Radiotherapy can be safely omitted as a treatment for many breast cancer patients who have had a mastectomy and are taking anti-cancer drugs, a study shows.

A population of tumor-associated macrophages (TAMs) fosters resistance to targeted therapies such as tamoxifen in estrogen receptor-positive breast cancer, according to new research involving mice and patient-derived cultures. The research also revealed that a combined immunotherapy regimen could suppress these cells and slow tumor growth, suggesting that similar regimens could overcome treatment resistance in these tumors. Estrogen receptor-positive breast cancer constitutes as much as 75% of new breast cancer cases. When treating patients, clinicians first turn to targeted therapies such as tamoxifen and fulvestrant, which block or degrade the estrogen receptor to starve the tumors. However, many patients don’t respond to these therapies or develop resistance after initial treatment, and the five-year survival rate for tamoxifen-treated patients is only 20%. Researchers are investigating whether immunotherapies could improve clinical outcomes in these endocrine-resistant tumors, but more research is needed to define the role of immune cells in the tumor microenvironment. However, Shailesh Singh and colleagues have now identified TAMs that promote endocrine resistance in estrogen receptor-positive breast tumors. In mouse models of breast cancer, the TAMs supported resistance to tamoxifen and fulvestrant by maintaining the activity of cancer stem cells, which often survive targeted treatments. These TAMs also expressed PD-L1 – an immune-suppressing receptor that’s often targeted by immunotherapies – and were recruited to tumors through a protein named DLL1. Singh et al. found that combining low doses of tamoxifen with antibodies that target PD-L1 and DLL1 sensitized previously resistant breast tumors to treatment in the mice. “By incorporating low-dose [tamoxifen] alongside other agents, we aim to offer a treatment that targets a broader range of patients with [estrogen receptor-positive] luminal breast cancer and reduce severe side effects,” they conclude.