Persistence of HER2 overexpression on circulating tumor cells in patients after systemic treatment for HER2-positive breast cancer: Follow-up results of the German Success B trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11043-11043 ◽  
Author(s):  
Julia Katharina Neugebauer ◽  
Brigitte Kathrin Rack ◽  
Bernadette Anna Sophia Jaeger ◽  
Ulrich Andergassen ◽  
Aurelia Pestka ◽  
...  

11043 Background: The discordance between HER2-expression on circulating tumor cells (CTC) in peripheral blood and the primary tumor has already been shown by our study group for early breast cancer patients with HER2-positive tumors. Here, we compare the results to CTC prevalence and HER2-status of CTC after adjuvant chemotherapy. Methods: The SUCCESS B trial compares FEC-Docetaxel vs. FEC-Docetaxel-Gemcitabine and HER2-targeted therapy as adjuvant treatment for patients with early, HER2-positive, node positive or high risk node negative primary breast cancer. We prospectively analyzed 23ml peripheral blood before and after chemotherapy. CTC and HER2-status were assessed with the CellSearchSystem (Veridex, USA). After immunomagnetic enrichment with an anti-Epcam-antibody, cells were labeled with anti-CK 8/18/19, anti-CD45 antibodies as well as a fluorescein conjugate antibody for HER2-phenotyping. Cutoff for CTC positivity was ≥ 1 CTC. HER-positivity of CTC was assigned if at least one CTC showed strong HER2 staining (3+). Results: CTCs and their HER2-status both before and after chemotherapy were available for 392 patients. In 179 (45.7%) patients no CTC were detected before and after chemotherapy. CTC status changed from positive before to negative after chemotherapy in 104 (26.5%) patients and from negative before to positive after chemotherapy in 69 (17.6%) patients, while 40 (10.2%) patients had a consistently positive CTC status. Patients were significantly more likely to change their CTC status from positive to negative than from negative to positive (p = 0.01). Of the 40 patients with CTC both before and after chemotherapy, 14 (35%) patients had HER2-positive CTC before and after therapy, and 9 (22%) patients had HER2-negative CTC at both time points. 7 (18%) patients had HER2-positive CTC before but not after chemotherapy, while 10 (25%) patients showed the reverse pattern (p = 0.63). Conclusions: Cytotoxic treatment does not seem to influence the HER2-status on CTC. Follow-up data within the Success B trial will analyze the relevance of the HER2-expression of CTC to predict the efficacy of targeted treatment.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10535-10535 ◽  
Author(s):  
Saswati Hazra ◽  
Jeeyun Lee ◽  
Phillip Sangwook Kim ◽  
Kyoung-Mee Kim ◽  
Limin Liu ◽  
...  

10535 Background: Gastric cancer (GCA) is the second leading cause of cancer mortality in the world. Survival of patients with advanced GCA treated with chemotherapy remains low. New targeted therapies are urgently needed. There is mounting evidence of the role of HER2 overexpression in patients with GCA, and it has been highly correlated to poor outcomes with more aggressive disease. The ability to accurately determine HER2 status by testing circulating tumor cells (CTCs) may improve patient treatment by allowing ongoing assessment of HER2 status during treatment and/or identifying additional patients who could potentially benefit from HER2- targeted therapy. Methods: The Collaborative Enzyme Enhanced Reactive-immunoassay (CEER) was utilized to determine the expression and activation (phosphorylation) levels of HER2 in CTCs isolated from blood specimens obtained from 105 metastatic GCA patients. Results: Utilizing the CEER platform, the levels of HER2 expression and phosphorylation were determined for CTCs isolated from metastatic GCA patients. Evaluable CTCs were found in 33% (35/105) of enrolled patients. Out of 35 patients, 7 patients (20%) have high HER2 over expression, 6 patients (17%) have moderate HER2 expression and 11 patients (31%) have HER2 activation (phospho positive) with no HER2 over-expression. Conclusions: When CTCs were present, the CEER assay identified varying levels of HER2 involvements in 68% of metastatic GCA patients. HER2 positive CTCs could serve as a prognostic and/or predictive marker in patients with advanced GCA and CTC-HER2 profile shifts can be utilized to monitor the treatment efficacy.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 11094-11094
Author(s):  
B. Saleh ◽  
S. Jader ◽  
J. Singer ◽  
S. Jenkins ◽  
H. Bradpiece ◽  
...  

11094 Background: The human epidermal growth factor receptor 2 (HER2) overexpression, has been correlated with higher histological grade, increased tumour size, positive lymph node status, and negative or lower oestrogen receptor (ER) expression. Our aim was to look at the association between HER2 status, patient age and tumour histopathologic characteristics. Methods: We analysed retrospectively 735 cases of invasive breast cancer treated between the years 2000 and 2004. HER2 was measured by immunohistochemistry (IHC) and all IHC 2+ tumours were also tested by fluorescent in situ hybridisation (FISH). All information was collected from pathology reports in patient case records. Results: A total of 143 (19.5%) tumours were HER2 positive (120 IHC 3+ and 23 IHC 2+/FISH+). Of the 66 tumours that were IHC 2+, 23 (34.8%) were FISH-positive. The age of most patients (75.8%) was over 50 years but there was a higher incidence (28%) of HER2 overexpresion in the 40–49 age group compared to all other age groups, the incidence of HER2 overexpression was still at least 17–18% in all age groups, including patients aged =70 years. Although, a high proportion of patients (62.2%) had tumours less than 2 cm in size, comparison of tumours less than 2 cm with those greater than 2 cm showed no predictive effect of size on HER2 expression. Over half of the patients had lymph node-negative disease (55.2%) and despite some association of HER2 expression with lymph node involvement (odds ratio of 1.23 for comparison of lymph node-positive versus negative), 19% of lymph node-negative tumours overexpressed HER2. Most tumours were high grade (32.8% grade 3, 44.1% grade 2 ) and although the proportion of HER2 overexpression increased with increasing tumour grade, some grade 1 tumours still overexpressed HER2. A higher proportion (28%) of ER-negative tumours was HER2 positive compared to ER-positive tumours (18%); however, co-expression of HER2 and ER occurred in 14% (105/735) of all primary cancers. Conclusions: In conclusion, it is not possible to predict which patients will be HER2 positive. Therefore, it is essential that HER2 status should be determined in all patients with invasive breast cancer to allow a decision on the use of trastuzumab and guide the choice of chemotherapy. No significant financial relationships to disclose.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10541-10541
Author(s):  
Satoshi Matsusaka ◽  
Keisho Chin ◽  
Mariko Ogura ◽  
Mitsukuni Suenaga ◽  
Eiji Shinozaki ◽  
...  

10541 Background: This study was aimed at detecting and HER2-expressiong circulating tumor cells (CTC) in peripheral blood of chemo-naïve or chemo-resistant patients with advanced gastric cancer. Methods: All patients were enrolled using institutional review board-approved protocols at the Cancer Institute Hospital in the Japanese Foundation for Cancer Research and provided informed consent. The study population consisted of patients of age 18 years or older with histologically proven advanced gastric cancer. A total of 140 patients with advanced gastric cancer were enrolled into a prospective study. We used CellSearch system for detection and HER2 expression for CTC. Results: We detected ≥1 CTC/7.5ml in 80 of 140 patients (57.1%). HER2-positive CTC were observed in 19 of 80 CTC-positive patients (23.8%), including 6 patients with HSR2-negative primary tumors. 21 patients with HER2-positive primary tumors administered trastuzumab in combination with chemotherapy (Xeloda+cisplatin; 15, weekly Paclitaxel; 5). We detected ≥1 CTC/7.5ml at the baseline in 11 of 20 patients with trastuzumab treatment. HER2-positive CTCs were observed in 6 of 11 CTC-positive patients (54.5%). Patients with HER2-positive CTC at the baseline were shorter PFS than those with HER2-negative CTC at the baseline. Conclusions: HER2 expression on CTC was associated with chemo-resistance. Information on the HER2 status of CTC might be helpful for stratification of HER2-directed therapies.


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