Evaluation of Degree of Conversion of HER2 Receptor Between Primary Breast Cancer and Metastasis

March 9, 2023 updated by: Spanish Breast Cancer Research Group
This is a Prospective Clinical Trial without drugs, to determine the HER2 status in the metastasis of patients with primary breast cancer HER2. 32 Sites have been taking part in this Clinical Trial.

Study Overview

Status

Completed

Conditions

Detailed Description

Population definition: Women previously diagnosed with a primary breast carcinoma who present locally recurrent or metastatic lesions and who meet the selection criteria. The expected sample size is 175 patients.

Observation period: Each patient in the study will be observed from their inclusion in the study until 1 year after the inclusion of the last patient in the study. These visits will match with the scheduled follow-up visits made by the patient according to the usual clinical practice of the site.

Determination of sample size: The calculation of the sample size will be based on determining a number of patients that will achieve the main objective of the study.

The fulfillment of the secondary objectives of the study will be obtained from the size determined by the main objective.

Main objective of the study is to: Prospectively determine the probability of conversion of the HER2 stage between the different subtypes of primary breast cancer (luminal, triple negative and HER2) and their respective metastases.

A review of the literature has allowed to find several published works with varying percentages of HER2 disagreements determined by IHQ + FISH or FISH, which have allowed to estimate an average percentage of disagreements of 10.45% (range between 4% and 20%). Considering the hypothesis that the level of disagreement in each of the different subtypes of primary, luminal, triple negative and HER2 breast cancer, is presented in an approximately similar frequency, that is to say approximately 10.45%.

From the aforementioned data, an average conversion rate to be expected of 10% will be assumed. An alpha risk of 0.05 will be accepted, with an accuracy of +/- 0.09 percentage units, with a bilateral contrast, for which it would be necessary to include 43 patients for each of the three groups mentioned above (luminal, triple negative and HER2), which consequently includes 129 patients. If a loss rate is assumed (patients registered with biopsies finally not performed or not valid, or with inconclusive results or reflecting other diagnoses) of approximately 25%, the necessary size would increase to a total of 172 patients.

Based on these calculations, the final sample size would be 175 patients

Study Type

Observational

Enrollment (Actual)

236

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Barcelona, Spain, 08003
        • Hospital del Mar
      • Barcelona, Spain, 08036
        • Hospital Clinic i Provincial de Barcelona
      • Cáceres, Spain, 10003
        • Hospital San Pedro de Alcántara
      • Gerona, Spain, 17007
        • Hospital Universitari de Girona Doctor Josep Trueta
      • Granada, Spain, 18014
        • Hospital Universitario Virgen de Las Nieves
      • Granada, Spain, 18016
        • Hospital Universitario San Cecilio
      • Guadalajara, Spain, 19002
        • Hospital Universitario de Guadalajara
      • Madrid, Spain, 28034
        • Hospital Universitario Ramón y Cajal
      • Madrid, Spain, 28040
        • Hospital Clínico San Carlos
      • Murcia, Spain, 30008
        • Hospital General Universitario Morales Meseguer
      • Sevilla, Spain, 41009
        • Hospital Universitario Virgen Macarena
      • Toledo, Spain, 45004
        • Hospital Virgen de la Salud
      • Valencia, Spain, 46026
        • Hospital Universitari i Politècnic La Fe
      • Valencia, Spain, 46010
        • Hospital Clinico Universitario de Valencia
      • Valencia, Spain, 46009
        • Instituto Valenciano de Oncología
      • Valencia, Spain, 46017
        • Hospital Universitario Doctor Peset
      • Valencia, Spain, 46015
        • Hospital Arnau Vilanova
      • Zaragoza, Spain, 50009
        • Hospital Universitario Miguel Servet
    • Alicante
      • Alcoy, Alicante, Spain, 03804
        • Hospital Virgen de los Lirios
      • Elda, Alicante, Spain, 03600
        • Hospital General de Elda
    • Barcelona
      • Manresa, Barcelona, Spain, 08243
        • Althaia Xarxa Asistencial de Manresa
    • Castellón
      • Castello de la Plana, Castellón, Spain, 12002
        • Consorcio Hospitalario Provincial de Castellon
    • Cádiz
      • Algeciras, Cádiz, Spain, 11207
        • Hospital Punta de Europa
      • Jerez De La Frontera, Cádiz, Spain, 11407
        • Hospital Jerez de la Frontera
    • Islas Baleares
      • Palma De Mallorca, Islas Baleares, Spain, 07198
        • Hospital de Son Llàtzer
    • La Coruña
      • A Coruña, La Coruña, Spain, 15006
        • Complejo Hospitalario Universitario de A Coruña
    • Las Palmas
      • Las Palmas De Gran Canaria, Las Palmas, Spain, 35016
        • Hospital Materno Insular de Canarias
    • Madrid
      • Alcorcón, Madrid, Spain, 28922
        • Fundacion Hospital Alcorcon
      • Leganés, Madrid, Spain, 28911
        • Hospital Universitario Severo Ochoa
      • Pozuelo De Alarcón, Madrid, Spain, 28223
        • Hospital Universitario Quirón Salud Madrid
    • Tenerife
      • Santa Cruz De Tenerife, Tenerife, Spain, 38010
        • Hospital Universitario Nuestra Señora de Candelaria
    • Valencia
      • Sagunto, Valencia, Spain, 46520
        • Hospital de Sagunto

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Sampling Method

Non-Probability Sample

Study Population

Female patients diagnosed of primary breast carcinoma with locally recurrent breast carcinoma or metastasic

Description

Inclusion Criteria:

  • Patients who have given their written informed consent to participate in the study.
  • Women over 18 years.
  • Breast cancer locally recurrent or metastatic at first relapse or after successive progressions.
  • Patient has to have available a sample of the primary tumor in paraffin.
  • Patients who are planning for the next 6 weeks, the biopsy (fine needle aspiration / drainage of fluid cavities, open biopsy, core biopsy) of locally recurrent or metastatic lesion [local relapse in the chest wall, nodal , cutaneous or subcutaneous metastases, peripheral lymph nodes and other soft tissues accessible, bone metastases, visceral metastases (lung, liver, brain, etc..) or pleural effusion / ascites / pericardial / cerebrospinal] according to clinical practice center.

Exclusion Criteria:

  • Patients with cognitive impairment that might impede a proper understanding of the written informed consent, according to medical criteria.
  • Ipsilateral breast local relapses or contralateral breast away.
  • Patients diagnosed with a second neoplasm, with the exception of cervical carcinoma in situ and non-melanoma skin carcinoma treated properly.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Other
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Not treatment
Locally recurrent breast carcinoma or metastatic

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluation of degree of conversion of human epidermal growth factor receptor 2 (HER2) receptor between primary breast cancer and metastases
Time Frame: 2 years since the beginning of the Study

The conversion of HER2 is defined as the variation of the HER2 status between the primary tumor and the metastases, both from an initially negative to positive state and from an initially positive to negative state.

The definition of the different molecular subtypes of primary breast cancer will be the following:

  • Luminal: immunohistochemical phenotype Estrogen Receptor (ER) positive and/or Progesterone Receptor (PR) positive, independently of HER2 status.
  • Triple negative: immunohistochemical phenotype ER negative, PR negative and HER2 negative.
  • HER2: immunohistochemical phenotype ER negative, PR negative and HER2 positive. For the calculation of this probability, a sample of the remnant of the primary tumor and the biopsy of the metastasis, performed according to the usual clinical practice of the site, will be sent to the central laboratory for analysis by immunohistochemistry (IHQ) and in situ hybridization (FISH) analysis.
2 years since the beginning of the Study

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To determine the probability of changes in ER and PR between different subtypes of primary breast cancer and their metastases
Time Frame: 2 years since beginning of the Study
To obtain the contingency table to calculate the probability of changes in ER and PR between different subtypes of primary breast cancers and their metastases.
2 years since beginning of the Study
Analyze the variability in the measurement of HER2, ER and PR between local laboratories and central laboratory
Time Frame: 2 years since the beginning of the Study
The contingency table will compare the measurement between the local laboratory in relation to the central laboratory, for each of the HER2 receptor ER and PR (for these two last ones of joint form)
2 years since the beginning of the Study
Evaluate HER2 conversion rate compared to previously received treatment
Time Frame: 2 years since the beginning of the Study
For each of the types of treatment received will obtain the contingency table that allows to evaluate the conversion rate between the primary tumour HER2 and HER2 for metastases
2 years since the beginning of the Study
Evaluate whether the location of biopsied metastases relates to the probability of conversion of HER2.
Time Frame: 2 years since the beginning of the Study
The frequency distribution of HER2 conversions according to biopsied metastases sites will be obtained to evaluate the possibility of finding statistically significant differences between them
2 years since the beginning of the Study
Compare the disease-free survival (DFS) and survival post relapse (SPR) of patients with or without conversion of HER2 and ER/PR
Time Frame: 2 years since the beginning of the Study
Survival curves and disease-free survival post-relapse among patients with and without conversion of HER2 are compared using the log-rank test.In addition, for the analysis of post-relapse survival, also will be analyzed under stratified manner the patients with first metastases and subsequent progression.
2 years since the beginning of the Study
Compare the response rate (RR) and time to progression (TTP) for subsequent anti-tumor treatment of patients with or without conversion of HER2
Time Frame: 2 years since the beginning of the Study
To compare statistically response rates and median time to progression (TTP) for patients with and without conversion of HER 2
2 years since the beginning of the Study
Analyze the extent to which discrepancies in the HER2 receptor status, ER and PR between the primary tumor and metastases alter the clinical management of patients.
Time Frame: 2 years since the beginning of the Study
To obtain contingency tables between the variables HER2, ER and PR in relation to the change variable clinical management of patients and determine their statistical significance
2 years since the beginning of the Study
Analyze the feasibility of performing biopsies.
Time Frame: 2 years since the beginning of the Study
To obtain the distribution of absolute and relative frequencies for the variable "viability of biopsies (analyzable / not studied)".
2 years since the beginning of the Study
Evaluate if the HER2 status conversion is associated with activation of intracellular markers of the HER2 signaling pathway: phosphorylated MAPK (pMAPK), phosphorylated ERK (pERK), phosphorylated AKT (pAKT), PTEN, PIGF-1R in primary tumor and metastases
Time Frame: 2 years since the beginning of the Study
To obtain contingency tables for each of pMAPK, pERK, pAKT, pTEN, PIGF-1R proteins that relate their condition (+/-) in the primary tumor and metastases in HER2-discordant cases.
2 years since the beginning of the Study
Check if there is any change in the molecular subtypes (luminal, triple negative, HER2) between primary tumors and metastases in patients with HER2 conversion
Time Frame: 2 years since the beginning of the Study
To obtain contingency tables to evaluate if there is any change of molecular phenotype between primary tumor and metastasis in patients with conversion HER2.Contingency tables will be obtained according to molecular subtype (luminal, triple negative, HER2) and based on molecular markers of the subtype.
2 years since the beginning of the Study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Spanish Breast Cancer Research Group

Collaborators

Roche Farma, S.A

Investigators

  • Study Director: Study Director, Hospital Clinico Universitario de Valencia
  • Study Director: Study Director, Consorcio Hospitalario Provincial de Castellon

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 11, 2009

Primary Completion (Actual)

November 30, 2012

Study Completion (Actual)

November 30, 2012

Study Registration Dates

First Submitted

June 8, 2011

First Submitted That Met QC Criteria

June 20, 2011

First Posted (Estimate)

June 21, 2011

Study Record Updates

Last Update Posted (Estimate)

March 10, 2023

Last Update Submitted That Met QC Criteria

March 9, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CONVERTHER/GEICAM 2009-03

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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