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Clinical and molecular characteristics of estrogen receptor-positive ultralow risk breast cancer tumors identified by the 70-gene signature
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- Johansson, Annelie (författare)
- Karolinska Institutet
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- Yu, Nancy Y. (författare)
- Karolinska Inst, Sweden
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- Iftimi, Adina (författare)
- Karolinska Inst, Sweden
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- Tobin, Nicholas P. (författare)
- Karolinska Institutet
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- Van 'T Veer, Laura (författare)
- Univ Calif San Francisco, CA USA; Univ Calif San Francisco, CA 94140 USA
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- Nordenskjöld, Bo, 1940- (författare)
- Linköpings universitet,Avdelningen för kirurgi, ortopedi och onkologi,Medicinska fakulteten,Region Östergötland, Onkologiska kliniken US
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- Benz, Christopher C. (författare)
- Univ Calif San Francisco, CA 94143 USA; Buck Inst Res Aging, CA USA
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- Fornander, Tommy (författare)
- Karolinska Institutet
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- Pérez-Tenorio, Gizeh, 1971- (författare)
- Linköpings universitet,Avdelningen för kirurgi, ortopedi och onkologi,Medicinska fakulteten,Region Östergötland, Onkologiska kliniken US
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- Stål, Olle, 1952- (författare)
- Linköpings universitet,Avdelningen för kirurgi, ortopedi och onkologi,Medicinska fakulteten,Region Östergötland, Onkologiska kliniken US
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- Esserman, Laura J. (författare)
- Univ Calif San Francisco, CA USA
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- Yau, Christina (författare)
- Buck Inst Res Aging, CA USA; Univ Calif San Francisco, CA USA
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- Lindström, Linda S. (författare)
- Karolinska Institutet
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(creator_code:org_t)
- 2022-03-07
- 2022
- Engelska.
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 150:12, s. 2072-2082
- Relaterad länk:
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https://liu.diva-por... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- The metastatic potential of estrogen receptor (ER)-positive breast cancers is heterogeneous and distant recurrences occur months to decades after primary diagnosis. We have previously shown that patients with tumors classified as ultralow risk by the 70-gene signature have a minimal long-term risk of fatal breast cancer. Here, we evaluate the previously unexplored underlying clinical and molecular characteristics of ultralow risk tumors in 538 ER-positive patients from the Stockholm tamoxifen randomized trial (STO-3). Out of the 98 ultralow risk tumors, 89% were luminal A molecular subtype, whereas 26% of luminal A tumors were of ultralow risk. Compared to other ER-positive tumors, ultralow risk tumors were significantly (Fishers test, P < .05) more likely to be of smaller tumor size, lower grade, progesterone receptor (PR)-positive, human epidermal growth factor 2 (HER2)-negative and have low Ki-67 levels (proliferation-marker). Moreover, ultralow risk tumors showed significantly lower expression scores of multi-gene modules associated with the AKT/mTOR-pathway, proliferation (AURKA), HER2/ERBB2-signaling, IGF1-pathway, PTEN-loss and immune response (IMMUNE1 and IMMUNE2) and higher expression scores of the PIK3CA-mutation-associated module. Furthermore, 706 genes were significantly (FDR < 0.001) differentially expressed in ultralow risk tumors, including lower expression of genes involved in immune response, PI3K/Akt/mTOR-pathway, histones, cell cycle, DNA repair, apoptosis and higher expression of genes coding for epithelial-to-mesenchymal transition and homeobox proteins, among others. In conclusion, ultralow risk tumors, associated with minimal long-term risk of fatal disease, differ from other ER-positive tumors, including luminal A molecular subtype tumors. Identification of these characteristics is important to improve our prediction of nonfatal vs fatal breast cancer.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- 70-gene signature; breast cancer; gene expression; long-term survival; prognosis; ultralow risk
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Johansson, Annel ...
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Yu, Nancy Y.
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Iftimi, Adina
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Tobin, Nicholas ...
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Van 'T Veer, Lau ...
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Nordenskjöld, Bo ...
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Benz, Christophe ...
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Fornander, Tommy
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Pérez-Tenorio, G ...
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Stål, Olle, 1952 ...
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Esserman, Laura ...
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Yau, Christina
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Lindström, Linda ...
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