Corellation of Mutations, TILs and Age in Breast Cancer

NCT04033965 | Completed

• 1 other identifier: HE10/mut
• Study Type: observational
• Target: 345
• Locations: 0 countries
• Sites: N/A

Brief Summary

Age may pertain to different tumor genotype characteristics which may interfere with treatment efficacy and prognosis. The investigators investigated the distribution and prognostic effect of mutations (mut) and tumor infiltrating lymphocyte (TILs) in young and elderly early breast cancer patients (pts).

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (6)

• Assessment of the prevalence of gene mutations in women <=35 years old with early breast cancer.

  Up to 13 years

• Assessment of the prevalence of gene mutations in women >65years old with early breast cancer.

  Up to 13 years

• Evaluation of Tumor Infiltrating Lymphocytes (TILs) density using descriptive statistics in women <=35 years old with early breast cancer.

  Up to 13 years

• Evaluation of Tumor Infiltrating Lymphocytes (TILs) density using descriptive statistics in women >65 years old with early breast cancer.

  Up to 13 years

• Evaluation of the prognostic effect of gene mutations and Tumor Infiltrating Lymphocytes with respect to Overall Survival in women <=35 years old with early breast cancer

  Up to 13 years

• Evaluation of the prognostic effect of gene mutations and Tumor Infiltrating Lymphocytes with respect to Overall Survival in women >65 years old with early breast cancer.

  Up to 13 years

Study Arms (2)

women <35 with early breast cancer

Genetic: Corellation of Mutations, TILs and Age in Breast Cancer

women>65 years old with early breast cancer

Genetic: Corellation of Mutations, TILs and Age in Breast Cancer

Interventions

Corellation of Mutations, TILs and Age in Breast Cancer GENETIC

women <35 with early breast cancer; women>65 years old with early breast cancer

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

women with early breast cancer \<35 years old or \>65 years old

You may qualify if:

• women with early breast cancer \<35 years old or \>65 years old

Sponsors & Collaborators

• Hellenic Cooperative Oncology Group: lead

Related Publications (32)

• Gnerlich JL, Deshpande AD, Jeffe DB, Sweet A, White N, Margenthaler JA. Elevated breast cancer mortality in women younger than age 40 years compared with older women is attributed to poorer survival in early-stage disease. J Am Coll Surg. 2009 Mar;208(3):341-7. doi: 10.1016/j.jamcollsurg.2008.12.001. Epub 2009 Jan 21.

  PMID: 19317994 BACKGROUND

• Stickeler E. Prognostic and Predictive Markers for Treatment Decisions in Early Breast Cancer. Breast Care (Basel). 2011;6(3):193-198. doi: 10.1159/000329471. Epub 2011 Jun 14.

  PMID: 21779224 BACKGROUND

• Bonnier P, Romain S, Charpin C, Lejeune C, Tubiana N, Martin PM, Piana L. Age as a prognostic factor in breast cancer: relationship to pathologic and biologic features. Int J Cancer. 1995 Jul 17;62(2):138-44. doi: 10.1002/ijc.2910620205.

  PMID: 7622286 BACKGROUND

• Sweeney C, Blair CK, Anderson KE, Lazovich D, Folsom AR. Risk factors for breast cancer in elderly women. Am J Epidemiol. 2004 Nov 1;160(9):868-75. doi: 10.1093/aje/kwh276.

  PMID: 15496539 BACKGROUND

• Gomez-Flores-Ramos L, Castro-Sanchez A, Pena-Curiel O, Mohar-Betancourt A. Molecular Biology In Young Women With Breast Cancer: From Tumor Gene Expression To DNA Mutations. Rev Invest Clin. 2017 Jul-Aug;69(4):181-192. doi: 10.24875/ric.17002225.

  PMID: 28776603 BACKGROUND

• Azim HA Jr, Partridge AH. Biology of breast cancer in young women. Breast Cancer Res. 2014 Aug 27;16(4):427. doi: 10.1186/s13058-014-0427-5.

  PMID: 25436920 BACKGROUND

• Aebi S, Gelber S, Castiglione-Gertsch M, Gelber RD, Collins J, Thurlimann B, Rudenstam CM, Lindtner J, Crivellari D, Cortes-Funes H, Simoncini E, Werner ID, Coates AS, Goldhirsch A. Is chemotherapy alone adequate for young women with oestrogen-receptor-positive breast cancer? Lancet. 2000 May 27;355(9218):1869-74. doi: 10.1016/s0140-6736(00)02292-3.

  PMID: 10866443 BACKGROUND

• Arriagada R, Le MG, Dunant A, Tubiana M, Contesso G. Twenty-five years of follow-up in patients with operable breast carcinoma: correlation between clinicopathologic factors and the risk of death in each 5-year period. Cancer. 2006 Feb 15;106(4):743-50. doi: 10.1002/cncr.21659.

  PMID: 16411216 BACKGROUND

• Goldhirsch A, Gelber RD, Yothers G, Gray RJ, Green S, Bryant J, Gelber S, Castiglione-Gertsch M, Coates AS. Adjuvant therapy for very young women with breast cancer: need for tailored treatments. J Natl Cancer Inst Monogr. 2001;(30):44-51. doi: 10.1093/oxfordjournals.jncimonographs.a003459.

  PMID: 11773291 BACKGROUND

• Kroman N, Jensen MB, Wohlfahrt J, Mouridsen HT, Andersen PK, Melbye M. Factors influencing the effect of age on prognosis in breast cancer: population based study. BMJ. 2000 Feb 19;320(7233):474-8. doi: 10.1136/bmj.320.7233.474.

  PMID: 10678859 BACKGROUND

• Encinas G, Sabelnykova VY, de Lyra EC, Hirata Katayama ML, Maistro S, de Vasconcellos Valle PWM, de Lima Pereira GF, Rodrigues LM, de Menezes Pacheco Serio PA, de Gouvea ACRC, Geyer FC, Basso RA, Pasini FS, Del Pilar Esteves Diz M, Brentani MM, Guedes Sampaio Goes JC, Chammas R, Boutros PC, Koike Folgueira MAA. Somatic mutations in early onset luminal breast cancer. Oncotarget. 2018 Apr 27;9(32):22460-22479. doi: 10.18632/oncotarget.25123. eCollection 2018 Apr 27.

  PMID: 29854292 BACKGROUND

• Kotoula V, Karavasilis V, Zagouri F, Kouvatseas G, Giannoulatou E, Gogas H, Lakis S, Pentheroudakis G, Bobos M, Papadopoulou K, Tsolaki E, Pectasides D, Lazaridis G, Koutras A, Aravantinos G, Christodoulou C, Papakostas P, Markopoulos C, Zografos G, Papandreou C, Fountzilas G. Effects of TP53 and PIK3CA mutations in early breast cancer: a matter of co-mutation and tumor-infiltrating lymphocytes. Breast Cancer Res Treat. 2016 Jul;158(2):307-21. doi: 10.1007/s10549-016-3883-z. Epub 2016 Jul 1.

  PMID: 27369359 BACKGROUND

• Papaxoinis G, Kotoula V, Alexopoulou Z, Kalogeras KT, Zagouri F, Timotheadou E, Gogas H, Pentheroudakis G, Christodoulou C, Koutras A, Bafaloukos D, Aravantinos G, Papakostas P, Charalambous E, Papadopoulou K, Varthalitis I, Efstratiou I, Zaramboukas T, Patsea H, Scopa CD, Skondra M, Kosmidis P, Pectasides D, Fountzilas G. Significance of PIK3CA Mutations in Patients with Early Breast Cancer Treated with Adjuvant Chemotherapy: A Hellenic Cooperative Oncology Group (HeCOG) Study. PLoS One. 2015 Oct 9;10(10):e0140293. doi: 10.1371/journal.pone.0140293. eCollection 2015.

  PMID: 26452060 BACKGROUND

• Kotoula V, Chatzopoulos K, Lakis S, Alexopoulou Z, Timotheadou E, Zagouri F, Pentheroudakis G, Gogas H, Galani E, Efstratiou I, Zaramboukas T, Koutras A, Aravantinos G, Samantas E, Psyrri A, Kourea H, Bobos M, Papakostas P, Kosmidis P, Pectasides D, Fountzilas G. Tumors with high-density tumor infiltrating lymphocytes constitute a favorable entity in breast cancer: a pooled analysis of four prospective adjuvant trials. Oncotarget. 2016 Jan 26;7(4):5074-87. doi: 10.18632/oncotarget.6231.

  PMID: 26506242 BACKGROUND

• Kotoula V, Lyberopoulou A, Papadopoulou K, Charalambous E, Alexopoulou Z, Gakou C, Lakis S, Tsolaki E, Lilakos K, Fountzilas G. Evaluation of two highly-multiplexed custom panels for massively parallel semiconductor sequencing on paraffin DNA. PLoS One. 2015 Jun 3;10(6):e0128818. doi: 10.1371/journal.pone.0128818. eCollection 2015.

  PMID: 26039550 BACKGROUND

• Sun H, Yu G. New insights into the pathogenicity of non-synonymous variants through multi-level analysis. Sci Rep. 2019 Feb 7;9(1):1667. doi: 10.1038/s41598-018-38189-9.

  PMID: 30733553 BACKGROUND

• Martincorena I, Raine KM, Gerstung M, Dawson KJ, Haase K, Van Loo P, Davies H, Stratton MR, Campbell PJ. Universal Patterns of Selection in Cancer and Somatic Tissues. Cell. 2017 Nov 16;171(5):1029-1041.e21. doi: 10.1016/j.cell.2017.09.042. Epub 2017 Oct 19.

  PMID: 29056346 BACKGROUND

• Poggio F, Lambertini M, Bighin C, Conte B, Blondeaux E, D'Alonzo A, Dellepiane C, Boccardo F, Del Mastro L. Management of young women with early breast cancer. ESMO Open. 2018 Nov 14;3(Suppl 1):e000458. doi: 10.1136/esmoopen-2018-000458. eCollection 2018.

  PMID: 30559981 BACKGROUND

• Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature. 2012 Oct 4;490(7418):61-70. doi: 10.1038/nature11412. Epub 2012 Sep 23.

  PMID: 23000897 BACKGROUND

• Hobert JA, Eng C. PTEN hamartoma tumor syndrome: an overview. Genet Med. 2009 Oct;11(10):687-94. doi: 10.1097/GIM.0b013e3181ac9aea.

  PMID: 19668082 BACKGROUND

• Usary J, Llaca V, Karaca G, Presswala S, Karaca M, He X, Langerod A, Karesen R, Oh DS, Dressler LG, Lonning PE, Strausberg RL, Chanock S, Borresen-Dale AL, Perou CM. Mutation of GATA3 in human breast tumors. Oncogene. 2004 Oct 7;23(46):7669-78. doi: 10.1038/sj.onc.1207966.

  PMID: 15361840 BACKGROUND

• Fararjeh AS, Tu SH, Chen LC, Liu YR, Lin YK, Chang HL, Chang HW, Wu CH, Hwang-Verslues WW, Ho YS. The impact of the effectiveness of GATA3 as a prognostic factor in breast cancer. Hum Pathol. 2018 Oct;80:219-230. doi: 10.1016/j.humpath.2018.06.004. Epub 2018 Jun 11.

  PMID: 29902578 BACKGROUND

• Jiang YZ, Yu KD, Zuo WJ, Peng WT, Shao ZM. GATA3 mutations define a unique subtype of luminal-like breast cancer with improved survival. Cancer. 2014 May 1;120(9):1329-37. doi: 10.1002/cncr.28566. Epub 2014 Jan 29.

  PMID: 24477928 BACKGROUND

• Takaku M, Grimm SA, Roberts JD, Chrysovergis K, Bennett BD, Myers P, Perera L, Tucker CJ, Perou CM, Wade PA. GATA3 zinc finger 2 mutations reprogram the breast cancer transcriptional network. Nat Commun. 2018 Mar 13;9(1):1059. doi: 10.1038/s41467-018-03478-4.

  PMID: 29535312 BACKGROUND

• Annunziato S, de Ruiter JR, Henneman L, Brambillasca CS, Lutz C, Vaillant F, Ferrante F, Drenth AP, van der Burg E, Siteur B, van Gerwen B, de Bruijn R, van Miltenburg MH, Huijbers IJ, van de Ven M, Visvader JE, Lindeman GJ, Wessels LFA, Jonkers J. Comparative oncogenomics identifies combinations of driver genes and drug targets in BRCA1-mutated breast cancer. Nat Commun. 2019 Jan 23;10(1):397. doi: 10.1038/s41467-019-08301-2.

  PMID: 30674894 BACKGROUND

• Sheridan W, Scott T, Caroline S, Yvonne Z, Vanessa B, David V, Karen G, Stephen C. Breast cancer in young women: have the prognostic implications of breast cancer subtypes changed over time? Breast Cancer Res Treat. 2014 Oct;147(3):617-29. doi: 10.1007/s10549-014-3125-1. Epub 2014 Sep 11.

  PMID: 25209005 BACKGROUND

• Alabdulkareem H, Pinchinat T, Khan S, Landers A, Christos P, Simmons R, Moo TA. The impact of molecular subtype on breast cancer recurrence in young women treated with contemporary adjuvant therapy. Breast J. 2018 Mar;24(2):148-153. doi: 10.1111/tbj.12853. Epub 2017 Jul 14.

  PMID: 28707744 BACKGROUND

• Sonderstrup IMH, Jensen MB, Ejlertsen B, Eriksen JO, Gerdes AM, Kruse TA, Larsen MJ, Thomassen M, Laenkholm AV. Evaluation of tumor-infiltrating lymphocytes and association with prognosis in BRCA-mutated breast cancer. Acta Oncol. 2019 Mar;58(3):363-370. doi: 10.1080/0284186X.2018.1539239. Epub 2019 Jan 7.

  PMID: 30614364 BACKGROUND

• Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S, Biankin AV, Bignell GR, Bolli N, Borg A, Borresen-Dale AL, Boyault S, Burkhardt B, Butler AP, Caldas C, Davies HR, Desmedt C, Eils R, Eyfjord JE, Foekens JA, Greaves M, Hosoda F, Hutter B, Ilicic T, Imbeaud S, Imielinski M, Jager N, Jones DT, Jones D, Knappskog S, Kool M, Lakhani SR, Lopez-Otin C, Martin S, Munshi NC, Nakamura H, Northcott PA, Pajic M, Papaemmanuil E, Paradiso A, Pearson JV, Puente XS, Raine K, Ramakrishna M, Richardson AL, Richter J, Rosenstiel P, Schlesner M, Schumacher TN, Span PN, Teague JW, Totoki Y, Tutt AN, Valdes-Mas R, van Buuren MM, van 't Veer L, Vincent-Salomon A, Waddell N, Yates LR; Australian Pancreatic Cancer Genome Initiative; ICGC Breast Cancer Consortium; ICGC MMML-Seq Consortium; ICGC PedBrain; Zucman-Rossi J, Futreal PA, McDermott U, Lichter P, Meyerson M, Grimmond SM, Siebert R, Campo E, Shibata T, Pfister SM, Campbell PJ, Stratton MR. Signatures of mutational processes in human cancer. Nature. 2013 Aug 22;500(7463):415-21. doi: 10.1038/nature12477. Epub 2013 Aug 14.

  PMID: 23945592 BACKGROUND

• Thomas A, Routh ED, Pullikuth A, Jin G, Su J, Chou JW, Hoadley KA, Print C, Knowlton N, Black MA, Demaria S, Wang E, Bedognetti D, Jones WD, Mehta GA, Gatza ML, Perou CM, Page DB, Triozzi P, Miller LD. Tumor mutational burden is a determinant of immune-mediated survival in breast cancer. Oncoimmunology. 2018 Jul 30;7(10):e1490854. doi: 10.1080/2162402X.2018.1490854. eCollection 2018.

  PMID: 30386679 BACKGROUND

• Fountzilas G, Giannoulatou E, Alexopoulou Z, Zagouri F, Timotheadou E, Papadopoulou K, Lakis S, Bobos M, Poulios C, Sotiropoulou M, Lyberopoulou A, Gogas H, Pentheroudakis G, Pectasides D, Koutras A, Christodoulou C, Papandreou C, Samantas E, Papakostas P, Kosmidis P, Bafaloukos D, Karanikiotis C, Dimopoulos MA, Kotoula V. TP53 mutations and protein immunopositivity may predict for poor outcome but also for trastuzumab benefit in patients with early breast cancer treated in the adjuvant setting. Oncotarget. 2016 May 31;7(22):32731-53. doi: 10.18632/oncotarget.9022.

  PMID: 27129168 BACKGROUND

• Partridge AH, Hughes ME, Warner ET, Ottesen RA, Wong YN, Edge SB, Theriault RL, Blayney DW, Niland JC, Winer EP, Weeks JC, Tamimi RM. Subtype-Dependent Relationship Between Young Age at Diagnosis and Breast Cancer Survival. J Clin Oncol. 2016 Sep 20;34(27):3308-14. doi: 10.1200/JCO.2015.65.8013. Epub 2016 Aug 1.

  PMID: 27480155 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

formalin-fixed paraffin-embedded

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Aging

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Growth and Development; Physiological Phenomena

Study Officials

• Adamantia Nikolaidi, MD

  Oncology Department, MITERA Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Oncologist

Study Record Dates

• First Submitted: July 16, 2019
• First Posted: July 26, 2019
• Study Start: September 3, 1997
• Primary Completion: October 1, 2010
• Study Completion: October 1, 2010
• Last Updated: July 26, 2019

Record last verified: 2019-07