1,122
Views
1
CrossRef citations to date
0
Altmetric
Review

Combination therapies for the treatment of HER2-positive breast cancer: current and future prospects

, , , , , & show all
Pages 629-649 | Received 15 Feb 2018, Accepted 14 May 2018, Published online: 24 May 2018

References

  • Wolff AC, Hammond MEH, Hicks DG, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Update. J Clin Oncol. 2013;31:3997–4013.
  • Gingras I, Gebhart G, De Azambuja E, et al. HER2-positive breast cancer is lost in translation: time for patient-centered research. Nat Rev Clin Oncol. 2017;14:669–681.
  • Roth J, Bajaj P, Sullivan S, et al. 263PSurvival gains from advances in first-line systemic therapy for HER2-positive metastatic breast cancer in the U.S., 1995–2015. Ann Oncol 2017;28: mdx365.026-mdx365.026.
  • Cameron D, Piccart-Gebhart MJ, Gelber RD, et al. 11 years’ follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. The Lancet. 2017;389:1195–1205.
  • Tolaney SM, Barry WT, Dang CT, et al. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer. N Engl J Med. 2015;372:134–141.
  • Tolaney SM, Barry WT, Guo H, et al. 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;35:511.
  • Schettini F, Buono G, Cardalesi C, et al. Hormone receptor/human epidermal growth factor receptor 2-positive breast cancer: where we are now and where we are going. Cancer Treat Rev. 2016;46:20–26.
  • Carey LA, Berry D, Cirrincione CT, et al. Molecular heterogeneity and response to neoadjuvant human epidermal growth factor receptor 2 targeting in CALGB 40601, a randomized phase III trial of paclitaxel plus trastuzumab with or without lapatinib. J Clin Oncol. 2015;34:542-549.
  • 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. The Lancet. 2012;379:633–640.
  • Huober JB, Holmes EM, Baselga J, et al. Survival outcomes of the NeoALTTO study: updated results of a randomized multicenter phase III neoadjuvant trial. J Clin Oncol. 2017;35:512.
  • Guarneri V, Frassoldati A, Bottini A, et al. Preoperative chemotherapy plus trastuzumab, lapatinib, or both in human epidermal growth factor receptor 2-positive operable breast cancer: results of the randomized phase II CHER-LOB study. J Clin Oncol. 2012;30:1989–1995.
  • Robidoux A, Tang G, Rastogi P, et al. Lapatinib as a component of neoadjuvant therapy for HER2-positive operable breast cancer (NSABP protocol B-41): an open-label, randomised phase 3 trial. Lancet Oncol. 2013;14:1183–1192.
  • Robidoux A, Tang G, Rastogi P, et al. Evaluation of lapatinib as a component of neoadjuvant therapy for HER2+ operable breast cancer: 5-year outcomes of NSABP protocol B-41. J Clin Oncol. 2016;34:501.
  • Carey LA, Berry DA, Cirrincione CT, et al. Molecular heterogeneity and response to neoadjuvant human epidermal growth factor receptor 2 targeting in CALGB 40601, a randomized phase III trial of paclitaxel plus trastuzumab with or without lapatinib. J Clin Oncol. 2016;34:542–549.
  • Hurvitz S, Miller J, Dichmann R, et al. Abstract S1-02: final analysis of a phase II 3-arm randomized trial of neoadjuvant trastuzumab or lapatinib or the combination of trastuzumab and lapatinib, followed by six cycles of docetaxel and carboplatin with trastuzumab and/or lapatinib in patients with HER2+ breast cancer (TRIO-US B07). Cancer Res. 2013;73: S1-02.
  • Holmes FA, Espina V, Liotta LA, et al. Pathologic complete response after preoperative anti-HER2 therapy correlates with alterations in PTEN, FOXO, phosphorylated Stat5, and autophagy protein signaling. BMC Res Notes. 2013;6:507.
  • Bonnefoi H, Jacot W, Saghatchian M, et al. Neoadjuvant treatment with docetaxel plus lapatinib, trastuzumab, or both followed by an anthracycline-based chemotherapy in HER2-positive breast cancer: results of the randomised phase II EORTC 10054 study. Ann Oncol. 2015;26:325–332.
  • Krop I, Hillman D, Polley M-Y, et al. Abstract GS3-02: Invasive disease-free survival and gene expression signatures in CALGB (Alliance) 40601, a randomized phase III neoadjuvant trial of dual HER2-targeting with lapatinib added to chemotherapy plus trastuzumab. Cancer Res. 2018;78:GS3-02-GS3-02..
  • Clavarezza M, Puntoni M, Gennari A, et al. Dual block with lapatinib and trastuzumab versus single-agent trastuzumab combined with chemotherapy as neoadjuvant treatment of HER2-positive breast cancer: a meta-analysis of randomized trials. Clin Cancer Res. 2016;22:4594–4603.
  • Gianni L, Pienkowski T, Im Y-H, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13:25–32.
  • Gianni L, Pienkowski T, Im Y-H, et al. 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial. Lancet Oncol. 2016;17:791–800.
  • Loibl S, Jackisch C, Schneeweiss A, et al. Dual HER2-blockade with pertuzumab and trastuzumab in HER2-positive early breast cancer: a subanalysis of data from the randomized phase III GeparSepto trial. Ann Oncol Off J Eur Soc Med Oncol. 2017;28:497–504.
  • Schneeweiss A, Chia S, Hickish T, et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013;24:2278–2284.
  • Schneeweiss A, Chia S, Hickish T, et al. Long-term efficacy analysis of the randomised, phase II TRYPHAENA cardiac safety study: evaluating pertuzumab and trastuzumab plus standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer. Eur J Cancer. 2018;89:27–35.
  • Swain SM, Ewer MS, Viale G, et al. Pertuzumab, trastuzumab, and standard anthracycline- and taxane-based chemotherapy for the neoadjuvant treatment of patients with HER2-positive localized breast cancer (BERENICE): a phase II, open-label, multicenter, multinational cardiac safety study. Ann Oncol. 2018;29:646-653.
  • Hurvitz SA, Martin M, Symmans WF, et al. Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer (KRISTINE): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2018;19:115–126.
  • Nitz UA, Gluz O, Christgen M, et al. De-escalation strategies in HER2-positive early breast cancer (EBC): final analysis of the WSG-ADAPT HER2+/HR− phase II trial: efficacy, safety, and predictive markers for 12 weeks of neoadjuvant dual blockade with trastuzumab and pertuzumab ± weekly paclitaxel. Ann Oncol. 2017;28:2768–2772.
  • Hanusch C, Schneeweiss A, Loibl S, et al. Dual blockade with AFatinib and Trastuzumab as NEoadjuvant treatment for patients with locally advanced or operable breast cancer receiving taxane-anthracycline containing chemotherapy-DAFNE (GBG-70). Clin Cancer Res. 2015;21:2924–2931.
  • Jacobs S, Robidoux A, Garcia J, et al. Abstract PD5-04: NSABP FB-7: a phase II randomized trial evaluating neoadjuvant therapy with weekly paclitaxel (P) plus neratinib (N) or trastuzumab (T) or neratinib and trastuzumab (N+T) followed by doxorubicin and cyclophosphamide (AC) with postoperative T in women with locally advanced HER2-positive breast cancer. Cancer Res. 2016;76: PD5-04.
  • Wilks ST. Potential of overcoming resistance to HER2-targeted therapies through the PI3K/Akt/mTOR pathway. The Breast. 2015;24:548–555.
  • Maira S-M, Pecchi S, Huang A, et al. Identification and Characterization of NVP-BKM120, an Orally Available Pan-Class I PI3-Kinase Inhibitor. Mol Cancer Ther. 2012;11:317–328.
  • Loibl S, De La Pena L, Nekljudova V, et al. Neoadjuvant buparlisib plus trastuzumab and paclitaxel for women with HER2+ primary breast cancer: a randomised, double-blind, placebo-controlled phase II trial (NeoPHOEBE). Eur J Cancer. 2017;85:133–145.
  • Gianni L, Bisagni G, Colleoni M, et al. 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 [Internet]. 2018. cited 2018 Jan 11. Available from http://linkinghub.elsevier.com/retrieve/pii/S1470204518300019
  • Piccart-Gebhart M, Holmes E, Baselga J, et al. Adjuvant lapatinib and trastuzumab for early human epidermal growth factor receptor 2-positive breast cancer: results from the randomized phase III adjuvant lapatinib and/or trastuzumab treatment optimization trial. J Clin Oncol. 2016;34:1034–1042.
  • Moreno-Aspitia A, Holmes EM, Jackisch C, et al. Updated results from the phase III ALTTO trial (BIG 2-06; NCCTG (Alliance) N063D) comparing one year of anti-HER2 therapy with lapatinib alone (L), trastuzumab alone (T), their sequence (T→L) or their combination (L+T) in the adjuvant treatment of HER2-positive early breast cancer. J Clin Oncol. 2017;35:502.
  • Von Minckwitz G, Procter M, De Azambuja E, et al. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer. N Engl J Med. 2017;377:122–131.
  • Chan A, Delaloge S, Holmes FA, et al. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2016;17:367–377.
  • Martin M, Holmes FA, Ejlertsen B, et al. 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;18:1688-1700.
  • Ibrahim E, Tripathy D, Wilkinson M, et al. Abstract CT128: effects of adding budesonide or colestipol to loperamide prophylaxis on neratinib-associated diarrhea in patients (pts) with HER2+ early-stage breast cancer (eBC): the CONTROL trial. Cancer Res. 2017;77:CT128.
  • Konecny GE, Meng YG, Untch M, et al. Association between HER-2/neu and Vascular Endothelial Growth Factor Expression Predicts Clinical Outcome in Primary Breast Cancer Patients. Clin Cancer Res. 2004;10:1706.
  • Slamon D, Swain S, Buyse M, et al. Abstract S1-03: primary results from BETH, a phase 3 controlled study of adjuvant chemotherapy and trastuzumab ± bevacizumab in patients with HER2-positive, node-positive or high risk node-negative breast cancer. Cancer Res. 2013;73: S1-03.
  • 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;344:783–792.
  • Swain SM, Kim S-B, Cortes J, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2013;14:461–471.
  • Seferina SC, Lobbezoo DJA, De Boer M, et al. Real-Life Use and Effectiveness of Adjuvant Trastuzumab in Early Breast Cancer Patients: a Study of the Southeast Netherlands Breast Cancer Consortium. Oncologist. 2015;20:856–863.
  • Perez EA, López-Vega JM, Petit T, et al. Safety and efficacy of vinorelbine in combination with pertuzumab and trastuzumab for first-line treatment of patients with HER2-positive locally advanced or metastatic breast cancer: VELVET Cohort 1 final results. Breast Cancer Res. 2016;18:126.
  • Andersson M, Lopez-Vega JM, Petit T, et al. Efficacy and safety of pertuzumab and trastuzumab administered in a single infusion bag, followed by vinorelbine: VELVET cohort 2 final results. Oncologist. 2017;22:1160–1168.
  • Cardoso F, Costa A, Senkus E, et al. 3rd ESO–ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 3). Ann Oncol. 2017;28:16–33.
  • Miles D, Puglisi F, Schneeweiss A, et al. Preliminary safety results from PERUSE, a study of 1436 patients (pts) treated with first-line pertuzumab (P) combined with trastuzumab (H) and taxane therapy for HER2-positive locally recurrent/metastatic breast cancer (LR/mBC). Eur J Cancer. 1816;51:S271.
  • Wildiers H, Tryfonidis K, Dal Lago L, et al. Pertuzumab and trastuzumab with or without metronomic chemotherapy for older patients with HER2-positive metastatic breast cancer (EORTC 75111-10114): an open-label, randomised, phase 2 trial from the Elderly Task Force/Breast Cancer Group. Lancet Oncol. 2018;19:323–336.
  • Perez EA, Barrios C, Eiermann W, et al. Trastuzumab emtansine with or without pertuzumab versus trastuzumab plus taxane for human epidermal growth factor receptor 2-positive, advanced breast cancer: primary results from the phase III MARIANNE study. J Clin Oncol. 2016;35:141–148.
  • Phillips GDL, Fields CT, Li G, et al. Dual Targeting of HER2-Positive Cancer with Trastuzumab Emtansine and Pertuzumab: critical Role for Neuregulin Blockade in Antitumor Response to Combination Therapy. Clin Cancer Res. 2014;20:456.
  • Miller KD, Diéras V, Harbeck N, et al. Phase IIa trial of trastuzumab emtansine with pertuzumab for patients with human epidermal growth factor receptor 2-positive, locally advanced, or metastatic breast cancer. J Clin Oncol. 2014;32:1437–1444.
  • National Comprehensive Cancer Network: NCCN clinical practice guidelines in oncology: breast cancer version 3.2017. [Internet]. 2017. [cited 2018 Jan 5]. Available from: https://www.nccn.org/professionals/physician_gls/default.aspx#site.
  • Blackwell KL, Burstein HJ, Storniolo AM, et al. Overall survival benefit with lapatinib in combination with trastuzumab for patients with human epidermal growth factor receptor 2-positive metastatic breast cancer: final results from the EGF104900 Study. J Clin Oncol Off J Am Soc Clin Oncol. 2012;30:2585–2592.
  • Urruticoechea A, Rizwanullah M, Im S-A, et al. Randomized phase III trial of trastuzumab plus capecitabine with or without pertuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who experienced disease progression during or after trastuzumab-based therapy. J Clin Oncol. 2017;35:3030–3038.
  • Hurvitz SA, Andre F, Jiang Z, et al. Combination of everolimus with trastuzumab plus paclitaxel as first-line treatment for patients with HER2-positive advanced breast cancer (BOLERO-1): a phase 3, randomised, double-blind, multicentre trial. Lancet Oncol. 2015;16:816–829.
  • André F, O’Regan R, Ozguroglu M, et al. Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2014;15:580–591.
  • Isaacs C, O’Regan R, Xu B, et al. Abstract P4-13-12: everolimus plus trastuzumab and vinorelbine for trastuzumab-resistant, taxane-pretreated, HER2+ advanced breast cancer: overall survival results from BOLERO-3. Cancer Res. 2016;76: P4-13–12.
  • Baselga J, Im S-A, Iwata H, et al. Buparlisib plus fulvestrant versus placebo plus fulvestrant in postmenopausal, hormone receptor-positive, HER2-negative, advanced breast cancer (BELLE-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017;18:904–916.
  • Di LA, Johnston S, Lee KS, et al. Buparlisib plus fulvestrant in postmenopausal women with hormone-receptor-positive, HER2-negative, advanced breast cancer progressing on or after mTOR inhibition (BELLE-3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2018;19:87-100.
  • Jain S, Santa-Maria CA, Rademaker A, et al. Phase I study of alpelisib (BYL-719) and T-DM1 in HER2-positive metastatic breast cancer after trastuzumab and taxane therapy. J Clin Oncol. 2017;35:1026.
  • Hudis C, Swanton C, Janjigian YY, et al. A phase 1 study evaluating the combination of an allosteric AKT inhibitor (MK-2206) and trastuzumab in patients with HER2-positive solid tumors. Breast Cancer Res. 2013;15:R110.
  • Wisinski KB, Tevaarwerk AJ, Burkard ME, et al. Phase 1 study of an AKT-inhibitor (MK-2206) combined with lapatinib in adult solid tumors followed by dose-expansion in advanced HER2+ breast cancer. Clin Cancer Res Off J Am Assoc Cancer Res. 2016;22:2659–2667.
  • Kaufman B, Mackey JR, Clemens MR, et al. 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;27:5529–5537.
  • Arpino G, Ferrero J-M, De La Haba-Rodriguez J, et al. Abstract S3-04: 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: S3-04.
  • Swain SM, Baselga J, Kim S-B, et al. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015;372:724–734.
  • Polasik A, Schramm A, Friedl T, et al. Abstract OT1-02-04: the DETECT V-study – comparison of dual HER2-targeted therapy with trastuzumab plus pertuzumab in combination with chemo- or endocrine therapy in patients with HER2-positive and hormone-receptor positive metastatic breast cancer. Cancer Res. 2017;77: OT1-02–04.
  • Johnston SRD, Hegg R, Im S-A, et al. Phase III, randomized study of dual human epidermal growth factor receptor 2 (HER2) blockade with lapatinib plus trastuzumab in combination with an aromatase inhibitor in postmenopausal women with HER2-positive, hormone receptor-positive metastatic breast cancer: ALTERNATIVE. J Clin Oncol. 2018;36:741-748.
  • Zardavas D, Pondé N, Tryfonidis K. CDK4/6 blockade in breast cancer: current experience and future perspectives. Expert Opin Investig Drugs. 2017;26:1357–1372.
  • Goel S, Wang Q, Watt AC, et al. Overcoming therapeutic resistance in HER2-positive breast cancers with CDK4/6 inhibitors. Cancer Cell. 2016;29:255–269.
  • Patnaik A, Rosen LS, Tolaney SM, et al. Efficacy and safety of abemaciclib, an inhibitor of CDK4 and CDK6, for patients with breast cancer, non-small cell lung cancer, and other solid tumors. Cancer Discov. 2016;6:740.
  • Clark A, Wang X, Troxel A, et al. Abstract P4-22-14: single agent palbociclib with or without trastuzumab for the treatment of Rb+ advanced breast cancer. Cancer Res. 2017;77: P4-22–14.
  • Awada A, Colomer R, Inoue K, et al. Neratinib plus paclitaxel vs trastuzumab plus paclitaxel in previously untreated metastatic erbb2-positive breast cancer: the NEFERT-T randomized clinical trial. JAMA Oncol. 2016;2:1557–1564.
  • Canonici A, Gijsen M, Mullooly M, et al. Neratinib overcomes trastuzumab resistance in HER2 amplified breast cancer. Oncotarget. 2013;4:1592–1605.
  • Abraham J, Puhalla SL, Sikov WM, et al. Abstract CT013: NSABP FB-10: phase Ib dose-escalation trial evaluating trastuzumab emtansine (T-DMI) with neratinib (N) in women with metastatic HER2+ breast cancer (MBC). Cancer Res. 2017;77:CT013.
  • Dzimitrowicz H, Berger M, Vargo C, et al. T-DM1 activity in metastatic human epidermal growth factor receptor 2-positive breast cancers that received prior therapy with trastuzumab and pertuzumab. J Clin Oncol. 2016;34:3511–3517.
  • Moulder S, Hamilton E, Ferrario C, et al. 264PProgression-free survival (PFS) and site of first progression in HER2+ metastatic breast cancer (MBC) patients (pts) with (w) or without (w/o) brain metastases: a pooled analysis of tucatinib phase I studies. Ann Oncol 2017;28: mdx365.027-mdx365.027.
  • Alsina M, Boni V, Schellens JHM, et al. First-in-human phase 1/2 study of MCLA-128, a full length IgG1 bispecific antibody targeting HER2 and HER3: final phase 1 data and preliminary activity in HER2+ metastatic breast cancer (MBC). J Clin Oncol. 2017;35:2522.
  • LoRusso P, Krop I, Miller K, et al. Abstract CT234: a phase I study of MM-302, a HER2-targeted PEGylated liposomal doxorubicin, in patients with HER2+ metastatic breast cancer. Cancer Res. 2015;75:CT234.
  • Miller K, Cortes J, Hurvitz SA, et al. HERMIONE: a randomized Phase 2 trial of MM-302 plus trastuzumab versus chemotherapy of physician’s choice plus trastuzumab in patients with previously treated, anthracycline-naïve, HER2-positive, locally advanced/metastatic breast cancer. BMC Cancer. 2016;16:352.
  • Shah PD, Chandarlapaty S, Dickler MN, et al. Phase I study of LJM716, BYL719, and trastuzumab in patients (pts) with HER2-amplified (HER2+) metastatic breast cancer (MBC). J Clin Oncol. 2015;33:590.
  • García-Teijido P, Cabal ML, Fernández IP, et al. Tumor-Infiltrating Lymphocytes in Triple Negative Breast Cancer: the Future of Immune Targeting. Clin Med Insights Oncol. 2016;10:31–39.
  • Curtis C, Shah SP, Chin S-F, et al. The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature. 2012;486:346.
  • Luen SJ, Salgado R, Fox S, et al. 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.
  • Stagg J, Loi S, Divisekera U, et al. Anti-ErbB-2 mAb therapy requires type I and II interferons and synergizes with anti-PD-1 or anti-CD137 mAb therapy. Proc Natl Acad Sci U S A. 2011;108:7142–7147.
  • Loi S, Giobbe-Hurder A, Gombos A, et al. 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:GS2-06-GS2-06.
  • Loi S, Adams S, Schmid P, et al. LBA13Relationship between tumor infiltrating lymphocyte (TIL) levels and response to pembrolizumab (pembro) in metastatic triple-negative breast cancer (mTNBC): results from KEYNOTE-086. Ann Oncol 2017;28: mdx440.005-mdx440.005.
  • Loibl S, Majewski I, Guarneri V, et al. PIK3CA mutations are associated with reduced pathological complete response rates in primary HER2-positive breast cancer: pooled analysis of 967 patients from five prospective trials investigating lapatinib and trastuzumab†. Ann Oncol. 2016;27:1519–1525.
  • Loi S, Michiels S, Salgado R, et al. Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trial. Ann Oncol. 2014;25:1544–1550.
  • Solinas C, Ceppi M, Lambertini M, et al. 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.
  • Gebhart G, Gamez C, Holmes E, et al. 18F-FDG PET/CT for early prediction of response to neoadjuvant lapatinib, trastuzumab, and their combination in HER2-positive breast cancer: results from Neo-ALTTO. J Nucl Med Off Publ Soc Nucl Med. 2013;54:1862–1868.
  • Gebhart G, Lamberts LE, Wimana Z, et al. Molecular imaging as a tool to investigate heterogeneity of advanced HER2-positive breast cancer and to predict patient outcome under trastuzumab emtansine (T-DM1): the ZEPHIR trial. Ann Oncol Off J Eur Soc Med Oncol. 2016;27:619–624.
  • Ma F, Zhu W, Guan Y, et al. ctDNA dynamics: a novel indicator to track resistance in metastatic breast cancer treated with anti-HER2 therapy. Oncotarget. 2016;7:66020–66031.
  • Cortes J, Baselga J, Im Y-H, et al. Health-related quality-of-life assessment in CLEOPATRA, a phase III study combining pertuzumab with trastuzumab and docetaxel in metastatic breast cancer. Ann Oncol Off J Eur Soc Med Oncol. 2013;24:2630–2635.
  • Attard CL, Pepper AN, Brown ST, et al. Cost-effectiveness analysis of neoadjuvant pertuzumab and trastuzumab therapy for locally advanced, inflammatory, or early HER2-positive breast cancer in Canada. J Med Econ. 2015;18:173–188.
  • Squires H, Pandor A, Thokala P, et al. Pertuzumab for the neoadjuvant treatment of early-stage HER2-positive breast cancer: an evidence review group perspective of a NICE single technology appraisal. PharmacoEconomics [Internet]. 2017. DOI:10.1007/s40273-017-0556-7.
  • Durkee BY, Qian Y, Pollom EL, et al. Cost-effectiveness of pertuzumab in human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol. 2016;34:902–909.
  • Bach PB. Walking the Tightrope Between Treatment Efficacy and Price. J Clin Oncol. 2016;34:889–890.
  • Fleeman N, Bagust A, Beale S, et al. Pertuzumab in combination with trastuzumab and docetaxel for the treatment of HER2-positive metastatic or locally recurrent unresectable breast cancer. PharmacoEconomics. 2015;33:13–23.
  • Tripathy D, Rugo HS, Kaufman PA, et al. The SystHERs registry: an observational cohort study of treatment patterns and outcomes in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. BMC Cancer. 2014;14:307.
  • Daniels B, Lord SJ, Kiely BE, et al. Use and outcomes of targeted therapies in early and metastatic HER2-positive breast cancer in Australia: protocol detailing observations in a whole of population cohort. BMJ Open [Internet]. 2017;7. Available from http://bmjopen.bmj.com/content/7/1/e014439.abstract
  • ASCO CancerLinQ | Enhance Cancer Diagnosis & Treatment [Internet]. [ cited 2018 Jan 25]. Available from: https://cancerlinq.org/.
  • Curigliano G, Burstein HJ, Winer EP, et al. De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Ann Oncol Off J Eur Soc Med Oncol. 2017;28:1700–1712.
  • Llombart-Cussac A, Cortés J, Paré L, et al. 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;18:545–554.
  • Lambertini M, Ferreira AR, Poggio F, et al. Patterns of care and clinical outcomes of first-line trastuzumab-based therapy in HER2-positive metastatic breast cancer patients relapsing after (neo)adjuvant trastuzumab: an Italian multicenter retrospective cohort study. Oncologist. 2015;20:880–889.
  • Lambertini M, Pondé NF, Solinas C, et al. Adjuvant trastuzumab: a 10-year overview of its benefit. Expert Rev Anticancer Ther. 2017;17:61–74.
  • Van Ramshorst MS, Van Werkhoven E, Mandjes IA, et al. A phase III trial of neoadjuvant chemotherapy with or without anthracyclines in the presence of dual HER2-blockade for HER2+ breast cancer: the TRAIN-2 study (BOOG 2012-03). J Clin Oncol. 2017;35:507.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.