Lapatinib plus Capecitabine for HER2-Positive Advanced Breast Cancer
Charles E. Geyer, M.D., John Forster, M.Sc., Deborah Lindquist, M.D., Stephen Chan, M.D., C. Gilles Romieu, M.D., Tadeusz Pienkowski, M.D., Ph.D., Agnieszka Jagiello-Gruszfeld, M.D., John Crown, M.D., Arlene Chan, M.D., Bella Kaufman, M.D., Dimosthenis Skarlos, M.D., Mario Campone, M.D., Neville Davidson, M.D., Mark Berger, M.D., Cristina Oliva, M.D., Stephen D. Rubin, M.D., Steven Stein, M.D., and David Cameron, M.D.
Background Lapatinib, a tyrosine kinase inhibitor of human epidermalgrowth factor receptor type 2 (HER2, also referred to as HER2/neu)and epidermal growth factor receptor (EGFR), is active in combinationwith capecitabine in women with HER2-positive metastatic breastcancer that has progressed after trastuzumab-based therapy.In this trial, we compared lapatinib plus capecitabine withcapecitabine alone in such patients.
Methods Women with HER2-positive, locally advanced or metastaticbreast cancer that had progressed after treatment with regimensthat included an anthracycline, a taxane, and trastuzumab wererandomly assigned to receive either combination therapy (lapatinibat a dose of 1250 mg per day continuously plus capecitabineat a dose of 2000 mg per square meter of body-surface area ondays 1 through 14 of a 21-day cycle) or monotherapy (capecitabinealone at a dose of 2500 mg per square meter on days 1 through14 of a 21-day cycle). The primary end point was time to progression,based on an evaluation by independent reviewers under blindedconditions.
Results The interim analysis of time to progression met specifiedcriteria for early reporting on the basis of superiority inthe combination-therapy group. The hazard ratio for the independentlyassessed time to progression was 0.49 (95% confidence interval,0.34 to 0.71; P<0.001), with 49 events in the combination-therapygroup and 72 events in the monotherapy group. The median timeto progression was 8.4 months in the combination-therapy groupas compared with 4.4 months in the monotherapy group. This improvementwas achieved without an increase in serious toxic effects orsymptomatic cardiac events.
Conclusions Lapatinib plus capecitabine is superior to capecitabinealone in women with HER2-positive advanced breast cancer thathas progressed after treatment with regimens that included ananthracycline, a taxane, and trastuzumab. (ClinicalTrials.govnumber, NCT00078572
[ClinicalTrials.gov]
.)
Source Information
From Allegheny General Hospital, Pittsburgh (C.E.G.); GlaxoSmithKline, Greenford, United Kingdom (J.F.); US Oncology, Sedona, AZ (D.L.); Nottingham University Hospitals, Nottingham, United Kingdom (S.C.); Centre Régional de Lutte contre le Cancer Val d'Aurelle, Montpellier, France (C.G.R.); Centrum Onkologii Klinika Nowotworów Piersi i Chirurgii, Warsaw, Poland (T.P.); Zaklad Opieki Zdrowotnej MSWiA, Olsztyn, Poland (A.J.-G.); Ireland Cooperative Oncology Research Group, Dublin (J.C.); Mount Medical Centre, Perth, Australia (A.C.); Chaim Sheba Medical Center, Tel-Hashomer, Israel (B.K.); Errikos Dynan Hospital, Athens (D.S.); Centre René Gauducheau, Saint Herblain, France (M.C.); Broomfield Hospital, Chelmsford, United Kingdom (N.D.); GlaxoSmithKline, Collegeville, PA (M.B., S.D.R., S.S.); GlaxoSmithKline, Middlesex, United Kingdom (C.O.); and Western General Hospital, Edinburgh (D.C.).
Address reprint requests to Dr. Geyer at the Allegheny Cancer Center, Allegheny General Hospital, 320 E. North Ave., 5th Floor, Pittsburgh, PA 15212, or at cgeyer{at}wpahs.org.
Gril, B., Palmieri, D., Bronder, J. L., Herring, J. M., Vega-Valle, E., Feigenbaum, L., Liewehr, D. J., Steinberg, S. M., Merino, M. J., Rubin, S. D., Steeg, P. S.
(2008). Effect of Lapatinib on the Outgrowth of Metastatic Breast Cancer Cells to the Brain. JNCI J Natl Cancer Inst
100: 1092-1103
[Abstract][Full Text]
Dodd, L. E., Korn, E. L., Freidlin, B., Jaffe, C. C., Rubinstein, L. V., Dancey, J., Mooney, M. M.
(2008). Blinded Independent Central Review of Progression-Free Survival in Phase III Clinical Trials: Important Design Element or Unnecessary Expense?. JCO
26: 3791-3796
[Abstract][Full Text]
Paoletti, P.
(2008). Drug Development in the Targeted Therapy Era. JCO
26: 3815-3816
[Full Text]
Park, I. H., Ro, J., Lee, K. S., Nam, B. H., Kwon, Y., Shin, K. H.
(2008). Trastuzumab treatment beyond brain progression in HER2-positive metastatic breast cancer. Ann Oncol
0: mdn539v1-mdn539
[Abstract][Full Text]
Lee-Hoeflich, S. T., Crocker, L., Yao, E., Pham, T., Munroe, X., Hoeflich, K. P., Sliwkowski, M. X., Stern, H. M.
(2008). A Central Role for HER3 in HER2-Amplified Breast Cancer: Implications for Targeted Therapy. Cancer Res.
68: 5878-5887
[Abstract][Full Text]
Chu, Q. S.C., Cianfrocca, M. E., Goldstein, L. J., Gale, M., Murray, N., Loftiss, J., Arya, N., Koch, K. M., Pandite, L., Fleming, R. A., Paul, E., Rowinsky, E. K.
(2008). A Phase I and Pharmacokinetic Study of Lapatinib in Combination with Letrozole in Patients with Advanced Cancer. Clin. Cancer Res.
14: 4484-4490
[Abstract][Full Text]
Turner, N. C, Jones, A. L
(2008). Management of breast cancer--Part II. BMJ
337: a540-a540
[Full Text]
Zhang, D., Pal, A., Bornmann, W. G., Yamasaki, F., Esteva, F. J., Hortobagyi, G. N., Bartholomeusz, C., Ueno, N. T.
(2008). Activity of lapatinib is independent of EGFR expression level in HER2-overexpressing breast cancer cells. Molecular Cancer Therapeutics
7: 1846-1850
[Abstract][Full Text]
Trotta, F., Apolone, G., Garattini, S., Tafuri, G.
(2008). Stopping a trial early in oncology: for patients or for industry?. Ann Oncol
19: 1347-1353
[Abstract][Full Text]
Chen, M. H., Kerkela, R., Force, T.
(2008). Mechanisms of Cardiac Dysfunction Associated With Tyrosine Kinase Inhibitor Cancer Therapeutics. Circulation
118: 84-95
[Full Text]
Stemmler, H.-J., Heinemann, V.
(2008). Central Nervous System Metastases in HER-2-Overexpressing Metastatic Breast Cancer: A Treatment Challenge. The Oncologist
13: 739-750
[Abstract][Full Text]
LoRusso, P. M., Jones, S. F., Koch, K. M., Arya, N., Fleming, R. A., Loftiss, J., Pandite, L., Gadgeel, S., Weber, B. L., Burris, H. A. III
(2008). Phase I and Pharmacokinetic Study of Lapatinib and Docetaxel in Patients With Advanced Cancer. JCO
26: 3051-3056
[Abstract][Full Text]
Gomez, H. L., Doval, D. C., Chavez, M. A., Ang, P. C.-S., Aziz, Z., Nag, S., Ng, C., Franco, S. X., Chow, L. W.C., Arbushites, M. C., Casey, M. A., Berger, M. S., Stein, S. H., Sledge, G. W.
(2008). Efficacy and Safety of Lapatinib As First-Line Therapy for ErbB2-Amplified Locally Advanced or Metastatic Breast Cancer. JCO
26: 2999-3005
[Abstract][Full Text]
Seruga, B., Tannock, I. F.
(2008). Mathematics in the Realm of Lapatinib: 500 + 500 = 1,500?. JCO
26: 2940-2942
[Full Text]
Burstein, H. J., Storniolo, A. M., Franco, S., Forster, J., Stein, S., Rubin, S., Salazar, V. M., Blackwell, K. L.
(2008). A phase II study of lapatinib monotherapy in chemotherapy-refractory HER2-positive and HER2-negative advanced or metastatic breast cancer. Ann Oncol
19: 1068-1074
[Abstract][Full Text]
Cristofanilli, M., Morandi, P., Krishnamurthy, S., Reuben, J. M., Lee, B.-N., Francis, D., Booser, D. J., Green, M. C., Arun, B. K., Pusztai, L., Lopez, A., Islam, R., Valero, V., Hortobagyi, G. N.
(2008). Imatinib mesylate (Gleevec(R)) in advanced breast cancer-expressing C-Kit or PDGFR-{beta}: clinical activity and biological correlations. Ann Oncol
0: mdn352v1-mdn352
[Abstract][Full Text]
Contessa, J. N., Bhojani, M. S., Freeze, H. H., Rehemtulla, A., Lawrence, T. S.
(2008). Inhibition of N-Linked Glycosylation Disrupts Receptor Tyrosine Kinase Signaling in Tumor Cells. Cancer Res.
68: 3803-3809
[Abstract][Full Text]
Matsubara, J., Yamada, Y., Hirashima, Y., Takahari, D., Okita, N. T., Kato, K., Hamaguchi, T., Shirao, K., Shimada, Y., Shimoda, T.
(2008). Impact of Insulin-Like Growth Factor Type 1 Receptor, Epidermal Growth Factor Receptor, and HER2 Expressions on Outcomes of Patients with Gastric Cancer. Clin. Cancer Res.
14: 3022-3029
[Abstract][Full Text]
Ravaud, A., Hawkins, R., Gardner, J. P., von der Maase, H., Zantl, N., Harper, P., Rolland, F., Audhuy, B., Machiels, J.-P., Petavy, F., Gore, M., Schoffski, P., El-Hariry, I.
(2008). Lapatinib Versus Hormone Therapy in Patients With Advanced Renal Cell Carcinoma: A Randomized Phase III Clinical Trial. JCO
26: 2285-2291
[Abstract][Full Text]
Li, X., Lewis, M. T., Huang, J., Gutierrez, C., Osborne, C. K., Wu, M.-F., Hilsenbeck, S. G., Pavlick, A., Zhang, X., Chamness, G. C., Wong, H., Rosen, J., Chang, J. C.
(2008). Intrinsic Resistance of Tumorigenic Breast Cancer Cells to Chemotherapy. JNCI J Natl Cancer Inst
100: 672-679
[Abstract][Full Text]
Schmid, P., Kuhnhardt, D., Kiewe, P., Lehenbauer-Dehm, S., Schippinger, W., Greil, R., Lange, W., Preiss, J., Niederle, N., Brossart, P., Freier, W., Kummel, S., Van de Velde, H., Regierer, A., Possinger, K.
(2008). A phase I/II study of bortezomib and capecitabine in patients with metastatic breast cancer previously treated with taxanes and/or anthracyclines. Ann Oncol
19: 871-876
[Abstract][Full Text]
Telli, M. L., Witteles, R. M., Fisher, G. A., Srinivas, S.
(2008). Cardiotoxicity associated with the cancer therapeutic agent sunitinib malate. Ann Oncol
0: mdn168v1-mdn168
[Abstract][Full Text]
Lin, N. U., Carey, L. A., Liu, M. C., Younger, J., Come, S. E., Ewend, M., Harris, G. J., Bullitt, E., Van den Abbeele, A. D., Henson, J. W., Li, X., Gelman, R., Burstein, H. J., Kasparian, E., Kirsch, D. G., Crawford, A., Hochberg, F., Winer, E. P.
(2008). Phase II Trial of Lapatinib for Brain Metastases in Patients With Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer. JCO
26: 1993-1999
[Abstract][Full Text]
Trowe, T., Boukouvala, S., Calkins, K., Cutler, R. E. Jr., Fong, R., Funke, R., Gendreau, S. B., Kim, Y. D., Miller, N., Woolfrey, J. R., Vysotskaia, V., Yang, J. P., Gerritsen, M. E., Matthews, D. J., Lamb, P., Heuer, T. S.
(2008). EXEL-7647 Inhibits Mutant Forms of ErbB2 Associated with Lapatinib Resistance and Neoplastic Transformation. Clin. Cancer Res.
14: 2465-2475
[Abstract][Full Text]
Kumar, A., Petri, E. T., Halmos, B., Boggon, T. J.
(2008). Structure and Clinical Relevance of the Epidermal Growth Factor Receptor in Human Cancer. JCO
26: 1742-1751
[Abstract][Full Text]
Frei, B. L., Soefje, S. A.
(2008). A Review of the Cardiovascular Effects of Oncology Agents. Journal of Pharmacy Practice
21: 146-158
[Abstract]
Polli, J. W., Humphreys, J. E., Harmon, K. A., Castellino, S., O'Mara, M. J., Olson, K. L., John-Williams, L. St., Koch, K. M., Serabjit-Singh, C. J.
(2008). The Role of Efflux and Uptake Transporters in N-{3-Chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamine (GW572016, Lapatinib) Disposition and Drug Interactions. Drug Metab. Dispos.
36: 695-701
[Abstract][Full Text]
Dang, C., Fornier, M., Sugarman, S., Troso-Sandoval, T., Lake, D., D'Andrea, G., Seidman, A., Sklarin, N., Dickler, M., Currie, V., Gilewski, T., Moynahan, M. E., Drullinsky, P., Robson, M., Wasserheit-Leiblich, C., Mills, N., Steingart, R., Panageas, K., Norton, L., Hudis, C.
(2008). The Safety of Dose-Dense Doxorubicin and Cyclophosphamide Followed by Paclitaxel With Trastuzumab in HER-2/neu Overexpressed/Amplified Breast Cancer. JCO
26: 1216-1222
[Abstract][Full Text]
Dowlati, A., Fu, P.
(2008). Is Response Rate Relevant to the Phase II Trial Design of Targeted Agents?. JCO
26: 1204-1205
[Full Text]
Johnston, S., Trudeau, M., Kaufman, B., Boussen, H., Blackwell, K., LoRusso, P., Lombardi, D. P., Ben Ahmed, S., Citrin, D. L., DeSilvio, M. L., Harris, J., Westlund, R. E., Salazar, V., Zaks, T. Z., Spector, N. L.
(2008). Phase II Study of Predictive Biomarker Profiles for Response Targeting Human Epidermal Growth Factor Receptor 2 (HER-2) in Advanced Inflammatory Breast Cancer With Lapatinib Monotherapy. JCO
26: 1066-1072
[Abstract][Full Text]
Ocana, A., Pandiella, A.
(2008). Identifying Breast Cancer Druggable Oncogenic Alterations: Lessons Learned and Future Targeted Options. Clin. Cancer Res.
14: 961-970
[Abstract][Full Text]
Takeuchi, E. E., Alison, D. L.
(2008). What's new in oncology: targeted therapy. Contin Educ Anaesth Crit Care Pain
8: 36-38
[Full Text]
Finetti, P., Cervera, N., Charafe-Jauffret, E., Chabannon, C., Charpin, C., Chaffanet, M., Jacquemier, J., Viens, P., Birnbaum, D., Bertucci, F.
(2008). Sixteen-Kinase Gene Expression Identifies Luminal Breast Cancers with Poor Prognosis. Cancer Res.
68: 767-776
[Abstract][Full Text]
Andre, F., Nahta, R., Conforti, R., Boulet, T., Aziz, M., Yuan, L. X. H., Meslin, F., Spielmann, M., Tomasic, G., Pusztai, L., Hortobagyi, G. N., Michiels, S., Delaloge, S., Esteva, F. J.
(2008). Expression patterns and predictive value of phosphorylated AKT in early-stage breast cancer. Ann Oncol
19: 315-320
[Abstract][Full Text]
Findlay, M., von Minckwitz, G., Wardley, A.
(2008). Effective oral chemotherapy for breast cancer: pillars of strength. Ann Oncol
19: 212-222
[Abstract][Full Text]
Gilmer, T. M., Cable, L., Alligood, K., Rusnak, D., Spehar, G., Gallagher, K. T., Woldu, E., Carter, H. L., Truesdale, A. T., Shewchuk, L., Wood, E. R.
(2008). Impact of Common Epidermal Growth Factor Receptor and HER2 Variants on Receptor Activity and Inhibition by Lapatinib. Cancer Res.
68: 571-579
[Abstract][Full Text]
Saad, A., Beto, R., Abraham, J., Remick, S. C.
(2008). Cardiovascular Safety and Toxicity Profile of New Molecularly Targeted Anticancer Agents. Am Soc Clin Oncol Ed Book
2008: 428-434
[Abstract][Full Text]
Modi, S., Stopeck, A. T., Gordon, M. S., Mendelson, D., Solit, D. B., Bagatell, R., Ma, W., Wheler, J., Rosen, N., Norton, L., Cropp, G. F., Johnson, R. G., Hannah, A. L., Hudis, C. A.
(2007). Combination of Trastuzumab and Tanespimycin (17-AAG, KOS-953) Is Safe and Active in Trastuzumab-Refractory HER-2 Overexpressing Breast Cancer: A Phase I Dose-Escalation Study. JCO
25: 5410-5417
[Abstract][Full Text]
Sapino, A., Montemurro, F., Marchio, C., Viale, G., Kulka, J., Donadio, M., Bottini, A., Botti, G., dei Tos, A. P., Bersiga, A., Di Palma, S., Truini, M., Sanna, G., Aglietta, M., Bussolati, G.
(2007). Patients with advanced stage breast carcinoma immunoreactive to biotinylated Herceptin(R) are most likely to benefit from trastuzumab-based therapy: an hypothesis-generating study. Ann Oncol
18: 1963-1968
[Abstract][Full Text]
Widakowich, C., de Castro, G. Jr., de Azambuja, E., Dinh, P., Awada, A.
(2007). Review: Side Effects of Approved Molecular Targeted Therapies in Solid Cancers. The Oncologist
12: 1443-1455
[Abstract][Full Text]
Harris, L., Fritsche, H., Mennel, R., Norton, L., Ravdin, P., Taube, S., Somerfield, M. R., Hayes, D. F., Bast, R. C. Jr
(2007). American Society of Clinical Oncology 2007 Update of Recommendations for the Use of Tumor Markers in Breast Cancer. JCO
25: 5287-5312
[Abstract][Full Text]
Thomas, E. S., Gomez, H. L., Li, R. K., Chung, H.-C., Fein, L. E., Chan, V. F., Jassem, J., Pivot, X. B., Klimovsky, J. V., de Mendoza, F. H., Xu, B., Campone, M., Lerzo, G. L., Peck, R. A., Mukhopadhyay, P., Vahdat, L. T., Roche, H. H.
(2007). Ixabepilone Plus Capecitabine for Metastatic Breast Cancer Progressing After Anthracycline and Taxane Treatment. JCO
25: 5210-5217
[Abstract][Full Text]
Nieto, Y., Nawaz, F., Jones, R. B., Shpall, E. J., Nawaz, S.
(2007). Prognostic Significance of Overexpression and Phosphorylation of Epidermal Growth Factor Receptor (EGFR) and the Presence of Truncated EGFRvIII in Locoregionally Advanced Breast Cancer. JCO
25: 4405-4413
[Abstract][Full Text]
Kwak, E. L., Clark, J. W., Chabner, B.
(2007). Targeted Agents: The Rules of Combination. Clin. Cancer Res.
13: 5232-5237
[Abstract][Full Text]
Harari, P. M., Allen, G. W., Bonner, J. A.
(2007). Biology of Interactions: Antiepidermal Growth Factor Receptor Agents. JCO
25: 4057-4065
[Abstract][Full Text]
Sweeney, K. J., Boland, P. J., King, T.
(2007). The Management of Asymptomatic Skeletal Breast Cancer: A Paradigm Shift. Ann. Surg. Oncol.
14: 2430-2431
[Full Text]
Bartsch, R., Wenzel, C., Altorjai, G., Pluschnig, U., Rudas, M., Mader, R. M., Gnant, M., Zielinski, C. C., Steger, G. G.
(2007). Capecitabine and Trastuzumab in Heavily Pretreated Metastatic Breast Cancer. JCO
25: 3853-3858
[Abstract][Full Text]
Park, J. W., Melisko, M. E., Esserman, L. J., Jones, L. A., Wollan, J. B., Sims, R.
(2007). Treatment With Autologous Antigen-Presenting Cells Activated With the HER-2 Based Antigen Lapuleucel-T: Results of a Phase I Study in Immunologic and Clinical Activity in HER-2 Overexpressing Breast Cancer. JCO
25: 3680-3687
[Abstract][Full Text]
Chu, Q. S.C., Schwartz, G., de Bono, J., Smith, D. A., Koch, K. M., Versola, M. J., Pandite, L., Arya, N., Curtright, J., Fleming, R. A., Ho, P. T.C., Rowinsky, E. K.
(2007). Phase I and Pharmacokinetic Study of Lapatinib in Combination With Capecitabine in Patients With Advanced Solid Malignancies. JCO
25: 3753-3758
[Abstract][Full Text]
Ritter, C. A., Perez-Torres, M., Rinehart, C., Guix, M., Dugger, T., Engelman, J. A., Arteaga, C. L.
(2007). Human Breast Cancer Cells Selected for Resistance to Trastuzumab In vivo Overexpress Epidermal Growth Factor Receptor and ErbB Ligands and Remain Dependent on the ErbB Receptor Network. Clin. Cancer Res.
13: 4909-4919
[Abstract][Full Text]
Ratain, M. J., Cohen, E. E.
(2007). The Value Meal: How to Save $1,700 Per Month or More on Lapatinib. JCO
25: 3397-3398
[Full Text]
Hudis, C. A.
(2007). Trastuzumab -- Mechanism of Action and Use in Clinical Practice. NEJM
357: 39-51
[Full Text]
Moy, B., Goss, P. E.
(2007). Lapatinib-Associated Toxicity and Practical Management Recommendations. The Oncologist
12: 756-765
[Abstract][Full Text]
Gori, S., Rimondini, S., De Angelis, V., Colozza, M., Bisagni, G., Moretti, G., Sidoni, A., Basurto, C., Aristei, C., Anastasi, P., Crino, L.
(2007). Central Nervous System Metastases in HER-2 Positive Metastatic Breast Cancer Patients Treated with Trastuzumab: Incidence, Survival, and Risk Factors. The Oncologist
12: 766-773
[Abstract][Full Text]
Spector, N. L., Yarden, Y., Smith, B., Lyass, L., Trusk, P., Pry, K., Hill, J. E., Xia, W., Seger, R., Bacus, S. S.
(2007). Activation of AMP-activated protein kinase by human EGF receptor 2/EGF receptor tyrosine kinase inhibitor protects cardiac cells. Proc. Natl. Acad. Sci. USA
104: 10607-10612
[Abstract][Full Text]
Di Leo, A
(2007). The state of HER-2 status. Ann Oncol
18: 813-815
[Full Text]
Hegde, P. S., Rusnak, D., Bertiaux, M., Alligood, K., Strum, J., Gagnon, R., Gilmer, T. M.
(2007). Delineation of molecular mechanisms of sensitivity to lapatinib in breast cancer cell lines using global gene expression profiles. Molecular Cancer Therapeutics
6: 1629-1640
[Abstract][Full Text]
Sonpavde, G., Geyer, C. E., Forster, J., Cameron, D.
(2007). Lapatinib plus Capecitabine in Breast Cancer. NEJM
356: 1471-1472
[Full Text]
Tripathy, D.
(2007). Capecitabine in Combination with Novel Targeted Agents in the Management of Metastatic Breast Cancer: Underlying Rationale and Results of Clinical Trials. The Oncologist
12: 375-389
[Abstract][Full Text]
Jorgensen, J. T., Nielsen, K. V., Ejlertsen, B.
(2007). Pharmacodiagnostics and Targeted Therapies--A Rational Approach for Individualizing Medical Anticancer Therapy in Breast Cancer. The Oncologist
12: 397-405
[Abstract][Full Text]
Aragon-Ching, J. B., Zujewski, J. A.
(2007). CNS Metastasis: An Old Problem in a New Guise. Clin. Cancer Res.
13: 1644-1647
[Abstract][Full Text]
Lin, N. U., Winer, E. P.
(2007). Brain Metastases: The HER2 Paradigm. Clin. Cancer Res.
13: 1648-1655
[Abstract][Full Text]
Colozza, M., de Azambuja, E., Personeni, N., Lebrun, F., Piccart, M. J., Cardoso, F.
(2007). Achievements in Systemic Therapies in the Pregenomic Era in Metastatic Breast Cancer. The Oncologist
12: 253-270
[Abstract][Full Text]
(2007). Lapatinib for HER2-Positive Breast Cancer Patients. JWatch Oncology and Hematology
2007: 1-1
[Full Text]
Muss, H. B.
(2006). Targeted Therapy for Metastatic Breast Cancer. NEJM
355: 2783-2785
[Full Text]
A correction has been published: N Engl J Med 2007;356(14):1487.
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