The clinical promise of immunotherapy in triple-negative breast cancer

Abstract

Triple-negative breast cancer (TNBC) is a heterogeneous disease with poorer outcomes compared to other breast cancer subtypes. Contributing to the worse prognosis in TNBC is the higher rates of relapse and rapid progression after relapse. Advances in targeted therapeutics and conventional chemotherapy for TNBC have been stymied due to the lack of specific targets. Moreover, the responses to chemotherapy in TNBC lack durability, partially accounting for the higher rates of relapse. Immunotherapy, notably immune-checkpoint blockade, has shown to improve survival and maintain robust antitumor responses in both hematologic and solid malignancies. Unlike lung cancer, melanoma, and bladder cancer, most breast cancers are not inherently immunogenic and typically have low T cell infiltration. However, among breast cancer subtypes, TNBC is characterized by greater tumor immune infiltrate and higher degree of stromal and intratumoral tumor-infiltrating lymphocytes (TILs), a predictive marker for responses to immunotherapy. Moreover, in TNBC, the high number of stromal TILs is predictive of more favorable survival outcomes and response to chemotherapy. Immunotherapy is being extensively explored in TNBC and clinical trials are showing some promising results. This article focuses on the rationale for immunotherapy in TNBC, to explore and discuss preclinical data, results from early clinical trials, and to summarize some ongoing trials. We will also discuss the potential application of immunotherapy in TNBC from a clinician’s perspective.

B7-H3 and B7-H4 Expression in Breast Cancer and Their Association with Clinicopathological Variables and T Cell Infiltration

“…Immunotherapy with PD-1/PD-L1 pathway inhibitors has also shown clinical responses in breast cancer, but it appears to be beneficial only in a subset of breast cancer patients [9-12]. The combination of immune-checkpoint blockade with other drugs or targets of additional immune checkpoints is gaining attention in the treatment of breast cancer [13-15]. Recently, the Food and Drug Administration approved the combination therapy of atezolizumab, a monoclonal antibody drug targeting PD-L1 along with chemotherapy for the treatment of patients with PD-L1-positive, unresectable, locally advanced, or metastatic triple-negative breast cancer [15].…”

“…Antibodies targeting the PD-1/PD-L1 pathway generate robust clinical responses in breast cancer, but only a subset of patients benefit from such therapy [9-12]. Efforts are now being made to combine PD-1/PD-L1 blockades with other drugs or modulators of immune checkpoints for breast cancer therapy [13-15].…”

Single peptides and combination modalities for triple negative breast cancer

“…Long lasting responses have been achieved with anti‐PD‐1 and anti‐PD‐L1 mAbs in up to 30% of TNBC patients selected based on their IHC results of PD‐L1 expression, whereas the response in unselected TNBC patients was about 10%. The higher presence of TILs in the TME of TNBC have been shown to positively affect the response and is associated with improved OS and longer lasting treatment outcome (Management, ). The exploitation of vaccines prepared from specific tumor antigens impose a selection pressure on cancer cells to overcome the epitope targeting by evolving different molecular mechanisms.…”

Chemotherapy-induced immunological breast cancer dormancy: a new function for old drugs?

“…A complementary strategy to IFN administration could be the use of check point inhibitors, in particular anti-PD-1/PD-L1 antibodies to relieve tumor-induced immunosuppression [265] . In breast cancer, immunotherapy is being explored, in particular in patients with tumors expressing PD-L1 and infiltrated with lymphocytes [266] . Potential response to PD-1 or PD-L1 inhibitors was demonstrated in metastatic TNBC [267] and HER2 + breast cancers [268] .…”