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      Anti-HER-2 therapy following severe trastuzumab-induced cardiac toxicity

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          Abstract

          The human epidermal growth factor receptor 2 (HER2) is overexpressed in 25%–30% of breast cancer patients. Anti-HER2 therapies have changed the aggressive course of HER2+ breast cancer. In spite of the therapeutic benefits, their cardiotoxicities are major concerns, especially when used concurrently with anthracyclines.

          Here we present an elderly patient with relapsed HER2+ breast cancer. Her presentation for relapsed disease was unusual for the physical finding as well as the history of trastuzumab-induced severe cardiotoxicity while requiring additional anti-HER2 therapy. She received neoadjuvant anti-HER2 treatment for stage III breast caner. Due to severe reduction of cardiac ejection fraction (EF), she only received five doses of adjuvant transtuzumab. Unfortunately her disease relapsed one year later with chest wall lesions and a persistent low EF. We treated the patient with lapatinib combined with capecitabine which resulted rapid resolution of her chest wall lesion. More importantly, the patient had one year of disease control without deterioration in her ejection fraction. We discussed the management of recurrent HER2+ breast cancer with chest wall disease and the choice of anti-HER2 therapy in patients with a history of transtuzumab-induced cardiac dysfunction.

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          Most cited references16

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          Effect of Enalapril on Mortality and the Development of Heart Failure in Asymptomatic Patients with Reduced Left Ventricular Ejection Fractions

          New England Journal of Medicine, 327(10), 685-691
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            Randomized study of Lapatinib alone or in combination with trastuzumab in women with ErbB2-positive, trastuzumab-refractory metastatic breast cancer.

            Preclinical studies in ErbB2-positive cell lines demonstrated a synergistic interaction between lapatinib and trastuzumab, suggesting that dual blockade is more effective than a single agent alone. EGF104900 compared the activity of lapatinib alone or in combination with trastuzumab in patients with ErbB2-positive, trastuzumab-refractory metastatic breast cancer (MBC). Patients with ErbB2-positive MBC who experienced progression on prior trastuzumab-containing regimens were randomly assigned to receive either lapatinib alone or in combination with trastuzumab. The primary end point was progression-free survival (PFS). Secondary efficacy end points included overall response rate (ORR), clinical benefit rate (CBR; complete response, partial response, and stable disease for >/= 24 weeks), and overall survival (OS). In the intent-to-treat population (N = 296) who received a median of three prior trastuzumab-containing regimens, the combination of lapatinib with trastuzumab was superior to lapatinib alone for PFS (hazard ratio [HR] = 0.73; 95% CI, 0.57 to 0.93; P = .008) and CBR (24.7% in the combination arm v 12.4% in the monotherapy arm; P = .01). A trend for improved OS in the combination arm was observed (HR = 0.75; 95% CI, 0.53 to 1.07; P = .106). There was no difference in ORR (10.3% in the combination arm v 6.9% in the monotherapy arm; P = .46). The most frequent adverse events were diarrhea, rash, nausea, and fatigue; diarrhea was higher in the combination arm (P = .03). The incidence of symptomatic and asymptomatic cardiac events was low (combination therapy = 2% and 3.4%; monotherapy = 0.7% and 1.4%, respectively). Despite disease progression on prior trastuzumab-based therapy, lapatinib in combination with trastuzumab significantly improved PFS and CBR versus lapatinib alone, thus offering a chemotherapy-free option with an acceptable safety profile to patients with ErbB2-positive MBC.
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              Trastuzumab emtansine (T-DM1) versus lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer and central nervous system metastases: a retrospective, exploratory analysis in EMILIA†

              In a retrospective analysis of the EMILIA study, the rate of central nervous system (CNS) progression in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer was similar for trastuzumab emtansine (T-DM1) and for capecitabine–lapatinib. In patients with treated, asymptomatic CNS metastases at baseline, T-DM1 was associated with significantly improved overall survival versus capecitabine–lapatinib.
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                Author and article information

                Contributors
                Journal
                Genes Dis
                Genes Dis
                Genes & Diseases
                Chongqing Medical University
                2352-4820
                2352-3042
                03 August 2017
                September 2017
                03 August 2017
                : 4
                : 3
                : 159-162
                Affiliations
                [a ]Georgia Cancer Center, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA
                [b ]Tianjin Medical University Cancer Institute and Hospital, Huanhuxi Road, Hexi District, Tianjin 300060, China
                Author notes
                []Corresponding author. Georgia Cancer Center, Augusta University, 1411 Laney Walker Blvd., Augusta, GA 30912, USA. Fax: +1 706 721 0360. stang@ 123456augusta.edu
                Article
                S2352-3042(17)30046-6
                10.1016/j.gendis.2017.07.007
                6147109
                1b99d42e-0902-402e-81f0-1931878bfc99
                © 2017 Chongqing Medical University. Production and hosting by Elsevier B.V.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 4 July 2017
                : 25 July 2017
                Categories
                Article

                diagnosis and management,her2 positive breast cancer,lapatinib,trastuzumab-induced cardiac toxicity,unusual presentation

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