A Hormone Immunotherapy (HIT) Combination in Advanced Breast Cancer

The NCCN guidelines on the use of hormone therapy (HT), immunotherapy (IT), and hormone immunotherapy (HIT) in advanced breast cancer are briefly reported. Then, investigational and clinical findings supporting the relationships between tumor growth and immune evasion and its impact on both HT and IT are examined. Finally, the rationale for an efficacious combination of a novel IT with conventional HT (HIT) in the largest subset of ER+ breast cancer patients is introduced and discussed. ER+ breast cancer is considered not amenable for IT as being immunologically “cold,” and currently, aromatase inhibitors (AIs) and fulvestrant, a selective estrogen receptor downregulator (SERD), are recommended as first-line hormone therapy (HT) in association with cyclin kinase inhibitors (CKIs) for ER+ HER2− breast cancer patients. However, a pilot clinical study and a successive larger, observational, retrospective 2:1 ratio control-case study where ER+ breast cancer patients who benefited clinically during conventional first-line antiestrogen HT additionally received cyclic interferon beta interleukin-2 sequence, showed superior results to those who received HT alone, and results also were comparable to those receiving HT-CKIs. In the observational 2:1 ratio control-case study, the median PFS and OS were significantly longer in the 42 cases than in the 95 controls (median time 33 vs. 18 months, p = 0.002 and 81 vs. 62 months, p = 0.019, respectively). In the 42 cases, unlike the HT-CKI combination where grade 3–4 adverse events (AEs) occurred, grade 1–2 flu-like syndrome and injection site reaction were the only two more commonly observed serious AEs. Moreover, the proposed IT is 8–18 times cheaper than HT combined with CKIs. Despite the promising findings, no prospective multicenter validation trial has been sponsored and launched by pharmaceutical industries or government agencies. Overall, this and other considerations raise a major concern for the ongoing promotion of research in oncology.