PAM50- and immunohistochemistry-based subtypes of breast cancer and their relationship with breast cancer mortality in a population-based study

• Published in: Breast cancer (Tokyo, Japan) Vol. 28; no. 6; pp. 1235 - 1242
• Main Authors: Wang, Lin, Li, Qian, Aushev, Vasily N., Neugut, Alfred I., Santella, Regina M., Teitelbaum, Susan, Chen, Jia
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 01.11.2021; Springer
• Subjects: Adult; Analysis; Biomarkers, Tumor; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Cancer; Cancer Research; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Medical records; Medicine; Medicine & Public Health; Middle Aged; Mortality; Oncology; Oncology, Experimental; Original Article; Patient outcomes; Proportional Hazards Models; Receptor, ErbB-2; Surgery; Surgical Oncology; Immunohistochemistry; Hormone receptor; PAM50; Survival analysis; Breast cancer; Human epidermal growth factor receptor 2
• ISSN: 1340-6868; 1880-4233
• DOI: 10.1007/s12282-021-01261-w

Purpose We evaluated the prognostic ability of immunohistochemistry (IHC)-based vs. PAM50-based subtypes for breast cancer mortality in a population-based study of breast cancer. Methods We included a total of 463 breast cancer cases from the population-based Long Island Breast Cancer Study Project (LIBCSP). IHC-based markers were abstracted from the medical records, while the PAM50-based intrinsic subtypes were assessed from tumor tissues using NanoString nCounter ® Analysis System. Cox proportional hazards models were used to estimate hazards ratios (HRs) for breast cancer-specific mortality associated with subtypes. Results For IHC-based hormone receptor-positive (HR+) tumors ( n  = 361), 68.7% were classified as luminal subtypes by PAM50; for HR− tumors ( n  = 102), 95.1% were classified as non-luminal subtypes. Compared to HR+/HER2− subtype, HR− patients had significantly higher breast cancer mortality (HR−/HER2+: HR = 2.84, 95% CI = 1.58–5.11; triple-negative breast cancer: HR = 2.42, 95% CI = 1.44–4.06). Compared to luminal A, a higher mortality rate was observed for all other PAM50-based subtypes: luminal B (HR = 4.03, 95% CI = 1.97–8.22), HER2-enriched (HR = 6.82, 95% CI = 3.29–14.14) and basal-like (HR = 4.71, 95% CI = 2.24–9.93). Additional subtyping of HR+ patients by PAM50 provided future risk stratification where luminal B patients in this group had significant higher mortality than luminal A patients (HR = 3.93, 95% CI = 1.92–8.03). Similar results were also observed among 291 HR+/HER2− patients, but not among the HR− patients. Conclusions Our study suggests that for HR+ patients, especially HR+/HER2− patients, additional PAM50-based subtyping would provide better prognostic stratification and improve disease management.