Couple of studies in early breast cancer--many more studies in metastatic breast cancer (even one tied to AI efficacy prediction). Here are abstracts:
J BUON. 2008 Jul-Sep;13(3):409-13.
Extracellular domain of HER2: A useful marker for the initial workup and follow- up of HER2-positive breast cancer.
Garoufali A, Kyriakou F, Kountourakis P, Yioti I, Malliou S, Nikaki A, Kardara E, Frangos I, Koumna S, Baziotis N, Scorilas A, Ardavanis A.
Nuclear Medicine Laboratory, "St. Savvas" Anticancer Hospital, Athens, Greece.
Purpose: The extracellular domain (ECD) of the HER2 receptor is proposed as a real-time marker of HER2-positive breast cancer (BC). In this study, ECD-HER2 levels were compared with standard clinical and pathological prognostic factors. Patients and methods: In 247 consecutive patients (116 with early or localized BC, 116 with advanced or metastatic BC, and 16 with benign mastopathies), serum ECD-HER2 levels were measured. In 116 advanced-disease patients ECD-HER2 status was also studied by immunohistochemistry (IHC) and compared with established clinical and pathological variables. Results: Mean serum ECD-HER2 value was 19.62 ng/ml (median 10.35, range 3 - >250). Mean value in benign mastopathies was 9.04 ng/ml, 9.4 ng/ml in early disease and 34.5 ng/ml in advanced disease. No difference between benign mastopathies and early BC was observed, while significant difference between early and advanced BC (p<0.001) was noted. However, in advanced-disease patients a positive correlation of ECD-HER2 with IHC (p=0.002), disease grade (p=0.034) and level II axillary node involvement (p=0.011) was noted, as well as a significant negative correlation with estrogen receptor (ER) and progesterone receptor (PR) (p= 0.035 and p=0.011, respectively). Conclusion: ECD-HER2 is a reliable marker for breast cancer, as suggested from the existing literature; therefore, its integration in the initial workup and follow-up routine of breast cancer, particularly the HER2-positive, is proposed.
PMID: 18979558
: Ann Oncol. 2008 May;19(5):883-90. Epub 2008 Jan 10. Links
Evaluation of serum HER2 extracellular domain in early breast cancer patients: correlation with clinicopathological parameters and survival.
Ludovini V, Gori S, Colozza M, Pistola L, Rulli E, Floriani I, Pacifico E, Tofanetti FR, Sidoni A, Basurto C, Rulli A, Crinò L.
Medical Oncology Division, Azienda Ospedaliera of Perugia, Perugia, Italy.
oncolab@hotmail.com
BACKGROUND: We explored the correlation between serum human epidermal growth factor receptor-2 (HER2) extracellular domain (ECD) and tissue HER2 status, their relationship with clinicopathological parameters and their impact on disease-free survival (DFS) and overall survival in early breast cancer patients. PATIENTS AND METHODS: This prospective trial included patients with stage I-III breast cancer. Serum HER2 ECD levels were measured by two enzyme-linked immunosorbent assays before surgical treatment. Tissue HER2 status was analyzed by immunohistochemistry (IHC) in all tumors; FISH assay was utilized in HER2 2+ tumors by IHC. RESULTS: From May 2000 to July 2005, 256 consecutive stage I-III breast cancer patients were included in this study. High serum HER2 ECD levels (>or=15 ng/ml) were reported in 23 patients (9.0%) and HER2-positive status in tumor tissue was observed in 42 patients (16.4%) with a concordance of 87.1%. High HER2 ECD levels were significantly associated with high histological grade (P = 0.003), stage III (P = 0.008), lymph node involvement (P = 0.035) and negativity of both estrogen (P = 0.016) and progesterone (P = 0.007) receptors. At multivariate analysis, high serum HER2 ECD levels were a significant independent prognostic factor of worse DFS (P = 0.009). CONCLUSIONS: A statistically significant association was observed between high serum HER2 ECD levels and worse DFS in early breast cancer patients.
PMID: 18187484
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Most other papers discuss changes in serum ECD in METASTATIC BC AND WHAT THEY say re whether herceptin will work:
Clinical utility of serum HER2/neu in monitoring and prediction of progression-free survival in metastatic breast cancer patients treated with trastuzumab-based therapies.
Esteva FJ, Cheli CD, Fritsche H, Fornier M, Slamon D, Thiel RP, Luftner D, Ghani F.
The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
festeva@mdanderson.org
INTRODUCTION: The purpose of this retrospective study was to determine the clinical utility of serum HER2/neu in monitoring metastatic breast cancer patients undergoing trastuzumab-based therapy and to compare these results with those obtained using cancer antigen (CA) 15-3. We also sought to determine whether early changes in serum HER2/neu concentrations could be a predictor of progression-free survival. METHODS: Sera were obtained retrospectively from 103 women at four medical institutions. Patients eligible for participation were women with metastatic breast cancer who had HER2/neu tissue overexpression and were scheduled to be treated with trastuzumab with or without additional therapies as per the established practices of the treating physicians. A baseline serum sample for each patient was taken before trastuzumab-based therapy was started. Patients were subsequently monitored over 12 to 20 months and serum samples were taken at the time of clinical assessment and tested with Bayer's HER2/neu and CA15-3 assays. RESULTS: Concordance between clinical status in patients undergoing trastuzumab-based treatment and HER2/neu and CA15-3 used as single tests was 0.793 and 0.627, respectively, and increased to 0.829 when the tests were used in combination. Progression-free survival times did not differ significantly in patients with elevated baseline HER2/neu concentrations (> or = 15 ng/mL) and those with normal concentrations (<15 ng/mL). However, progression-free survival differed significantly (P = 0.043) according to whether the patient's HER2/neu concentration at 2 to 4 weeks after the start of therapy was >77% or < or = 77% of her baseline concentration. The median progression-free survival times for these two groups were 217 and 587 days, respectively. A similar trend was observed for a subcohort of patients treated specifically with a combination of trastuzumab and taxane. CONCLUSION: These findings indicate that serum HER2/neu testing is clinically valuable in monitoring metastatic breast cancer patients undergoing trastuzumab-based treatment and provides additional value over the commonly used CA15-3 test. The percentage of baseline HER2/neu concentrations in the early weeks after the start of therapy may be an early predictor of progression-free-survival.
PMID: 15987448
Breast Cancer Res Treat. 2008 Apr 25. [Epub ahead of print]
Changes over time of extracellular domain of HER2 (ECD/HER2) serum levels have prognostic value in metastatic breast cancer.
Bramwell VH, Doig GS, Tuck AB, Wilson SM, Tonkin KS, Tomiak A, Perera F, Vandenberg TA, Chambers AF.
London Regional Cancer Program, London, ON, Canada,
vivienbr@cancerboard.ab.ca.
Background Blood levels of the extracellular domain of HER-2/neu (ECD/HER2) have been suggested to have potential as a tumor marker in breast cancer. Our aim was to assess the prognostic value of baseline levels of ECD/HER2, but more importantly changes in levels over time, in women with metastatic breast cancer. Methods Baseline and serial levels of ECD/HER2 were measured in 158 women with newly-diagnosed metastatic breast cancer, in whom we previously performed serial measurement of plasma osteopontin. ECD/HER2 was measured in 1,282 serum samples using a validated ELISA at baseline and every 3-12 weeks during and after therapy until death (median, n = 8 samples per patient). Multivariate time-dependent survival analyses were conducted using models that right-censored patient outcomes 3, 6 and 12 months after last known ECD/HER2 measurement. Results Thirty-four patients (22%) had elevated baseline ECD/HER2 (median 10.2 ng/ml: range 4.1-40.4 ng/ml). In univariate analysis, elevated baseline ECD/HER2 was associated with short survival (P = 0.001). In a multivariate model incorporating standard clinical prognostic factors, baseline ECD/HER2 was significantly associated with survival duration (RR 1.029; P = 0.020). Presence of visceral metastases and ECOG status 2-4 also retained significance. In a multivariate model incorporating standard prognostic factors and changes in sequential ECD/HER2 levels, an ECD/HER2 increase of >12 ng/ml at any time was the variable with most prognostic value for poor survival (RR 6.10; P = 0.0003); poor ECOG status also retained significance. Conclusion Increases over time of ECD/HER2 levels were strongly associated with poor survival in this cohort of women with metastatic breast cancer.
PMID: 18437556
Cancer. 2008 Jul 25. [Epub ahead of print]
Serum HER-2/neu and relative resistance to trastuzumab-based therapy in patients with metastatic breast cancer.
Ali SM, Carney WP, Esteva FJ, Fornier M, Harris L, Köstler WJ, Lotz JP, Luftner D, Pichon MF, Lipton A; the Serum HER‐2/neu Study Group.
Department of Hematology-Oncology, Penn State Hershey Cancer Center, Penn State University/Hershey Medical Center, Hershey, Pennsylvania.
BACKGROUND.: Previous reports based on small patient numbers suggested that changes in serum HER-2/neu levels may predict response or lack of response to trastuzumab-based therapies in metastatic breast cancer (MBC). The objectives of this study were to pool data from 307 patients with MBC from 7 medical institutions to validate that the serum HER-2/neu profile predicts patient resistance to trastuzumab and to establish a clinically relevant cutoff. METHODS.: This was an international, multicenter, retrospective analysis of individual pooled data from 307 patients with MBC who were treated with first-line trastuzumab-based therapy. Serum was collected at baseline and 30 to 120 days after the initiation of trastuzumab therapy. A serum HER-2/neu decrease >/=20% (receiver operating curve analysis) was defined as a significant HER-2/neu change. RESULTS.: Of the 307 patients with MBC, 191 patients (62%) had a significant decline (>20%) in serum HER-2/neu and 116 patients (38%) did not. The objective response rate was 57% for patients who achieved this decline in serum HER-2/neu (>20%) compared with 28% for patients who did not. Patients who achieved this decline in serum HER-2/neu also had a significantly longer time to disease progression (320 days vs 180 days; P < .0001), longer duration of response (369 days vs 230 days; P = .008), and longer overall survival (898 days vs 593 days; P < .018). CONCLUSIONS.: In this pooled analysis of 307 patients with MBC, individuals who did not achieve a significant decline (>/=20%) in serum HER-2/neu levels had decreased benefit from trastuzumab-based therapy, and these patients should be considered for clinical trials evaluating additional HER-2/neu-targeted interventions. Cancer 2008. (c) 2008 American Cancer Society.
Med Oncol. 2008 Oct 15. [Epub ahead of print] Links
Clinical significance and prognostic value of serum sHER-2/neu levels in patients with solid tumors.
Papila C, Uzun H, Balci H, Zerdali H, Sezgin C, Can G, Yanardag H.
Department of Internal Medicine, Cerrahpasa Medical Faculty, University of Istanbul, Istanbul, Turkey.
The purpose of this study was to determine HER-2/neu in the serum of patients with solid tumors and to investigate its potential usefulness in predicting the clinical course of the disease. At the same time, we compared the ability of serum HER-2/neu, CA15.3, CA12-5, CA19-9, carcino embryonic antigen (CEA), and alpha-feto-protein (AFP) in breast, colorectal, and lung cancer patients. Forty, thirty-six, and twenty-three patients with lung, colon and breast cancer were included in this study, respectively. Serum levels of HER-2/neu, CA15.3, CA12-5, CA19-9, CEA, and AFP were measured. Her-2 neu levels were significantly higher in the breast cancer groups than colorectal and lung cancer and controls groups (P < 0.01). There is no significant difference when compared with others groups (P > 0.05). There was a positive correlation between the HER-2/neu and CA15-3 values in breast cancer groups. We found 0.75(0.59-0.90) for Her-2/neu from the area under the curve (AUC). P-value for breast cancer is 0.003, and we discovered that 9 ng/ml was the best inersection point. In this situation, we calculated that sensitivity was 65.2%, specificity was 100%, positive predictive value was 100%, negative predictive value 75.8%, and accuracy was 83.4%. These findings indicate that serum HER2/neu levels are clinically valuable in monitoring metastatic breast cancer and non-small cell lung cancer patients. Prognosis of breast cancer provides an additional value over the commonly used CA15-3 test. Measurements of levels of serum HER-2/neu provide prognostic and predictive information to the clinician and can especially be used for monitoring metastatic breast cancer patients. Further clinical validation is needed to confirm these findings.
PMID: 18855148
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and even one paper having to do with determining whether AIs efficacious in metastatic breast cancer
Cancer. 2007 Nov 15;110(10):2178-85. Links
High circulating HER2 extracellular domain levels correlate with reduced efficacy of an aromatase inhibitor in hormone receptor-positive metastatic breast cancer: a confirmatory prospective study.
Colomer R, Llombart-Cussac A, Lloveras B, Ramos M, Mayordomo JI, Fernández R, Tusquets I, Gil M, Barnadas A, Constenla M, Gilabert M, Alba E.
M. D. Anderson Cancer Center Spain, Madrid, Spain.
rcolomer@seom.org
BACKGROUND: In this specifically designed, prospective study, the authors addressed the predictive value of circulating levels of the extracellular domain (ECD) of HER2 in patients with metastatic breast cancer who were treated with letrozole. METHODS: Two hundred twenty-six patients with hormone receptor-positive, metastatic breast cancer received letrozole (2.5 mg daily) until they developed either disease progression or unacceptable toxicity. Efficacy was measured primarily as the time to progression (TTP) and, secondarily, as the objective response rate (ORR) and overall survival. HER2 ECD levels were determined by using a sandwich enzyme HER2/neu immunoassay before letrozole treatment was initiated. Positive HER2 ECD status was correlated with treatment efficacy. RESULTS: Forty-two patients (19%) had elevated HER2 ECD levels, which were associated with primary tumor HER2 expression (P < .001) but not with age, performance status, location, or number of metastatic sites. The median TTP was significantly shorter among patients who had elevated HER2 ECD compared with the median TTP among patients who had normal levels (4 months vs 14 months; P = .0004), and the ORR was lower in the group with elevated HER2 ECD levels (14% vs 30%; P < .036). Overall survival was significantly shorter among patients with elevated serum HER-2 ECD (P < .0005). CONCLUSIONS: Elevated HER2 ECD concentrations predicted poorer outcomes in postmenopausal women with metastatic hormone receptor-positive breast cancer who were treated with aromatase inhibitors like letrozole. (c) 2007 American Cancer Society.
PMID: 17926331