PIK3CA mutations, PTEN, and pHER2 expression and impact on outcome in HER2-positive early-stage breast cancer patients treated with adjuvant chemotherapy and trastuzumab

Annals of Oncology

Volumn 23, Issue 8, 2012, Pages 2034-2042

  Jensen, J D ^a,b   Knoop, A ^a,b   Laenkholm, A V ^c   Grauslund, M ^d   Jensen, M B ^e   Santoni Rugiu, E ^d   Andersson, M ^d   Ewertz, M ^a,b  

^a ODENSE UNIVERSITY HOSPITAL   (Denmark)

^b UNIVERSITY OF SOUTHERN DENMARK   (Denmark)

^c SLAGELSE HOSPITAL   (Denmark)

^d International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health   (Denmark)

^e Danish Breast Cancer Cooperative Group Data Center   (Denmark)

Author keywords

HER2 positive early stage breast cancer; PHER2; PI3K activity; PIK3CA mutations; PTEN; Trastuzumab resistance

Indexed keywords

CYCLOPHOSPHAMIDE; EPIDERMAL GROWTH FACTOR RECEPTOR 2; EPIRUBICIN; FLUOROURACIL; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; TRASTUZUMAB;

ARTICLE; BREAST CANCER; CANCER ADJUVANT THERAPY; CANCER PROGNOSIS; CANCER STAGING; DISEASE FREE SURVIVAL; EXON; FEMALE; GENE MUTATION; HUMAN; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; LOADING DRUG DOSE; MAJOR CLINICAL STUDY; MULTIPLE CYCLE TREATMENT; MUTATIONAL ANALYSIS; OVERALL SURVIVAL; PI3CA GENE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; PYROSEQUENCING;

EID: 84864945212     PISSN: 09237534     EISSN: 15698041     Source Type: Journal    
DOI: 10.1093/annonc/mdr546     Document Type: Article

References (64)

1. Yuan TL, Cantley LC. PI3K pathway alterations in cancer: variations on a theme. Oncogene 2008; 27(41): 5497-5510.
2. Rasmussen BB, Andersson M, Christensen IJ, Moller S. Evaluation of and quality assurance in HER2 analysis in breast carcinomas from patients registered in Danish Breast Cancer Group (DBCG) in the period of 2002-2006. A nationwide study including correlation between HER-2 status and other prognostic variables. Acta Oncol 2008; 47(4): 784-788.
3. Kataoka Y, Mukohara T, Shimada H et al. Association between gain-of-function mutations in PIK3CA and resistance to HER2-targeted agents in HER2-amplified breast cancer cell lines. Ann Oncol 2010; 21(2): 255-262.
4. Slamon DJ, Godolphin W, Jones LA et al. Studies of the HER-2/neu protooncogene in human breast and ovarian cancer. Science 1989; 244(4905): 707-712.
5. Slamon DJ, Clark GM, Wong SG et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987; 235 (4785): 177-182.
6. Bachman KE, Argani P, Samuels Y et al. The PIK3CA gene is mutated with high frequency in human breast cancers. Cancer Biol Ther 2004; 3(8): 772-775.
7. Barbareschi M, Buttitta F, Felicioni L et al. Different prognostic roles of mutations in the helical and kinase domains of the PIK3CA gene in breast carcinomas. Clin Cancer Res 2007; 13(20): 6064-6069.
8. Buttitta F, Felicioni L, Barassi F et al. PIK3CA mutation and histological type in breast carcinoma: high frequency of mutations in lobular carcinoma. J Pathol 2006; 208(3): 350-355.
9. Campbell IG, Russell SE, Choong DYH et al. Mutation of the PIK3CA gene in ovarian and breast cancer. Cancer Res 2004; 64(21): 7678-7681.
10. Kalinsky K, Jacks LM, Heguy A et al. PIK3CA mutation associates with improved outcome in breast cancer. Clin Cancer Res 2009; 15(16): 5049-5059.
11. Li S, Rong M, Grieu F, Iacopetta B. PIK3CA mutations in breast cancer are associated with poor outcome. Breast Cancer Res Treat 2006; 96(1): 91-95.
12. Perez-Tenorio G, Alkhori L, Olsson B et al. PIK3CA mutations and PTEN loss correlate with similar prognostic factors and are not mutually exclusive in breast cancer. Clin Cancer Res 2007; 13(12): 3577-3584.
13. Saal LH, Holm K, Maurer M et al. PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma. Cancer Res 2005; 65(7): 2554-2559.
14. Wu G, Xing M, Mambo E et al. Somatic mutation and gain of copy number of PIK3CA in human breast cancer. Breast Cancer Res 2005; 7(5): R609-R616.
15. Bader AG, Kang S, Vogt PK. Cancer-specific mutations in PIK3CA are oncogenic in vivo. Proc Natl Acad Sci U S A 2006; 103(5): 1475-1479.
16. Isakoff SJ, Engelman JA, Irie HY et al. Breast cancer-associated PIK3CA mutations are oncogenic in mammary epithelial cells. Cancer Res 2005; 65(23): 10992-11000.
17. Kang S, Bader AG, Vogt PK. Phosphatidylinositol 3-kinase mutations identified in human cancer are oncogenic. Proc Natl Acad Sci U S A 2005; 102802-807.
18. Keniry M, Parsons R. The role of PTEN signaling perturbations in cancer and in targeted therapy. Oncogene 2008; 27(41): 5477-5485.
19. Cobleigh MA, Vogel CL, Tripathy D et al. Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol 1999; 17(9): 2639-2648.
20. Piccart-Gebhart MJ, Procter M, Leyland-Jones B et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 2005; 353(16): 1659-1672.
21. Romond EH, Perez EA, Bryant J et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 2005; 353(16): 1673-1684.
22. 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 2001; 344(11): 783-792.
23. Smith I, Procter M, Gelber RD et al. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet 2007; 369(9555): 29-36.
24. Slamon D, Eiermann W, Robert N et al. Phase III randomized trial comparing doxorubicin and cyclophosphamide followed by docetaxel (AC-T) with doxorubicin and cyclophosphamide followed by docetaxel and trastuzumab (AC-TH) with docetaxel, carboplatin and trastuzumab (TCH) in HER2 positive early breast cancer patients: BCIRG 006 study. Breast Cancer Res Treat 2005; 94Suppl 1 (Abstr 1).
25. Perez EA, Romond EH, Suman VJ et al. Updated results of the combined analysis of NCCTG N9831 and NSABP B-31 adjuvant chemotherapy with/without trastuzumab in patients with HER2-positive breast cancer. J Clin Oncol (Meeting Abstracts) 2007; 2518 Suppl(Abstr 512).
26. Gianni L, Dafni U, Gelber RD et al. Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial. Lancet Oncol 2011; 12(3): 236-244.
27. Perez EA, Romond EH, Suman VJ et al. Four-year follow-up of trastuzumab plus adjuvant chemotherapy for operable human epidermal growth factor receptor 2-positive breast cancer: joint analysis of data from NCCTG N9831 and NSABP B- J Clin Oncol 2011; 29(25): 3366-3373.
28. Vogel CL, Cobleigh MA, Tripathy D et al. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 2002; 20(3): 719-726.
29. Montemurro F, Donadio M, Clavarezza M et al. Outcome of patients with HER2-positive advanced breast cancer progressing during trastuzumab-based therapy. Oncologist 2006; 11(4): 318-324.
30. Pohlmann PR, Mayer IA, Mernaugh R. Resistance to trastuzumab in breast cancer. Clin Cancer Res 2009; 15(24): 7479-7491.
31. Eichhorn PJA, Gili M, Scaltriti M et al. Phosphatidylinositol 3-kinase hyperactivation results in lapatinib resistance that is reversed by the mTOR/phosphatidylinositol 3-kinase inhibitor NVP-BEZ235. Cancer Res 2008; 68(22): 9221-9230.
32. 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 2007; 12(4): 395-402.
33. Razis E, Bobos M, Kotoula V et al. Evaluation of the association of PIK3CA mutations and PTEN loss with efficacy of trastuzumab therapy in metastatic breast cancer. Breast Cancer Res Treat 2011; 128(2): 447-456.
34. Fujita T, Doihara H, Kawasaki K et al. PTEN activity could be a predictive marker of trastuzumab efficacy in the treatment of ErbB2-overexpressing breast cancer. Br J Cancer 2006; 94(2): 247-252.
35. Faratian D, Goltsov A, Lebedeva G et al. Systems biology reveals new strategies for personalizing cancer medicine and confirms the role of PTEN in resistance to trastuzumab. Cancer Res 2009; 69(16): 6713-6720.
36. 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 2004; 6(2): 117-127.
37. Dave B, Migliaccio I, Gutierrez MC et al. Loss of phosphatase and tensin homolog or phosphoinositol-3 kinase activation and response to trastuzumab or lapatinib in human epidermal growth factor receptor 2-overexpressing locally advanced breast cancers. J Clin Oncol 2011; 29(2): 166-173.
38. Frogne T, Laenkholm AV, Lyng M et al. Determination of HER2 phosphorylation at tyrosine 1221/1222 improves prediction of poor survival for breast cancer patients with hormone receptor-positive tumors. Breast Cancer Res 2009; 11(1): R11.
39. Esteva FJ, Yu D, Hung MC, Hortobagyi GN. Molecular predictors of response to trastuzumab and lapatinib in breast cancer. Nat Rev Clin Oncol 2010; 7(2): 98-107.
40. Thor AD, Liu S, Edgerton S et al. Activation (tyrosine phosphorylation) of ErbB-2 (HER-2/neu): a study of incidence and correlation with outcome in breast cancer. J Clin Oncol 2000; 18(18): 3230-3239.
41. DiGiovanna MP, Stern DF. Activation state-specific monoclonal antibody detects tyrosine phosphorylated p185neu/erbB-2 in a subset of human breast tumors overexpressing this receptor. Cancer Res 1995; 55(9): 1946-1955.
42. Hudelist G, Kostler WJ, Czerwenka K et al. Her-2/neu and EGFR tyrosine kinase activation predict the efficacy of trastuzumab-based therapy in patients with metastatic breast cancer. Int J Cancer 2006; 118(5): 1126-1134.
43. Hudelist G, Kostler WJ, Attems J et al. Her-2/neu-triggered intracellular tyrosine kinase activation: in vivo relevance of ligand-independent activation mechanisms and impact upon the efficacy of trastuzumab-based treatment. Br J Cancer 2003; 89(6): 983-991.
44. Cicenas J, Urban P, Kung W et al. Phosphorylation of tyrosine 1248-ERBB2 measured by chemiluminescence-linked immunoassay is an independent predictor of poor prognosis in primary breast cancer patients. Eur J Cancer 2006; 42(5): 636-645.
45. Ginestier C, Adelaide J, Goncalves A et al. ERBB2 phosphorylation and trastuzumab sensitivity of breast cancer cell lines. Oncogene 2007; 26(50): 7163-7169.
46. http://www.dbcg.dk/PDF%20Filer/Mammaskema%20260607.pdf (13 November 2011, date last accessed).
47. Jensen JD, Laenkholm AV, Knoop A et al. PIK3CA mutations may be discordant between primary and corresponding metastatic disease in breast cancer. Clin Cancer Res 2011; 17(4): 667-677.
48. Schemper M, Smith TL. A note on quantifying follow-up in studies of failure time. Control Clin Trials 1996; 17(4): 343-346.
49. Hudis CA, Barlow WE, Costantino JP et al. Proposal for standardized definitions for efficacy end points in adjuvant breast cancer trials: the STEEP system. J Clin Oncol 2007; 25(15): 2127-2132.
50. Costa RB, Kurra G, Greenberg L, Geyer CE. Efficacy and cardiac safety of adjuvant trastuzumab-based chemotherapy regimens for HER2-positive early breast cancer. Ann Oncol 2010; 21(11): 2153-2160.
51. Stemke-Hale K, Gonzalez-Angulo AM, Lluch A et al. An integrative genomic and proteomic analysis of PIK3CA, PTEN, and AKT mutations in breast cancer. Cancer Res 2008; 68(15): 6084-6091.
52. Esteva FJ, Guo H, Zhang S et al. PTEN, PIK3CA, p-AKT, and p-p70S6K status: association with trastuzumab response and survival in patients with HER2-positive metastatic breast cancer. Am J Pathol 2010; 177(4): 1647-1656.
53. Tsiatis AC, Norris-Kirby A, Rich RG et al. Comparison of Sanger sequencing, pyrosequencing, and melting curve analysis for the detection of KRAS mutations: diagnostic and clinical implications. J Mol Diagn 2010; 12(4): 425-432.
54. Gori S, Sidoni A, Colozza M et al. EGFR, pMAPK, pAkt and PTEN status by immunohistochemistry: correlation with clinical outcome in HER2-positive metastatic breast cancer patients treated with trastuzumab. Ann Oncol 2009; 20 (4): 648-654.
55. Sakr RA, Barbashina V, Morrogh M et al. Protocol for PTEN expression by immunohistochemistry in formalin-fixed paraffin-embedded human breast carcinoma. Appl Immunohistochem Mol Morphol 2010; 18(4): 371-374.
56. Schulze WX, Deng L, Mann M. Phosphotyrosine interactome of the ErbB-receptor kinase family. Mol Syst Biol 2005; 11-13.
57. Baker AF, Dragovich T, Ihle NT et al. Stability of phosphoprotein as a biological marker of tumor signaling. Clin Cancer Res 2005; 11(12): 4338-4340.
58. Pinhel IF, Macneill FA, Hills MJ et al. Extreme loss of immunoreactive p-Akt and p-Erk1/2 during routine fixation of primary breast cancer. Breast Cancer Res 2010; 12(5): R76.
59. Esserman LJ, Moore DH, Tsing PJ et al. Biologic markers determine both the risk and the timing of recurrence in breast cancer. Breast Cancer Res Treat 2011; 129(2): 607-616.
60. Ellis MJ, Lin L, Crowder R et al. Phosphatidyl-inositol-3-kinase alpha catalytic subunit mutation and response to neoadjuvant endocrine therapy for estrogen receptor positive breast cancer. Breast Cancer Res Treat 2010; 119(2): 379-390.
61. Lai YL, Mau BL, Cheng WH et al. PIK3CA exon 20 mutation is independently associated with a poor prognosis in breast cancer patients. Ann Surg Oncol 2008; 15(4): 1064-1069.
62. Hayes DF. Markers of increased risk for failure of adjuvant therapies. Breast 2003; 12(6): 543-549.
63. O'Brien NA, Browne BC, Chow L et al. Activated phosphoinositide 3-kinase/AKT signaling confers resistance to trastuzumab but not lapatinib. Mol Cancer Ther 2010; 9(6): 1489-1502.
64. Piccart M. Circumventing de novo and acquired resistance to trastuzumab: new hope for the care of ErbB2-positive breast cancer. Clin Breast Cancer 2008; 8 (Suppl 3): S100-S113.