nach oben

Erschienen in:

01.09.2017 | Preclinical study

Inverse relationship between Ki67 and survival in early luminal breast cancer: confirmation in a multivariate analysis

verfasst von: Alberto Gallardo, Barbara Garcia-Valdecasas, Paola Murata, Rolando Teran, Laura Lopez, Agusti Barnadas, Enrique Lerma

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 1/2018

Einloggen, um Zugang zu erhalten

Abstract

Introduction

Ki67 is a prognostic marker in early breast cancer, but its real usefulness remains controversial. The standard cut-off values for Ki67 have not been universally accepted and different values may be used depending on the type of biopsy (fine needle biopsy versus surgical specimen biopsy). The objective of this study was to evaluate the prognostic significance of Ki67 and to determine the most accurate prognostic cut-off.

Materials and methods

495 tissue samples from patients with luminal tumours who underwent breast surgery between 2005 and 2011 were collected from the Department of Pathology at Hospital de la Santa Creu i Sant Pau, Barcelona. Patients with stage IV, HER2-positive tumours or triple-negative breast carcinoma were excluded from the study. Pathology data including tumour grading and ki67 percentage were obtained retrospectively from clinical records. In all cases, the percentage of ki67 was evaluated in fine needle biopsies.

Results

In the multivariate analysis, Ki67 as a continuous variable was associated with poor overall survival (OS) and cancer-specific survival (CSS) (OS p = 0.0001, HR 1.037, CI 1.014–1.059; CSS p = 0.0001, HR 1.063, CI 1.031–1.096) (Cox regression model). CSS was poor when associated with a KI67 cut-off point >14% (p = 0.013, HR 14.85; CI 1.074–120.53) (Cox regression model). Disease-free survival (DFS) was not associated with Ki67

Conclusions

Prognosis of luminal breast carcinoma can be predicted using Ki67 as a continuous variable and a standard cut-off value of 14%. Information about the specimen type used to determine ki67 should be recorded in the pathological report.

Nur mit Berechtigung zugänglich

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):1999–2009. doi:10.1056/NEJMoa021967 CrossRefPubMed

Parker JS, Mullins M, Cheang MC, Leung S, Voduc D, Vickery T, Davies S, Fauron C, He X, Hu Z, Quackenbush JF, Stijleman IJ, Palazzo J, Marron JS, Nobel AB, Mardis E, Nielsen TO, Ellis MJ, Perou CM, Bernard PS (2009) Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol 27(8):1160–1167. doi:10.1200/JCO.2008.18.1370 CrossRefPubMedPubMedCentral

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, Lonning PE, Borresen-Dale AL (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 98(19):10869–10874. doi:10.1073/pnas.191367098 CrossRefPubMedPubMedCentral

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):2817–2826. doi:10.1056/NEJMoa041588 CrossRefPubMed

Coates AS, Winer EP, Goldhirsch A, Gelber RD, Gnant M, Piccart-Gebhart M, Thurlimann B, Senn HJ, Panel M (2015) Tailoring therapies-improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015. Ann Oncol. doi:10.1093/annonc/mdv221

Dowsett M, Nielsen TO, A’Hern R, Bartlett J, Coombes RC, Cuzick J, Ellis M, Henry NL, Hugh JC, Lively T, McShane L, Paik S, Penault-Llorca F, Prudkin L, Regan M, Salter J, Sotiriou C, Smith IE, Viale G, Zujewski JS, Hayes DF, International Ki-67 in Breast Cancer Working G (2011) Assessment of Ki67 in breast cancer: recommendations from the International Ki67 in Breast Cancer working group. J Natl Cancer Inst 103(22):1656–1664. doi:10.1093/jnci/djr393 CrossRefPubMedPubMedCentral

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. doi:10.1093/annonc/mdt303 CrossRefPubMedPubMedCentral

Criscitiello C, Disalvatore D, De Laurentiis M, Gelao L, Fumagalli L, Locatelli M, Bagnardi V, Rotmensz N, Esposito A, Minchella I, De Placido S, Santangelo M, Viale G, Goldhirsch A, Curigliano G (2014) High Ki-67 score is indicative of a greater benefit from adjuvant chemotherapy when added to endocrine therapy in luminal B HER2 negative and node-positive breast cancer. Breast 23(1):69–75. doi:10.1016/j.breast.2013.11.007 CrossRefPubMed

Alco G, Bozdogan A, Selamoglu D, Pilanci KN, Tuzlali S, Ordu C, Igdem S, Okkan S, Dincer M, Demir G, Ozmen V (2015) Clinical and histopathological factors associated with Ki-67 expression in breast cancer patients. Oncol Lett 9(3):1046–1054. doi:10.3892/ol.2015.2852 CrossRefPubMedPubMedCentral

10.

Knutsvik G, Stefansson IM, Aziz S, Arnes J, Eide J, Collett K, Akslen LA (2014) Evaluation of Ki67 expression across distinct categories of breast cancer specimens: a population-based study of matched surgical specimens, core needle biopsies and tissue microarrays. PLoS ONE 9(11):e112121. doi:10.1371/journal.pone.0112121 CrossRefPubMedPubMedCentral

11.

Inwald EC, Klinkhammer-Schalke M, Hofstadter F, Zeman F, Koller M, Gerstenhauer M, Ortmann O (2013) Ki-67 is a prognostic parameter in breast cancer patients: results of a large population-based cohort of a cancer registry. Breast Cancer Res Treat 139(2):539–552. doi:10.1007/s10549-013-2560-8 CrossRefPubMedPubMedCentral

12.

Munzone E, Botteri E, Sciandivasci A, Curigliano G, Nole F, Mastropasqua M, Rotmensz N, Colleoni M, Esposito A, Adamoli L, Luini A, Goldhirsch A, Viale G (2012) Prognostic value of Ki-67 labeling index in patients with node-negative, triple-negative breast cancer. Breast Cancer Res Treat 134(1):277–282. doi:10.1007/s10549-012-2040-6 CrossRefPubMed

13.

Aleskandarany MA, Green AR, Benhasouna AA, Barros FF, Neal K, Reis-Filho JS, Ellis IO, Rakha EA (2012) Prognostic value of proliferation assay in the luminal, HER2-positive, and triple-negative biologic classes of breast cancer. Breast Cancer Res 14(1):R3. doi:10.1186/bcr3084 CrossRefPubMedPubMedCentral

14.

DeCensi A, Guerrieri-Gonzaga A, Gandini S, Serrano D, Cazzaniga M, Mora S, Johansson H, Lien EA, Pruneri G, Viale G, Bonanni B (2011) Prognostic significance of Ki-67 labeling index after short-term presurgical tamoxifen in women with ER-positive breast cancer. Ann Oncol 22(3):582–587. doi:10.1093/annonc/mdq427 CrossRefPubMed

15.

Nishimura R, Osako T, Okumura Y, Hayashi M, Toyozumi Y, Arima N (2010) Ki-67 as a prognostic marker according to breast cancer subtype and a predictor of recurrence time in primary breast cancer. Exp Ther Med 1(5):747–754. doi:10.3892/etm.2010.133 CrossRefPubMedPubMedCentral

16.

Hammond G, Sullivan M, Posthumus J, King A (2010) Assessment of three radiographic projections for detection of fluid in the rabbit tympanic bulla. Vet Radiol Ultrasound 51(1):48–51CrossRefPubMed

17.

Carlson RW, Moench SJ, Hammond ME, Perez EA, Burstein HJ, Allred DC, Vogel CL, Goldstein LJ, Somlo G, Gradishar WJ, Hudis CA, Jahanzeb M, Stark A, Wolff AC, Press MF, Winer EP, Paik S, Ljung BM, Force NHTiBCT (2006) HER2 testing in breast cancer: NCCN Task Force report and recommendations. J Natl Comprehensive Cancer Netw 4(Suppl 3):S1–22; quiz S23–24

18.

Cheang MC, Chia SK, Voduc D, Gao D, Leung S, Snider J, Watson M, Davies S, Bernard PS, Parker JS, Perou CM, Ellis MJ, Nielsen TO (2009) Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst 101(10):736–750. doi:10.1093/jnci/djp082 CrossRefPubMedPubMedCentral

19.

Oyama T, Ishikawa Y, Hayashi M, Arihiro K, Horiguchi J (2007) The effects of fixation, processing and evaluation criteria on immunohistochemical detection of hormone receptors in breast cancer. Breast Cancer 14(2):182–188CrossRefPubMed

20.

Leong TY, Leong AS (2006) Controversies in the assessment of HER-2: more questions than answers. Adv Anat Pathol 13(5):263–269. doi:10.1097/01.pap.0000213043.16200.92 CrossRefPubMed

21.

de Azambuja E, Cardoso F, de Castro G Jr., Colozza M, Mano MS, Durbecq V, Sotiriou C, Larsimont D, Piccart-Gebhart MJ, Paesmans M (2007) Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12,155 patients. Br J Cancer 96(10):1504–1513. doi:10.1038/sj.bjc.6603756 CrossRefPubMedPubMedCentral

22.

Stuart-Harris R, Caldas C, Pinder SE, Pharoah P (2008) Proliferation markers and survival in early breast cancer: a systematic review and meta-analysis of 85 studies in 32,825 patients. Breast 17(4):323–334. doi:10.1016/j.breast.2008.02.002 CrossRefPubMed

23.

Keshgegian AA, Cnaan A (1995) Proliferation markers in breast carcinoma. Mitotic figure count, S-phase fraction, proliferating cell nuclear antigen, Ki-67 and MIB-1. Am J Clin Pathol 104(1):42–49CrossRefPubMed

24.

Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thurlimann B, Senn HJ, Panel M (2011) Strategies for subtypes–dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol 22(8):1736–1747. doi:10.1093/annonc/mdr304 CrossRefPubMedPubMedCentral

25.

Clahsen PC, van de Velde CJ, Duval C, Pallud C, Mandard AM, Delobelle-Deroide A, van den Broek L, van de Vijver MJ (1999) The utility of mitotic index, oestrogen receptor and Ki-67 measurements in the creation of novel prognostic indices for node-negative breast cancer. Eur J Surg Oncol 25(4):356–363. doi:10.1053/ejso.1999.0657 CrossRefPubMed

26.

Joensuu H, Isola J, Lundin M, Salminen T, Holli K, Kataja V, Pylkkanen L, Turpeenniemi-Hujanen T, von Smitten K, Lundin J (2003) Amplification of erbB2 and erbB2 expression are superior to estrogen receptor status as risk factors for distant recurrence in pT1N0M0 breast cancer: a nationwide population-based study. Clin Cancer Res 9(3):923–930PubMed

27.

Petrelli F, Viale G, Cabiddu M, Barni S (2015) Prognostic value of different cut-off levels of Ki-67 in breast cancer: a systematic review and meta-analysis of 64,196 patients. Breast Cancer Res Treat 153(3):477–491. doi:10.1007/s10549-015-3559-0 CrossRefPubMed

28.

Goodson WH 3rd, Moore DH 2nd, Ljung BM, Chew K, Mayall B, Smith HS, Waldman FM (2000) The prognostic value of proliferation indices: a study with in vivo bromodeoxyuridine and Ki-67. Breast Cancer Res Treat 59(2):113–123. doi:10.1023/A:1006344010050 CrossRefPubMed

29.

Liu S, Edgerton SM, Moore DH 2nd, Thor AD (2001) Measures of cell turnover (proliferation and apoptosis) and their association with survival in breast cancer. Clin Cancer Res 7(6):1716–1723PubMed

30.

Giltnane JM, Rimm DL (2004) Technology insight: Identification of biomarkers with tissue microarray technology. Nat Clin Pract Oncol 1(2):104–111. doi:10.1038/ncponc0046 CrossRefPubMed

31.

Camp RL, Charette LA, Rimm DL (2000) Validation of tissue microarray technology in breast carcinoma. Lab Investig 80(12):1943–1949CrossRefPubMed

32.

Bustreo S, Osella-Abate S, Cassoni P, Donadio M, Airoldi M, Pedani F, Papotti M, Sapino A, Castellano I (2016) Optimal Ki67 cut-off for luminal breast cancer prognostic evaluation: a large case series study with a long-term follow-up. Breast Cancer Res Treat 157(2):363–371. doi:10.1007/s10549-016-3817-9 CrossRefPubMedPubMedCentral

33.

Urruticoechea A, Smith IE, Dowsett M (2005) Proliferation marker Ki-67 in early breast cancer. J Clin Oncol 23(28):7212–7220. doi:10.1200/JCO.2005.07.501 CrossRefPubMed

34.

Domagala W, Markiewski M, Harezga B, Dukowicz A, Osborn M (1996) Prognostic significance of tumor cell proliferation rate as determined by the MIB-1 antibody in breast carcinoma: its relationship with vimentin and p53 protein. Clin Cancer Res 2(1):147–154PubMed

35.

Trihia H, Murray S, Price K, Gelber RD, Golouh R, Goldhirsch A, Coates AS, Collins J, Castiglione-Gertsch M, Gusterson BA, International Breast Cancer Study G (2003) Ki-67 expression in breast carcinoma: its association with grading systems, clinical parameters, and other prognostic factors–a surrogate marker? Cancer 97(5):1321–1331. doi:10.1002/cncr.11188 CrossRefPubMed

36.

Penault-Llorca F, Andre F, Sagan C, Lacroix-Triki M, Denoux Y, Verriele V, Jacquemier J, Baranzelli MC, Bibeau F, Antoine M, Lagarde N, Martin AL, Asselain B, Roche H (2009) Ki67 expression and docetaxel efficacy in patients with estrogen receptor-positive breast cancer. J Clin Oncol 27(17):2809–2815. doi:10.1200/JCO.2008.18.2808 CrossRefPubMed

37.

Ellis MJ, Coop A, Singh B, Tao Y, Llombart-Cussac A, Janicke F, Mauriac L, Quebe-Fehling E, Chaudri-Ross HA, Evans DB, Miller WR (2003) Letrozole inhibits tumor proliferation more effectively than tamoxifen independent of HER1/2 expression status. Can Res 63(19):6523–6531

38.

Dowsett M, Smith IE, Ebbs SR, Dixon JM, Skene A, A’Hern R, Salter J, Detre S, Hills M, Walsh G, Group IT (2007) Prognostic value of Ki67 expression after short-term presurgical endocrine therapy for primary breast cancer. J Natl Cancer Inst 99(2):167–170. doi:10.1093/jnci/djk020 CrossRefPubMed

Titel: Inverse relationship between Ki67 and survival in early luminal breast cancer: confirmation in a multivariate analysis
verfasst von: Alberto Gallardo
Barbara Garcia-Valdecasas
Paola Murata
Rolando Teran
Laura Lopez
Agusti Barnadas
Enrique Lerma
Publikationsdatum: 01.09.2017
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 1/2018
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-017-4486-z

Springer Medizin

Inverse relationship between Ki67 and survival in early luminal breast cancer: confirmation in a multivariate analysis