), overall survival (OS), clinical benefit rate (CBR) defined as the proportion of partial or complete responses (CR, PR) or stable disease (SD) lasting ‡6 months were analyzed. Results: Six, 32, 33 and 12 patients received F as 1st, 2nd, 3rd and 4thline of HT for MBC, respectively. Fulvestrant resulted in an overall CBR of 38.6% (32/83) with 0% C...

Journal of Clinical Oncology, 2010

e11025 Background: Taxane-based adjuvant chemotherapy regimens for EBC yield on average an improv... more e11025 Background: Taxane-based adjuvant chemotherapy regimens for EBC yield on average an improvement of disease-free-survival (DFS) and overall survival (OS) as compared to anthracycline-based regimens (De Laurentiis et al., JCO 2008). It has been questioned, however, that this average benefit may results from a markedly improved outcome for some subsets of patients, with others not receiving any advantage. To check this hypothesis, we performed a meta-analysis of the predictive effects both of HER2 and of ER status by pooling subsets data of the available randomized trials (RTs). The efficacy of taxane-based regimens in the subgroup of triple-negative (TN) pts was also evaluated. Methods: We searched the Pubmed database to identify randomized trials that compared taxane-based with non-taxane-based adjuvant chemotherapy regimens for EBC and reported efficacy data according to: HER2 or ER or the combination HER2/ER or the TN status. We also searched the proceedings of major international conferences to i...

Current Cancer Drug Targets, 2018

Over the last 15 years, we have seen a huge expansion of the development of drugs directed agains... more Over the last 15 years, we have seen a huge expansion of the development of drugs directed against biomolecular targets within breast cancer cells. The over-expression of certain receptors (ER, PgR, HER-2, VEGF-R), as well as alteration of several intracellular signal transduction pathways (the PI3K-AKT-mTOR pathway, MEK-MAPK pathway, loss of PTEN, etc ...) has a great impact on the likelihood of recurrence and progression of the disease, influencing the natural history of breast cancer. The recent biomolecular classification of breast cancer (Luminal A / B, HER2- driven, Basal Like) allowed finally to identify specific treatments against molecular target to associate or not to traditional chemotherapy, and to use in relation to the prognosis of the disease. In the following paragraphs, we will set out the major targeted drug that have received indications in breast cancer, both in the localized and in advanced disease, referring to the specific target (hormonal receptors, HER2, VEG...

The Breast, 2017

Background: According to current guidelines, endocrine therapy (ET) is recommended as first-line ... more Background: According to current guidelines, endocrine therapy (ET) is recommended as first-line treatment of luminal-like metastatic breast cancer (MBC), whereas chemotherapy (CT) should be considered in presence of life-threatening disease. In daily practice, CT is often used outside of this clinical circumstance. Factors influencing first-line choice and the relative impact on outcome are unknown. Methods: A consecutive series of luminal-like HER2-negative MBC patients treated from 2004 to 2014 was analyzed to test the association of disease-and patient-related factors with the choice of first-line treatment (ET vs. CT). A propensity score method was used to estimate impact of first-line strategy on outcome. Results: Of 604 consecutive luminal-like MBC patients identified, 158 cases were excluded due to unknown or positive HER2-status. Among 446 HER2-negative cases, 171 (38%) received first-line CT. On multivariate analysis, the only factors significantly associated with lower CT use were old age (OR 0.25, 95%C.I. 0.13e0.49) or presence of bone metastases only (OR 0.26, 95%C.I. 0.13e0.53). In propensity score matched population, no differences were observed between CT and ET as first-line treatment either in terms of overall survival (37.5 months and 33.4 months respectively, log-rank test, P ¼ 0.62) or progression-free survival (13.3 months and 9.9 months respectively, log-rank test, P ¼ 0.92). Conclusions: High percentage of patients with luminal-like MBC received CT as first-line therapy in reallife. The choice was mainly driven by age and site of metastases. With the limitations of a nonrandomized comparison, no differences on patients' outcome were observed depending on the firstline strategy.

Expert Opinion on Pharmacotherapy, 2016

The introduction of Highly Active Antiretroviral Therapy (HAART) into clinical practice has drama... more The introduction of Highly Active Antiretroviral Therapy (HAART) into clinical practice has dramatically changed the outcome of HIV-infected patients by prolonging their survival. The increase in life expectancy has led to an increased risk of non-AIDS-related mortality and morbidity, including cardiovascular diseases, neurocognitive diseases, neuroendocrine dysfunctions and cancer.

Combination Products in Therapy, 2013

In the last few decades the approach to metastatic breast cancer (MBC) treatment using chemothera... more In the last few decades the approach to metastatic breast cancer (MBC) treatment using chemotherapy, either as single or combination agents, has been largely studied and a wide spectrum of therapeutic options is now available. Anthracyclines and taxanes remain the cornerstone of treatment in this setting. The choice of combination chemotherapy versus monochemotherapy is still open to debate since results from clinical trials are, unfortunately, conflicting. Despite improvements in response and disease-free survival rates, there has been no overall survival benefit reported although toxicity is increased. Therefore, based on available data, clinical decision-making for a busy practitioner should consider not only patient/tumor characteristics and the potential benefits of treatments, but also their toxicity profiles and patient preferences. Novel cytotoxic compounds have been approved for clinical use and combination regimens incorporating these agents may bring new treatment opportunities for MBC patients. In this review, we summarize the main achievements and the currently available and future combinations of cytotoxic drugs for patients with HER2-negative MBC.

Cancer Treatment Reviews, 2010

Breast cancer is not considered anymore a unique disease. Microarray gene expression analysis led... more Breast cancer is not considered anymore a unique disease. Microarray gene expression analysis led to the identification of 4 major breast cancer "intrinsic" subtypes, including hormone receptor (HR)-positive luminal A and B, human epidermal growth receptor 2 (HER2)-positive and basallike breast cancer (BLBC). These subtypes have distinct phenotypes, molecular profiles, clinical behaviour and response to therapy, with the BLBC carrying the worst outcome. Microarray analysis is not feasible in routine practice and therefore oncologists rely on a simpler immunohistochemical (IHC) classification to identify relevant breast cancer subtypes. Triple negative breast cancer (TNBC) is defined by the absence of oestrogen receptor, progesterone receptor and HER2 expression at IHC analysis. TNBC is strictly related to BLBC and, given the lack of common therapeutic targets, represent a major challenge for breast oncologist. In this review we will summarize the updated knowledge on TNBC, with emphasis on its current treatment and on the new therapeutic options under development.

International Journal of Molecular Sciences

ROS proto-oncogene 1 (ROS1) rearrangements occur in 0.9–2.6% of patients with non small cell lung... more ROS proto-oncogene 1 (ROS1) rearrangements occur in 0.9–2.6% of patients with non small cell lung cancer (NSCLC), conferring sensitivity to treatment with specific tyrosine-kinase inhibitors (TKI). Crizotinib, a first-generation TKI, was the first target-therapy approved for the first-line treatment of ROS1-positive NSCLC. Recently, entrectinib, a multitarget inhibitor with an anti-ROS1 activity 40 times more potent than crizotinib and better activity on the central nervous system (CNS), received approval for treatment-naive patients. After a median time-to-progression of 5.5–20 months, resistance mechanisms can occur, leading to tumor progression. Therefore, newer generation TKI with greater potency and brain penetration have been developed and are currently under investigation. This review summarizes the current knowledge on clinicopathological characteristics of ROS1-positive NSCLC and its therapeutic options.

Journal of Thoracic Oncology

In Vivo, 2021

Background: Osimertinib is a third-generation EGFR-tyrosine kinase inhibitor approved for the tre... more Background: Osimertinib is a third-generation EGFR-tyrosine kinase inhibitor approved for the treatment of T790M-positive non-small-cell lung cancer. More recently, osimertinib demonstrated improved disease control compared to other EGFR-TKIs. Multiple mechanisms of resistance have been described in T790M-positive patients who experienced treatment failure with osimertinib. Case Report: We report the case of a 78-year-old non-smoker woman with stage IV EGFR L858R-positive lung adenocarcinoma presented with T790M mutation after five years of treatment with gefitinib. The patient was started on osimertinib, but after two and a half years of treatment experienced disease progression. The analyses of circulating tumor DNA using next-generation sequencing showed, together with the pre-existing T790M and exon 21 L858R, the presence of the EGFR C797G resistance mutation. Conclusion: Our case report revealed a rare EGFRdependent acquired resistance mutation to osimertinib in circulating tumor DNA. Liquid biopsy appears to be a promising resource to understand the biology of osimertinib resistance by clonal evolution monitoring and the identification of novel resistance mechanisms.

BMC cancer, Feb 6, 2018

Metastases to the thyroid gland are more frequent than previously thought, although most of them ... more Metastases to the thyroid gland are more frequent than previously thought, although most of them are occult or not clinically relevant. Overall, only 42 cases of metastases to thyroid from breast cancer have been reported thus far. Here we report the case of a patient with breast cancer metastatic to the thyroid. We also review the 42 previously reported cases (published between 1962 and 2012). This is the first review about metastases to thyroid gland from breast cancer. A 64-year-old woman of Caucasian origin was diagnosed with a lobular invasive carcinoma of the breast (luminal A, stage II). She received adjuvant chemotherapy, followed by endocrine therapy. During follow-up, fine-needle cytology of a thyroid nodule revealed malignant cells that were estrogen-positive, which suggested a diagnosis of metastases to the thyroid. Imaging did not reveal any other metastatic site and showed only enlargement of the left thyroid lobe and an inhomogeneous pattern of colloid and cystic dege...

Oncotarget, 2017

HCC represents the sixth most common cancer worldwide and the second leading cause of cancer-rela... more HCC represents the sixth most common cancer worldwide and the second leading cause of cancer-related death. Despite the high incidence, treatment options for advanced HCC remain limited and unsuccessful, resulting in a poor prognosis. Despite the major advances achieved in the diagnostic management of HCC, only one third of the newly diagnosed patients are presently eligible for curative treatments. Advances in technology and an increased understanding of HCC biology have led to the discovery of novel biomarkers. Improving our knowledge about serum and tissutal markers could ultimately lead to an early diagnosis and better and early treatment strategies for this deadly disease. Serum biomarkers are striking potential tools for surveillance and early diagnosis of HCC thanks to the non-invasive, objective, and reproducible assessments they potentially enable. To date, many biomarkers have been proposed in the diagnosis of HCC. Cholangiocarcinoma (CCA) is an aggressive malignancy, characterized by early lymph node involvement and distant metastasis, with 5-year survival rates of 5%-10%. The identification of new biomarkers with diagnostic, prognostic or predictive value is especially important as resection (by surgery or combined with a liver transplant) has shown promising results and novel therapies are emerging. However, the relatively low incidence of CCA, high frequency of co-existing cholestasis or cholangitis (primary sclerosing cholangitis-PSC-above all), and difficulties with obtaining adequate samples, despite advances in sampling techniques and in endoscopic visualization of the bile ducts, have complicated the search for accurate biomarkers. In this review, we attempt to analyze the existing literature on this argument. HEPATOCELLULAR CARCINOMA

European review for medical and pharmacological sciences, 2015

To study the expression of programmed death-ligand1 (PD-L1) in hepatocellular carcinoma and its r... more To study the expression of programmed death-ligand1 (PD-L1) in hepatocellular carcinoma and its relationship with clinicopathological characteristics and, prognosis of hepatocellular carcinoma and APE1, P53 protein expression levels. A total of 128 patients with hepatocellular carcinoma were enrolled in this study. The expression of PD-L1, APE1 and P53 were detected by immunohistochemistry.Use immunohistochemical ABC staining method to detect the expression levels of PD-L1, APE1 and P53 protein in the hepatocellular carcinoma of 128 cases. Positive The positive expression rates levels of PD-L1, APE1, and P53 protein in hepatocellular carcinoma tissues are were 82.03%, 92.19%, and 60.94%. PD-L1 positive expression were significantly associated with clinical stage, The PD-L1 protein has a high expression in patients with I ~ II stage liver cancerHBV infection positive and nonportal vein thrombosis (p=0.041; p=0.030; p=0.014). It is inversely correlated with P53 and PD-L1 expression (c...