Study of Human Epidermal Growth Receptor (HER2) Status Evaluation in Breast Cancer Pathology Samples

Breast Cancer Clinical Trial

Official title:

Immunohistochemical HER2 Status Evaluation In Breast Cancer Pathology Samples: A Multicenter, Parallel-Design Concordance Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02580799
• Other study ID #: ML28731
• Status: Completed
• Phase: N/A
• First received: October 19, 2015
• Last updated: January 26, 2016
• Start date: February 2014
• Est. completion date: October 2014

Study information

• Verified date: January 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: Turkey:Turkish Ministry of Health
• Study type: Observational

Clinical Trial Summary

A multi-center non-interventional, in-vitro trial for evaluation of concordance of the results for Human Epidermal Growth Factor Receptor 2 (HER2) expression by the Immunohistochemical (IHC) method in pathological samples collected from participants with breast cancer.

Description:

For accurate selection of participants who will be treated with anti-HER2, primary crucial thing to do is the right identification of HER2 in breast tumor cells. The advantages and disadvantages of IHC and In-Situ Hybridization (ISH) for the detection of HER2 status is still disputable. It is generally agreed on that HER2 study should be applied on all invasive breast cancer participants. It can be used together with IHC which measures HER2 protein expression or ISH which assesses HER2 gene amplification. With regard to IHC, the inconsistency of sensitivity and specificity of marketed antibodies, differences in interpretation and technical artifacts cause problems in diagnosis on occasion. There is not enough study on reasons which cause the consistence and discrepancies between laboratories in HER2 detection with IHC method.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 74 Years

Eligibility

Inclusion Criteria:

Samples that fulfill all of the criteria will be evaluated for the study.

• Samples of women aged greater than or equal to (>/=) 18 and less than (<) 75 years

• Tumor samples already diagnosed based on the IHC score of 0 to +3

• Samples of primary lesions excluding lymph nodes

• 10 percent (%) neutral buffered formalin-fixed and paraffin embedded tissue samples

Exclusion Criteria:

Samples that fulfill any of the criteria below will not be included in the study.

• Non-invasive ductal carcinoma (NOS) samples

• Tru-cut biopsies

• Non-breast cancer pathological samples

Study Design

Observational Model: Case Control, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Locations

Country	Name	City	State
Turkey	Ankara University Medical Faculty	Ankara
Turkey	Istanbul University Cerrahpasa Medical Faculty	Istanbul
Turkey	Istanbul University Istanbul Medical Faculty	Istanbul
Turkey	Dokuz Eylul University Medical Faculty	Izmir
Turkey	Ege University Medical Faculty	Izmir

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Immunohistochemical (IHC) Evaluation Between Site A and Others (Sites B, C, D and E)	IHC is a staining process performed on fresh/frozen breast cancer tissue. IHC is used to show whether or not the cancer cells have Human Epidermal Growth Receptor (HER2) and/or hormone receptors on their surface. The IHC test gives a score of 0 to 3+ that measures the amount of HER2 receptor protein on the surface of cells in a breast cancer tissue sample. Score 0: cells free from immune staining, score 1 (+): is concluded in the case of stains not completely membranous and which do not surround the membranes regardless of quantity in the cells, or weak stains surrounding the entire membrane in less than 10% of the cells. Score 2 (++): is concluded in the presence of a moderate staining surrounding the cytoplasmic membrane in at least 10%, or strong membranous staining in less than 30% of the invasive carcinoma cells. Score 3 (+++): is concluded where IHC yields strong staining surrounding the entire cytoplasmic membrane in at least 30% of the invasive carcinoma cells.	Up to 70 days	No
Primary	Kappa Coefficient (K) as a Measure of Agreement Between Site A and Others (Sites B, C, D and E) Concerning the IHC Test of Breast Tissue Samples	Inter-laboratory variation between the sites was assessed using Kappa test, K values were interpreted as follows: a) less than (<) 0: less than chance agreement, b) 0.01-0.20: slight agreement, c) 0.21-0.40: fair agreement, d) 0.41-0.60: moderate agreement, e) 0.61-0.80: substantial agreement, and f) 0.81-0.99: almost perfect agreement.	Up to 70 days	No
Primary	Percentage of Participants With IHC Evaluation Between Sites B and Others (Sites C, D and E)	IHC is a staining process performed on fresh/frozen breast cancer tissue. IHC is used to show whether or not the cancer cells have HER2 and/or hormone receptors on their surface. The IHC test gives a score of 0 to 3+ that measures the amount of HER2 receptor protein on the surface of cells in a breast cancer tissue sample. Score 0: cells free from immune staining, score 1 (+): is concluded in the case of stains not completely membranous and which do not surround the membranes regardless of quantity in the cells, or weak stains surrounding the entire membrane in less than 10% of the cells. Score 2 (++): is concluded in the presence of a moderate staining surrounding the cytoplasmic membrane in at least 10%, or strong membranous staining in less than 30% of the invasive carcinoma cells. Score 3 (+++): is concluded where IHC yields strong staining surrounding the entire cytoplasmic membrane in at least 30% of the invasive carcinoma cells.	Up to 70 days	Yes
Primary	Kappa Coefficient as a Measure of Agreement Between Site B and Others (Sites C, D and E) Concerning the IHC Test of Breast Tissue Samples	Inter-laboratory variation between the sites was assessed using Kappa test, K values to be interpreted as follows: a) <0: less than chance agreement, b) 0.01-0.20: slight agreement, c) 0.21-0.40: fair agreement, d) 0.41-0.60: moderate agreement, e) 0.61-0.80: substantial agreement, and f) 0.81-0.99: almost perfect agreement.	Up to 70 days	No
Primary	Percentage of Participants With IHC Evaluation Between Site C and Others (Sites D and E)	IHC is a staining process performed on fresh/frozen breast cancer tissue. IHC is used to show whether or not the cancer cells have HER2 and/or hormone receptors on their surface. The IHC test gives a score of 0 to 3+ that measures the amount of HER2 receptor protein on the surface of cells in a breast cancer tissue sample. Score 0: cells free from immune staining, score 1 (+): is concluded in the case of stains not completely membranous and which do not surround the membranes regardless of quantity in the cells, or weak stains surrounding the entire membrane in less than 10% of the cells. Score 2 (++): is concluded in the presence of a moderate staining surrounding the cytoplasmic membrane in at least 10%, or strong membranous staining in less than 30% of the invasive carcinoma cells. Score 3 (+++): is concluded where IHC yields strong staining surrounding the entire cytoplasmic membrane in at least 30% of the invasive carcinoma cells.	Up to 70 days	No
Primary	Kappa Coefficient as a Measure of Agreement Between Sites C, D and E Concerning the IHC Test of Breast Tissue Samples	Inter-laboratory variation between the sites was assessed using Kappa test, K values to be interpreted as follows: a) <0: less than chance agreement, b) 0.01-0.20: slight agreement, c) 0.21-0.40: fair agreement, d) 0.41-0.60: moderate agreement, e) 0.61-0.80: substantial agreement, and f) 0.81-0.99: almost perfect agreement.	Up to 70 days	No
Primary	Percentage of Participants With IHC Evaluation Between Abroad and Trial Sites (A, B, C, D and E)	IHC is a staining process performed on fresh/frozen breast cancer tissue. IHC is used to show whether or not the cancer cells have HER2 and/or hormone receptors on their surface. The IHC test gives a score of 0 to 3+ that measures the amount of HER2 receptor protein on the surface of cells in a breast cancer tissue sample. Score 0: cells free from immune staining, score 1 (+): is concluded in the case of stains not completely membranous and which do not surround the membranes regardless of quantity in the cells, or weak stains surrounding the entire membrane in less than 10% of the cells. Score 2 (++): is concluded in the presence of a moderate staining surrounding the cytoplasmic membrane in at least 10%, or strong membranous staining in less than 30% of the invasive carcinoma cells. Score 3 (+++): is concluded where IHC yields strong staining surrounding the entire cytoplasmic membrane in at least 30% of the invasive carcinoma cells.	Up to 70 days	No
Primary	Kappa Coefficient as a Measure of Agreement Between Abroad and Trial Sites (A, B, C, D and E) Concerning the IHC Test of Breast Tissue Samples	Inter-laboratory variation between the sites was assessed using Kappa test, K values to be interpreted as follows: a) <0: less than chance agreement, b) 0.01-0.20: slight agreement, c) 0.21-0.40: fair agreement, d) 0.41-0.60: moderate agreement, e) 0.61-0.80: substantial agreement, and f) 0.81-0.99: almost perfect agreement.	Up to 70 days	No
Secondary	Percentage of Participants With Diagnosis of Primary Tumor	Primary tumor diagnosis was classified into invasive ductal carcinoma, invasive ductal carcinoma + integrin linked kinase (ILK) antibody and mixed (invasive ductal + lobular) and reported.	Up to 70 days	No
Secondary	Percentage of Participants With Initial Tumor Node Metastasis (TNM) Stage According to Council Decision	TNM system is based on size of primary tumor (T), amount of spread to lymph nodes (N) and presence of metastasis (M). T1: tumor =20 millimeters (mm), T2: tumor >20 mm to =50 mm, T3: >50 mm and TX: tumor cannot be assessed. N0: no lymph node metastasis, N1: metastasis to ipsilateral level I, II axillary lymph nodes, N2: N1 metastasis that is clinically fixed/matted or in clinically detected ipsilateral internal mammary nodes, N3: metastases in ipsilateral infraclavicular lymph nodes, with/without level I, II axillary node involvement, or in clinically detected ipsilateral internal mammary lymph nodes and clinically evident level I, II axillary lymph node metastasis; or metastasis in ipsilateral supraclavicular lymph nodes, NX: Regional lymph nodes cannot be assessed. M0: no clinical/radiographic evidence of distant metastasis, M1: distant detectable metastases as determined by clinical and radiographic means and/or histologically proven >0.2 mm, and MX: metastases cannot be assessed.	Up to 70 days	No
Secondary	Percentage of Participants With Pathological Score	Modified Bloom-Richardson Grade scoring system was used which considers the amount of glandular/tubular differentiation, nuclear features and the mitotic activity of tumor cells. Tubular score (TS) 1: >75 percent (%) of tumor area forming tubular structures, TS 2: 10% to 75% of tumor area forming tubular structures, TS 3: <10% of tumor area forming tubular structures. Nuclear score (NS) 1: nuclei small with little increase in size in comparison with normal breast epithelial cells, regular outlines, uniform nuclear chromatin, little variation in size, NS 2: cells larger than normal with open vesicular nuclei, visible nucleoli, and moderate variability in both size and shape, NS 3: Vesicular nuclei, often with prominent nucleoli, exhibiting marked variation in size and shape, occasionally with very large and bizarre forms. Mitosis score (MS) 1: =7 mitoses per 10 high power fields, MS 2: 8-14 mitoses per 10 high power fields and MS 3: =15 mitoses per 10 high power fields.	Up to 70 days	No
Secondary	Percentage of Participants With Pathological Grade	Modified Bloom-Richardson Grade scoring system was used which considers the amount of glandular/tubular differentiation, nuclear features and the mitotic activity of tumor cells. Tubular, Nuclear and Mitosis scoring pattern was discussed in outcome 11, each score was added to give a final total score ranging from 3-9. Tumors with 3, 4 or 5 points are classified as being of low malignancy or Grade I, those with 6 or 7 points of intermediate malignancy or Grade II, and those with 8 or 9 points of high malignancy or Grade III.	Up to 70 days	No
Secondary	Percentage of Participants With Different Hormone Receptors	Presence of hormone receptors was examined by the amount of uptake of estrogen and progesterone hormones when analyzed using IHC staining procedure.	Up to 70 days	No
Secondary	Percentage of Participants With Specified Density of Hormone Receptors	The specific density of hormone receptors was examined by the amount of uptake of estrogen and progesterone hormones when analyzed using IHC staining procedure. Score 0: cells free from immune staining, score 1 (+): is concluded in the case of stains not completely membranous and which do not surround the membranes regardless of quantity in the cells, or weak stains surrounding the entire membrane in less than 10% of the cells. Score 2 (++): is concluded in the presence of a moderate staining surrounding the cytoplasmic membrane in at least 10%, or strong membranous staining in less than 30% of the invasive carcinoma cells. Score 3 (+++): is concluded where IHC yields strong staining surrounding the entire cytoplasmic membrane in at least 30% of the invasive carcinoma cells.	Up to 70 days	No
Secondary	Percentage of Participants With HER2 Test Form Based on Country	Reference site was considered as Abroad and the tests were performed in a laboratory in Amsterdam, Netherlands. A total of 150 data registration forms (120 forms from trial sites [24 from each site] and 30 from the reference site) were collected.	Up to 70 days	No
Secondary	Percentage of Participants With HER2 Test Form Based on Different Automated Slide Stainers	Different slide stainers like Ventana, Ventana Benchmark 4XT, Ventana Benchmark Ultra and Ventana Benchmark XT were used to report HER2 test results on data registration forms (120 forms from trial sites [24 from each site] and 30 from the reference site).	Up to 70 days	No
Secondary	Percentage of Participants With HER2 Test Form Based on Antigen Retrieval	Fixation of tissue samples cross-link proteins and masks antigenic sites; antigen retrieval process was performed before IHC staining in order to reverse the masking of antigenic sites. Antigen retrieval process was performed in this study using the following solutions: 1 hour Cell Conditioning 1 (CC1), 30 minutes (min) CC1 mild, 64 min CC1, CC1 Ethylenediaminetetraacetic acid (EDTA) standard, and Cell Conditioning 2 (CC2) 30 min.	Up to 70 days	No
Secondary	Percentage of Participants With HER2 Test Form Based on Primary Antibody	The primary antibodies included; Biocabe EP 10454, Cerb B2 (SP3 clone), Her2 Neu (SP3) Cell marque, Neomarkers (thermo) cerb B2-Ab-17 and Thermo SP3.	Up to 70 days	No
Secondary	Percentage of Participants With Different IHC Results	The IHC test gives a score of 0 to 3+ that measures the amount of HER2 receptor protein on the surface of cells in a breast cancer tissue sample. If the score is 0 to 1+, it's called "HER2 negative." If the score is 2+, it's called "borderline." A score of 3+ is called "HER2 positive." Score 0: cells free from immune staining, score 1 (+): is concluded in the case of stains not completely membranous and which do not surround the membranes regardless of quantity in the cells, or weak stains surrounding the entire membrane in less than 10% of the cells. Score 2 (++): is concluded in the presence of a moderate staining surrounding the cytoplasmic membrane in at least 10%, or strong membranous staining in less than 30% of the invasive carcinoma cells. Score 3 (+++): is concluded where IHC yields strong staining surrounding the entire cytoplasmic membrane in at least 30% of the invasive carcinoma cells.	Up to 70 days	No