Evaluation of Degree of Conversion of HER2 Receptor Between Primary Breast Cancer and Metastasis
- Conditions
- Breast Cancer
- Registration Number
- NCT01377363
- Lead Sponsor
- Spanish Breast Cancer Research Group
- Brief Summary
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.
- 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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 236
- 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.
- 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 & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Evaluation of degree of conversion of human epidermal growth factor receptor 2 (HER2) receptor between primary breast cancer and metastases 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.
- Secondary Outcome Measures
Name Time Method Analyze the variability in the measurement of HER2, ER and PR between local laboratories and central laboratory 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)
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 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.
Compare the response rate (RR) and time to progression (TTP) for subsequent anti-tumor treatment of patients with or without conversion of HER2 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
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. 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
Evaluate whether the location of biopsied metastases relates to the probability of conversion of HER2. 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
Analyze the feasibility of performing biopsies. 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)".
To determine the probability of changes in ER and PR between different subtypes of primary breast cancer and their metastases 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.
Evaluate HER2 conversion rate compared to previously received treatment 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
Compare the disease-free survival (DFS) and survival post relapse (SPR) of patients with or without conversion of HER2 and ER/PR 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.
Check if there is any change in the molecular subtypes (luminal, triple negative, HER2) between primary tumors and metastases in patients with HER2 conversion 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.
Trial Locations
- Locations (32)
Hospital General de Elda
馃嚜馃嚫Elda, Alicante, Spain
Hospital de Sagunto
馃嚜馃嚫Sagunto, Valencia, Spain
Hospital Virgen de los Lirios
馃嚜馃嚫Alcoy, Alicante, Spain
Hospital de Son Ll脿tzer
馃嚜馃嚫Palma De Mallorca, Islas Baleares, Spain
Hospital Universitario Nuestra Se帽ora de Candelaria
馃嚜馃嚫Santa Cruz De Tenerife, Tenerife, Spain
Hospital Universitario Virgen Macarena
馃嚜馃嚫Sevilla, Spain
Hospital Universitario Ram贸n y Cajal
馃嚜馃嚫Madrid, Spain
Hospital Virgen de la Salud
馃嚜馃嚫Toledo, Spain
Hospital Cl铆nico San Carlos
馃嚜馃嚫Madrid, Spain
Hospital Jerez de la Frontera
馃嚜馃嚫Jerez De La Frontera, C谩diz, Spain
Hospital Punta de Europa
馃嚜馃嚫Algeciras, C谩diz, Spain
Consorcio Hospitalario Provincial de Castell贸n
馃嚜馃嚫Castello de la Plana, Castell贸n, Spain
Hospital San Pedro de Alcantara
馃嚜馃嚫C谩ceres, Spain
Hospital Universitari de Girona Doctor Josep Trueta
馃嚜馃嚫Gerona, Spain
Hospital Universitario de Guadalajara
馃嚜馃嚫Guadalajara, Spain
Althaia Xarxa Asistencial de Manresa
馃嚜馃嚫Manresa, Barcelona, Spain
Hospital General Universitario Morales Meseguer
馃嚜馃嚫Murcia, Spain
Hospital Materno Insular de Canarias
馃嚜馃嚫Las Palmas De Gran Canaria, Las Palmas, Spain
Hospital Universitario Quir贸n salud Madrid
馃嚜馃嚫Pozuelo De Alarc贸n, Madrid, Spain
Hospital Universitario Miguel Servet
馃嚜馃嚫Zaragoza, Spain
Complejo Hospitalario Universitario de A Coru帽a
馃嚜馃嚫A Coru帽a, La Coru帽a, Spain
Hospital Universitario Virgen de las Nieves
馃嚜馃嚫Granada, Spain
Hospital Universitario San Cecilio
馃嚜馃嚫Granada, Spain
Hospital Cl铆nico Universitario de Valencia
馃嚜馃嚫Valencia, Spain
Hospital Universitario Severo Ochoa
馃嚜馃嚫Legan茅s, Madrid, Spain
Hospital Universitario Doctor Peset
馃嚜馃嚫Valencia, Spain
Instituto Valenciano de Oncolog铆a
馃嚜馃嚫Valencia, Spain
Hospital Arnau Vilanova
馃嚜馃嚫Valencia, Spain
Hospital Universitari i Polit猫cnic La Fe
馃嚜馃嚫Valencia, Spain
Hospital del Mar
馃嚜馃嚫Barcelona, Spain
Hospital Clinic i Provincial de Barcelona
馃嚜馃嚫Barcelona, Spain
Fundaci贸n Hospital Alcorc贸n
馃嚜馃嚫Alcorc贸n, Madrid, Spain