What is Luminal A (breast cancer subtype)?

Luminal A Breast Cancer Subtype

Luminal A breast cancer is a hormone receptor-positive, HER2-negative subtype characterized by strong ER and PgR expression, low Ki67 proliferation index (<20%), low histologic grade, and favorable prognosis, representing the most common and least aggressive molecular subtype of breast cancer. 1

Defining Characteristics

Immunohistochemical Profile

• ER-positive (strongly positive) 1
• HER2-negative 1
• Ki67 low (suggested cut-off <20%, with values <10% considered clearly low) 1
• PgR high (high progesterone receptor expression) 1
• Low-risk molecular signature when genomic testing is available 1

Pathological Features

• Low histologic grade (typically grade I or II) 1, 2
• Low proliferative fraction 1, 2
• Special histologic types often fall into this category, including tubular, mucinous, and cribriform carcinomas 1

Clinical Significance and Prognosis

Prognostic Implications

• Best prognosis among all breast cancer subtypes 3
• High endocrine responsiveness due to strong hormone receptor expression 2
• Lower risk of early relapse compared to Luminal B subtypes 4

Treatment Approach

• Endocrine therapy alone is sufficient for the majority of Luminal A cases 2
• Chemotherapy should be reserved only for high tumor burden (≥4 positive lymph nodes, T3 or higher) or grade 3 tumors 2
• Evidence shows no benefit from cyclophosphamide-based chemotherapy in high-risk premenopausal Luminal A patients in randomized trials 5

Distinction from Luminal B

Key Differentiating Features

• Luminal B has higher Ki67 (>20%) or low PgR expression, whereas Luminal A has low Ki67 and high PgR 1, 2
• Luminal B is higher grade (26% grade III) compared to Luminal A (8% grade III) 2
• Luminal B requires chemotherapy in addition to endocrine therapy, while Luminal A typically does not 2

Important Clinical Considerations

Quality Control Requirements

• Ki67 interpretation must be standardized in light of local laboratory values; quality assurance programs are essential 1
• Surrogate assessment requires meticulous quality control to ensure accurate subtype classification 2

Common Pitfalls to Avoid

• Do not assume all ER-positive tumors are the same: Ki67 and PgR levels are critical for distinguishing Luminal A from Luminal B and determining appropriate treatment 2
• Do not over-treat with chemotherapy: Luminal A patients derive minimal to no benefit from cytotoxic chemotherapy when tumor burden is low 2, 5
• Consider genomic assays (Oncotype DX, MammaPrint, Prosigna, Endopredict) to refine individual recurrence risk and predict chemotherapy benefit in borderline cases 2

Molecular Heterogeneity

• Luminal A is molecularly diverse despite its favorable prognosis, with distinct copy-number and mutation profiles including PIK3CA, GATA3, AKT1, and MAP3K1 mutations 6
• Rare alterations in co-repressor complexes (N-Cor and SMRT) may predict resistance to endocrine therapy 6