Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2019, 163(4):285-292 | DOI: 10.5507/bp.2019.060

Therapeutic significance of hormone receptor positivity in patients with HER-2 positive breast cancer

Iveta Kolarovaa,b, Jaroslav Vanasekb,c,d, Karel Odrazkac,d,e,f,g, Bohuslav Melichara,h,i, Ales Ryskaj, Jiri Peteraa,h, Milan Vosmika,h, Martin Dolezele,i
a Department of Oncology and Radiotherapy, University Hospital Hradec Kralove, Czech Republic
b Faculty of Health Studies, Pardubice University, Pardubice, Czech Republic
c Oncology Centre, Multiscan, Pardubice, Czech Republic
d Department of Clinical and Radiation Oncology, Pardubice Hospital, Pardubice, Czech Republic
e Department of Oncology, First Faculty of Medicine, Charles University, Prague, Czech Republic
f Department of Radiotherapy and Oncology, Third Faculty of Medicine, Charles University, Prague, Czech Republic
g Institute for Postgraduate Medical Education, Prague, Czech Republic
h Department of Oncology and Radiotherapy, Faculty of Medicine in Hradec Kralove, Charles University, Czech Republic
i Department of Oncology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital, Olomouc, Czech Republic
j The Fingerland Department of Pathology, Charles University Medical Faculty and University Hospital Hradec Kralove, Czech Republic

Breast cancer with high expression of human epidermal growth factor receptor (HER)-2 represents a biologically and clinically heterogeneous group of neoplastic disorders. Importantly, hormone receptor expression has an effect on biological properties and affects the selection of therapies. On the basis of molecular genetics, four principal subtypes, including luminal A, luminal B, HER2-enriched (HER-2-E), and basal-like can be distinguished. Breast tumors characterized by HER-2 positivity and simultaneous expression of hormone receptors, triple positive breast cancers (TPBC) are of increasing interest owing to the unique biological characteristics associated with complex interactions between HER-2 and hormone receptor signaling pathways. Interactions between hormone receptors and HER-2 explain the decreased efficacy of hormonal therapy in comparison with HER-2-negative patients. The expression of estrogen receptors in HER-2 positive tumors may also be associated with resistance to anti-HER-2 treatment. Multiple available therapeutic options, including hormonal therapy, anti-HER-2 agents and cytotoxic drugs explain favorable prognosis of TPBC. Escalation and de-escalation therapeutic strategies that could result in lower toxicities are being investigated as well as combinations of anti-HER-2 agents with hormonal therapy, immunotherapy, cyclin dependent kinase 4/6 and phosphatidyl inositol-3-kinase inhibitors. Distinction between subtypes of HER-2-positive breast cancer and treatment diversification may result in improved outcomes in TPBC. A response to neoadjuvant therapy may serve in the tailoring of therapy management.

Keywords: breast cancer, estrogen receptor, HER-2

Received: July 30, 2019; Revised: October 30, 2019; Accepted: November 26, 2019; Published: December 11, 2019  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Kolarova, I., Vanasek, J., Odrazka, K., Melichar, B., Ryska, A., Petera, J., Vosmik, M., & Dolezel, M. (2019). Therapeutic significance of hormone receptor positivity in patients with HER-2 positive breast cancer. Biomedical papers, 163(4), 285-292. doi: 10.5507/bp.2019.060
Share...
Download citation
  • BibTeX (.bib)
  • Bookends (.ris)
  • EasyBib (.ris)
  • EndNote (.enw)
  • EndNote 8 (.xml)
  • ISI WoS (.isi)
  • Medlars (.medlars)
  • Mendeley (.ris)
  • MODS (.xml)
  • Papers (.ris)
  • RefWorks (.txt)
  • RefManager (.ris)
  • RIS (.ris)
  • MS Word (.xml)
  • Zotero (.ris)
    • Open full article

    References

    1. Giuliano M, Trivedi MV, Schiff R. Bidirectional crosstalk between the estrogen receptor and human epidermal growth factor receptor 2 signaling pathways in breast cancer: molecular basis and clinical implications. Breast Care 2013;8(4):256-62. Go to original source... Go to PubMed...
    2. Llombart-Cussac A, Cortés J, Paré L, Galván P, Bermejo B, Martínez N, Vidal M, Pernas S, López R, Muñoz M, Nuciforo P, Morales S, Oliveira M, de la Peña L, Peláez A, Prat A. HER2-enriched subtype as a predictor of pathological complete response following trastuzumab and lapatinib without chemotherapy in early-stage HER2-positive breast cancer (PAMELA): an open-label, single-group, multicentre, phase 2 trial. Lancet Oncol 2017;18(4):545-54. Go to original source... Go to PubMed...
    3. Osborne CK, Schiff R. Mechanisms of endocrine resistance in breast cancer. Annu Rev Med 2011;62:233-47. Go to original source... Go to PubMed...
    4. Lal P, Tan LK, Chen B. Correlation of HER-2 status with estrogen and progesterone receptors and histologic features in 3655 invasive breast carcinomas. Am J Clin Pathol 2005;123(4):541-6. Go to original source...
    5. Konecny G, Pauletti G, Pegram M, Untch M, Dandekar S, Aguilar Z, Wilson C, Rong HM, Bauerfeind I, Felber M, Wang HJ, Beryt M, Seshadri R, Hepp H, Slamon DJ. Quantitative association between HER-2/neu and steroid hormone receptors in hormone receptor-positive primary breast cancer. J Natl Cancer Inst 2003;95(2):142-53. Go to original source... Go to PubMed...
    6. Wang YC, Morrison G, Gillihan R, Guo J, Ward RM, Fu X, Botero MF, Healy NA, Hilsenbeck SG, Phillips GL, Chamness GC, Rimawi MF, Osborne CK, Schiff R. Different mechanisms for resistance to trastuzumab versus lapatinib in HER2-positive breast cancers - role of estrogen receptor and HER2 reactivation. Breast Cancer Res 2011;13(6):R121. Go to original source... Go to PubMed...
    7. Giuliano M, Hu H, Wang YC, Fu X, Nardone A, Herrera S, Mao S, Contreras A, Gutierrez C, Wang T, Hilsenbeck SG, De Angelis C, Wang NJ, Heiser LM, Gray JW, Lopez-Tarruella S, Pavlick AC, Trivedi MV, Chamness GC, Chang JC, Osborne CK, Rimawi MF, Schiff R. Upregulation of ER signaling as an adaptive mechanism of cell survivalin HER2-positive breast tumors treated with anti-HER2 therapy. Clin Cancer Res 2015;21(17):3995-4003. Go to original source... Go to PubMed...
    8. Vici P, Pizzuti L, Sperduti I, Frassoldati A, Natoli C, Gamucci T, Tomao S, Michelotti A, Moscetti L, Gori S, Baldini E, Giotta F, Cassano A, Santini D, Giannarelli D, Di Lauro L, Corsi DC, Marchetti P, Sini V, Sergi D, Barba M, Maugeri-Saccà M, Russillo M, Mentuccia L, D'Onofrio L, Iezzi L, Scinto AF, Da Ros L, Bertolini I, Basile ML, Rossi V, De Maria R, Montemurro F. "Triple positive" early breast cancer: an observational multicenter retrospective analysis of outcome. Oncotarget 2016;7(14):17932-44. Go to original source... Go to PubMed...
    9. NCCN. Breast Cancer Guidelines, Ver. 1.2018. (2018). Available from: www.nccn.org (Accessed: March 20, 2018). Go to original source...
    10. Giordano SH, Temin S, Kirshner JJ, Chandarlapaty S, Crews JR, Davidson NE, Esteva FJ, Gonzalez-Angulo AM, Krop I, Levinson J, Lin NU, Modi S, Patt DA, Perez EA, Perlmutter J, Ramakrishna N, Winer EP; American Society of Clinical Oncology. Systemic therapy for patients with advanced human epidermal growth factor receptor 2-positive breast cancer: American society of clinical oncology clinical practice guideline. J Clin Oncol 2014;32(19):2078-99. Go to original source... Go to PubMed...
    11. Larionov AA. Current Therapies for Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer Patients. Front Oncol 2018;8:89. Go to original source... Go to PubMed...
    12. Colleoni M, Sun Z, Price KN, Karlsson P, Forbes JF, Thürlimann B, Gianni L, Castiglione M, Gelber RD, Coates AS, Goldhirsch A. Annual Hazard Rates of Recurrence for Breast Cancer During 24 Years of Follow-Up: Results From the International Breast Cancer Study Group Trials I to V. J Clin Oncol 2016;34:927-35. Go to original source... Go to PubMed...
    13. Harvey JM, Clark GM, Osborne CK, Allred DC. Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. J Clin Oncol 1999;17:1474-81. Go to original source... Go to PubMed...
    14. Pertschuk LP, Kim DS, Nayer K, Feldman JG, Eisenberg KB, Carter AC, Rong ZT, Thelmo WL, Fleisher J, Greene GL.Immunocytochemical estrogen and progestin receptor assays in breast cancer with monoclonal antibodies. Histopathologic, demographic, and biochemical correlations and relationship to endocrine response and survival. Cancer 1990;66:1663-70. Go to original source... Go to PubMed...
    15. Bartlett JM, Brookes CL, Robson T, van de Velde CJ, Billingham LJ, Campbell FM, Grant M, Hasenburg A, Hille ET, Kay C, Kieback DG, Putter H, Markopoulos C, Kranenbarg EM, Mallon EA, Dirix L, Seynaeve C, Rea D. Estrogen receptor and progesterone receptor as predictive biomarkers of response to endocrine therapy: a prospectively powered pathology study in the Tamoxifen and Exemestane Adjuvant Multinational trial. J Clin Oncol 2011;29:1531-38. Go to original source... Go to PubMed...
    16. Colzani E, Liljegren A, Johansson AL, Adolfsson J, Hellborg H, Hall PF, Czene K. Prognosis of patients with breast cancer: causes of death and effects of time since diagnosis, age, and tumor characteristics. J Clin Oncol 2011;29:4014-21. Go to original source... Go to PubMed...
    17. Pogue-Geile KL, Song N, Jeong JH, Gavin PG, Kim SR, Blackmon NL, Finnigan M, Rastogi P, Fehrenbacher L, Mamounas EP, Swain SM, Wickerham DL, Geyer CE Jr, Costantino JP, Wolmark N, Paik S. Intrinsic subtypes, PIK3CA mutation, and the degree of benefit from adjuvant trastuzumab in the NSABP B-31 trial. J Clin Oncol 2015;33(12):1340-47. Go to original source... Go to PubMed...
    18. Perez EA, Ballman KV, Mashadi-Hossein A, Tenner KS, Kachergus JM, Norton N, Necela BM, Carr JM, Ferree S, Perou CM, Baehner F, Cheang MC, Thompson EA. Intrinsic subtype and therapeutic response among HER2-positive breast tumors from the NCCTG (Alliance) N9831 trial. J Natl Cancer Inst 2017;109(2). Go to original source... Go to PubMed...
    19. Colleoni M, Bagnardi V, Rotmensz N, Gelber RD, Viale G, Pruneri G, Veronesi P, Torrisi R, Cardillo A, Montagna E, Campagnoli E, Luini A, Intra M, Galimberti V, Scarano E, Peruzzotti G, Goldhirsch A. Increasing steroid hormone receptors expression defines breast cancer subtypes non responsive to preoperative chemotherapy. Breast Cancer Res Treat 2009;116(2):359-69. Go to original source... Go to PubMed...
    20. Howlader N, Cronin KA, Kurian AW, Andridge R. Differences in breast cancer survival by molecular subtypes in the United States. Cancer Epidemiol Biomarkers Prev 2018,27(6):619-26. doi: 10.1158/1055-9965 Go to original source...
    21. Vaz-Luis I, Ottesen RA, Hughes ME, Marcom PK, Moy B, Rugo HS, Theriault RL, Wilson J, Niland JC, Weeks JC, Lin NU. Impact of hormone receptor status on patterns of recurrence and clinical outcomes among patients with human epidermal growth factor-2-positive breast cancer in the National Comprehensive Cancer Network: a prospective cohort study. Breast Cancer Res 2012,14(5):R129. Go to original source... Go to PubMed...
    22. Chumsri S, Li Z, Serie DJ, Mashadi-Hossein A, Otero G, Song N, Pogue-Geile K, Gavin P, Paik S, Moreno-Aspitia A, Perez E, Thompson EA. Abstract PD3-02: Incidence of late relapse in HER2-positive (HER2+) breast cancer patients receiving adjuvant trastuzumab: Combined analysis of NCCTG (Alliance) N9831 and NSABP (NRG) B31. Cancer Res 2019;79(S4):PD3-02. Go to original source... Go to PubMed...
    23. Swain SM, Baselga J, Kim SB, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Heeson S, Clark E, Ross G, Benyunes MC, Cortés J; CLEOPATRA Study Group. Pertuzumab, trastuzumab and docetaxel in HER2-pozitive metastatic breast cancer. N Engl J Med 2015;372(8):724-34. Go to original source... Go to PubMed...
    24. Vici P, Pizzuti L, Natoli C, Gamucci T, Di Lauro L, Barba M, Sergi D, Botti C, Michelotti A, Moscetti L, Mariani L, Izzo F, D'Onofrio L, Sperduti I, Conti F, Rossi V, Cassano A, Maugeri-Saccà M, Mottolese M, Marchetti P. Triple positive breast cancer: a distinct subtype? Cancer Treat Rev 2015;41(2):69-76. Go to original source... Go to PubMed...
    25. Loi S, Dafni U, Karlis D, Polydoropoulou V, Young BM, Willis S, Long B, de Azambuja E, Sotiriou C, Viale G, Rüschoff J, Piccart MJ, Dowsett M, Michiels S, Leyland-Jones B. Effects of estrogen receptor and human epidermal growth factor receptor-2 levels on the efficacy of trastuzumab: a secondary analysis of the HERA trial. JAMA Oncology 2016;2(8):1040-7. Go to original source... Go to PubMed...
    26. Harbeck N. Neoadjuvant treatment of HER2-positive breast cancer: should therapy differ based on hormone receptor status? Ther Adv Med Oncol 2018;10:1-3. Go to original source... Go to PubMed...
    27. Prat A, De Angelis C, Pascual T, Gutierrez C, Llombart-Cussac A, Wang T, Cortes J, Rexer BN, Veeraraghavan J, Forero-Torres A, Wolff AC, Morales S, Krop IE, Pavlick AC, Bermejo B, Hilsenbeck SG, Oliveira M, Schiff R, Osborne CK, Rimawi MF. HER2-enriched subtype and ERBB2 mRNA as predictors of pathological complete response following trastuzumab and lapatinib without chemotherapy in early-stage HER2-positive breast cancer: A combined analysis of TBCRC006/023 and PAMELA trials. J Clin Oncol 2018;36(15):509. Go to original source...
    28. Harbeck N, Gluz O, Christgen M, Kates RE, Braun M, Küemmel S, Schumacher C, Potenberg J, Kraemer S, Kleine-Tebbe A, Augustin D, Aktas B, Forstbauer H, Tio J, von Schumann R, Liedtke C, Grischke EM, Schumacher J, Wuerstlein R, Kreipe HH, Nitz UA. De-escalation strategies in human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (BC): final analysis of the west german study group adjuvant dynamic marker-adjusted personalized therapy trial optimizing risk assessment and therapy response prediction in early BC HER2-and hormone receptor-positive phase II randomized trial-efficacy, safety, and predictive markers for 12 weeks of neoadjuvant trastuzumab emtansine with or without endocrine therapy (ET) versus trastuzumab Plus ET. J Clin Oncol 2017;35(26):3046-54. Go to original source... Go to PubMed...
    29. Untch M, von Minckwitz G, Gerber B, Schem C, Rezai M, Fasching PA, Tesch H, Eggemann H, Hanusch C, Huober J, Solbach C, Jackisch C, Kunz G, Blohmer JU, Hauschild M, Fehm T, Nekljudova V, Loibl S; GBG and the AGO-B Study Group.Survival Analysis After Neoadjuvant Chemotherapy With Trastuzumab or Lapatinib in Patients With Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer in the GeparQuinto (G5) Study (GBG 44). J Clin Oncol 2018;36(13):1308-16. Go to original source... Go to PubMed...
    30. Nahta R, O'Regan RM. Therapeutic implications of estrogen receptor signaling in HER2-positive breast cancers. Breast Cancer Res Treat 2012;135(1):39-48. Go to original source... Go to PubMed...
    31. Guarneri V, Dieci MV, Bisagni G, Frassoldati A, Bianchi GV, De Salvo GL, Orvieto E, Urso L, Pascual T, Paré L, Galván P, Ambroggi M, Giorgi CA, Moretti G, Griguolo G, Vicini R, Prat A, Conte PF. De-escalated therapy for HR+/HER2+ breast cancer patients with Ki67 response after 2 weeks letrozole: results of the PerELISA neoadjuvant study. Ann Oncol 2019,30(6): 921-6. Go to original source... Go to PubMed...
    32. Regan MM, Fleming GF, Walley B, Francis PA, Pagani O. Adjuvant Systemic Treatment of Premenopausal Women With Hormone Receptor-Positive Early Breast Cancer: Lights and Shadows. J Clin Oncol 2019;37(11):862-6. Go to original source... Go to PubMed...
    33. Lambertini M, Campbell C, Bines J, Korde LA, Izquierdo M, Fumagalli D, Del Mastro L, Ignatiadis M, Pritchard K, Wolff AC, Jackisch C, Lang I, Untch M, Smith I, Boyle F, Xu B, Barrios CH, Baselga J, Moreno-Aspitia A, Piccart M, Gelber RD, de Azambuja E. Adjuvant anti-HER2 therapy, treatment-related amenorrhea, and survival in premenopausal HER2-positive early breast cancer patients. J Natl Cancer Inst 2019;111(1):86-94. Go to original source... Go to PubMed...
    34. von Minckwitz G, Huang CS, Mano MS, Loibl S, Mamounas EP, Untch M, Wolmark N, Rastogi P, Schneeweiss A, Redondo A, Fischer HH, Jacot W, Conlin AK, Arce-Salinas C, Wapnir IL, Jackisch C, DiGiovanna MP, Fasching PA, Crown JP, Wülfing P, Shao Z, Rota Caremoli E, Wu H, Lam LH, Tesarowski D, Smitt M, Douthwaite H, Singel SM, Geyer CE Jr; KATHERINE Investigators. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med 2019;380(7):617-28. Go to original source... Go to PubMed...
    35. Martin M, Holmes FA, Ejlertsen B, Delaloge S, Moy B, Iwata H, von Minckwitz G, Chia SKL, Mansi J, Barrios CH, Gnant M, Tomaąević Z, Denduluri N, ©eparović R, Gokmen E, Bashford A, Ruiz Borrego M, Kim SB, Jakobsen EH, Ciceniene A, Inoue K, Overkamp F, Heijns JB, Armstrong AC, Link JS, Joy AA, Bryce R, Wong A, Moran S, Yao B, Xu F, Auerbach A, Buyse M, Chan A; ExteNET Study Group. Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2017;18(12):1688-700. Go to original source... Go to PubMed...
    36. Tolaney SM, Barry WT, Guo H, Dillon D, Dang CT, Yardley DA, Moy B, Marcom PK, Albain KS, Rugo HS, Ellis MJ, Shapira J, Wolff AC, Carey LA, Overmoyer B, Partridge AH, Hudis CA, Krop IE, Burstein HJ, Winer EP. Seven-year (yr) follow-up of adjuvant paclitaxel (T) and trastuzumab (H) (APT trial) for node-negative, HER2-positive breast cancer (BC). J Clin Oncol 2017;35(15):511-511. doi: 10.1200/JCO.2017.35.15_suppl.511 Go to original source...
    37. Kaufman B, Mackey JR, Clemens MR, Bapsy PP, Vaid A, Wardley A, Tjulandin S, Jahn M, Lehle M, Feyereislova A, Révil C, Jones A. Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: results from the randomized phase III TAnDEM study. J Clin Oncol 2009;27(33):5529-37. Go to original source... Go to PubMed...
    38. Johnston S, Pippen J Jr, Pivot X, Lichinitser M, Sadeghi S, Dieras V, Gomez HL, Romieu G, Manikhas A, Kennedy MJ, Press MF, Maltzman J, Florance A, O'Rourke L, Oliva C, Stein S, Pegram M. 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(33):5538-46. Go to original source... Go to PubMed...
    39. Schwartzberg LS, Franco SX, Florance A, O'Rourke L, Maltzman J, Johnston S. Lapatinib plus letrozole as first-line therapy for HER-2+ hormone receptor-positive metastatic breast cancer. Oncologist 2010;15(2):122-9. Go to original source... Go to PubMed...
    40. Huober J, Fasching PA, Barsoum M, Petruzelka L, Wallwiener D, Thomssen C, Reimer T, Paepke S, Azim HA, Ragosch V, Kubista E, Baumgärtner AK, Beckmann MW, May C, Nimmrich I, Harbeck N. Higher efficacy of letrozole in combination with trastuzumab compared to letrozole monotherapy as first-line treatment in patients with HER2-positive, hormone-receptor-positive metastatic breast cancer - results of the eLEcTRA trial. Breast 2012;21(1):27-33. Go to original source... Go to PubMed...
    41. Hayashi N, Niikura N, Yamauchi H, Nakamura S, Ueno NT. Adding hormonal therapy to chemotherapy and trastuzumab improves prognosis in patients with hormone receptor-positive and human epidermal growth factor receptor 2-positive primary breast cancer. Breast Cancer Res Treat 2013;137(2):523-31. Go to original source... Go to PubMed...
    42. Cardoso F, Costa A, Senkus E, Aapro M, André F, Barrios CH, Bergh J, Bhattacharyya G, Biganzoli L, Cardoso MJ, Carey L, Corneliussen-James D, Curigliano G, Dieras V, El Saghir N, Eniu A, Fallowfield L, Fenech D, Francis P, Gelmon K, Gennari A, Harbeck N, Hudis C, Kaufman B, Krop I, Mayer M, Meijer H, Mertz S, Ohno S, Pagani O, Papadopoulos E, Peccatori F, Penault-Llorca F, Piccart MJ, Pierga JY, Rugo H, Shockney L, Sledge G, Swain S, Thomssen C, Tutt A, Vorobiof D, Xu B, Norton L, Winer E. 3rd ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 3). Ann Oncol 2017;28(1):16-33. Go to original source... Go to PubMed...
    43. Arpino G, Ferrero JM, De la Haba-Rodriguez J, Easton V, Schuhmacher C, Restuccia E, Rimawi M. Primary analysis of PERTAIN: a randomized, two-arm, open-label, multicenter phase II trial assessing the efficacy and safety of pertuzumab given in combination with trastuzumab plus an aromatase inhibitor in first-line patients with HER2-positive and hormone receptor-positive metastatic or locally advanced breast cancer. Cancer Res 2017;77(4 Suppl):S3-04. Go to original source...
    44. Gradishar WJ, Hegg R, Im SA, Park IH, Tjulandin S, Kenny S, Sarp S, Williams L, Izquierdo MA, Johnston SRD. Phase III study of lapatinib (L) plus trastuzumab (T) and aromatase inhibitor (AI) vs T+AI vs L+AI in postmenopausal women (PMW) with HER2+, HR+ metastatic breast cancer (MBC): ALTERNATIVE. J Clin Oncol 2017;35(15):1004. Go to original source...
    45. Melichar B, ©tudentová H, Kalábová H, Vitásková D, Čermáková P, Hornychová H, Ryąka A. Predictive and prognostic significance of tumor-infiltrating lymphocytes in patients with breast cancer treated with neoadjuvant systemic therapy. Anticancer Research 2014;34:1115-26. Go to PubMed...
    46. Salgado R, Denkert C, Campbell C, Savas P, Nuciforo P, Aura C, de Azambuja E, Eidtmann H, Ellis CE, Baselga J, Piccart-Gebhart MJ, Michiels S, Bradbury I, Sotiriou C, Loi S. Tumor-infiltrating lymphocytes and associations with pathological complete response and event-free survival in HER2-positive early-stage breast cancer treated with lapatinib and trastuzumab: a secondary analysis of the NeoALTTO trial. JAMA Oncol 2015;1(4):448-54. Go to original source... Go to PubMed...
    47. Bianchini G, Pusztai L, Pienkowski T, Im YH, Bianchi GV, Tseng LM, Liu MC, Lluch A, Galeota E, Magazzù D, de la Haba-Rodríguez J, Oh DY, Poirier B, Pedrini JL, Semiglazov V, Valagussa P, Gianni L. Immune modulation of pathologic complete response after neoadjuvant HER2-directed therapies in the NeoSphere trial. Ann Oncol 2015;26(12):2429-36. Go to original source... Go to PubMed...
    48. Solinas C, Ceppi M, Lambertini M, Scartozzi M, Buisseret L, Garaud S, Fumagalli D, de Azambuja E, Salgado R, Sotiriou C, Willard-Gallo K, Ignatiadis M. Tumor-infiltrating lymphocytes in patients with HER2-positive breast cancer treated with neoadjuvant chemotherapy plus trastuzumab, lapatinib or their combination: a meta-analysis of randomized controlled trials. Cancer Treat Rev 2017;57:8-15. Go to original source... Go to PubMed...
    49. Luen SJ, Salgado R, Fox S, Savas P, Eng-Wong J, Clark E, Kiermaier A, Swain SM, Baselga J, Michiels S, Loi S. Tumour-infiltrating lymphocytes in advanced HER2-positive breast cancer treated with pertuzumab or placebo in addition to trastuzumab and docetaxel: a retrospective analysis of the CLEOPATRA study. Lancet Oncol 2017;18:52-62. Go to original source... Go to PubMed...
    50. Loi S, Giobbe-Hurder A, Gombos A, Bachelot T, Hui R, Curigliano G, Campone M, Biganzoli L, Bonnefoi H, Jerusalem G, Bartsch R, Rabaglio-Poretti M, Kammler R, Maibach R, Smyth MJ, Di Leo A, Colleoni M, Viale G, Regan MM, Andre F. Abstract GS2-06: Phase Ib/II study evaluating safety and efficacy of pembrolizumab and trastuzumab in patients with trastuzumab-resistant HER2-positive metastatic breast cancer: Results from the PANACEA (IBCSG 45-13/BIG 4-13/KEYNOTE-014) study. Cancer Res 2018;78(4 Suppl):GS2-06. Go to original source...
    51. Dieci MV, Prat A, Tagliafico E, Paré L, Ficarra G, Bisagni G, Piacentini F, Generali DG, Conte P, Guarneri V. Integrated evaluation of PAM50 subtypes and immune modulation of pCR in HER2-positive breast cancer patients treated with chemotherapy and HER2-targeted agents in the CherLOB trial. Ann Oncol 2016;27(10):1867-73. Go to original source... Go to PubMed...
    52. Nuciforo P, Pascual T, Cortés J, Llombart-Cussac A, Fasani R, Paré L, Oliveira M, Galvan P, Martínez N, Bermejo B, Vidal M, Pernas S, López R, Muñoz M, Garau I, Manso L, Alarcón J, Martínez E, Rodrik-Outmezguine V, Brase JC, Villagrasa P, Prat A, Holgado E. A predictive model of pathological response based on tumor cellularity and tumor-infiltrating lymphocytes (CelTIL) in HER2-positive breast cancer treated with chemo-free dual HER2 blockade. Ann Oncol 2018;29(1):170-7. Go to original source... Go to PubMed...
    53. Pernas S, Tolaney SM, Winer EP, Goel S. CDK4/6 inhibition in breast cancer: current practice and future directions. Ther Adv Med Oncol 2018;10:1-15. Go to original source... Go to PubMed...
    54. Ciruelos E, Villagrasa P, Paré L, Oliveira M, Pernas S, Cortés J, Soberino J, Adamo B, Vazquez S, Martínez N, Perelló A, Bermejo B, Martínez E, Garau I, Melé M, Morales S, Galván P, Pascual T, Canes J, Nuciforo P, Gonzalez X, Prat A. Abstract PD3-03: SOLTI-1303 PATRICIA phase II trial (STAGE 1)-Palbociclib and trastuzumab in postmenopausal patients with HER2-positive metastatic breast cancer. Cancer Res 2019;79(4 Suppl):PD3-03. Go to original source...
    55. Gianni L, Bisagni G, Colleoni M, Del Mastro L, Zamagni C, Mansutti M, Zambetti M, Frassoldati A, De Fato R, Valagussa P, Viale G. Neoadjuvant treatment with trastuzumab and pertuzumab plus palbociclib and fulvestrant in HER2-positive, ER-positive breast cancer (NA-PHER2): an exploratory, open-label, phase 2 study. Lancet Oncol 2018;19(2):249-56. Go to original source... Go to PubMed...
    56. Pernas S, Tolaney SM. HER2-positive breast cancer: new therapeutic frontiers and overcoming resistance. Ther Adv Med Oncol 2019;19(11):1-16. Go to original source... Go to PubMed...
    57. André F, Hurvitz S, Fasolo A, Tseng LM, Jerusalem G, Wilks S, O'Regan R, Isaacs C, Toi M, Burris H, He W, Robinson D, Riester M, Taran T, Chen D, Slamon D. Molecular alterations and everolimus efficacy in human epidermal growth factor receptor 2-overexpressing metastatic breast cancers: combined exploratory biomarker analysis from BOLERO-1 and BOLERO-3. J Clin Oncol 2016;34(18):2115-24. Go to original source... Go to PubMed...
    58. Sirohi B, Rastogi S, Dawood S. Buparlisib in breast cancer. Future Oncol 2015;11(10):1463-70. Go to original source... Go to PubMed...
    59. Jain S, Nye L, Santa-Maria C, Bontemps L, Williams A, Garrett H, Dammrich E, Giles F, Gradishar W. Abstract P6-13-11: Phase I study of alpelisib and T-DM1 in trastuzumab-refractory HER2-positive metastatic breast cancer. Cancer Res 2016;76(4 Suppl):P6-13-11. Go to original source...
    60. Melichar, B. Laboratory medicine and medical oncology: the tale of two Cinderellas. Clin Chem Lab Med 2013;51(1):99-112. Go to original source... Go to PubMed...

    This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC BY 4.0), which permits use, distribution, and reproduction in any medium, provided the original publication is properly cited. No use, distribution or reproduction is permitted which does not comply with these terms.


    Return to the content