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      Treatment strategies to prevent and reduce gynecomastia and/or breast pain caused by antiandrogen therapy for prostate cancer : Statement from the DEGRO working group prostate cancer

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          Abstract

          Aim

          To provide an overview on the available treatments to prevent and reduce gynecomastia and/or breast pain caused by antiandrogen therapy for prostate cancer.

          Methods

          The German Society of Radiation Oncology (DEGRO) expert panel summarized available evidence published and assessed the validity of the information on efficacy and treatment-related toxicity.

          Results

          Eight randomized controlled trials and one meta-analysis were identified. Two randomized trials demonstrated that prophylactic radiation therapy (RT) using 1 × 10 Gy or 2 × 6 Gy significantly reduced the rate of gynecomastia but not breast pain, as compared to observation. A randomized dose-finding trial identified the daily dose of 20 mg tamoxifen (TMX) as the most effective prophylactic dose and another randomized trial described that daily TMX use was superior to weekly use. Another randomized trial showed that prophylactic daily TMX is more effective than TMX given at the onset of gynecomastia. Two other randomized trials described that TMX was clearly superior to anastrozole in reducing the risk for gynecomastia and/or breast pain. One comparative randomized trial between prophylactic RT using 1 × 12 Gy and TMX concluded that prophylactic TMX is more effective compared to prophylactic RT and furthermore that TMX appears to be more effective to treat gynecomastia and/or breast pain when symptoms are already present. A meta-analysis confirmed that both prophylactic RT and TMX can reduce the risk of gynecomastia and/or breast pain with TMX being more effective; however, the rate of side effects after TMX including dizziness and hot flushes might be higher than after RT and must be taken into account. Less is known regarding the comparative effectiveness of different radiation fractionation schedules and more modern RT techniques.

          Conclusions

          Prophylactic RT as well as daily TMX can significantly reduce the incidence of gynecomastia and/or breast pain. TMX appears to be an effective alternative to RT also as a therapeutic treatment in the presence of gynecomastia but its side effects and off-label use must be considered.

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          Most cited references23

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          Evaluation of tamoxifen and anastrozole in the prevention of gynecomastia and breast pain induced by bicalutamide monotherapy of prostate cancer.

          To determine whether tamoxifen or anastrozole prevents gynecomastia and breast pain caused by bicalutamide (150 mg) without compromising efficacy, safety, or sexual functioning. A double-blind, placebo-controlled trial was performed in patients with localized, locally advanced, or biochemically recurrent prostate cancer. Patients (N = 114) were randomly assigned to either bicalutamide (150 mg/d) plus placebo or in combination with tamoxifen (20 mg/d) or anastrozole (1 mg/d) for 48 weeks. Gynecomastia, breast pain, prostate-specific antigen (PSA), sexual functioning, and serum levels of hormones were assessed. Gynecomastia developed in 73% of patients in the bicalutamide group, 10% of patients in the bicalutamide-tamoxifen group, and 51% of patients in the bicalutamide-anastrozole group (P or = 50% in 97%, 97%, and 83% of patients in the bicalutamide, bicalutamide-tamoxifen, and bicalutamide-anastrozole groups, respectively (P = .07); and adverse events were reported in 37%, 35%, and 69% of patients, respectively (P = .004). There were no major differences among treatments in sexual functioning parameters from baseline to month 6. Elevated testosterone levels occurred in each group; however, free testosterone levels remained unchanged in the bicalutamide-tamoxifen group because of increased sex hormone-binding globulin levels. Anastrozole did not significantly reduce the incidence of bicalutamide-induced gynecomastia and breast pain. In contrast, tamoxifen was effective, without increasing adverse events, at least in the short-term follow-up. These data support the need for a larger study to determine any effect on mortality.
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            Long-term Efficacy and Safety of Enzalutamide Monotherapy in Hormone-naïve Prostate Cancer: 1- and 2-Year Open-label Follow-up Results

            Enzalutamide is an androgen receptor inhibitor with a demonstrated overall survival benefit in metastatic castration-resistant prostate cancer. A phase 2 study of enzalutamide monotherapy in patients with hormone-naïve prostate cancer (HNPC) showed a high response rate for the prespecified primary endpoint (ie, prostate-specific antigen [PSA] response at week 25), regardless of metastases at baseline, and favorable tolerability.
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              Use of androgen deprivation and salvage radiation therapy for patients with prostate cancer and biochemical recurrence after prostatectomy

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                Author and article information

                Contributors
                Pirus.ghadjar@charite.de
                Journal
                Strahlenther Onkol
                Strahlenther Onkol
                Strahlentherapie Und Onkologie
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0179-7158
                1439-099X
                12 March 2020
                12 March 2020
                2020
                : 196
                : 7
                : 589-597
                Affiliations
                [1 ]Department of Radiation Oncology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany, Augustenburger Platz 1, 13353 Berlin, Germany
                [2 ]Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
                [3 ]GRID grid.419835.2, ISNI 0000 0001 0729 8880, Klinikum Nürnberg Nord, ; Nürnberg, Germany
                [4 ]GRID grid.411760.5, ISNI 0000 0001 1378 7891, Universitätsklinikum Würzburg, ; Würzburg, Germany
                [5 ]GRID grid.5361.1, ISNI 0000 0000 8853 2677, Innsbruck Medical University, ; Innsbruck, Austria
                [6 ]Xcare Praxis für Strahlentherapie Saarlouis, Xcare Gruppe, Saarlouis, Germany
                [7 ]GRID grid.4488.0, ISNI 0000 0001 2111 7257, Universitätsklinikum Carl Gustav Carus, , Technische Universität Dresden, ; Dresden, Germany
                [8 ]GRID grid.411544.1, ISNI 0000 0001 0196 8249, Universitätsklinikum Tübingen, ; Tübingen, Germany
                [9 ]GRID grid.419837.0, Sana Klinikum Offenbach, ; Offenbach, Germany
                [10 ]MediClin Robert Janker Klinik, Bonn, Germany
                [11 ]Landeskrankenhaus, Universitätsklinikum der Paracelsus Medizinischen Privatuniversität, Salzburg, Austria
                [12 ]GRID grid.410712.1, Universitätsklinikum Ulm, ; Ulm, Germany
                Article
                1598
                10.1007/s00066-020-01598-9
                7305090
                32166452
                eb75c79d-01a6-431f-ab81-d9b876a46d86
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 5 February 2020
                : 18 February 2020
                Funding
                Funded by: Charité (3093)
                Categories
                Review Article
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2020

                Oncology & Radiotherapy
                gynecomastia,breast pain,prostate cancer,antiandrogen therapy,treatment
                Oncology & Radiotherapy
                gynecomastia, breast pain, prostate cancer, antiandrogen therapy, treatment

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