Molecular subtype and tumor characteristics of breast cancer metastases as assessed by gene expression significantly influence patient post-relapse survival

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Molecular subtype and tumor characteristics of breast cancer metastases as assessed by gene expression significantly influence patient post-relapse survival. / Tobin, N. P.; Harrell, J. C.; Lovrot, J.; Egyhazi Brage, S.; Frostvik Stolt, M.; Carlsson, L.; Einbeigi, Z.; Linderholm, B.; Loman, Niklas; Malmberg, Martin; Walz, T.; Fernö, Mårten; Perou, C. M.; Bergh, J.; Hatschek, T.; Lindstrom, L. S.

In: Annals of Oncology, Vol. 26, No. 1, 2015, p. 81-88.

Research output: Contribution to journalArticle

Harvard

Tobin, NP, Harrell, JC, Lovrot, J, Egyhazi Brage, S, Frostvik Stolt, M, Carlsson, L, Einbeigi, Z, Linderholm, B, Loman, N, Malmberg, M, Walz, T, Fernö, M, Perou, CM, Bergh, J, Hatschek, T & Lindstrom, LS 2015, 'Molecular subtype and tumor characteristics of breast cancer metastases as assessed by gene expression significantly influence patient post-relapse survival', Annals of Oncology, vol. 26, no. 1, pp. 81-88. https://doi.org/10.1093/annonc/mdu498

APA

Tobin, N. P., Harrell, J. C., Lovrot, J., Egyhazi Brage, S., Frostvik Stolt, M., Carlsson, L., Einbeigi, Z., Linderholm, B., Loman, N., Malmberg, M., Walz, T., Fernö, M., Perou, C. M., Bergh, J., Hatschek, T., & Lindstrom, L. S. (2015). Molecular subtype and tumor characteristics of breast cancer metastases as assessed by gene expression significantly influence patient post-relapse survival. Annals of Oncology, 26(1), 81-88. https://doi.org/10.1093/annonc/mdu498

CBE

Tobin NP, Harrell JC, Lovrot J, Egyhazi Brage S, Frostvik Stolt M, Carlsson L, Einbeigi Z, Linderholm B, Loman N, Malmberg M, Walz T, Fernö M, Perou CM, Bergh J, Hatschek T, Lindstrom LS. 2015. Molecular subtype and tumor characteristics of breast cancer metastases as assessed by gene expression significantly influence patient post-relapse survival. Annals of Oncology. 26(1):81-88. https://doi.org/10.1093/annonc/mdu498

MLA

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Author

Tobin, N. P. ; Harrell, J. C. ; Lovrot, J. ; Egyhazi Brage, S. ; Frostvik Stolt, M. ; Carlsson, L. ; Einbeigi, Z. ; Linderholm, B. ; Loman, Niklas ; Malmberg, Martin ; Walz, T. ; Fernö, Mårten ; Perou, C. M. ; Bergh, J. ; Hatschek, T. ; Lindstrom, L. S. / Molecular subtype and tumor characteristics of breast cancer metastases as assessed by gene expression significantly influence patient post-relapse survival. In: Annals of Oncology. 2015 ; Vol. 26, No. 1. pp. 81-88.

RIS

TY - JOUR

T1 - Molecular subtype and tumor characteristics of breast cancer metastases as assessed by gene expression significantly influence patient post-relapse survival

AU - Tobin, N. P.

AU - Harrell, J. C.

AU - Lovrot, J.

AU - Egyhazi Brage, S.

AU - Frostvik Stolt, M.

AU - Carlsson, L.

AU - Einbeigi, Z.

AU - Linderholm, B.

AU - Loman, Niklas

AU - Malmberg, Martin

AU - Walz, T.

AU - Fernö, Mårten

AU - Perou, C. M.

AU - Bergh, J.

AU - Hatschek, T.

AU - Lindstrom, L. S.

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

KW - breast cancer metastases

KW - metastasis characteristics

KW - TEX randomized

KW - trial

KW - gene expression

KW - gene modules

KW - biopsy at relapse

U2 - 10.1093/annonc/mdu498

DO - 10.1093/annonc/mdu498

M3 - Article

C2 - 25361981

VL - 26

SP - 81

EP - 88

JO - Annals of Oncology

JF - Annals of Oncology

SN - 1569-8041

IS - 1

ER -