Assessment of the Impact of RNA Genomic Profile on Treatment Decision-making in HER2 Equivocal Breast Cancer Patients

Not Applicable

Terminated

• Conditions: Breast Cancer
• Interventions: Diagnostic Test: PAM 50 test

• Registration Number: NCT03197805
• Lead Sponsor: Centre Jean Perrin

Brief Summary

The American Society of Clinical Oncology (ASCO) and the /College of American Pathologists (CAP) recommend that HER2 status (negative or positive) must be determined in all patients with invasive breast cancer. The knowledge of HER2 status will help the oncologist in prescribing or not a HER2-targeted therapy to patients. Presently, two main methods are used to assess HER2 status: immunohistochemistry (IHC, protein expression) and in situ hybridization (ISH, gene expression) in order to classify tumor sample as positive, negative or equivocal. When a tumor is classified HER 2+ by IHC method, a second test is performed using ISH methods (FISH, SISH, CISH). In case of HER2 equivocal result with ISH method (4 ≤HER2 gene number copy \<6), the patient is eligible to an anti-HER2 therapy after discussed during MD-MM. This decision should be individualized on the basis of patient status (comorbidities and prognosis) and patient preferences after discussing available clinical evidence.

Based on molecular classification, RNA expression could help to discriminate breast cancer subtypes (luminal A, luminal B, HER2-overexpressed and triple negative). Prosigna is a genomic test, developed by NanoString® based on the PAM50 gene signature, which measures the expression of 50 genes to classify tumors into 1 of 4 intrinsic subtypes and could allow determining the HER2 status.

This study was designed in order to define if such a test could help the oncologist to define the better therapeutic decision in a HER2 equivocal population. In addition, concordance tests will be performed. The aim of this study is to assess the modification decision rate between the first and the second multidisciplinary decision-making meeting in HER2 equivocal patients using genomic testing.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-06-19
• Study First Submitted QC: 2017-06-22
• Study First Posted: 2017-06-23
• Study Start: 2017-10-16
• Primary Completion: 2019-05-28
• Study Completion: 2019-05-28
• Status Verified: 2019-07
• Last Update Submitted: 2019-07-24
• Last Update Posted: 2019-07-25

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Female
• Target Recruitment: 26

Inclusion Criteria

• Performance status ≤ 2 (according to WHO criteria)
• Patient with early invasive breast cancer histologically confirmed stage I to IIIA)
• Positive or negative lymph node involvement
• Positive or negative Hormonal Receptors (Estrogens and/or Progesterone),
• Equivocal HER2 status (IHC Score 2 and equivocal ISH defined as HER2/Chr17 ratio <2 and 4 ≤ HER2 gene number copy < 6) as assessed on surgical specimen
• Adequate Hematological, Hepatic, Renal and Cardiac Functions
• Patient potentially eligible for an anti-HER2 therapy
• Patient eligible to receive an adjuvant therapy
• Signed Informed Consent
• Patient with social insurance.

Exclusion Criteria

• Non-measurable tumor
• Unknown Hormonal Receptors
• Unknown node involvement
• Positive or negative HER2 status (Score 0, 1 or 3 IHC, or Negative or positive ISH)
• Disease stage ≥IIIB
• Patient not able to follow the trial.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Use of PAM 50 test in Her2 equivocal breast cancer patient	PAM 50 test	Patients with an equivocal-HER2 breast cancer (IHC Score 2 and equivocal ISH defined as HER2/Chr17 ratio \<2 and 4 ≤HER2 gene number copy \< 6) will be eligible for RNA genomic test (PAM 50 test).

Primary Outcome Measures

Name	Time	Method
The modification of therapeutical decision between the first and the second multidisciplinary decision-making meeting (MD-MM) using a genomic testing	The measure will be realised after the second multidisciplinary decision-making meeting that is about one month after patient's inclusion.	Percentage of therapeutical strategy changes between the first and the second multidisciplinary decision-making meetings.

Secondary Outcome Measures

Name	Time	Method
The concordance between the second multidisciplinary decision-making meeting decision and the HER2 genomic test result	The measure will be done when the genomic test is realised, that is about three weeks after patient's inclusion.	Percentage of second multidisciplinary decision-making meeting decision in accordance with genomic test result and reasons justifying discrepancies (check-list and comments)
The HER2 overexpression incidence according to RNA genomic profile among equivocal-HER2 patients	The measure will be done when the genomic test is realised, that is about three weeks after patient's inclusion.	Percentage of HER2 classified patients using a genomic test among equivocal-HER2 patients

Trial Locations

Locations (16)

CHRU Jean Minoz; 🇫🇷 Besançon, France

Institut Bergonie; 🇫🇷 Bordeaux, France

Centre François Baclesse; 🇫🇷 Caen, France

Centre Jean Perrin; 🇫🇷 Clermont-Ferrand, France

Centre Georges François Leclerc; 🇫🇷 Dijon, France

Centre Léon Bérard; 🇫🇷 Lyon, France

CHU Albert Michalon; 🇫🇷 Grenoble, France

Hopital DUPUYTREN; 🇫🇷 Limoges, France

Institut Paoli Calmettes; 🇫🇷 Marseille, France

Institut de Cancérologie de Montpellier; 🇫🇷 Montpellier, France

Institut Jean Godinot; 🇫🇷 Reims, France

Institut du Cancer COURLANCY; 🇫🇷 Reims, France

Institut de Cancérologie de l'Ouest; 🇫🇷 Saint-Herblain, France

Centre Paul Strauss; 🇫🇷 Strasbourg, France

Institut Claudius Regaud; 🇫🇷 Toulouse, France

Institut de Cancérologie de Lorraine; 🇫🇷 Vandœuvre-lès-Nancy, France