Molecular Subtypes of Breast Cancer: A Review for Breast Radiologists

Karen S Johnson; Emily F Conant; Mary Scott Soo

doi:10.1093/jbi/wbaa110

Molecular Subtypes of Breast Cancer: A Review for Breast Radiologists

J Breast Imaging. 2021 Jan 26;3(1):12-24. doi: 10.1093/jbi/wbaa110.

Authors

Karen S Johnson¹, Emily F Conant², Mary Scott Soo¹

Affiliations

¹ Duke University Hospital, Department of Diagnostic Radiology, Durham, NC.
² Perelman School of Medicine, Hospital of the University of Pennsylvania, Department of Radiology, Philadelphia, PA.

PMID: 38424845
DOI: 10.1093/jbi/wbaa110

Abstract

Gene expression profiling has reshaped our understanding of breast cancer by identifying four molecular subtypes: (1) luminal A, (2) luminal B, (3) human epidermal growth factor receptor 2 (HER2)-enriched, and (4) basal-like, which have critical differences in incidence, response to treatment, disease progression, survival, and imaging features. Luminal tumors are most common (60%-70%), characterized by estrogen receptor (ER) expression. Luminal A tumors have the best prognosis of all subtypes, whereas patients with luminal B tumors have significantly shorter overall and disease-free survival. Distinguishing between these tumors is important because luminal B tumors require more aggressive treatment. Both commonly present as irregular masses without associated calcifications at mammography; however, luminal B tumors more commonly demonstrate axillary involvement at diagnosis. HER2-enriched tumors are characterized by overexpression of the HER2 oncogene and low-to-absent ER expression. HER2+ disease carries a poor prognosis, but the development of anti-HER2 therapies has greatly improved outcomes for women with HER2+ breast cancer. HER2+ tumors most commonly present as spiculated masses with pleomorphic calcifications or as calcifications alone. Basal-like cancers (15% of all invasive breast cancers) predominate among "triple negative" cancers, which lack ER, progesterone receptor (PR), and HER2 expression. Basal-like cancers are frequently high-grade, large at diagnosis, with high rates of recurrence. Although imaging commonly reveals irregular masses with ill-defined or spiculated margins, some circumscribed basal-like tumors can be mistaken for benign lesions. Incorporating biomarker data (histologic grade, ER/PR/HER2 status, and multigene assays) into classic anatomic tumor, node, metastasis (TNM) staging can better inform clinical management of this heterogeneous disease.

Keywords: HER2-enriched; basal; breast cancer; luminal; molecular subtype.