Corellation of Mutations, TILs and Age in Breast Cancer

Breast Cancer Clinical Trial

Official title:

Tumor Mutational Patterns and Infiltrating Lymphocyte Density in Young and Old Patients With Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04033965
• Other study ID #: HE10/mut
• Status: Completed
• Start date: September 3, 1997
• Est. completion date: October 1, 2010

Study information

• Verified date: July 2019
• Source: Hellenic Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 345
• Est. completion date: October 1, 2010
• Est. primary completion date: October 1, 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

• NA

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hellenic Cooperative Oncology Group

References & Publications (32)

Aebi S, Gelber S, Castiglione-Gertsch M, Gelber RD, Collins J, Thürlimann 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. Review. — View Citation

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. — View Citation

Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S, Biankin AV, Bignell GR, Bolli N, Borg A, Børresen-Dale AL, Boyault S, Burkhardt B, Butler AP, Caldas C, Davies HR, Desmedt C, Eils R, Eyfjörd JE, Foekens JA, Greaves M, Hosoda F, Hutter B, Ilicic T, Imbeaud S, Imielinski M, Jäger N, Jones DT, Jones D, Knappskog S, Kool M, Lakhani SR, López-Otín 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, Valdés-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. Erratum in: Nature. 2013 Oct 10;502(7470):258. Imielinsk, Marcin [corrected to Imielinski, Marcin]. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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 Gouvêa ACRC, Geyer FC, Basso RA, Pasini FS, Del Pilar Esteves Diz M, Brentani MM, Guedes Sampaio Góes 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Gómez-Flores-Ramos L, Castro-Sánchez A, Peña-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. Review. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Erratum in: Cell. 2018 Jun 14;173(7):1823. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Sønderstrup 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. — View Citation

Stickeler E. Prognostic and Predictive Markers for Treatment Decisions in Early Breast Cancer. Breast Care (Basel). 2011;6(3):193-198. Epub 2011 Jun 14. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Usary J, Llaca V, Karaca G, Presswala S, Karaca M, He X, Langerød A, Kåresen R, Oh DS, Dressler LG, Lønning PE, Strausberg RL, Chanock S, Børresen-Dale AL, Perou CM. Mutation of GATA3 in human breast tumors. Oncogene. 2004 Oct 7;23(46):7669-78. — View Citation

* Note: There are 32 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of the prevalence of gene mutations in women <=35 years old with early breast cancer.		Up to 13 years
Primary	Assessment of the prevalence of gene mutations in women >65years old with early breast cancer.		Up to 13 years
Primary	Evaluation of Tumor Infiltrating Lymphocytes (TILs) density using descriptive statistics in women <=35 years old with early breast cancer.		Up to 13 years
Primary	Evaluation of Tumor Infiltrating Lymphocytes (TILs) density using descriptive statistics in women >65 years old with early breast cancer.		Up to 13 years
Primary	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
Primary	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