Summary
BACKGROUND: In the ASCO Annual Meeting, important recent developments in haematology and oncology were presented. In the 2010 ASCO meeting, interest in the field of metastatic breast cancer focused on Poly-(ADP-Ribose)-Polymerase-1 (PARP-1) inhibitors and novel treatment options in Her2-positive disease. METHODS: For this review article, authors searched proceedings of the 2010 ASCO Annual Meeting. Abstracts providing important new insights were included and discussed. RESULTS: Results from phase I and II studies of new drugs and novel combinations in Her2-positive disease were presented. Data suggested considerable activity of those therapies upon trastuzumab failure. Much interest focused on the role of PARP-1 inhibitors in triple-negative or BRCA-mutated disease. In those trials, PARP inhibitors were given either alone or in combination with conventional chemotherapy. While a combination of olaparib and paclitaxel produced inacceptable myelotoxicity, a combination of veliparib and temozolomide showed activity in BRCA carriers only. The same was true for PARP inhibitors alone: Activity, in general, was limited to patients harbouring BRCA mutations. Further studies evaluated the activity of VEGF and VEGF receptor blockade: While treatment with an anti-VEGF-antibody is active in metastatic breast cancer, the multi-target tyrosine kinase inhibitor sunitinib did not add additional benefit to chemotherapy in two randomized studies. CONCLUSION: No praxis changing data were presented in the field of metastatic breast cancer in the ACSO 2010 Annual Meeting. Still, data on PARP-1 inhibitors and new therapies for Her2-positive tumours yielded insights that will eventually lead the path to novel and effective treatment options.
Similar content being viewed by others
References
Weide R, Mergenthaler U, Pandorf A, et al. Improved survival of patients with metastatic breast cancer in routine care: results of a retrospective study in a community-based oncology group practice 1995–2005. Onkologie, 32: 107–113, 2009
Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med, 344: 783–792, 2001
Marty M, Cognetti F, Maraninchi D, et al. Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group. J Clin Oncol, 23: 4265–4274, 2005
Geyer CE, Forster J, Lindquist D, et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med, 355: 2733–2743, 2006
Sørlie T, Tibshirani R, Parker J, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA, 100: 8418–8423, 2003
Futreal PA, Liu Q, Shattuk-Eidens D, et al. BRCA1 mutations in primary breast and ovarian carcinomas. Science, 266: 120–122, 1994
Turner N, Tutt A, Ashworth A. Hallmarks of "BRCAness" in sporadic cancers. Nat Rev Cancer, 4: 814–819, 2004
Turner NC, Reis-Filho JS, Russel AM, et al. BRCA1 dysfunction in sporadic basal-like breast cancer. Oncogene, 26: 2126–2132, 2007
Krop IE, Beeram M, Modi S, et al. Phase I study of trastuzumab-DM1, an her2 antibody-drug conjugate, given every 3 weeks to patients with hER2-positive metastatic breast cancer. J Clin Oncol, 28: 2698–2704, 2010
Baselga J, Gelmon KA, Verma S, et al. Phase II trial of pertuzumab and trastuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer that progressed during prior trastuzumab therapy. J Clin Oncol, 28: 1138–1144, 2010
Sergina NV Rausch M, Wang D, et al. Escape from HER-family tyrosine kinase inhibitor therapy by the kinase-inactive HER3. Nature, 445: 437–441, 2007
Chen FL, Xia W, Spector NL. Acquired resistance to small molecule ErbB2 tyrosine kinase inhibitors. Clin Cancer Res, 14: 6730–6734, 2008
Gianni L, Lladó A, Bianchi G, et al. Open-label, phase II, multicenter, randomized study of the efficacy and safety of two dose levels of Pertuzumab, a human epidermal growth factor receptor 2 dimerization inhibitor, in patients with human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol, 28: 1131–1137, 2010
Scheuer W Friess T, Burtscher H, et al. Strongly enhanced antitumor activity of trastuzumab and pertuzumab combination treatment on HER2-positive human xenograft tumor models. Cancer Res, 69: 9330–9336, 2009
Miller K, Gianni L, Andre F, et al. A phase Ib/II trial of trastuzumab-DM1 (T-DM1) with pertuzumab (P) for women with HER2-positive, locally advanced or metastatic breast cancer (BC) who were previously treated with trastuzumab (T). J Clin Oncol, 28(Suppl. 15): 117S, 2010
Berns K, Horlings HM, Hennessy BT, et al. A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer. Cancer Cell, 12: 395–402, 2007
Nagata Y, Lan KH, Zhou X, et al. PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients. Cancer Cell, 6: 117–127, 2004
Morrow HP, Wulf GM, Booser DJ, et al. Phase I/II trial of everolimus (RAD001) and trastuzumab in patients with trastuzumab-resistant, HER2-overexpressing breast cancer. J Clin Oncol, 28(Suppl. 15): 117S, 2010
Khoury T, Kanehira K, Wang D, et al. Breast carcinoma with amplified HER2: a gene expression signature specific for trastuzumab resistance and poor prognosis. J Clin Oncol, 28(Suppl. 15): 106S, 2010
O'Shaughnessy J, Osborne C, Pippen J, et al. Efficacy of BSI-201, a poly (ADP-ribose) polymerase-1 (PARP1) inhibitor, in combination wih gemcitabine/carboplatin (G/C) in patients with metastatic triple-negative breast cancer (TNBC): results of a randomized phase II trial. J Clin Oncol, 27(Suppl. 15): 793S, 2009
Tutt A, Robson M, Garber JE, et al. Phase II trial of the oral PARP inhibitor olaparib in BRCA-deficient advanced breast cancer. J Clin Oncol, 27(Suppl. 18): 803S, 2009
Farmer H, McCabe N, Lord CJ, et al. Targeting the DNA-repair defect in BRCA mutant cells as a therapeutic strategy. Nature, 434: 917–921, 2005
Dent RA, Lindeman GJ, Clemons M, et al. Safety and efficacy of the oral PARP inhibitor olaparib (AZD2281) in combination with paclitaxel for the first- or second-line treatment of patients with metastatic triple-negative breast cancer: results from the safety cohort of a phase I/II multicenter trial. J Clin Oncol, 25(Suppl. 18): 118S, 2010
Isakoff S, Overmoyer JB, Tung NM, et al. A phase II trial of the PARP inhibitor veliparib (ABT888) and temozolomide for metastatic breast cancer. J Clin Oncol, 25(Suppl. 18): 118S, 2010
Gelmon KA, Hirte HW, Robidoux A, et al. Can we define tumors that will respond to PARP inhibitors? A phase II correlative study of olaparib in advanced serous ovarian cancer and triple-negative breast cancer. J Clin Oncol, 25(Suppl. 18): 233S, 2010
Folkman J, Klagsbrun M. Angiogenic factors. Science, 235: 442–447, 1987
Miller KD, Wang M, Gralow J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med, 357: 2666–2676, 2007
Miles D, Chan A, Romieu G, et al. Randomised, double-blind, placebo-controlled phase III study of bevacizumab with docetaxel or docetaxel with placebo as first-line therapy for patients with locally recurrent or metastatic breast cnacer: AVADOJ Clin Oncol, 26(Suppl. 18): 1008S, 2008
Robert N, Dieras V, Glaspy J, et al. RIBBON-1: a randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of HER2-negative locally recurrent or metastatic breast cancer. J Clin Oncol, 27(Suppl. 15): 42S, 2009
O'Shaughnessy J, Miles D, Gray RJ, et al. A meta-analysis of overall survival data from three randomized trials of bevacizumab (BV) and first-line chemotherapy as treatment for patients with metastatic breast cancer (MBC). J Clin Oncol, 28(Suppl. 15): 115S, 2010
Bergh J, Greil R, Voytko N, et al. Sunitinib (SU) in combination with docetaxel (D) versus D alone for the first-line treatment of advanced breast cancer (ABC). J Clin Oncol, 28(Suppl. 18): 949S, 2010
Crown J, Dieras V, Staroslawska E, et al. Phase III trial of sunitinib (SU) in combination with capecitabine (C) versus C in previously treated advanced breast cancer (ABC). J Clin Oncol, 28(Suppl. 18): 949S, 2010
Baselga J, Segalla JG, Roché H, et al. 3LBA SOLTI-0701: a double-blind, randomized phase 2b study evaluating the efficacy and safety of sorafenib (SOR) compared to placebo (PL) when administered in combination with capecitabine (CAP) in patients (pts) with locally advanced (adv) or metastatic (met) breast cancer (BC). Eur J Cancer, 7(Suppl. 2): 3S–4S, 2009
Li HZ, Gao Y, Zhao XL, et al. Effects of raf kinase inhibitor protein expression on metastasis and progression of human breast cancer. Mol Cancer Res, 7: 832–840, 2009
Jäger E, Al-Batran S, Saupe S, et al. A randomized phase III study evaluating pegylated liposomal doxorubicin (PLD) versus capecitabine (CAP) as first-line therapy for metastatic breast cancer (MBC): results of the PELICAN study. J Clin Oncol, 28(Suppl. 15): 119S, 2010
Wahl AF, Donaldson KL, Fairchild C, et al. Loss of normal p53 function confers sensitization to Taxol by increasing G2/M arrest and apoptosis. Nat Med, 2: 72–79, 1996
Zhang CC, Yang JM, White E, et al. The role of MAP4 expression in the sensitivity to paclitaxel and resistance to vinca alkaloids in p53 mutant cells. Oncogene, 16: 1617–1624, 1998
Cheang MC, Voduc D, Bajdik C, et al. Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype. Clin Cancer Res, 14: 1368–1376, 2008
Chabalier C, Lamare C, Racca C, et al. BRCA1 downregulation leads to premature inactivation of spindel checkpoint and confers paclitaxel resistance. Cell Cycle, 5: 1001–1007, 2006
Seynaeve C, Jager A, Hooning M, et al. Activity of taxane chemotherapy for metastatic breast cancer (MBC) in BRCA1 and BRCA2 mutation carriers compared to sporadic BC patients. J Clin Oncol, 28(Suppl. 15): 118S, 2010
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Bartsch, R., Ziebermayr, R. Metastatic breast cancer – ASCO 2010. memo 3, 159–162 (2010). https://doi.org/10.1007/s12254-010-0226-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12254-010-0226-3