Differences in molecular features of triple‐negative breast cancers based on the age at diagnosis

• Published in: Cancer Vol. 124; no. 24; pp. 4676 - 4684
• Main Authors: Gulbahce, H. Evin, Bernard, Philip S., Weltzien, Erin K., Factor, Rachel E., Kushi, Lawrence H., Caan, Bette J., Sweeney, Carol
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 15.12.2018
• Subjects: Adult; Age; Age Factors; Age of Onset; Aged; Aged, 80 and over; Breast cancer; Cancer; Classification; Confidence intervals; Diagnosis; epidemiology; Epidermal growth factor; ErbB-2 protein; Female; Gene expression; Gene Expression Profiling - methods; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Genes; Growth factors; Health risk assessment; Health risks; Humans; Immunohistochemistry; Medical diagnosis; Middle Aged; molecular subtype; Neoplasm Staging; older women; Oncology; Population studies; prognosis; Receptor, ErbB-2 - genetics; Sensitivity; Survival Analysis; Triple Negative Breast Neoplasms - classification; Triple Negative Breast Neoplasms - diagnosis; Triple Negative Breast Neoplasms - genetics; Triple Negative Breast Neoplasms - pathology; epidemiology; breast cancer; older women; prognosis; molecular subtype
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.31776

Background Although the proportion of triple‐negative breast cancers (TNBCs) diagnosed among older women is low, the number of TNBC cases is substantial because of the high incidence of breast cancer after the age of 65 years. The molecular features of TNBC in this age group have not been well described. Methods This study examined a population‐based cohort of women with stage I to III TNBC diagnosed between the ages of 25 and 91 years with the PAM50 gene expression subtyping assay. The concordance between the TNBC classification by immunohistochemistry and the gene expression classification by PAM50, the expression of individual genes, and 5‐year recurrence and breast cancer mortality in older women (≥65 years old) and younger women (<50 years old) was assessed. Results The molecular subtype distribution in TNBC was significantly different according to the age at diagnosis. TNBC was more likely to be classified as basal‐like in women younger than 50 years (sensitivity, 0.91; 95% confidence interval, 0.77‐0.97) than women 65 years old or older (sensitivity, 0.72; 95% confidence interval, 0.48‐0.87); 35% of clinical TNBC cases in the latter group were the human epidermal growth factor receptor 2 (HER2)–enriched subtype by molecular classification. Older women with TNBC also had significantly higher expression of ERBB2 and lower expression of all 10 proliferation‐associated genes tested (P < .01). The risk of breast cancer death within 5 years was significantly higher in women with TNBC in comparison with women with hormone receptor–positive cancers in all age groups. Conclusions This study revealed differences in molecular subtypes among clinical TNBC cases based on patient age. A potentially targetable HER2‐enriched group raises the possible need for intrinsic subtyping in older women with TNBC. Triple‐negative breast cancers have different molecular subtypes among older women in comparison with younger women. A potentially targetable human epidermal growth factor receptor 2–enriched subtype is more common among women older than 65 years.