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雄性化丸激素疗法降低了PIK3CA突变/ER+乳腺癌的发生率,但不是与BRCA1相关的三阴性乳腺癌

Lin Wang, Brian R Sardella, Abhishek Thavamani

medRxiv : the preprint server for health sciences

|September 26, 2025

概括

性别确认丸激素治疗 (TT) 在小鼠中降低了81%的雌激素受体阳性 (ER +) 乳腺癌风险,但不会影响与BRCA1相关的三阴性乳腺癌风险. 推对TT使用者进行持续的乳腺癌查.

科学领域:

内分泌学和瘤学在内分泌学和瘤学.
在乳腺癌的翻译研究.

背景情况:

研究了 gender-affirming testosterone therapy (TT) 对乳腺癌 (BC) 风险和瘤进展的影响.
检查了TT对终端导管叶状单元 (TDLU) 卷积和乳腺组织标记物的影响.

研究的目的:

为了确定TT是否影响乳腺癌发病率和进展.
评估TT对乳腺组织和瘤微环境特征的影响.
为了评估跨性别男性个体的乳腺癌瘤特征.

主要方法:

用一个大型的人类乳腺组织数据集 (n=417) 进行TDLU卷积分析.
使用临床前模型 (MMTV-Cre Pik3ca和K14-Cre Brca Tp53) 来评估BC发生率和乳腺结构.
在人体组织和小鼠瘤上进行了转录基因组分析.

主要成果:

TT促进了TDLU的卷积,并改变了树皮细胞标记物.
在小鼠中,TT显著降低了PIK3CA相关的ER+BC发生率,降低了81%,但没有影响与BRCA1相关的三阴性BC发生率.
TT没有影响瘤进展,但调节了ER+瘤微环境.

结论:

TT可以降低ER+BC风险,但不能消除它;对BRCA1相关的BC风险的影响是可以忽略不计的.
TT调节瘤的微环境,但不会影响瘤建立后的生长.
支持需要进行乳腺癌查和针对使用TT的跨性别男性个体进行量身定制的监测.

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