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Breast Cancer Research and Treatment

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17.09.2018 | Epidemiology

Young age at diagnosis is associated with worse prognosis in the Luminal A breast cancer subtype: a retrospective institutional cohort study

verfasst von: Zhiyang Liu, Zeyad Sahli, Yongchun Wang, Antonio C. Wolff, Leslie M. Cope, Christopher B. Umbricht

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 3/2018

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Abstract

Purpose

Although age is a recognized independent prognostic risk factor, its relative importance among molecular subtypes of Breast cancer (BCA) is not well documented. The aim of this study was to evaluate the prognostic role of age at diagnosis among different immunohistochemical subtypes of BCA.

Methods

We conducted a retrospective study of women with invasive BCA undergoing surgery at the Johns Hopkins Hospital, excluding patients presenting with stage IV breast cancer. Patients were stratified into three age groups: ≤ 40, 41–60, and > 60 years, and multivariable analysis was performed using Cox regression. We also identified differentially expressed genes (DEG) between age groups among BCA subtypes in the public TCGA dataset. Finally, we identified key driver genes within the DEGs using a weighted gene co-expression network analysis.

Results

Luminal A breast cancer patients had significantly lower 5 year disease-free survival (DFS) and distant metastasis-free survival (DMFS) in the ≤ 40 year age group compared to the 41–60 year age group, while the other molecular subtypes showed no significant association of DFS or DMFS with age. Age was a stronger outcome predictor than tumor grade or proliferative index in Luminal A BCA patients, but not other subtypes. BCA TCGA gene expression data were divided into two groups (≤ 40 years, > 40 years). We identified 374 DEGs in the Luminal A BCA subset, which were enriched in seven pathways and two modules of co-expressed genes. No age group-specific DEGs were identified in non-Luminal A subtypes.

Conclusions

Age at diagnosis may be an important prognostic factor in Luminal A BCA.

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Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. CA Cancer J Clin 68(1):7–30. https://doi.org/10.3322/caac.21442 CrossRefPubMed

Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, Thorsen T, Quist H, Matese JC, Brown PO, Botstein D, Eystein Lonning P, Borresen-Dale AL (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 98(19):10869–10874CrossRefPubMedPubMedCentral

Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, Thurlimann B, Senn HJ, Panel m (2013) Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol 24(9):2206–2223. https://doi.org/10.1093/annonc/mdt303 CrossRefPubMedPubMedCentral

Carey LA, Perou CM, Livasy CA, Dressler LG, Cowan D, Conway K, Karaca G, Troester MA, Tse CK, Edmiston S, Deming SL, Geradts J, Cheang MC, Nielsen TO, Moorman PG, Earp HS, Millikan RC (2006) Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA 295(21):2492–2502. https://doi.org/10.1001/jama.295.21.2492 CrossRefPubMed

Engstrom MJ, Opdahl S, Hagen AI, Romundstad PR, Akslen LA, Haugen OA, Vatten LJ, Bofin AM (2013) Molecular subtypes, histopathological grade and survival in a historic cohort of breast cancer patients. Breast Cancer Res Treat 140(3):463–473. https://doi.org/10.1007/s10549-013-2647-2 CrossRefPubMedPubMedCentral

Kennecke H, Yerushalmi R, Woods R, Cheang MC, Voduc D, Speers CH, Nielsen TO, Gelmon K (2010) Metastatic behavior of breast cancer subtypes. J Clin Oncol 28(20):3271–3277. https://doi.org/10.1200/JCO.2009.25.9820 CrossRefPubMed

Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, Deng S, Johnsen H, Pesich R, Geisler S, Demeter J, Perou CM, Lonning PE, Brown PO, Borresen-Dale AL, Botstein D (2003) Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA 100(14):8418–8423CrossRefPubMedPubMedCentral

Voduc KD, Cheang MC, Tyldesley S, Gelmon K, Nielsen TO, Kennecke H (2010) Breast cancer subtypes and the risk of local and regional relapse. J Clin Oncol 28(10):1684–1691CrossRefPubMed

Alieldin NH, Abo-Elazm OM, Bilal D, Salem SE, Gouda E, Elmongy M, Ibrahim AS (2014) Age at diagnosis in women with non-metastatic breast cancer: is it related to prognosis? J Egypt Natl Cancer Inst 26(1):23–30. https://doi.org/10.1016/j.jnci.2013.08.005 CrossRef

10.

Azim HA Jr, Michiels S, Bedard PL, Singhal SK, Criscitiello C, Ignatiadis M, Haibe-Kains B, Piccart MJ, Sotiriou C, Loi S (2012) Elucidating prognosis and biology of breast cancer arising in young women using gene expression profiling. Clin Cancer Res 18(5):1341–1351. https://doi.org/10.1158/1078-0432.CCR-11-2599 CrossRefPubMed

11.

Ferguson NL, Bell J, Heidel R, Lee S, Vanmeter S, Duncan L, Munsey B, Panella T, Orucevic A (2013) Prognostic value of breast cancer subtypes, Ki-67 proliferation index, age, and pathologic tumor characteristics on breast cancer survival in Caucasian women. Breast J 19(1):22–30. https://doi.org/10.1111/tbj.12059 CrossRefPubMed

12.

Liedtke C, Rody A, Gluz O, Baumann K, Beyer D, Kohls EB, Lausen K, Hanker L, Holtrich U, Becker S, Karn T (2015) The prognostic impact of age in different molecular subtypes of breast cancer. Breast Cancer Res Treat 152(3):667–673. https://doi.org/10.1007/s10549-015-3491-3 CrossRefPubMed

13.

van de Water W, Markopoulos C, van de Velde CJ, Seynaeve C, Hasenburg A, Rea D, Putter H, Nortier JW, de Craen AJ, Hille ET, Bastiaannet E, Hadji P, Westendorp RG, Liefers GJ, Jones SE (2012) Association between age at diagnosis and disease-specific mortality among postmenopausal women with hormone receptor-positive breast cancer. JAMA 307(6):590–597. https://doi.org/10.1001/jama.2012.84 CrossRefPubMed

14.

Wray CJ, Phatak UR, Robinson EK, Wiatek RL, Rieber AG, Gonzalez A, Ko TC, Kao LS (2013) The effect of age on race-related breast cancer survival disparities. Ann Surg Oncol 20(8):2541–2547. https://doi.org/10.1245/s10434-013-2913-x CrossRefPubMed

15.

Network TCGAR (2012) Comprehensive molecular portraits of human breast tumours. Nature 490(7418):61–70. https://doi.org/10.1038/nature11412 CrossRef

16.

Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, Fitzgibbons PL, Francis G, Goldstein NS, Hayes M, Hicks DG, Lester S, Love R, Mangu PB, McShane L, Miller K, Osborne CK, Paik S, Perlmutter J, Rhodes A, Sasano H, Schwartz JN, Sweep FC, Taube S, Torlakovic EE, Valenstein P, Viale G, Visscher D, Wheeler T, Williams RB, Wittliff JL, Wolff AC (2010) American Society of Clinical Oncology/College Of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol 28(16):2784–2795CrossRefPubMedPubMedCentral

17.

Wolff AC, Hammond MEH, Allison KH, Harvey BE, Mangu PB, Bartlett JMS, Bilous M, Ellis IO, Fitzgibbons P, Hanna W, Jenkins RB, Press MF, Spears PA, Vance GH, Viale G, McShane LM, Dowsett M (2018) Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. Arch Pathol Lab Med. https://doi.org/10.5858/arpa.2018-0902-SA CrossRefPubMed

18.

Ignatiadis M, Buyse M, Sotiriou C (2015) St Gallen International Expert Consensus on the primary therapy of early breast cancer: an invaluable tool for physicians and scientists. Ann Oncol 26(8):1519–1520. https://doi.org/10.1093/annonc/mdv259 CrossRefPubMed

19.

Breiman L (2001) Random forests. Mach Learn 45(1):5–32. https://doi.org/10.1023/A:101093340 CrossRef

20.

Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S, Ellis B, Gautier L, Ge Y, Gentry J, Hornik K, Hothorn T, Huber W, Iacus S, Irizarry R, Leisch F, Li C, Maechler M, Rossini AJ, Sawitzki G, Smith C, Smyth G, Tierney L, Yang JY, Zhang J (2004) Bioconductor: open software development for computational biology and bioinformatics. Genome Biol 5(10):R80CrossRefPubMedPubMedCentral

21.

He XM, Zou DH (2017) The association of young age with local recurrence in women with early-stage breast cancer after breast-conserving therapy: a meta-analysis. Sci Rep 7(1):11058. https://doi.org/10.1038/s41598-017-10729-9 CrossRefPubMedPubMedCentral

22.

Lian W, Fu F, Lin Y, Lu M, Chen B, Yang P, Zeng B, Huang M, Wang C (2017) The impact of young age for prognosis by subtype in women with early breast cancer. Sci Rep 7(1):11625. https://doi.org/10.1038/s41598-017-10414-x CrossRefPubMedPubMedCentral

23.

Partridge AH, Hughes ME, Warner ET, Ottesen RA, Wong YN, Edge SB, Theriault RL, Blayney DW, Niland JC, Winer EP, Weeks JC, Tamimi RM (2016) Subtype-dependent relationship between young age at diagnosis and breast cancer survival. J Clin Oncol 34(27):3308–3314. https://doi.org/10.1200/JCO.2015.65.8013 CrossRefPubMed

24.

Tammemagi CM, Nerenz D, Neslund-Dudas C, Feldkamp C, Nathanson D (2005) Comorbidity and survival disparities among black and white patients with breast cancer. JAMA 294(14):1765–1772. https://doi.org/10.1001/jama.294.14.1765 CrossRefPubMed

25.

Carter CL, Allen C, Henson DE (1989) Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases. Cancer 63(1):181–187CrossRefPubMed

26.

Ehinger A, Malmstrom P, Bendahl PO, Elston CW, Falck AK, Forsare C, Grabau D, Ryden L, Stal O, Ferno M, South, South-East Swedish Breast Cancer G (2017) Histological grade provides significant prognostic information in addition to breast cancer subtypes defined according to St Gallen 2013. Acta Oncol 56(1):68–74. https://doi.org/10.1080/0284186X.2016.1237778 CrossRefPubMed

27.

Liberzon A, Birger C, Thorvaldsdottir H, Ghandi M, Mesirov JP, Tamayo P (2015) The Molecular Signatures Database (MSigDB) hallmark gene set collection. Cell Syst 1(6):417–425. https://doi.org/10.1016/j.cels.2015.12.004 CrossRefPubMedPubMedCentral

28.

Langfelder P, Horvath S (2008) WGCNA: an R package for weighted correlation network analysis. BMC Bioinform 9:559. https://doi.org/10.1186/1471-2105-9-559 CrossRef

29.

Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13(11):2498–2504. https://doi.org/10.1101/gr.1239303 CrossRefPubMedPubMedCentral

30.

Fowble BL, Schultz DJ, Overmoyer B, Solin LJ, Fox K, Jardines L, Orel S, Glick JH (1994) The influence of young age on outcome in early stage breast cancer. Int J Radiat Oncol Biol Phys 30(1):23–33CrossRefPubMed

31.

Orucevic A, Bell JL, McNabb AP, Heidel RE (2017) Oncotype DX breast cancer recurrence score can be predicted with a novel nomogram using clinicopathologic data. Breast Cancer Res Treat 163(1):51–61. https://doi.org/10.1007/s10549-017-4170-3 CrossRefPubMedPubMedCentral

32.

Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, Baehner FL, Walker MG, Watson D, Park T, Hiller W, Fisher ER, Wickerham DL, Bryant J, Wolmark N (2004) A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 351(27):2817–2826CrossRefPubMed

33.

van de Vijver MJ, He YD, van’t Veer LJ, Dai H, Hart AA, Voskuil DW, Schreiber GJ, Peterse JL, Roberts C, Marton MJ, Parrish M, Atsma D, Witteveen A, Glas A, Delahaye L, van der Velde T, Bartelink H, Rodenhuis S, Rutgers ET, Friend SH, Bernards R (2002) A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med 347(25):1999–2009CrossRefPubMed

34.

Morrison DH, Rahardja D, King E, Peng Y, Sarode VR (2012) Tumour biomarker expression relative to age and molecular subtypes of invasive breast cancer. Br J Cancer 107(2):382–387. https://doi.org/10.1038/bjc.2012.219 CrossRefPubMedPubMedCentral

35.

Perez-Fidalgo JA, Rosello S, Garcia-Garre E, Jorda E, Martin-Martorell P, Bermejo B, Chirivella I, Guzman C, Lluch A (2010) Incidence of chemotherapy-induced amenorrhea in hormone-sensitive breast cancer patients: the impact of addition of taxanes to anthracycline-based regimens. Breast Cancer Res Treat 120(1):245–251. https://doi.org/10.1007/s10549-009-0426-x CrossRefPubMed

36.

Saha P, Regan MM, Pagani O, Francis PA, Walley BA, Ribi K, Bernhard J, Luo W, Gomez HL, Burstein HJ, Parmar V, Torres R, Stewart J, Bellet M, Perello A, Dane F, Moreira A, Vorobiof D, Nottage M, Price KN, Coates AS, Goldhirsch A, Gelber RD, Colleoni M, Fleming GF, Soft, Investigators T, International Breast Cancer Study G (2017) Treatment efficacy, adherence, and quality of life among women younger than 35 years in the International Breast Cancer Study Group TEXT and SOFT Adjuvant Endocrine Therapy Trials. J Clin Oncol 35(27):3113–3122. https://doi.org/10.1200/JCO.2016.72.0946 CrossRefPubMedPubMedCentral

37.

Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100(1):57–70CrossRefPubMed

38.

Wang Y, Zhou BP (2013) Epithelial-mesenchymal transition—a hallmark of breast cancer metastasis. Cancer Hallmarks 1(1):38–49. https://doi.org/10.1166/ch.2013.1004 CrossRefPubMedPubMedCentral

39.

Radisky ES, Radisky DC (2010) Matrix metalloproteinase-induced epithelial-mesenchymal transition in breast cancer. J Mamm Gland Biol Neoplasia 15(2):201–212. https://doi.org/10.1007/s10911-010-9177-x CrossRef

40.

Cichon MA, Nelson CM, Radisky DC (2015) Regulation of epithelial–mesenchymal transition in breast cancer cells by cell contact and adhesion. Cancer Inform 14(Suppl 3):1–13. https://doi.org/10.4137/CIN.S18965 CrossRefPubMedPubMedCentral

41.

Barcellos-Hoff MH, Akhurst RJ (2009) Transforming growth factor-beta in breast cancer: too much, too late. Breast Cancer Res 11(1):202. https://doi.org/10.1186/bcr2224 CrossRefPubMedPubMedCentral

42.

Xu J, Lamouille S, Derynck R (2009) TGF-beta-induced epithelial to mesenchymal transition. Cell Res 19(2):156–172. https://doi.org/10.1038/cr.2009.5 CrossRefPubMed

43.

Broude EV, Gyorffy B, Chumanevich AA, Chen M, McDermott MS, Shtutman M, Catroppo JF, Roninson IB (2015) Expression of CDK8 and CDK8-interacting Genes as Potential Biomarkers in Breast Cancer. Curr Cancer Drug Targets 15(8):739–749CrossRefPubMedPubMedCentral

44.

Dai M, Lu JJ, Guo W, Yu W, Wang Q, Tang R, Tang Z, Xiao Y, Li Z, Sun W, Sun X, Qin Y, Huang W, Deng WG, Wu T (2015) BPTF promotes tumor growth and predicts poor prognosis in lung adenocarcinomas. Oncotarget 6(32):33878–33892. https://doi.org/10.18632/oncotarget.5302 CrossRefPubMedPubMedCentral

45.

Rasheed SA, Teo CR, Beillard EJ, Voorhoeve PM, Zhou W, Ghosh S, Casey PJ (2015) MicroRNA-31 controls G protein alpha-13 (GNA13) expression and cell invasion in breast cancer cells. Mol Cancer 14:67. https://doi.org/10.1186/s12943-015-0337-x CrossRefPubMedPubMedCentral

46.

Rasheed SAK, Leong HS, Lakshmanan M, Raju A, Dadlani D, Chong FT, Shannon NB, Rajarethinam R, Skanthakumar T, Tan EY, Hwang JSG, Lim KH, Tan DS, Ceppi P, Wang M, Tergaonkar V, Casey PJ, Iyer NG (2018) GNA13 expression promotes drug resistance and tumor-initiating phenotypes in squamous cell cancers. Oncogene 37(10):1340–1353. https://doi.org/10.1038/s41388-017-0038-6 CrossRefPubMed

47.

Lin XY, Cai FF, Wang MH, Pan X, Wang F, Cai L, Cui RR, Chen S, Biskup E (2017) Mammalian sterile 20-like kinase 1 expression and its prognostic significance in patients with breast cancer. Oncol Lett 14(5):5457–5463. https://doi.org/10.3892/ol.2017.6852 CrossRefPubMedPubMedCentral

Titel: Young age at diagnosis is associated with worse prognosis in the Luminal A breast cancer subtype: a retrospective institutional cohort study
verfasst von: Zhiyang Liu
Zeyad Sahli
Yongchun Wang
Antonio C. Wolff
Leslie M. Cope
Christopher B. Umbricht
Publikationsdatum: 17.09.2018
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 3/2018
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-018-4950-4

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25.04.2024 | Nierenkarzinom | Nachrichten

Springer Medizin

Young age at diagnosis is associated with worse prognosis in the Luminal A breast cancer subtype: a retrospective institutional cohort study

Abstract

Purpose

Methods

Results

Conclusions

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Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

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