HER2 and Response to Paclitaxel in Node-Positive Breast Cancer
Daniel F. Hayes, M.D., Ann D. Thor, M.D., Lynn G. Dressler, Dr.Ph., Donald Weaver, M.D., Susan Edgerton, M.A., David Cowan, B.A., Gloria Broadwater, M.S., Lori J. Goldstein, M.D., Silvana Martino, D.O., James N. Ingle, M.D., I. Craig Henderson, M.D., Larry Norton, M.D., Eric P. Winer, M.D., Clifford A. Hudis, M.D., Matthew J. Ellis, M.B., Ph.D., Donald A. Berry, Ph.D., for the Cancer and Leukemia Group B (CALGB) Investigators
Background The status of human epidermal growth factor receptortype 2 (HER2) in breast-cancer cells predicts clinical outcomesin women who receive adjuvant anthracycline-based chemotherapy.We hypothesized that HER2 positivity predicts a benefit fromadjuvant doxorubicin doses above standard levels, from the additionof paclitaxel after adjuvant chemotherapy with doxorubicin pluscyclophosphamide, or from both.
Methods We randomly selected 1500 women from 3121 women withnode-positive breast cancer who had been randomly assigned toreceive doxorubicin (60, 75, or 90 mg per square meter of body-surfacearea) plus cyclophosphamide (600 mg per square meter) for fourcycles, followed by four cycles of paclitaxel (175 mg per squaremeter) or observation. Tissue blocks from 1322 of these 1500women were available. Immunohistochemical analyses of thesetissue specimens for HER2 with the CB11 monoclonal antibodyagainst HER2 or with a polyclonal-antibody assay kit and fluorescencein situ hybridization for HER2 amplification were performed.
Results No interaction was observed between HER2 positivityand doxorubicin doses above 60 mg per square meter. HER2 positivitywas, however, associated with a significant benefit from paclitaxel.The interaction between HER2 positivity and the addition ofpaclitaxel to the treatment was associated with a hazard ratiofor recurrence of 0.59 (P=0.01). Patients with a HER2-positivebreast cancer benefited from paclitaxel, regardless of estrogen-receptorstatus, but paclitaxel did not benefit patients with HER2-negative,estrogen-receptor–positive cancers.
Conclusions The expression or amplification, or both, of HER2by a breast cancer is associated with a benefit from the additionof paclitaxel after adjuvant treatment with doxorubicin (<60mg per square meter) plus cyclophosphamide in node-positivebreast cancer, regardless of estrogen-receptor status. Patientswith HER2-negative, estrogen-receptor–positive, node-positivebreast cancer may gain little benefit from the administrationof paclitaxel after adjuvant chemotherapy with doxorubicin pluscyclophosphamide.
Source Information
From the University of Michigan Comprehensive Cancer Center, Ann Arbor (D.F.H.); the University of Colorado Comprehensive Cancer Center, Aurora (A.D.T., S.E.); the Lineberger Comprehensive Cancer Center at the University of North Carolina, Chapel Hill (L.G.D., D.C.); the University of Vermont Cancer Center, Fletcher Allen Health Care, Burlington (D.W.); Cancer and Leukemia Group B Statistical Center, Duke University, Durham, NC (G.B.); Fox Chase Comprehensive Cancer Center, Philadelphia (L.J.G.); the Angeles Clinic and Research Institute, Santa Monica, CA (S.M.); the Mayo Clinic, Rochester, MN (J.N.I.); the University of California at San Francisco, San Francisco (I.C.H.); Memorial Sloan-Kettering Cancer Center, New York (L.N., C.A.H.); the Dana–Farber Cancer Institute, Boston (E.P.W.); the Siteman Cancer Center, Washington University School of Medicine, St. Louis (M.J.E.); and the M.D. Anderson Cancer Center, Houston (D.A.B.).
Address reprint requests to Dr. Hayes at the Breast Oncology Program, 6312 Cancer Center, University of Michigan, 1500 E. Medical Center Dr., Ann Arbor, MI 48109, or at hayesdf{at}umich.edu.
Anderson, W. F., Jatoi, I., Sherman, M. E.
(2009). Qualitative Age Interactions in Breast Cancer Studies: Mind the Gap. JCO
27: 5308-5311
[Full Text]
Simon, R. M., Paik, S., Hayes, D. F.
(2009). Use of Archived Specimens in Evaluation of Prognostic and Predictive Biomarkers. JNCI J Natl Cancer Inst
101: 1446-1452
[Abstract][Full Text]
Ambrosone, C. B., Barlow, W. E., Reynolds, W., Livingston, R. B., Yeh, I-T., Choi, J.-Y., Davis, W., Rae, J. M., Tang, L., Hutchins, L. R., Ravdin, P. M., Martino, S., Osborne, C. K., Lyss, A. P., Hayes, D. F., Albain, K. S.
(2009). Myeloperoxidase Genotypes and Enhanced Efficacy of Chemotherapy for Early-Stage Breast Cancer in SWOG-8897. JCO
27: 4973-4979
[Abstract][Full Text]
Gianni, L., Norton, L., Wolmark, N., Suter, T. M., Bonadonna, G., Hortobagyi, G. N.
(2009). Role of Anthracyclines in the Treatment of Early Breast Cancer. JCO
27: 4798-4808
[Abstract][Full Text]
Sikov, W. M., Dizon, D. S., Strenger, R., Legare, R. D., Theall, K. P., Graves, T. A., Gass, J. S., Kennedy, T. A., Fenton, M. A.
(2009). Frequent Pathologic Complete Responses in Aggressive Stages II to III Breast Cancers With Every-4-Week Carboplatin and Weekly Paclitaxel With or Without Trastuzumab: A Brown University Oncology Group Study. JCO
27: 4693-4700
[Abstract][Full Text]
Robson, D., Verma, S.
(2009). Anthracyclines in Early-Stage Breast Cancer: Is It the End of an Era?. The Oncologist
14: 950-958
[Abstract][Full Text]
Thomas, J. St. J.
(2009). Quality Assurance in Her-2 Testing--Redefining the Gold Standard. Clin. Chem.
55: 1265-1267
[Full Text]
Pullarkat, V., Slovak, M. L., Dagis, A., Bedell, V., Somlo, G., Nakamura, R., Stein, A. S., O'Donnell, M. R., Nademanee, A., Teotico, A. L., Bhatia, S., Forman, S. J.
(2009). Acute leukemia and myelodysplasia after adjuvant chemotherapy for breast cancer: durable remissions after hematopoietic stem cell transplantation. Ann Oncol
0: mdp232v1-mdp232
[Abstract][Full Text]
Hugh, J., Hanson, J., Cheang, M., Nielsen, T., Perou, C., Dumontet, C., Reed, J., Krajewska, M., Treilleux, I., Rupin, M., Magherini, E., Mackey, J., Martin, M., Vogel, C.
(2009). Reply to R.S. Mehta et al. JCO
27: 3068-3069
[Full Text]
Penault-Llorca, F., Andre, F., Sagan, C., Lacroix-Triki, M., Denoux, Y., Verriele, V., Jacquemier, J., Baranzelli, M. C., Bibeau, F., Antoine, M., Lagarde, N., Martin, A.-L., Asselain, B., Roche, H.
(2009). Ki67 Expression and Docetaxel Efficacy in Patients With Estrogen Receptor-Positive Breast Cancer. JCO
27: 2809-2815
[Abstract][Full Text]
Onitilo, A. A., Engel, J. M., Greenlee, R. T., Mukesh, B. N.
(2009). Breast Cancer Subtypes Based on ER/PR and Her2 Expression: Comparison of Clinicopathologic Features and Survival. Clin Med Res
7: 4-13
[Abstract][Full Text]
Ross, J. S., Slodkowska, E. A., Symmans, W. F., Pusztai, L., Ravdin, P. M., Hortobagyi, G. N.
(2009). The HER-2 Receptor and Breast Cancer: Ten Years of Targeted Anti-HER-2 Therapy and Personalized Medicine. The Oncologist
14: 320-368
[Abstract][Full Text]
Hugh, J., Hanson, J., Cheang, M. C. U., Nielsen, T. O., Perou, C. M., Dumontet, C., Reed, J., Krajewska, M., Treilleux, I., Rupin, M., Magherini, E., Mackey, J., Martin, M., Vogel, C.
(2009). Breast Cancer Subtypes and Response to Docetaxel in Node-Positive Breast Cancer: Use of an Immunohistochemical Definition in the BCIRG 001 Trial. JCO
27: 1168-1176
[Abstract][Full Text]
Jones, S., Holmes, F. A., O'Shaughnessy, J., Blum, J. L., Vukelja, S. J., McIntyre, K. J., Pippen, J. E., Bordelon, J. H., Kirby, R. L., Sandbach, J., Hyman, W. J., Richards, D. A., Mennel, R. G., Boehm, K. A., Meyer, W. G., Asmar, L., Mackey, D., Riedel, S., Muss, H., Savin, M. A.
(2009). Docetaxel With Cyclophosphamide Is Associated With an Overall Survival Benefit Compared With Doxorubicin and Cyclophosphamide: 7-Year Follow-Up of US Oncology Research Trial 9735. JCO
27: 1177-1183
[Abstract][Full Text]
Jeruss, J. S., Woodruff, T. K.
(2009). Preservation of Fertility in Patients with Cancer. NEJM
360: 902-911
[Full Text]
Lu, J., Tan, M., Huang, W.-C., Li, P., Guo, H., Tseng, L.-M., Su, X.-h., Yang, W.-T., Treekitkarnmongkol, W., Andreeff, M., Symmans, F., Yu, D.
(2009). Mitotic Deregulation by Survivin in ErbB2-Overexpressing Breast Cancer Cells Contributes to Taxol Resistance. Clin. Cancer Res.
15: 1326-1334
[Abstract][Full Text]
de Azambuja, E., Paesmans, M., Beauduin, M., Vindevoghel, A., Cornez, N., Finet, C., Ries, F., Closon-Dejardin, M. T., Kerger, J., Gobert, P., Focan, C., Tagnon, A., Dolci, S., Nogaret, J. M., di Leo, A., Piccart-Gebhart, M. J.
(2009). Long-Term Benefit of High-Dose Epirubicin in Adjuvant Chemotherapy for Node-Positive Breast Cancer: 15-Year Efficacy Results of the Belgian Multicentre Study. JCO
27: 720-725
[Abstract][Full Text]
Baselga, J., Zambetti, M., Llombart-Cussac, A., Manikhas, G., Kubista, E., Steger, G. G., Makhson, A., Tjulandin, S., Ludwig, H., Verrill, M., Ciruelos, E., Egyhazi, S., Xu, L.-A., Zerba, K. E., Lee, H., Clark, E., Galbraith, S.
(2009). Phase II Genomics Study of Ixabepilone as Neoadjuvant Treatment for Breast Cancer. JCO
27: 526-534
[Abstract][Full Text]
Schneider, B. P., Winer, E. P., Foulkes, W. D., Garber, J., Perou, C. M., Richardson, A., Sledge, G. W., Carey, L. A.
(2008). Triple-Negative Breast Cancer: Risk Factors to Potential Targets. Clin. Cancer Res.
14: 8010-8018
[Abstract][Full Text]
Dowsett, M., Dunbier, A. K.
(2008). Emerging Biomarkers and New Understanding of Traditional Markers in Personalized Therapy for Breast Cancer. Clin. Cancer Res.
14: 8019-8026
[Abstract][Full Text]
Bartlett, J. M.S., Munro, A., Cameron, D. A., Thomas, J., Prescott, R., Twelves, C. J.
(2008). Type 1 Receptor Tyrosine Kinase Profiles Identify Patients With Enhanced Benefit From Anthracyclines in the BR9601 Adjuvant Breast Cancer Chemotherapy Trial. JCO
26: 5027-5035
[Abstract][Full Text]
Pusztai, L., Broglio, K., Andre, F., Symmans, W. F., Hess, K. R., Hortobagyi, G. N.
(2008). Effect of Molecular Disease Subsets on Disease-Free Survival in Randomized Adjuvant Chemotherapy Trials for Estrogen Receptor-Positive Breast Cancer. JCO
26: 4679-4683
[Abstract][Full Text]
Simon, R.
(2008). The Use of Genomics in Clinical Trial Design. Clin. Cancer Res.
14: 5984-5993
[Abstract][Full Text]
Ding, Q., Huo, L., Yang, J.-Y., Xia, W., Wei, Y., Liao, Y., Chang, C.-J., Yang, Y., Lai, C.-C., Lee, D.-F., Yen, C.-J., Chen, Y.-J. R., Hsu, J.-M., Kuo, H.-P., Lin, C.-Y., Tsai, F.-J., Li, L.-Y., Tsai, C.-H., Hung, M.-C.
(2008). Down-regulation of Myeloid Cell Leukemia-1 through Inhibiting Erk/Pin 1 Pathway by Sorafenib Facilitates Chemosensitization in Breast Cancer. Cancer Res.
68: 6109-6117
[Abstract][Full Text]
Peppercorn, J., Partridge, A. H.
(2008). Breast Cancer in Young Women: A New Color or a Different Shade of Pink?. JCO
26: 3303-3305
[Full Text]
O'Brien, C., Cavet, G., Pandita, A., Hu, X., Haydu, L., Mohan, S., Toy, K., Rivers, C. S., Modrusan, Z., Amler, L. C., Lackner, M. R.
(2008). Functional Genomics Identifies ABCC3 as a Mediator of Taxane Resistance in HER2-Amplified Breast Cancer. Cancer Res.
68: 5380-5389
[Abstract][Full Text]
Grube, B. J., Christy, C. J., Black, D., Martel, M., Harris, L., Weidhaas, J., DiGiovanna, M. P., Chung, G., Abu-Khalaf, M. M., Miller, K. D., Higgins, S. A., Philpotts, L., Tavassoli, F. A., Lannin, D. R.
(2008). Breast Sentinel Lymph Node Dissection Before Preoperative Chemotherapy. Arch Surg
143: 692-700
[Abstract][Full Text]
Martin, M., Rodriguez-Lescure, A., Ruiz, A., Alba, E., Calvo, L., Ruiz-Borrego, M., Munarriz, B., Rodriguez, C. A., Crespo, C., de Alava, E., Lopez Garcia-Asenjo, J. A., Guitian, M. D., Almenar, S., Gonzalez-Palacios, J. F., Vera, F., Palacios, J., Ramos, M., Gracia Marco, J. M., Lluch, A., Alvarez, I., Segui, M. A., Mayordomo, J. I., Anton, A., Baena, J. M., Plazaola, A., Modolell, A., Pelegri, A., Mel, J. R., Aranda, E., Adrover, E., Alvarez, J. V., Garcia Puche, J. L., Sanchez-Rovira, P., Gonzalez, S., Lopez-Vega, J. M., On behalf of the GEICAM 9906 Study Investigators,
(2008). Randomized Phase 3 Trial of Fluorouracil, Epirubicin, and Cyclophosphamide Alone or Followed by Paclitaxel for Early Breast Cancer. JNCI J Natl Cancer Inst
100: 805-814
[Abstract][Full Text]
Hudis, C., Dang, C.
(2008). The Taxane Limbo: How Low Can We Go?. JNCI J Natl Cancer Inst
100: 761-763
[Full Text]
Andre, F., Broglio, K., Roche, H., Martin, M., Mackey, J. R., Penault-Llorca, F., Hortobagyi, G. N., Pusztai, L.
(2008). Estrogen Receptor Expression and Efficacy of Docetaxel-Containing Adjuvant Chemotherapy in Patients With Node-Positive Breast Cancer: Results From a Pooled Analysis. JCO
26: 2636-2643
[Abstract][Full Text]
Sparano, J. A., Wang, M., Martino, S., Jones, V., Perez, E. A., Saphner, T., Wolff, A. C., Sledge, G. W. Jr., Wood, W. C., Davidson, N. E.
(2008). Weekly Paclitaxel in the Adjuvant Treatment of Breast Cancer. NEJM
358: 1663-1671
[Abstract][Full Text]
Pusztai, L.
(2008). Current Status of Prognostic Profiling in Breast Cancer. The Oncologist
13: 350-360
[Abstract][Full Text]
Colleoni, M., Viale, G., Zahrieh, D., Bottiglieri, L., Gelber, R. D., Veronesi, P., Balduzzi, A., Torrisi, R., Luini, A., Intra, M., Dellapasqua, S., Cardillo, A., Ghisini, R., Peruzzotti, G., Goldhirsch, A.
(2008). Expression of ER, PgR, HER1, HER2, and response: a study of preoperative chemotherapy. Ann Oncol
19: 465-472
[Abstract][Full Text]
Gul, O., Basaga, H., Kutuk, O.
(2008). Apoptotic blocks and chemotherapy resistance: strategies to identify Bcl-2 protein signatures. Brief Funct Genomic Proteomic
0: eln002v1-eln002
[Abstract][Full Text]
Pritchard, K. I., Messersmith, H., Elavathil, L., Trudeau, M., O'Malley, F., Dhesy-Thind, B.
(2008). HER-2 and Topoisomerase II As Predictors of Response to Chemotherapy. JCO
26: 736-744
[Abstract][Full Text]
Ellis, M. J.
(2008). Improving Outcomes for Patients With Hormone Receptor-Positive Breast Cancer: Back to the Drawing Board. JNCI J Natl Cancer Inst
100: 159-161
[Full Text]
Tran, L.-P. P., Grabinski, J. L.
(2008). Chemotherapy for Early-Stage Breast Cancer: A Paradigm in Flux. Journal of Pharmacy Practice
21: 46-56
[Abstract]
Roukos, D. H., Ferretti, G., Felici, A., Cognetti, F., Mehta, R., Nash, I., Hayes, D. F., Berry, D., Moore, A.
(2008). HER2 and Response to Paclitaxel in Node-Positive Breast Cancer. NEJM
358: 197-199
[Full Text]
Paik, S., Taniyama, Y., Geyer, C. E. Jr
(2008). Anthracyclines in the Treatment of HER2-Negative Breast Cancer. JNCI J Natl Cancer Inst
100: 2-4
[Full Text]
Hayes, D. F.
(2008). Markers for Predicting and Evaluating Response to Therapy for Breast Cancer. Am Soc Clin Oncol Ed Book
2008: 30-34
[Abstract][Full Text]
Moore, A.
(2007). Breast-Cancer Therapy -- Looking Back to the Future. NEJM
357: 1547-1549
[Full Text]
(2007). Who Needs a Taxane? Tailoring Breast Cancer Therapy. JWatch Oncology and Hematology
2007: 1-1
[Full Text]
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