Clinical validation of the EndoPredict test in node-positive, chemotherapy-treated ER+/HER2- breast cancer patients: results from the GEICAM 9906 trial

Miguel Martin, Jan C Brase, Lourdes Calvo, Kristin Krappmann, Manuel Ruiz-Borrego, Karin Fisch, Amparo Ruiz, Karsten E Weber, Blanca Munarriz, Christoph Petry, Cesar A Rodriguez, Ralf Kronenwett, Carmen Crespo, Emilio Alba, Eva Carrasco, Maribel Casas, Rosalia Caballero, Alvaro Rodriguez-Lescure, Miguel Martin, Jan C Brase, Lourdes Calvo, Kristin Krappmann, Manuel Ruiz-Borrego, Karin Fisch, Amparo Ruiz, Karsten E Weber, Blanca Munarriz, Christoph Petry, Cesar A Rodriguez, Ralf Kronenwett, Carmen Crespo, Emilio Alba, Eva Carrasco, Maribel Casas, Rosalia Caballero, Alvaro Rodriguez-Lescure

Abstract

Introduction: EndoPredict (EP) is an RNA-based multigene test that predicts the likelihood of distant recurrence in patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC) who are being treated with adjuvant endocrine therapy. Herein we report the prospective-retrospective clinical validation of EP in the node-positive, chemotherapy-treated, ER+/HER2- BC patients in the GEICAM 9906 trial.

Methods: The patients (N = 1,246) were treated either with six cycles of fluorouracil, epirubicin and cyclophosphamide (FEC) or with four cycles of FEC followed by eight weekly courses of paclitaxel (FEC-P), as well as with endocrine therapy if they had hormone receptor-positive disease. The patients were assigned to EP risk categories (low or high) according to prespecified cutoff levels. The primary endpoint in the clinical validation of EP was distant metastasis-free survival (MFS). Metastasis rates were estimated using the Kaplan-Meier method, and multivariate analysis was performed using Cox regression.

Results: The molecular EP score and the combined molecular and clinical EPclin score were successfully determined in 555 ER+/HER2- tumors from the 800 available samples in the GEICAM 9906 trial. On the basis of the EP, 25% of patients (n = 141) were classified as low risk. MFS was 93% in the low-risk group and 70% in the high-risk group (absolute risk reduction = 23%, hazard ratio (HR) = 4.8, 95% confidence interval (CI) = 2.5 to 9.5; P < 0.0001). Multivariate analysis showed that, in this ER+/HER2- cohort, EP results are an independent prognostic parameter after adjustment for age, grade, lymph node status, tumor size, treatment arm, ER and progesterone receptor (PR) status and proliferation index (Ki67). Using the predefined EPclin score, 13% of patients (n = 74) were assigned to the low-risk group, who had excellent outcomes and no distant recurrence events (absolute risk reduction vs high-risk group = 28%; P < 0.0001). Furthermore, EP was prognostic in premenopausal patients (HR = 6.7, 95% CI = 2.4 to 18.3; P = 0.0002) and postmenopausal patients (HR = 3.3, 95% CI = 1.3 to 8.5; P = 0.0109). There were no statistically significant differences in MFS between treatment arms (FEC vs FEC-P) in either the high- or low-risk groups. The interaction test results between the chemotherapy arm and the EP score were not significant.

Conclusions: EP is an independent prognostic parameter in node-positive, ER+/HER2- BC patients treated with adjuvant chemotherapy followed by hormone therapy. EP did not predict a greater efficacy of FEC-P compared to FEC alone.

Figures

Figure 1
Figure 1
Kaplan-Meier metastasis-free survival curves for ER+/HER2− breast cancers. (A) Curves representing EndoPredict (EP) test results indicating estimated high and low risk of metastasis-free survival (MFS). The cutoff point was prespecified at 5. (B) Curves representing EPclin results indicating estimated high and low risk of MFS. The cutoff point was prespecified at 3.3. Numbers in parentheses indicate the 95% confidence intervals of the hazard ratios. ARR: Absolute risk reduction estimated at 10 years; ER+/HER2−: Estrogen receptor–positive/human epidermal growth factor receptor 2–negative. The MFS in the EP score–based low-risk category was 93% vs 70% in the EP score–based high-risk group. The MFS in the EPclin-based low-risk category was 100% vs 72% in the EPclin score–based high-risk group.
Figure 2
Figure 2
C-index plot for clinicopathological parameters and EndoPredict test results between breast cancer patients with ER+/HER2− tumors. C-index estimates for different groupings of prognostic parameters are shown: ER + PR + Ki67, ER + PR + Ki67 + tumor size, ER + PR + Ki67 + tumor size + nodal status, all clinicopathological parameters (nodal status, tumor size, grade, treatment arm, and ER and PR status and Ki67 index), all clinicopathological parameters + EndoPredict (EP) score, and combined molecular and clinical EPclin. ER: Estrogen receptor; PR: Progesterone receptor. P-values indicate whether additional molecular parameters add significant prognostic information to clinical variables.
Figure 3
Figure 3
Kaplan-Meier metastasis-free survival curves for ER+/HER2− breast cancers. (A) Curves representing EndoPredict (EP) test results indicating estimated high and low risk of metastasis-free survival (MFS). The cutoff point for EP score–based risk stratification was prespecified at 5. For the premenopausal patients, MFS in the EP score–based low-risk category was 93% vs 67% in the EP score–based high-risk group. For the postmenopausal patients, MFS in the EP score–based low-risk category was 92% vs 74% in the EP score–based high-risk group. (B) Curves representing results based on the combined molecular and clinical EPclin indicating estimated high and low risk of MFS. The cutoff point for EPclin score–based risk stratification was prespecified at 3.3. In the EPclin premenopausal patients, MFS in the EPclin score–based low-risk group was 100% vs 70% in the EPclin score–based high-risk category. In the postmenopausal patients, MFS in the EPclin score–based low-risk category was 100% vs 76% in the EPclin score–based high-risk group. The samples included 300 premenopausal patients and 255 postmenopausal patients. Numbers in parentheses indicate the 95% confidence intervals of the hazard ratios. ARR: Absolute risk reduction estimated at 10 years.
Figure 4
Figure 4
Kaplan-Meier metastasis-free survival curves for ER+/HER2- breast cancer. Comparison of treatment arms (FEC vs. FEC-P) in (A) the EP low-risk group (n = 141) and (B) the EP high-risk group (n = 414). The cutoff point for EP was prespecified at 5. Numbers in parentheses indicate the 95% confidence intervals of the hazard ratios. FEC: fluorouracil, epirubicin and cyclophosphamide; FEC+P: fluorouracil, epirubicin and cyclophosphamide followed by eight weekly courses of paclitaxel.

References

    1. 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. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004;351:2817–2826. doi: 10.1056/NEJMoa041588.
    1. 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. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002;347:1999–2009. doi: 10.1056/NEJMoa021967.
    1. van ’t Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, Peterse HL, van der Kooy K, Marton MJ, Witteveen AT, Schreiber GJ, Kerkhoven RM, Roberts C, Linsley PS, Bernards R, Friend SH. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002;415:530–536. doi: 10.1038/415530a.
    1. Nielsen TO, Parker JS, Leung S, Voduc D, Ebbert M, Vickery T, Davies SR, Snider J, Stijleman IJ, Reed J, Cheang MC, Mardis ER, Perou CM, Bernard PS, Ellis MJ. A comparison of PAM50 intrinsic subtyping with immunohistochemistry and clinical prognostic factors in tamoxifen-treated estrogen receptor–positive breast cancer. Clin Cancer Res. 2010;16:5222–5232. doi: 10.1158/1078-0432.CCR-10-1282.
    1. 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. Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol. 2009;27:1160–1167. doi: 10.1200/JCO.2008.18.1370.
    1. Filipits M, Rudas M, Jakesz R, Dubsky P, Fitzal F, Singer CF, Dietze O, Greil R, Jelen A, Sevelda P, Freibauer C, Müller V, Jänicke F, Schmidt M, Kölbl H, Rody A, Kaufmann M, Schroth W, Brauch H, Schwab M, Fritz P, Weber KE, Feder IS, Hennig G, Kronenwett R, Gehrmann M, Gnant M. EP Investigators. A new molecular predictor of distant recurrence in ER-positive, HER2−negative breast cancer adds independent information to conventional clinical risk factors. Clin Cancer Res. 2011;17:6012–6020. doi: 10.1158/1078-0432.CCR-11-0926.
    1. Paik S, Tang G, Shak S, Kim C, Baker J, Kim W, Cronin M, Baehner FL, Watson D, Bryant J, Costantino JP, Geyer CE Jr, Wickerham DL, Wolmark N. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol. 2006;24:3726–3734. doi: 10.1200/JCO.2005.04.7985.
    1. Dowsett M, Cuzick J, Wale C, Forbes J, Mallon EA, Salter J, Quinn E, Dunbier A, Baum M, Buzdar A, Howell A, Bugarini R, Baehner FL, Shak S. Prediction of risk of distant recurrence using the 21-gene recurrence score in node-negative and node-positive postmenopausal patients with breast cancer treated with anastrozole or tamoxifen: a TransATAC study. J Clin Oncol. 2010;28:1829–1834. doi: 10.1200/JCO.2009.24.4798.
    1. Albain KS, Barlow WE, Shak S, Hortobagyi GN, Livingston RB, Yeh IT, Ravdin P, Bugarini R, Baehner FL, Davidson NE, Sledge GW, Winer EP, Hudis C, Ingle JN, Perez EA, Pritchard KI, Shepherd L, Gralow JR, Yoshizawa C, Allred DC, Osborne CK, Hayes DF. Breast Cancer Intergroup of North America. Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial. Lancet Oncol. 2010;11:55–65. doi: 10.1016/S1470-2045(09)70314-6.
    1. Mamounas EP, Tang G, Paik S, Baehner FL, Liu Q, Jeong JH, Kim SR, Butler SM, Jamshidian F, Cherbavaz DB, Shak S, Julian TB, Lembersky BC, Wickerham DL, Costantino JP, Wolmark N. Association between the 21-gene recurrence score (RS) and benefit from adjuvant paclitaxel (Pac) in node-positive (N+), ER-positive breast cancer patients (pts): results from NSABP B-28 [Abstract] Cancer Res. 2012;72:S1-10. doi: 10.1158/1538-7445.AM2012-110.
    1. Martín M, Prat A, Rodríguez-Lescure A, Caballero R, Ebbert MT, Munárriz B, Ruiz-Borrego M, Bastien RR, Crespo C, Davis C, Rodríguez CA, López-Vega JM, Furió V, García AM, Casas M, Ellis MJ, Berry DA, Pitcher BN, Harris L, Ruiz A, Winer E, Hudis C, Stijleman IJ, Tuck DP, Carrasco E, Perou CM, Bernard PS. PAM50 proliferation score as a predictor of weekly paclitaxel benefit in breast cancer. Breast Cancer Res Treat. 2013;138:457–466. doi: 10.1007/s10549-013-2416-2.
    1. Cheang MC, Voduc KD, Tu D, Jiang S, Leung S, Chia SK, Shepherd LE, Levine MN, Pritchard KI, Davies S, Stijleman IJ, Davis C, Ebbert MT, Parker JS, Ellis MJ, Bernard PS, Perou CM, Nielsen TO. Responsiveness of intrinsic subtypes to adjuvant anthracycline substitution in the NCIC.CTG MA.5 randomized trial. Clin Cancer Res. 2012;18:2402–2412. doi: 10.1158/1078-0432.CCR-11-2956.
    1. Dubsky P, Filipits M, Jakesz R, Rudas M, Singer C, Greil R, Dietze O, Luisser I, Klug E, Sedivy R, Bachner M, Mayr D, Schmidt M, Gehrmann MC, Petry C, Weber KE, Kronenwett R, Brase JC, Gnant M. Austrian Breast and Colorectal Cancer Study Group (ABCSG) EndoPredict improves the prognostic classification derived from common clinical guidelines in ER-positive, HER2−negative early breast cancer. Ann Oncol. 2013;24:640–647. doi: 10.1093/annonc/mds334.
    1. Denkert C, Kronenwett R, Schlake W, Bohmann K, Penzel R, Weber KE, Höfler H, Lehmann U, Schirmacher P, Specht K, Rudas M, Kreipe HH, Schraml P, Schlake G, Bago-Horvath Z, Tiecke F, Varga Z, Moch H, Schmidt M, Prinzler J, Kerjaschki D, Sinn BV, Müller BM, Filipits M, Petry C, Dietel M. Decentral gene expression analysis for ER+/Her2− breast cancer: results of a proficiency testing program for the EndoPredict assay. Virchows Arch. 2012;460:251–259. doi: 10.1007/s00428-012-1204-4.
    1. Kronenwett R, Bohmann K, Prinzler J, Sinn BV, Haufe F, Roth C, Averdick M, Ropers T, Windbergs C, Brase JC, Weber KE, Fisch K, Müller BM, Schmidt M, Filipits M, Dubsky P, Petry C, Dietel M, Denkert C. Decentral gene expression analysis: analytical validation of the EndoPredict genomic multianalyte breast cancer prognosis test. BMC Cancer. 2012;12:456. doi: 10.1186/1471-2407-12-456.
    1. Martín M, Rodríguez-Lescure Á, Ruiz A, Alba E, Calvo L, Ruiz-Borrego M, Munárriz B, Rodríguez CA, Crespo C, de Alava E, López García-Asenjo JA, Guitián MD, Almenar S, González-Palacios JF, Vera F, Palacios J, Ramos M, Gracia Marco JM, Lluch A, Alvarez I, Seguí MA, Mayordomo JI, Antón A, Baena JM, Plazaola A, Modolell A, Pelegrí A, Mel JR, Aranda E, Adrover E. et al.Randomized phase 3 trial of fluorouracil, epirubicin, and cyclophosphamide alone or followed by paclitaxel for early breast cancer. J Natl Cancer Inst. 2008;100:805–814. doi: 10.1093/jnci/djn151.
    1. Martín M, Rodríguez-Lescure Á, Ruiz A, Alba E, Calvo L, Ruiz-Borrego M, Santaballa A, Rodríguez CA, Crespo C, Abad M, Domínguez S, Florián J, Llorca C, Méndez M, Godes M, Cubedo R, Murias A, Batista N, García MJ, Caballero R, de Alava E. Molecular predictors of efficacy of adjuvant weekly paclitaxel in early breast cancer. Breast Cancer Res Treat. 2010;123:149–157. doi: 10.1007/s10549-009-0663-z.
    1. Allred DC, Harvey JM, Berardo M, Clark GM. Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol. 1998;11:155–168.
    1. Bohmann K, Hennig G, Rogel U, Poremba C, Mueller BM, Fritz P, Stoerkel S, Schaefer KL. RNA extraction from archival formalin-fixed paraffin-embedded tissue: a comparison of manual, semiautomated, and fully automated purification methods. Clin Chem. 2009;55:1719–1727. doi: 10.1373/clinchem.2008.122572.
    1. Hennig G, Gehrmann M, Stropp U, Brauch H, Fritz P, Eichelbaum M, Schwab M, Schroth W. Automated extraction of DNA and RNA from a single formalin-fixed paraffin-embedded tissue section for analysis of both single-nucleotide polymorphisms and mRNA expression. Clin Chem. 2010;56:1845–1853. doi: 10.1373/clinchem.2010.151233.
    1. Müller BM, Kronenwett R, Hennig G, Euting H, Weber K, Bohmann K, Weichert W, Altmann G, Roth C, Winzer KJ, Kristiansen G, Petry C, Dietel M, Denkert C. Quantitative determination of estrogen receptor, progesterone receptor, and HER2 mRNA in formalin-fixed paraffin-embedded tissue—a new option for predictive biomarker assessment in breast cancer. Diagn Mol Pathol. 2011;20:1–10. doi: 10.1097/PDM.0b013e3181e3630c.
    1. Simon RM, Paik S, Hayes DF. Use of archived specimens in evaluation of prognostic and predictive biomarkers. J Natl Cancer Inst. 2009;101:1446–1452. doi: 10.1093/jnci/djp335.
    1. Goss PE. Letrozole in the extended adjuvant setting: MA.17. Breast Cancer Res Treat. 2007;105:45–53. A published erratum appears in Breast Cancer Res Treat 2008, 112:369.
    1. Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Livingston RB, Davidson NE, Perez EA, Chavarri-Guerra Y, Cameron DA, Pritchard KI, Whelan T, Shepherd LE, Tu D. Impact of premenopausal status at breast cancer diagnosis in women entered on the placebo-controlled NCIC CTG MA17 trial of extended adjuvant letrozole. Ann Oncol. 2013;24:355–361. doi: 10.1093/annonc/mds330.
    1. Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Tu D, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Cameron DA, Palmer MJ, Pater JL. Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17. J Natl Cancer Inst. 2005;97:1262–1271. doi: 10.1093/jnci/dji250.
    1. Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Tu D, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Cameron DA, Palmer MJ, Pater JL. Efficacy of letrozole extended adjuvant therapy according to estrogen receptor and progesterone receptor status of the primary tumor: National Cancer Institute of Canada Clinical Trials Group MA.17. J Clin Oncol. 2007;25:2006–2011. doi: 10.1200/JCO.2006.09.4482.
    1. Davies C, Pan H, Godwin J, Gray R, Arriagada R, Raina V, Abraham M, Medeiros Alencar VH, Badran A, Bonfill X, Bradbury J, Clarke M, Collins R, Davis SR, Delmestri A, Forbes JF, Haddad P, Hou MF, Inbar M, Khaled H, Kielanowska J, Kwan WH, Mathew BS, Mittra I, Müller B, Nicolucci A, Peralta O, Pernas F, Petruzelka L, Pienkowski T. et al.Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 2013;381:805–816. doi: 10.1016/S0140-6736(12)61963-1.
    1. Mamounas EP, Jeong JH, Wickerham DL, Smith RE, Ganz PA, Land SR, Eisen A, Fehrenbacher L, Farrar WB, Atkins JN, Pajon ER, Vogel VG, Kroener JF, Hutchins LF, Robidoux A, Hoehn JL, Ingle JN, Geyer CE Jr, Costantino JP, Wolmark N. Benefit from exemestane as extended adjuvant therapy after 5 years of adjuvant tamoxifen: intention-to-treat analysis of the National Surgical Adjuvant Breast and Bowel Project B-33 trial. J Clin Oncol. 2008;26:1965–1971. doi: 10.1200/JCO.2007.14.0228.
    1. Klang SH, Hammerman A, Liebermann N, Efrat N, Doberne J, Hornberger J. Economic implications of 21-gene breast cancer risk assay from the perspective of an Israeli-managed health-care organization. Value Health. 2010;13:381–387. doi: 10.1111/j.1524-4733.2010.00724.x.
    1. Kondo M, Hoshi SL, Yamanaka T, Ishiguro H, Toi M. Economic evaluation of the 21-gene signature (Oncotype DX) in lymph node-negative/positive, hormone receptor-positive early-stage breast cancer based on Japanese validation study (JBCRG-TR03) Breast Cancer Res Treat. 2011;127:739–749. doi: 10.1007/s10549-010-1243-y.
    1. Yang M, Rajan S, Issa AM. Cost effectiveness of gene expression profiling for early stage breast cancer: a decision-analytic model. Cancer. 2012;118:5163–5170. doi: 10.1002/cncr.27443.
    1. Cuzick J, Dowsett M, Pineda S, Wale C, Salter J, Quinn E, Zabaglo L, Mallon E, Green AR, Ellis IO, Howell A, Buzdar AU, Forbes JF. Prognostic value of a combined estrogen receptor, progesterone receptor, Ki-67, and human epidermal growth factor receptor 2 immunohistochemical score and comparison with the Genomic Health recurrence score in early breast cancer. J Clin Oncol. 2011;29:4273–4278. doi: 10.1200/JCO.2010.31.2835.
    1. Bartlett JM, Thomas J, Ross DT, Seitz RS, Ring BZ, Beck RA, Pedersen HC, Munro A, Kunkler IH, Campbell FM, Jack W, Kerr GR, Johnstone L, Cameron DA, Chetty U. Mammostrat as a tool to stratify breast cancer patients at risk of recurrence during endocrine therapy. Breast Cancer Res. 2010;12:R47. doi: 10.1186/bcr2604.
    1. Ward S, Scope A, Rafia R, Pandor A, Harnan S, Evans P, Wyld L. Gene expression profiling and expanded immunohistochemistry tests to guide the use of adjuvant chemotherapy in breast cancer management: a systematic review and cost-effectiveness analysis. Health Technol Assess. 2013;17:1–302.
    1. Dubsky P, Brase JC, Jakesz R, Rudas M, Singer CF, Greil R, Dietze O, Luisser I, Klug E, Sedivy R, Bachner M, Mayr D, Schmidt M, Gehrmann MC, Petry C, Weber KE, Fisch K, Kronenwett R, Gnant M, Filipits M. Austrian Breast and Colorectal Cancer Study Group (ABCSG) The EndoPredict score provides prognostic information on late distant metastases in ER+/HER2− breast cancer patients. Br J Cancer. 2013;109:2959–2964. doi: 10.1038/bjc.2013.671.
    1. Sgroi DC, Sestak I, Cuzick J, Zhang Y, Schnabel CA, Schroeder B, Erlander MG, Dunbier A, Sidhu K, Lopez-Knowles E, Goss PE, Dowsett M. Prediction of late distant recurrence in patients with oestrogen-receptor-positive breast cancer: a prospective comparison of the breast-cancer index (BCI) assay, 21-gene recurrence score, and IHC4 in the TransATAC study population. Lancet Oncol. 2013;14:1067–1076. doi: 10.1016/S1470-2045(13)70387-5.
    1. Sestak I, Dowsett M, Zabaglo L, Lopez-Knowles E, Ferree S, Cowens JW, Cuzick J. Factors predicting late recurrence for estrogen receptor-positive breast cancer. J Natl Cancer Inst. 2013;105:1504–1511. doi: 10.1093/jnci/djt244.
    1. Henderson IC, Berry DA, Demetri GD, Cirrincione CT, Goldstein LJ, Martino S, Ingle JN, Cooper MR, Hayes DF, Tkaczuk KH, Fleming G, Holland JF, Duggan DB, Carpenter JT, Frei E 3rd, Schilsky RL, Wood WC, Muss HB, Norton L. Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol. 2003;21:976–983. doi: 10.1200/JCO.2003.02.063.
    1. Mamounas EP, Bryant J, Lembersky B, Fehrenbacher L, Sedlacek SM, Fisher B, Wickerham DL, Yothers G, Soran A, Wolmark N. Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. J Clin Oncol. 2005;23:3686–3696. doi: 10.1200/JCO.2005.10.517.
    1. Roché H, Fumoleau P, Spielmann M, Canon JL, Delozier T, Serin D, Symann M, Kerbrat P, Soulié P, Eichler F, Viens P, Monnier A, Vindevoghel A, Campone M, Goudier MJ, Bonneterre J, Ferrero JM, Martin AL, Genève J, Asselain B. Sequential adjuvant epirubicin-based and docetaxel chemotherapy for node-positive breast cancer patients: the FNCLCC PACS 01 Trial. J Clin Oncol. 2006;24:5664–5671. doi: 10.1200/JCO.2006.07.3916.
    1. Jones SE, Savin MA, Holmes FA, O’Shaughnessy JA, Blum JL, Vukelja S, McIntyre KJ, Pippen JE, Bordelon JH, Kirby R, Sandbach J, Hyman WJ, Khandelwal P, Negron AG, Richards DA, Anthony SP, Mennel RG, Boehm KA, Meyer WG, Asmar L. Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol. 2006;24:5381–5387. doi: 10.1200/JCO.2006.06.5391.
    1. Martin M, Romero A, Cheang MC, López García-Asenjo JA, García-Saenz JA, Oliva B, Román JM, He X, Casado A, de la Torre J, Furio V, Puente J, Caldés T, Vidart JA, Lopez-Tarruella S, Diaz-Rubio E, Perou CM. Genomic predictors of response to doxorubicin versus docetaxel in primary breast cancer. Breast Cancer Res Treat. 2011;128:127–136. doi: 10.1007/s10549-011-1461-y.
    1. Dumontet C, Krajewska M, Treilleux I, Mackey JR, Martin M, Rupin M, Lafanechère L, Reed JC. BCIRG 001 molecular analysis: prognostic factors in node-positive breast cancer patients receiving adjuvant chemotherapy. Clin Cancer Res. 2010;16:3988–3997. doi: 10.1158/1078-0432.CCR-10-0079.
    1. Penault-Llorca F, André F, Sagan C, Lacroix-Triki M, Denoux Y, Verriele V, Jacquemier J, Baranzelli MC, Bibeau F, Antoine M, Lagarde N, Martin AL, Asselain B, Roché H. Ki67 expression and docetaxel efficacy in patients with estrogen receptor-positive breast cancer. J Clin Oncol. 2009;27:2809–2815. doi: 10.1200/JCO.2008.18.2808.
    1. Rouzier R, Perou CM, Symmans WF, Ibrahim N, Cristofanilli M, Anderson K, Hess KR, Stec J, Ayers M, Wagner P, Morandi P, Fan C, Rabiul I, Ross JS, Hortobagyi GN, Pusztai L. Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res. 2005;11:5678–5685. doi: 10.1158/1078-0432.CCR-04-2421.
    1. Hugh J, Hanson J, Cheang MC, Nielsen TO, Perou CM, Dumontet C, Reed J, Krajewska M, Treilleux I, Rupin M, Magherini E, Mackey J, Martin M, Vogel C. Breast cancer subtypes and response to docetaxel in node-positive breast cancer: use of an immunohistochemical definition in the BCIRG 001 trial. J Clin Oncol. 2009;27:1168–1176. doi: 10.1200/JCO.2008.18.1024.

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere