FAQs

• Over the last 20 years, precision medicine has transformed the standard of treatment for some cancers.¹ It takes an individualized approach in analyzing a person’s genetic, proteomic and environmental factors to prevent, diagnose, and treat cancer.^2,3 This increasingly precise identification of cancer subtypes through biomarker testing informs targeted therapy, with the aim to direct the right treatment, at the right time⁴

• Genetic counselors use a patient’s genetic information to discuss their risk of common and rare disease and support decision-making for further diagnostics and/or therapeutic approaches. Their risk assessment incorporates environmental factors and a patient’s health status.³ Genetic counselors educate patients on what their genetic results may mean to them and their families, while also contributing to the wider oncology multidisciplinary team (MDT) to aid diagnoses and treatment decisions^3,5

• Cancer is a complex, heterogeneous condition spanning multiple organs and tissues which can be classified further by molecular subtype. However, despite cancer heterogeneity, many cancers are treated with the same generic therapies such as chemotherapy and radiotherapy⁶
• Such standard treatments are ineffective in large percentages of patients, indicating an unmet need to account for several factors based on a patient's cancer subtype when deciding on treatment pathways⁶
• Precision medicine identifies the underlying genetic and proteomic causes of a patient's cancer, allowing more tailored treatment regimens to be employed which directly aim to mitigate the specific genetic/proteomic effects in tumor cells⁶

• Biomarker testing identifies specific biological molecules or genetic characteristics/alterations in patients and their tumors that provide insight into a patient’s disease. This critical information not only aids in diagnosis on the onset of cancer treatment, but it can be used throughout treatment to help guide treatment decisions^7,8
• Given that precision medicine relies on identification of these biomarkers to inform personalized treatment decisions and eligibility for clinical trials, biomarker testing is an important step before optimal treatment planning and has become standard of care in oncology^8,9
  • NCCN Clinical Practice Guidelines In Oncology ( NCCN Guidelines^®) recommend comprehensive biomarker testing at diagnosis to identify cancer subtypes early and, in turn, help inform treatment decisions¹⁰
• Educating and counseling patients about the significance of biomarker testing, its potential benefits, and the role it plays in personalized treatment is a currently underutilized cornerstone of precision medicine¹¹
• Learn more about the current state of biomarker testing and how it is evolving:

• Support your patients with patient-friendly resources

• Actionable biomarkers are defined as genetic alterations that are functional in driving malignancy and may be targeted by an FDA-approved treatment regimen¹²
• Learn more about key actionable biomarkers by tumor type:

• Biomarker testing looks for biological molecules or genetic characteristics found within the body that provide insight into a patient’s disease.⁸.Genetic testing looks for inherited mutations that may put someone at risk of cancer^13,14

• Prognostic biomarkers provide insights on possible clinical outcomes and the pace of disease recurrence and progression. They enable monitoring of anticancer therapy efficacy, evaluation of tumor stage and its potential malignancy, as well as the prognosis for disease remission^7,15

• A prognostic biomarker is a clinical or biological characteristic that provides information on the likely health outcome to the patient (e.g. disease recurrence), irrespective of the treatment. A predictive biomarker indicates the probable response to targeted therapy compared to not having biomarker testing⁷
• Biomarkers can have both prognostic and predictive values but tend to be either more prognostic or more predictive by their nature⁷

• The accuracy of a biomarker test depends on its sensitivity and specificity. Sensitivity refers to the biomarker's ability to correctly detect the condition whereas specificity relates to the biomarker's ability to correctly reject healthy individuals without the condition. For example, if 100 patients known to have a disease were tested for the specific biomarker, and 50 test positive, then the test has 50% sensitivity. If 100 with no disease are tested and 90 return a negative result, then the test has 90% specificity¹⁶
• Test accuracy and reliability depend on the type of assay performed and the sample used¹⁷
• A review of biomarker testing in non-small cell lung cancer (NSCLC) found the sensitivity of next-generation sequencing (NGS) vs. single-gene testing to range from 86 to 100%¹⁸
• Sample: When compared to tissue biopsy, liquid biopsy has high specificity but lower sensitivity for targetable mutations. This could be due to the circulating tumor DNA (ctDNA) or circulating tumor cells (CTCs) present in the biopsy coming from a benign source or that the genes present in them represent a small fraction of the tumor in comparison to tissue testing. Levels of ctDNA can also be low in blood and plasma, especially in early disease^19–21

• Genetic and genomic testing are not synonyms
  • Genetic counselors fulfill a key role in explaining the differences between these two tests to people³; however, access to genetic counseling remains scarce in some communities²²
• While genetic testing refers to a person’s genetic makeup i.e., inherited traits, genomic testing refers to the molecular composition of a tumor i.e., cancer-specific mutations. Therefore, genetic testing results in germline mutation detection and genomic testing focuses on discovering acquired somatic mutations^23,24
• Genetic testing requires a patient sample such as a cheek swab or blood test; whereas genomic testing requires a tissue/ circulating tumor DNA sample from the tumor^23,24
• Examples of genetic testing in cancer include determining²⁴:
  • Inherited mutations that may increase risk of cancer development
  • Contributing gene mutations for existing cancer diagnoses
  • Risk of cancer recurrence (this can be the same or different type of cancer)
• Examples of genomic testing in cancer include determining²⁴:
  • Which mutations within the tumor cause the cells to be different to normal cells
  • Whether a tumor contains mutations that may respond to particular therapies

• Single-gene tests look for any genetic changes in one gene. This is useful when identifying common variants e.g.  BRCA1/2 and if a fast turnaround time is required.²⁵ Inconclusive or negative results may require additional testing for more comprehensive coverage²⁶
• Multi-gene panel testing looks for variants in more than one gene at once. This is often employed when the genetic cause or tumorigenesis is unknown and could be caused by a variant in many genes. It could also be used to assess heredity for certain cancers and to predict treatment outcomes^27,28

• A companion diagnostic is a laboratory test, often an in vitro device (IVD), which is used in conjunction with a drug or biological product to determine a patient’s suitability for that treatment^9,29
• Companion diagnostics are essential for effective use of their corresponding targeted therapy^9,29; visit the following pages to see specific diagnostic tests for featured biomarkers:

Established lung tumor biomarkers^a

Established breast tumor biomarkers

Established ovarian tumor biomarkers

Established prostate tumor biomarkers

• IHC is a semiquantitative method to assess protein overexpression^30,31:
  • It uses monoclonal/polyclonal antibodies to bind to the protein of interest. Expression is measured by the intensity, pattern and percentage of tumor cells stained

• NGS is a genetic sequencing method that determines mutations and gene amplification by copy number variation^32,33:
  • NGS panels assess multiple genomic alterations including point mutations, copy number variations (amplifications and deletions), and gene rearrangements

• Using HER2 as an example, there are biologically distinct types of HER2 alteration that can contribute to cancer development: Protein overexpression, gene amplification, and gene mutation^34,35
  • IHC is recommended to test for HER2 overexpression in breast cancer and Sanger sequencing, targeted PCR, and NGS are recommended options to detect ERBB2 (HER2) amplification or mutation in non-small cell lung cancer^10,36

• A liquid (plasma) biopsy can be performed from blood, urine, or other body fluid to detect particular genetic mutations in circulating tumor DNA (ctDNA), which can help inform optimal treatment for each patient³⁷
• Liquid biopsy allows multiple samples to be taken over time. It is recommended for the evaluation of various biomarkers across multiple tumor types, including EGFR and ERBB2 (HER2) in mNSCLC,³⁶.HRD in ovarian,³⁸ and HRRm, including BRCA1/2 in prostate cancer.³⁹  Liquid biopsy should not be used in lieu of a tissue biopsy, but may be used as a concurrent method (in mNSCLC), or when tissue testing is not feasible (in mNSCLC, ovarian and prostate cancer)^36–39
• Concurrent testing may deliver more comprehensive results faster^40,41 which may reduce time to diagnosis and earlier initiation of appropriate treatment⁴¹

• Liquid biopsy assays can vary in the information they provide, which largely depends on factors that influence tumor DNA shedding (e.g. tumor size, location, and vascularity). Liquid biopsy demonstrates a specificity of ~100% and a sensitivity of ~80% when compared to tissue next-generation sequencing (NGS).⁴² However, liquid biopsy should not be taken in lieu of tissue and should only be used concurrently (in mNSCLC) or when tissue testing is not feasible (in mNSCLC, ovarian and prostate cancer)^36–39
• High concordance between tissue testing and liquid biopsies has been demonstrated in multiple tumor types, including metastatic non-small cell lung cancer (mNSCLC) and metastatic castration-resistant prostate cancer (mCRPC)⁴²
• Find more information on how liquid biopsies can supplement tissue biopsy

• By informing therapeutic decisions, biomarker test results may significantly affect outcomes, so prompt testing immediately following cancer diagnosis is recommended for many tumors. This can help ensure that the most appropriate targeted therapy is identified as soon as possible to avoid treatment delays, use of ineffective therapies, and unnecessary treatment-related toxicity^10,35,43

• Clinical practice guidelines recommend upfront biomarker testing for certain advanced malignancies to better inform diagnosis, prognosis, and assessment of targeted therapeutic options. This is particularly important for those with advanced malignancies who often have a shorter life expectancy and may not benefit from non-targeted therapies^10,36,38,39
• The following NCCN Guidelines^® advise on when to perform biomarker testing:

• Concurrent testing genetically tests tumors for actionable biomarkers with both tissue and liquid biopsy samples. It is important as it may expand the delivery of molecularly guided therapy and improve patient outcomes⁴⁴

• Reflex testing is an approach to testing where the pathologist is responsible for initiating and controlling testing for a set of prespecified biomarkers, without the need for a formal request from an oncologist⁴⁵
• Reflex testing allows biomarker testing to begin as soon as the pathological diagnosis is confirmed, rather than waiting for the patient’s first post-biopsy appointment with the oncologist. It helps to ensure all eligible patients with cancer are given optimal care at the local level when it comes to biomarker evaluation⁴⁵
• Reflex testing relies on protocol and is systematic rather than requiring clinical consideration of the oncologist, which may influence the decision on which tests to request. This should result in fewer patients being overlooked for biomarker testing⁴⁵

• According to GINA, insurance providers are prohibited from discriminating against people based on their genetic information
• This video explains GINA to patients:

• The turnaround time (TAT) for biomarker testing results depends on several factors, including the type of testing, the institution conducting the analysis (in-house vs. commercial laboratory), and the logistics involved in the testing process⁴⁶
• In general, liquid biopsy results may take up to 2 weeks, while tumor tissue-based assays have longer TATs.^46,47 For tumor tissue-based testing, multigene sequencing with next-generation sequencing (NGS) may have turnaround times of >10 days while sequential single-gene testing may take longer. You can help speed up these times by performing reflexive testing^45,48,49
• Find solutions to help you streamline biomarker test times when TAT is a barrier to optimal test times

• Challenges include issues related to testing itself (such as identifying patients for testing, availability of approved tests, and cost of testing), multidisciplinary team (MDT) education and knowledge (awareness of guidelines, interpretation of test results, and application of results for decision making), multidisciplinary coordination (both for the MDT and tumor boards), individual patient financial or insurance limitations, and health inequities^50–53
• Pathologists have a key role in identifying and discussing biomarker testing challenges with their MDT⁴⁵
• Find guidance on overcoming common biomarker testing challenges in practice

• Many biomarker testing labs offer financial assistance programs to help with individual out-of-pocket costs⁵⁴
• For inquiries regarding financial assistance programs offered by testing labs, view contact information provided by major testing labs across the US

This information is intended as educational and is not intended as a complete list of available testing options. AstraZeneca is not responsible for any test provider and does not endorse any particular diagnostic test. The accuracy and results of diagnostic tests vary, and AstraZeneca shall have no liability arising from such testing. Information provided herein should in no way be considered a guarantee of coverage, reimbursement, or patient assistance. Providers should contact third-party laboratories for information on their patient assistance programs. While diagnostic testing may assist providers in identifying appropriate treatment for patients, the decision and action should be decided by a provider in consultation with the patient. All products are trademarks of their respective holders, all rights reserved.

• Find information on billing and the "14-day rule"

• All information included in healthcare records is consistent and easily integrated throughout the multidisciplinary team (MDT). Consistency reduces errors and improves communication between specialties^55,56
• Less time is spent searching for data^55,56
• Improved decision-making, as uniform data makes it easier to spot trends and outliers^55,56
• That all data reported are compliant according to regulations^55,56

• HRR-related genes encode a group of proteins that work together to repair DNA damage through homologous recombination⁵⁷
• Genetic mutations in the HRR pathway result in an inability to repair DNA through homologous recombination and may contribute to cancer development⁵⁷
• Common HRR pathway mutations include BRCA1/2, PTEN, ATM and CHEK2^58,59
• Biomarker testing for genetic mutations within the HRR pathway may help inform targeted treatment decisions^57,58

• We’ve created several videos for genetic counselors and the multidisciplinary team (MDT) to share with patients with cancer, their families, and carers, to give them a better understanding of genetic testing:

• The College of American Pathologists (CAP)/Association for Molecular Pathology (AMP)/International Association for the Study of Lung Cancer (IASLC) recommend a TAT of 10 days between sample receipt and reporting of all results to be acceptable.​​⁶⁰