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

An observational study of Breast Cancer, run by Hoffmann-La Roche at 5 sites in Turkey (Türkiye).

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

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. Read more about this study

Who is it for?: Ages 18 to 74 years, women only
Conditions the study is for: Breast Cancer
How many people: 30 participants
Where: 5 sitesTurkey (Türkiye)
Study dates: Feb 2014to Oct 2014
Phase: Observational
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 74 years
Women only
No healthy volunteers
Adult, Older adult

Study population: Breast tissue samples from female participants with a breast cancer diagnosis

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

5 sites in 1 country.

City, postcode or hospital

5 sites in 1 country

Turkey (Türkiye)5 sites

Ankara University Medical Faculty
Ankara, 06230
Istanbul University Istanbul Medical Faculty
Istanbul, 34093
Istanbul University Cerrahpasa Medical Faculty
Istanbul, 34098
Ege University Medical Faculty
Izmir, 35100
Dokuz Eylul University Medical Faculty
Izmir, 35210

Other trials in Turkey (Türkiye)

About this study

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

Read the detailed 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.

Conditions: Breast Cancer
Medical subject headings: Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02580799
Study group	Role	What they receive
Breast Cancer Pathology Samples		Breast cancer pathology samples were evaluated for a period of 70 days.

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Up to 70 days
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.
Measured: Up to 70 days
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.
Measured: Up to 70 days
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.
Measured: Up to 70 days
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.
Measured: Up to 70 days
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.
Measured: Up to 70 days
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.
Measured: Up to 70 days
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.
Measured: Up to 70 days

Secondary outcomes (11)

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.
Measured: Up to 70 days
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.
Measured: Up to 70 days
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.
Measured: Up to 70 days
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.
Measured: Up to 70 days
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.
Measured: Up to 70 days
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.
Measured: Up to 70 days
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.
Measured: Up to 70 days
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).
Measured: Up to 70 days
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.
Measured: Up to 70 days
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.
Measured: Up to 70 days
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.
Measured: Up to 70 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 2014Oct 2014

First posted20 Oct 2015 (estimated)
Study startFeb 2014
Primary completionOct 2014
Study completionOct 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Breast CancerStudies of the same condition, open and under way.
More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Observational
Observational model: Case-control
Time perspective: Cross-sectional
Enrolment: 30 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02580799
Sponsor's protocol ID: ML28731
Status last verified: Jan 2016
First submitted: 19 Oct 2015
Last updated: 22 Feb 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 22 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Immunohistochemical HER2 Status Evaluation In Breast Cancer Pathology Samples: A Multicenter, Parallel-Design Concordance Study
ClinicalTrials.gov ID: NCT02580799
Acronym / sponsor ID: ML28731
Conditions: Breast Cancer
Study type: Observational
Recruitment status: Completed
Enrolment: 30 participants (actual)
Lead sponsor: Hoffmann-La RocheIndustry (pharma, biotech, devices)
Study start: Feb 2014
Primary completion: Oct 2014 (actual)
Study completion: Oct 2014 (actual)
First posted: 20 Oct 2015 (estimated)
Results: Posted 22 Feb 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Observational model: Case-control
Time perspective: Cross-sectional
Number of arms: 1

Arm	Type	Receives
Breast Cancer Pathology Samples	–	–Breast cancer pathology samples were evaluated for a period of 70 days.

Who may qualify

Ages: 18 to 74 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult
Study population: Breast tissue samples from female participants with a breast cancer diagnosis

Key inclusion criteria (5 listed)

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

Key exclusion criteria (4 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Primary outcome

Percentage of Participants With Immunohistochemical (IHC) Evaluation Between Site A and Others (Sites B, C, D and E)
Time frame: Up to 70 days
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.
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
Time frame: Up to 70 days
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.
Percentage of Participants With IHC Evaluation Between Sites B and Others (Sites C, D and E)
Time frame: Up to 70 days
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.
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
Time frame: Up to 70 days
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.
Percentage of Participants With IHC Evaluation Between Site C and Others (Sites D and E)
Time frame: Up to 70 days
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.
Kappa Coefficient as a Measure of Agreement Between Sites C, D and E Concerning the IHC Test of Breast Tissue Samples
Time frame: Up to 70 days
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.
Percentage of Participants With IHC Evaluation Between Abroad and Trial Sites (A, B, C, D and E)
Time frame: Up to 70 days
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.
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
Time frame: Up to 70 days
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.

11 secondary outcomes

Percentage of Participants With Diagnosis of Primary Tumor
Time frame: Up to 70 days
Percentage of Participants With Initial Tumor Node Metastasis (TNM) Stage According to Council Decision
Time frame: Up to 70 days
Percentage of Participants With Pathological Score
Time frame: Up to 70 days
Percentage of Participants With Pathological Grade
Time frame: Up to 70 days
Percentage of Participants With Different Hormone Receptors
Time frame: Up to 70 days
Percentage of Participants With Specified Density of Hormone Receptors
Time frame: Up to 70 days
Percentage of Participants With HER2 Test Form Based on Country
Time frame: Up to 70 days
Percentage of Participants With HER2 Test Form Based on Different Automated Slide Stainers
Time frame: Up to 70 days
Percentage of Participants With HER2 Test Form Based on Antigen Retrieval
Time frame: Up to 70 days
Percentage of Participants With HER2 Test Form Based on Primary Antibody
Time frame: Up to 70 days
Percentage of Participants With Different IHC Results
Time frame: Up to 70 days

Results and safety

Results posted to the registry on 22 Feb 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Breast Cancer Pathology Participants	30	30

Primary outcome: Percentage of Participants With Immunohistochemical (IHC) Evaluation Between Site A and Others (Sites B, C, D and E)

Time frame: Up to 70 days. Number. Unit: percentage of participants

Measure	Breast Cancer Pathology Participants n = 24
Site A (0): Site B (0) (n=9)	16.7
Site A (0): Site B (1+) (n=9)	12.5
Site A (0): Site B (2+) (n=9)	0.0
Site A (0): Site B (3+) (n=9)	8.3
Site A (1+): Site B (0) (n=6)	4.2
Site A (1+): Site B (1+) (n=6)	12.5
Site A (1+): Site B (2+) (n=6)	4.2
Site A (1+): Site B (3+) (n=6)	4.2

Population analysed: FAS population. Here "number of participants analyzed" included evaluable for the outcome measure and "n" included the number of participants evaluable for the specified category.

Primary outcome: 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

Time frame: Up to 70 days. Number. Unit: kappa coefficient

Measure	Breast Cancer Pathology Participants n = 24
Site A: Site B	0.171
Site A: Site C	0.090
Site A: Site D	-0.148
Site A: Site E	-0.124

Breast Cancer Pathology Participants: p =0.137, Chi-squared
Breast Cancer Pathology Participants: p =0.454, Chi-squared
Breast Cancer Pathology Participants: p =0.211, Chi-squared

Population analysed: FAS population. Here "number of participants analyzed" included evaluable for the outcome measure.

Primary outcome: Percentage of Participants With IHC Evaluation Between Sites B and Others (Sites C, D and E)

Time frame: Up to 70 days. Number. Unit: percentage of participants

Measure	Breast Cancer Pathology Participants n = 24
Site B (0): Site C (0) (n=5)	12.5
Site B (0): Site C (1+) (n=5)	4.2
Site B (0): Site C (2+) (n=5)	0.0
Site B (0): Site C (3+) (n=5)	4.2
Site B (1+): Site C (0) (n=7)	4.2
Site B (1+): Site C (1+) (n=7)	12.5
Site B (1+): Site C (2+) (n=7)	0.0
Site B (1+): Site C (3+) (n=7)	12.5

Primary outcome: 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

Time frame: Up to 70 days. Number. Unit: kappa coefficient

Measure	Breast Cancer Pathology Participants n = 24
Site B: Site C	0.224
Site B: Site D	0.000
Site B: Site E	0.05

Breast Cancer Pathology Participants: p =0.054, Chi-squared
Breast Cancer Pathology Participants: p =1.000, Chi-squared
Breast Cancer Pathology Participants: p =0.968, Chi-squared

Population analysed: FAS population. Here "number of participants analyzed" included evaluable for the outcome measure.

11 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Breast Cancer Pathology Participants	0 of 0	0 of 0	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

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A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Clinical Trials study director

Hoffmann-La Roche

5 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

An observational study of Breast Cancer, run by Hoffmann-La Roche at 5 sites in Turkey (Türkiye).

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Turkey (Türkiye). Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Feb 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Immunohistochemical (IHC) Evaluation Between Site A and Others (Sites B, C, D and E) (time frame: Up to 70 days). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02580799.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Feb 2016.