New Biomarkers in Metastatic Breast Cancer & Awareness on ESR1 and Liquid Biopsy: Analysis of a European Patient Survey

This survey was initiated and promoted by CPE and aimed to tackle the interest of a group of Breast Cancer patients (metastatic Breast Cancer) with an incurable and resilient disease. The goal was to create awareness and improve the level of information that these patients have regarding new advances, using biomarkers, that bring better therapeutic and diagnostic options. By raising awareness and spreading the latest information to the patients, it will help to combat the burden presented by the tumor’s resistance to current treatments and the side-effects of current treatment; ultimately giving them hope for a better quality of life.

Advisory Board

Oncologists

• Prof. Dr. Ellen Copson – Co-Chair, Wessex Molecular Tumour Board
• Dr. Arnaud Bayle – Assistant Clinic Chief, Department of Drug Development, Centre Gustave Roussy
• Dr. Lucia Del Mastro – Director of the Clinical Oncology Unit, School of Medicine, University of Genoa

Pathologists

• Dr. Federico Rojo Todo – Head of Pathology,Department of Molecular Pathology, Hospital Fundacion Jimenez Diaz
• Dr. Umberto Malapelle – Chief Suepervisor of the Molecular Pathology laboratory in the Department of Public Health, University of Naples Federico II
• Dr. Raed Al Dieri – Chief Executive Officer, European Society of Pathology

Geneticists

• Prof. Mike Hubank – Scientific Director, NHS England Genomic Lab Hub

Breast Cancer Patients

• Gema Rodriguez – Asociación Española de Cáncer de Mama Metastásico
• Conchi Biurrun – Treasurer, Federación Española de Cáncer de Mama (FECMA)

METHODOLOGY

The survey was designed by CPE as a 42-question questionnaire, reviewed and approved by the Advisory Board. The questionnaire was disseminated by CPE, local patient organisations and individuals in five European countries: France, Spain, Italy, UK, and Germany.

Structure and target population
The survey was intended to obtain information and create awareness among breast cancer patients about new innovative therapies and diagnostic tools, and in particular the mutated ESR1 and the use of liquid biopsy for genetic detection.
The survey is divided in five sections: Demographics and treatment background; Awareness and information sources; Knowledge and perception of ESR1; Biopsy preferences and awareness; Treatment preferences.
The channels used to distribute the survey included: Social media (Facebook, Instagram), CPE newsletter (delivered to breast cancer patient associations).

RESULTS

The survey was available for a six-week period. There was a total of 1268 respondents across the five participant countries: UK: 205; Germany: 161; Spain: 237; Italy: 364; France: 301.

• Almost 100% (99.9) self-identified as women. 54% diagnosed with metastatic Breast Cancer (mBC) and 59%with an ER+/HER2- subtype. 43% were ER+/HER2- and mBC patients (the target population for ESR1 mutant diagnostic and therapeutic new advances).
• 67% of the respondents were between the range of 50-69 years old.

Key Findings

The survey shows obvious signs of a lack of information about the use and analysis of biomarkers and their importance for the use of new targeted therapies:

• 70% of total respondents did not know the markers they had been tested for and 75% had not discussedbiomarker testing with their oncologists.
• 70% of ER+/HER2- mBC respondents were unaware of the role of ESR1 mutations in tumor resistance to hormone therapy.
• Only 16% of ER+/HER2- mBC patients that answered, were aware of new drugs targeting mutant ESR1. Even in the countries where anti-ESR1 drugs are available, awareness is very limited (24% in Germany; 22% UK) in the target community.
• Only 23% of ER+/HER2- mBC respondents in Germany had been tested for ESR1 mutations (in the total of the five countries only 12%). We have to consider that almost 50% of mBC with the ER+/HER2- subtype that follow hormone therapy develop ESR1 mutations.
• There is an overall lack of knowledge about the new uses of liquid biopsies in cancer diagnosis. 53% of respondents did not know that cancers release DNA to the bloodstream and a 60% had no information that liquid biopsy can detect that cell-free DNA. Almost 30% of the respondents did not trust the use of liquid biopsy to test their tumor and that may be due to the fact that 60% (of the total) did not know that liquid biopsy can give reliable information about the type of their cancer.

Country variations

Nevertheless, there are some interesting variations amongst the participant countries:

Awareness about the importance of ESR1 mutations in mBC ER+/HER2-:

Awareness about drugs targeting ESR1 mutations:

ESR1 Mutations:

Waiting time for biomarkers test results (more than 2 weeks):

Use of liquid biopsy for diagnosis of the cancer type:

There are some differences amongst the participant countries, mostly related to the guidelines that every country uses about the testing of markers (ESR1) and the type of diagnostic tool chosen (liquid biopsy).

The results from this survey show a significant gap between the incredible development in new therapeutical and diagnostic solutions during the last years and the time they reach the cancer patients. New, more specific drugs, are addressing the needs for those cancer patients that had limited treatment options. Advanced therapies give not only hope to extend the life of those patients, but also offer the possibility of less severe side effects, and thus, an improvement of the quality of life. A proper profiling of the patient and tumor genetic status is absolutely necessary to select the most advanced and proper therapy for patients. Detection of specific mutations and other genetic markers are now possible with the use of less invasive and more accessible diagnostic tools such as liquid biopsy.
A proper information about the possibilities of these new advances is needed for cancer patients, but also for clinicians in order to make the best out of them.

For policy makers

The absence of a common standard for healthcare in the EU results in huge gaps of the time when new advanced therapies can be accessible to all cancer patients. New legislation at European level such as the new HTA regulation can help to reduce the inequalities in accessing highly developed therapeutical and diagnostic tools. In addition, even in those countries of the EU where advanced therapies are faster and more readily available, differences in the standards in terms of application create disparities and inequalities. This is the case for mBC patients, resulting in reduced solutions when the tumor becomes resistant to the standard hormonal therapy. A homogenisation of the protocols and guidelines are necessary regarding the use of new testing tools across EU health systems. To ensure the accessibility for all patients, biomarker testing needs to be properly funded by the health systems, considering the reimbursement of treatment and testing, as they need to be used together.

For healthcare professionals

Guidelines and recommendations about the implementation of new therapeutical options and diagnostic tools can only be successful with the active support of the healthcare community. Proper and continuous updates about the new available therapeutical options and their potential are needed for clinical professionals. In addition, there is a need to improve the way that information is disseminated to cancer patients. Giving mBC patients easily digestible information pertaining to their options will allow them to participate in their own treatment’s decisions. A well-informed mBC patient is not only more receptive to a new treatment but can also provide better feedback to the clinical staff to improve the implementation and use of therapies and diagnostic solutions.
Differences in standard decisions on biomarker testing should also be homogenised. Testing for ESR1 is very different amongst the participant countries. Some healthcare systems consider it only useful as any drug is available. However, other countries consider the test as a prognostic factor (to early detection of treatment resistance) to preview and foster decision on treatment changes even if the specific drug is not available. A general compromise using scientific evidence within the clinical community should be arranged at European level to create a framework where all patients in the EU can access the best treatments and the best quality of their lives.

For patient associations

Healthcare professionals are the main source of information for cancer patients. However, this can be limited by the clinician knowledge and sometimes it may reach the patient too late. For that reason, cancer patient associationsshould provide a closer avenue for the patients allowing them to access reliable and up-to-date information about the new therapies and diagnostic possibilities. Cancer patient associations can create awareness in the cancer patient community to reduce toxic sources that may induce mistrust and unwillingness towards the use of advanced medications. For mBC patients, better information about drugs that can overcome the resistance of their cancer to the standard treatment, will give them a faster access to the new therapies. Detailed and easy to understand explanations of the potential and reliability of new diagnostic tools, their use and their application can also create trust and facilitate the patient’s acceptance.