Leczenie systemowe chorych na raka piersi z nadekspresją HER2. Część I

• Authors: Sylwia Dębska

Title variants

EN

Systemic treatment of HER2+ breast cancer patients. Part 1

• Languages of publication: EN PL

Abstracts

EN

In Poland, morbidity associated with breast cancer has been increasing over the past 40 years. Current advances in our understanding of breast cancer biology preclude considering this condition as a homogenous nosologic entity. Several subtypes of breast cancer: luminal A (ER+, PR+, HER2-), luminal B (ER+, PR+, HER2+), HER2-dependent (ER-, PR-, HER2+) and the so-called triple-negative or basic (ER-, PR-, HER2-) differ in clinical course and prognosis and require an individualized therapeutic approach. HER2 receptor is one of a family of human growth factor receptors. It may become expressed in different tissues, participating in growth and differentiation of cells. HER2 overexpression in breast cancer cells correlates with worse prognosis, but also enables implementation of targeted, anti-HER2 molecular therapies. As estimated, about 25% of breast tumors are HER2-positive and in these patients the use of “targeted” therapy should be considered. Therefore, at present, standard histological study of breast cancer should include immunohistochemical assessment of HER2 receptor expression. Patients with equivocal result of the IHC study (HER2 2+) require quantitative analysis of HER2 gene copies in cancer cells using the FISH technique. Only patients with HER2 receptor overexpression (HER2 3+) or HER2 gene amplification are candidates for targeted molecular treatment. The first drug of this kind is monoclonal antibody trastuzumab, binding with the HER2 receptor and blocking HER2-dependent intracellular processes, while triggering a cytotoxic cellular antibody-dependent immune reaction directed against cancer cells.

PL

W Polsce od 40 lat obserwuje się rosnącą umieralność z powodu raka piersi. Poszerzająca się wiedza o biologii raka piersi nie pozwala obecnie postrzegać tego nowotworu jako jednorodnej jednostki chorobowej. Różne podtypy raka piersi - luminalny A (ER+ lub PR+ i HER2-), luminalny B (ER+ lub PR+ i HER2+), HER2-zależny (ER- i PR- i HER2+) czy tzw. potrójnie ujemny/podstawny (ER- i PR- i HER2-) - charakteryzują się odmiennym przebiegiem klinicznym i rokowaniem, a także wymagają indywidualnej strategii terapeutycznej. Receptor HER2 należy do rodziny ludzkich receptorów dla czynników wzrostu. Może ulegać ekspresji w różnych tkankach, gdzie zaangażowany jest we wzrost i różnicowanie komórek. Nadekspresja HER2 w komórkach raka piersi związana jest z gorszym rokowaniem, ale także z możliwością zastosowania u tych chorych terapii ukierunkowanych molekularnie anty-HER2. Szacuje się, że około 25% guzów piersi jest HER2-pozytywnych - u tych chorych należy rozważyć wdrożenie leczenia „celowanego”. Z tego względu w chwili obecnej standardowym elementem każdego badania histopatologicznego raka piersi powinna być immunohisto-chemiczna ocena ekspresji receptora HER2. U chorych z niejednoznacznym wynikiem badania IHC (HER2 2+) należy ocenić ilość kopii genu HER2 w komórkach raka piersi metodą FISH. Tylko chore z nadekspresją receptora (HER2 3+) albo amplifikacją genu HER2 kwalifikują się do leczenia ukierunkowanego molekularnie. Pierwszym lekiem z tej grupy jest przeciwciało monoklonalne trastuzumab, które po połączeniu z HER2 nie tylko blokuje procesy wewnątrzkomórkowe zależne od pobudzenia receptora, ale także uruchamia odpowiedź immunologiczną przeciw komórkom nowotworowym w mechanizmie cytotoksyczności komórkowej zależnej od przeciwciał.

Keywords

EN

HER receptor family; HER2 gene amplification; HER2 overexpression; amplifikacja genu HER2; antibody-dependent cellular cytotoxic reaction; cytotoksyczność komórkowa zależna od przeciwciał; czynniki prognostyczne w raku piersi; nadekspresja HER2; prognostic factors in breast cancer; rodzina receptorów HER; trastuzumab

Discipline

• MEDICINE: MEDICINE

• Publisher: Medical Communications
• Journal: Current Gynecologic Oncology
• Year: 2011
• Volume: 9
• Issue: 4
• Pages: 227-237

Contributors

author

Sylwia Dębska

• Klinika Chemioterapii Nowotworów Katedry Onkologii Uniwersytetu Medycznego w Łodzi. Kierownik Kliniki: dr hab. n. med. Piotr Potemski, prof. UM. Correspondence to: Szpital Specjalistyczny im. M. Kopernika w Łodzi, ul. Paderewskiego 4, 93-509 Łódź, tel.: [phone], faks: 42 689 54 32

References

• 1. Frogne T, Laenkholm A.V, Lyng M.B. i wsp.: 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: R11.
• 2. Ross J.S., Slodkowska E.A., Symmans WF. i wsp.: The HER-2 receptor and breast cancer: ten years of targeted anti-HER-2 therapy and personalized medicine. Oncologist 2009; 14: 320-368.
• 3. Schechter A.L., Stern D.F., Vaidyanathan L. i wsp.: The neu oncogene: an erb-B-related gene encoding a 185,000-Mr tumour antigen. Nature 1984; 312: 513-516.
• 4. Scaltriti M., Rojo F., Ocańa A. i wsp.: Expression of p95HER2, a truncated form of the HER2 receptor, and response to anti-HER2 therapies in breast cancer. J. Natl Cancer Inst. 2007; 99: 628-638.
• 5. Brennan P.J., Kumagai T., Berezov A. i wsp.: HER2/Neu: mechanisms of dimerization/oligomerization. Oncogene 2000; 19: 6093-6101.
• 6. Koutras A.K., Evans T.R.: The epidermal growth factor receptor family in breast cancer. Onco. Targets Ther. 2008; 1: 5-19.
• 7. Mukohara T.: Mechanisms of resistance to anti-human epidermal growth factor receptor 2 agents in breast cancer. Cancer Sci. 2011; 102: 1-8.
• 8. Riese D.J., Kim E.D., Elenius K. i wsp.: The epidermal growth factor receptor couples transforming growth factor-alpha, heparin-binding epidermal growth factor-like factor, and amphiregulin to Neu, ErbB-3, and ErbB-4. J. Biol. Chem. 1996; 271: 20047-20052.
• 9. Knowlden J.M., Gee J.M., Seery L.T. i wsp.: C-erbB3 and c-erbB4 expression is a feature of the endocrine responsive phenotype in clinical breast cancer. Oncogene 1998; 17: 1949-1957.
• 10. Culouscou J.M., Carlton G.W., Aruffo A.: HER4 receptor activation and phosphorylation of Shc proteins by recombinant heregulin-Fc fusion proteins. J. Biol. Chem. 1995; 270: 12857-12863.
• 11. Li X., Perez L., Pan Z., Fan H.: The transmembrane domain of TACE regulates protein ectodomain shedding. Cell Res. 2007; 17: 985-998.
• 12. Sunnarborg S.W, Hinkle C.L., Stevenson M. i wsp.: Tumor necrosis factor-alpha converting enzyme (TACE) regulates epidermal growth factor receptor ligand availability. J. Biol. Chem. 2002; 227: 12838-12845.
• 13. Pedersen K., Angelini P.D., Laos S. i wsp.: A naturally occurring HER2 carboxy-terminal fragment promotes mammary tumor growth and metastasis. Mol. Cell Biol. 2009; 29: 3319-3331.
• 14. Spector N.L., Blackwell K.L.: Understanding the mechanisms behind trastuzumab therapy for human epidermal growth factor receptor 2-positive breast cancer. J. Clin. Oncol. 2009; 27: 5838-5847.
• 15. Lenferink A.E., Pinkas-Kramarski R., van de Poll M.L. i wsp.: Differential endocytic routing of homo- and hetero-dimeric ErbB tyrosine kinases confers signaling superiority to receptor heterodimers. EMBO J. 1998; 17: 3385-3397.
• 16. Burden S., Yarden Y.: Neuregulins and their receptors: a versatile signaling module in organogenesis and oncogenesis. Neuron 1997; 18: 847-855.
• 17. Cho H.S., Mason K., Ramyar K.X. i wsp.: Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab. Nature 2003; 421: 756-760.
• 18. Fleishman S.J., Schlessinger J., Ben-Tal N.: A putative molec-ular-activation switch in the transmembrane domain of erbB2. Proc. Natl Acad. Sci. USA 2002; 99: 15937-15940.
• 19. Bargmann C.I., Hung M.C., Weinberg R.A.: Multiple independent activations of the neu oncogene by a point mutation altering the transmembrane domain of p185. Cell 1986; 45: 649-657.
• 20. Segatto O., King C.R., Pierce J.H. i wsp.: Different structural alterations upregulate in vitro tyrosine kinase activity and transforming potency of the erbB-2 gene. Mol. Cell. Biol. 1988; 8: 5570-5574.
• 21. Arribas J., Parra-Palau J.L., Pedersen K: HER2 fragmentation and breast cancer stratification. Clin. Cancer Res. 2010: 16: 4071-4073.
• 22. Christianson T.A., Doherty J.K., Lin Y.J. i wsp.: NH2-termi-nally truncated Her-2/neu protein: relationship with shedding of the extracellular domain and with prognostic factors in breast cancer. Cancer Res. 1998; 58: 5123-5129.
• 23. Singer C.F., Kostler WJ., Hudelist G.: Predicting the efficacy of trastuzumab-based therapy in breast cancer: current standards and future strategies. Biochim. Biophys. Acta. 2008; 1786: 105-113.
• 24. Anido J., Scaltriti M., Bech Serra J.J. i wsp.: Biosynthesis of tumorigenic HER2 C-terminal fragments by alternative initiation of translation. EMBO J. 2006; 25: 3234-3244.
• 25. Saez R., Molina M.A., Ramsey E.E. i wsp.: p95HER-2 predicts worse outcome in patients with HER-2-positive breast cancer. Clin. Cancer Res. 2006; 12: 424-431.
• 26. Adamson E.D.: Oncogenes in development. Development 1987; 99: 449-471.
• 27. Lemoine N.R., Jain S., Silvestre F. i wsp.: Amplification and overexpression of the EGF receptor and c-erbB-2 protooncogenes in human stomach cancer. Br. J. Cancer 1991; 64: 79-83.
• 28. van Dam P.A., Vergote I.B., Lowe D.G. i wsp.: Expression of c-erbB-2, c-myc, and c-ras oncoproteins, insulin-like growth factor receptor I, and epidermal growth factor receptor in ovarian carcinoma. J. Clin. Pathol. 1994; 47: 914-919.
• 29. Grushko T.A., Filiaci VL., Mundt A.J. i wsp.: An exploratory analysis of HER-2 amplification and overexpression in advanced endometrial carcinoma: a gynecologic oncology group study. Gynecol. Oncol. 2008; 108: 3-9.
• 30. Slamon D.J., Godolphin W., Jones L.A. i wsp.: Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 1989; 244: 707-712.
• 31. Tiwari R.K., Borgen P.I., Wong G.Y. i wsp.: HER-2/neu amplification and overexpression in primary human breast cancer is associated with early metastasis. Anticancer Res. 1992; 12: 419-425.
• 32. Borg A., Tandon A.K., Sigurdsson H. i wsp.: HER-2/neu amplification predicts poor survival in node-positive breast cancer. Cancer Res. 1990; 50: 4332-4337.
• 33. Tandon A.K., Clark G.M., Chamness G.C. i wsp.: HER-2/neu oncogene protein and prognosis in breast cancer. J. Clin. Oncol. 1989; 7: 1120-1128.
• 34. Bacus S.S., Ruby S.G., Weinberg D.S. i wsp.: HER-2/neu oncogene expression and proliferation in breast cancers. Am. J. Pathol. 1990; 137: 103-111.
• 35. Hofmann M., Stoss O., Gaiser T. i wsp.: Central HER2 IHC and FISH analysis in a trastuzumab (Herceptin) phase II monotherapy study: assessment of test sensitivity and impact of chromosome 17 polysomy. J. Clin. Pathol. 2008; 61: 89-94.
• 36. Kraus M.H., Popescu N.C., Amsbaugh S.C., King C.R.: Overexpression of the EGF receptor-related proto-oncogene erbB-2 in human mammary tumor cell lines by different molecular mechanisms. EmBo J. 1987; 6: 605-610.
• 37. Parkes H.C., Lillycrop K., Howell A., Craig R.K.: C-erbB2 mRNA expression in human breast tumours: comparison with c-erbB2 DNA amplification and correlation with prognosis. Br. J. Cancer 1990; 61: 39-45.
• 38. Berger M.S., Locher G.W., Saurer S. i wsp.: Correlation of c-erbB-2 gene amplification and protein expression in human breast carcinoma with nodal status and nuclear grading. Cancer Res. 1988; 48: 1238-1243.
• 39. Ellis C.M., Dyson M.J., Stephenson T.J., Maltby E.L.: HER2 amplification status in breast cancer: a comparison between immunohistochemical staining and fluorescence in situ hybridisation using manual and automated quantitative image analysis scoring techniques. J. Clin. Pathol. 2005; 58: 710-714.
• 40. Paterson M.C., Dietrich K.D., Danyluk J. i wsp.: Correlation between c-erbB-2 amplification and risk of recurrent disease in node-negative breast cancer. Cancer Res. 1991; 51: 556-567.
• 41. Sassen A., Rochon J., Wild P. i wsp.: Cytogenetic analysis of HER1/EGFR, HER2, HER3 and HER4 in 278 breast cancer patients. Breast Cancer Res. 2008; 10: R2.
• 42. Pawlowski V, Revillion F., Hebbar M. i wsp.: Prognostic value of the type I growth factor receptors in a large series of human primary breast cancers quantified with a real-time reverse transcription-polymerase chain reaction assay. Clin. Cancer Res. 2000; 6: 4217-4225.
• 43. Lee Y., Cho S., Seo J.H. i wsp.: Correlated expression of erbB-3 with hormone receptor expression and favorable clinical outcome in invasive ductal carcinomas of the breast. Am. J. Clin. Pathol. 2007; 128: 1041-1049.
• 44. Slamon D.J., Clark G.M., Wong S.G. i wsp.: Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987; 235: 177-182.
• 45. Gasparini G., Gullick WJ., Bevilacqua P. i wsp.: Human breast cancer: prognostic significance of the c-erbB-2 oncoprotein compared with epidermal growth factor receptor, DNA ploidy, and conventional pathologic features. J. Clin. Oncol. 1992; 10: 686-695.
• 46. Voduc K.D., Cheang M.C., Tyldesley S. i wsp.: Breast cancer subtypes and the risk of local and regional relapse. J. Clin. Oncol. 2010; 28: 1684-1691.
• 47. Andrulis I.L., Bull S.B., Blackstein M.E. i wsp.: Neu/erbB-2 amplification identifies a poor-prognosis group of women with node-negative breast cancer. Toronto Breast Cancer Study Group. J. Clin. Oncol. 1998; 16: 1340-1349.
• 48. Potemski P., Płuciennik E., Bednarek A.K. i wsp.: A comparative assessment of HER2 status in operable breast cancer by real-time RT-PCR and by immunohistochemistry. Med. Sci. Monit. 2006; 12: MT57-MT61.
• 49. McCann A.H., Dervan P.A., O’Regan M. i wsp.: Prognostic significance of c-erbB-2 and estrogen receptor status in human breast cancer. Cancer Res. 1991; 51: 3296-3303.
• 50. Ainsworth R., Bartlett J.M., Going J.J. i wsp.: IHC for HER2 with CBE356 antibody is a more accurate predictor of HER2 gene amplification by FISH than HercepTest in breast carcinoma. J. Clin. Pathol. 2005; 58: 1086-1090.
• 51. Somerville J.E., Clarke L.A., Biggart J.D.: c-erbB-2 overexpression and histological type of in situ and invasive breast carcinoma. J. Clin. Pathol. 1992; 45: 16-20.
• 52. Paik S., Hazan R., Fisher E.R. i wsp.: Pathologic findings from the national surgical adjuvant breast and bowel project: prognostic significance of erbB-2 protein overexpression in primary breast cancer. J. Clin. Oncol. 1990; 8: 103-112.
• 53. Carr J.A., Havstad S., Zarbo R.J. i wsp.: The association of HER-2/neu amplification with breast cancer recurrence. Arch. Sur. 2000; 135: 1469-1474.
• 54. Leong A.S., Sormunen R.T., Vinyuvat S. i wsp.: Biologic markers in ductal carcinoma in situ and concurrent infiltrating carcinoma. A comparison of eight contemporary grading systems. Am. J. Clin. Pathol. 2001; 115: 709-718.
• 55. Siegel P.M., Ryan E.D., Cardiff R.D., Muller WJ.: Elevated expression of activated forms of Neu/ErbB-2 and ErbB-3 are involved in the induction of mammary tumors in transgenic mice: implications for human breast cancer. EMBO J. 1999; 18: 2149-2164.
• 56. Meijnen P., Peterse J.L., Antonini N. i wsp.: Immunohis-tochemical categorisation of ductal carcinoma in situ of the breast. Br. J. Cancer 2008; 98: 137-142.
• 57. Leal C.B., Schmitt F.C., Bento M.J. i wsp.: Ductal carcinoma in situ of the breast. Histologic categorization and its relationship to ploidy and immunohistochemical expression of hormone receptors, p53, and c-erbB-2 protein. Cancer 1995; 75: 2123-2131.
• 58. Quinn C.M., Ostrowski J.L., Harkins L. i wsp.: Loss of bcl-2 expression in ductal carcinoma in situ of the breast relates to poor histological differentiation and to expression of p53 and c-erbB-2 proteins. Histopathology 1998; 33: 531-536.
• 59. Mack L., Kerkvliet N., Doig G., O’Malley F.P.: Relationship of a new histological categorization of ductal carcinoma in situ of the breast with size and the immunohistochemical expression of p53, c-erb B2, bcl-2, and ki-67. Hum. Pathol. 1997; 28: 974-979.
• 60. Freudenberg J.A., Wang Q., Katsumata M. i wsp.: The role of HER2 in early breast cancer metastasis and the origins of resistance to HER2-targeted therapies. Exp. Mol. Pathol. 2009; 87: 1-11.
• 61. Baselga J., Tripathy D., Mendelsohn J. i wsp.: Phase II study of weekly intravenous recombinant humanized anti-p185 HER2 monoclonal antibody in patients with HER2/neu-over-expressing metastatic breast cancer. J. Clin. Oncol. 1996; 14: 737-744.
• 62. Vogel C.L., Cobleigh M.A., Tripathy D.: Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J. Clin. Oncol. 2002; 20: 719-726.
• 63. Johnston S., Pippen J. Jr, Pivot X. i wsp.: Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J. Clin. Oncol. 2009; 27: 5538-5546.
• 64. Treish I., Schwartz R., Lindley C.: Pharmacology and therapeutic use of trastuzumab in breast cancer. Am. J. Health. Syst. Pharm. 2000; 57: 2063-2076.
• 65. Zhao J., Wu R., Au A. i wsp.: Determination of HER2 gene amplification by Chromogenic In Situ Hybridization (CISH) in archival breast carcinoma. Mod. Pathol. 2002; 15: 657-665.
• 66. Arnould L., Denoux Y., MacGrogan G. i wsp.: Agreement between chromogenic in situ hybridisation (CISH) and FISH in the determination of HER2 status in breast cancer. Br. J. Cancer 2003; 88: 1587-1591.
• 67. Valabrega G., Montemurro F., Aglietta M.: Trastuzumab: mechanism of action, resistance and future perspectives in HER2-overexpressing breast cancer. Ann. Oncol. 2007; 18: 977-984.
• 68. Molina M.A., Codony-Servat J., Albanell J. i wsp.: Trastuzumab (Herceptin), a humanized anti-HER2 receptor monoclonal antibody, inhibits basal and activated HER2 ectodo-main cleavage in breast cancer cells. Cancer Res. 2001; 61: 4744-4749.

• Document Type: article