Skip to main content

Advertisement

SpringerLink
Log in

Mutant p53 in breast cancer: potential as a therapeutic target and biomarker

  • Review
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Objective

The aim of this article is to discuss mutant p53 as a possible therapeutic target and biomarker for breast cancer.

Results

TP53 (p53) is the most frequently mutated gene in invasive breast cancer. Although mutated in 30–35% of all cases, p53 is mutated in approximately 80% of triple-negative (TN) tumors (i.e., tumors negative for ER, PR, and HER2). Because of this high prevalence, mutated p53 is both a potential biomarker and therapeutic target for patients with breast cancer, especially for those with the TN subtype. Although several retrospective studies have investigated a potential prognostic and therapy predictive role for mutant p53 in breast cancer, the results to date are mixed. Thus, at present, mutant p53 cannot be recommended as a prognostic or therapy predictive biomarker in breast cancer. In contrast to the multiple reports on a potential biomarker role, few studies had until recently, investigated mutant p53 as a potential target for breast cancer treatment. In the last decade, however, several compounds have become available which can reactivate mutant p53 protein and convert it to a conformation with wild-type properties. Some of these compounds, especially PRIMA-1, APR-246 PK11007, and COTI-2, have been found to exhibit anticancer activity in preclinical models of breast cancer.

Conclusion

Since p53 is mutated in the vast majority of TN breast cancers, compounds such as APR-246, PK11007, and COTI-2 are potential treatments for patients with this subform of the disease. Further research is necessary to identify a potential biomarker role for mutant p53 in breast cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Lawrence MS, Stojanov P, Mermel CH, Robinson JT, Garraway LA, Golub TR, Meyerson M, Gabriel SB, Lander ES, Getz G (2014) Discovery and saturation analysis of cancer genes across 21 tumour types. Nature 505:495–501

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C, Xie M, Zhang Q, McMichael JF, Wyczalkowski MA, Leiserson MD, Miller CA, Welch JS, Walter MJ, Wendl MC, Ley TJ, Wilson RK, Raphael BJ, Ding L (2013) Mutational landscape and significance across 12 major cancer types. Nature 502:333–339

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Hoadley KA, Yau C, Wolf DM, Cherniack AD, Tamborero D, Ng S, Leiserson MD, Niu B, McLellan MD, Uzunangelov V, Zhang J, Kandoth C, Akbani R, Shen H, Omberg L, Chu A, Margolin AA, Van’t Veer LJ, Lopez-Bigas N, Laird PW, Raphael BJ, Ding L, Robertson AG, Byers LA, Mills GB, Weinstein JN, Van Waes C, Chen Z, Collisson EA, Cancer Genome Atlas Research Network, Benz CC, Perou CM, Stuart JM (2014) Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin. Cell 158:929–944

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Yaeger R, Chatila WK, Lipsyc MD, Hechtman JF, Cercek A, Sanchez-Vega F, Jayakumaran G, Middha S, Zehir A, Donoghue MTA, You D, Viale A, Kemeny N, Segal NH, Stadler ZK, Varghese AM, Kundra R, Gao J, Syed A, Hyman DM, Vakiani E, Rosen N, Taylor BS, Ladanyi M, Berger MF, Solit DB, Shia J, Saltz L, Schultz N (2018) Clinical sequencing defines the genomic landscape of metastatic colorectal cancer. Cancer Cell 33:125–136

    Article  PubMed  CAS  Google Scholar 

  5. Cancer Genome Atlas Network (2012) Comprehensive molecular portraits of human breast tumours. Nature 490:61–70

    Article  CAS  Google Scholar 

  6. Shah SP, Roth A, Goya R, Oloumi A, Ha G, Zhao Y, Turashvili G, Ding J, Tse K, Haffari G, Bashashati A, Prentice LM, Khattra J, Burleigh A, Yap D, Bernard V, McPherson A, Shumansky K, Crisan A, Giuliany R, Heravi-Moussavi A, Rosner J, Lai D, Birol I, Varhol R, Tam A, Dhalla N, Zeng T, Ma K, Chan SK, Griffith M, Moradian A, Cheng SW, Morin GB, Watson P, Gelmon K, Chia S, Chin SF, Curtis C, Rueda OM, Pharoah PD, Damaraju S, Mackey J, Hoon K, Harkins T, Tadigotla V, Sigaroudinia M, Gascard P, Tlsty T, Costello JF, Meyer IM, Eaves CJ, Wasserman WW, Jones S, Huntsman D, Hirst M, Caldas C, Marra MA, Aparicio S (2012) The clonal and mutational evolution spectrum of primary triple-negative breast cancers. Nature 486:395–399

    Article  PubMed  CAS  Google Scholar 

  7. Silwal-Pandit L, Vollan HK, Chin SF, Rueda OM, McKinney S, Osako T, Quigley DA, Kristensen VN, Aparicio S, Børresen-Dale AL, Caldas C, Langerød A (2014) TP53 mutation spectrum in breast cancer is subtype specific and has distinct prognostic relevance. Clin Cancer Res 20:3569–3580

    Article  PubMed  CAS  Google Scholar 

  8. Nik-Zainal S, Davies H, Staaf J, Ramakrishna M, Glodzik D, Zou X, Martincorena I, Alexandrov LB, Martin S, Wedge DC, Van Loo P, Ju YS, Smid M, Brinkman AB, Morganella S, Aure MR, Lingjærde OC, Langerød A, Ringnér M, Ahn SM, Boyault S, Brock JE, Broeks A, Butler A, Desmedt C, Dirix L, Dronov S, Fatima A, Foekens JA, Gerstung M, Hooijer GK, Jang SJ, Jones DR, Kim HY, King TA, Krishnamurthy S, Lee HJ, Lee JY, Li Y, McLaren S, Menzies A, Mustonen V, O’Meara S, Pauporté I, Pivot X, Purdie CA, Raine K, Ramakrishnan K, Rodríguez-González FG, Romieu G, Sieuwerts AM, Simpson PT, Shepherd R, Stebbings L, Stefansson OA, Teague J, Tommasi S, Treilleux I, Van den Eynden GG, Vermeulen P, Vincent-Salomon A, Yates L, Caldas C, Veer LV, Tutt A, Knappskog S, Tan BK, Jonkers J, Borg Å, Ueno NT, Sotiriou C, Viari A, Futreal PA, Campbell PJ, Span PN, Van Laere S, Lakhani SR, Eyfjord JE, Thompson AM, Birney E, Stunnenberg HG, van de Vijver MJ, Martens JW, Børresen-Dale AL, Richardson AL, Kong G, Thomas G, Stratton MR (2016) Landscape of somatic mutations in 560 breast cancer whole-genome sequences. Nature 534:47–54

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Kriegsmann M, Endris V, Wolf T, Pfarr N, Stenzinger A, Loibl S, Denkert C, Schneeweiss A, Budczies J, Sinn P, Weichert W (2014) Mutational profiles in triple-negative breast cancer defined by ultradeep multigene sequencing show high rates of PI3 K pathway alterations and clinically relevant entity subgroup specific differences. Oncotarget 5:9952–9965

    Article  PubMed  PubMed Central  Google Scholar 

  10. Kastenhuber ER, Lowe SW (2017) Putting p53 in context. Cell 170:1062–1078

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  11. Bieging KT, Mello SS, Attardi LD (2014) Unravelling mechanisms of p53-mediated tumour suppression. Nat Rev Cancer 14:359–370

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Kruiswijk F, Labuschagne CF, Vousden KH (2015) P53 in survival, death and metabolic health: a lifeguard with a licence to kill. Nat Rev Mol Cell Biol 16:393–405

    Article  PubMed  CAS  Google Scholar 

  13. Holstege H, Horlings HM, Velds A, Langerød A, Børresen-Dale AL, van de Vijver MJ, Nederlof PM, Jonkers J (2010) BRCA1-mutated and basal-like breast cancers have similar aCGH profiles and a high incidence of protein truncating TP53 mutations. BMC Cancer 10:654

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. McGranahan N, Favero F, de Bruin EC, Birkbak NJ, Szallasi Z, Swanton C (2015) Clonal status of actionable driver events and the timing of mutational processes in cancer evolution. Sci Transl Med 7:283ra54

    Article  PubMed  PubMed Central  Google Scholar 

  15. Yates LR, Gerstung M, Knappskog S, Desmedt C, Gundem G, Van Loo P, Aas T, Alexandrov LB, Larsimont D, Davies H, Li Y, Ju YS, Ramakrishna M, Haugland HK, Lilleng PK, Nik-Zainal S, McLaren S, Butler A, Martin S, Glodzik D, Menzies A, Raine K, Hinton J, Jones D, Mudie LJ, Jiang B, Vincent D, Greene-Colozzi A, Adnet PY, Fatima A, Maetens M, Ignatiadis M, Stratton MR, Sotiriou C, Richardson AL, Lønning PE, Wedge DC, Campbell PJ (2015) Subclonal diversification of primary breast cancer revealed by multiregion sequencing. Nat Med 21:751–759

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Casasent AK, Schalck A, Gao R, Sei E, Long A, Pangburn W, Casasent T, Meric-Bernstam F, Edgerton ME, Navin NE (2018) Multiclonal invasion in breast tumors identified by topographic single cell sequencing. Cell 172:205–217

    Article  PubMed  CAS  Google Scholar 

  17. Done SJ, Eskandarian S, Bull S, Redston M, Andrulis IL (2001) p53 missense mutations in microdissected high-grade ductal carcinoma in situ of the breast. J Natl Cancer Inst 93:700–704

    Article  PubMed  CAS  Google Scholar 

  18. Ful Zhou W, Muggerud AA, Vu P, Due EU, Sørlie T, Børresen-Dale AL, Wärnberg F, Langerød A (2009) Full sequencing of TP53 identifies identical mutations within in situ and invasive components in breast cancer suggesting clonal evolution. Mol Oncol 3:214–219

    Article  CAS  Google Scholar 

  19. Done SJ, Arneson CR, Ozçelik H, Redston M, Andrulis IL (2001) P53 missense mutations in microdissected high-grade ductal carcinoma in situ of the breast. Breast Cancer Res Treat 65(111–8):53

    Google Scholar 

  20. Done SJ, Arneson NC, Ozçelik H, Redston M, Andrulis IL (1998) p53 mutations in mammary ductal carcinoma in situ but not in epithelial hyperplasias. Cancer Res 58:785–789

    PubMed  CAS  Google Scholar 

  21. Troester MA, Hoadley KA, D’Arcy M et al (2016) DNA defects, epigenetics and gene expression in cancer-adjacent breast: a study from the Cancer Genome Atlas. NPJ Breast Cancer 2:160007. https://doi.org/10.1038/npjcancer.2016.7

    Article  Google Scholar 

  22. Duffy MJ, McGowan PM, Crown J (2012) Targeted therapy for triple-negative breast cancer: where are we? Int J Cancer 131:2471–2477

    Article  PubMed  CAS  Google Scholar 

  23. Lo Nigro C, Vivenza D, Monteverde M, Lattanzio L, Gojis O, Garrone O, Comino A, Merlano M, Quinlan PR, Syed N, Purdie CA, Thompson A, Palmieri C, Crook T (2012) High frequency of complex TP53 mutations in CNS metastases from breast cancer. Br J Cancer 106:397–404

    Article  PubMed  CAS  Google Scholar 

  24. Bykov VJ, Wiman KG (2014) Mutant p53 reactivation by small molecules makes its way to the clinic. FEBS Lett 588:2622–2627

    Article  PubMed  CAS  Google Scholar 

  25. Zhao D, Tahaney WM, Mazumdar A, Savage MI, Brown PH (2017) Molecularly targeted therapies for p53-mutant cancers. Cell Mol Life Sci 74:4171–4187

    Article  PubMed  CAS  Google Scholar 

  26. Duffy MJ, Synnott NC, Crown J (2017) Mutant p53 as a target for cancer treatment. Eur J Cancer 83:258–265

    Article  PubMed  CAS  Google Scholar 

  27. Bykov VJ, Issaeva N, Shilov A, Hultcrantz M, Pugacheva E, Chumakov P, Bergman J, Wiman KG, Selivanova G (2002) Restoration of the tumor suppressor function to mutant p53 by a low-molecular-weight compound. Nat Med 8:282–288

    Article  PubMed  CAS  Google Scholar 

  28. Bykov VJ, Zache N, Stridh H, Westman J, Bergman J, Selivanova G, Wiman KG (2005) PRIMA-1(MET) synergizes with cisplatin to induce tumor cell apoptosis. Oncogene 24:3484–3491

    Article  PubMed  CAS  Google Scholar 

  29. Liang Y, Besch-Williford C, Benakanakere I, Hyder SM (2007) Re-activation of the p53 pathway inhibits in vivo and in vitro growth of hormone-dependent human breast cancer cells. Int J Oncol 31:777–784

    PubMed  CAS  Google Scholar 

  30. Liang Y, Besch-Williford C, Hyder SM (2009) PRIMA-1 inhibits growth of breast cancer cells by re-activating mutant p53 protein. Int J Oncol 35:1015–1023

    PubMed  CAS  Google Scholar 

  31. Liang Y, Besch-Williford C, Benakanakere I, Thorpe PE, Hyder SM (2011) Targeting mutant p53 protein and the tumor vasculature: an effective combination therapy for advanced breast tumors. Breast Cancer Res Treat 125:407–420

    Article  PubMed  CAS  Google Scholar 

  32. Synnott NC, Murray A, McGowan PM, Kiely M, Kiely PA, O’Donovan N, O’Connor DP, Gallagher WM, Crown J, Duffy MJ (2017) Mutant p53: a novel target for the treatment of patients with triple-negative breast cancer? Int J Cancer 140:234–246

    Article  PubMed  CAS  Google Scholar 

  33. Synnott NC, Murray AM, O’Donovan N, Duffy MJ, Crown J (2017) Combined treatment using the anti-p53 drug, APR-246 and eribulin: synergistic growth inhibition in p53-mutated breast cancer cells. J Clin Oncol 35:e14098

    Article  Google Scholar 

  34. Saha MN, Jiang H, Yang Y, Reece D, Chang H (2013) PRIMA-1Met/APR-246 displays high antitumor activity in multiple myeloma by induction of p73 and Noxa. Mol Cancer Ther 12:2331–2341

    Article  PubMed  CAS  Google Scholar 

  35. Sobhani M, Abdi J, Chen C, Chang H (2015) PRIMA-1Met induces apoptosis in Waldenström’s Macroglobulinemia cells independent of p53. Cancer Biol Ther 16:799–806

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Rökaeus N, Shen J, Eckhardt I, Bykov VJ, Wiman KG, Wilhelm MT (2010) PRIMA-1(MET)/APR-246 targets mutant forms of p53 family members p63 and p73. Oncogene 29:6442–6451

    Article  PubMed  CAS  Google Scholar 

  37. Gorrini C, Harris IS, Mak TW (2013) Modulation of oxidative stress as an anticancer strategy. Nat Rev Drug Discov 12:931–947

    Article  PubMed  CAS  Google Scholar 

  38. Peng X, Zhang MQ, Conserva F, Hosny G, Selivanova G, Bykov VJ, Arnér ES, Wiman KG (2013) APR-246/PRIMA-1MET inhibits thioredoxin reductase 1 and converts the enzyme to a dedicated NADPH oxidase. Cell Death Dis 4:e881

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Liu DS, Duong CP, Haupt S, Montgomery KG, House CM, Azar WJ, Pearson HB, Fisher OM, Read M, Guerra GR, Haupt Y, Cullinane C, Wiman KG, Abrahmsen L, Phillips WA, Clemons NJ (2017) Inhibiting the system xC-/glutathione axis selectively targets cancers with mutant-p53 accumulation. Nat Commun 8:14844

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Lehmann S, Bykov VJ, Ali D, Andrén O, Cherif H, Tidefelt U, Uggla B, Yachnin J, Juliusson G, Moshfegh A, Paul C, Wiman KG, Andersson PO (2012) Targeting p53 in vivo: a first-in-human study with p53-targeting compound APR-246 in refractory hematologic malignancies and prostate cancer. J Clin Oncol 30:3633–3639

    Article  PubMed  CAS  Google Scholar 

  41. Gourley C, Green J, Gabra H, Vergote I, Basu B, Brenton JD, Björklund U, Smith A, Von Euler M (2016) PISARRO: a EUTROC phase Ib study of APR-246 in combination with carboplatin (C) and pegylated liposomal doxorubicin (PLD) in platinum sensitive relapsed high grade serous ovarian cancer (HGSOC). J Clin Oncol 34 (suppl; abstr 5571)

  42. Gourley C, Gabra H, Vergote I, Basu B, Brenton J, Von Euler M, Björklund U, Smith AM, Green J (2015) EUTROC PiSARRO: a phase Ib study combining APR-246 with standard chemotherapy in platinum sensitive relapsed high grade serous ovarian carcinoma (HGSOC). J Clin Oncol 33 (suppl; abstr TPS5605)

  43. Bauer MR, Joerger AC, Fersht AR (2016) 2-Sulfonylpyrimidines: mild alkylating agents with anticancer activity toward p53-compromised cells. Proc Natl Acad Sci U S A 113:E5271–E5280

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Synnott NC, Bauer MR, Madden S, Murray A, Klinger R, O’Donovan N, O’Connor D, Gallagher WM, Crown J, Fersht AR, Duffy MJ (2018) Mutant p53 as a therapeutic target for the treatment of triple-negative breast cancer: preclinical investigation with the anti-p53 drug, PK11007. Cancer Lett 414:99–106

    Article  PubMed  CAS  Google Scholar 

  45. Synnott NC, Bauer MR, Madden SF, Murray AM, Klinger R, O’Donovan N, O’Connor D, Gallagher WM, Crown J, Fersht AR, Duffy MJ (2017) Targeting mutant p53 with PK11007: a new approach for the treatment of patients with triple-negative breast cancer? J Clin Oncol 35 (suppl; abstr e14099)

  46. Salim KY, Maleki Vareki S, Danter WR, Koropatnick J (2016) COTI-2, a novel small molecule that is active against multiple human cancer cell lines in vitro and in vivo. Oncotarget 7:41363–41379

    Article  PubMed  PubMed Central  Google Scholar 

  47. http://www.pharmaceutical-technology.com/news/newscritical-outcome-seeks-fda-orphan-drug-status-for-ovarian-cancer-drug-coti-2-4210077/. Accessed 6 Apr 2014

  48. Thor AD, Moore DH II, Edgerton SM, Kawasaki ES, Reihsaus E, Lynch HT, Marcus JN, Schwartz L, Chen LC, Mayall BH et al (1992) Accumulation of p53 tumor suppressor gene protein: an independent marker of prognosis in breast cancers. J Natl Cancer Inst 84:845–855

    Article  PubMed  CAS  Google Scholar 

  49. Isola J, Visakorpi T, Holli K, Kallioniemi OP (1992) Association of overexpression of tumor suppressor protein p53 with rapid cell proliferation and poor prognosis in node-negative breast cancer patients. J Natl Cancer Inst 84:1109–1114

    Article  PubMed  CAS  Google Scholar 

  50. Lipponen P, Ji H, Aaltomaa S, Syrjänen S, Syrjänen K (1993) p53 protein expression in breast cancer as related to histopathological characteristics and prognosis. Int J Cancer 55:51–56

    Article  PubMed  CAS  Google Scholar 

  51. Pharoah PD, Day NE, Caldas C (1999) Somatic mutations in the p53 gene and prognosis in breast cancer: a meta-analysis. Br J Cancer 80:1968–1973

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Olivier M, Langerød A, Carrieri P, Bergh J, Klaar S, Eyfjord J, Theillet C, Rodriguez C, Lidereau R, Bièche I, Varley J, Bignon Y, Uhrhammer N, Winqvist R, Jukkola-Vuorinen A, Niederacher D, Kato S, Ishioka C, Hainaut P, Børresen-Dale AL (2006) The clinical value of somatic TP53 gene mutations in 1,794 patients with breast cancer. Clin Cancer Res 12:1157–1167

    Article  PubMed  CAS  Google Scholar 

  53. Petitjean A, Achatz MI, Borresen-Dale AL, Hainaut P, Olivier M (2007) TP53 mutations in human cancers: functional selection and impact on cancer prognosis and outcomes. Oncogene 26:2157–2165

    Article  PubMed  CAS  Google Scholar 

  54. Langerød A, Zhao H, Borgan Ø, Nesland JM, Bukholm IR, Ikdahl T, Kåresen R, Børresen-Dale AL, Jeffrey SS (2007) TP53 mutation status and gene expression profiles are powerful prognostic markers of breast cancer. Breast Cancer Res 9:R30

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Vijayakumaran R, Tan KH, Miranda PJ, Haupt S, Haupt Y (2015) Regulation of mutant p53 protein expression. Front Oncol 5:284. https://doi.org/10.3389/fonc.2015.00284

    Article  PubMed  PubMed Central  Google Scholar 

  56. Wynford-Thomas D (1992) P53 in tumour pathology: can we trust immunocytochemistry? J Pathol 166:329–330

    Article  PubMed  CAS  Google Scholar 

  57. Bouchalova P, Nenutil R, Muller P, Hrstka R, Appleyard MV, Murray K, Jordan LB, Purdie CA, Quinlan P, Thompson AM, Vojtesek B, Coates PJ (2014) Mutant p53 accumulation in human breast cancer is not an intrinsic property or dependent on structural or functional disruption but is regulated by exogenous stress and receptor status. J Pathol 233:238–246

    Article  PubMed  CAS  Google Scholar 

  58. Save V, Nylander K, Hall PA (1998) Why is p53 protein stabilized in neoplasia? some answers but many more questions? J Pathol 184:348–350

    Article  PubMed  CAS  Google Scholar 

  59. Coates AS, Millar EK, O’Toole SA, Molloy TJ, Viale G, Goldhirsch A, Regan MM, Gelber RD, Sun Z, Castiglione-Gertsch M, Gusterson B, Musgrove EA, Sutherland RL (2012) Prognostic interaction between expression of p53 and estrogen receptor in patients with node-negative breast cancer: results from IBCSG Trials VIII and IX. Breast Cancer Res 14:R143

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Lara JF, Thor AD, Dressler LG, Broadwater G, Bleiweiss IJ, Edgerton S, Cowan D, Goldstein LJ, Martino S, Ingle JN, Henderson IC, Norton L, Winer EP, Hudis CA, Ellis MJ, Berry DA, Hayes DF (2011) p53 Expression in node-positive breast cancer patients: results from the Cancer and Leukemia Group B 9344 Trial (159905). Clin Cancer Res 17:5170–5178

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Bonnefoi H, Piccart M, Bogaerts J, Mauriac L, Fumoleau P, Brain E, Petit T, Rouanet P, Jassem J, Blot E, Zaman K, Cufer T, Lortholary A, Lidbrink E, Andre S, Litiere S, Lago LD, Becette V, Cameron DA, Bergh J, Iggo R (2011) TP53 status for prediction of sensitivity to taxane versus non-taxane neoadjuvant chemotherapy in breast cancer (EORTC 10994/BIG 1-00): a randomised phase 3 trial. Lancet Oncol 12:527–539

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Fernandez-Cuesta L, Oakman C, Falagan-Lotsch P, Smoth KS, Quinaux E, Buyse M, Dolci MS, De Azambuja E, Hainaut P, Dell’orto P, Larsimont D, Francis PA, Crown J, Piccart-Gebhart M, Viale G, Di Leo A, Olivier M (2012) Prognostic and predictive value of TP53 mutations in node-positive breast cancer patients treated with anthracycline- or anthracycline/taxane based adjuvant therapy: results from the BIG 02-98 phase III trial. Breast Cancer Res 14:R70

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Fountzilas G, Giannoulatou E, Alexopoulou Z, Zagouri F, Timotheadou E, Papadopoulou K, Lakis S, Bobos M, Poulios C, Sotiropoulou M, Lyberopoulou A, Gogas H, Pentheroudakis G, Pectasides D, Koutras A, Christodoulou C, Papandreou C, Samantas E, Papakostas P, Kosmidis P, Bafaloukos D, Karanikiotis C, Dimopoulos MA, Kotoula V (2016) TP53 mutations and protein immunopositivity may predict for poor outcome but also for trastuzumab benefit in patients with early breast cancer treated in the adjuvant setting. Oncotarget 7:32731–32753

    Article  PubMed  PubMed Central  Google Scholar 

  64. Marcel V, Dichtel-Danjoy ML, Sagne C, Hafsi H, Ma D, Ortiz-Cuaran S, Olivier M, Hall J, Mollereau B, Hainaut P, Bourdon JC (2011) Biological functions of p53 isoforms through evolution: lessons from animal and cellular models. Cell Death Differ 18:1815–1824

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Bourdon JC, Khoury MP, Diot A, Baker L, Fernandes K, Aoubala M, Quinlan P, Purdie CA, Jordan LB, Prats AC, Lane DP, Thompson AM (2011) p53 mutant breast cancer patients expressing p53γ have as good a prognosis as wild-type p53 breast cancer patients. Breast Cancer Res 13:R7

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Avery-Kiejda KA, Morten B, Wong-Brown MW, Mathe A, Scott RJ (2014) The relative mRNA expression of p53 isoforms in breast cancer is associated with clinical features and outcome. Carcinogenesis 35:586–596

    Article  PubMed  CAS  Google Scholar 

  67. Hwang LA, Phang BH, Liew OW, Iqbal J, Koh XH, Koh XY, Othman R, Xue Y, Richards AM, Lane DP, Sabapathy K (2018) Monoclonal antibodies against specific p53 hotspot mutants as potential tools for precision medicine. Cell Rep 22:299–312

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors wish to thank the Science Foundation Ireland; the Strategic Research Cluster Award (08/SRC/B1410) to Molecular Therapeutics for Cancer Ireland; the Clinical Cancer Research Trust and the Irish Cancer Society Collaborative Cancer Research Centre BREAST-PREDICT programme (CCRC13GAL); and the Health Research Board Clinician Scientist Award (CSA/2007/11).

Disclosures

None.

Author information

Authors and Affiliations

  1. UCD Clinical Research Centre, St. Vincent’s University Hospital, Dublin 4, Ireland

    Michael J. Duffy

  2. UCD School of Medicine, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland

    Michael J. Duffy & Naoise C. Synnott

  3. Department of Medical Oncology, St. Vincent’s University Hospital, Dublin, Ireland

    John Crown

Authors
  1. Michael J. Duffy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Naoise C. Synnott
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. John Crown
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael J. Duffy.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Duffy, M.J., Synnott, N.C. & Crown, J. Mutant p53 in breast cancer: potential as a therapeutic target and biomarker. Breast Cancer Res Treat 170, 213–219 (2018). https://doi.org/10.1007/s10549-018-4753-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-018-4753-7

Keywords

Search

Navigation