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Importance: Current chemotherapy regimens for patients with ERBB2 (formerly HER2)-positive breast cancer are associated with considerable morbidity. These patients may benefit from more effective and less toxic therapies., Objective: To evaluate the safety, immunogenicity, and preliminary efficacy of intratumoral (IT) delivery of conventional type 1 dendritic cells (cDC1) in combination with ERBB2-targeted therapies., Design, Setting, and Participants: This phase 1 (lead-in phase of a single-center phase 2 trial) nonrandomized clinical trial was conducted at Moffitt Cancer Center (Tampa, Florida). Patients were enrolled from October 2021 to October 2022. Data were analyzed in 2023 Patients with early-stage ERBB2-positive breast cancer with tumors 1 cm or larger were eligible., Interventions: Treatment included IT delivery of cDC1, 6 times weekly, followed by paclitaxel, 80 mg/m2, intravenously, 12 times weekly. Trastuzumab (8 mg/kg loading dose, then 6 mg/kg) and pertuzumab (840 mg loading dose, then 420 mg) were administered intravenously every 3 weeks for 6 cycles starting from day 1 of cDC1 injections. Two dose levels (DLs) of IT cDC1 (DL1 = 50 million and DL2 = 100 million cells) were evaluated, including 6 patients in each DL., Main Outcomes and Measures: The primary outcomes were the safety and immune response, and the secondary outcomes were the antitumor efficacy as measured by breast magnetic resonance imaging and residual cancer burden at surgery following neoadjuvant therapy., Results: Twelve ERBB2-positive patients were enrolled and received treatment (DL1 = 6 and DL2 = 6). Nine patients had hormone receptor-positive disease and 3 had hormone receptor-negative disease, with clinical stage I (n = 5), II (n = 4), and III (n = 3). The most frequently observed adverse events with cDC1 were grade 1 to 2 chills (50%), fatigue (41.7%), headache (33%), and injection site reactions (33%). DL2 was associated with a diminished anti-ERBB2 CD4 T-helper 1 blood response with a concomitant increase in innate and adaptive responses within the tumor. Preimmunotherapy and postimmunotherapy breast magnetic resonance imaging results showed 9 objective responses, 6 partial responses, 3 complete responses, and 3 stable diseases. Following surgery, 7 patients had a pathologic complete response., Conclusions and Relevance: In this nonrandomized clinical trial, the addition of IT cDC1 and trastuzumab/pertuzumab before neoadjuvant chemotherapy was well tolerated with manageable adverse effects. Based on safety and immunogenicity, DL2 was selected for the phase 2 dose., Trial Registration: ClinicalTrials.gov Identifier: NCT05325632.

Purpose: Estrogen receptor-positive (ER + ) breast cancer (BC) is a heterogeneous disease, and there is an ongoing debate regarding the optimal cut point for clinically relevant ER expression. We used a real-world database to assess the prognostic and predictive values of lower ER expression levels on treatment outcomes with endocrine therapy., Methods: We used a nationwide electronic health record database. Descriptive statistics were used to evaluate the association between ER expression, tumor characteristics, and treatment patterns among patients with early-stage BC. We used Kaplan-Meier survival curves to estimate recurrence-free survival (RFS) and overall survival (OS). We assessed associations between an alternative ER expression-level cut point and clinical outcomes., Results: Among 4697 patients with early-stage HER2-negative BC, 83 (2.04%) had ER + -low BC (ER expression, 1-9.99%) and 36 (0.88%) had ER + -intermediate BC (10-19.9%). ER + -low tumors were associated with higher tumor grade, larger size, and higher axillary tumor burden than ER + -high tumors (≥20% ER expression). African Americans had a higher prevalence of both triple-negative BC (TNBC) and ER + -low BC than ER + -high BC. Patients with ER + -low and ER + -intermediate tumors had survival outcomes similar to patients with TNBC and worse survival outcomes than patients with ER + -high tumors ( P < 0.001). Tumors with <20% ER expression were associated with worse outcomes., Conclusion: In our cohort, patients with BCs with ER expression levels <20% had poor clinical outcomes similar to those of patients with TNBC., Competing Interests: R. L. B. Costa received honorarium from Bristol Meyers Squib, Pfizer, Athenex Oncology, Daiichi Sankyo and Astra Zeneca. All other authors declare no conflicts of interest., (© 2022 Bari et al.)