ESMO Asia 2025 | How can we move beyond endocrine therapy in HR+/HER2- breast cancer?

Yes. I also had an opportunity to talk on moving beyond endocrine therapy and the present future perspective. That is so wide. So I focused on the immunotherapy in hormone receptor positive space. That was delivered in educational session during asthma Asia. As you know, hormone receptor-positive tumors generally have an immune-called tumor-mitering environment and are characterized by low TIL and low PD-L1 expression, yet signaling in hormone receptor-positive tumors may lead to more pronounced immunosuppression. This explains why immune checkpoint inhibitor monotherapy has a limited payoff in unselected hormone receptor positive or to negative disease. Nonetheless, among hormone receptor positive breast cancer, there is an immunoreactive subset who can benefit from immune chakra inhibitor. According to recent RNA-seq data from 980 patients, the unsupervised cluster analysis revealed seven clusters, among which cluster seven turned out to be immunogenic cluster in hormone receptor positive. So my message is that there is some subset who could benefit from immune checkpoint, even inhibitor, even in hormone receptor positive patient population. So based on the representative trials, the keynote 756 and the checkmate is 7-FL, I spy 2, current evidence of a neoadjuvant immune checkpoint inhibitor in early breast cancer trials revealed that neoadjuvant immune checkpoint inhibitor plus chemotherapy improves the PCR-RCV-01 rate in high-risk hormonal setup, heart-negative early breast cancer, particularly in patients with high CPS and stromal teal, larger than 1%, low ER expression, and mama-printed two tumors. And only PCR-RCCP data is available at the present, but reporting events will take additional time. And none of the patients in TNO2-5, 7, 5, 6, and CHECMET-7FL did not receive azimuth CDK4-6 inhibitor, which is currently a center of care in high-risk patients, especially azimuth CDK4-6 inhibitor, which is currently a center of care in the high-risk patients, especially in adjuvant setting. Keynote 756 and the checkmate 46 did not include adjuvant immune checkpoint inhibitor component. In metastatic setting, a broad combination of approaches are under active investigation to elicit a more immunogenic microenvironment. For example, CDK4-6 inhibitor plus immune checkpoint inhibitor plus with or without endocrine therapy. Another is the POP inhibitor plus immunotherapy in BRCA mutated disease, so-called mediolar trial, immunotherapy with AKT, MEG, angiogenesis inhibitor, immunotherapy plus with PIX3C, AKT inhibitor, immunotherapy with radiotherapy, next generation immunotherapy included by specific antibody, a CAR T cell. In summary, hormone receptor positive,itive heart-negative breast cancer is an immunologically cold subtype with a limited benefit from immunotherapy due to estrogen-driven immune suppression. Immune checkpoint inhibitor combination with chemotherapy in neosmetic setting or endocrine therapy with CDK460-inhibited metastatic setting may overcome estrogen-driven immune suppression in hormone receptor tumors. Integrated biomarker-driven treatment sequencing, for example, PD-L1 positivity, high TMB, BRCA, HLD score, high TIL infiltration, will be critical to maximize the survival in the hormone receptor space. And next-generation immunotherapy, including biospecific antibiotic cortisol, looks promising but remains investigational.