In hormone receptor-positive (HR+) breast cancer, the tumor immune microenvironment (TIM) is uniquely shaped by estrogen signaling, which not only suppresses immune activity but also fosters a microenvironment conducive to late recurrence. This makes late recurrence a critical issue that must not be underestimated in these patients. 

Estrogen promotes immunosuppressive mechanisms, such as polarizing macrophages toward the M2 subtype and enhancing Tregs and myeloid-derived suppressor cells (MDSCs). Conversely, CDK4/6 inhibitors and endocrine therapies offer a dual benefit: they block estrogen signaling while also reshaping the TIM. CDK4/6 inhibitors, in particular, have shown promise in triggering anti-tumor immunity and reducing recurrence risk. Excitingly, ongoing research is exploring how different CDK4/6 inhibitors uniquely modulate the TIM, potentially paving the way for more precise and effective treatment strategies in HR+ breast cancer.

Sacituzumab Govitecan (SG; Trodelvy) is a targeted therapy designed for adults with hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) who have received hormone therapy and at least two additional treatments for metastatic disease. It is an antibody-drug conjugate that binds to the Trop-2 antigen, delivering a potent chemotherapy directly to cancer cells6. Clinical trials have demonstrated that SG significantly improves progression-free survival and overall survival compared to traditional chemotherapy in this patient population. This therapy offers a new treatment option for patients with HR+/HER2- MBC, who historically have had limited treatment choices and poor survival outcomes. SG's mechanism of action and clinical efficacy make it a valuable addition to the treatment landscape for this challenging form of breast cancer.

Human trophoblast cell-surface antigen-2 (Trop-2) is a membrane glycoprotein involved in cell proliferation and motility, frequently overexpressed in epithelial tumors. Thus, it represents an attractive target for anticancer therapies. Sacituzumab govitecan (SG) is a third-generation antibody-drug conjugate (ADC), consisting of an anti-Trop-2 monoclonal antibody (hRS7), a hydrolysable linker, and a cytotoxin (SN38), which inhibits topoisomerase 1. Specific pharmacological features, such as the high antibody to payload ratio, the ultra-toxic nature of SN38, and the capacity to kill surrounding tumor cells (the bystander effect), make SG a very promising drug for cancer treatment. Moreover, unprecedented results have been observed with SG in patients with heavily pretreated advanced triple-negative breast cancer and hormone-positive/HER2-negative metastatic breast cancer, and the drug has already received approval for these indications in Taiwan. 

The treatment landscape of breast cancer has been greatly changed by the innovative targeting therapies. Antibody-drug conjugates (ADCs) with a representative of trastuzumab deruxtecan (T-DXd) are the most successful ones. The revolutionary next-generation design of ADC transformed to the unprecedented clinical data. T-DXd has been evaluated as treatment of several HER2-expressing cancers, including HER2-positive and HER2-low breast cancer. This is the first HER2-targeted therapy active for HER2-low breast cancer.

In this review we focus on efficacy and toxicity profile of this novel anti-HER2 compound, and provide an update on the most recent results of ongoing clinical trials of T-DXd.

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活動日期：114年10月18日(週六)12:30-17:20(含課前及課後測驗時間)   課程直播過程如有異常請及時洽詢台灣乳房醫學會(02-2523-9118；bcst@ms46.hinet.net)
活動地點：線上直播。
主辦單位：台灣乳房醫學會
指導單位：衛生福利部國民健康署
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