Miriam Lobo - Academia.edu (original) (raw)

Papers by Miriam Lobo

Journal of Thoracic Oncology, Oct 1, 2018

Clinical & Translational Oncology, May 23, 2018

Oncology, 2016

To analyse the evolution of a multidisciplinary heredofamilial cancer unit (HFCU) in a university... more To analyse the evolution of a multidisciplinary heredofamilial cancer unit (HFCU) in a university hospital. This was a retrospective analysis of the activity of our HFCU in its first 5 years of existence. Between July 2010 and July 2015, 1,518 patients from 1,318 families attended our HFCU. Genetic testing was offered to 862 patients. Of those, 833 (96.6%) accepted testing, with available results for 636 (76.4%). Pathogenic mutations in BRCA1 and BRCA2 were found in 175 patients. Lynch syndrome and adenomatous polyposis were the most frequent syndromes diagnosed (151/175, 86.3%) among 17 different syndromes studied. Of the 404 patients without a previous genetic diagnosis in the family, 62 (15.3%) were found to have mutations in disease-causing genes. Prophylactic surgery and follow-up (33.7%) or follow-up only (66.3%) was proposed for mutation carriers according to international guidelines and patients' preferences. We have a high mutation detection rate, genetic test acceptance, and compliance with risk reduction strategies. However, there is room for improvement, especially in genetic testing timing, considering that an increase in the indications for genetic testing is expected.

Archives of Clinical and Medical Case Reports

Introduction: Biliary tract cancer (BTC) is an uncommon tumor with bad prognosis. There is no cur... more Introduction: Biliary tract cancer (BTC) is an uncommon tumor with bad prognosis. There is no curative treatment for patients with unresectable disease at diagnosis. There is a limited experience with second-line chemotherapy in advanced BTC since clinical trials are difficult to perform due to the rarity and heterogeneity of these tumors. Recent molecular studies have increased our understanding of the pathogenetic mechanism that underly the development of cholangiocarcinoma. These will help us to determine the significance of molecular alterations that occur in this disease and will direct the development of targeted therapy. Case Report: This case report describes a radiological complete response after three cycles of second-line chemotherapy with the combination of capecitabine and oxaliplatin in a patient with unresectable extrahepatic cholangiocarcinoma, after treatment with the combination of gemcitabine and cisplatin as first-line chemotherapy. Conclusion: Our case suggests that selected patients may demonstrate very good responses to chemotherapy. There is an urgent need to identify different molecular subtypes that could direct management of these patients.

Journal of genetic counseling, Jan 15, 2017

The identification of patients at risk for breast cancer by genetic testing has proven to reduce ... more The identification of patients at risk for breast cancer by genetic testing has proven to reduce breast cancer mortality. In 2010, due to a lack of systematization in hereditary cancer assistance in our center, we implemented a multidisciplinary Heredofamilial Cancer Unit (HFCU). We analyze if the HFCU improved the rates of referrals and preventive management of breast cancer patients with genetic risk. We retrospectively compared family history records, referrals of high-risk patients to genetic counseling, and detection and management of patients with BRCA1/2 mutations in two cohorts of breast cancer patients diagnosed before (first period: 2007-2010) and after the creation of the HFCU (second period: 2010-2013). In the first period, 893 patients were included, and 902 were included in the second. Due to the inability to establish their genetic risk, 142 patients (15.9%) vs. 70 (7.8%) were excluded from analysis (p < 0.001). Among the evaluable patients, 194 (25.8%) vs. 223 (26...

Breast Cancer Research and Treatment, 2016

In an era where neoadjuvant dual blockade is emerging as the standard of care for early and local... more In an era where neoadjuvant dual blockade is emerging as the standard of care for early and locally advanced HER2-positive breast cancer, we aimed to identify predictors of response to single-blockade chemotherapy. This retrospective analysis reviewed all the incident stage I-III HER2-positive breast cancer patients who received neoadjuvant docetaxel, carboplatin, and trastuzumab (TCH) in three institutions. pCR was defined as the absence of invasive tumor in breast and axillary nodes (ypT0/isypN0). From 2008 to 2015, 84 patients receiving neoadjuvant TCH were identified within our institutions. The mean age at diagnosis was 51.8 years. 59.5% of the patients were hormone receptor (HR) positive, lymph node involvement occurred in 67.9%, and clinical distribution was 2.4, 65.5, and 32.1% for stage I, II, and III, respectively. pCR rate was 47.6%; there was a significantly lower response in HR-positive patients compared to HR-negative ones (34 vs 67.6%, p = 0.005). pCR rate was associated with tumor size, whereas differences did not reach significance either for stage or for nodal status. Multivariate analysis found that only HR status was associated with response (p = 0.003). At a median follow-up of 31.7 months, disease-free survival, distant disease-free survival, and overall survival were 78.6, 85.7, and 94%, respectively. Breast-conserving surgery was performed in 44% of the patients. Overall, TCH was well tolerated, with low rates of grade 3-4 adverse events, and neither late toxicities nor cardiac dysfunctions were reported. Neoadjuvant TCH, an anthracycline-free single-blockade regimen, achieved a pCR of 47.6%. Further molecular analyses are required in order to identify stronger predictive markers of pCR and thus for an accurate selection of patients who do not benefit from dual blockade.

Breast Cancer Research and Treatment, 2016

We describe the status and frequency of germline DNA genetic findings in an unselected prospectiv... more We describe the status and frequency of germline DNA genetic findings in an unselected prospective cohort of triple negative breast cancer patients participating in a platinum-based neoadjuvant chemotherapy trial. Study population includes 124 consecutive patients with stage II-III TNBC from a trial exploring the antitumor activity of neoadjuvant carboplatin/docetaxel chemotherapy enrolled between 2012 and March 2015, to determine the frequency of germline DNA genetic mutations. 17.1 % of the patients with germline DNA tested had deleterious mutations in any of the analyzed genes (12.38 % in BRCA1, 1.9 % in BRCA2 and BARD1 and 0.95 % in RAD51D). Attending the intrinsic subtype, all the BRCA1/2 carriers tested had basal-like subtype. Among wild-type (WT) patients, 70.11 % had basal subtype, 16.09 % HER2 enriched, 1.15 % Luminal B, and 4.60 % Normal-like. Mean age at diagnosis was significantly lower in mutation-carriers compared with no carriers (43.72 vs 53.10, p = 0.004). 3 BRCA1/2 carriers were detected between 51 and 60 years, and only one deleterious mutation (BARD1) over 60 years. A positive familiar history of breast and ovarian cancer was more frequent in patients with deleterious mutations (39.39 vs 17.94 %, p = 0.043). Our study confirms the prevalence of BRCA1/2 mutations in TNBC patients. TNBC should therefore be considered by itself as a criterion for BRCA1/2 genetic testing. Determination of other breast cancer predisposition genes implicated in homologous recombination should also be discussed in this population. However, no definitive conclusions can be reached due to the low prevalence and the uncertain clinical impact of most of the genes included.

Current Breast Cancer Reports, 2014

A precise knowledge of cell-cycle machinery and its effect on tumorigenesis has led to the develo... more A precise knowledge of cell-cycle machinery and its effect on tumorigenesis has led to the development of a large number of anticancer drugs targeting this pathway. In breast cancer research, the promising results of recent clinical trials of novel selective CDK-inhibitors, for example palbociclib, have generated high expectations for this field. This review gathers the results of the most recent clinical trials of CDK inhibitors for breast cancer, and outlines their potential as anticancer therapy.

Breast cancer research and treatment, Sep 18, 2017

SUMMARY : Over the past two decades significant progress has been made in breast cancer treatment... more SUMMARY : Over the past two decades significant progress has been made in breast cancer treatment resulting in a substantial improvement in patients9 outcome. But we have to think about who promotes all this research and the consequences of the type of fundingThis project aims to evaluate the implication of finance in clinical research and the variance according to the type of funding. OBJETIVES : To evaluate the financial evolvement of breast cancer clinical trials in the past two decades, regarding the phase of development design of the studies, the collaboration between Academy (Acad) and Industry (Ind), the sample size, the study results and the statistical analyses conducted. METHODS: A systematic review was performed using MEDLINE to identify breast cancer randomized clinical trials published between January1990 and December2010. Studies that involved chemotherapy, endocrine and/or targeted therapies, wherethe primary endpoint was considered adequate to support a drug approval...

Chinese Clinical Oncology

Introduction: Biliary tract cancer (BTC) is an uncommon tumor with bad prognosis. There is no cur... more Introduction: Biliary tract cancer (BTC) is an uncommon tumor with bad prognosis. There is no curative treatment for patients with unresectable disease at diagnosis. There is a limited experience with second-line chemotherapy in advanced BTC since clinical trials are difficult to perform due to the rarity and heterogeneity of these tumors. Recent molecular studies have increased our understanding of the pathogenetic mechanism that underly the development of cholangiocarcinoma. These will help us to determine the significance of molecular alterations that occur in this disease and will direct the development of targeted therapy. Case Report: This case report describes a radiological complete response after three cycles of second-line chemotherapy with the combination of capecitabine and oxaliplatin in a patient with unresectable extrahepatic cholangiocarcinoma, after treatment with the combination of gemcitabine and cisplatin as first-line chemotherapy. Conclusion: Our case suggests that selected patients may demonstrate very good responses to chemotherapy. There is an urgent need to identify different molecular subtypes that could direct management of these patients.

World Journal of Clinical Cases, Jul 26, 2019

Biliary tract cancer, or cholangiocarcinoma, comprises a heterogeneous group of malignant tumors ... more Biliary tract cancer, or cholangiocarcinoma, comprises a heterogeneous group of malignant tumors that can emerge at any part of the biliary tree. This group is the second most common type of primary liver cancer. Diagnosis is usually based on symptoms, which may be heterogeneous, and nonspecific biomarkers in serum and biopsy specimens, as well as on imaging techniques. Endoscopy-based diagnosis is essential, since it enables biopsy specimens to be taken. In addition, it can help with locoregional staging of distal tumors. Endoscopic retrograde cholangiopancreatography is a key technique for the evaluation and treatment of malignant biliary tumors. Correct staging of cholangiocarcinoma is essential in order to be able to determine the degree of resectability and assess the results of treatment. The tumor is staged based on the TNM classification of the American Joint Committee on Cancer. The approach will depend on the classification of the tumor. Thus, some patients with early-stage disease could benefit from surgery; complete surgical resection is the cornerstone of cure. However, only a minority of patients are diagnosed in the early stages and are suitable candidates for resection. In the subset of patients diagnosed with locally advanced or metastatic disease, chemotherapy has been used to improve outcome and to delay tumor progression. The approach to biliary tract tumors should be multidisciplinary, involving experienced endoscopists, oncologists, radiologists, and surgeons.

Journal of Thoracic Oncology, Oct 1, 2018

Clinical & Translational Oncology, May 23, 2018

Oncology, 2016

To analyse the evolution of a multidisciplinary heredofamilial cancer unit (HFCU) in a university... more To analyse the evolution of a multidisciplinary heredofamilial cancer unit (HFCU) in a university hospital. This was a retrospective analysis of the activity of our HFCU in its first 5 years of existence. Between July 2010 and July 2015, 1,518 patients from 1,318 families attended our HFCU. Genetic testing was offered to 862 patients. Of those, 833 (96.6%) accepted testing, with available results for 636 (76.4%). Pathogenic mutations in BRCA1 and BRCA2 were found in 175 patients. Lynch syndrome and adenomatous polyposis were the most frequent syndromes diagnosed (151/175, 86.3%) among 17 different syndromes studied. Of the 404 patients without a previous genetic diagnosis in the family, 62 (15.3%) were found to have mutations in disease-causing genes. Prophylactic surgery and follow-up (33.7%) or follow-up only (66.3%) was proposed for mutation carriers according to international guidelines and patients&amp;amp;amp;amp;amp;amp;#39; preferences. We have a high mutation detection rate, genetic test acceptance, and compliance with risk reduction strategies. However, there is room for improvement, especially in genetic testing timing, considering that an increase in the indications for genetic testing is expected.

Archives of Clinical and Medical Case Reports

Introduction: Biliary tract cancer (BTC) is an uncommon tumor with bad prognosis. There is no cur... more Introduction: Biliary tract cancer (BTC) is an uncommon tumor with bad prognosis. There is no curative treatment for patients with unresectable disease at diagnosis. There is a limited experience with second-line chemotherapy in advanced BTC since clinical trials are difficult to perform due to the rarity and heterogeneity of these tumors. Recent molecular studies have increased our understanding of the pathogenetic mechanism that underly the development of cholangiocarcinoma. These will help us to determine the significance of molecular alterations that occur in this disease and will direct the development of targeted therapy. Case Report: This case report describes a radiological complete response after three cycles of second-line chemotherapy with the combination of capecitabine and oxaliplatin in a patient with unresectable extrahepatic cholangiocarcinoma, after treatment with the combination of gemcitabine and cisplatin as first-line chemotherapy. Conclusion: Our case suggests that selected patients may demonstrate very good responses to chemotherapy. There is an urgent need to identify different molecular subtypes that could direct management of these patients.

Journal of genetic counseling, Jan 15, 2017

The identification of patients at risk for breast cancer by genetic testing has proven to reduce ... more The identification of patients at risk for breast cancer by genetic testing has proven to reduce breast cancer mortality. In 2010, due to a lack of systematization in hereditary cancer assistance in our center, we implemented a multidisciplinary Heredofamilial Cancer Unit (HFCU). We analyze if the HFCU improved the rates of referrals and preventive management of breast cancer patients with genetic risk. We retrospectively compared family history records, referrals of high-risk patients to genetic counseling, and detection and management of patients with BRCA1/2 mutations in two cohorts of breast cancer patients diagnosed before (first period: 2007-2010) and after the creation of the HFCU (second period: 2010-2013). In the first period, 893 patients were included, and 902 were included in the second. Due to the inability to establish their genetic risk, 142 patients (15.9%) vs. 70 (7.8%) were excluded from analysis (p < 0.001). Among the evaluable patients, 194 (25.8%) vs. 223 (26...

Breast Cancer Research and Treatment, 2016

In an era where neoadjuvant dual blockade is emerging as the standard of care for early and local... more In an era where neoadjuvant dual blockade is emerging as the standard of care for early and locally advanced HER2-positive breast cancer, we aimed to identify predictors of response to single-blockade chemotherapy. This retrospective analysis reviewed all the incident stage I-III HER2-positive breast cancer patients who received neoadjuvant docetaxel, carboplatin, and trastuzumab (TCH) in three institutions. pCR was defined as the absence of invasive tumor in breast and axillary nodes (ypT0/isypN0). From 2008 to 2015, 84 patients receiving neoadjuvant TCH were identified within our institutions. The mean age at diagnosis was 51.8 years. 59.5% of the patients were hormone receptor (HR) positive, lymph node involvement occurred in 67.9%, and clinical distribution was 2.4, 65.5, and 32.1% for stage I, II, and III, respectively. pCR rate was 47.6%; there was a significantly lower response in HR-positive patients compared to HR-negative ones (34 vs 67.6%, p = 0.005). pCR rate was associated with tumor size, whereas differences did not reach significance either for stage or for nodal status. Multivariate analysis found that only HR status was associated with response (p = 0.003). At a median follow-up of 31.7 months, disease-free survival, distant disease-free survival, and overall survival were 78.6, 85.7, and 94%, respectively. Breast-conserving surgery was performed in 44% of the patients. Overall, TCH was well tolerated, with low rates of grade 3-4 adverse events, and neither late toxicities nor cardiac dysfunctions were reported. Neoadjuvant TCH, an anthracycline-free single-blockade regimen, achieved a pCR of 47.6%. Further molecular analyses are required in order to identify stronger predictive markers of pCR and thus for an accurate selection of patients who do not benefit from dual blockade.

Breast Cancer Research and Treatment, 2016

We describe the status and frequency of germline DNA genetic findings in an unselected prospectiv... more We describe the status and frequency of germline DNA genetic findings in an unselected prospective cohort of triple negative breast cancer patients participating in a platinum-based neoadjuvant chemotherapy trial. Study population includes 124 consecutive patients with stage II-III TNBC from a trial exploring the antitumor activity of neoadjuvant carboplatin/docetaxel chemotherapy enrolled between 2012 and March 2015, to determine the frequency of germline DNA genetic mutations. 17.1 % of the patients with germline DNA tested had deleterious mutations in any of the analyzed genes (12.38 % in BRCA1, 1.9 % in BRCA2 and BARD1 and 0.95 % in RAD51D). Attending the intrinsic subtype, all the BRCA1/2 carriers tested had basal-like subtype. Among wild-type (WT) patients, 70.11 % had basal subtype, 16.09 % HER2 enriched, 1.15 % Luminal B, and 4.60 % Normal-like. Mean age at diagnosis was significantly lower in mutation-carriers compared with no carriers (43.72 vs 53.10, p = 0.004). 3 BRCA1/2 carriers were detected between 51 and 60 years, and only one deleterious mutation (BARD1) over 60 years. A positive familiar history of breast and ovarian cancer was more frequent in patients with deleterious mutations (39.39 vs 17.94 %, p = 0.043). Our study confirms the prevalence of BRCA1/2 mutations in TNBC patients. TNBC should therefore be considered by itself as a criterion for BRCA1/2 genetic testing. Determination of other breast cancer predisposition genes implicated in homologous recombination should also be discussed in this population. However, no definitive conclusions can be reached due to the low prevalence and the uncertain clinical impact of most of the genes included.

Current Breast Cancer Reports, 2014

A precise knowledge of cell-cycle machinery and its effect on tumorigenesis has led to the develo... more A precise knowledge of cell-cycle machinery and its effect on tumorigenesis has led to the development of a large number of anticancer drugs targeting this pathway. In breast cancer research, the promising results of recent clinical trials of novel selective CDK-inhibitors, for example palbociclib, have generated high expectations for this field. This review gathers the results of the most recent clinical trials of CDK inhibitors for breast cancer, and outlines their potential as anticancer therapy.

Breast cancer research and treatment, Sep 18, 2017

SUMMARY : Over the past two decades significant progress has been made in breast cancer treatment... more SUMMARY : Over the past two decades significant progress has been made in breast cancer treatment resulting in a substantial improvement in patients9 outcome. But we have to think about who promotes all this research and the consequences of the type of fundingThis project aims to evaluate the implication of finance in clinical research and the variance according to the type of funding. OBJETIVES : To evaluate the financial evolvement of breast cancer clinical trials in the past two decades, regarding the phase of development design of the studies, the collaboration between Academy (Acad) and Industry (Ind), the sample size, the study results and the statistical analyses conducted. METHODS: A systematic review was performed using MEDLINE to identify breast cancer randomized clinical trials published between January1990 and December2010. Studies that involved chemotherapy, endocrine and/or targeted therapies, wherethe primary endpoint was considered adequate to support a drug approval...

Chinese Clinical Oncology

Introduction: Biliary tract cancer (BTC) is an uncommon tumor with bad prognosis. There is no cur... more Introduction: Biliary tract cancer (BTC) is an uncommon tumor with bad prognosis. There is no curative treatment for patients with unresectable disease at diagnosis. There is a limited experience with second-line chemotherapy in advanced BTC since clinical trials are difficult to perform due to the rarity and heterogeneity of these tumors. Recent molecular studies have increased our understanding of the pathogenetic mechanism that underly the development of cholangiocarcinoma. These will help us to determine the significance of molecular alterations that occur in this disease and will direct the development of targeted therapy. Case Report: This case report describes a radiological complete response after three cycles of second-line chemotherapy with the combination of capecitabine and oxaliplatin in a patient with unresectable extrahepatic cholangiocarcinoma, after treatment with the combination of gemcitabine and cisplatin as first-line chemotherapy. Conclusion: Our case suggests that selected patients may demonstrate very good responses to chemotherapy. There is an urgent need to identify different molecular subtypes that could direct management of these patients.

World Journal of Clinical Cases, Jul 26, 2019

Biliary tract cancer, or cholangiocarcinoma, comprises a heterogeneous group of malignant tumors ... more Biliary tract cancer, or cholangiocarcinoma, comprises a heterogeneous group of malignant tumors that can emerge at any part of the biliary tree. This group is the second most common type of primary liver cancer. Diagnosis is usually based on symptoms, which may be heterogeneous, and nonspecific biomarkers in serum and biopsy specimens, as well as on imaging techniques. Endoscopy-based diagnosis is essential, since it enables biopsy specimens to be taken. In addition, it can help with locoregional staging of distal tumors. Endoscopic retrograde cholangiopancreatography is a key technique for the evaluation and treatment of malignant biliary tumors. Correct staging of cholangiocarcinoma is essential in order to be able to determine the degree of resectability and assess the results of treatment. The tumor is staged based on the TNM classification of the American Joint Committee on Cancer. The approach will depend on the classification of the tumor. Thus, some patients with early-stage disease could benefit from surgery; complete surgical resection is the cornerstone of cure. However, only a minority of patients are diagnosed in the early stages and are suitable candidates for resection. In the subset of patients diagnosed with locally advanced or metastatic disease, chemotherapy has been used to improve outcome and to delay tumor progression. The approach to biliary tract tumors should be multidisciplinary, involving experienced endoscopists, oncologists, radiologists, and surgeons.