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Association between...
Association between breast cancer risk and disease aggressiveness : Characterizing underlying gene expression patterns
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- Ugalde-Morales, Emilio (author)
- Karolinska Institutet,Karolinska Institute
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- Grassmann, Felix (author)
- Karolinska Institutet,Karolinska Institute,University of Aberdeen
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- Humphreys, Keith (author)
- Karolinska Institutet,Karolinska Institute
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- Li, Jingmei (author)
- Karolinska Institute,National University of Singapore,A*Star, Genome Institute of Singapore (GIS)
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- Eriksson, Mikael (author)
- Karolinska Institutet,Karolinska Institute
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- Tobin, Nicholas P. (author)
- Karolinska Institutet
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- Borg, Åke (author)
- Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Familjär bröstcancer,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Familial Breast Cancer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Vallon-Christersson, Johan (author)
- Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Hall, Per (author)
- Karolinska Institutet,Karolinska Institute,Stockholm South General Hospital
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- Czene, Kamila (author)
- Karolinska Institutet,Karolinska Institute
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(creator_code:org_t)
- 2020-09-05
- 2021
- English 11 s.
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 148:4, s. 884-894
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Abstract
Subject headings
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- The association between breast cancer risk defined by the Tyrer-Cuzick score (TC) and disease prognosis is not well established. Here, we investigated the relationship between 5-year TC and disease aggressiveness and then characterized underlying molecular processes. In a case-only study (n = 2474), we studied the association of TC with molecular subtypes and tumor characteristics. In a subset of patients (n = 672), we correlated gene expression to TC and computed a low-risk TC gene expression (TC-Gx) profile, that is, a profile expected to be negatively associated with risk, which we used to test for association with disease aggressiveness. We performed enrichment analysis to pinpoint molecular processes likely to be altered in low-risk tumors. A higher TC was found to be inversely associated with more aggressive surrogate molecular subtypes and tumor characteristics (P <.05) including Ki-67 proliferation status (P < 5 × 10−07). Our low-risk TC-Gx, based on the weighted sum of 37 expression values of genes strongly correlated with TC, was associated with basal-like (P < 5 × 10−13), HER2-enriched subtype (P < 5 × 10−07) and worse 10-year breast cancer-specific survival (log-rank P < 5 × 10−04). Associations between low-risk TC-Gx and more aggressive molecular subtypes were replicated in an independent cohort from The Cancer Genome Atlas database (n = 975). Gene expression that correlated with low TC was enriched in proliferation and oncogenic signaling pathways (FDR < 0.05). Moreover, higher proliferation was a key factor explaining the association with worse survival. Women who developed breast cancer despite having a low risk were diagnosed with more aggressive tumors and had a worse prognosis, most likely driven by increased proliferation. Our findings imply the need to establish risk factors associated with more aggressive breast cancer subtypes.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- breast cancer
- gene expression
- prognosis
- subtypes
- Tyrer-Cuzick risk score
Publication and Content Type
- art (subject category)
- ref (subject category)
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