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Molecular subtype a...
Molecular subtype and tumor characteristics of breast cancer metastases as assessed by gene expression significantly influence patient post-relapse survival
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- Tobin, N. P. (author)
- Karolinska Institutet
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- Harrell, J. C. (author)
- University of N Carolina, NC 27599 USA
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- Lovrot, J. (author)
- Karolinska Institutet
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- Egyhazi Brage, S. (author)
- Karolinska Institutet
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- Frostvik Stolt, M. (author)
- Karolinska Institutet
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- Carlsson, L. (author)
- Sundsvall Gen Hospital, Sweden
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- Einbeigi, Z. (author)
- Sahlgrens University Hospital, Sweden
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- Linderholm, B. (author)
- Karolinska Institutet
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- Loman, Niklas (author)
- Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital, Sweden
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- Malmberg, Martin (author)
- Lund University,Lunds universitet,Kliniska Vetenskaper, Helsingborg,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Clinical Sciences, Helsingborg,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University, Sweden,University of N Carolina, NC 27599 USA
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- Walz, Thomas (author)
- Östergötlands Läns Landsting,Linköpings universitet,Avdelningen för kliniska vetenskaper,Hälsouniversitetet,Onkologiska kliniken US,Karolinska Institute, Sweden; University Hospital, Sweden
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- Fernö, Mårten (author)
- Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Individuell Bröstcancerbehandling,Forskargrupper vid Lunds universitet,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Personalized Breast Cancer Treatment,Lund University Research Groups
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Perou, C. M. (author)
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- Bergh, J. (author)
- Karolinska Institutet
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- Hatschek, T. (author)
- Karolinska Institutet
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- Lindstrom, L. S. (author)
- Karolinska Institutet
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(creator_code:org_t)
- Elsevier BV, 2015
- 2015
- English.
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In: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 26:1, s. 81-88
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Abstract
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- We and others have recently shown that tumor characteristics are altered throughout tumor progression. These findings emphasize the need for re-examination of tumor characteristics at relapse and have led to recommendations from ESMO and the Swedish Breast Cancer group. Here, we aim to determine whether tumor characteristics and molecular subtypes in breast cancer metastases confer clinically relevant prognostic information for patients. The translational aspect of the Swedish multicenter randomized trial called TEX included 111 patients with at least one biopsy from a morphologically confirmed locoregional or distant breast cancer metastasis diagnosed from December 2002 until June 2007. All patients had detailed clinical information, complete follow-up, and metastasis gene expression information (Affymetrix array GPL10379). We assessed the previously published gene expression modules describing biological processes [proliferation, apoptosis, human epidermal receptor 2 (HER2) and estrogen (ER) signaling, tumor invasion, immune response, and angiogenesis] and pathways (Ras, MAPK, PTEN, AKT-MTOR, PI3KCA, IGF1, Src, Myc, E2F3, and beta-catenin) and the intrinsic subtypes (PAM50). Furthermore, by contrasting genes expressed in the metastases in relation to survival, we derived a poor metastasis survival signature. A significant reduction in post-relapse breast cancer-specific survival was associated with low-ER receptor signaling and apoptosis gene module scores, and high AKT-MTOR, Ras, and beta-catenin module scores. Similarly, intrinsic subtyping of the metastases provided statistically significant post-relapse survival information with the worst survival outcome in the basal-like [hazard ratio (HR) 3.7; 95% confidence interval (CI) 1.3-10.9] and HER2-enriched (HR 4.4; 95% CI 1.5-12.8) subtypes compared with the luminal A subtype. Overall, 25% of the metastases were basal-like, 32% HER2-enriched, 10% luminal A, 28% luminal B, and 5% normal-like. We show that tumor characteristics and molecular subtypes of breast cancer metastases significantly influence post-relapse patient survival, emphasizing that molecular investigations at relapse provide prognostic and clinically relevant information.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
Keyword
- breast cancer metastases
- metastasis characteristics
- TEX randomized
- trial
- gene expression
- gene modules
- biopsy at relapse
- breast cancer metastases; metastasis characteristics; TEX randomized trial; gene expression; gene modules; biopsy at relapse
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Tobin, N. P.
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Harrell, J. C.
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Lovrot, J.
-
Egyhazi Brage, S ...
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Frostvik Stolt, ...
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Carlsson, L.
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show more...
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Einbeigi, Z.
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Linderholm, B.
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Loman, Niklas
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Malmberg, Martin
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Walz, Thomas
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Fernö, Mårten
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Perou, C. M.
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Bergh, J.
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Hatschek, T.
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Lindstrom, L. S.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
- Articles in the publication
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Annals of Oncolo ...
- By the university
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Lund University
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Linköping University
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Karolinska Institutet