A systematic review of dual targeting in HER2-positive breast cancer

Background

Human epidermal growth factor receptor 2 (HER2) is overexpresed in 15–20% of all breast cancers. Treatment with trastuzumab has led to an improved outcome and prolonged survival of HER2-positive breast cancer patients and today the drug is established as standard of care in both the adjuvant and metastatic settings. However, trastuzumab resistance is common and a major focus in the treatment of HER2-positive breast cancer has been developing therapeutic agents to either potentiate the effect of trastuzumab or to target cells which have become resistant to trastuzumab. The present review addresses efficacy and toxicity of dual targeting in HER2-positive breast cancer.

Materials and methods

A computer-based literature search was carried out using PubMed; data reported at international meetings and clinicaltrials.gov was included.

Results

This paper describes efficacy and safety of lapatinib, pertuzumab or trastuzumab-DM1 in combination with trastuzumab in the (neo)adjuvant and metastatic settings. Furthermore, combinations of trastuzumab and drugs targeting the downstream pathway are described.

Conclusion

Dual blockade is likely to represent a substantial advance for patients with HER2-positive breast cancer. However, the relevant subpopulation remains to be defined and side effects including cardiotoxicity might be a limiting factor to the use. There is an urgent need for prospective biomarker-driven trials to identify patients for whom dual targeting is cost-effective.     

克痒舒洗液对128株阴道感染细菌的抗菌作用

目的：研究克痒舒洗液对引起非特异性阴道炎细菌的抗菌作用。方法：用克痒舒洗液及其中药和西药组分对从病人体内分离出的7种125株病原菌及3株标准菌种检测了最低抑菌浓度（MIC）,最低杀菌浓度（MBC）及琼脂扩散试验。结果：该药组分对受试的7种病原菌都有不同程度的抑菌、杀菌作用,合剂克痒舒则有协同作用。结论：克痒舒洗液对细菌性阴道病及霉菌性阴道炎将有较好的疗效。     

头孢硫咪体外抗菌活性测定

目的：评价第一代头孢菌素头孢硫脒对近期从临床分离的致病菌的体外抗菌活性。方法：用对倍稀释法测定头孢硫咪的最小抑菌浓度（ＭＩＣ）并与头孢唑啉、头孢呋辛、头孢他啶体外抗菌活性进行了对比。结果：头孢硫脒对肺炎球菌、化脓性链球菌、ＭＳＳＡ、ＭＳＳＥ和卡他布汉氏菌有较强的抗菌活性。结论：头孢硫脒对Ｇ^＋球菌有较强的抑菌活性和杀菌活性,对肠球菌亦显示有很强的体外抗菌活性。     

米诺环素的药效学研究

国产米诺环素（ｍｉｎｏｃｙｃｌｉｎｅ，ＭＩＮＯ）的体内外抗菌活性研究结果表明：ＭＩＮＯ是一个对革兰氏阳性菌和革兰氏阴性菌均有较强抗菌活性的广谱抗生素，对金葡球菌、表葡球菌的抗菌活性优于四环素（ＴＣ）、青霉素（ＰＣＧ）、麦迪霉素（ＭＤＭ）、庆大霉素（ＧＭ）和依诺沙星（ＥＮＸ），并对耐四环素金葡球菌和表葡球菌有很强的抗菌活性。ＭＩＮＯ对化脓性链球菌的抗菌活性优于ＴＣ、ＭＤＭ、ＧＭ、ＥＮＸ，弱于ＰＣＧ；对大肠杆菌、肺炎克雷伯氏菌的抗菌活性优于ＴＣ、ＧＭ，弱于ＥＮＸ；对变形杆菌的抗菌活性优于ＴＣ，弱于ＧＭ、ＥＮＸ。口服ＭＩＮＯ对金葡球菌感染小鼠的ＥＤ５０为０．９９ｍｇ／ｋｇ，优于强力霉素（ＤＯＸＹ）和ＴＣ；对大肠杆菌感染小鼠的ＥＤ５０为１０．９６ｍｇ／ｋｇ，优于ＴＣ，与ＤＯＸＹ的ＥＤ５０无显著性差异；对耐ＴＣ金葡球菌感染小鼠的ＥＤ５０为０．６５ｍｇ／ｋｇ，明显优于ＤＯＸＹ和ＴＣ。杀菌试验表明：ＭＩＮＯ在２～４ＭＩＣ时，对金葡球菌和大肠杆菌具有杀菌作用。     

环丙沙星注射液的抗菌作用

环丙沙星注射液对常见致病菌的ＭＩＣ为：绿脓杆菌０．６２５μｇ／ｍＬ，大肠杆菌０．０３９μｇ／ｍＬ，脑膜炎球菌０．３１３μｇ／ｍＬ，金黄色葡萄球菌０．６２５μｇ／ｍＬ，伤寒杆菌０．０３９μｇ／ｍＬ，肺炎球菌０．１２５μｇ／ｍＬ，溶血性链球菌０．６２５μｇ／ｍＬ．环丙沙星注射液对常见致病菌的ＭＢＣ为：绿脓杆菌２．５μｇ／ｍＬ，脑膜炎球菌１．２５μｇ／ｍＬ，大肠杆菌０．１５６μｇ／ｍＬ，伤寒杆菌０．１５６μｇ／ｍＬ，肺炎球菌２．５μｇ／ｍＬ，溶血性链球菌１．２５μｇ／ｍＬ，金黄色葡萄球菌１．２５μｇ／ｍＬ．体内感染治疗试验对接种大肠杆菌０．５×０７个／只静脉给药的ＥＰ５０为（０．７８７±０．１２９）ｍｇ／ｋｇ，对接种肺炎链球菌０．８×１０６个／只静脉给药的ＥＰ５０为（３．３１３±０．５６７）ｍｇ／ｋｇ．     

Trastuzumab,Pertuzumab, and Docetaxel as the First Line for HER-2-Positive Metastatic Breast Cancer among Arabs

IntroductionHuman epidermal growth factor receptor 2 (HER-2) targeted therapy regimens can improve tumor response in HER-2-positive metastatic breast cancer (MBC), with overall survival benefits.ObjectiveWe evaluated the efficacy of dual HER-2 blockade combined with chemotherapy for HER-2-positive MBC patients as a first-line therapy in our patient population.Patients and MethodsWe identified 75 patients at King Faisal Specialist Hospital and Research Center that received trastuzumab, pertuzumab, and docetaxel as a first-line therapy in HER-2 positive MBC in 2013–2016.ResultsMedian age at diagnosis was 45 years; 54.7% were estrogen receptor (ER)-positive. 10% of patients presented with only bone metastasis. The median follow-up time was 36 months with an objective response rate of 74.7% (complete response [CR] 18.7%; partial response [PR] 56%). The 5-year progression-free survival (PFS) and overall survival (OS) were 21% and 71.9% respectively, with a median PFS of 36 months (95% confidence interval [CI] 23.6–48.4). The 5-year OS for ER-negative and ER-positive patients was 93.9% and 59.4% respectively (p = 0.189); 23 patients experienced grade 1/2 toxicity and 2 patients had grade 3/4 toxicity. In terms of OS and PFS, the site of metastasis did not make any significant difference.ConclusionsFirst line pertuzumab, trastuzumab, and docetaxel for HER-2-positive MBC patients was found to be an effective and safe therapy in the Saudi population. This finding was consistent with the results seen in the CLEOPATRA trials.     

Lobular Metastatic Breast Cancer Patients With Gastrointestinal Involvement: Features and Outcomes

Introduction

Metastatic breast cancer typically involves the lungs, bones, brain, and liver and only occasionally affects the gastrointestinal (GI) tract. The relevant published data have been limited to case reports and small series of patients.

Imaging in the evaluation and follow-up of early and advanced breast cancer: When,why, and how often?

Imaging in the evaluation and follow-up of patients with early or advanced breast cancer is an important aspect of cancer care. The role of imaging in breast cancer depends on the goal and should only be performed to guide clinical decisions. Imaging is valuable if a finding will change the course of treatment and improve outcomes, whether this is disease-free survival, overall survival or quality-of-life. In the last decade, imaging is often overused in oncology and contributes to rising healthcare costs. In this context, we review the data that supports the appropriate use of imaging for breast cancer patients. We will discuss: 1) the optimal use of staging imaging in both early (Stage 0–II) and locally advanced (Stage III) breast cancer, 2) the role of surveillance imaging to detect recurrent disease in Stage 0–III breast cancer and 3) how patients with metastatic breast cancer should be followed with advanced imaging.     

The Role of CYP2D6 Polymorphisms in Determining Response to Tamoxifen in Metastatic Breast Cancer Patients: Review and Egyptian Experience

Background: Metastatic breast cancer (MBC) represents a major health problem in Egypt and worldwide. Prognostic and predictive factors for patients with MBC are highly required for better management and improved survival. The aim of this study was to assess the prognostic and predictive value(s) of CYP2D6 polymorphisms in Tamoxifen responders and non-responders. Methods: A cohort of 157 hormone receptor positive, locally recurrent inoperable and/or metastatic (MBC) Egyptian female patients was assessed for CYP2D6 polymorphisms. Data were correlated to relevant clinic-pathological features of the patients, response to tamoxifen, and survival rates. Results: CYP2D6 polymorphisms were detected in 44/157 cases (28%), 30 of them (68.2%) were refractory and 14 (31.8%) were responders (P=0.027). The CYP2D6 *3,*4 variants were significantly prevalent in the refractory group 26/30 (86.6%), while the *10/*10 and *10/*3 variants were more common in the responders 12/14 (85.71%, P=0.027). CYP2D6 polymorphism associated significantly with Her-2 amplification (P=0.001) as well as reduced overall survival rates in both refractory and responder patients (p < 0.001). Conclusion: CYP2D6 polymorphisms can significantly predict response to Tamoxifen treatment, and also associates with poor overall survival rates in MBC patients