Clinical value of circulating tumor cells in metastatic breast cancer
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1) Circulating tumor cells (CTCs) in patients with metastatic breast cancer provide important clinical information and can help guide treatment decisions. The number of CTCs before and during therapy correlates with progression-free and overall survival. 2) Molecular characterization of CTCs can reveal discordance between primary tumors and metastases, as well as heterogeneity within metastatic sites, helping to identify appropriate targeted therapies. Serial CTC analysis during treatment can detect emerging resistance mutations. 3) Monitoring changes in CTC counts during therapy provides an early indicator of treatment effectiveness compared to imaging, and may help determine when to switch treatments for better outcomes.
![ctDNA from 587 patients was analyzed for
PIK3CA mutations by BEAMing technology
In a group of pts with PI3KCA mutations identified by
ctDNA during liquid biopsy, the overall response rate
with fulvestrant and buparlisib was 18.4%, compared
with 3.5% with fulvestrant and placebo (Δ: 14.9%).
In a group of pts with PI3K activation in archival
tissue (primary tumor) the overall response rate with
fulvestrant and buparlisib was 10.6%, compared with
8.2% with fulvestrant and placebo (Δ: 2.4%)
BELLE-2: Phase III, randomized, placebo-controlled study
of buparlisib with fulvestrant in postmenopausal women
with HR+/HER2[ndash] advanced breast cancer
progressing on or after an aromatase inhibitor
Baselga J, SABCS 2015 S6](https://image.slidesharecdn.com/clinicalvalueofcirculatingtumorcellsinmetastaticbreastcancer-171208210340/85/Clinical-value-of-circulating-tumor-cells-in-metastatic-breast-cancer-39-320.jpg)
Clinical value of circulating tumor cells in metastatic breast cancer
- 1. Clinical value of CTCs in metastatic Breast Cancer N. Xenidis, Democritus University of Thrace
- 4. What we can do ? Systemic therapy Against ? Metastatic Breast Cancer Cells Based on what ?.
- 5. ? Are all metastatic sites composed of the same cell population, identical to primary tumor population ?. Based on primary tumor characteristics Is this right ? 1st line Chemo
- 6. Krøigard A. Breast J. 2016 Jul;22(4):420-30 Molecular Concordance Between Primary Breast Cancer and Matched Metastases Probably not There are many reports about discordance of hormone receptors expression between primary tumors and metastatic lesions .
- 7. KrøigardA.BreastJ.2016Jul;22(4):420-30 MolecularConcordanceBetweenPrimaryBreastCancer andMatchedMetastases as well as for HER2 expression
- 8. Moreover various factors, such as - microenvironment - epigenetics - chemotherapy - …… lead to a higher genotype and phenotype diversity Different metastatic clones differ in their ability to colonize specific organs …and probably every metastatic lesion harbors more than one cellular population.
- 10. What we can do ? Repeated biopsies in every new lesion ? invasive time spending costly …….
- 11. Even if… Focus 1 Focus 2 Necrosis Inflammatory cells Obtained information depends on the point of biopsy.
- 12. samples obtained from primary renal carcinomas and associated metastatic sites. Gerlinger M. N Engl J Med. 2012 Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing
- 13. Gerlinger M. N Engl J Med. 2012 Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing 128 mutations 40 ubiquitous mutations 31 mutations shared by primary tumor regions 28 mutations shared by metastatic regions 29 mutations that were unique to specific regions (private mutations) more branched than linear evolution.
- 14. Anderberg C. J Exp Med. 2013 210(3) Deficiency for endoglin in tumor vasculature weakens the endothelial barrier to metastatic dissemination ‘Gaps’ on immature and abnormal tumor vessels permit thousands tumor cells to reach bloodstream every day.
- 15. These tumor cells can be collected by a single venipuncture.
- 16. cell-free DNA represents the genomic DNA fragments released from all tumor sites, from viable and apoptotic cells Apart from circulating tumor cells (CTCs), from peripheral blood can be isolated various components of the tumor, such as circulating cell-free DNA (ccfDNA) or exosomes (cell-derived vesicles) In contrast, circulating tumor cells are clearly related to the disease process, predict more aggressive disease and increased metastasis. As such, CTC reflect the dynamic and metastatic subset of tumor cells.
- 18. Clinical validity of circulating tumor cells in patients with metastatic breast cancer
- 19. Cristofanilli M, N Engl J Med 351;8 19, 2004 Circulating Tumor Cells, Disease Progression, and Survival in Metastatic Breast Cancer Patients with more than 5 CTCs per 7.5ml of whole blood before the treatment had a shorter median PFS and shorter OS The multivariate Cox proportional-hazards regression showed that, the levels of CTCs at baseline were the most significant predictors of progression-free and overall survival. What is prognostic impact of CTCs detection in Metastatic BC patients ?
- 20. 1944 patients with MBC from 20 studies CTC count >5/7.5 mL at baseline associated with decreased PFS (HR 1.92, p<0.0001) and overall survival (HR 2.78, p<0.0001). Bidard FC, Lancet Oncol. 2014 Apr;15(4):406-14 Clinical validity of circulating tumour cells in patients with metastatic breast cancer: a pooled analysis of individual patient data
- 21. Banys-Paluchowski M, Front. Oncol., 01 December 2016 Potential Role of Circulating Tumor Cell Detection and Monitoring in Breast Cancer: A Review of Current evidence Detection and count of CTCs in patients with metastatic BC significantly correlates with disease-free survival and overall survival
- 22. Daniel L Adams, Breast Cancer Res. 2016; 18: 44 Mitosis in circulating tumor cells stratifies highly aggressive breast carcinomas 36 women with stage III or stage IV breast cancer Aim: evaluation of prognostic value of the mitotic status of CTCs Patients without mitotic CTCs had a median survival >24 mo, whereas patients with ≥1 mitotic events had a median survival of 5.7 mo hazard ratio 11.1. Does all collected CTCs have the same importance ?
- 23. Giuliano M, Breast Cancer Research 2014, 16:440 Circulating tumor cells as early predictors of metastatic spread in breast cancer patients with limited metastatic dissemination Peripheral blood from 492 women with MBC collected within 30 days before starting any systemic treatment Aim: correlation between CTCs count before therapy and type of disease progression (‘local’ or expanded) Development of new metastatic sites was significantly more frequent among patients with ≥5 CTCs compared to those with <5 CTCs (progression of pre- existing lesions) 186 patients without visceral metastasis Development of visceral metastases was significantly more frequent in the group with ≥5 CTCs. can CTCs count predict the severity of the upcoming progression ?
- 24. Giuliano M, Breast Cancer Research 2014, 16:440 Circulating tumor cells as early predictors of metastatic spread in breast cancer patients with limited metastatic dissemination time to the development of visceral disease was remarkably different between the CTC groups (42.1 months versus 15.9 months in women with <5 CTCs/7.5 ml versus ≥5 CTCs) Pretreatment CTC counts may identify in advance patients who have higher risk of developing widespread visceral disease and consequently might benefit from early administration of more aggressive systemic treatments. Also useful in patients with limited metastatic dissemination and potentially eligible for locoregional treatments with a curative intent.
- 25. Could CTCs count contribute to decision of therapy ?
- 26. Hayes DF, Clin Cancer Res. 2006 Jul 15;12 Circulating tumor cells at each follow-up time point during therapy of metastatic breast cancer patients predict progression-free and overall survival. Detection of elevated CTCs at any time during therapy is an accurate indication of subsequent rapid disease progression and mortality for MBC patients. What about the effectiveness of therapy on CTCs ? (fluctuation of CTCs count during therapy)
- 27. Bidard FC, Lancet Oncol. 2014 Apr;15(4):406-14 Clinical validity of circulating tumour cells in patients with metastatic breast cancer: a pooled analysis of individual patient data Increased CTC counts 3-5 weeks after start of treatment, adjusted for CTC count at baseline, were associated with shortened progression-free survival (HR 1.85, p<0.0001) and overall survival (HR 2.26, p<0.0001)
- 28. 50 studies with 6712 patients, neoadjuvant, adjuvant & metastatic Reduction of CTC-positive rate was associated with - lower probability of disease progression (OR = 0.54, P = 0.01) - longer progression-free survival period (mean difference = 5.07 months, P < 0.0001) - longer overall survival period (mean difference = 11.61 months, P < 0.00001) These results demonstrate that CTC status can serve as an indicator to monitor the effectiveness of treatments. Wen-Ting Yan, Nature Scientific Reports 2017, 7:43464 Circulating tumor cell status monitors the treatment responses in breast cancer patients: a meta-analysis
- 29. Budd T, Clin Cancer Res. 2006 Nov 1;12(21) Circulating Tumor Cells versus Imaging Predicting Overall Survival in Metastatic Breast Cancer <5 CTCs and stable disease/partial response by radiology <5 CTCs and progressive disease by radiology ≥5 CTCs and stable disease/partial response by radiology ≥5 CTCs and progressive disease by radiology 138 metastatic breast cancer patients Use of CTCs Vs radiology for prediction of overall survival Multivariate Cox proportional hazards regression, hazard ratios: - 2.00 (P = 0.006) radiology assessment - 2.53 (P < 0.001) for CTCs. Radiology assessment is not enough ? Assessment of CTCs is an earlier, more reproducible indication of disease status than current imaging methods. CTCs may be a superior surrogate end point, as they are highly reproducible and correlate better with overall survival than do changes determined by traditional radiology.
- 30. Smerage J, JCO 2014 Circulating Tumor Cells and Response to Chemotherapy in Metastatic Breast Cancer: SWOG S0500 Is this information (impact of therapy on CTCs count) adequate for treatment guidance ? Did early discontinuation of an ineffective treatment (in terms of CTCs elimination) and switch to an alternate therapy improves outcome ?.
- 31. For patients with persistently increased CTCs after 21 days of first-line chemotherapy, early switching to an alternate cytotoxic therapy was not effective in prolonging PFS or OS Smerage J, JCO 2014 Circulating Tumor Cells and Response to Chemotherapy in Metastatic Breast Cancer: SWOG S0500
- 33. Aktas B, Gynecol Oncol. 2011;122(2):356–60 Comparison of estrogen and progesterone receptor status of circulating tumor cells and the primary tumor in metastatic breast cancer patients Overall detection rate for CTCs was 45% (87/193 patients) 77% patients with ER(+) tumors, have ER(-) CTCs 87% patients with PR(+) tumors have PR(-) CTCs Primary tumors and CTCs displayed a concordant ER and PR status in only 41% and 45% of cases, respectively. Loss of hormonal receptor expression during the course of the disease is considered as a cause for poor response to endocrine therapy in primarily hormonal receptor-positive breast cancer patients. Reassessment of ER and RP in CTCs and in recurrent tumor samples could guide treatment decisions in metastatic treatments. Re-assessment of therapy targets How molecular characterization of CTCs can improve management of patients with MBC ?
- 34. Re-assessment of hormone receptor status… Is adequate ? One half of patients with HR(+) metastatic breast cancer does not respond in hormone depletion Paoletti B, San Antonio Breast Cancer Symposium 2016 Circulating tumor cell number and CTC-endocrine therapy index predict clinical outcomes in ER positive metastatic breast cancer patients: Results of the COMETI Phase 2 trial CTC expression of 4 markers: - low expression of ER and BCL-2, - high expression of HER2 and Ki67 as markers of endocrine therapy resistance (CTC-Endocrine Therapy Index, CTC-ETI) 80% of patients with high CTC-ETI experienced rapid progression vs 40% of patients with low CTC-ETI .
- 35. Shaw J, Clin Cancer Res. 2017 Jan 1;23(1):88-96 Mutation Analysis of Cell-Free DNA and Single Circulating Tumor Cells in Metastatic Breast Cancer Patients with High Circulating Tumor Cell Counts CTCs were isolated by DEPArray and compared with matched cfDNA and primary tumor tissue by targeted next-generation sequencing (NGS) of about 2,200 COSMIC mutations in 50 cancer genes NGS analysis of CTCs from 5 patients with MBC revealed mutational heterogeneity in PIK3CA, TP53, ESR1, and KRAS genes between individual CTCs. ESR1 and KRAS gene mutations were absent from primary tumor tissue The ESR1 p.D538G, p.Y537 mutations leads to ligand- independent activation of ERa and in primary resistance to endocrine therapy. what about ESR1 mutations ?
- 36. But, almost all patients, after an initial response, eventually become resistance in endocrine therapy… PI3K-activating mutations can activate AKT-ER pathway in the absence of estrogen and may this way contribute to resistance to endocrine therapy.
- 37. Guttery D, Clin Chem. 2015 Jul;61(7) Next Generation Sequencing (NGS) for detection of hot-spot mutations in ESR1, PIK3CA, TP53, FGFR1 & 2 PIK3CA p.E545K mutation emerged 4 months into the study, and the mutation frequency increased through treatment and correlated with the clinical course of the disease as assessed using the serum marker CA15-3 Mutation Analysis of Cell-Free DNA and Single Circulating Tumor Cells in Metastatic Breast Cancer Patients with High Circulating Tumor Cell Counts Analysis of serial samples collected in patients while on therapy Suppression of AKT pathway with pan-PI3K inhibitors (burpalisib-BELLE-2 trial), and mTOR inhibitors (everolimus-BOLERO-3 trial) probably overcomes acquired resistance.
- 38. BELLE-2: Phase III, randomized, placebo-controlled study of buparlisib with fulvestrant in postmenopausal women with HR(+)/HER2(-) advanced breast cancer progressing on or after an aromatase inhibitor Baselga J, SABCS 2015 S6 Study met the primary endpoint: addition of Buparlisib to Fulvestrant improves PFS .
- 39. ctDNA from 587 patients was analyzed for PIK3CA mutations by BEAMing technology In a group of pts with PI3KCA mutations identified by ctDNA during liquid biopsy, the overall response rate with fulvestrant and buparlisib was 18.4%, compared with 3.5% with fulvestrant and placebo (Δ: 14.9%). In a group of pts with PI3K activation in archival tissue (primary tumor) the overall response rate with fulvestrant and buparlisib was 10.6%, compared with 8.2% with fulvestrant and placebo (Δ: 2.4%) BELLE-2: Phase III, randomized, placebo-controlled study of buparlisib with fulvestrant in postmenopausal women with HR+/HER2[ndash] advanced breast cancer progressing on or after an aromatase inhibitor Baselga J, SABCS 2015 S6
- 40. Current molecular profile of the disease can predicts accurately the response in a certain therapeutical intervention Comparison of the PI3KCA pathway in circulating tumor cells and corresponding tumor tissue of patients with metastatic breast cancer Bredemeier M, Mol Med Rep. 2017 May;15(5):2957-2968 90 metastatic BC patients 41% (25/61) of patients with PI3KCA wild-type tumors had PI3KCA(+) CTCs 55% (16/29) of patients with PI3KCA mutated tumors had PI3KCA(-) CTCs maximal benefit of buparlisib no benefit of buparlisib.
- 41. Jaeger B, PLoS One. 2017 Jun 6;12(6) The HER2 phenotype of circulating tumor cells in HER2-positive early breast cancer: A translational research project of a prospective randomized phase III trial HER2 status of CTCs in 258 patients with HER2-positive primary breast cancer at the time of diagnosis Aim: reveal discordance rate of HER2 status between primary tumor and CTCs 32% of the CTC-positive patients exclusively had CTCs with strong HER2 staining 12% had only CTCs with negative HER2 staining.
- 42. Kallergi G, Breast Cancer Research (2015) 17:113 Expression of truncated HER2 on circulating tumor cells of breast cancer patients The truncated form of human epidermal growth factor receptor 2 (p95HER2) lacks the HER2 extracellular domain and has been associated with poor prognosis and resistance to trastuzumab p95HER2 receptor was identified in 40% of patients with metastatic disease Treatment with Trastuzumab increased the percentage of patients with p95HER2-positive CTCs from 40 % to 63 %. Overall survival of patients with p95HER2-positive CTCs was significantly decreased (p=0.03).
- 43. Kallergi G, Intern. Conference on Antimicrobial Agents and Chemo. 2015 Isolation and characterization of circulating tumor cells (CTCs) in triple negative breast cancer patients in response to chemotherapy 55 early Triple negative breast cancer patients before and after adjuvant chemotherapy CTCs were detected in 60% after the completion of adjuvant chemotherapy But, the goal is not only to exclude useless therapies More important: detection of new targets in a certain patient, targets that didn’t exist in primary tumor and have been raised during metastasis formation. These targets can be omitted by a spot biopsy of a metastatic lesion Agelaki S, Oncotarget, 2017, Vol. 8, (No. 3) Phenotypic characterization of circulating tumor cells in triple negative breast cancer patients 26%, 34% and 51% of CTCs from patients with triple negative MBC express ER, PR and HER2 respectively. The percentage of ER-, PR-, HER2-expressing CTCs was 26%, 34% and 57% respectively
- 44. Fehm T, Breast Cancer Res Treat. 2010 Nov;124(2):403-12 HER2 status of circulating tumor cells in patients with metastatic breast cancer: a prospective, multicenter trial 245 patients with metastatic breast cancer HER2(+) CTCs in HER2(-) primary tumors: 32% CellSearch assay 49% AdnaTest BreastCancer Addition anti-HER2 therapy in patients with HER2(-) tumors and HER2 (+) CTCs ? Apostolaki S, Breast Cancer Res Treat. 2008 Nov Detection of occult HER2 mRNA-positive tumor cells in the peripheral blood of patients with operable breast cancer: evaluation of their prognostic relevance 216 women with early breast cancer HER2mRNA(+) CTCs were detected in 25% of patients with HER2(-) primary tumors Why not ? Why administrate hormonal therapy in metastatic patients with 1% ER(+) tumors.
- 45. Phase II Studies with Single Agent Lapatinib PR: 1.4%, Clinical Benefit: 5.7% PR: 5.1%, Clinical Benefit: 9.0% Burstein HJ, Ann Oncol. 2008 Blackwell KL, Ann Oncol. 2009. Disappointing results ? Agelaki S, PLoS One. 2015 Jun 17;10(6) Efficacy of Lapatinib in Therapy-Resistant HER2-Positive Circulating Tumor Cells in Metastatic Breast Cancer 22 patients with HER2(-) tumors and HER2(+) CTCs In 5 (23.8%) patients, HER2(+) CTC counts increased in 14 (66.6%) patients HER2(+) CTC counts decreased the decrease was significant only among patients presenting disease stabilization (p = 0.018) but not among those with disease progression during lapatinib treatment no objective responses, stable disease 11 (52.4%) patients median PFS 4.0 months, 1-year PFS rate 14.3%
- 46. Anti-HER2 treatment in advanced metastatic HER2-negative breast cancer patients with elevated serum levels of the HER2 extracellular domain and/or HER2 overexpressing circulating tumor cells Kurbacher C, ASCO 2017 abstr 597 31 pts with HER2(-) MBC exhibiting sHER2 values > 15 ng/mL (n = 8), HER2+ CTCs (n = 7), or both (n = 16) Pts received Anti-HER2 (H, L or P) treatment alone or in combination with another treatment Anti-HER2 Tx is effective in pts with pretreated occult HER2(+) MBC and HER2(-) primary tumor. Median number of prior treatments: 7
- 47. 20% of HER2(-) MBC patients were screened with at least 1 HER2 (+) CTC
- 49. Adapted from: T. N. Schumacher and R. D. Schreiber (2015) Science 348, 69 and L. B. Alexandrov et al. (2013) Nature 500, 415 Immunotherapy It is known that mutational load of primary breast cancer is moderate, thus is not a suitable tumor for immunotherapy.
- 50. Luen SJ, Lancet Oncol. 2017 Jan;18(1):52-62 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 pre-existing T-cells vary by site of metastasis. But, the cancer immune microenvironment is not static. It evolves and differentiate during metastasiogenesis…
- 51. …and changes with therapeutic intervention Accumulation of CD11c+ dendritic cells and enhanced CD8+ activation in breast tumors were demonstrated in mice treated with cisplatin Elevation of TIL percentage has been demonstrated after taxane neoadjuvant therapy, and this reaction correlated with clinical response Anthracyclines can stimulate CD8+ lymphocyte proliferation in tumors trastuzumab could modulate immune activity by reducing the level of circulating Tregs Kang TH, Cancer Res. 2013;73(8):2493-2504. Demaria S, Clin Cancer Res. 2001;7(10):3025-3030. Mattarollo SR, Cancer Res. 2011;71(14):4809-4820. Horlock C, Br J Cancer. 2009;100(7):1061-1067.
- 52. Ali HR, Annals of Oncology 26: 1488–1493, 2015 PD-L1 protein expression in breast cancer is rare, enriched in basal-like tumours and associated with infiltrating lymphocytes 3916 primary tumour samples from 3 clinical studies (SEARCH, NEAT and METABRIC) (Basal-like) PD-L1 expression by immune cells was observed in 6% of tumours and expression by tumour cells was observed in just 1.7%. PD-L1 was most frequently expressed in basal-like tumours (39% of IntClust 10 in METABRIC study and 19% of basal-like in SEARCH and NEAT studies). PD-L1 has been used in many studies as a bio-marker and in many tumors correlates with immunotherapy effectiveness
- 53. Zhang M, Oncotarget, 2017, Vol. 8, (No. 19) Expression of PD-L1 and prognosis in breast cancer: a meta-analysis 5 studies containing 2,546 cases PDL1 expression was increased in patients with - positive lymph node metastasis (P=0.02) - higher histological grade (P < 0.001) - estrogen receptor (ER)-negativity (P=0.008) - triple negative breast cancer (TNBC) (P < 0.001)
- 54. But, PD-L1 expression is a dynamic process which regulated by various cytokines during the course of disease Upregulation Downregulation primary breast tumor PD-L1(-) lung metastasis PD-L1(+) Ashley Cimino-Mathews , Hum Pathol. 2016 January ; 47(1): 52–63. As result, metastatic lesions obtain a different profile of immune reactivity than primary tumors.
- 55. Additionally, PD-L1 expression can changes after therapeutic interventions… Mengqi Y, Molecular Oncology11(2017) 358–372 Chemotherapy induces tumor immune evasion by upregulation of programmed cell death ligand 1expression in bone marrow stromal cells Sun W et al., abstract JCSE 01.16 Altered Expression of Programmed Death-1 Receptor (PD-1) and its Ligand PD-L1, PD-L2 after Neo-Adjuvant Chemotherapy in Lung Cancer McDaniel A, European Urology Focus 2016, 265-268 Expression of PDL1 (B7-H1) Before and After Neoadjuvant Chemotherapy in Urothelial Carcinoma Song Z et al., Lung Cancer 2016, V99 166-171 Altered expression of programmed death-ligand 1 after neo-adjuvant chemotherapy in patients with lung squamous cell carcinoma Sharabi AB et al., Lancet Oncology 2015, Volume 16, No. 13, e498–e509 Radiation and checkpoint blockade immunotherapy: radiosensitisation and potential mechanisms of synergy
- 56. Mazel M, Mol Oncol. 2015 Nov;9(9) Frequent expression of PD-L1 on circulating breast cancer cells Peripheral blood samples from 16 HR(+), HER2(-) metastatic breast cancer patients with a CTC count >1 using the CellSearch system Eleven patients out of 16 showed a subpopulation of CTCs expressing PD-L1 (68.8%) The fraction of PD-L1(+) CTCs varied from 0.2 - 100%.
- 57. Pizon M, ASCO 2016 abstr 3071 Frequency of PDL-1 expressed on circulating epithelial tumor cells (CETCs) compared to PDL-2 and role in immune evasion in cancer progression CETCs were determined from blood of 66 patients (16 MBC, 50 early BC) PDL-1 expressing CETCs were detected in 95 % PD-L2 in 75% in all stages… more frequent after RT Metastatic tumors that harbor PD-L1(+) CTCs might benefit from check-point inhibitors, irrespectively of PD-L1 expression of (long ago) excised primary tumor.
- 58. Pizon M, Breast Cancer Symposium, 2014 In vitro chemosensitivity testing of mammospheres cultured from circulating epithelial tumor cells (CETCs) of breast cancer patients: Comparision to chemosensitivity of total CETCs A subpopulation of CTCs with proliferation activity has the ability to form floating spheres in suspension culture - CTCs isolation (Maintrac) - Culture in conditions favoring growth of epithelial cells - Determination of sphere formation - Addition of anticancer drugs - Image analysis of CTCs and spheroids using the Scan^R Fluorescence microscopy
- 59. Min Yu, Science. 2014 July 11; 345(6193): 216–220 Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility Long-term oligoclonal CTC cultures from six patients with metastatic luminal subtype breast cancers Cell viability after treatment of CTC lines with selected anticancer drugs, according to detected mutations that have been previously recognized by NGS
- 60. In Summary… Detection, enumeration and characterization of circulating tumor cells in metastatic breast cancer could be useful for - estimate risk of progression and death from disease - real time monitoring therapeutic response - guidance of therapeutic strategy - recognition of heterogeneous resistance mechanism - identification of new therapeutic targets - understanding the biology of metastatic development.