JCT  Vol.3 No.6 , December 2012
Breast Cancer Therapies Present and Future
ABSTRACT
Significant advances in breast cancer treatment have been made where it is now possible to treat localized disease to a curable state. However, for approximately 30% of women with primary disease, metastatic breast cancer (MBC) or recurrent disease, treatment has remained challenging. Major obstacles in the effective treatment of breast cancer in these populations include: 1) the molecular heterogeneity of the disease; 2) treatment of MBC and more specifically brain metastasis; and 3) defining combination therapies that address the evolution of resistance with disease relapse. The acknowledgement of these difficulties has led to an effort to further understand the roadblocks to therapy with the anticipation that more appropriate treatments will result. Here we describe the current state of breast cancer treatment, and the potential for improved therapy.

Cite this paper
J. Kalra and L. Edwards, "Breast Cancer Therapies Present and Future," Journal of Cancer Therapy, Vol. 3 No. 6, 2012, pp. 1140-1150. doi: 10.4236/jct.2012.36149.
References
[1]   American Cancer Society, “Breast Cancer Facts & Figures 2011-2012,” American Cancer Society, Atlanta, 2012.

[2]   J. Ferlay, et al., “Estimates of the Cancer Incidence and Mortality in Europe in 2006,” Annals of Oncology, Vol. 18, 2007, pp. 581-592. doi:10.1093/annonc/mdl498

[3]   American Cancer Society, “Cancer Facts & Figures 2012,” American Cancer Society, Atlanta, 2012.

[4]   B. Groner and N. E. Hynes, “Unfavorable Drug interactions in Targeted Breast Cancer Therapy,” Cancer Cell, Vol. 18, No. 5, 2010, pp. 401-402. doi:10.1016/j.ccr.2010.10.027

[5]   C. Andreetta, A. M. Minisi, M. Misicoria and F. Puglisi, “First-Line Chemotherapy with or without Biologic Agents for Metastatic Breast Cancer,” Critical Reviews in Oncology/Hematology, Vol. 76, No. 2, 2010, pp. 99-111. doi:10.1016/j.critrevonc.2010.01.007

[6]   V. Guarneri and P. F. Conte, “The Curability of Breast Cancer and the Treatment of Advanced Disease,” European Journal of Nuclear Medicine and Molecular Imaging, Vol. 31, No. 1, 2004, pp. S149-S161. doi:10.1007/s00259-004-1538-5

[7]   C. K. Baumann and M. Castiglione-Gertsch, “Clinical Use of Selective Estrogen Receptor Modulators and Down Regulators with the Main Focus on Breast Cancer,” Minerva Ginecologica, Vol. 61, No. 6, 2009, pp. 517-539.

[8]   W. Dean-Colomb and F. J. Esteva, “Her2-Positive Breast Cancer: Herceptin and Beyond,” European Journal of Cancer, Vol. 44, No. 18, 2008, pp. 2806-2812. doi:10.1016/j.ejca.2008.09.013

[9]   D. J. Slamon, “Proto-Oncogenes and Human Cancers,” New England Journal of Medicine, Vol. 317, No. 15, 1987, pp. 955-957. doi:10.1056/NEJM198710083171509

[10]   M. Kurosumi, “Recent Trends of HER-2 Testing and Trastuzumab Therapy for Breast Cancer,” Breast Cancer, Vol. 16, No. 4, 2009, pp. 284-287. doi:10.1007/s12282-009-0159-z

[11]   N. Normanno, et al., “Target-Based Therapies in Breast Cancer: Current Status and Future Perspectives,” Endocrine-Related Cancer, Vol. 16, No. 3, 2009, pp. 675-702. doi:10.1677/ERC-08-0208

[12]   N. L. Spector and K. L. Blackwell, “Understanding the Mechanisms behind Trastuzumab Therapy for Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer,” Journal of Clinical Oncology, Vol. 27, No. 34, 2009, pp. 5838-5847. doi:10.1200/JCO.2009.22.1507

[13]   J. E. Frampton, “Lapatinib: A Review of Its Use in the Treatment of HER2-Overexpressing, Trastuzumab-Refractory, Advanced or Metastatic Breast Cancer,” Drugs, Vol. 69, No. 15, 2009, pp. 2125-2148.

[14]   J. S. Frenel, et al., “Lapatinib in Metastatic Breast Cancer,” Womens Health, Vol. 5, No. 6, 2009, pp. 603-612. doi:10.2217/whe.09.54

[15]   V. Roy and E. A. Perez, “Beyond Trastuzumab: Small Molecule Tyrosine Kinase Inhibitors in HER-2-Positive Breast Cancer,” Oncologist, Vol. 14, No. 11, 2009, pp. 1061-1069. doi:10.1634/theoncologist.2009-0142

[16]   J. A. Ligibel and E. P. Winer, “Trastuzumab/Chemotherapy Combinations in Metastatic Breast Cancer,” Seminars in Oncology, Vol. 29, No. 3, 2002, pp. 38-43. doi:10.1016/S0093-7754(02)70125-5

[17]   A. Lin and H. S. Rugo, “The Role of Trastuzumab in Early Stage Breast Cancer: Current Data and Treatment Recommendations,” Current Treatment Options in Oncology, Vol. 8, No. 1, 2007, pp. 47-60. doi:10.1007/s11864-007-0008-2

[18]   Q. Ryan, et al., “FDA Drug Approval Summary: Lapatinib in Combination with Capecitabine for Previously Treated Metastatic Breast Cancer That Overexpresses HER-2,” Oncologist, Vol. 13, No. 10, 2008, pp. 1114-1119.

[19]   P. Manders, et al., “The Prognostic Value of Vascular Endothelial Growth Factor in 574 Node-Negative Breast Cancer Patients Who Did Not Receive Adjuvant Systemic Therapy,” British Journal of Cancer, Vol. 87, No. 7, 2002, pp. 772-778. doi:10.1038/sj.bjc.6600555

[20]   G. W. Sledge Jr., “Vascular Endothelial Growth Factor in Breast Cancer: Biologic and Therapeutic Aspects,” Seminars in Oncology, Vol. 29, No. 3, 2002, pp. 104-110. doi:10.1016/S0093-7754(02)70133-4

[21]   D. F. Hayes, K. Miller and G. Sledge, “Angiogenesis as Targeted Breast Cancer Therapy,” Breast, Vol. 16, Suppl. 2, 2007, pp. S17-S19.

[22]   P. K. Shahi, A. S. Lovelle and G. P. Manga, “Tumoral Angiogenesis and Breast Cancer,” Clinical & Translational Oncology, Vol. 11, No. 3, 2009, pp. 138-142. doi:10.1007/S12094-009-0329-7

[23]   T. A. Traina, “Bevacizumab in the Treatment of Metastatic Breast Cancer,” Oncology, Vol. 23, No. 4, 2009, pp. 327-332.

[24]   L. Q. Chow and S. G. Eckhardt, “Sunitinib: From Rational Design to Clinical Efficacy,” Journal of Clinical Oncology, Vol. 25, No. 7, 2007, pp. 884-896. doi:10.1200/JCO.2006.06.3602

[25]   S. P. Ivy, J. Y. Wick and B. M. Kaufman, “An Overview of Small-Molecule Inhibitors of VEGFR Signaling,” Nature Reviews Clinical Oncology, Vol. 6, No. 10, 2009, pp. 569-579. doi:10.1038/nrclinonc.2009.130

[26]   D. Pytel, T. Sliwinski, T. Poplawski, D. Ferriola and I. Majsterek, “Tyrosine Kinase Blockers: New Hope for Successful Cancer Therapy,” Anti-Cancer Agents in Medicinal Chemistry, Vol. 9, No. 1, 2009, pp. 66-76.

[27]   O. Dizdar and K. Altundag, “Emerging Drugs in Metastatic Breast Cancer,” Expert Opinion on Emerging Drugs, Vol. 14, No. 1, 2009, pp. 85-98. doi:10.1517/14728210802625671

[28]   G. M. Higa, “Breast Cancer: Beyond the Cutting Edge,” Expert Opinion on Pharmacotherapy, Vol. 10, No. 15, 2009, pp. 2479-2498. doi:10.1517/14656560903167957

[29]   G. M. Higa and J. Abraham, “Biological Mechanisms of Bevacizumab-Associated Adverse Events,” Expert Review of Anticancer Therapy, Vol. 9, No. 7, 2009, pp. 999-1007. doi:10.1586/era.09.68

[30]   P. G. Morris and C. A. Hudis, “Personalizing Therapy for Metastatic Breast Cancer,” Expert Review of Anticancer Therapy, Vol. 9, No. 9, 2009, pp. 1223-1226. doi:10.1586/era.09.89

[31]   P. G. Morris, H. L. McArthur and C. A. Hudis, “Therapeutic Options for Metastatic Breast Cancer,” Expert Opinion on Pharmacotherapy, Vol. 10, No. 6, 2009, pp. 967-981. doi:10.1517/14656560902834961

[32]   N. U. Lin, et al., “A Phase II Study of Afatinib (BIBW 2992), an Irreversible ErbB Family Blocker, in Patients with HER2-Positive Metastatic Breast Cancer Progressing after Trastuzumab,” Breast Cancer Research and Treatment, Vol. 133, No. 3, 2012, pp. 1057-1065. doi:10.1007/s10549-012-2003-y

[33]   M. Schuler, et al., “A Phase II Trial to Assess Efficacy and Safety Of Afatinib in Extensively Pretreated Patients with HER2-Negative Metastatic Breast Cancer,” Breast Cancer Research and Treatment, Vol. 134, No. 3, 2012, pp. 1149-1159. doi:10.1007/s10549-012-2126-1

[34]   Y. Ito, et al., “Safety, Efficacy and Pharmacokinetics of Neratinib (HKI-272) in Japanese Patients with Advanced Solid Tumors: A Phase 1 Dose-Escalation Study,” Japanese Journal of Clinical Oncology, Vol. 42, No. 4, 2012, pp. 278-286. doi:10.1093/jjco/hys012

[35]   K. K. Wong, et al., “A Phase I Study with Neratinib (HKI-272), an Irreversible Pan ErbB Receptor Tyrosine Kinase Inhibitor, in Patients with Solid Tumors,” Clinical Cancer Research, Vol. 15, No. 7, 2009, pp. 2552-2558. doi:10.1158/1078-0432.CCR-08-1978

[36]   N. Isambert, et al., “Phase I Dose-Escalation Study of Intravenous Aflibercept in Combination with Docetaxel in Patients with Advanced Solid Tumors,” Clinical Cancer Research, Vol. 18, No. 6, 2012, pp. 1743-1750. doi:10.1158/1078-0432.CCR-11-1918

[37]   C. H. Barrios, et al., “Phase III Randomized Trial of Sunitinib versus Capecitabine in Patients with Previously Treated HER2-Negative Advanced Breast Cancer,” Breast Cancer Research and Treatment, Vol. 121, No. 1, 2010, pp. 121-131. doi:10.1007/s10549-010-0788-0

[38]   J. Bergh, et al., “First-Line Treatment of Advanced Breast Cancer with Sunitinib in Combination with Docetaxel Versus Docetaxel Alone: Results of a Prospective, Randomized Phase III Study,” Journal of Clinical Oncology, Vol. 30, No. 9, 2012, pp. 921-929. doi:10.1200/JCO.2011.35.7376

[39]   J. Baselga, et al., “Sorafenib in Combination with Capecitabine: An Oral Regimen for Patients with HER2-Negative Locally Advanced or Metastatic Breast Cancer,” Journal of Clinical Oncology, Vol. 30, No. 13, 2012, pp. 1484-1491. doi:10.1200/JCO.2011.36.7771

[40]   C. Isaacs, et al., “Phase I/II Study of Sorafenib with Anastrozole in Patients with Hormone Receptor Positive Aromatase Inhibitor Resistant Metastatic Breast Cancer,” Breast Cancer Research and Treatment, Vol. 125, No. 1, 2011, pp. 137-143. doi:10.1007/s10549-010-1226-z.

[41]   H. S. Rugo, et al., “Randomized, Placebo-Controlled, Double-Blind, Phase II Study of Axitinib plus Docetaxel Versus Docetaxel plus Placebo in Patients with Metastatic Breast Cancer,” Journal of Clinical Oncology, Vol. 29, No. 18, 2011, pp. 2459-465. doi:10.1200/JCO.2010.31.2975

[42]   K. Boer, et al., “Vandetanib with Docetaxel as SecondLine Treatment for Advanced Breast Cancer: A Double-Blind, Placebo-Controlled, Randomized Phase II Study,” Investigational New Drugs, Vol. 30, No. 2, 2012, pp. 681-687. doi:10.1007/s10637-010-9538-8.

[43]   S. K. Taylor, et al., “A Phase II Study of Pazopanib in Patients with Recurrent or Metastatic Invasive Breast Carcinoma: A Trial of the Princess Margaret Hospital Phase II Consortium,” Oncologist, Vol. 15, No. 8, 2010, pp. 810-818. doi:10.1634/theoncologist.2010-0081

[44]   N. R. Bertos and M. Park, “Breast Cancer—One Term, Many Entities?” Journal of Clinical Investigation, Vol. 121, No. 10, 2011, pp. 3789-3796. doi:10.1172/JCI57100

[45]   M. Hergueta-Redondo, J. Palacios, A. Cano and G. Moreno-Bueno, “New Molecular Taxonomy in Breast Cancer,” Clinical & Translational Oncology, Vol. 10, No. 12, 2008, pp. 777-785. doi:10.1007/s12094-008-0290-x

[46]   J. Peppercorn, C. M. Perou and L. A. Carey, “Molecular Subtypes in Breast Cancer Evaluation and Management: Divide and Conquer,” Cancer Investigation, Vol. 26, No. 1, 2008, pp. 1-10. doi:10.1080/07357900701784238

[47]   K. Polyak, “Breast Cancer: Origins and Evolution,” Journal of Clinical Investigation, Vol. 117, No. 11, 2007, pp. 3155-3163. doi:10.1172/JCI33295

[48]   T. W. Miller, B. N. Rexer, J. T. Garrett and C. L. Arteaga, “Mutations in the Phosphatidylinositol 3-Kinase Pathway: Role in Tumor Progression and Therapeutic Implications in Breast Cancer,” Breast Cancer Research, Vol. 13, No. 6, 2011, pp. 224-236. doi:10.1186/bcr3039

[49]   J. Baselga, et al., “Phase II Randomized Study of Neoadjuvant Everolimus plus Letrozole Compared with Placebo plus Letrozole in Patients with Estrogen Receptor-Positive Breast Cancer,” Journal of Clinical Oncology, Vol. 27, No. 16, 2009, pp. 2630-2637. doi:10.1200/JCO.2008.18.8391

[50]   J. Kalra, et al., “QLT0267, a Small Molecule Inhibitor Targeting Integrin-Linked Kinase (ILK), and Docetaxel Can Combine to Produce Synergistic Interactions Linked to Enhanced Cytotoxicity, Reductions in P-AKT Levels, Altered F-Actin Architecture and Improved Treatment Outcomes in an Orthotopic Breast Cancer Model,” Breast Cancer Research, Vol. 11, No. 3, 2009, pp. R25-R40. doi:10.1186/bcr2252

[51]   J. Kalra, et al., “ILK Inhibition Engenders Suppression of Her2/neu Expression through a Pathway Involving TWIST and YB-1,” Oncogene, Vol. 29, No. 48, 2010, pp. 6343-6356. doi:10.1038/onc.2010.366

[52]   S. Dedhar, B. Williams and G. Hannigan, “Integrin-Linked Kinase (ILK): A Regulator of Integrin and Growth-Factor Signaling,” Trends in Cell Biology, Vol. 9, No. 8, 1999, pp. 319-323. doi:10.1016/S0962-8924(99)01612-8

[53]   K. R. Legate and R. Fassler, “Mechanisms That Regulate Adaptor Binding to Beta-Integrin Cytoplasmic Tails,” Journal of Cell Science, Vol. 122, 2009, pp. 187-198. doi:10.1242/jcs.041624

[54]   K. R. Legate, E. Montanez and R. Fussler, “ILK, PINCH and Parvin: The tIPP of Integrin Signaling,” Nature Reviews Molecular Cell Biology, Vol. 7, No. 1, 2006, pp. 20-31. doi:10.1038/nrm1789

[55]   P. C. McDonald, A. B. Fielding and S. Dedhar, “Integrin-Linked Kinase—Essential Roles in Physiology and Cancer Biology,” Journal of Cell Science, Vol. 121, 2008, pp. 3121-3132. doi:10.1242/jcs.017996.

[56]   S. Persad and S. Dedhar, “The Role of Integrin-Linked Kinase (ILK) in Cancer Progression,” Cancer and Metastasis Reviews, Vol. 22, No. 4, 2003, pp. 375-384. doi:10.1023/A:1023777013659

[57]   F. Li, Y. Zhang and C. Wu, “Integrin-Linked Kinase Is Localized to Cell-Matrix Focal Adhesions but Not Cell-Cell Adhesion Sites and the Focal Adhesion Localization of Integrin-Linked Kinase Is Regulated by the PINCH-Binding ANK Repeats,” Journal of Cell Science, Vol. 112, 1999, pp. 4589-4599.

[58]   S. N. Nikolopoulos and C. E. Turner, “Integrin-Linked Kinase (ILK) Binding to Paxillin LD1 Motif Regulates ILK Localization to Focal Adhesions,” Journal of Biological Chemistry, Vol. 276, No. 26, 2001, pp. 23499-23505. doi:10.1074/jbc.M102163200

[59]   Y. Tu, Y. Huang, Y. Zhang, Y. Hua and C. Wu, “A New Focal Adhesion Protein That Interacts with Integrin-Linked Kinase and Regulates Cell Adhesion and Spreading,” Journal of Cell Biology, Vol. 153, No. 3, 2001, pp. 585-598. doi:10.1083/jcb.153.3.585

[60]   Y. Yang, et al., “Structural Basis of Focal Adhesion Localization of LIM-Only Adaptor PINCH by Integrin-Linked Kinase,” Journal of Biological Chemistry, Vol. 284, No. 9, 2009, pp. 5836-5844. doi:10.1074/jbc.M805319200

[61]   E. R. Abboud, et al., “Integrin-Linked Kinase: A Hypoxia-Induced Anti-Apoptotic Factor Exploited by Cancer Cells,” International Journal of Oncology, Vol. 30, No. 1, 2007, pp. 113-122.

[62]   N. Ahmed, et al., “Integrin-Linked Kinase Expression Increases with Ovarian Tumour Grade and Is Sustained by Peritoneal Tumour Fluid,” Journal of Pathology, Vol. 201, No. 2, 2003, pp. 229-237. doi:10.1002/path.1441

[63]   A. Oloumi, T. McPhee and S. Dedhar, “Regulation of E-Cadherin Expression and Beta-Catenin/Tcf Transcriptional Activity by the Integrin-Linked Kinase,” Biochimica et Biophysica Acta, Vol. 1691, No. 1, 2004, pp. 1-15.

[64]   A. Oloumi, S. Syam and S. Dedhar, “Modulation of Wnt3a-Mediated Nuclear Beta-Catenin Accumulation and Activation by Integrin-Linked Kinase in Mammalian Cells,” Oncogene, Vol. 25, No. 59, 2006, pp. 7747-7757. doi:10.1038/sj.onc.1209752

[65]   G. Radeva, et al., “Overexpression of the Integrin-Linked Kinase Promotes Anchorage-Independent Cell Cycle Progression,” Journal of Biological Chemistry, Vol. 272, No. 21, 1997, pp. 13937-13944. doi:10.1074/jbc.272.21.13937.

[66]   N. Yoganathan, et al., “Integrin-Linked Kinase, a Promising Cancer Therapeutic Target: Biochemical and Biological Properties,” Pharmacology & Therapeutics, Vol. 93, No. 2-3, 2002, pp. 233-242. doi:10.1016/S0163-7258(02)00192-4.

[67]   T. N. Yoganathan, et al., “Integrin-Linked Kinase (ILK): A ‘Hot’ Therapeutic Target,” Biochemical Pharmacology, Vol. 60, No. 8, 2000, pp. 1115-9. doi:10.1016/S0006-2952(00)00444-5.

[68]   M. S. Duxbury, et al., “RNA Interference Demonstrates a Novel Role for Integrin-Linked Kinase as a Determinant of Pancreatic Adenocarcinoma Cell Gemcitabine Chemoresistance,” Clinical Cancer Research, Vol. 11, No. 9, 2005, pp. 3433-3438. doi:10.1158/1078-0432.CCR-04-1510

[69]   S. Persad, et al., “Inhibition of Integrin-Linked Kinase (ILK) Suppresses Activation of Protein Kinase B/Akt and Induces Cell Cycle Arrest and Apoptosis of PTEN-Mutant Prostate Cancer Cells,” Proceedings of the National Academy of Sciences, Vol. 97, No. 7, 2000, pp. 3207-3212.

[70]   L. A. Edwards, et al., “Integrin-Linked Kinase (ILK) in Combination Molecular Targeting,” Cancer Treatment and Research, Vol. 119, 2004, pp. 59-75. doi:10.1007/1-4020-7847-1_4

[71]   A. B. Fielding and S. Dedhar, “The Mitotic Functions of Integrin-Linked Kinase,” Cancer and Metastasis Reviews, Vol. 28, No. 1-2, 2009, pp. 99-111. doi:10.1007/s10555-008-9177-0

[72]   G. Hannigan, A. A. Troussard and S. Dedhar, “Integrin-Linked Kinase: A Cancer Therapeutic Target Unique among Its ILK,” Nature Reviews Cancer, Vol. 5, No. 1, 2005, pp. 51-63. doi:10.1038/nrc1524

[73]   S. Hehlgans, M. Haase and N. Cordes, “Signalling via Integrins: Implications for Cell Survival and Anticancer Strategies,” Biochimica et Biophysica Acta, Vol. 1775, No. 1, 2007, pp. 163-180.

[74]   S. M. Pontier, et al., “Integrin-Linked Kinase Has a Critical Role in ErbB2 Mammary Tumor Progression: Implications for Human Breast Cancer,” Oncogene, Vol. 29, No. 23, 2010, pp. 3374-3385. doi:10.1038/onc.2010.86

[75]   P. K. Lo and S. Sukumar, “Epigenomics and Breast Cancer,” Pharmacogenomics, Vol. 9, No. 12, 2008, pp. 1879-1902. doi:10.2217/14622416.9.12.1879

[76]   P. N. Munster, et al., “Phase I Trial of Vorinostat and Doxorubicin in Solid Tumours: Histone Deacetylase 2 Expression as a Predictive Marker,” British Journal of Cancer, Vol. 101, No. 7, 2009, pp. 1044-1050. doi:10.1038/sj.bjc.6605293

[77]   P. N. Munster, et al., “A Phase II Study of the Histone Deacetylase Inhibitor Vorinostat Combined with Tamoxifen for the Treatment of Patients with Hormone Therapy-Resistant Breast Cancer,” British Journal of Cancer, Vol. 104, No. 12, 2011, pp. 1828-1835. doi:10.1038/bjc.2011.156

[78]   B. Ramaswamy, et al., “Phase I-II Study of Vorinostat plus Paclitaxel and Bevacizumab in Metastatic Breast Cancer: Evidence for Vorinostat-Induced Tubulin Acetylation and Hsp90 Inhibition in Vivo,” Breast Cancer Research and Treatment, Vol. 132, No. 3, 2012, pp. 1063-1072. doi:10.1007/s10549-011-1928-x

[79]   R. Weil, D. Palmieri, J. Bronder, A. Stark and P. Steeg, “Breast Cancer Metastasis to the Central Nervous System,” American Journal of Pathology, Vol. 167, No. 4, 2005, pp. 913-920. doi:10.1016/S0002-9440(10)61180-7

[80]   Y. Tsukada, A. Fouad, J. W. Pickren and W. W. Lane, “Central Nervous System Metastasis from Breast Carcinoma. Autopsy Study,” Cancer, Vol. 52, No. 12, 1983, pp. 2349-2354.

[81]   V. Patanaphan, O. M. Salazar and R. Risco, “Breast Cancer: Metastastic Patterns and Their Prognosis,” Southern Medical Journal, Vol. 81, No. 9, 1988, pp. 1109-1112. doi:10.1097/00007611-198809000-00011

[82]   S. Y. Cho and H. Y. Choi, “Causes of Death and Metastatic Patterns in Patients with Mammary Cancer,” American Journal of Clinical Pathology, Vol. 73, No. 2, 1980, pp. 232-234.

[83]   H. Kennecke, et al., “Metastatic Behavior of Breast Cancer Subtypes,” Journal of Clinical Oncology, Vol. 28, 2010, pp. 3271-3277. doi:10.1200/JCO.2009.25.9820

[84]   C. Sezgin, E. Gokmen, M. Esassolak, N. Ozdemir and E. Goker, “Risk Factors for Central Nervous System Metastasis in Patients with Metastatic Breast Cancer,” Medical Oncology, Vol. 24, No. 2, 2007, pp. 155-161. doi:10.1007/BF02698034

[85]   K. Miller, T. Weathers, L. Hanley, et al., “Occult Central Nervous System Involvement in Patients with Metastatic Breast Cancer:Prevalence, Predictive Factors and Impact on Overall Survival,” Annals of Oncology, Vol. 14, 2003, pp. 1072-1077. doi:10.1093/annonc/mdg300

[86]   L. A. Carey, et al., “Central Nervous System Metastases in Women after Multimodality Therapy for High Risk Breast Cancer,” Breast Cancer Research and Treatment, Vol. 88, No. 3, 2004, pp. 273-280. doi:10.1007/s10549-004-0999-3

[87]   B. C. Pestalozzi, et al., “Identifying Breast Cancer Patients at Risk for Central Nervous System (CNS) Metastases in Trials of the International Breast Cancer Study Group (IBCSG),” Annals of Oncology,, Vol. 17, No. 6, 2006, pp. 935-944. doi:10.1093/annonc/mdl064

[88]   A. DiStefano, Y. Y. Yap, G. N. Hortobagyi and G. R. Blumenschein, “The Natural History of Breast-Cancer Patients with Brain Metastases,” Cancer, Vol. 44, No. 5, 1979, pp. 1913-1918. doi:10.1002/1097-0142(197911)44:5<1913::AID-CNCR2820440554>3.0.CO;2-D

[89]   P. A. Forsyth and J. B. Posner, “Headaches in Patients with Brain Tumors: A Study of 111 Patients,” Neurology, Vol. 43, No. 9, 1993, pp. 1678-1683. doi:10.1212/WNL.43.9.1678

[90]   C. M. Issa, R. Semrau, R. Kath and K. Hoffken, “Isolated Brain Metastases as the Sole Manifestation of a Late Relapse in Breast Cancer,” Journal of Cancer Research and Clinical Oncology, Vol. 128, No. 1, 2002, pp. 61-63. doi:10.1007/s004320100286

[91]   N. U. Lin, J. R. Bellon and E. P. Winer, “CNS Metastasis in Breast Cancer,” Journal of Clinical Oncology, Vol. 22, No. 17, pp. 3608-3617. doi:10.1200/JCO.2004.01.175

[92]   R. J. Weil, D. C. Palmieri, J. L. Bronder, A. M. Stark and P. S. Steeg, “Breast Cancer Metastasis to the Central Nervous System,” American Journal of Pathology, Vol. 167, No. 4, 2005, pp. 913-920. doi:10.1016/S0002-9440(10)61180-7.

[93]   J. Engel, et al., “Determinants and Prognoses of Locoregional and Distant Progression in Breast Cancer,” International Journal of Radiation Oncology*Biology*Physics, Vol. 55, 2003, pp. 1186-1195. doi:10.1016/S0360-3016(02)04476-0

[94]   R. Soffietti, R. Ruda and E. Trevisan, “Brain Metastases: Current Management and New Developments,” Current Opinion in Oncology, Vol. 20, No. 6, 2008, pp. 676-684. doi:10.1097/CCO.0b013e32831186fe

[95]   S. S. Lee, et al., “Brain Metastases in Breast Cancer: Prognostic Factors and Management,” Breast Cancer Research and Treatment, Vol. 111, No. 3, 2008, pp. 523-530. doi:10.1007/s10549-007-9806-2

[96]   D. Palmieri, et al., “Brain Metastases of Breast Cancer,” Breast Disease, Vol. 26, No. 1, 2006, pp. 139-147.

[97]   L. L. Muldoon, et al., “Chemotherapy Delivery Issues in Central Nervous System Malignancy: A Reality Check,” Journal of Clinical Oncology, Vol. 25, No. 16, 2007, pp. 2295-2305. doi:10.1200/JCO.2006.09.9861.

[98]   N. U. Lin, J. R. Bellon and E. P. Winer, “CNS Metastases in Breast Cancer,” Journal of Clinical Oncology, Vol. 22, No. 17, 2004, pp. 3608-3617. doi:10.1200/JCO.2004.01.175

[99]   M. L. Wang, W. K. Yung, M. E. Royce, D. F. Schomer and R. L. Theriault, “Capecitabine for 5-Fluorouracil-Resistant Brain Metastases from Breast Cancer,” American Journal of Clinical Oncology, Vol. 24, No. 4, 2001, pp. 421-424. doi:10.1097/00000421-200108000-00026

[100]   W. Wick, M. Platten and M. Weller, “New (Alternative) Temozolomide Regimens for the Treatment of Glioma,” Neuro-Oncology, Vol. 11, No. 1, 2009, pp. 69-79. doi:10.1215/15228517-2008-078

[101]   L. E. Abrey, et al., “A Phase II Trial of Temozolomide for Patients with Recurrent or Progressive Brain Metastases,” Journal of Neuro-Oncology, Vol. 53, No. 3, 2001, pp. 259-265. doi:10.1023/A:1012226718323

[102]   C. Christodoulou, et al., “Phase II Study of Temozolomide in Heavily Pretreated Cancer Patients with Brain Metastases,” Annals of Oncology, Vol. 12, No. 2, 2001, pp. 249-254. doi:10.1023/A:1008354323167

[103]   I. Preuss, et al., “O6-Methylguanine-DNA Methyltransferase Activity in Breast and Brain Tumors,” International Journal of Cancer, Vol. 61, No. 3, 1995, pp. 321-326. doi:10.1002/ijc.2910610308

[104]   R. Addeo, et al., “Phase 2 Trial of Temozolomide Using Protracted Low-Dose and Whole Brain Radiotherapy for Non Small Cell Lung Cancer and Breast-Cancer Patients with Brain Metastases,” Cancer, Vol. 113, No. 9, 2008, pp. 2524-2531. doi:10.1002/cncr.23859

[105]   E. Rivera, “Phase I Study of Capecitabine in Combination with Temozolomide in the Treatment of Patients with Brain Metastases from Breast Carcinoma,” Cancer, Vol. 107, No. 6, 2006, pp. 1348-1354. doi:10.1002/cncr.22127

[106]   M. Kurt, S. Aksoy, M. Hayran and N. Guler, “A Retrospective Review of Breast-Cancer Patients with Central Nervous System Metastasis Treated with Capecitabine,” ASCO Annual Meeting, Abstract No 1098.

[107]   V. Guarneri, A. Frassoldati, S. Giovannelli, F. Borghi and P. Conte, “Primary Systemic Therapy for Operable Breast Cancer: A Review of Clinical Trials and Perspectives,” Cancer Letters, Vol. 248, No. 2, 2007, pp. 175-185. doi:10.1016/j.canlet.2006.07.001

[108]   J. A. O’Shaughnessy, “The Evolving Role of Capectiabine in Breast Cancer,” Clinical Breast Cancer, Suppl. 1, 2003, pp. S20-S25.

[109]   J. Baselga, et al., “Pertuzumab plus Trastuzumab plus Docetaxel for Metastatic Breast Cancer,” New England Journal of Medicine, Vol. 366, No. 2, 2012, pp. 109119. doi:10.1056/NEJMoa1113216

[110]   B. C. Pestalozzi, D. Zahrieh, K. N. Price, et al., “Identifying Breast Cancer Patients at Risk for Central Nervous System (CNS) Metastases in Trials of the International Breast Cancer Study Group (IBCSG),” Annals of Oncology, Vol. 17, No. 6, 2006, pp. 935-944. doi:10.1093/annonc/mdl064

[111]   W. Zoli, L. Ricotti, A. Tesei, F. Barzanti and D. Amadori, “In Vitro Preclinical Models for a Rational Design of Chemotherapy Combinations in Human Tumors,” Critical Reviews in Oncology/Hematology, Vol. 37, No. 1, 2001, pp. 69-82. doi:10.1016/S1040-8428(00)00110-4

 
 
Top