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      Difficulty Diagnosing a Brain Tumor during Clinical Maintenance of a Complete Response to anti-HER2 Treatments for Metastatic Breast Cancer: A Case Report

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          A 46-year-old woman with erythema of the right breast presented to our hospital and was diagnosed with stage IV breast cancer (HER2-positive invasive ductal carcinoma). She received 4 courses of anthracycline-based regimens and 4 courses of trastuzumab + pertuzumab + docetaxel (Tmab + Pmab + DTX). Since she responded well to these therapies, only Tmab + Pmab was continued thereafter. Twenty-three months after starting treatment, she developed a headache. A tumor was identified in the right temporal lobe. Craniotomy was performed for definitive diagnosis. Intraoperative pathological assessment suggested the tumor to be brain metastasis of breast cancer. However, the final pathological diagnosis was diffuse large B-cell lymphoma of central nervous system (DLBCL-CNS) based on re-assessment with immunohistochemical examinations. Therefore, the Tmab + Pmab was discontinued, and 6 courses of high-dose methotrexate therapy were administered. This case highlights the importance of considering rare entities, such as DLBCL, when diagnosing a solitary brain tumor in a patient with a primary cancer, based on imaging and pathological findings.

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          Most cited references 10

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          Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial.

          The antibody-drug conjugate trastuzumab emtansine is indicated for the treatment of patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane. Approval of this drug was based on progression-free survival and interim overall survival data from the phase 3 EMILIA study. In this report, we present a descriptive analysis of the final overall survival data from that trial.
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            Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer.

            The anti-human epidermal growth factor receptor 2 (HER2) humanized monoclonal antibody trastuzumab improves the outcome in patients with HER2-positive metastatic breast cancer. However, most cases of advanced disease eventually progress. Pertuzumab, an anti-HER2 humanized monoclonal antibody that inhibits receptor dimerization, has a mechanism of action that is complementary to that of trastuzumab, and combination therapy with the two antibodies has shown promising activity and an acceptable safety profile in phase 2 studies involving patients with HER2-positive breast cancer. We randomly assigned 808 patients with HER2-positive metastatic breast cancer to receive placebo plus trastuzumab plus docetaxel (control group) or pertuzumab plus trastuzumab plus docetaxel (pertuzumab group) as first-line treatment until the time of disease progression or the development of toxic effects that could not be effectively managed. The primary end point was independently assessed progression-free survival. Secondary end points included overall survival, progression-free survival as assessed by the investigator, the objective response rate, and safety. The median progression-free survival was 12.4 months in the control group, as compared with 18.5 months in the pertuzumab group (hazard ratio for progression or death, 0.62; 95% confidence interval, 0.51 to 0.75; P<0.001). The interim analysis of overall survival showed a strong trend in favor of pertuzumab plus trastuzumab plus docetaxel. The safety profile was generally similar in the two groups, with no increase in left ventricular systolic dysfunction; the rates of febrile neutropenia and diarrhea of grade 3 or above were higher in the pertuzumab group than in the control group. The combination of pertuzumab plus trastuzumab plus docetaxel, as compared with placebo plus trastuzumab plus docetaxel, when used as first-line treatment for HER2-positive metastatic breast cancer, significantly prolonged progression-free survival, with no increase in cardiac toxic effects. (Funded by F. Hoffmann-La Roche/Genentech; ClinicalTrials.gov number, NCT00567190.).
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              Central nervous system metastases in patients with HER2-positive metastatic breast cancer: incidence, treatment, and survival in patients from registHER.

              registHER is a prospective, observational study of 1,023 newly diagnosed HER2-positive metastatic breast cancer (MBC) patients. Baseline characteristics of patients with and without central nervous system (CNS) metastases were compared; incidence, time to development, treatment, and survival after CNS metastases were assessed. Associations between treatment after CNS metastases and survival were evaluated. Of the 1,012 patients who had confirmed HER2-positive tumors, 377 (37.3%) had CNS metastases. Compared with patients with no CNS metastases, those with CNS metastases were younger and more likely to have hormone receptor-negative disease and higher disease burden. Median time to CNS progression among patients without CNS disease at initial MBC diagnosis (n = 302) was 13.3 months. Treatment with trastuzumab, chemotherapy, or surgery after CNS diagnosis was each associated with a statistically significant improvement in median overall survival (OS) following diagnosis of CNS disease (unadjusted analysis: trastuzumab vs. no trastuzumab, 17.5 vs. 3.8 months; chemotherapy vs. no chemotherapy, 16.4 vs. 3.7 months; and surgery vs. no surgery, 20.3 vs. 11.3 months). Although treatment with radiotherapy seemed to prolong median OS (13.9 vs. 8.4 months), the difference was not significant (P = 0.134). Results of multivariable proportional hazards analyses confirmed the independent significant effects of trastuzumab and chemotherapy (HR = 0.33, P < 0.001; HR = 0.64, P = 0.002, respectively). The effects of surgery and radiotherapy did not reach statistical significance (P = 0.062 and P = 0.898, respectively). For patients with HER2-positive MBC evaluated in registHER, the use of trastuzumab, chemotherapy, and surgery following CNS metastases were each associated with longer survival.

                Author and article information

                Case Reports in Ophthalmology
                S. Karger AG
                September - December 2020
                23 October 2020
                : 13
                : 3
                : 1311-1316
                aDepartment of Breast Oncology, Juntendo University School of Medicine, Tokyo, Japan
                bDepartment of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan
                cDepartment of Hematology, Juntendo University School of Medicine, Tokyo, Japan
                Author notes
                *Ryoko Semba, Department of Breast Oncology, Juntendo University School of Medicine, 2-1-1 Hongo Bunkyo-ku, Tokyo 113-0033 (Japan), r-semba@juntendo.ac.jp
                511051 Case Rep Oncol 2020;13:1311–1316
                © 2020 The Author(s). Published by S. Karger AG, Basel

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                Figures: 4, Pages: 6
                Case Report


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