Use Of Trastuzumab Research Articles

Clinical case of a successful treatment of stage IV esophagal adenocarcinoma

Background. Esophageal adenocarcinoma is often diagnosed at an advanced stage. The overall five-year survival rate of metastatic esophageal adenocarcinoma is less than 15 %. The main treatment strategy is drug therapy. The search for new drugs is still ongoing. Therefore, the assessment of the effectiveness of currently existing options is of great significance.Description of the clinical case. A 45-year-old patient with advanced esophageal cancer with omental, mediastinal and subclavian lymph node metastases received 4 cycles of CF chemotherapy and 3 cycles of DCF + trastuzumab chemotherapy. After 25 cycles of maintenance therapy with trastuzumab, stable disease was observed. There were no significant adverse events associated with the use of trastuzumab. Currently, the patient has no any symptoms of disease.Conclusion. Trastuzumab for the treatment of HER2- overexpressing esophageal cancer was shown to be very effective. The presented clinical case demonstrates not only the feasibility of controlling metastatic disease using targeted therapy, but also maintaining a high level of quality of life.

193P A national retrospective multicentre audit of long-term trastuzumab use in metastatic breast cancer: Breast Cancer Trainees Collaborative Group

Approximately 25% of breast cancers overexpress HER2 which was previously associated with a poor prognosis [Eiermann 2001]. The addition of anti-HER2 targeted agents has improved prognosis for metastatic HER2-positive patients [Slamon 2001]. UK guidance is to continue trastuzumab until evidence of extra-cranial disease progression [NICE TA34 2002]. Complete radiological responses are not uncommon, ranging from 15-20% [Beda 2007]. Long term trastuzumab is not without impact on quality of life, risk of cardiotoxicity and cost.

The effect of trastuzumab on cardiac function in patients with HER2‐positive metastatic breast cancer and reduced baseline left ventricular ejection fraction

We investigated the effect of trastuzumab on cardiac function in a real‐world historic cohort of patients with HER2‐positive metastatic breast cancer (MBC) with reduced baseline left ventricular ejection fraction (LVEF). Thirty‐seven patients with HER2‐positive MBC and baseline LVEF of 40% to 49% were included. Median LVEF was 46% (interquartile range [IQR] 44%‐48%) and median follow‐up was 18 months (IQR 9‐34 months). During this period, the LVEF did not worsen in 24/37 (65%) patients, while 13/37 (35%) patients developed severe cardiotoxicity defined as LVEF <40% with median time to severe cardiotoxicity of 7 months (IQR 4‐10 months) after beginning trastuzumab. Severe cardiotoxicity was reversible (defined as LVEF increase to a value <5%‐points below baseline value) in 7/13 (54%) patients, partly reversible (defined as absolute LVEF increase ≥10%‐points from nadir to a value >5%‐points below baseline) in 3/13 (23%) patients and irreversible (defined as absolute LVEF increase <10%‐points from nadir and to a value >5%‐points below baseline) in 3/13 (23%) patients. Likelihood of reversibility was numerically higher in patients who received cardio‐protective medications (CPM), including ACE‐inhibitors, beta‐blockers and angiotensine‐2 inhibitors, compared to those who did not receive any CPM (71% vs 13%, P = .091). Sixty‐five percent of patients who received trastuzumab for HER2‐positive MBC did not develop severe cardiotoxicity during a median follow‐up of 18 months, despite having a compromised baseline LVEF. If severe cardiotoxicity occurred, it was at least partly reversible in more than two‐thirds of the cases. Risks and benefits of trastuzumab use should be balanced carefully in this vulnerable population.

Cardiac Biomarker for Acute Cardiac Toxicity in Breast cancer Patient Receiving Anthracycline or Trastuzumab in King Abdulaziz University Hospital, Observation Study

Aim: To determine if using cardiac biomarker will predict cardiotoxicity in patients with breast cancer receiving cardiotoxic anti-cancer therapy. Chemotherapy, biological therapy and immunotherapy are associated with this type of toxicity. In our study we focused on the use of anthracycline and trastuzumab. Methods: We conducted an observational study in which we followed patients who received cardiotoxic medication and assessed cardiac biomarker before therapy, 48-72 hours after and before next cycle. A mixed effect linear regression model was used with patient as a random intercept to model the clinical endpoints before and after the chemotherapy while controlling important demographics Results: 30 patients with early breast cancer who are receiving treatment at King Abdulaziz University Hospital were eligible. Two patients developed drop in left ventricular ejection fraction. No patient developed symptoms of congestive heart failure. There was no correlation between the elevation in cardiac markers and the decrease in the ejection fraction. Conclusion: In a small observational study on breast cancer patients at KAUH, there was no correlation between cardiac markers changes and reduction in the left ventricular ejection fraction. A larger cohort will be of benefit to prove if there is a significant correlation. Key Words: Breast cancer, Anthracycline, Trastuzumab, Cardiac biomark

Oral Etoposide and Trastuzumab Use for HER2-Positive Metastatic Breast Cancer: A Retrospective Study from the Institut Curie Hospitals.

Simple SummaryOral etoposide (VP16), an inhibitor of topoisomerase-II, has demonstrated clinical activity in metastatic breast cancer (MBC). To our knowledge, oral VP16 combined with trastuzumab (VP16-T) in HER2+ MBC has not been evaluated before. This combination is biologically relevant, as TOP2A, the gene encoding topoisomerase II, is often co-amplified with ERBB2. We report a retrospective analysis of the impact of oral VP16-trastuzumab on HER2+ MBC patients, together with TOP2A/ERBB2 co-amplification status, assessed through shallow whole genome sequencing. In addition to its low cost and convenience, the oral VP16-trastuzumab regimen has shown a satisfactory activity and excellent tolerability.Background: The TOP2A and ERBB2 genes are co-amplified in about 40% of HER2 positive (HER2+) breast cancers. Oral etoposide (VP16), an inhibitor of topoisomerase-II (encoded by TOP2A), has demonstrated clinical activity in metastatic breast cancer (MBC). The benefit of oral VP16 combined with trastuzumab (VP16-T) in HER2+ MBC has not yet been evaluated. Methods: Patients treated at the Institut Curie Hospitals with VP16-T for HER2+ MBC were retrieved by an in silico search. Progression-free survival (PFS), overall survival (OS), response rate, prolonged PFS (defined as at least 6 months), clinical benefit, and toxicity were assessed. The co-amplification of ERBB2 and TOP2A was assessed by shallow whole genome sequencing on tumor tissue whenever available. Results: Forty-three patients received VP16-T after a median number of six prior treatment lines for HER2+ MBC. Median PFS and OS were 2.9 months (95% CI [2.4–4.7]) and 11.3 months (95% CI [8.3–25.0]), respectively. Three patients had a complete response, while 12/40 (30%) experienced clinical benefit. Only three patients stopped treatment for toxicity. Seven (35%) patients displayed a TOP2A/ERBB2 co-amplification. No statistically significant correlation was found between outcome and TOP2A/ERBB2 co-amplification. Conclusion: Our analysis suggests a favorable efficacy and toxicity profile for VP16-T in patients with heavily pretreated HER2+ MBC.

Signal Detection of Adverse Events Associated with Trastuzumab in a Cohort of Elderly Patients with Breast Cancer.

AimUtilization of signal detection methods in longitudinal claims data can improve post-marketing drug surveillance, but to date there has been limited application. The aim of this study is to use 3 approaches, the proportional reporting ratio, Gamma Poisson Shrinker, and tree-based scan statistic in detecting adverse drug events (ADEs) attributed to trastuzumab using an administrative claims dataset.MethodsUsing data from the Texas Cancer Registry and SEER linked to Medicare from 2010 to 2013, we conducted 1:2 propensity score matching. Breast cancer HER2+ patients treated with trastuzumab in addition to standard chemotherapy were matched to HER2– patients treated with standard chemotherapy. Inpatient and outpatient encounters up to 6 months from start of therapy were used to identify adverse events.ResultsA total of 4191 patients were included in the study. Across all methods, use of trastuzumab generated signals on 9 distinct body systems. Cardiomyopathy and heart valve disease were the most consistently detected signals. Clinical review determined that most signals represented known ADEs.ConclusionsWe showed that claims data can be used to complement current ADE monitoring using common data mining methods with propensity score matching. Our analysis identified all expected ADEs associated with trastuzumab, and additional signals of valvular heart disorders.

Clinicopathological features of HER2 positive metastatic colorectal cancer and survival analysis of anti-HER2 treatment

BackgroundWe aimed to investigate response and prognostic factors in patients with human epidermal growth factor receptor 2 (HER2) positive metastatic colorectal cancer (mCRC) and compare the curative effect on patients who received different therapy regimens (including chemotherapy and chemotherapy combined with targeted drugs).MethodsWe retrospectively analyzed all HER2 positive mCRC patients treated at Peking University Cancer Hospital between September 2011 and February 2021. We divided 63 HER2 positive mCRC into group A and group B according to the use of trastuzumab or not. Besides, we assigned four subgroups according to the first-line therapies of KRAS/NRAS/BRAF WT patients. The Kaplan–Meier estimator was used to calculate PFS and OS. Univariable analysis and Cox proportional hazards models were used to analyze the association between clinicopathological features and survival outcomes.ResultsAmong 63 patients, 54 (85.7%) were KRAS/NRAS/BRAF wild-type (WT). Univariate analysis showed that the male sex, primary lesions in the right colon, simultaneous metastasis, and unresectable primary lesions were significant risk factors for poor survival of HER2 positive mCRC (P < 0.05). Using Cox proportional hazards models, we found that the two factors of gender and resection of primary lesions were independent prognostic factors (P < 0.05). The median PFS and median OS of HER2-positive patients with mCRC who received first-line treatment were 8.4 months [95% confidence interval (CI): 5.0–11.7] and 48.2 months (95% CI: 23.5–72.8), respectively. The log-rank test revealed a significant difference in median OS survival between group A and group B (χ2 = 5.852, P = 0.016), and the two groups were divided according to the use or absence of trastuzumab treatment. In KRAS/NRAS/BRAF WT patients, there was a significant difference in median PFS and median OS between the fourth group patients (chemotherapy plus trastuzumab) and each of the other three groups (P < 0.05).ConclusionsThe two factors of gender and resection for primary lesion may be independent prognostic factors of advanced HER2 positive colorectal cancer patients. For patients with HER2-positive mCRC, patients in the chemotherapy combined with trastuzumab group have better efficacy than those without trastuzumab.

IS ADVANCED ALPHA-FETOPROTEIN PRODUCING GASTRIC CANCER TREATABLE?

We illustrated a patient with advanced alpha-fetoprotein producing gastric cancer, who was treated with chemotherapy combined with trastuzumab, resulting in complete response in four months after therapy. It has been 5 years after his initial therapy, he is now healthy and shows no evidence of tumor recurrence. The efcacy of the trastuzumab therapy in breast cancer patients prompted studies to evaluate potential clinical benet of the drug in patients with HER2 positive gastric cancer. The largest study, ToGA trial, has published a promising result leading FDA to approve the use of trastuzumab for HER2 positive gastric and gastroesophageal cancer. We discuss the need for the standardized assay method for HER2 status. We also bring attention to the existence of intratumoral heterogeneity in gastric cancer tissue which may cause false negative test for HER2 assay

Abstract P2-11-02: Subsequent breast cancer among women with HER2+ disease in a large integrated healthcare system

Abstract BACKGROUND: Women with breast cancer are living longer, including those with risk factors like HER2+ tumors or diagnosed at later stages, but a dearth of information exists on patients’ outcomes beyond clinical trials. We aimed to describe the risk of subsequent breast cancer (recurrence, second primary breast cancer, breast cancer-specific death) in women with HER2+ disease in a large community health plan. METHODS: We assembled a cohort of 3550 women (≥18 years) with HER2+ breast cancer (Stages I-III) during 2009-2017 whom were Kaiser Permanente Southern California members and followed them through December 2018. Subjects were identified from the plan’s NCI-SEER tumor registry. Data elements were captured from the tumor registry, pathology reports, and electronic health records. Hormone receptor (HR, ER and/or PR+), and HER2 status were assessed by immunohistochemistry or FISH. Subsequent breast cancer (SBC) events were identified from pathology report review (2/3 of cohort) or a validated computerized algorithm (1/3 of cohort without pathology reports). We computed SBC rates by trastuzumab use, HR status and tumor size and followed women from the index date to the date of SBC, disenrollment, death, or end of study in December 2018, whichever occurred first. Multivariable Cox proportional hazards regression was used to estimated adjusted hazard ratios (HR) and 95% confidence intervals. RESULTS: Of the 3550 women, the median age at diagnosis was 57 years. The cohort comprised 46% White; 13% Black; 16% Asian/Pacific Islander; and 24% Hispanic. 83% had stage I-II disease and 68% were HR+. Among these women, 81% received adjuvant trastuzumab; 3% other chemotherapy only and 16% neither. Less than 20 women used neoadjuvant trastuzumab. The cohort was followed a mean of 4.1 years (IQR: 1.5-6.3), with a maximum of 10 years. In the trastuzumab treated group, the cumulative 1-, 3-, 5-, and 10-year SBC risk were: 9.8%, 24.6%, 27.8%, and 30.4%, respectively. The mean time to SBC was 2.0 years (IQR: 0.9-2.5). SBC rate was lower in women who had trastuzumab (73.5/1,000 PY) therapy than those who did not (90.8/1,000 PY), corresponding to 22% reduced risk (adjusted HR=0.78, 95% CI: 0.66-0.91) (Table 1). Compared to women diagnosed at stage I, those with stage II-III disease were 1.19 times (adj HR=1.19, 95% CI: 1.01-1.40) more likely to develop SBC. Tumor size≥2cm was associated with a 23% greater risk of SBC (adj HR=1.23, 95% CI: 1.00-1.51) versus tumors&amp;lt;2cm. The multivariable analyses included these covariates: trastuzumab use; diagnosis age and year; stage; race/ethnicity; geocoded income; ER/PR; surgery type; other adjuvant therapy (endocrine, radiation, chemotherapy); lymph node status; histology; BMI; comorbidity; neoadjuvant trastuzumab, and other chemotherapy. CONCLUSION: This population-based study using one of the most comprehensive electronic medical records in California, we observed that the cumulative SBC risk persists, and was 30.4% at 10 years in women with HER2+ breast cancer treated with trastuzumab. Further, the SBC risk was greater in those with higher stages, large tumors (≥2 cm) and lymph node positive, even after accounting for trastuzumab use. Table. Multivariable HRs (95% CI) for subsequent breast-cancer in women with HER2+ invasive diseaseTotal Women*SBCSBC rates per 1,000 woman-yearsCrude modelMultivariable modelNNHR (95% CI)HR (95% CI)All Women 3550110176.5 TrastuzumabNo67522790.81.00 (ref)1.00 (ref)Yes287587473.50.86 (0.74-0.99)0.78 (0.66-0.91) Stage at dxI147138862.31.00 (ref)1.00 (ref)II-III207971387.31.45 (1.28-1.65)1.19 (1.01-1.40) Tumor sizeTumors&amp;lt;2 cm53012657.11.00 (ref)1.00 (ref)Tumors≥2 cm291094380.11.51 (1.25-1.83)1.23 (1.00-1.51) Lymph NodesPositive (ref)117043387.11.00 (ref)1.00 (ref)Negative206254363.90.69 (0.61-0.79)0.75 (0.65-0.88)*Some variables do not sum to N=3550 due to missing Citation Format: Reina Haque, Lie H Chen, Karen Kwan, Nina Oestreicher, Rowan T. Chlebowski, Deepa Lalla. Subsequent breast cancer among women with HER2+ disease in a large integrated healthcare system [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-11-02.

Multicenter phase Ib/II study of second-line trastuzumab, ramucirumab, and paclitaxel in patients with HER2-positive advanced gastric or gastroesophageal junction cancer: Updated HER-RAM study with biomarker analysis.

330 Background: HER-RAM study is the phase Ib/II multicenter study to evaluate the safety and efficacy of adding trastuzumab to ramucirumab and paclitaxel as a second-line treatment in HER2-positive advanced gastric or gastroesophageal junction (G/GEJ) cancer progressed from trastuzumab containing chemotherapy. We report survival follow up and exploratory biomarker results. Methods: Patients with HER2-positive advanced G/GEJ cancer who progressed after first-line trastuzumab containing chemotherapy were enrolled. Trastuzumab 4mg/kg on day 1 followed by 2mg/kg on days 8, 15, and 22, ramucirumab 8mg/kg on days 1 and 15, and paclitaxel (dose level 1: 80mg/m2, dose level -1: 70 mg/m2) on days 1, 8, and 15 of a 28-day cycle was tested. After safety analysis of lead-in safety cohort (phase 1b), phase 2 part was conducted to evaluate the primary endpoint of progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: No dose limiting toxicity at the dose level 1 was observed at the phase Ib part, the dose level 1 with full dose combination was determined as recommended phase 2 dose. At the time of data lock on September 7th, 2021, 50 patients including 3 patients from the phase 1b part were evaluable for response and safety. Median age was 60 years old (range 29-82) and most patients were male (40/50). At baseline, 39 patients had tumors with HER-2 3+ by immunohistochemistry (IHC) and 11 had those with HER-2 2+ by IHC with ERBB2 amplification by in situ hybridization. With median follow-up duration of 18.8 months, median PFS and OS were 7.0 months (95% confidence interval [CI]: 4.9-9.2 months) and 13.6 months (95% CI: 9.5-17.6 months), respectively. ORR was 54% (27/50, complete response = 1, partial response = 26) and DCR was 96% (48/50), respectively. On the exploratory analysis, HER-2 positivity of tumor tissue was lost after fist-line chemotherapy in 8 of 23 patients (34.7%) without any definite association between loss of HER-2 and outcomes. Most common hematologic adverse event (AE) was neutropenia (all grade: 64%, grade 3/4: 52%) with 1 case of febrile neutropenia (2%). Most common non-hematologic AE was peripheral sensory neuropathy and anorexia (all grade: 32%, grade 3: 2%, respectively). Gastrointestinal (GI) bleeding occurred in 6 cases (grade 3 upper GI bleeding: 3 patients, grade 1/2 lower GI bleeding: 3 patients), whereas GI perforation was not observed. Hypertension occurred in 3 patients (grade 1/2: 1 patient, grade 3: 2 patients). No new or unexpected AEs were observed. Conclusions: The continuous use of trastuzumab in combination with ramucirumab and paclitaxel showed promising activity and manageable safety profile in HER2-positive G/GEJ cancer patients who progressed after trastuzumab containing chemotherapy. Clinical trial information: NCT04888663.

The benefits of trastuzumab in the treatment of HER2+ breast cancer as a function of exposure time.

BackgroundBreast cancer is a heterogeneous disease with overexpression of several receptors, such as human epidermal receptor 2 (HER2), which is a prognostic and predictive biomarker for treatment with the anti-HER2 monoclonal antibody trastuzumab. This study aimed to test the contribution of this regimen in patients with overexpression/amplification of HER2 for periods shorter than the 1-year treatment recommendation.MethodsA retrospective single-centre study involving 155 patients with non-metastatic (stages I–III) invasive ductal HER2+ breast carcinoma, with a median follow-up of 48.9 months after completion of adjuvant therapy, except endocrine therapy.ResultsAbout 60% of patients received trastuzumab therapy for a median time of 365 days. Although the use of trastuzumab for a short period has provided some benefit, analyses of survival with a continuous dependent variable have revealed a minimum time for improved survival. In the multivariate analysis by Cox regression, trastuzumab use duration exceeding 9 weeks resulted in protection against distant metastasis (adjusted HR: 0.307 (0.139–0.678), p = 0.004), disease progression (adjusted hazard ratio (HR) 0.353 (0.175–0.714), p = 0.004) and death (adjusted HR: 0.267 (0.105–0.678), p = 0.005), being superior to multimodal systemic therapy with chemotherapy and to endocrine therapy without trastuzumab, but inferior to almost 1 year of administration of this monoclonal antibody, especially regarding overall survival (adjusted HR: 0.203 (0.069–0.596), p = 0.004).ConclusionDespite showing some benefits, the protective effect derived from a suboptimal time of trastuzumab exposure is inferior to the standard course of 1 year.

НЕОАДЪЮВАНТНАЯ ХИМИОТЕРАПИЯ HER2-ПОЛОЖИТЕЛЬНОГО РАКА МОЛОЧНОЙ ЖЕЛЕЗЫ С ИСПОЛЬЗОВАНИЕМ ТРАСТУЗУМАБА И ПЕРТУЗУМАБА

Breast cancer is the most common malignant tumor in women. HER2-positive (HER2+) breast cancer is a molecular subtype characterized by an aggressive course, a tendency for tumor cells to spread rapidly, and resistance to standard cytostatic regimens. A number of large randomized trials have shown that the use of neoadjuvant chemotherapy provides the same overall survival rates as adjuvant regimens. In addition, the use of neoadjuvant chemotherapy makes it possible to achieve therapeutic pathomorphosis. The discovery of new chemotherapeutic drugs has made it possible to use a dual blockade of HER2 receptors due to interaction with different subdomains of this protein. In particular, chemotherapy using Trastuzumab, Pertuzumab, and Docetaxel has proven to be an effective regimen to achieve high rates of therapeutic pathomorphosis and survival. The paper analyzes the mechanism of action and effectiveness of the combined use of Trastuzumab and Pertuzumab, presents two clinical cases of practical treatment using dual targeted blockade.

Next-generation sequencing, should I use anti-HER2 therapy for HER2-amplified tumors off-label? Illustrating an extrapolation framework.

Background:Next-generation sequencing is used to increase targeted treatment opportunities, particularly for patients who have exhausted standard options. Where randomized controlled trial evidence for a targeted therapy is available for molecular alterations in one tumor type, the dilemma for the clinician is whether ‘matching’ targeted agents should be recommended off-label for the same molecular alterations detected in other tumor types, for which no trial data are available to guide practice. To judge the likely benefits, it may be possible to extrapolate evidence from cancers where treatment benefits have been established.Methods:We present a framework for assessing the appropriateness of extrapolation using trastuzumab, an anti-HER2 antibody, for HER2-amplified tumors where trastuzumab use would be off-label as an illustrative example.Results:The following should be considered for the tumor type where trastuzumab would be off-label: (a) reliability of the NGS assay for detecting HER2 amplification; (b) criteria for defining HER2 positivity; (c) strength of evidence supporting the actionability of HER2 amplification and trastuzumab; (d) whether better clinical outcomes with trastuzumab are due to a more favorable natural history rather than trastuzumab effect; (e) signals of trastuzumab activity and whether it translates to clinically meaningful benefit; (f) whether the safety profile of trastuzumab differs from established indications; and (g) discussion points for shared decision making (SDM) to facilitate informed consent.Conclusion:We present a systematic approach for appraising evidence to support extrapolating trastuzumab benefits from established indications to off-label applications. Extrapolation criteria and areas of uncertainty to inform SDM are outlined. This framework is potentially generalizable to other tumor-agnostic biomarker-targeted therapy scenarios. It is a practical approach for clinicians to apply in routine practice and should be considered by molecular tumor boards who make off-label recommendations.

Role of Post-Neoadjuvant therapy with trastuzumab emtansine in HER2-positive breast cancer

The widespread introduction of anti-HER2 agents has changed the natural course of Her2-positive breast cancer. The use of trastuzumab, and later dual anti-HER2 blockade with pertuzumab, in neoadjuvant regimens significantly increased the chances of complete cure. However, among patients with early and locally advanced forms of Her2-positive cancer, there is a cohort with an extremely unfavorable prognosis – tumors that have not achieved complete pathomorphological regression after neoadjuvant chemotherapy.The presence of a residual tumor in Her2-positive breast cancer has long been only a prognostically unfavorable factor without the potential to influence disease outcome. The results of the international phase III study KATHERINE, which demonstrated the high efficacy of post-adjuvant therapy with trastuzumab emtansine (T-DM1) in this patient cohort, have established a new standard of care. Due to T-DM1 adjuvant therapy, the possibility to significantly improve long-term results determined the predictive characteristics of the morphological response to the choice of treatment tactics, which became an important argument in favor of neoadjuvant therapy in patients with not only locally advanced but also primarily resectable Her2-positive breast cancer, followed by personalization of therapy.This article presents our own experience with post-neoadjuvant therapy with trastuzumab emtansine in a young patient with a residual tumor. The data of the main studies in early Her2-positive breast cancer are summarized.

HER2 in gastric adenocarcinoma: where do we stand today?

Aim:HER2is a proto-oncogene expressed in 10-30% of gastric adenocarcinomasand is an ideal target for inhibition in malignancy withhigh recurrence and dismal survival rates. Materials & methods: A systematic search was conducted via PubMed, Google Scholarand theclinicaltrials.gov database to report the results of ongoing and past studies investigating HER2 inhibitors in gastric cancer. Results: Twenty-five studies were included; ToGA trial is the pivotal trial approving the use of trastuzumab in metastatic gastric cancer, followed by more studies investigating other HER2 inhibitors in this setting, as well as in local and locoregional malignancy. Conclusion: Anti-HER2 molecules are proving efficacy and safety in gastric cancer; the evidence is growingand association with other cancer agents is under investigation.

Immunohistochemical expression of FOXP3 in gastric carcinoma; its relation to Ki-67 proliferation marker, HER2/neu expression, and other clinicopathological parameters

ABSTRACT Gastric cancer is common cancer in the world. Contradictory results regarding FOXP3 expression in gastric carcinoma were detected and the role of Ki-67 in prognosis is not completely understood. Furthermore, due to increasing use of anti-HER2 drug trastuzumab for gastric cancer, assessment of HER2 expression becomes important. This study tried to assess the FOXP3 expression in gastric carcinoma and to study the relation between its expression and Ki-67 and HER2/neu expression and relation between their expression and other clinicopathological variables. This retrospective study was carried out on 60 gastric adenocarcinoma cases. Tissue microarrays and immunohistochemical staining for FOXP3, Ki-67 and HER2/neu were done and then assessed and scored. HER2/neu expression showed significant relation to Lauren histological type and lymph node status. High Ki-67 index was related significantly to patients’ age, lympho-vascular tumor emboli, peri-neural invasion, tumor grade, lymph node status, and cancer stage. There was significant relation between high FOXP3 expression and patients’ age, lympho-vascular tumor emboli, peri-neural invasion, tumor grade, lymph node status, and cancer stage. Direct positive significant relationships between HER2/neu, Ki-67, and FOXP3 expression were noticed. Finally, high FOXP3 expression, positive HER2/neu, and high Ki-67 nuclear proliferation index may be an indication of the aggressiveness of gastric carcinoma.

Nanotechnology to Cure Breast Cancer and Obstacles in its Way

Nanomaterials owing to their remarkable pharmaceutical properties and potential to load large quantities of drugs are considered an ideal vector for carrying medicine to the target site. The treatment of breast cancer has been a pressing issue due the use of conventional methods of treatment resulting in many side effects. Nanotechnology offers a more targeted approach in breast cancer treatment. The present review examines the role of Carbon Nanotubes (CNTs) and nanoparticles in the treatment of breast cancer and the obstacles in the way of nanotechnology in becoming one of the best methods in breast cancer treatment and drug delivery. Use of monoclonal antibody trastuzumab against HER-2 biomarkers by attaching it with nanotubes or nanoparticles is considered the best-targeted therapy along with photo thermal ablation. The absence of human tumor models and lack of toxicological assays are the major factors contributing to differences between the preclinical and clinical trial results.

Demographic, tumour, and treatment characteristics of female patients with breast cancer in Sri Lanka; results from a hospital-based cancer registry

BackgroundAlthough breast cancer is the most common cancer among Sri Lankan women, there is little published data on patient characteristics and treatment in the local context. We aimed to describe disease characteristics and management in a large contemporary cohort of women with breast cancer at the National Cancer Institute of Sri Lanka (NCISL).MethodsAll women with invasive primary breast cancers diagnosed during 2016–2020 were identified from the NCISL breast cancer registry. The NCISL sees approximately 40% of all cancer patients in Sri Lanka. Cancer stage at diagnosis was defined according to the Tumour, Node, and Metastasis (TNM) staging system and the Estrogen (ER) and progesterone (PR) receptor status was determined based on the results of immunohistochemistry tests. Descriptive statistics were used to describe the study cohort and treatment patterns.ResultsOver 5100 patients were diagnosed with breast cancer during the study period at the NCISL. The mean age of the women was 56 (SD 12) years. Common co-morbidities were hypertension (n = 1566, 30%) and diabetes mellitus (n = 1196, 23%). Two thirds (66%) of the cancers were early stage (stage I & II) at diagnosis. ER/PR positivity rate was 72% and HER-2 positivity rate was 22%. Two thirds of the women had undergone mastectomy while 68% had undergone axillary clearance. The rate of chemotherapy delivery was 91% for women with node positive disease while 77% of eligible women (i.e., after wide local excision or with > 3 positive lymph nodes) had received adjuvant radiotherapy. Endocrine therapy was initiated in 88% of eligible women with hormone receptor positive disease while rate of trastuzumab use was 59% among women with HER2 positive breast cancer.ConclusionsHigh percentage of advanced breast cancer at diagnosis and high prevalence of comorbidities are some of the major challenges faced in the management of breast cancer in Sri Lanka. Given that stage at diagnosis is the most important prognostic factor determining survival, greater efforts are needed to promote early diagnosis of breast cancer. Considerable lapses in the concordance between guideline recommendations and the delivery of cancer care warrants closer assessment and intervention.

Changes in the detection of human epidermal growth factor receptor 2 gene (Her-2) status for Her-2 fluorescent in situ hybridization testing

Changes in the detection of human epidermal growth factor receptor 2 gene (Her-2) status for Her-2 fluorescent in situ hybridization testing

Risks of trastuzumab-related cardiotoxicity in breast cancer patients in Taiwan

Abstract Aims Despite being an essential therapy for breast cancer, trastuzumab has potential risks of cardiotoxicity. The incidence of trastuzumab-related major adverse cardiac and cerebrovascular event (MACCE) and its predictors remain unknown in Taiwan. Methods and results Through a three-hospital retrospective cohort study, we analyzed the incidence of MACCE in 386 breast cancer patients exposure to trastuzumab from 2010 to 2018. To further reconfirm our findings, in a nationwide study using the Taiwanese National Health Insurance Research Database and National Cancer Registry, we identified 13502 women diagnosed with breast cancer who received chemotherapy from 2010 to 2015 and found 6751 women who received initial treatment with trastuzumab. After 1:1 propensity score matching with trastuzumab nonusers, the incidence of MACCE was measured with a median follow-up of 36 months. In the hospital-based study, among 386 patients receiving trastuzumab, the 5-year incidences of MACCE and heart failure (HF) were 5.4% and 2.8%, respectively. In the national cohort, the crude incidences of MACCEs and HF were 4.67% and 3.21%, respectively. After adjustment for age and comorbidities, the hazard ratio of MACCE was 1.485 (95% CI 1.246–1.769). Notably, among the endpoints, only the hazard ratio of HF was significantly higher in patients receiving trastuzumab than in nonusers. In the subgroup analysis, except for patients also using taxanes, those receiving trastuzumab had a higher risk of MACCE than nonusers. Conclusions From clinical observations in a nationwide cohort, we found an increased risk of MACCE, especially HF, in patients receiving trastuzumab. Given that its cardiotoxicity is independent of traditional cardiovascular risks, our findings highlight critical concerns regarding the cardiac safety of trastuzumab use. Funding Acknowledgement Type of funding sources: Private hospital(s). Main funding source(s): Chi-Mei Medical Center, National Cheng Kung University Hospital