Dynamic single-cell systemic immune responses in immunotherapy-treated early-stage HR+ breast cancer patients.

The limited added benefit of immune checkpoint inhibitors in breast cancer indicates the pressing need to identify biomarkers of response to minimize risk and maximize benefit. We used single cell RNA sequencing and T cell receptor (TCR) sequencing of peripheral blood mononuclear cells (for 28 samples comprising 79,284 cells) to monitor the peripheral immune dynamic of an exploratory cohort of hormone receptor positive breast cancer patients treated with neoadjuvant nab-paclitaxel+pembrolizumab with the ultimate goal of identifying potential peripheral blood predictive biomarkers. In responsive patients, Granzyme B positive (GZMB+) cytotoxic CD8 T cells expanded post-nab-paclitaxel+pembrolizumab, accompanied by rapid changes in TCR clones.

Nivolumab plus low-dose ipilimumab in hypermutated HER2-negative metastatic breast cancer: a phase II trial (NIMBUS).

In the phase II NIMBUS trial, patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) and high tumor mutational burden (TMB ≥ 9 mut/Mb) received nivolumab (3 mg/kg biweekly) and low-dose ipilimumab (1 mg/kg every 6 weeks) for 2 years or until progression. The primary endpoint was objective response rate (ORR) per RECIST 1.1 criteria.

Phase I study of ribociclib (CDK4/6 inhibitor) with spartalizumab (PD-1 inhibitor) with and without fulvestrant in metastatic hormone receptor-positive breast cancer or advanced ovarian cancer.

Background: Preclinical evidence suggests that cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors enhance antitumor immunity. We conducted a phase I trial of ribociclib (CDK4/6 inhibitor) plus spartalizumab (PD-1 inhibitor) in patients with hormone receptor (HR)-positive/HER2-negative metastatic breast cancer (MBC) or advanced ovarian cancer (AOC). The combination was also evaluated with fulvestrant in MBC.

A Phase II Study of Abemaciclib for Patients with Retinoblastoma-Positive, Metastatic Triple-Negative Breast Cancer.

Purpose: Cyclin-dependent kinase 4/6 inhibitors can significantly extend survival when given in combination with endocrine therapy in patients with hormone receptor-positive metastatic breast cancer. However, their activity has been relatively underexplored in patients with metastatic triple-negative breast cancer (mTNBC).

Patients And Methods: We conducted a single-arm phase II study of abemaciclib monotherapy in patients with Rb-positive mTNBC.

A Phase II Study of Atezolizumab, Pertuzumab, and High-Dose Trastuzumab for Central Nervous System Metastases in Patients with HER2-Positive Breast Cancer.

Purpose: Patients with HER2-positive breast cancer brain metastases have few effective systemic therapy options. In a prior study, pertuzumab with high-dose trastuzumab demonstrated a high clinical benefit rate (CBR) in the central nervous system (CNS) in patients with brain metastases. The current trial evaluated whether the addition of atezolizumab to this regimen would produce further improvements in CNS response.

Integrative Multiomic Profiling of Triple-Negative Breast Cancer for Identifying Suitable Therapies.

Purpose: Triple-negative breast cancer (TNBC) is a heterogeneous disease that carries the poorest prognosis of all breast cancers. Although novel TNBC therapies in development are frequently targeted toward tumors carrying a specific genomic, transcriptomic, or protein biomarker, it is poorly understood how these biomarkers are correlated.

Experimental Design: To better understand the molecular features of TNBC and their correlation with one another, we performed multimodal profiling on a cohort of 95 TNBC.

Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer: final 10-year analysis of the open-label, single-arm, phase 2 APT trial.

Background: We aimed to report on long-term outcomes of patients with small, node-negative, HER2-positive breast cancer treated with adjuvant paclitaxel and trastuzumab and to establish potential biomarkers to predict prognosis.

Methods: In this open-label, single-arm, phase 2 study, patients aged 18 years or older, with small (≤3 cm), node-negative, HER2-positive breast cancer, and an Eastern Cooperative Oncology Group performance status of 0-1, were recruited from 16 institutions in 13 cities in the USA. Eligible patients were given intravenous paclitaxel (80 mg/m) with intravenous trastuzumab (loading dose of 4 mg/kg, subsequent doses 2 mg/kg) weekly for 12 weeks, followed by trastuzumab (weekly at 2 mg/kg or once every 3 weeks at 6 mg/kg) for 40 weeks to complete a full year of trastuzumab.