PAM50 Molecular Intrinsic Subtypes in the Nurses' Health Study Cohorts
| Autor: | Kevin H. Kensler, V N Sankar, Rulla M. Tamimi, Gabrielle M. Baker, Jianghua Wang, Andreea Lucia Stancu, Christopher A. Rubadue, Yujing J. Heng, Laura C. Collins, Joel S. Parker, Katherine A. Hoadley, A H Eliassen, Susan E. Hankinson, David J. Hunter, Michael E. Pyle, Xuehong Zhang |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Oncology Adult Male medicine.medical_specialty Future studies Epidemiology Nurses Article 03 medical and health sciences 0302 clinical medicine Breast cancer Text mining Internal medicine medicine Biomarkers Tumor Humans Relapse risk Tumor size business.industry Proportional hazards model Middle Aged medicine.disease Health Surveys 030104 developmental biology 030220 oncology & carcinogenesis Immunohistochemistry Nurses' Health Study Female business |
| Zdroj: | Cancer epidemiology, biomarkersprevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 28(4) |
| ISSN: | 1538-7755 |
| Popis: | Background: Modified median and subgroup-specific gene centering are two essential preprocessing methods to assign breast cancer molecular subtypes by PAM50. We evaluated the PAM50 subtypes derived from both methods in a subset of Nurses' Health Study (NHS) and NHSII participants; correlated tumor subtypes by PAM50 with IHC surrogates; and characterized the PAM50 subtype distribution, proliferation scores, and risk of relapse with proliferation and tumor size weighted (ROR-PT) scores in the NHS/NHSII. Methods: PAM50 subtypes, proliferation scores, and ROR-PT scores were calculated for 882 invasive breast tumors and 695 histologically normal tumor-adjacent tissues. Cox proportional hazards models evaluated the relationship between PAM50 subtypes or ROR-PT scores/groups with recurrence-free survival (RFS) or distant RFS. Results: PAM50 subtypes were highly comparable between the two methods. The agreement between tumor subtypes by PAM50 and IHC surrogates improved to fair when Luminal subtypes were grouped together. Using the modified median method, our study consisted of 46% Luminal A, 18% Luminal B, 14% HER2-enriched, 15% Basal-like, and 8% Normal-like subtypes; 53% of tumor-adjacent tissues were Normal-like. Women with the Basal-like subtype had a higher rate of relapse within 5 years. HER2-enriched subtypes had poorer outcomes prior to 1999. Conclusions: Either preprocessing method may be utilized to derive PAM50 subtypes for future studies. The majority of NHS/NHSII tumor and tumor-adjacent tissues were classified as Luminal A and Normal-like, respectively. Impact: Preprocessing methods are important for the accurate assignment of PAM50 subtypes. These data provide evidence that either preprocessing method can be used in epidemiologic studies. |
| Databáze: | OpenAIRE |
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