Wolff AC, Hammond MEH, Allison KH, Harvey BE, Mangu PB, Bartlett JMS, Bilous M, Ellis IO, Fitzgibbons P, Hanna W et al (2018) Human epidermal growth factor receptor 2 testing in breast cancer: american society of clinical oncology/college of american pathologists clinical practice guideline focused update. J Clin Oncol 36(20):2105–2122. https://doi.org/10.1200/JCO.2018.77.8738

Article  CAS  PubMed  Google Scholar 

Curtit E, Nerich V, Mansi L, Chaigneau L, Cals L, Villanueva C, Bazan F, Montcuquet P, Meneveau N, Perrin S et al (2013) Discordances in estrogen receptor status, progesterone receptor status, and HER2 status between primary breast cancer and metastasis. Oncologist 18(6):667–674. https://doi.org/10.1634/theoncologist.2012-0350

Article  PubMed  PubMed Central  Google Scholar 

Walter V, Fischer C, Deutsch TM, Ersing C, Nees J, Schütz F, Fremd C, Grischke E-M, Sinn P, Brucker SY et al (2020) Estrogen, progesterone, and human epidermal growth factor receptor 2 discordance between primary and metastatic breast cancer. Breast Cancer Res Treat 183(1):137–144. https://doi.org/10.1007/s10549-020-05746-8

Article  CAS  PubMed  PubMed Central  Google Scholar 

Aurilio G, Disalvatore D, Pruneri G, Bagnardi V, Viale G, Curigliano G, Adamoli L, Munzone E, Sciandivasci A, De Vita F et al (2014) A meta-analysis of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 discordance between primary breast cancer and metastases. Eur J Cancer 50(2):277–289. https://doi.org/10.1016/j.ejca.2013.10.004

Article  CAS  PubMed  Google Scholar 

Van Raemdonck E, Floris G, Berteloot P, Laenen A, Vergote I, Wildiers H, Punie K, Neven P (2021) Efficacy of anti-HER2 therapy in metastatic breast cancer by discordance of HER2 expression between primary and metastatic breast cancer. Breast Cancer Res Treat 185(1):183–194

Article  PubMed  Google Scholar 

Gennari A, Andre F, Barrios CH, Cortes J, de Azambuja E, DeMichele A, Dent R, Fenlon D, Gligorov J, Hurvitz SA et al (2021) ESMO clinical practice guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer. Ann Oncol 32(12):1475–1495. https://doi.org/10.1016/j.annonc.2021.09.019

Article  CAS  PubMed  Google Scholar 

Keller L, Pantel K (2019) Unravelling tumour heterogeneity by single-cell profiling of circulating tumour cells. Nat Rev Cancer 19(10):553–567. https://doi.org/10.1038/s41568-019-0180-2

Article  CAS  PubMed  Google Scholar 

Bidard F-C, Peeters DJ, Fehm T, Nolé F, Gisbert-Criado R, Mavroudis D, Grisanti S, Generali D, Garcia-Saenz JA, Stebbing J et al (2014) Clinical validity of circulating tumour cells in patients with metastatic breast cancer: a pooled analysis of individual patient data. Lancet Oncol 15(4):406–414. https://doi.org/10.1016/S1470-2045(14)70069-5

Article  PubMed  Google Scholar 

Riethdorf S, Muller V, Zhang L, Rau T, Loibl S, Komor M, Roller M, Huober J, Fehm T, Schrader I et al (2010) Detection and HER2 expression of circulating tumor cells: prospective monitoring in breast cancer patients treated in the neoadjuvant geparquattro trial. Clin Cancer Res 16(9):2634–2645. https://doi.org/10.1158/1078-0432.CCR-09-2042

Article  CAS  PubMed  Google Scholar 

Verschoor N, Deger T, Jager A, Sleijfer S, Wilting SM, Martens JWM (2022) Validity and utility of HER2/ERBB2 copy number variation assessed in liquid biopsies from breast cancer patients: a systematic review. Cancer Treat Rev 106:102384

Article  CAS  PubMed  Google Scholar 

Meng S, Tripathy D, Shete S, Ashfaq R, Haley B, Perkins S, Beitsch P, Khan A, Euhus D, Osborne C et al (2004) HER-2 gene amplification can be acquired as breast cancer progresses. Proc Natl Acad Sci U S A 101(25):9393–9398

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jones SE, Erban J, Overmoyer B, Budd GT, Hutchins L, Lower E, Laufman L, Sundaram S, Urba WJ, Pritchard KI et al (2005) Randomized phase III study of docetaxel compared with paclitaxel in metastatic breast Cancer. J Clin Oncol 23(24):5542–5551. https://doi.org/10.1200/jco.2005.02.027

Article  CAS  PubMed  Google Scholar 

A’Hern RP (2001) Sample size tables for exact single-stage phase II designs. Stat Med 20(6):859–866

Article  CAS  PubMed  Google Scholar 

Sauerbrei W, Taube SE, McShane LM, Cavenagh MM, Altman DG (2018) Reporting recommendations for tumor marker prognostic studies (REMARK): an abridged explanation and elaboration. J Natl Cancer Inst 110(8):803–811. https://doi.org/10.1093/jnci/djy088

Article  PubMed  PubMed Central  Google Scholar 

Beije N, Onstenk W, Kraan J, Sieuwerts AM, Hamberg P, Dirix LY, Brouwer A, de Jongh FE, Jager A, Seynaeve CM et al (2016) Prognostic impact of HER2 and ER status of circulating tumor cells in metastatic breast cancer patients with a HER2-negative primary tumor. Neoplasia 18(11):647–653. https://doi.org/10.1016/j.neo.2016.08.007

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sieuwerts AM, Mostert B, Bolt-de Vries J, Peeters D, de Jongh FE, Stouthard JML, Dirix LY, van Dam PA, Van Galen A, de Weerd V et al (2011) mRNA and microRNA expression profiles in circulating tumor cells and primary tumors of metastatic breast cancer patients. Clin Cancer Res 17(11):3600–3618. https://doi.org/10.1158/1078-0432.Ccr-11-0255

Article  CAS  PubMed  Google Scholar 

Reijm EA, Sieuwerts AM, Smid M, Vries JB-d, Mostert B, Onstenk W, Peeters D, Dirix LY, Seynaeve CM, Jager A et al (2016) An 8-gene mRNA expression profile in circulating tumor cells predicts response to aromatase inhibitors in metastatic breast cancer patients. BMC Cancer 16(1):123. https://doi.org/10.1186/s12885-016-2155-y

Article  CAS  PubMed  PubMed Central  Google Scholar 

Fehm T, Mueller V, Banys-Paluchowski M, Fasching PA, Friedl TWP, Hartkopf A, Huober J, Loehberg C, Rack B, Riethdorf S et al (2021) Abstract PD3–12: efficacy of the tyrosine kinase inhibitor lapatinib in the treatment of patients with HER2-negative metastatic breast cancer and HER2-positive circulating tumor cells - results from the randomized phase III DETECT III trial. Cancer Res. https://doi.org/10.1158/1538-7445.Sabcs20-pd3-12

Article  Google Scholar 

Hainsworth JD, Murphy PB, Alemar JR, Daniel BR, Young RR, Yardley DA (2016) Use of a multiplexed immunoassay (PRO Onc assay) to detect HER2 abnormalities in circulating tumor cells of women with HER2-negative metastatic breast cancer: lack of response to HER2-targeted therapy. Breast Cancer Res Treat 160(1):41–49

Article  CAS  PubMed  Google Scholar 

Jacot W, Cottu P, Berger F, Dubot C, Venat-Bouvet L, Lortholary A, Bourgeois H, Bollet M, Servent V, Luporsi E et al (2019) Actionability of HER2-amplified circulating tumor cells in HER2-negative metastatic breast cancer: the CirCe T-DM1 trial. Breast Cancer Res 21(1):121. https://doi.org/10.1186/s13058-019-1215-z

Article  CAS  PubMed  PubMed Central  Google Scholar 

Parsons HA, Macrae ER, Guo H, Li T, Barry WT, Tayob N, Wulf GM, Isakoff SJ, Krop IE (2021) Phase II single-arm study to assess trastuzumab and vinorelbine in advanced breast cancer patients with HER2-negative tumors and HER2-positive circulating tumor cells. JCO Precis Oncol 5(5):896–903. https://doi.org/10.1200/PO.20.00461

Article  PubMed  Google Scholar 

Pestrin M, Bessi S, Puglisi F, Minisini AM, Masci G, Battelli N, Ravaioli A, Gianni L, Di Marsico R, Tondini C et al (2012) Final results of a multicenter phase II clinical trial evaluating the activity of single-agent lapatinib in patients with HER2-negative metastatic breast cancer and HER2-positive circulating tumor cells. A proof-of-concept study. Breast Cancer Res Treat 134(1):283–289. https://doi.org/10.1007/s10549-012-2045-1

Article  CAS  PubMed  Google Scholar 

De Gregorio A, Friedl TWP, Huober J, Scholz C, De Gregorio N, Rack B, Trapp E, Alunni-Fabbroni M, Riethdorf S, Mueller V et al (2017) Discordance in human epidermal growth factor receptor 2 (HER2) phenotype between primary tumor and circulating tumor cells in women with HER2-negative metastatic breast cancer. JCO Precis Oncol 2017(1):1–12

Article  Google Scholar 

Jaeger BAS, Neugebauer J, Andergassen U, Melcher C, Schochter F, Mouarrawy D, Ziemendorff G, Clemens M, E VA, Heinrich G, et al (2017) The HER2 phenotype of circulating tumor cells in HER2-positive early breast cancer: a translational research project of a prospective randomized phase III trial. PLoS One 12(6):e0173593. https://doi.org/10.1371/journal.pone.0173593

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nanou A, Zeune LL, Bidard FC, Pierga JY, Terstappen L (2020) HER2 expression on tumor-derived extracellular vesicles and circulating tumor cells in metastatic breast cancer. Breast Cancer Res 22(1):86. https://doi.org/10.1186/s13058-020-01323-5

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang S, Li L, Wang T, Bian L, Hu H, Xu C, Liu B, Liu Y, Cristofanilli M, Jiang Z (2016) Real-time HER2 status detected on circulating tumor cells predicts different outcomes of anti-HER2 therapy in histologically HER2-positive metastatic breast cancer patients. BMC Cancer 16(1):526. https://doi.org/10.1186/s12885-016-2578-5

Article  CAS  PubMed  PubMed Central  Google Scholar 

Muller V, Banys-Paluchowski M, Friedl TWP, Fasching PA, Schneeweiss A, Hartkopf A, Wallwiener D, Rack B, Meier-Stiegen F, Huober J et al (2021) Prognostic relevance of the HER2 status of circulating tumor cells in metastatic breast cancer patients screened for participation in the DETECT study program. ESMO Open 6(6):100299. https://doi.org/10.1016/j.esmoop.2021.100299

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jordan NV, Bardia A, Wittner BS, Benes C, Ligorio M, Zheng Y, Yu M, Sundaresan TK, Licausi JA, Desai R et al (2016) HER2 expression identifies dynamic functional states within circulating breast cancer cells. Nature 537(7618):102–106. https://doi.org/10.1038/nature19328

Article  CAS  PubMed  PubMed Central  Google Scholar 

Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, Tsurutani J, Ueno NT, Prat A, Chae YS et al (2022) Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med 387(1):9–20. https://doi.org/10.1056/NEJMoa2203690

Article  CAS  PubMed  PubMed Central