Molecular subtypes of breast cancer in relation to paclitaxel response and outcomes in women with metastatic disease: results from CALGB 9342
Tóm tắt
The response to paclitaxel varies widely in metastatic breast cancer. We analyzed data from CALGB 9342, which tested three doses of paclitaxel in women with advanced disease, to determine whether response and outcomes differed according to HER2, hormone receptor, and p53 status. Among 474 women randomly assigned to paclitaxel at a dose of 175, 210, or 250 mg/m2, adequate primary tumor tissue was available from 175. Immunohistochemistry with two antibodies and fluorescence in situ hybridization were performed to evaluate HER2 status; p53 status was determined by immunohistochemistry and sequencing. Hormone receptor status was obtained from pathology reports. Objective response rate was not associated with HER2 or p53 status. There was a trend toward a shorter median time to treatment failure among women with HER2-positive tumors (2.3 versus 4.2 months; P = 0.067). HER2 status was not related to overall survival (OS). Hormone receptor expression was not associated with differences in response but was associated with longer OS (P = 0.003). In contrast, women with p53 over-expression had significantly shorter OS than those without p53 over-expression (11.5 versus 14.4 months; P = 0.002). In addition, triple negative tumors were more frequent in African-American than in Caucasian patients, and were associated with a significant reduction in OS (8.7 versus 12.9 months; P = 0.008). None of the biomarkers was predictive of treatment response in women with metastatic breast cancer; however, survival differed according to hormone receptor and p53 status. Triple negative tumors were more frequent in African-American patients and were associated with a shorter survival.
Tài liệu tham khảo
Henderson IC, Berry DA, Demetri GD, Cirrincione CT, Goldstein LJ, Martino S, Ingle JN, Cooper MR, Hayes DF, Tkaczuk KH, et al: 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. 10.1200/JCO.2003.02.063.
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. 10.1200/JCO.2005.10.517.
Reichman BS, Seidman AD, Crown JP, Heelan R, Hakes TB, Lebwohl DE, Gilewski TA, Surbone A, Currie V, Hudis CA, et al: Paclitaxel and recombinant human granulocyte colony-stimulating factor as initial chemotherapy for metastatic breast cancer. J Clin Oncol. 1993, 11: 1943-1951.
Seidman AD, Tiersten A, Hudis C, Gollub M, Barrett S, Yao TJ, Lepore J, Gilewski T, Currie V, Crown J, et al: Phase II trial of paclitaxel by 3-hour infusion as initial and salvage chemotherapy for metastatic breast cancer. J Clin Oncol. 1995, 13: 2575-2581.
Nabholtz JM, Gelmon K, Bontenbal M, Spielmann M, Catimel G, Conte P, Klaassen U, Namer M, Bonneterre J, Fumoleau P, Winograd B: Multicenter, randomized comparative study of two doses of paclitaxel in patients with metastatic breast cancer. J Clin Oncol. 1996, 14: 1858-1867.
Paridaens R, Biganzoli L, Bruning P, Klijn JG, Gamucci T, Houston S, Coleman R, Schachter J, Van Vreckem A, Sylvester R, et al: Paclitaxel versus doxorubicin as first-line single-agent chemotherapy for metastatic breast cancer: a European Organization for Research and Treatment of Cancer Randomized Study with cross-over. J Clin Oncol. 2000, 18: 724-733.
Sledge GW, Neuberg D, Bernardo P, Ingle JN, Martino S, Rowinsky EK, Wood WC: Phase III trial of doxorubicin, paclitaxel, and the combination of doxorubicin and paclitaxel as front-line chemotherapy for metastatic breast cancer: an intergroup trial (E1193). J Clin Oncol. 2003, 21: 588-592. 10.1200/JCO.2003.08.013.
Winer EP, Berry DA, Woolf S, Duggan D, Kornblith A, Harris LN, Michaelson RA, Kirshner JA, Fleming GF, Perry MC, et al: Failure of higher-dose paclitaxel to improve outcome in patients with metastatic breast cancer: cancer and leukemia group B trial 9342. J Clin Oncol. 2004, 22: 2061-2068. 10.1200/JCO.2004.08.048.
Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL: Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987, 235: 177-182. 10.1126/science.3798106.
Thor AD, Berry DA, Budman DR, Muss HB, Kute T, Henderson IC, Barcos M, Cirrincione C, Edgerton S, Allred C, et al: erbB-2, p53, and efficacy of adjuvant therapy in lymph node-positive breast cancer. J Natl Cancer Inst. 1998, 90: 1346-1360. 10.1093/jnci/90.18.1346.
Paik S, Bryant J, Park C, Fisher B, Tan-Chiu E, Hyams D, Fisher ER, Lippman ME, Wickerham DL, Wolmark N: erbB-2 and response to doxorubicin in patients with axillary lymph node-positive, hormone receptor-negative breast cancer. J Natl Cancer Inst. 1998, 90: 1361-1370. 10.1093/jnci/90.18.1361.
Montgomery RB, Guzman J, O'Rourke DM, Stahl WL: Expression of oncogenic epidermal growth factor receptor family kinases induces paclitaxel resistance and alters beta-tubulin isotype expression. J Biol Chem. 2000, 275: 17358-17363. 10.1074/jbc.M000966200.
Yu D, Jing T, Liu B, Yao J, Tan M, McDonnell TJ, Hung MC: Overexpression of ErbB2 blocks Taxol-induced apoptosis by upregulation of p21Cip1, which inhibits p34Cdc2 kinase. Mol Cell. 1998, 2: 581-591. 10.1016/S1097-2765(00)80157-4.
Knuefermann C, Lu Y, Liu B, Jin W, Liang K, Wu L, Schmidt M, Mills GB, Mendelsohn J, Fan Z: HER2/PI-3K/Akt activation leads to a multidrug resistance in human breast adenocarcinoma cells. Oncogene. 2003, 22: 3205-3212. 10.1038/sj.onc.1206394.
Pegram MD, Finn RS, Arzoo K, Beryt M, Pietras RJ, Slamon DJ: The effect of HER-2/neu overexpression on chemotherapeutic drug sensitivity in human breast and ovarian cancer cells. Oncogene. 1997, 15: 537-547. 10.1038/sj.onc.1201222.
Baselga J, Seidman AD, Rosen PP, Norton L: HER2 overexpression and paclitaxel sensitivity in breast cancer: therapeutic implications. Oncology (Williston Park). 1997, 11: 43-48.
Van Poznak C, Tan L, Panageas KS, Arroyo CD, Hudis C, Norton L, Seidman AD: Assessment of molecular markers of clinical sensitivity to single-agent taxane therapy for metastatic breast cancer. J Clin Oncol. 2002, 20: 2319-2326. 10.1200/JCO.2002.08.125.
Hamilton A, Larsimont D, Paridaens R, Drijkoningen M, van de Vijver M, Bruning P, Hanby A, Houston S, Treilleux I, Guastalla JP, et al: A study of the value of p53, HER2, and Bcl-2 in the prediction of response to doxorubicin and paclitaxel as single agents in metastatic breast cancer: a companion study to EORTC 10923. Clin Breast Cancer. 2000, 1: 233-240. discussion: 241-232.
Colomer R, Montero S, Lluch A, Ojeda B, Barnadas A, Casado A, Massuti B, Cortes-Funes H, Lloveras B: Circulating HER2 extracellular domain and resistance to chemotherapy in advanced breast cancer. Clin Cancer Res. 2000, 6: 2356-2362.
Gianni L: Future directions of paclitaxel-based therapy of breast cancer. Semin Oncol. 1997, 24(5 Suppl 17): S17-91-S17-96.
Konecny GE, Thomssen C, Luck HJ, Untch M, Wang HJ, Kuhn W, Eidtmann H, du Bois A, Olbricht S, Steinfeld D, et al: Her-2/neu gene amplification and response to paclitaxel in patients with metastatic breast cancer. J Natl Cancer Inst. 2004, 96: 1141-1151.
Muller V, Witzel I, Luck HJ, Kohler G, von Minckwitz G, Mobus V, Sattler D, Wilczak W, Loning T, Janicke F, et al: Prognostic and predictive impact of the HER-2/neu extracellular domain (ECD) in the serum of patients treated with chemotherapy for metastatic breast cancer. Breast Cancer Res Treat. 2004, 86: 9-18. 10.1023/B:BREA.0000032919.83803.48.
Pharoah PD, Day NE, Caldas C: Somatic mutations in the p53 gene and prognosis in breast cancer: a meta-analysis. Br J Cancer. 1999, 80: 1968-1973. 10.1038/sj.bjc.6690628.
Alsner J, Yilmaz M, Guldberg P, Hansen LL, Overgaard J: Heterogeneity in the clinical phenotype of TP53 mutations in breast cancer patients. Clin Cancer Res. 2000, 6: 3923-3931.
Wahl AF, Donaldson KL, Fairchild C, Lee FY, Foster SA, Demers GW, Galloway DA: Loss of normal p53 function confers sensitization to Taxol by increasing G2/M arrest and apoptosis. Nat Med. 1996, 2: 72-79. 10.1038/nm0196-72.
Zhang CC, Yang JM, White E, Murphy M, Levine A, Hait WN: The role of MAP4 expression in the sensitivity to paclitaxel and resistance to vinca alkaloids in p53 mutant cells. Oncogene. 1998, 16: 1617-1624. 10.1038/sj.onc.1201658.
Zhang CC, Yang JM, Bash-Babula J, White E, Murphy M, Levine AJ, Hait WN: DNA damage increases sensitivity to vinca alkaloids and decreases sensitivity to taxanes through p53-dependent repression of microtubule-associated protein 4. Cancer Res. 1999, 59: 3663-3670.
Strobel T, Kraeft SK, Chen LB, Cannistra SA: BAX expression is associated with enhanced intracellular accumulation of paclitaxel: a novel role for BAX during chemotherapy-induced cell death. Cancer Res. 1998, 58: 4776-4781.
Gualberto A, Aldape K, Kozakiewicz K, Tlsty TD: An oncogenic form of p53 confers a dominant, gain-of-function phenotype that disrupts spindle checkpoint control. Proc Natl Acad Sci USA. 1998, 95: 5166-5171. 10.1073/pnas.95.9.5166.
Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, et al: Molecular portraits of human breast tumours. Nature. 2000, 406: 747-752. 10.1038/35021093.
Gruvberger S, Ringner M, Chen Y, Panavally S, Saal LH, Borg A, Ferno M, Peterson C, Meltzer PS: Estrogen receptor status in breast cancer is associated with remarkably distinct gene expression patterns. Cancer Res. 2001, 61: 5979-5984.
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, et al: Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002, 415: 530-536. 10.1038/415530a.
West M, Blanchette C, Dressman H, Huang E, Ishida S, Spang R, Zuzan H, Olson JA, Marks JR, Nevins JR: Predicting the clinical status of human breast cancer by using gene expression profiles. Proc Natl Acad Sci USA. 2001, 98: 11462-11467. 10.1073/pnas.201162998.
Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, et al: Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA. 2001, 98: 10869-10874. 10.1073/pnas.191367098.
Carey LA, Perou CM, Livasy CA, Dressler LG, Cowan D, Conway K, Karaca G, Troester MA, Tse CK, Edmiston S, et al: Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA. 2006, 295: 2492-2502. 10.1001/jama.295.21.2492.
Livasy CA, Karaca G, Nanda R, Tretiakova MS, Olopade OI, Moore DT, Perou CM: Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma. Mod Pathol. 2006, 19: 264-271. 10.1038/modpathol.3800528.
Wang ZC, Lin M, Wei LJ, Li C, Miron A, Lodeiro G, Harris L, Ramaswamy S, Tanenbaum DM, Meyerson M, et al: Loss of heterozygosity and its correlation with expression profiles in subclasses of invasive breast cancers. Cancer Res. 2004, 64: 64-71. 10.1158/0008-5472.CAN-03-2570.
Universal Mutation Database: [http://www.umd.necker.fr/]
Norberg T, Lennerstrand J, Inganas M, Bergh J: Comparison between p53 protein measurements using the luminometric immunoassay and immunohistochemistry with detection of p53 gene mutations using cDNA sequencing in human breast tumors. Int J Cancer. 1998, 79: 376-383. 10.1002/(SICI)1097-0215(19980821)79:4<376::AID-IJC12>3.0.CO;2-3.
McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM: Reporting recommendations for tumor marker prognostic studies (REMARK). J Natl Cancer Inst. 2005, 97: 1180-1184.
Henderson IC NL, Berry DA: In reply: Benefit of paclitaxel in estrogen receptor-negative versus estrogen receptor-positive early breast cancer [letter]. J Clin Oncol. 2003, 21: 4465-4466. 10.1200/JCO.2003.99.185.
Martin M, Pienkowski T, Mackey J, Pawlicki M, Guastalla JP, Weaver C, Tomiak E, Al-Tweigeri T, Chap L, Juhos E, et al: Adjuvant docetaxel for node-positive breast cancer. N Engl J Med. 2005, 352: 2302-2313. 10.1056/NEJMoa043681.
Jemal A, Tiwari RC, Murray T, Ghafoor A, Samuels A, Ward E, Feuer EJ, Thun MJ: Cancer statistics, 2004. CA Cancer J Clin. 2004, 54: 8-29.
Polite BN CC, Fleming GF, Berry DA, Seidman AD, Muss H, Norton L, Hudis C, Winer EP: Understanding racial differences in outcome from metastatic breast cancer (MBC): A pooled analysis of Cancer and Leukemia Group B (CALGB) 9342 and 9840 [abstract 3097]. Breast Cancer Res Treat. 2005, 3097-Suppl 1
Zidan J, Dashkovsky I, Stayerman C, Basher W, Cozacov C, Hadary A: Comparison of HER-2 overexpression in primary breast cancer and metastatic sites and its effect on biological targeting therapy of metastatic disease. Br J Cancer. 2005, 93: 552-556. 10.1038/sj.bjc.6602738.
Chang JC, Wooten EC, Tsimelzon A, Hilsenbeck SG, Gutierrez MC, Elledge R, Mohsin S, Osborne CK, Chamness GC, Allred DC, O'Connell P: Gene expression profiling for the prediction of therapeutic response to docetaxel in patients with breast cancer. Lancet. 2003, 362: 362-369. 10.1016/S0140-6736(03)14023-8.
Rouzier R, Rajan R, Wagner P, Hess KR, Gold DL, Stec J, Ayers M, Ross JS, Zhang P, Buchholz TA, et al: Microtubule-associated protein tau: a marker of paclitaxel sensitivity in breast cancer. Proc Natl Acad Sci USA. 2005, 102: 8315-8320. 10.1073/pnas.0408974102.
Harris LN, Perou C, Szallasi Z, Eklund A, Carter S, You F, Broadwater G, Monovich L, Winer E, Erlander M, Ellis M: Microarray profiling is feasible using archived tissue from a Cooperative Group Clinical Trial: results from a pilot study in CALGB 9342. ASCO Meeting Abstracts. 2005, 23 (Suppl 16): 545-