Survival outcomes of Zo-NAnTAx: a five-year analysis of zoledronic acid added to a neoadjuvant regimen for HER2-positive breast cancer.

Background: Zoledronic acid (ZA) improved outcomes in breast cancer. In pre-clinical studies, ZA increased tumour regression in combination chemotherapy and anti-human epidermal growth factor receptor 2 (HER2) target therapy. The Zo-NAnTax study, a clinical trial combining ZA with neoadjuvant therapy for HER2-positive tumours met the primary endpoint, showing a higher pathological complete response (pCR) rate than predicted in patients receiving surgery. Here, we report the exploratory relapse-free survival (RFS) and overall survival (OS) analysis after five years of follow-up. Methods: Adult women with HER2-positive breast cancer amendable to curative surgery who consented to the study received four cycles of ZA at 4 mg + doxorubicin 60 mg/m2 + cyclophosphamide 600 mg/m2 followed by four cycles of ZA at 4 mg + docetaxel 100 mg/m2 + trastuzumab 6 mg/kg (8 mg/kg as a loading dose), all in a 21 days-cycle, totalizing 8 cycles before surgery. To achieve the primary endpoint of pCR rate between 22% and 35%, 56 patients were needed. The secondary endpoints included safety, gene expression according to treatment response, prediction of pCR rate by an interim breast magnetic resonance imaging (bMRI). Results: Beyond the overall pCR rate of 42%, alongside a good safety profile, we showed similar pCR rates in both hormonal receptor (HR) positive (40%) and HR-negative (44%). RFS and OS at five years were evaluated in 58 subjects, and the overall rate was 79.3% and 86.2%, respectively. Numerically higher values of both RFS and OS were observed in patients achieving pCR vs. non-achieving, respectively 83.3% vs. non-pCR 76.5% (P=0.57) and 95.8% vs. non-pCR 79.4% (P=0.08). Although not statistically significant, OS was numerically equivalent according to HR status, respectively 85.7% vs. 87.5% for HR-positive and HR-negative (P=0.91), which contrasted with RFS, HR-positive 81% vs. HR-negative 75% (P=0.58). None of the assessed clinicopathological biomarkers significantly correlated with survival. Conclusions: ZA plus neoadjuvant therapy in HER2-positive breast cancer shows provoking survival outcomes. Clinical and pre-clinical investigation with dual anti-HER2 blockage is warranted.

Do proton pump inhibitors affect the effectiveness of cyclin-dependent kinase 4/6 inhibitors in advanced HR positive, HER2 negative breast cancer? A meta-analysis.

Background: The CDK 4/6 inhibitors, including palbociclib and ribociclib, are the standard first-line treatment for hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer. Proton pump inhibitors are one of the most globally prescribed types of medications as part of the treatment for gastroesophageal reflux and heartburn complaints. Medication interactions have been demonstrated, leading to a decrease in the effectiveness of chemotherapy drugs such as capecitabine and pazopanib. However, their role and interaction with targeted therapies such as CDK inhibitors are still poorly understood. Methods: We searched PubMed, Embase and Web of Science databases for studies that investigated the use of PPI with CDK 4/6 inhibitors versus CDK4/6 alone for advanced or metastatic breast cancer. We systematically searched for the currently available CDK inhibitors: palbociclib, ribociclib and abemaciclib. We computed hazard ratios (HRs), with 95% confidence intervals (CIs). We used DerSimonian and Laird random-effect models for all endpoints. Heterogeneity was assessed using I2 statistics. R, version 4.2.3, was used for statistical analyses. Results: A total of 2,737 patients with advanced breast cancer in 9 studies were included, with six studies described the status menopausal as 217 (7.9%) pre-menopause and 1851 (67.6%) post-menopause, for endocrine sensitivity only five studies described1489 (54.4%) patients were endocrine-sensitive and 498 (182%) endocrine-resistent, 910 (33.2%) patients used PPIs. The overall Progression-Free Survival was in favor of the PPI non-users (HR 2.0901; 95% CI 1.410-2.9498; p < 0.001). As well as the subgroup taking palbociclib, revealing statistical relevance for the PPI non-users (HR 2.2539; 95% CI 1.3213-3.8446; p = 0.003) and ribociclib subgroup with a slight decrease in hazard ratio (HR 1.74 95% CI 1.02-2.97; p = 0.04; I2 = 40%). In the multivariate analysis, there was no statistical signifance with ECOG (HR 0.9081; 95% CI 0.4978-16566; p 0.753) and Age (HR 1.2772; 95% CI 0.8790-1.8559; p = 0.199). Either, the univariate analysis did not show statistical significance. Conclusion: Women with HR+ and HER2-advanced metastatic breast undergoing treatment with targeted therapies, specifically CDK 4/6 inhibitors, should be monitored for the use of proton pump inhibitors. Therefore, the use of PPIs should be discussed, weighing the advantages and disadvantages for specific cases. It should be individualized based on the necessity in clinical practice for these cases. Systematic Review Registration: identifier CRD42023484755.

Trastuzumab deruxtecan in human epidermal growth factor receptor 2-positive breast cancer brain metastases: a systematic review and meta-analysis.

BACKGROUND: Trastuzumab deruxtecan (T-DXd) has shown promising results in patients with breast cancer brain metastases (BCBMs). We conducted a systematic review and meta-analysis to evaluate the effectiveness and safety of T-DXd in the human epidermal growth factor receptor 2 (HER2)-positive BCBM population. PATIENTS AND METHODS: We searched PubMed, Embase, and Cochrane Library databases as well as American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), and San Antonio Breast Cancer Symposium (SABCS) websites for clinical trials (CTs) and observational studies evaluating T-DXd in patients with HER2-positive BCBM. Heterogeneity was assessed with I2 statistics. Random effects models were used for all statistical analyses, which were carried out using R software (version 4.2.2). RESULTS: Ten studies were included, six CTs (n = 189) and four observational studies (n = 130), with a total of 319 patients. The median progression-free survival was 15 months [95% confidence interval (CI) 13.9-16.1 months]. The objective response rate (ORR) was 61% (95% CI 52% to 70%), and the intracranial (IC)-ORR was 61% (95% CI 54% to 69%). No significant differences in ORR and IC-ORR were observed between CTs and observational studies (P = 0.31 and 0.58, respectively). The clinical benefit rate (CBR) was 80% (95% CI 52% to 94%), and the IC-CBR was 70% (95% CI 54% to 82%). The ORR was 68% (95% CI 57% to 77%) in the subgroup of patients with stable BMs and 60% (95% CI 48%-72%) in patients with active BM, with no significant difference between groups (P = 0.35). CONCLUSIONS: Our systematic review and meta-analysis supports the IC activity of T-DXd in patients with stable BM and active BM. TRIAL REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) under the protocol number CRD42023422589.

Clinical significance of CD166 and HER-2 in different types of gastric cancer.

INTRODUCTION: Cluster of differentiation 166 (CD166), a cancer stem cell (CSC) marker, and human epidermal growth factor receptor 2 (HER-2) are expressed in a diversity of malignancies and is associated with tumor progression. Although studies regarding the importance of CSC markers and HER-2 in gastric cancer (GC) have rapidly developed, their clinicopathological, prognosis, and diagnosis value still remain unsatisfying in GC. Therefore, the present study aims to investigate the clinical, prognostic, and diagnostic significance of CD166 and HER-2 in different histological types of GC. MATERIALS AND METHODS: Bioinformatic analysis was applied to determine the clinical importance of CD166 and HER-2 expression based on their tissue localization in primary GC tumors and the normal adjacent samples. The expression patterns, clinical significance, prognosis, and diagnosis value of CD166 and HER-2 proteins in tissue microarrays (TMAs) of 206 GC samples, including Signet Ring Cell (SRC) and intestinal types and also 28 adjacent normal tissues were evaluated using immunohistochemistry (IHC). RESULTS: The results indicated that the expression of CD166 (membranous and cytoplasmic) and HER-2 were significantly up-regulated in tumor cells compared to adjacent normal tissues (P = 0.010, P < 0.001, and P = 0.011, respectively). A statistically significant association was detected between a high level of membranous expression of CD166 and lymphovascular invasion (P = 0.006); We also observed a statistically significant association between high cytoplasmic expression of CD166 protein and more invasion of the subserosa (P = 0.040) in the SRC type. In contrast, there was no correlation between the expression of HER-2 and clinicopathologic characteristics. Both CD166 and HER-2 showed reasonable accuracy and high specificity as diagnostic markers. CONCLUSION: Our results confirmed that increased membranous and cytoplasmic expression of CD166 showed clinical significance in the SRC type and is associated with the progression of the disease and more aggressive tumor behaviors. These findings can be used to assist in designating subgroups of patients that require different follow-up strategies, and also, they might be utilized as the prognostic or diagnostic biomarkers in these types of GC for prospective clinical application.

Cost-Effectiveness Analysis of Pertuzumab Plus Trastuzumab and Docetaxel Compared With Trastuzumab and Docetaxel in the Adjuvant Treatment of Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer in Colombia.

OBJECTIVES: The addition of pertuzumab to the scheme of docetaxel plus trastuzumab (TH) in patients with metastatic breast cancer with overexpression of human epidermal growth factor receptor 2 increases survival. Nevertheless, this addition could represent a high cost for the health system of a middle-income country such as Colombia. Therefore, it is necessary to evaluate the efficiency of the pertuzumab plus TH (PTH) scheme in comparison with TH. METHODS: A partitioned survival model-based cost-utility analysis was performed. Progression-free survival and overall survival curves for each scheme were obtained from the CLEOPATRA study. The time horizon was 30 years with a discount rate of 5% for costs and quality-adjusted life-years. Total direct costs were calculated using national tariffs. Utilities were obtained from external sources. Model uncertainty was evaluated by deterministic and probabilistic sensitivity analysis. A willingness to pay value of 5180 US dollars was used. RESULTS: The discounted total average costs of TH and PTH were $24 109 and $60 846, respectively. These regimens' average life-years were 5.78 and 8.38, and their quality-adjusted life-years were 3.28 and 4.51, respectively. The incremental cost-effectiveness ratio was $29 867. One-way sensitivity analysis showed that the cost of pertuzumab was the variable that explained the uncertainty in the model. The probability that PTH is cost-effective in the probabilistic sensitivity analysis is 0.0724. CONCLUSIONS: The addition of pertuzumab to the TH regimen in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer has a low probability of being cost-effective from the payer's perspective in the Colombian health system.

Molecular recognition of tak-285 and lapatinib by inactive, active, and middle active-inactive HER2.

Experimental and theoretical studies have provided structural information regarding the shift from inactive to active EGFR, throughout which both conformations are linked via binding to specific tyrosine kinase inhibitors. For HER2, an intermediate active-inactive receptor conformation is present in the PDB, which has been co-crystallized with tak-285. The affinity of HER2 in monomeric state to tak-285 has been previously reported. However, the lack of structural knowledge of HER2 limits our capacity to understand whether tak-285, or other known HER2 inhibitors, selectively bind active, inactive, or intermediate forms of HER2. To elucidate mechanisms by which tak-285 binds to HER2, we first obtained information regarding the structural features of the active state of HER2 via microsecond MD simulations from the crystallized intermediate structure previously determined. Based on these HER2 conformers, together with the inactive HER2 conformer obtained in a previous study, we used docking and MD simulations coupled to MMGBSA approach to assess binding of tak-285 and lapatinib, known HER2/EGFR dual inhibitors, to HER2. Structural and energetic studies revealed that tak-285 binds with a greater affinity than lapatinib to active and intermediate active-inactive forms of HER2. This is in accordance with experimental findings that showed the tak-285 inhibitor has increased activity relative to lapatinib in breast cancer cell lines.

Hepatoid esophagogastric adenocarcinoma and tumoral heterogeneity: a case report.

Hepatoid adenocarcinoma of the stomach is an uncommon subtype of gastric cancer remarkably similar to hepatocellular carcinoma in histopathological analysis. It is also commonly associated with high serum alfa-fetoprotein and a poorer prognosis, despite the emergence of new therapeutic options. In recent years, next generation sequencing (NGS) technology has made it possible to identify and describe the genes and molecular alterations common to gastric cancer thereby contributing to the advancement of targeted therapies. A 62-year-old patient, with no prior risk factor for hepatocellular carcinoma (HCC), presented to the emergency room with dysphagia for solids, abdominal pain and weight loss of about 3 kilograms over 3 months. Histopathological analysis presented with disparities regarding HER2 and programmed death-ligand 1 (PD-L1) status in the primary and metastatic sites. We describe a case of a de novo metastatic, human epidermal growth factor receptor 2 (HER2) positive esophagogastric junction hepatoid adenocarcinoma. Although this is a rare subgroup of gastric cancer, treatment strategies were based in recent studies in immunotherapy and guided therapy, taking into consideration the molecular findings from the patient's tumor NGS analysis. Data about HER2 and PDL1 heterogeneity were also reviewed. Despite the aggressiveness and rarity of this histology, the patient had a good response to treatment.

Osteopontin expression and its relationship with prognostic biomarkers in canine mammary carcinomas / Expressão de osteopontina e sua relação com biomarcadores prognóstico nos carcinomas mamários caninos

Osteopontin is a glycophosphoprotein implicated in different physiologic and pathologic processes and is known to be involved in progression and metastasis of various cancers in humans, but this relation is still little explored in the veterinary. The aim was to evaluate the expression of osteopontin in canine mammary carcinomas and its relation with well-established canine mammary tumor biomarkers. For that, expression of OPN, EGFR, HER2, and c-Kit were evaluated along with Ki67 rate in 43 mammary carcinomas. Osteopontin was demonstrated to be expressed by neoplastic epithelial cells in all carcinomas as well as in stromal cells from the tumor microenvironment. Relation between high osteopontin expression and EGFR positivity (P<0.001) and HER2 overexpression (P=0.012) was demonstrated. In conclusion, high OPN expression seems to be related to poor prognosis and MAPK pathway activation, given the association with EGFR and HER2, members of the MAPK signaling pathway.(AU)

A osteopontina é uma glicofosfoproteina implicada em diferentes processos fisiológicos e patológicos, sendo conhecida por estar envolvida na progressão e metástase de vários cânceres nos humanos, no entanto, essa relação é ainda pouco explorada na veterinária. O objetivo deste trabalho foi avaliar a expressão da osteopontina nos carcinomas mamários caninos e sua relação com biomarcadores bem estabelecidos para esta neoplasia. Para isto, foi avaliada a expressão de OPN, EGRH, HER2 e c-Kit juntamente com a taxa de Ki67 em 43 carcinomas mamários. A osteopontina foi expressa pelas células epiteliais neoplásicas em todos os carcinomas, assim como, nas células estromais do microambiente tumoral. Foi demonstrada uma relação entre uma alta expressão de osteopontina e positividade para EGFR (P<0.001) e superexpressão de HER2 (P=0.012). Em conclusão, alta expressão de OPN parece estar relacionada com mau prognóstico e ativação da via MAPK, devido a sua associação com EGRF e HER2, os quais são membros desta via de sinalização.(AU)

Osteopontin expression and its relationship with prognostic biomarkers in canine mammary carcinomas / Expressão de osteopontina e sua relação com biomarcadores prognóstico nos carcinomas mamários caninos

Osteopontin is a glycophosphoprotein implicated in different physiologic and pathologic processes and is known to be involved in progression and metastasis of various cancers in humans, but this relation is still little explored in the veterinary. The aim was to evaluate the expression of osteopontin in canine mammary carcinomas and its relation with well-established canine mammary tumor biomarkers. For that, expression of OPN, EGFR, HER2, and c-Kit were evaluated along with Ki67 rate in 43 mammary carcinomas. Osteopontin was demonstrated to be expressed by neoplastic epithelial cells in all carcinomas as well as in stromal cells from the tumor microenvironment. Relation between high osteopontin expression and EGFR positivity (P<0.001) and HER2 overexpression (P=0.012) was demonstrated. In conclusion, high OPN expression seems to be related to poor prognosis and MAPK pathway activation, given the association with EGFR and HER2, members of the MAPK signaling pathway.(AU)

A osteopontina é uma glicofosfoproteina implicada em diferentes processos fisiológicos e patológicos, sendo conhecida por estar envolvida na progressão e metástase de vários cânceres nos humanos, no entanto, essa relação é ainda pouco explorada na veterinária. O objetivo deste trabalho foi avaliar a expressão da osteopontina nos carcinomas mamários caninos e sua relação com biomarcadores bem estabelecidos para esta neoplasia. Para isto, foi avaliada a expressão de OPN, EGRH, HER2 e c-Kit juntamente com a taxa de Ki67 em 43 carcinomas mamários. A osteopontina foi expressa pelas células epiteliais neoplásicas em todos os carcinomas, assim como, nas células estromais do microambiente tumoral. Foi demonstrada uma relação entre uma alta expressão de osteopontina e positividade para EGFR (P<0.001) e superexpressão de HER2 (P=0.012). Em conclusão, alta expressão de OPN parece estar relacionada com mau prognóstico e ativação da via MAPK, devido a sua associação com EGRF e HER2, os quais são membros desta via de sinalização.(AU)

A retrospective, multicenter study of the efficacy of lapatinib plus trastuzumab in HER2-positive metastatic breast cancer patients previously treated with trastuzumab, lapatinib, or both: the Trastyvere study.

PURPOSE: To evaluate the efficacy and safety of lapatinib (L) and trastuzumab (T) combination in HER2-positive metastatic breast cancer (MBC) patients previously treated with T and/or L. MATERIALS AND METHODS: We conducted a retrospective, post-authorized, multicenter study including patients with HER2-positive MBC or locally advanced breast cancer (ABC) treated with the combination of L-T. Concomitant endocrine therapy, as well as brain metastasis and/or prior exposure to L, were allowed. RESULTS: One hundred and fifteen patients from 14 institutions were included. The median age was 59.8 years. The median number of prior T regimens in the advanced setting was 3 and 73 patients had received a prior L regimen. The clinical benefit rate (CBR) was 34.8% (95% CI 26.1-43.5). Among other efficacy endpoints, the overall response rate was 21.7%, and median progression-free survival (PFS) and overall survival were 3.9 and 21.6 months, respectively. Heavily pretreated and ≥ 3 metastatic organ patients showed lower CBR and PFS than patients with a low number of previous regimens and < 3 metastatic organs. Moreover, CBR did not significantly change in L-pretreated compared with L-naïve patients (31.5% versus 40.5% for L-pretreated versus L-naïve). Grade 3/4 adverse events were reported in 19 patients (16.5%). CONCLUSION: The combination of L-T is an effective and well-tolerated regimen in heavily pretreated patients and remains active among patients progressing on prior L-based therapy. Our study suggests that the L-T regimen is a safe and active chemotherapy-free option for MBC patients previously treated with T and/or L.

Osteopontin expression and its relationship with prognostic biomarkers in canine mammary carcinomas

ABSTRACT: Osteopontin is a glycophosphoprotein implicated in different physiologic and pathologic processes and is known to be involved in progression and metastasis of various cancers in humans, but this relation is still little explored in the veterinary. The aim was to evaluate the expression of osteopontin in canine mammary carcinomas and its relation with well-established canine mammary tumor biomarkers. For that, expression of OPN, EGFR, HER2, and c-Kit were evaluated along with Ki67 rate in 43 mammary carcinomas. Osteopontin was demonstrated to be expressed by neoplastic epithelial cells in all carcinomas as well as in stromal cells from the tumor microenvironment. Relation between high osteopontin expression and EGFR positivity (P 0.001) and HER2 overexpression (P=0.012) was demonstrated. In conclusion, high OPN expression seems to be related to poor prognosis and MAPK pathway activation, given the association with EGFR and HER2, members of the MAPK signaling pathway.

RESUMO: A osteopontina é uma glicofosfoproteina implicada em diferentes processos fisiológicos e patológicos, sendo conhecida por estar envolvida na progressão e metástase de vários cânceres nos humanos, no entanto, essa relação é ainda pouco explorada na veterinária. O objetivo deste trabalho foi avaliar a expressão da osteopontina nos carcinomas mamários caninos e sua relação com biomarcadores bem estabelecidos para esta neoplasia. Para isto, foi avaliada a expressão de OPN, EGRH, HER2 e c-Kit juntamente com a taxa de Ki67 em 43 carcinomas mamários. A osteopontina foi expressa pelas células epiteliais neoplásicas em todos os carcinomas, assim como, nas células estromais do microambiente tumoral. Foi demonstrada uma relação entre uma alta expressão de osteopontina e positividade para EGFR (P 0.001) e superexpressão de HER2 (P=0.012). Em conclusão, alta expressão de OPN parece estar relacionada com mau prognóstico e ativação da via MAPK, devido a sua associação com EGRF e HER2, os quais são membros desta via de sinalização.

HER2 testing in gastric cancer: An update.

Human epidermal growth factor receptor 2 (HER2) overexpression is increasingly recognized as a frequent molecular abnormality in gastric and gastroesophageal cancer. With the recent introduction of HER2 molecular targeted therapy for patients with advanced gastric cancer, determination of HER2 status is crucial in order to select patients who may benefit from this treatment. This paper provides an update on our knowledge of HER2 in gastric and gastroesophageal cancer, including the prognostic relevance of HER2, the key differences between HER2 protein expression interpretation in breast and gastric cancer, the detection methods and the immunohistochemistry scoring system.

HER2 overexpression reverses the relative resistance of EGFR-mutant H1975 cell line to gefitinib.

Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) that has been demonstrated to be clinically useful for the treatment of patients with non-small cell lung cancer (NSCLC). However, ~50% of patients do not respond to EGFR TKI treatment through the emergence of mutations, such as T790M. Therefore, it is important to determine which patients are eligible for treatment with gefitinib. As a preferred dimerization partner for EGFR, the role of EGFR 2 (HER2) in mediating sensitivity to gefitinib is poorly understood. In the present study, full-length human HER2 cDNA was introduced to the NSCLC cell lines H1975 and H1299, which have a low endogenous expression level of HER2. In addition, it was observed in the present study that the H1975 cell line harbored the L858R and T790M mutations in the EGFR kinase domain. Western blot analysis and MTT assay were used to evaluate the TKI sensitivity of HER2 expression status, and the activation of HER3 and HER2 downstream effectors. The results indicated that the sensitivity of H1975 cells to gefitinib was restored by the overexpression of HER2, which stimulated HER2-driven signaling cascades accompanied by the activation of protein kinase B. By contrast, ectopic HER2 overexpression in H1299 cells did not significantly alter the sensitivity to gefitinib treatment. In conclusion, the current study results suggested that the relatively resistance of the H1975 cell line to gefitinib could be reversed by the overexpression of HER2. Therefore, the expression of HER2 could also be considered when evaluate the patients' potential response to gefitinib, particularly in the subgroup of lung cancer patients who harbor an EGFR mutation.

A Phase II Randomized Study of Lapatinib Combined With Capecitabine, Vinorelbine, or Gemcitabine in Patients With HER2-Positive Metastatic Breast Cancer With Progression After a Taxane (Latin American Cooperative Oncology Group 0801 Study).

BACKGROUND: Novel targeted agents and combinations have become available in multiple lines of treatment for human epidermal growth factor receptor 2-positive (HER2(+)) metastatic breast cancer (MBC). In this context, alternatives to the lapatinib (L) and capecitabine (C) regimen, evaluating L combined with other cytotoxic drugs, are warranted. PATIENTS AND METHODS: In the present phase II, multicenter study, patients with HER2(+) MBC with progression after taxane were randomized between L, 1250 mg, combined with C, 2000 mg/m(2) on days 1 to 14 (LC), vinorelbine (V), 25 mg/m(2) on days 1 and 8 (LV), or gemcitabine (G), 1000 mg/m(2) on days 1 and 8 (LG), every 21 days. The primary endpoint was the overall response rate. RESULTS: A total of 142 patients were included from 2009 to 2012. No differences were found in the patient baseline characteristics. The median age was 51 years, 69% were postmenopausal, 32% had liver metastasis, 57% were hormone receptor negative, and 48% had been previously treated with trastuzumab. The overall response rate was 49% (95% confidence interval [CI], 34.8%-63.4%), 56% (95% CI, 40%-70.4%), and 41% (95% CI, 27%-56.8%) in the LC, LV, and LG groups, respectively. The median progression-free survival was 9 months in the LC arm and 7 months in the other 2 arms (P = .28). The most common grade 3 and 4 adverse events were hand-foot syndrome (18%), diarrhea (6%), and increased alanine aminotransferase/aspartate aminotransferase (4%) in the LC arm; neutropenia (36%), diarrhea (9%), and febrile neutropenia (6%) in the LV arm; and neutropenia (47%), alanine aminotransferase/aspartate aminotransferase (13%), and rash (4%) in the LG arm. CONCLUSION: LV and LG seem to be active combinations in patients with HER2(+) MBC after taxane failure. The overall toxicity was manageable in all regimens.

Human Epidermal Growth Factor Receptor 2-Positive Duodenal Adenocarcinoma: A Case Report and Review of the Literature.

Duodenal adenocarcinoma is a rare malignancy and carries a poor prognosis. The role of adjuvant therapy and the optimal chemotherapy regimen remain largely unclear. Treatment with trastuzumab results in prolonged survival in gastroesophageal cancer if human epidermal growth factor receptor 2 (HER2) is overexpressed or amplified in tumor cells. However, unlike gastric adenocarcinomas, duodenal cancers seem to rarely harbor HER2 amplification or overexpression. We report the case of a patient with HER2-positive stage III duodenal adenocarcinoma who has received adjuvant chemotherapy including trastuzumab.

Therapeutic options for HER-2 positive breast cancer: Perspectives and future directions.

During the last 15 years we have witnessed an unprecedented expansion in the drugs developed to target human epidermal growth factor receptor-2 (HER-2) positive breast cancer. Trastuzumab, pertuzumab, ado-trastuzumab emtansine and lapatinib are currently food and drug administration (FDA)-approved for the treatment of breast cancer patients with HER-2 over-expressed. However, given the amount of information gathered from years of uninterrupted clinical research, it is essential to have periodic updates that succinctly recapitulate what we have learnt over these last years and help us to apply that information in our daily practice. This review will pursue that objective. We will summarize the most relevant and updated information related to the state of the art management of HER-2 positive breast cancer in all the clinical scenarios including the adjuvant, neoadjuvant and metastatic settings. But we will also critically appraise that literature in order to highlight some key clinical concepts that should not be overlooked. Lastly, this review will also point out some of the most promising strategies that are currently being tested and may soon become available.

An economic evaluation of trastuzumab as adjuvant treatment of early HER2-positive breast cancer patients in Colombia / Evaluación económica del trastuzumab como tratamiento adyuvante en cáncer de mama HER2- positivo en Colombia

Objective: Trastuzumab (Herceptin®), a recombinant, humanized, monoclonal antibody targeting HER2 is well established as an effective treatment for HER2-positive breast cancer. Evidence from developed countries showed that trastuzumab was cost-effective; but there are few evidences in developing countries. This study assesses the cost-effectiveness of adjuvant trastuzumab treatment in Colombia. Methods: A Markov health-state transition model was built to estimate clinical and economic outcomes in HER2-positive breast cancer with or without 12 months trastuzumab adjuvant chemotherapy over a lifetime perspective with annual transition cycles. The model incorporated five health states (diseasefree, local recurrence, distant recurrence, cardiac failure, and death). Baseline event rates and 3-year hazard ratio (HR=0.51, IC 95% 0.44-0.59; p<0.0001) were derived from 4-year follow up of the N9831 and NSABP B-31 trial. Costs and utility weights were obtained from the literature and were discounted by 5% annually. Results: The model showed that the utilization of adjuvant trastuzumab treatment in early breast cancer can prolong 0.80 quality-adjusted life-years (QALY), compared with standard chemotherapy, an incremental cost-effectiveness ratio (ICER) of US$ 71,491 per QALY gained. Conclusion: The results suggest that 1-year adjuvant Trastuzumab treatment is not cost-effective in Colombia, using the definition of WHO cost-effectiveness threshold of 3 times GDP per capita.

Introducción. El trastuzumab es un anticuerpo monoclonal de reconocida efectividad para el tratamiento en mujeres con cáncer de mama positivo para HER2. Sin embargo, la mayoría de estudios de costo-efectividad se han llevado a cabo en países desarrollados. Objetivo. Determinar el costo-efectividad del tratamiento adyuvante con trastuzumab en mujeres con cáncer de mama HER2+ en Colombia. Materiales y métodos. Se construyó un modelo de Markov, con ciclos de transición anuales y desde la perspectiva del pagador, para estimar los resultados clínicos y económicos derivados de la administración de trastuzumab en mujeres con HER2 positivo. El modelo incorpora cinco estados de transición: libre de enfermedad, recurrencia local, metástasis, falla cardiaca y muerte. La tasa de eventos y la razón de tazas instantáneas (0,51; IC 95% 0,44-0,59; p<0,0001) se derivaron del reporte a cuatro años de los ensayos clínicos controlados N9831 y NSABP B-31. Los costos y las utilidades se estimados a partir de la literatura científica, utilizando una tasa de descuento del 5 % anual. Resultados. El modelo revela que la utilización de trastuzumab como tratamiento adyuvante prolonga la expectativa de vida ajustada por calidad en 0,8 años, en comparación con la quimioterapia sin trastuzumab; a una razón de costo efectividad incremental (sic.) de US$ 71.491 por año de vida ganado ajustado por calidad de vida. Conclusión. El tratamiento con trastuzumab durante un año no es costo-efectivo en Colombia, utilizando la definición de costo-efectividad de la OMS de menos de dos a tres veces el PIB per cápita por año de vida ganado ajustado por calidad de vida.