Morphological predictors of BRCA1 germline mutations in young women with breast cancer
| Autor: | Letitia D. Smith, John L. Hopper, James G. Dowty, Andrea Tesoriero, Graham Byrnes, Ee Ming Wong, Melissa C. Southey, Ingrid Winship, Gillian S. Dite, Susan J. Ramus, Kelly-Anne Phillips, Mark A. Jenkins, G.G. Giles |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Oncology Heterozygote Cancer Research medicine.medical_specialty Colorectal cancer DNA Mutational Analysis Population Genes BRCA1 Breast Neoplasms Biology 03 medical and health sciences 0302 clinical medicine Germline mutation Breast cancer Internal medicine medicine Humans Women Registries Family history education Germ-Line Mutation Retrospective Studies 030304 developmental biology Family Health Gynecology 0303 health sciences education.field_of_study tumour morphology Carcinoma Age Factors Cancer Odds ratio BRCA1 Prognosis medicine.disease Tumor Burden 3. Good health early-onset breast cancer 030220 oncology & carcinogenesis Clinical Study Female Breast disease Genome-Wide Association Study |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| Popis: | BACKGROUND: Knowing a young woman with newly diagnosed breast cancer has a germline BRCA1 mutation informs her clinical management and that of her relatives. We sought an optimal strategy for identifying carriers using family history, breast cancer morphology and hormone receptor status data. METHODS: We studied a population-based sample of 452 Australian women with invasive breast cancer diagnosed before age 40 years for whom we conducted extensive germline mutation testing (29 carried a BRCA1 mutation) and a systematic pathology review, and collected three-generational family history and tumour ER and PR status. Predictors of mutation status were identified using multiple logistic regression. Areas under receiver operator characteristic (ROC) curves were estimated using five-fold stratified cross-validation. RESULTS: The probability of being a BRCA1 mutation carrier increased with number of selected histology features even after adjusting for family history and ER and PR status (Po0.0001). From the most parsimonious multivariate model, the odds ratio for being a carrier were: 9.7 (95% confidence interval: 2.6-47.0) for trabecular growth pattern (P=0.001); 7.8 (2.7-25.7) for mitotic index over 50 mitoses per 10 high-powered field (P 0.0003); and 2.7 (1.3-5.9) for each first-degree relative with breast cancer diagnosed before age 60 years (P 0.01). The area under the ROC curve was 0.87 (0.83-0.90). CONCLUSION: Pathology review, with attention to a few specific morphological features of invasive breast cancers, can identify almost all BRCA1 germline mutation carriers among women with early-onset breast cancer without taking into account family history. British Journal of Cancer (2011) 104, 903-909. doi: 10.1038/ bjc. 2011.41 www. bjcancer. com |
| Databáze: | OpenAIRE |
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