Treatment strategies to prevent and reduce gynecomastia and/or breast pain caused by antiandrogen therapy for prostate cancer

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.K 590 Strahlenther Onkol (2020) 196:589-597 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.

A phase 2 randomized clinical trial of abiraterone plus ADT, apalutamide, or abiraterone and apalutamide in patients with advanced prostate cancer with non-castrate testosterone levels (LACOG 0415)

“…In this regard, a meta-analysis has shown that prophylactic radiotherapy, as well as daily tamoxifen, can significantly reduce the incidence of gynaecomastia and/or breast pain and therefore, one of these strategies should be considered in future studies. Also, the authors concluded that tamoxifen appears to be an effective alternative to radiotherapy as a therapeutic treatment in the presence of gynaecomastia, but its side effects and off-label use must be considered [21].…”

Targeted inhibition of ERα signaling and PIP5K1α/Akt pathways in castration‐resistant prostate cancer

“…Enzalutamide, an androgen receptor signaling inhibitor was shown to be associated with a 49% rate of gynecomastia within 2 years. Tamoxifen has been used as drug intervention to block the ERα in breast tissues and the data from 8 clinical randomized trials revealed that tamoxifen is well tolerated by PCa patients[41].…”

Gynécomastie en pratique clinique pour les urologues

“…Chez le patient présentant une contreindication au traitement par le tamoxifène, la radiothérapie est l' option de choix, l'avantage étant la courte durée du traitement. Par contre, les patients devraient être informés d'une possible cardiotoxicité [15][16][17]. En revanche, elle devrait être évitée chez le patient jeune au vu du risque de développement d'un cancer mammaire secondaire [18].…”