Evandro de Azambuja

Neoadjuvant chemotherapy plus trastuzumab (NCT) increases the rate of pathological complete response (pCR) and event-free survival (EFS) compared to neoadjuvant chemotherapy (NC) alone in women with HER2 positive breast cancer (BC). pCR in this setting is associated with improved EFS. Whether NCT preferentially improves EFS in comparison to NC followed by adjuvant trastuzumab initiated postoperatively (NCAT) has not been addressed. Using clinical data from women with HER2 positive BC treated at… Show more

Neoadjuvant chemotherapy plus trastuzumab (NCT) increases the rate of pathological complete response (pCR) and event-free survival (EFS) compared to neoadjuvant chemotherapy (NC) alone in women with HER2 positive breast cancer (BC). pCR in this setting is associated with improved EFS. Whether NCT preferentially improves EFS in comparison to NC followed by adjuvant trastuzumab initiated postoperatively (NCAT) has not been addressed. Using clinical data from women with HER2 positive BC treated at 7 European institutions between 2007 and 2010 we sought to investigate the impact on breast cancer outcomes of concomitant (NCT) versus sequential (NCAT) treatment in HER2 positive early BC. The unadjusted hazard ratio (HR) for event free survival with NCT compared with NCAT was 0.63 (95% CI 0.37-1.08; p = 0.091). Multivariable analysis revealed that treatment group, tumour size and ER status were significantly associated with EFS from diagnosis. In the whole group NCT was associated with a reduced risk of an event relative to NCAT, an effect that was confined to ER negative (HR: 0.25; 95% CI, 0.10-0.62; p = 0.003) as opposed to ER positive tumours (HR: 1.07; 95% CI, 0.46-2.52; p = 0.869). HER2 positive/ER negative BC treated with NC gain greatest survival benefit when trastuzumab is administered in both the neoadjuvant and adjuvant period rather than in the adjuvant period alone. These data support the early introduction of targeted combination therapy in HER2 positive/ER negative BC. Show less

PURPOSE:
We compared efficacy of trastuzumab versus no trastuzumab in patients with small (≤ 2 cm) human epidermal growth factor receptor 2 (HER2) -positive breast cancer treated in randomized trials.
METHODS:
A meta-analysis was conducted using data from five of the six adjuvant trastuzumab trials. Efficacy end points were disease-free survival (DFS) and overall survival (OS). Separate analyses were prospectively planned for hormone receptor (HR) -positive and HR-negative cohorts… Show more

PURPOSE:
We compared efficacy of trastuzumab versus no trastuzumab in patients with small (≤ 2 cm) human epidermal growth factor receptor 2 (HER2) -positive breast cancer treated in randomized trials.
METHODS:
A meta-analysis was conducted using data from five of the six adjuvant trastuzumab trials. Efficacy end points were disease-free survival (DFS) and overall survival (OS). Separate analyses were prospectively planned for hormone receptor (HR) -positive and HR-negative cohorts. Random effect models and Yusuf-Peto fixed effects models assessed the impact of heterogeneity on baseline hazards and treatment effects across studies. Peto-Pike cumulative incidence estimates were stratified by study and nodal status.
RESULTS:
Median follow-up time was 8 years. For 2,263 patients with HR-positive disease, 8-year cumulative incidence rates comparing trastuzumab versus no trastuzumab were 17.3% versus 24.3% (P < .001) for DFS and 7.8% versus 11.6% (P = .005) for OS, respectively; for 1,092 HR-positive patients with zero or one positive lymph nodes, results were 12.7% versus 19.4% (P = .005) for DFS and 5.3% versus 7.4% (P = .12) for OS, respectively. For 1,957 patients with HR-negative disease, 8-year cumulative incidence rates were 24.0% versus 33.4% (P < .001) for DFS and 12.4% versus 21.2% (P < .001) for OS, respectively; for 1,040 HR-negative patients with zero or one positive lymph nodes, results were 20.4% versus 26.3% (P = .05) for DFS and 8.2% versus 12.2% (P = .084) for OS, respectively.
CONCLUSION:
Women with HER2-positive tumors ≤ 2 cm in the randomized trastuzumab trials derived substantial DFS and OS benefit from adjuvant trastuzumab. Trastuzumab-treated patients with HR-positive disease and ≤ one positive lymph node may be candidates for trials assessing less aggressive treatment approaches. Show less

Demographic changes in the world population will cause a significant increase in the number of new cases of cancer. To handle this challenge, societies will need to adapt how they approach cancer prevention and treatment, with changes to the development and uptake of innovative anticancer drugs playing an important role. However, there are obstacles to implementing innovative drugs in clinical practice. Prior to being incorporated into daily practice, the drug must obtain regulatory and… Show more

Demographic changes in the world population will cause a significant increase in the number of new cases of cancer. To handle this challenge, societies will need to adapt how they approach cancer prevention and treatment, with changes to the development and uptake of innovative anticancer drugs playing an important role. However, there are obstacles to implementing innovative drugs in clinical practice. Prior to being incorporated into daily practice, the drug must obtain regulatory and reimbursement approval, succeed in changing the prescription habits of physicians, and ultimately gain the compliance of individual patients. Developing an anticancer drug and bringing it into clinical practice is, therefore, a lengthy and complex process involving multiple partners in several areas. To optimize patient treatment and increase the likelihood of implementing health innovation, it is essential to have an overview of the full process. This review aims to describe the process and discuss the hurdles arising at each step. Show less

Background: The development of trastuzumab is considered to be one of the greatest improvements in breast cancer treatment in recent years. This study aims to evaluate changes in the clinical use of trastuzumab over the last 12 years and to determine whether its use is proportional to patient needs in the European Union and the USA.
Methods: Using national registry data, the number of new cases of HER2-positive breast cancer patients per year was estimated. The number of likely trastuzumab… Show more

Background: The development of trastuzumab is considered to be one of the greatest improvements in breast cancer treatment in recent years. This study aims to evaluate changes in the clinical use of trastuzumab over the last 12 years and to determine whether its use is proportional to patient needs in the European Union and the USA.
Methods: Using national registry data, the number of new cases of HER2-positive breast cancer patients per year was estimated. The number of likely trastuzumab treatments per year was estimated using trastuzumab procurement data for each country. Usage trends were evaluated by linear regression. Variations in patterns of use before and after trastuzumab approval in the adjuvant setting were undertaken using the Wald test.
Results: Western Europe and the USA procure a quantity of trastuzumab sufficient to treat virtually all patients in need. Procurement trends have varied over the years; before approval in the adjuvant setting, Western European countries and the USA indicate trastuzumab use proportional to their needs. After this approval, the number of patients needing trastuzumab increased, and there was a lag of several years before proportional use was again reached. However, few countries in Eastern Europe acquired the needed quantity of trastuzumab, with procurement levels in these countries starting to increase only after approval in the adjuvant setting.
Conclusion: Significant differences in trastuzumab procurement are observed between Western Europe, the USA and Eastern Europe, with the latter geographic region acquiring insufficient amounts of the drug required to treat all patients in need. Show less

Background: The development of trastuzumab is considered to be one of the greatest improvements in breast cancer treatment in recent years. This study aims to evaluate changes in the clinical use of trastuzumab over the last 12 years and to determine whether its use is proportional to patient needs in the European Union and the USA.
Methods: Using national registry data, the number of new cases of HER2-positive breast cancer patients per year was estimated. The number of likely trastuzumab… Show more

Background: The development of trastuzumab is considered to be one of the greatest improvements in breast cancer treatment in recent years. This study aims to evaluate changes in the clinical use of trastuzumab over the last 12 years and to determine whether its use is proportional to patient needs in the European Union and the USA.
Methods: Using national registry data, the number of new cases of HER2-positive breast cancer patients per year was estimated. The number of likely trastuzumab treatments per year was estimated using trastuzumab procurement data for each country. Usage trends were evaluated by linear regression. Variations in patterns of use before and after trastuzumab approval in the adjuvant setting were undertaken using the Wald test.
Results: Western Europe and the USA procure a quantity of trastuzumab sufficient to treat virtually all patients in need. Procurement trends have varied over the years; before approval in the adjuvant setting, Western European countries and the USA indicate trastuzumab use proportional to their needs. After this approval, the number of patients needing trastuzumab increased, and there was a lag of several years before proportional use was again reached. However, few countries in Eastern Europe acquired the needed quantity of trastuzumab, with procurement levels in these countries starting to increase only after approval in the adjuvant setting.
Conclusion: Significant differences in trastuzumab procurement are observed between Western Europe, the USA and Eastern Europe, with the latter geographic region acquiring insufficient amounts of the drug required to treat all patients in need.
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Background: The development of trastuzumab is considered to be one of the greatest improvements in breast cancer treatment in recent years. This study aims to evaluate changes in the clinical use of trastuzumab over the last 12 years and to determine whether its use is proportional to patient needs in the European Union and the USA.
Methods: Using national registry data, the number of new cases of HER2-positive breast cancer patients per year was estimated. The number of likely trastuzumab… Show more

Background: The development of trastuzumab is considered to be one of the greatest improvements in breast cancer treatment in recent years. This study aims to evaluate changes in the clinical use of trastuzumab over the last 12 years and to determine whether its use is proportional to patient needs in the European Union and the USA.
Methods: Using national registry data, the number of new cases of HER2-positive breast cancer patients per year was estimated. The number of likely trastuzumab treatments per year was estimated using trastuzumab procurement data for each country. Usage trends were evaluated by linear regression. Variations in patterns of use before and after trastuzumab approval in the adjuvant setting were undertaken using the Wald test.
Results: Western Europe and the USA procure a quantity of trastuzumab sufficient to treat virtually all patients in need. Procurement trends have varied over the years; before approval in the adjuvant setting, Western European countries and the USA indicate trastuzumab use proportional to their needs. After this approval, the number of patients needing trastuzumab increased, and there was a lag of several years before proportional use was again reached. However, few countries in Eastern Europe acquired the needed quantity of trastuzumab, with procurement levels in these countries starting to increase only after approval in the adjuvant setting.
Conclusion: Significant differences in trastuzumab procurement are observed between Western Europe, the USA and Eastern Europe, with the latter geographic region acquiring insufficient amounts of the drug required to treat all patients in need.
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ene expression profiling has reshaped our understanding of breast cancer by defining and characterizing four main intrinsic molecular subtypes: human epidermal growth factor receptor 2–enriched, basal-like, luminal A, and luminal B subtypes. Luminal B breast cancer has been reported to have lower expression of hormone receptors, higher expression of proliferation markers, and higher histologic grade than luminal A. It also exhibits worse prognosis and has a distinct profile of response to… Show more

ene expression profiling has reshaped our understanding of breast cancer by defining and characterizing four main intrinsic molecular subtypes: human epidermal growth factor receptor 2–enriched, basal-like, luminal A, and luminal B subtypes. Luminal B breast cancer has been reported to have lower expression of hormone receptors, higher expression of proliferation markers, and higher histologic grade than luminal A. It also exhibits worse prognosis and has a distinct profile of response to hormone therapy and chemotherapy. Although luminal cancers share similarities, the studies conducted in recent years using next-generation sequencing technology show that luminal A and B breast cancers should be perceived as distinct entities, with specific oncogenic drivers, rather than more proliferative varieties of luminal tumors. This review discusses the definition and molecular characterization of luminal B breast cancer and presents the available clinical evidence for chemotherapy and endocrine therapy patterns of response. It also provides an overview of ongoing research on molecularly targeted agents for this disease. Show less

Whereas cancer incidence is higher in high and middle income countries, cancer survival is lower in low income countries. In this analysis we investigated the relationship between health expenditure and cancer-related survival in 168 countries. Methods: Health expenditure data from 168 countries and cancer indicators data from 28 cancer types from the same countries were extracted from the World Bank (WB) and the WHO databases. The mortality/incidence ratio was calculated to evaluate the… Show more

Whereas cancer incidence is higher in high and middle income countries, cancer survival is lower in low income countries. In this analysis we investigated the relationship between health expenditure and cancer-related survival in 168 countries. Methods: Health expenditure data from 168 countries and cancer indicators data from 28 cancer types from the same countries were extracted from the World Bank (WB) and the WHO databases. The mortality/incidence ratio was calculated to evaluate the fraction of patients dying after a cancer diagnosis. A regression analysis was conducted using a lin-log functional form that accounts for a non-linear relationship between (M/I) ratio and health expenditure. The coefficient of determination (R2), indicates the proportion of outcomes explained by the model. Results: Health expenditure was significantly higher in high income countries than in middle and low income countries. For cancers with effective screening and/or effective treatment options higher expenditure was strongly correlated with improved survival. For cancers with no screening and moderately efficient treatment options survival was moderately correlated with health expenditure. For cancers with no screening and poor treatment options survival was poorly correlated to health expenditure. The estimated non-linear relationship shows that increases in health expenditure have a much more significant effect when health expenditure is low, especially for the first two groups of diseases. Significant survival improvements are expected from increasing health expenditure of low and middle income countries as in South America, Africa and parts of Asia, and only marginal incremental improvements, if any, in high income countries. Conclusions: Higher health expenditure is correlated with improved survival in cancers with available effective screening methods and/or treatment options. For cancer with no effective treatment options health expenditure has little impact on survival. Show less

Background: Trastuzumab uptake is not homogeneous across different European countries. The European Union (EU) has adopted a common procedure for granting marketing authorization for cancer drugs. Nevertheless, pricing and reimbursement decisions are a competency of EU national governments, and their respective policies are diverse. We aimed to evaluate the time to reimbursement approval for trastuzumab and its association to health expenditure across EU countries, as well as to health… Show more

Background: Trastuzumab uptake is not homogeneous across different European countries. The European Union (EU) has adopted a common procedure for granting marketing authorization for cancer drugs. Nevertheless, pricing and reimbursement decisions are a competency of EU national governments, and their respective policies are diverse. We aimed to evaluate the time to reimbursement approval for trastuzumab and its association to health expenditure across EU countries, as well as to health policy performance, to the availability of cost-effectiveness studies, and finally to breast cancer outcome.
Methods: Cancer and health expenditure indicators were extracted from the World Health Organization and the World Bank databases. Trastuzumab reimbursement approval dates were provided by F. Hoffmann-La Roche Ltd. Spearman’s rank correlation and Wilcoxon rank-sum test were used to evaluate associations and/or differences between the variables studied. Additional analyses were made by grouping countries according to compliance to the 180 day timeframe stipulated in the 89/105/EEC Directive for drug pricing and reimbursement.
Results: A statistically significant inverse and strong correlation between breast cancer M/I ratio and health expenditure (rs= -0.730, p <0.001) and health policy performance (rs = -0.711, p <0.001) was found, meaning the better the score and the higher the expenditure, the fewer patients died after a breast cancer diagnosis. Factors associated with compliance to the timeframes of the 89/105/EEC Directive for pricing and reimbursement were better health policy score, higher health expenditure, and availability of cost-effectiveness studies.
Conclusion: Higher health policy scores and health expenditure are related to faster reimbursement of trastuzumab and better breast cancer outcome. A marked difference is observed between Eastern and Western Europe, with long delays and increased breast cancer mortality identified in Eastern European countries.
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A 62 year-old woman diagnosed with triple negative breast cancer receiving neoadjuvant chemotherapy presented with a 48 hour history of dyspnea and pain in the left leg. She was at the ninth infusion of weekly paclitaxel and had previously received four cycles of epirubicin and cyclophosphamide. She had no previous history of deep venous thrombosis or hereditary coagulopathy. D-dimer was 4420 ng/mL and doppler of the lower-limbs showed absence of flux in the left popliteal vein. A chest X-ray… Show more

A 62 year-old woman diagnosed with triple negative breast cancer receiving neoadjuvant chemotherapy presented with a 48 hour history of dyspnea and pain in the left leg. She was at the ninth infusion of weekly paclitaxel and had previously received four cycles of epirubicin and cyclophosphamide. She had no previous history of deep venous thrombosis or hereditary coagulopathy. D-dimer was 4420 ng/mL and doppler of the lower-limbs showed absence of flux in the left popliteal vein. A chest X-ray is depicted in Figure 1, while Figure 2 and 3 show the results of an angiotomography.What is your diagnosis?

link to the images
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Purpose: To explore the current clinical management of early stage breast cancer patients, identify areas of controversy, and interrogate how treating physicians implement latest advances.
Methods: We conducted a 27-item survey, disseminated in 2 stages: paper distribution at selected breast cancer sessions at the ESMO 2012 Congress, and dedicated mailings to ESMO members. Descriptive statistical analysis and logistic regression analysis were applied to explore potential associations between… Show more

Purpose: To explore the current clinical management of early stage breast cancer patients, identify areas of controversy, and interrogate how treating physicians implement latest advances.
Methods: We conducted a 27-item survey, disseminated in 2 stages: paper distribution at selected breast cancer sessions at the ESMO 2012 Congress, and dedicated mailings to ESMO members. Descriptive statistical analysis and logistic regression analysis were applied to explore potential associations between the demographic characteristics of the participants and replies.
Results: A total of 512 physicians from 79 countries participated in the study, accounting for 465 (91%) fully completed questionnaires. The majority of the participants were ESMO members (66%), medical oncologists (86.5%), and working in multidisciplinary teams (91.6%). Heterogeneous results were captured, such as the following: 40.9% of the participants consider no genetic test useful for making adjuvant treatment decisions; 15.3% consider PET-CT a useful imaging modality for staging; 68.8% consider that postmenopausal patients with hormone receptor positive disease should always be offered an aromatase inhibitor as part of their adjuvant therapy; 78.7% prefer to administer trastuzumab concurrently with the taxane component of chemotherapy; and 27% would consider bevacizumab in the neoadjuvant setting. The logistic regression analysis did not identify any strong predictor of the probability of giving a reply fully compatible with evidence in the literature.
Conclusion: This survey captures clinical practice and whether the latest research advances are implemented in the treatment of early stage breast cancer by an extended number of physicians. Significant individual differences were found. Areas of controversy were detected, and they deserve further exploration in order to generate 'tailored' educational tools, with the final goal being the standardization of the treatment of early stage breast cancer patients. Show less

Purpose: To explore the current clinical management of early stage breast cancer patients, identify areas of controversy, and interrogate how treating physicians implement latest advances.
Methods: We conducted a 27-item survey, disseminated in 2 stages: paper distribution at selected breast cancer sessions at the ESMO 2012 Congress, and dedicated mailings to ESMO members. Descriptive statistical analysis and logistic regression analysis were applied to explore potential associations between… Show more

Purpose: To explore the current clinical management of early stage breast cancer patients, identify areas of controversy, and interrogate how treating physicians implement latest advances.
Methods: We conducted a 27-item survey, disseminated in 2 stages: paper distribution at selected breast cancer sessions at the ESMO 2012 Congress, and dedicated mailings to ESMO members. Descriptive statistical analysis and logistic regression analysis were applied to explore potential associations between the demographic characteristics of the participants and replies.
Results: A total of 512 physicians from 79 countries participated in the study, accounting for 465 (91%) fully completed questionnaires. The majority of the participants were ESMO members (66%), medical oncologists (86.5%), and working in multidisciplinary teams (91.6%). Heterogeneous results were captured, such as the following: 40.9% of the participants consider no genetic test useful for making adjuvant treatment decisions; 15.3% consider PET-CT a useful imaging modality for staging; 68.8% consider that postmenopausal patients with hormone receptor positive disease should always be offered an aromatase inhibitor as part of their adjuvant therapy; 78.7% prefer to administer trastuzumab concurrently with the taxane component of chemotherapy; and 27% would consider bevacizumab in the neoadjuvant setting. The logistic regression analysis did not identify any strong predictor of the probability of giving a reply fully compatible with evidence in the literature.
Conclusion: This survey captures clinical practice and whether the latest research advances are implemented in the treatment of early stage breast cancer by an extended number of physicians. Significant individual differences were found. Areas of controversy were detected, and they deserve further exploration in order to generate 'tailored' educational tools, with the final goal being the standardization of the treatment of early stage breast cancer patients. Show less

Trastuzumab, a humanized anti-HER2 monoclonal antibody targeting the extracellular domain of this oncoprotein, represents the archetype of HER2 blocking agents. Its unprecedented efficacy for HER2-positive metastatic breast cancer (BC) led to its clinical development in the adjuvant setting. The HERceptin Adjuvant (HERA) is one of the pivotal adjuvant trastuzumab trials which proved that this compound can change the natural course of early stage HER2-positive BC. The HERA study led to the… Show more

Trastuzumab, a humanized anti-HER2 monoclonal antibody targeting the extracellular domain of this oncoprotein, represents the archetype of HER2 blocking agents. Its unprecedented efficacy for HER2-positive metastatic breast cancer (BC) led to its clinical development in the adjuvant setting. The HERceptin Adjuvant (HERA) is one of the pivotal adjuvant trastuzumab trials which proved that this compound can change the natural course of early stage HER2-positive BC. The HERA study led to the registration of trastuzumab for the adjuvant treatment of early HER2-positive BC. This trial randomized more than 5000 patients between 1 and 2 years of trastuzumab and observation after the completion of locoregional therapy and (neo)-adjuvant chemotherapy. Additionally, an abundance of subsequent substudies were conducted, addressing important clinical issues for this patient population. The present review article presents a comprehensive overview of the HERA study and its major contributions to the adjuvant treatment of HER2-positive BC patients. Emphasis is given on the lessons learned from this international collaborative experience and how this can be used as a stepping stone for further improvements in the field. Show less

Trastuzumab, a humanized anti-HER2 monoclonal antibody targeting the extracellular domain of this oncoprotein, represents the archetype of HER2 blocking agents. Its unprecedented efficacy for HER2-positive metastatic breast cancer (BC) led to its clinical development in the adjuvant setting. The HERceptin Adjuvant (HERA) is one of the pivotal adjuvant trastuzumab trials which proved that this compound can change the natural course of early stage HER2-positive BC. The HERA study led to the… Show more

Trastuzumab, a humanized anti-HER2 monoclonal antibody targeting the extracellular domain of this oncoprotein, represents the archetype of HER2 blocking agents. Its unprecedented efficacy for HER2-positive metastatic breast cancer (BC) led to its clinical development in the adjuvant setting. The HERceptin Adjuvant (HERA) is one of the pivotal adjuvant trastuzumab trials which proved that this compound can change the natural course of early stage HER2-positive BC. The HERA study led to the registration of trastuzumab for the adjuvant treatment of early HER2-positive BC. This trial randomized more than 5000 patients between 1 and 2 years of trastuzumab and observation after the completion of locoregional therapy and (neo)-adjuvant chemotherapy. Additionally, an abundance of subsequent substudies were conducted, addressing important clinical issues for this patient population. The present review article presents a comprehensive overview of the HERA study and its major contributions to the adjuvant treatment of HER2-positive BC patients. Emphasis is given on the lessons learned from this international collaborative experience and how this can be used as a stepping stone for further improvements in the field. Show less

Background The European Union (EU) is a confederation of 27 member states, the institutions of which work according to negotiated decisions. The EU has implemented similar legislation and a common market, and has adopted the same currency in most of its member states. Although financing health systems is a responsibility of the national governments, the EU has enacted the Charter of Fundamental Rights to standardize public health policies. However, for historical reasons, health policy and… Show more

Background The European Union (EU) is a confederation of 27 member states, the institutions of which work according to negotiated decisions. The EU has implemented similar legislation and a common market, and has adopted the same currency in most of its member states. Although financing health systems is a responsibility of the national governments, the EU has enacted the Charter of Fundamental Rights to standardize public health policies. However, for historical reasons, health policy and health expenditure is not uniform across the 27 EU member states (EU-27).

Material and methods We hypothesized that increased health expenditure would be associated with better cancer outcome and that this would be most apparent in breast cancer, because of the availability of effective screening methods and treatments. Using publically available data from the World Health Organization, the International Monetary Fund, and the World Bank, we assessed associations between cancer indicators and wealth and health indicators. To do so, we constructed scatter plots and used the Spearman's rank correlation coefficient.

Results A marked difference in wealth and health expenditure indicators was observed between Eastern and Western European countries, with Western European being the higher. Higher wealth and higher health expenditures were associated both with increased cancer incidence and decreased cancer mortality. In breast cancer, the association with incidence was stronger. We created mortality/incidence ratios and observed that the more spent on health, the fewer the deaths after a cancer diagnosis.

Conclusion Despite the initiatives to standardize public health policies of the EU-27, health expenditure continues to be higher in Western European countries and this is associated with better cancer outcome in these countries.
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Background: Brain metastases (BMs) pose a clinical challenge in breast cancer (BC). Lapatinib or temozolomide showed activity in BM. Our study assessed the combination of both drugs as treatment for patients with HER2-positive BC and BM.

Methods: Eighteen patients were enrolled, with sixteen of them having recurrent or progressive BM. Any type of previous therapy was allowed, and disease was assessed by gadolinium (Gd)-enhanced magnetic resonance imaging (MRI). The primary end points… Show more

Background: Brain metastases (BMs) pose a clinical challenge in breast cancer (BC). Lapatinib or temozolomide showed activity in BM. Our study assessed the combination of both drugs as treatment for patients with HER2-positive BC and BM.

Methods: Eighteen patients were enrolled, with sixteen of them having recurrent or progressive BM. Any type of previous therapy was allowed, and disease was assessed by gadolinium (Gd)-enhanced magnetic resonance imaging (MRI). The primary end points were the evaluation of the dose-limiting toxicities (DLTs) and the determination of the maximum-tolerated dose (MTD). The secondary end points included objective response rate, clinical benefit and duration of response.

Results: The lapatinib–temozolomide regimen showed a favorable toxicity profile because the MTD could not be reached. The most common adverse events (AEs) were fatigue, diarrhea and constipation. Disease stabilization was achieved in 10 out of 15 assessable patients. The estimated median survival time for the 16 patients with BM reached 10.94 months (95% CI: 1.09–20.79), whereas the median progression-free survival time was 2.60 months [95% confidence interval (CI): 1.82–3.37].

Conclusions: The lapatinib–temozolomide combination is well tolerated. Preliminary evidence of clinical activity was observed in a heavily pretreated population, as indicated by the volumetric reductions occurring in brain lesions. Show less

With the exception of endocrine therapy, no other systemic treatment of patients with breast cancer has reached such a magnitude of beneficial effect as trastuzumab. This targeted agent (monoclonal antibody) is associated with a significant improvement in both disease-free (DFS) and overall survival (OS) in women with HER-2 positive breast cancer when given in combination with or in sequence to adjuvant chemotherapy. This has been confirmed in a recent Cochrane meta-analysis of randomized… Show more

With the exception of endocrine therapy, no other systemic treatment of patients with breast cancer has reached such a magnitude of beneficial effect as trastuzumab. This targeted agent (monoclonal antibody) is associated with a significant improvement in both disease-free (DFS) and overall survival (OS) in women with HER-2 positive breast cancer when given in combination with or in sequence to adjuvant chemotherapy. This has been confirmed in a recent Cochrane meta-analysis of randomized controlled trials (RCTs), including 6 adjuvant and 2 neoadjuvant studies (NSABP B-31, NCCTG N9831, BCIRG 006, HERA, FinHer, PACS-04, Buzdar and NOAH), with data collection until February 2010. Overall, mortality is reduced by one-third and the risk of relapse by 40%. Show less

in press

Approximately 5-10% of breast cancer patients present with metastatic disease at diagnosis and these patients are unlikely to be cured. Locoregional treatment of the primary tumor has been reserved for symptom palliation and to improve quality of life by controlling bleeding, ulceration and infection. Local therapy improves survival in metastatic colorectal, ovarian, gastric and renal carcinomas. Nevertheless, in metastatic breast cancer patients there are no published randomized prospective… Show more

Approximately 5-10% of breast cancer patients present with metastatic disease at diagnosis and these patients are unlikely to be cured. Locoregional treatment of the primary tumor has been reserved for symptom palliation and to improve quality of life by controlling bleeding, ulceration and infection. Local therapy improves survival in metastatic colorectal, ovarian, gastric and renal carcinomas. Nevertheless, in metastatic breast cancer patients there are no published randomized prospective trials evaluating the impact of breast surgery in survival. This work aims to review the available evidence in the medical literature of the survival benefit of surgery to the primary tumor in metastatic breast cancer patients.
Most of the studies found a survival benefit for the group of metastatic patients where surgery was performed, however is it not possible to draw definitive conclusions about this finding as selection bias could have influenced those results. Young age, good performance status, low tumor burden and favorable tumor biology features could be factors used to predict survival benefit from this approach. Three randomized prospective trials addressing the question of breast surgery in the metastatic setting are currently ongoing and may hopefully shed light into this issue.
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