Immunity may play a greater role in breast cancer than traditionally believed, particularly in the hormone receptor–positive (HR+) subtype, according to a recent paper in Cancer Treatment Reviews.1

The authors reviewed clinical and preclinical data from studies that examined the immune system’s role in the HR+ subtype. They found evidence that the subtype can not only be recognized by the immune system, but that immune infiltration also provides prognostic value for this patient population.

“It is becoming evident that breast cancer is a heterogeneous disease, including many different entities even within the same molecular subtype,” said lead author Maria Vittoria Dieci, MD, of the University of Padua in Italy, in an interview with Cancer Therapy Advisor. “For this reason, targeting the immune system can represent a compelling strategy capable of overcoming the obstacle placed by this heterogeneity.”

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The immune system, however, may promote the growth of “immune-evasive” tumor cells through evolutionarily selective pressures, and tumor cells survive if the immune system is suppressed.

Systemic and local inflammation can influence HR+ carcinogenesis and promote more aggressive HR+ tumor phenotypes. Endocrine therapy, including selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs), may further alter the immune system’s ability to find and destroy tumor cells.

While none of the studies found a generalized correlation between tumor-infiltrating lymphocytes (TILs) and survival, there were “intriguing results” when specific TIL subsets were studied. CD8+i and FOXP3 TIL cells, for example, were correlated with worse prognoses in specific patient subgroups.

The authors discussed several combination therapies currently being investigated, including chemotherapy plus checkpoint inhibitors, endocrine therapy plus immunotherapy, tremelimumab, an anti-CTLA4 agent plus exemestane, and vaccine strategies.

They called for “finer evaluation” of the interactions between the immune system and HR+ breast cancer, as well as more research focused on understanding the role immunity plays in ER+ breast cancer. They also suggested future subtype-specific investigations of predictive biomarkers that can identify which patient populations will benefit from immunotherapy.

“It is mandatory to rationalize resources to identify those patients with breast cancer who may benefit the most from an immunotherapeutic agent, by outlining the proper subgroups, setting and timing,” said Dr Dieci. “It appears essential to focus future research on the identification of tissue or serum markers that could identify sensitive patients on the 1 hand, and spare potentially fatal toxicities to refractory patients on the other.

“Better results could be achieved if immunotherapeutic agents, such as immune checkpoint inhibitors, were administered in combination or in sequence with other immune drugs able to attract immune effector cells to the tumor bed or vaccines,” she concluded. “There is a chance that the combination of immune strategies that target the microenvironment with agents that target specific cancer cells could lead to interesting results.”


  1. Dieci MV, Griguolo G, Miglietta F, Guarneri V. The immune system and hormone-receptor positive breast cancer: Is it really a dead end? [published online ahead of print March 28, 2016]. Cancer Treatment Reviews. doi: 10.1016/j.ctrv.2016.03.011