We reviewed response to immune checkpoint inhibitors (ICI) of 207 patients with diagnoses of lung or head and neck cancer treated with chemotherapy/ICI combination therapy and ICI monotherapy between 2015 and 2020 at one of three clinical pavilions associated with the Dan L. Duncan Comprehensive Cancer Center at Baylor College of Medicine (Houston, TX). Two of these pavilions (Harris Health System and the Michael E. DeBakey Veterans Affairs Medical Center) serve large minority populations and provide equal access to care regardless of means. 174 patients had a diagnosis of lung cancer (non–small cell or small cell) and 33 had a diagnosis of head and neck squamous cell carcinoma (HNSCC). 38% self-identified as Black, 45% as non-Hispanic White, and 18% as Hispanic. The objective response rate (ORR) was similar for patients with lung cancer (35.057%) and HNSCC (30.3%; P = 0.894). The ORR for Hispanic and Black patients was lower compared with non-Hispanic White patients (H 27.0%, B 32.5%, W 38.7%; H vs. W P = 0.209; B vs. W P = 0.398). When considering only patients treated with ICI monotherapy, the ORR for Hispanic patients dropped further to 20.7% while the ORR of Black and non-Hispanic White patients remained about the same (B 29.3% and W 35.9%, H vs. W P = 0.133; B vs. W P = 0.419). Immune-related adverse events were the lowest in the Hispanic population occurring in only 30% of patients compared with 40% of patients in the Black cohort and 50% of the non-Hispanic White cohorts. Significance: To our knowledge, this report is the first to compare ICI effectiveness within a diverse patient population with a substantial Black and Hispanic NSCLC and HNSCC patient population treated in the context of equal access to care. The data presented in this article suggests reduced effectiveness of ICI monotherapy in Hispanic patients and thereby underscores the need for improved access and representation of racial/ethnic minority patients in ICI clinical trials. Watch the interview with Jan O. Kemnade, MD, PhD, and Vlad C. Sandulache, MD, PhD, corecipients of the inaugural Cancer Research Communications Award for Outstanding Journal Article: https://vimeo.com/992993122

Immune checkpoint inhibitors utilize the immune system to kill cancer cells and are now widely applied across numerous malignancies. Pembrolizumab has two breast-specific indications in triple-negative disease. Currently, programmed death ligand-1 (PD-L1) expression on tumor and surrounding immune cells is the only validated predictive biomarker for immune checkpoint inhibitors (ICIs) in breast cancer; however, it can be imprecise. Additional biomarkers are needed to identify the patient population who will derive the most benefit from these therapies. The tumor immune microenvironment contains many biomarker candidates. In tumor cells, tumor mutational burden has emerged as a robust biomarker across malignancies in general, with higher burden cancers demonstrating improved response, but will need further refinement for less mutated cancers. Preliminary studies suggest that mutations in breast cancer gene 2 (BRCA-2) are associated with increased immune infiltration and response to ICI therapy. Other genomic alterations are also being investigated as potential predictive biomarkers. In immune cells, increased quantity of tumor-infiltrating lymphocytes and CD8+ cytotoxic T cells have correlated with response to immunotherapy treatment. The role of other immune cell phenotypes is being investigated. Peripherally, many liquid-based biomarker strategies such as PD-L1 expression on circulating tumor cells and peripheral immune cell quantification are being studied; however, these strategies require further standardization and refinement prior to large-scale testing. Ultimately, multiple biomarkers utilized together may be needed to best identify the appropriate patients for these treatments.

The benefit of anthracyclines for patients with high 21-gene recurrence score (RS) is unclear, despite the widespread use of RS to guide adjuvant chemotherapy treatment for hormone receptor-positive (HR+)/HER2-negative (HER2-) breast cancer. This study aimed to assess whether patients with RS > 31 would have improved outcomes with the addition of anthracyclines to taxane-based chemotherapy. We included patients from TAILORx with RS ≥ 11 who received treatment with either taxanes with cyclophosphamide (TC) or taxane with anthracyclines/cyclophosphamide (T-AC). Distant recurrence-free interval (DRFI), distant recurrence-free survival (DRFS), overall survival (OS) were compared, controlling for age, tumor size and grade, receptor status, and RS. Spline regression was used to estimate adjusted hazard ratio (aHR) for receipt of T-AC (vs TC) for these endpoints as a function of RS. A total of 2,549 patients who received either T-AC or TC were included in the primary analysis. In patients with RS > 31, receipt of T-AC was associated with improved DRFI (5-year rate of 96.1% with T-AC vs 91.0% with TC; aHR, 0.31; P = 0.006), DRFS (95.4% vs 89.8%; aHR, 0.49; P = 0.032), and a trend towards improved OS (adjusted 5-year rate 97.3% vs 93.6%; aHR, 0.67; P = 0.31). Spline regression demonstrated increasing anthracycline benefit with increasing RS. Patients with early-stage, HR+/HER2- breast cancer with the highest genomic risk disease (RS > 31) may benefit from the addition of an anthracycline to taxane-based adjuvant chemotherapy. Genomic RS testing may predict anthracycline benefit more accurately than clinicopathologic factors such as nodal status.

Antibody–drug conjugates (ADCs) are a relatively new class of anti-cancer therapies approved for a number of malignancies, including breast cancer. Their unique structure, consisting of a monoclona...

Background: Over the past few decades, the gonadotropin-releasing hormone agonist goserelin has been evaluated in ovarian function suppression (OFS) with adjuvant endocrine therapy and ovarian function preservation (OFP) during chemotherapy. Objective: The goal of this systematic literature review was to assess the efficacy of goserelin in OFS and OFP in combination with endocrine therapies and chemotherapy, respectively, in pre- and perimenopausal women with early-stage breast cancer. Design: This study is a systematic review. Data sources and methods: The literature search was conducted using PubMed. Prospective clinical studies evaluating the efficacy of goserelin in OFS or OFP in pre- or perimenopausal breast cancer were identified by four reviewers working in teams of two. Results: Twenty-nine studies were included in this systematic review. The addition of goserelin as OFS to adjuvant endocrine therapy generally resulted in significant benefits in disease-free survival. Studies have shown better OFP results among women 40 years or younger compared with older patients. Chemotherapy in association with goserelin for OFP resulted in a higher recovery rate of menses within 6–24 months, a shorter time for menstrual recovery, and significantly higher pregnancy rates when compared with cytotoxic therapy without goserelin. Hormonal recovery with higher anti-Müllerian hormone and estradiol levels, and lower follicle-stimulating hormone and luteinizing hormone levels occurred more frequently among women who received goserelin during chemotherapy as compared with those receiving cytotoxic therapy alone. The benefits of goserelin in OFP were more substantial among women 40 years or younger than in older patients. Conclusion: The findings of this systematic review highlight the benefits of adding goserelin to endocrine therapies for OFS and chemotherapy for OFP in early-stage breast cancer. Additionally, scientific data supporting OFS (including goserelin) in combination with newer agents such as cyclin-dependent kinase 4 and 6 inhibitors and bone-modifying agents are emerging.

Purpose of Review: Triple-negative breast cancer (TNBC) is notoriously difficult to treat. Recent technological advances have led to the identification of novel targets and new approaches to treat this devastating disease. The aim of this review is to highlight therapeutic vulnerabilities of TNBC and discuss novel therapeutic strategies. Recent Findings: Interrogating the inherent heterogeneity and rich cellular and transcriptional diversity within TNBC has led to the discovery of vulnerabilities and actionable targets for therapeutic development. Characterization of the tumor immune environment, discovery of novel molecular targets, and identification of somatic alterations which confer sensitivity to DNA repair inhibitors are just a few examples. Summary: The key to developing effective strategies to treat TNBC is to exploit vulnerabilities using a multifaceted approach. The identification of actionable targets has led to numerous therapeutic advances for TNBC, resulting in substantial improvements in patient outcomes and quality of life.