nach oben

Erschienen in:

27.07.2017 | Clinical trial

Impact of tissue-based genomic profiling on clinical decision making in the management of patients with metastatic breast cancer at academic centers

verfasst von: Cesar A. Santa-Maria, Megan Kruse, Paola Raska, Mia Weiss, April Swoboda, Martin B. Mutonga, Jame Abraham, Sarika Jain, Rita Nanda, Alberto J. Montero

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 1/2017

Einloggen, um Zugang zu erhalten

Abstract

Background

Genomic profiling can identify targetable mutations; however, the impact of tissue-based genomic profiling on clinical decision making for patients with metastatic breast cancer has not been well characterized.

Methods

Patients with stage IV breast cancer who had undergone genomic profiling between 7/2013 and 3/2015 were identified at three academic cancer centers. Genomic analysis was determined to have impacted clinical decision if (A) a patient was enrolled onto a genotype-matched clinical trial or (B) prescribed off-label an FDA-approved therapy targeting an identified mutation. The frequency of mutated genes was determined.

Results

A total of 117 patients with stage IV breast cancer were identified. Median age was 46 (25–75). Fifty-three patients (45%) had ER-positive/HER2-negative disease, 50 (43%) had ER-negative/HER2-negative disease, and 14 (12%) had ER-any/HER2-positive disease. Median number of previous therapies received prior to genomic profiling was 2 (range 0–15), and median follow-up after testing was obtained after 5.8 months (range 0–24.4 months). Commercial reports indicated that 85 (73%) patients had at least one mutation targetable by an FDA-approved medication, and 112 (96%) patients had at least one clinical trial available; however, clinical management was only affected in 11 patients (9%). The most frequent mutations observed were those in TP53, FGF, PI3KCA, MYC, ZNF, FGFR, CCND, ARID1A, GATA3, and MAP; frequencies of these mutations varied by clinical subtype.

Conclusions

Tumor genomic profiling affected clinical management in a minority of patients with metastatic breast cancer, thus these data do not support the routine use of genomic profiling outside of a clinical trial.

Afghahi A, Sledge GW Jr (2015) Targeted therapy for cancer in the genomic era. Cancer J 21(4):294–298. doi:10.1097/PPO.0000000000000135 CrossRefPubMed

Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, Lu S, Zhang L, Hu C, Hu C, Luo Y, Chen L, Ye M, Huang J, Zhi X, Zhang Y, Xiu Q, Ma J, Zhang L, You C (2015) Final overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802). Annal Oncol 26(9):1877–1883. doi:10.1093/annonc/mdv276 CrossRef

Santa-Maria CA, Gradishar WJ (2015) Changing treatment paradigms in metastatic breast cancer: lessons learned. JAMA Oncol 1(4):528–534; quiz 549. doi:10.1001/jamaoncol.2015.1198

Krop I, Johnston S, Mayer IA, Dickler M, Ganju V, Forero-Torres A, Melichar B, Morales S, de Boer R, Gendreau S, Derynck M, Lackner M, Spoerke J, Yeh R-F, Levy G, Ng V, O’Brien C, Savage H, Xiao Y, Wilson T, Lee SC, Petrakova K, Vallentin S, Yardley D, Ellis M, Piccart M, Perez EA, Winer E, P S The FERGI phase II study of the PI3K inhibitor pictilisib (GDC-0941) plus fulvestrant vs fulvestrant plus placebo in patients with ER+, aromatase inhibitor (AI)-resistant advanced or metastatic breast cancer 2014 SABCS

Baselga J, Im S-A, Iwata H, Clemons M, Ito Y, Awada A, Chia S, Jagiello-Gruszfeld A, Pistilli B, Tseng L-M, Hurvitz S, Masuda N, Cortés J, De Laurentiis M, Arteaga CL, Jiang Z, Jonat W, Hachemi S, Le Mouhaër S, Di Tomaso E, Urban P, Massacesi C, Campone M PIK3CA status in circulating tumor DNA (ctDNA) predicts efficacy of buparlisib (BUP) plus fulvestrant (FULV) in postmenopausal women with endocrine-resistant HR+/HER2– advanced breast cancer (BC): First results from the randomized, phase III BELLE-2 trial. In. p 2015 SABCS

Finn RS, Crown JP, Lang I, Boer K, Bondarenko IM, Kulyk SO, Ettl J, Patel R, Pinter T, Schmidt M, Shparyk Y, Thummala AR, Voytko NL, Fowst C, Huang X, Kim ST, Randolph S, Slamon DJ (2015) The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol 16(1):25–35. doi:10.1016/S1470-2045(14)71159-3 CrossRefPubMed

Tripathy D, Harnden K, Blackwell K, Robson M (2014) Next generation sequencing and tumor mutation profiling: are we ready for routine use in the oncology clinic? BMC Med 12:140. doi:10.1186/s12916-014-0140-3 CrossRefPubMedPubMedCentral

Meric-Bernstam F, Brusco L, Shaw K, Horombe C, Kopetz S, Davies MA, Routbort M, Piha-Paul SA, Janku F, Ueno N, Hong D, De Groot J, Ravi V, Li Y, Luthra R, Patel K, Broaddus R, Mendelsohn J, Mills GB (2015) Feasibility of large-scale genomic testing to facilitate enrollment onto genomically matched clinical trials. J Clin Oncol 33(25):2753–2762. doi:10.1200/JCO.2014.60.4165 CrossRefPubMedPubMedCentral

Sohal DP, Rini BI, Khorana AA, Dreicer R, Abraham J, Procop GW, Saunthararajah Y, Pennell NA, Stevenson JP, Pelley R, Estfan B, Shepard D, Funchain P, Elson P, Adelstein DJ, Bolwell BJ (2015) Prospective clinical study of precision oncology in solid tumors. J Natl Cancer Inst. doi:10.1093/jnci/djv332 PubMed

10.

Foundation medicine (2015) http://www.foundationmedicine.com/. Accessed 12 Dec 2015

11.

Conley BA, Doroshow JH (2014) Molecular analysis for therapy choice: NCI MATCH. Semin Oncol 41(3):297–299. doi:10.1053/j.seminoncol.2014.05.002 CrossRefPubMed

12.

Chae YK, Davis AA, Carneiro BA, Chandra S, Mohindra N, Kalyan A, Kaplan J, Matsangou M, Pai S, Costa R, Jovanovic B, Cristofanilli M, Platanias LC, Giles FJ (2016) Concordance between genomic alterations assessed by next-generation sequencing in tumor tissue or circulating cell-free DNA. Oncotarget 7(40):65364–65373. doi:10.18632/oncotarget.11692 PubMedPubMedCentral

13.

Chae YK, Davis AA, Jain S, Santa-Maria C, Flaum L, Beaubier N, Platanias LC, Gradishar W, Giles FJ, Cristofanilli M (2017) Concordance of genomic alterations by next-generation sequencing in tumor tissue versus circulating tumor DNA in breast cancer. Mol Cancer Ther. doi:10.1158/1535-7163.MCT-17-0061

14.

Stephens PJ, Tarpey PS, Davies H, Van Loo P, Greenman C, Wedge DC, Nik-Zainal S, Martin S, Varela I, Bignell GR, Yates LR, Papaemmanuil E, Beare D, Butler A, Cheverton A, Gamble J, Hinton J, Jia M, Jayakumar A, Jones D, Latimer C, Lau KW, McLaren S, McBride DJ, Menzies A, Mudie L, Raine K, Rad R, Chapman MS, Teague J, Easton D, Langerod A, Oslo Breast Cancer C, Lee MT, Shen CY, Tee BT, Huimin BW, Broeks A, Vargas AC, Turashvili G, Martens J, Fatima A, Miron P, Chin SF, Thomas G, Boyault S, Mariani O, Lakhani SR, van de Vijver M, van’t Veer L, Foekens J, Desmedt C, Sotiriou C, Tutt A, Caldas C, Reis-Filho JS, Aparicio SA, Salomon AV, Borresen-Dale AL, Richardson AL, Campbell PJ, Futreal PA, Stratton MR (2012) The landscape of cancer genes and mutational processes in breast cancer. Nature 486(7403):400–404. doi:10.1038/nature11017

15.

Curigliano G, Criscitiello C (2014) Successes and limitations of targeted cancer therapy in breast cancer. Prog Tumor Res 41:15–35. doi:10.1159/000355896 CrossRefPubMed

16.

Ross JS, Ali SM, Wang K, Khaira D, Palma NA, Chmielecki J, Palmer GA, Morosini D, Elvin JA, Fernandez SV, Miller VA, Stephens PJ, Cristofanilli M (2015) Comprehensive genomic profiling of inflammatory breast cancer cases reveals a high frequency of clinically relevant genomic alterations. Breast Cancer Res Treat 154(1):155–162. doi:10.1007/s10549-015-3592-z CrossRefPubMed

Titel: Impact of tissue-based genomic profiling on clinical decision making in the management of patients with metastatic breast cancer at academic centers
verfasst von: Cesar A. Santa-Maria
Megan Kruse
Paola Raska
Mia Weiss
April Swoboda
Martin B. Mutonga
Jame Abraham
Sarika Jain
Rita Nanda
Alberto J. Montero
Publikationsdatum: 27.07.2017
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 1/2017
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-017-4415-1

Springer Medizin

Impact of tissue-based genomic profiling on clinical decision making in the management of patients with metastatic breast cancer at academic centers