Molecular characterization of HER2-negative breast cancers reveals a distinct patient subgroup with 17q12 deletion and heterozygous loss of ERBB2.

Background: The approval of trastuzumab deruxtecan has prompted the subgrouping of human epidermal growth factor receptor 2-negative (HER2-) breast cancers (BCs) to HER2 0 and HER2 low on the basis of immunohistochemistry, although the biological significance of these subgroups remains uncertain. This study is aimed to better understand the molecular and genetic differences among HER2- tumors stratified by quantitative levels of HER2.

Patients And Methods: We analyzed the transcriptomic and genomic data from the Molecular Taxonomy of BC International Consortium (discovery cohort) and The Cancer Genome Atlas (independent validation cohort).

HER2DX in HER2-positive inflammatory breast cancer: correlative insights and comparative analysis with noninflammatory breast cancers.

Background: The HER2DX assay predicts long-term prognosis and pathologic complete response (pCR) in patients with early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving neoadjuvant systemic therapy but has not been evaluated in inflammatory breast cancer (IBC).

Patients And Methods: HER2DX was analyzed in baseline biopsy tissues from 23 patients with stage III HER2-positive IBC on a phase II trial (NCT01796197) treated with neoadjuvant trastuzumab, pertuzumab, and paclitaxel (THP). To assess the assay's predictive accuracy for pCR in IBC, clinical-pathological features and outcomes from this IBC cohort were compared with 156 patients with stage III HER2-positive non-IBC from four different cohorts.

Efficacy, safety, and patient-reported outcomes across young to older age groups of patients with HR+/HER2- advanced breast cancer treated with ribociclib plus endocrine therapy in the randomized MONALEESA-2, -3, and -7 trials.

Background: Ribociclib + endocrine therapy (ET) showed significant progression-free survival (PFS) and overall survival (OS) benefits in the MONALEESA trials in patients with HR+ /HER2 - advanced breast cancer (ABC). We report efficacy, safety, and patient-reported outcomes (PROs) across age groups, including older patients, in these trials.

Methods: Data from the MONALEESA-2, -3, and -7 trials for pre- and postmenopausal patients receiving first-line treatment for ABC were pooled and analyzed by age (<65y, 65-74y, and ≥75y).

Antibody-Drug Conjugates in Breast Cancer: The Road Towards Biologically-Informed Selection and Sequencing.

Purpose Of Review: In this review, we discuss evidence supporting the use of antibody-drug conjugates (ADCs) in breast cancer treatment, describe novel ADCs and combination regimens under development, and examine our current understanding of resistance mechanisms and biomarkers to guide ADC selection and sequencing.

Recent Findings: Three ADCs have proven benefit in patients with metastatic breast cancer: trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd), and sacituzumab govitecan (SG). There are over two hundred investigational ADCs on the horizon, as pre-clinical studies work to identify novel ADC targets and structures.

HER2DX genomic test in early-stage HER2-positive breast cancer.

Therapies targeting human epidermal growth factor receptor 2 (HER2)-positive breast cancer significantly impact patient outcomes, quality of life, and health care systems. While chemotherapy and trastuzumab improve survival in early-stage HER2-positive breast cancer, variability in clinical and biological characteristics leads to different response to therapies and outcomes. Clinical guidelines provide general recommendations, but significant uncertainty persists in identifying an optimal treatment plan for individual patients.