What are the luminal A and luminal B breast cancer subtypes, how are they defined by estrogen receptor, progesterone receptor, HER2 status and Ki‑67 proliferation index, and what are the standard treatment approaches for each?

Luminal Breast Cancer Subtypes: Definitions and Treatment

Luminal A and Luminal B breast cancers are distinguished primarily by Ki-67 proliferation index, progesterone receptor expression, and HER2 status, with Luminal A requiring endocrine therapy alone in most cases while Luminal B typically necessitates combined chemotherapy and endocrine therapy. 1

Luminal A Subtype Definition

Luminal A-like tumors are defined as:

• ER-positive 1
• HER2-negative 1
• Ki-67 low (suggested cut-off ≤20%, though local laboratory values must guide interpretation) 1
• PgR high (suggested cut-off ≥20%) 1
• Low histologic grade (typically grade I or II) 1, 2
• Low-risk molecular signature when genomic testing is available 1, 2

These tumors are typically strongly ER-positive/PgR-positive with low proliferative fraction and represent the most common and least aggressive molecular subtype. 1, 2

Luminal B Subtype Definition

Luminal B encompasses two distinct categories:

Luminal B-like (HER2-negative):

• ER-positive 1
• HER2-negative 1
• Either Ki-67 high (>20%) or PgR low (<20%) 1
• Higher histologic grade than Luminal A 1
• High-risk molecular signature when available 1

Luminal B-like (HER2-positive):

• ER-positive 1
• HER2-positive 1
• Any Ki-67 level 1
• Any PgR level 1

Luminal B tumors demonstrate variable degrees of ER/PgR expression, higher grade, and higher proliferative fraction compared to Luminal A. 1

Critical Ki-67 Interpretation

Ki-67 scores must be interpreted in the context of local laboratory values. 1 As an example, if a laboratory has a median Ki-67 score in receptor-positive disease of 20%:

• Values ≥30% should be considered clearly high 1
• Values ≤10% should be considered clearly low 1
• Quality assurance programs are essential for laboratories reporting Ki-67 results 1, 2

Research data suggest that a Ki-67 cut point of approximately 13-14% can distinguish luminal subtypes prognostically, though the 20% threshold remains the guideline-recommended standard. 3, 4

Standard Treatment Approaches

Luminal A Treatment:

Endocrine therapy alone is sufficient for the majority of Luminal A cases. 1, 2

Consider adding chemotherapy only if:

• High tumor burden (≥4 positive lymph nodes or T3 or higher) 1
• Grade 3 histology 1

The 10-year breast cancer-specific survival with tamoxifen alone is approximately 79% for Luminal A tumors. 3

Luminal B (HER2-negative) Treatment:

Endocrine therapy plus chemotherapy for the majority of cases. 1 This reflects the higher proliferative fraction and poorer prognosis compared to Luminal A, with 10-year breast cancer-specific survival of approximately 64% with tamoxifen alone. 3

Luminal B (HER2-positive) Treatment:

Chemotherapy plus anti-HER2 therapy plus endocrine therapy for all patients. 1 If contraindications exist for chemotherapy, endocrine therapy plus anti-HER2 therapy may be considered, though no randomized data support this approach. 1

Prognostic Significance

Luminal B tumors (both HER2-negative and HER2-positive) are associated with significantly worse disease-free survival and breast cancer-specific survival compared to Luminal A across all adjuvant treatment categories. 3 The combination of Ki-67, PgR status, and TP53 status provides the most powerful prognostic stratification within ER-positive disease. 4

Common Pitfalls to Avoid

• Do not assume all ER-positive tumors have the same prognosis—Ki-67 and PgR levels fundamentally alter risk stratification and treatment decisions. 1, 3
• Do not use a single universal Ki-67 cut-off—interpretation must account for local laboratory median values and quality control. 1
• Do not omit chemotherapy in Luminal B (HER2-negative) disease based solely on hormone receptor positivity—the higher proliferative fraction and lower PgR expression indicate reduced endocrine responsiveness. 1, 5
• Retest ER/PgR/HER2 on surgical specimens if initially negative on biopsy to account for tumor heterogeneity; surgical specimen results are considered definitive in case of discrepancy. 1