Pi3k mutations in breast cancer: Prognostic and therapeutic implications

Breast Cancer: Targets and Therapy

Volumn 7, Issue , 2015, Pages 111-123

  Mukohara, Toru ^a  

^a KOBE UNIVERSITY HOSPITAL   (Japan)

Author keywords

PI3K; PIK3CA; Predictive factor; Prognostic factor; Trastuzumab

Indexed keywords

EPIDERMAL GROWTH FACTOR RECEPTOR; LAPATINIB; PERTUZUMAB; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3, 4, 5 TRISPHOSPHATE 3 PHOSPHATASE; PHOSPHATIDYLINOSITOL 4, 5 BISPHOSPHATE 3 KINASE; TAMOXIFEN; TRASTUZUMAB; UNCLASSIFIED DRUG;

ADJUVANT THERAPY; ARTICLE; BREAST CANCER; CANCER PROGNOSIS; CLINICAL TRIAL (TOPIC); DRUG EFFICACY; EXON; GENE; GENE AMPLIFICATION; GENE EXPRESSION; GENE MUTATION; GENETIC ASSOCIATION; GENOTYPE; HER2 GENE; HORMONAL THERAPY; HUMAN; META ANALYSIS (TOPIC); PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PHOSPHATIDYLINOSITOL 4, 5 BISPHOSPHATE 3 KINASE GENE; PREDICTIVE VALUE; RANDOMIZED CONTROLLED TRIAL (TOPIC); RECURRENCE FREE SURVIVAL; TREATMENT RESPONSE;

EID: 84930937277     PISSN: None     EISSN: 11791314     Source Type: Journal    
DOI: 10.2147/BCTT.S60696     Document Type: Article

References (67)

1. Sørlie T, Perou CM, Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001;98(19):10869–10874.
2. Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thurlimann B, Senn HJ. Strategies for subtypes – dealing with the diversity of breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol. 2011;22(8):1736–1747.
3. Samuels Y, Wang Z, Bardelli A, et al. High frequency of mutations of the PIK3CA gene in human cancers. Science. 2004;304(5670):554.
4. Liu P, Cheng H, Roberts TM, Zhao JJ. Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009;8(8):627–644.
5. Engelman JA. Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat Rev Cancer. 2009;9(8):550–562.
6. Zhao JJ, Liu Z, Wang L, Shin E, Loda MF, Roberts TM. The oncogenic properties of mutant p110α and p110β phosphatidylinositol 3-kinases in human mammary epithelial cells. Proc Natl Acad Sci U S A. 2005; 102(51):18443–18448.
7. 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.
8. Miled N, Yan Y, Hon WC, et al. Mechanism of two classes of cancer mutations in the phosphoinositide 3-kinase catalytic subunit. Science. 2007;317(5835):239–242.
9. Huang CH, Mandelker D, Schmidt-Kittler O, et al. The structure of a human p110α/p85α complex elucidates the effects of oncogenic PI3Kα mutations. Science. 2007;318(5857):1744–1748.
10. Gonzalez-Angulo AM, Chen H, Karuturi MS, et al. Frequency of mesenchymal-epithelial transition factor gene (MET) and the catalytic subunit of phosphoinositide-3-kinase (PIK3CA) copy number elevation and correlation with outcome in patients with early stage breast cancer. Cancer. 2013;119(1):7–15.
11. 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.
12. Cizkova M, Vacher S, Meseure D, et al. PIK3R1 underexpression is an independent prognostic marker in breast cancer. BMC Cancer. 2013;13:545.
13. Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490(7418):61–70.
14. Wallasch C, Weiss FU, Niederfellner G, Jallal B, Issing W, Ullrich A. Heregulin-dependent regulation of HER2/neu oncogenic signaling by heterodimerization with HER3. EMBO J. 1995;14(17):4267–4275.
15. Zhang K, Sun J, Liu N, et al. Transformation of NIH 3T3 cells by HER3 or HER4 receptors requires the presence of HER1 or HER2. J Biol Chem. 1996;271(7):3884–3890.
16. Pinkas-Kramarski R, Lenferink AE, Bacus SS, et al. The oncogenic ErbB-2/ErbB-3 heterodimer is a surrogate receptor of the epidermal growth factor and betacellulin. Oncogene. 1998;16(10):1249–1258.
17. Alimandi M, Romano A, Curia MC, et al. Cooperative signaling of ErbB3 and ErbB2 in neoplastic transformation and human mammary carcinomas. Oncogene. 1995;10(9):1813–1821.
18. Hynes NE, Lane HA. ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer. 2005;5(5):341–354.
19. Knuefermann C, Lu Y, Liu B, et al. HER2/PI-3K/Akt activation leads to a multidrug resistance in human breast adenocarcinoma cells. Oncogene. 2003;22(21):3205–3212.
20. Junttila TT, Akita RW, Parsons K, et al. Ligand-independent HER2/HER3/PI3K complex is disrupted by trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-0941. Cancer Cell. 2009;15(5):429–440.
21. Lee-Hoeflich ST, Crocker L, Yao E, et al. A central role for HER3 in HER2-amplified breast cancer: implications for targeted therapy. Cancer Res. 2008;68(14):5878–5887.
22. Hennessy BT, Smith DL, Ram PT, Lu Y, Mills GB. Exploiting the PI3K/AKT pathway for cancer drug discovery.Nat Rev Drug Discov. 2005;4(12):988–1004.
23. 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.
24. Carpten JD, Faber AL, Horn C, et al. A transforming mutation in the pleckstrin homology domain of AKT1 in cancer. Nature. 2007; 448(7152):439–444.
25. Gainor JF, Varghese AM, Ou SH, et al. ALK rearrangements are mutually exclusive with mutations in EGFR or KRAS: an analysis of 1,683 patients with non-small cell lung cancer. Clin Cancer Res. 2013;19(15):4273–4281.
26. 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.
27. Pérez-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.
28. 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.
29. 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.
30. Pang B, Cheng S, Sun SP, et al. Prognostic role of PIK3CA mutations and their association with hormone receptor expression in breast cancer: a meta-analysis. Sci Rep. 2014;4:6255.
31. Maruyama N, Miyoshi Y, Taguchi T, Tamaki Y, Monden M, Noguchi S. Clinicopathologic analysis of breast cancers with PIK3CA mutations in Japanese women. Clin Cancer Res. 2007;13(2 Pt 1):408–414.
32. 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.
33. 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.
34. Abramson VG, Cooper Lloyd M, Ballinger T, et al. Characterization of breast cancers with PI3K mutations in an academic practice setting using SNaPshot profiling. Breast Cancer Res Treat. 2014;145(2):389–399.
35. Cizkova M, Susini A, Vacher S, et al. PIK3CA mutation impact on survival in breast cancer patients and in ERα, PR and ERBB2-based subgroups. Breast Cancer Res. 2012;14(1):R28.
36. Ramirez-Ardila DE, Helmijr JC, Look MP, et al. Hotspot mutations in PIK3CA associate with first-line treatment outcome for aromatase inhibitors but not for tamoxifen. Breast Cancer Res Treat. 2013;139(1):39–49.
37. López-Knowles E, Segal CV, Gao Q, et al. Relationship of PIK3CA mutation and pathway activity with antiproliferative response to aromatase inhibition. Breast Cancer Res. 2014;16(3):R68.
38. Beelen K, Opdam M, Severson TM, et al. PIK3CA mutations, phosphatase and tensin homolog, human epidermal growth factor receptor 2, and insulin-like growth factor 1 receptor and adjuvant tamoxifen resistance in postmenopausal breast cancer patients. Breast Cancer Res. 2014;16(1):R13.
39. Loi S, Michiels S, Lambrechts D, et al. Somatic mutation profiling and associations with prognosis and trastuzumab benefit in early breast cancer. J Natl Cancer Inst. 2013;105(13):960–967.
40. Gonzalez-Angulo AM, Stemke-Hale K, Palla SL, et al. Androgen receptor levels and association with PIK3CA mutations and prognosis in breast cancer. Clin Cancer Res. 2009;15(7):2472–2478.
41. 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.
42. Lazaridis G, Lambaki S, Karayannopoulou G, et al. Prognostic and predictive value of p-Akt, EGFR, and p-mTOR in early breast cancer. Strahlenther Onkol. 2014;190(7):636–638, 640–645.
43. Hashimoto K, Tsuda H, Koizumi F, et al. Activated PI3K/AKT and MAPK pathways are potential good prognostic markers in node-positive, triple-negative breast cancer. Ann Oncol. 2014;25(10):1973–1979.
44. Bozhanov SS, Angelova SG, Krasteva ME, et al. Alterations in p53, BRCA1, ATM, PIK3CA, and HER2 genes and their effect in modifying clinicopathological characteristics and overall survival of Bulgarian patients with breast cancer. J Cancer Res Clin Oncol. 2010;136(11):1657–1669.
45. Jensen JD, Knoop A, Laenkholm AV, et al. PIK3CA mutations, PTEN, and pHER2 expression and impact on outcome in HER2-positive early-stage breast cancer patients treated with adjuvant chemotherapy and trastuzumab. Ann Oncol. 2012;23(8):2034–2042.
46. Liu YR, Jiang YZ, Zuo WJ, Yu KD, Shao ZM. PIK3CA mutations define favorable prognostic biomarkers in operable breast cancer: a systematic review and meta-analysis. Onco Targets Ther. 2014;7:543–552.
47. Xu B, Guan Z, Shen Z, et al. Association of phosphatase and tensin homolog low and phosphatidylinositol 3-kinase catalytic subunit alpha gene mutations on outcome in human epidermal growth factor receptor 2-positive metastatic breast cancer patients treated with first-line lapatinib plus paclitaxel or paclitaxel alone. Breast Cancer Res. 2014;16(4):405.
48. 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.
49. Zhao L, Vogt PK. Helical domain and kinase domain mutations in p110α of phosphatidylinositol 3-kinase induce gain of function by different mechanisms. Proc Natl Acad Sci U S A. 2008;105(7):2652–2657.
50. 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.
51. Eichhorn PJ, 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.
52. Kataoka Y, Mukohara T, Shimada H, Saijo N, Hirai M, Minami H. 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.
53. 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.
54. Cizkova M, Dujaric ME, Lehmann-Che J, et al. Outcome impact of PIK3CA mutations in HER2-positive breast cancer patients treated with trastuzumab. Br J Cancer. 2013;108(9):1807–1809.
55. Pogue-Geile KL, Song N, Jeong JH, et al. Intrinsic Subtypes, PIK3CA Mutation, and the Degree of Benefit From Adjuvant Trastuzumab in the NSABP B-31 Trial. J Clin Oncol. Epub January 5, 2015.
56. Loibl S, von Minckwitz G, Schneeweiss A, et al. PIK3CA mutations are associated with lower rates of pathologic complete response to anti-human epidermal growth factor receptor 2 (HER2) therapy in primary HER2-overexpressing breast cancer. J Clin Oncol. 2014;32(29):3212–3220.
57. Majewski IJ, Nuciforo P, Mittempergher L, et al. PIK3CA mutations are associated with decreased benefit to neoadjuvant human epidermal growth factor receptor 2-targeted therapies in breast cancer. J Clin Oncol. Epub January 5, 2015.
58. Toi M, Iwata H, Fujiwara Y, et al. Lapatinib monotherapy in patients with relapsed, advanced, or metastatic breast cancer: efficacy, safety, and biomarker results from Japanese patients phase II studies. Br J Cancer. 2009;101(10):1676–1682.
59. Schneeweiss A, Chia S, Hegg R, et al. Evaluating the predictive value of biomarkers for efficacy outcomes in response to pertuzumab- and trastuzumab-based therapy: an exploratory analysis of the TRYPHAENA study. Breast Cancer Res. 2014;16(4):R73.
60. Baselga J, Cortés J, Kim SB, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012;366(2):109–119.
61. Baselga J, Cortes J, Im SA, et al. Biomarker analyses in CLEOPATRA: a phase III, placebo-controlled study of pertuzumab in human epidermal growth factor receptor 2-positive, first-line metastatic breast cancer. J Clin Oncol. 2014;32(33):3753–3761.
62. Campbell RA, Bhat-Nakshatri P, Patel NM, Constantinidou D, Ali S, Nakshatri H. Phosphatidylinositol 3-kinase/AKT-mediated activation of estrogen receptor alpha: a new model for anti-estrogen resistance. J Biol Chem. 2001;276(13):9817–9824.
63. Mohseni M, Park BH. PIK3CA and KRAS mutations predict for response to everolimus therapy: now that’s RAD001. J Clin Invest. 2010;120(8):2655–2658.
64. Miller TW, Rexer BN, Garrett JT, Arteaga CL. Mutations in the phosphatidylinositol 3-kinase pathway: role in tumor progression and therapeutic implications in breast cancer. Breast Cancer Res. 2011;13(6):224.
65. Janku F, Wheler JJ, Naing A, et al. PIK3CA mutation H1047R is associated with response to PI3K/AKT/mTOR signaling pathway inhibitors in early-phase clinical trials. Cancer Res. 2013;73(1):276–284.
66. Baselga J, Bradbury I, Eidtmann H, et al. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012;379(9816):633–640.
67. Berruti A, Amoroso V, Gallo F, et al. Pathologic complete response as a potential surrogate for the clinical outcome in patients with breast cancer after neoadjuvant therapy: a meta-regression of 29 randomized prospective studies. J Clin Oncol. 2014;32(34):3883–3891.