The Evolving Landscape of Immune Checkpoint Inhibitors and Antibody Drug Conjugates in the Treatment of Early-Stage Breast Cancer.

For decades, chemotherapy has been the mainstay of breast cancer treatment. Novel therapies are expanding the therapeutic options and altering the treatment algorithms to manage this disease. The use and approval of immune checkpoint inhibitors (ICIs) and antibody-drug conjugates (ADCs) represent a few areas of progress. These therapies initially gained attention in the metastatic setting but have subsequently found a role in early-stage breast cancer. Although human epidermal growth factor receptor 2 (HER2) is at the center of ADC development, other surface antigens with a differential expression between tumor and normal cells may be appropriate for ADC targeting. This has led to the discovery of new ADCs targeting other receptors, including TROP-2, HER-3, and LIV-1, to name a few. Similarly, the addition of pembrolizumab in treating early-stage triple-negative breast cancer has led to exploring other ICIs in this setting. However, it has also raised important scientific questions regarding optimal patient selection, biomarkers that predict the success of ICIs, ideal chemotherapy partners, and the financial implications of bringing newer therapies to the forefront. In this review, we discuss the evolving landscape of ICIs and ADCs in managing early-stage breast cancer and provide an overview of potential future advancement in the field.

Advances in the Management of Early-Stage Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with both inter- and intratumor heterogeneity, thought to result in a more aggressive course and worse outcomes. Neoadjuvant therapy (NAT) has become the preferred treatment modality of early-stage TNBC as it allows for the downstaging of tumors in the breast and axilla, monitoring early treatment response, and most importantly, provides important prognostic information that is essential to determining post-surgical therapies to improve outcomes. It focuses on combinations of systemic drugs to optimize pathologic complete response (pCR). Excellent response to NAT has allowed surgical de-escalation in ideal candidates. Further, treatment algorithms guide the systemic management of patients based on their pCR status following surgery. The expanding knowledge of molecular pathways, genomic sequencing, and the immunological profile of TNBC has led to the use of immune checkpoint inhibitors and targeted agents, including PARP inhibitors, further revolutionizing the therapeutic landscape of this clinical entity. However, subgroups most likely to benefit from these novel approaches in TNBC remain elusive and are being extensively studied. In this review, we describe current practices and promising therapeutic options on the horizon for TNBC, surgical advances, and future trends in molecular determinants of response to therapy in early-stage TNBC.

Germline Genetic Testing in Breast Cancer: Systemic Therapy Implications.

PURPOSE OF REVIEW: In this article, we discuss recent advances in germline genetic testing for patients with breast cancer and highlight current limitations and impacts on clinical care. We also provide an update on the therapeutic implications of having a germline mutation, including targeted systemic therapy options for treating early and metastatic breast cancer. RECENT FINDINGS: Approximately 5 to 10% of women diagnosed with breast cancer have a pathogenic variant in a hereditary cancer susceptibility gene, which has significant implications for managing these patients. Previously, testing was done mainly to inform screening and risk-reduction treatment; however, more recently, germline genetic results have significant systemic therapy implications that can meaningfully improve outcomes in breast cancer patients, especially with oral poly-ADP-ribose polymerase (PARP) inhibitors. These systemic therapy advances implore a shift in paradigm for whom to test moving forward and how to modify the existing testing models to meet the increasing demand for germline testing, which is expected to grow exponentially.

Mucous Membrane Pemphigoid Causing Central Airway Obstruction.

Mucous membrane pemphigoid (MMP) is a rare variant of the skin disease pemphigoid, which predominantly involves the mucous membranes. This rare autoimmune disease that infrequently affects the respiratory tract is characterized by subepithelial blister formation that may result in scarring. Immunopathologic examination of mucous membranes reveals the deposition of immunoglobulins and complement within the subepithelial basement membrane. We describe a patient with undiagnosed MMP, with a near-fatal presentation of central airway obstruction causing acute respiratory distress. The patient was successfully treated with emergent rigid bronchoscopic resection of a ball valve-like endotracheal mass, and diagnosed with a rare variant of pemphigoid disease, MMP. The patient was treated with mycophenolate and was clinically in remission, with bronchoscopically stable lesions at 1 year of follow-up.