scholarly journals Cut-Off Analysis of CTC Change under Systemic Therapy for Defining Early Therapy Response in Metastatic Breast Cancer

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1055 ◽  
Author(s):  
Thomas M. Deutsch ◽  
Stefan Stefanovic ◽  
Manuel Feisst ◽  
Chiara Fischer ◽  
Fabian Riedel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Disease Progression ◽  
Systemic Therapy ◽  
Metastatic Breast ◽  
Therapy Response ◽  
Breast Cancer Patients ◽  
Early Therapy ◽  
System A ◽  
Negative Prognostic Factor ◽  
Independent Negative Prognostic Factor

Detection of circulating tumor cells (CTC) can distinguish between aggressive and indolent metastatic disease in breast cancer patients and is thus considered an independent, negative prognostic factor. A clear decline in CTCs is observed in patients who respond to systemic therapy. Nevertheless, CTCs can decrease in patients experiencing disease progression during systemic therapy, too. This study aims to determine the differences between CTC decline in patients responding to therapy and those in whom disease is progressing. Therefore, CTC values were compared at the start and after one cycle of a new line of systemic therapy. In all, 108 initially CTC-positive patients (with ≥5 intact CTCs in 7.5 mL blood) were enrolled in this study and intact and apoptotic CTCs were measured via the CellSearch® system. A cut-off analysis was performed using Youden’s J statistics to differentiate between CTC change in the two groups. Here, 64 (59.3%) patients showed stable disease or partial response vs. 44 (40.7%) presenting disease progression. Median overall survival was 23 (range: 4–92) vs. 7 (2–43) months (p < 0.001). Median intact CTC count at enrollment was 15.0 (5–2760) vs. 30.5 (5–200000) cells (p = 0.39) and 2.5 (0–420) vs. 8.5 (0–15000) cells after one cycle of systemic therapy (p = 0.001). Median apoptotic CTC count at enrollment was 10.5 (0–1500) vs. 9 (0–800) cells (p = 0.475) and 1 (0–200) vs. 3 (0–250) cells after one cycle of systemic therapy (p = 0.01). A 50% reduction in baseline apoptotic CTC count represents the optimal cut-off to differentiate between therapy response and disease progression. An apoptotic CTC reduction of ≤10% is 74% specific for early disease progression.

scholarly journals Dysmetabolic Circulating Tumor Cells Are Prognostic in Metastatic Breast Cancer

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1005 ◽  
Author(s):  
Giulia Brisotto ◽  
Eva Biscontin ◽  
Elisabetta Rossi ◽  
Michela Bulfoni ◽  
Aigars Piruska ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Metastatic Breast ◽  
Therapy Response ◽  
Label Free ◽  
Breast Cancer Patients ◽  
Combining Data ◽  
Definition Of

Circulating tumor cells (CTCs) belong to a heterogeneous pool of rare cells, and a unequivocal phenotypic definition of CTC is lacking. Here, we present a definition of metabolically-altered CTC (MBA-CTCs) as CD45-negative cells with an increased extracellular acidification rate, detected with a single-cell droplet microfluidic technique. We tested the prognostic value of MBA-CTCs in 31 metastatic breast cancer patients before starting a new systemic therapy (T0) and 3–4 weeks after (T1), comparing results with a parallel FDA-approved CellSearch (CS) approach. An increased level of MBA-CTCs was associated with: i) a shorter median PFS pre-therapy (123 days vs. 306; p < 0.0001) and during therapy (139 vs. 266 days; p = 0.0009); ii) a worse OS pre-therapy (p = 0.0003, 82% survival vs. 20%) and during therapy (p = 0.0301, 67% survival vs. 38%); iii) good agreement with therapy response (kappa = 0.685). The trend of MBA-CTCs over time (combining data at T0 and T1) added information with respect to separate evaluation of T0 and T1. The combined results of the two assays (MBA and CS) increased stratification accuracy, while correlation between MBA and CS was not significant, suggesting that the two assays are detecting different CTC subsets. In conclusion, this study suggests that MBA allows detection of both EpCAM-negative and EpCAM-positive, viable and label-free CTCs, which provide clinical information apparently equivalent and complementary to CS. A further validation of proposed method and cut-offs is needed in a larger, separate study.

Activity of trastuzumab-based therapy beyond disease progression in heavily pretreated metastatic breast cancer patients—Single institution experience

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13159-13159
Author(s):  
P. Tokajuk ◽  
B. Czartoryska-Arlukowicz ◽  
M. Z. Wojtukiewicz
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Disease Progression ◽  
Soft Tissues ◽  
Advanced Disease ◽  
Metastatic Breast ◽  
Second Line ◽  
Breast Cancer Patients ◽  
Heavily Pretreated ◽  
Her 2

13159 Background: Benefits from continuing trastuzumab-based (TZB) therapy beyond disease progression in HER-2-overexpressing metastatic breast cancer (MBC) patients (pts) remain obscure. Methods: A retrospective analysis was undertaken to assess activity of TZB therapy for MBC pts treated in our institution from 2002 to 2005 outside clinical trials. Results: 27 pts were evaluated. Median age: 52 years (range, 33–62). 9 pts (33.3%) were premenopausal. Hormonal receptors status: 9 pts ER(+), 4 pts PgR (+), 2 unknown. HER-2 overexpression was determined by IHC staining (3+ score) in all pts. Metastases location: 18 pts soft tissues/bone, 18 pts visceral disease. Median number of metastatic sites: 2 (range: 1–4). 9 pts (33.3%) had metastases in < 2 locations. 16 pts (59.2%) received neo/adjuvant chemotherapy: 11 pts doxorubicin, 8 pts CMF, 2 pts docetaxel, 4 pts other. Median previous chemotherapy lines for advanced disease: 2 (range: 0–6). 16 pts received doxorubicin/epirubicin, 14 pts docetaxel, 13 pts vinorelbine as a part of advanced disease chemotherapy regimen. Trastuzumab was administered at standard doses and combined with docetaxel, vinorelbine, cisplatin, capecitabine, etoposide, gemcitabine or administered as monotherapy. Response for the first-line TZB therapy was as follows: CR 5/27 pts (18.5%); PR 10/27 pts (37%). Median TTP was 5.8 months (range: 0–22). 14/27 pts (51.8%) received a second-line TZB therapy beyond disease progression. Response for the second-line therapy: CR 2/14 pts (14.3%); PR 5/14 pts (35.7%). Median TTP was 5.1 months (range: 0–24). 6/14 pts received a third-line and subsequent lines (up to five lines) of TZB therapy. PR for subsequent lines of therapy was observed in 4 pts. Median survival has not been reached. Pts who received ≥2 of TZB regimens survived significantly longer than pts who had received only 1 regimen (P = 0,02 logrank). Pts with metastasis in 1 location survived significantly longer than pts with metastasis in ≥2 sites (P = 0,01 logrank). Conclusions: Trastuzumab-based therapy seems to be active in MBC pts beyond disease progression even in heavily pretreated population. Durable responses were observed in some cases. No significant financial relationships to disclose.

Correlation between NK function and response to trastuzumab in metastatic breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 3036-3036
Author(s):  
A. Beano ◽  
E. Signorino ◽  
M. A. Polimeni ◽  
M. Mistrangelo ◽  
M. Ardine ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Nk Cells ◽  
Disease Progression ◽  
Mononuclear Cells ◽  
Metastatic Breast ◽  
Nk Activity ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Peripheral Blood Mononuclear ◽  
Effector Cells

3036 Background: Trastuzumab is a monoclonal antibody selectively directed against Her2 approved for the treatment of Her2 overexpressing breast cancer patients. Its proposed mechanisms of action include also a role in mediating antibody-dependent cellular cytotoxicity (ADCC), through the triggering of the FcγRIII on natural killer (NK) cells. This study addressed the correlation between overall NK function and clinical trastuzumab activity. Methods: Between March and September 2006 22 metastatic patients in treatment with trastuzumab alone (8 mg/kg load and then 6 mg/kg every 3 weeks until disease progression) as maintaining therapy after chemotherapy were analyzed for clinical and immunological responses. According to RECIST criteria, 14 patients obtained a response to trastuzumab, while 8 patients had a disease progression. Patient’s peripheral blood mononuclear cells were tested for cytotoxic activity against standard NK target (the MHC class I-negative K562 cell line) and trastuzumab-coated MCF7 (Her2-negative) and SKBR3 (Her2-positive) human cell lines in a 4-h 51Cr-release cytotoxicity assay in the presence of grading concentrations of effector cells. Results: NK activity was significantly (p<0.05) higher in responder compared to non responder patients at all the four effector:target (50:1 to 6:1) ratios tested. NK activity of non responder patients was significantly lower than that of 25 sex and age matched controls (p<0.02) and this was not merely due to chemotherapy- or tumor-associated immunosuppression, since the values of responder patients did not significantly differ from those of controls. ADCC activity against Her2-positive SKBR3 cells was also significantly higher in responder compared to non responder patients (p<0.05) and markedly so when compared to controls (p<0.001). Conclusions: The fact that, as shown here, normal levels of FcγR- independent and higher than normal levels of FcγR-dependent cytotoxicity are required for trastuzumab response, lends support to a paramount role of NK cells in the mechanism of action of this drug. No significant financial relationships to disclose.

Metastatic male breast cancer (mMBC): Prognosis and survival of 35 patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e12001-e12001
Author(s):  
R. Foerster ◽  
F. G. Foerster ◽  
D. Baaske ◽  
B. Schubotz ◽  
V. Wulff ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Male Breast Cancer ◽  
Systemic Therapy ◽  
Metastatic Breast ◽  
Male Breast ◽  
Tumor Characteristics ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Radio Therapy

e12001 Background: Only about 1% of breast cancers occur in men, respectively 400–500 new cases per year in Germany. Clinical studies on breast cancer in men are limited for case studies or retrospective analysis. In the recent years no studies have been published on the clinical course of mMBC. Therefore we here present a retrospective cohort study on this topic. Methods: Clinical and pathological tumor characteristics and the follow-up of male breast cancer patients with metastatic disease diagnosed in the region Chemnitz/Zwickau in the state of Saxony between 1995 and 2007 were documented and statistically evaluated. Results: 35 men (median age 64.7 years) were diagnosed with mMBC; 10 (28.6%) of them with primary metastasis. Median survival time: 37 months. 85.7% (n = 30) had an invasive-ductile carcinoma. Most common localizations of metastasis: bones (n = 19), lungs (n = 19), liver (n = 7). Tumor characteristics at the point of diagnosis: 63.9% (n = 22) T2-T4, 38.7% (n = 12) G3, 48.4% (n = 15) N+, 79.3% (n = 23) ER+, 72.4% (n = 21) PgR+, 12.5% (n = 3) HER-2+, 13.8% (n = 4) triple negatives, and 69.2% (n = 9) AR+. The therapy in the metastatic state was very heterogeneous and consisted of systemic endocrine therapy in 45.5% (n = 10), systemic chemo therapy in 9% (n = 2) or a combination of both in 45.5% (n = 10). In 14 (40%) cases a palliative radio therapy was administered. The initial tumor characteristics like tumor size, nodal state and grading were not of any prognostic relevance on a future development of metastasis. Prognostic unfortunate were a negative hormone receptor state (p < 0.001) and triple negative receptor state (n.s.). Patients with primary metastasis showed a tendency towards worse survival than patients who developed the metastasis during follow up (n.s.). If a systemic therapy was given the prognosis was significantly improved (p < 0.005). Conclusions: Patients suffering from metastatic male breast cancer had a comparatively good prognosis and showed significant benefit from systemic therapy in this study. In patients with negative receptor state and without systemic therapy the prognosis was especially worsened. Our data suggest that an up-to-date adequate systemic therapy is capable of improving survival in men with metastatic breast cancer. No significant financial relationships to disclose.

Stat5 expression predicts response to endocrine therapy and improves survival in estrogen receptor-positive breast cancer

2006 ◽  
Vol 13 (3) ◽  
pp. 885-893 ◽  
Author(s):  
H Yamashita ◽  
M Nishio ◽  
Y Ando ◽  
Z Zhang ◽  
M Hamaguchi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Epithelial Cell ◽  
Endocrine Therapy ◽  
Histological Grade ◽  
Metastatic Breast ◽  
Therapy Response ◽  
Breast Cancer Patients ◽  
Er Positive ◽  
Positive Breast Cancer

Constitutively activated signal transducers and activators of transcription (Stats), in particular Stat3 and Stat5, have been demonstrated to directly contribute to oncogenesis by stimulating cell proliferation and preventing apoptosis in various cancers. Stat3 is essential in mammary gland epithelial cell apoptosis and involution, whereas Stat5 is well established as a key factor in mammary epithelial cell growth and differentiation. Crosstalk between Stats and estrogen receptor (ER) has been demonstrated by several laboratories and we have focused on the role of Stat5 in ER-positive breast cancer. Using immunohistochemical techniques, we examined the expression of Stat3 and Stat5 in 517 human breast cancer tissues and analyzed their significance for prognosis and prediction of response to endocrine therapy. Stat5 expression was significantly correlated with histological grade (P < 0.0001), ER (P = 0.02), and progesterone receptor (P = 0.026) expression. There was no difference between Stat3 expression and clinicopathological factors. In 346 patients with ER-positive breast cancer, patients with Stat5 positive tumors had significantly increased overall survival (P = 0.0009) in multivariate analysis. There were 70 patients who received endocrine therapy as first-line treatment for metastatic breast cancer at relapse. The patients whose primary breast tumors were Stat5 positive, had significantly better response to endocrine therapy (P = 0.04), and longer survival after relapse (P = 0.0003), than those whose tumors were Stat5 negative. The present study demonstrates for the first time that Stat5 is a predictive factor for endocrine therapy response and a strong prognostic molecular marker in ER-positive breast cancer. Our data suggest that the expression of Stat5 is helpful in selecting patients who may benefit from endocrine therapy.

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