JoVE - Journal of Visualized Experiments
JoVE Visualize
Contact Us

Clinicopathologic and molecular characterization of low-grade, early-stage, and HER2-positive invasive breast carcinoma

  • 0Division of Hematology and Oncology and Oncology, University of Washington, Seattle, Washington, US.
American Journal of Clinical Pathology +

|

March 5, 2025

|

March 5, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Low-grade HER2-positive breast cancers are usually early-stage, luminal-type, and low-risk. Further research is needed to explore if less intensive therapies can maintain good outcomes while reducing side effects.

Area Of Science

  • Oncology
  • Genetics
  • Pathology

Background

  • HER2-positive breast carcinomas typically present with higher grade and faster progression.
  • HER2 positivity is uncommon in low-grade breast cancers, necessitating further characterization.

Purpose Of The Study

  • To define the clinicopathologic and molecular profiles of low-grade, HER2-positive invasive breast carcinomas.
  • To investigate the clinical behavior and treatment response in this specific patient subgroup.

Main Methods

  • Analysis of two cohorts: an institutional series (n=14) and the FLEX multicenter registry (n=59) of Nottingham grade 1, HER2-positive invasive breast carcinomas.
  • Utilized MammaPrint and BluePrint profiling for molecular subtyping and risk assessment.
  • Next-generation sequencing was performed on a subset of tumors to identify genetic alterations.

Main Results

  • The majority of tumors were estrogen receptor (ER) and progesterone receptor (PR)-positive, low-stage (T1N0), and of luminal phenotype.
  • ERBB2 copy number variations were common in sequenced tumors.
  • No recurrences were observed in the institutional cohort with a median follow-up of 43 months.
  • The FLEX cohort also showed predominantly ER-positive, PR-positive, low-stage, luminal-type, and low-risk (MammaPrint) tumors.

Conclusions

  • Low-grade HER2-positive breast carcinomas are characterized by low stage, luminal subtype, and low-risk molecular profiles.
  • These findings suggest potential for therapy de-escalation in this population to minimize toxicity while maintaining favorable outcomes.

Keywords: