Release Date: June 29, 2018
Expiration Date: June 29, 2019
Media: Internet - based
This activity, Advances inTM Tumor Testing: Interpreting Genomic Profiles to Optimize Breast Cancer Treatment, is designed to update clinicians on the current and evolving role of genomic profiling, including multigene expression assays and next-generation sequencing (NGS), in the management of their patients with breast cancer. As clinicians who treat patients with breast cancer, you require a solid understanding of the available prognostic multigene assays, how they differ from one other, and in which settings they have been validated. It is also important for you to understand how to integrate the results of these tests with other factors, such as clinical and pathologic tumor characteristics and patient preferences, in order to determine the optimal course of treatment for individual patients. Finally, you need to be aware of emerging technologies, such as NGS, which are limited to investigational uses in breast cancer at the present time, but which will likely impact decision-making paradigms in the future.
To help you meet these goals, we have developed an educational activity that features a review of the latest data and expert guidelines regarding the use of genomic tools in breast cancer, accompanied by video commentary from leading experts in the management of patients with breast cancer, who will provide their perspectives on integrating multigene assays into the clinical decision-making process.
Acknowledgment of Commercial Support
This activity is supported by educational grants from Foundation Medicine, Inc., Genomic Health, Inc., and Myriad Genetics Laboratories.
Instructions for This Activity and Receiving Credit
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Each presentation may contain an interactive question(s). You may move forward through the presentation; however, you may not go back to change answers or review videos/content until you finish the presentation.
At the end of the activity, “educational content/video files” will be available for your reference.
In order to receive a CME/CE certificate, participants must complete the activity.
Complete the posttest and pass with a score of 70% or higher, complete the evaluation and then click on request for credit. Participants may immediately download a CME/CE certificate upon completion of these steps.
This educational activity is directed toward medical oncologists, gynecologic oncologists, and fellows who treat patients with breast cancer. Nurse practitioners, nurses, physician assistants, pharmacists, researchers, and other healthcare professionals interested in the treatment of breast cancer are also invited to participate.
At the conclusion of this activity, you should be better prepared to:
Examine current and evolving biomarkers in breast cancer and their implications in the clinical setting
Discuss genomic testing strategies and determine how to appropriately utilize the results in the setting of breast cancer
Review clinical trials that have utilized biomarkers and genomic testing in patients with breast cancer
Apply evidence concerning genomic testing results to inform treatment decisions throughout the breast cancer disease continuum
Fabrice André, MD, PhD
Biomarker Group at UNICANCER
Research Director, Head of INSERM U981
Professor of Medical Oncology
Institut Gustave Roussy
Disclosures: Dr. Fabrice André has no relevant financial relationships with commercial interests to disclose.
William J. Gradishar, MD, FASCO, FACP
Betsy Bramsen Professor of Breast Oncology
Director, Maggie Daley Center for Women’s Cancer Care
Robert H. Lurie Comprehensive Cancer Center
Northwestern University Feinberg School of Medicine
Disclosure: Dr. William J. Gradishar has no relevant financial relationships with commercial interests to disclose.
The staff of Physicians’ Education Resource®, LLC, have no relevant financial relationships with commercial interests to disclose.
Disclosure Policy and Resolution of Conflicts of Interest (COI)
As a sponsor accredited by the ACCME, it is the policy of Physicians’ Education Resource®, LLC, (PER®) to ensure fair balance, independence, objectivity, and scientific rigor in all of its CME activities. In compliance with ACCME guidelines, PER® requires everyone who is in a position to control the content of a CME activity to disclose all relevant financial relationships with commercial interests. The ACCME defines relevant financial relationships as financial relationships in any amount occurring within the past 12 months that creates a conflict of interest (COI).
Additionally, PER® is required by ACCME to resolve all COI. PER® has identified and resolved all COI prior to the start of this activity by using a multistep process.
Off-Label Disclosure and Disclaimer
This CME activity may or may not discuss investigational, unapproved, or off-label use of drugs. Participants are advised to consult prescribing information for any products discussed. The information provided in this CME activity is for continuing medical education purposes only, and is not meant to substitute for the independent clinical judgment of a physician relative to diagnostic, treatment, or management options for a specific patient’s medical condition. The opinions expressed in the content are solely those of the individual faculty members, and do not reflect those of PER® or any of the companies that provided commercial support for this activity.
PER Pulse Recap™
PER Pulse Recap (1 of 3)
Advances in™ Tumor Testing: Interpreting Genomic Profiles to Optimize Breast Cancer Treatment
is designed to update clinicians on the current and evolving role of genomic profiling, including multigene expression assays as well as next-generation sequencing (NGS), in the management of their patients with breast cancer. Interviews with distinguished breast cancer experts, including Fabrice André, MD, PhD, and William Gradishar, MD, provide perspective on how to integrate the results of these tests with other tumor characteristics and patient-specific factors to individualize and optimize treatment decisions.
This first of 3 PER Pulse™ Recaps focuses on current biomarker standards and the emerging role of germline BRCA1/2
mutations in guiding treatment decisions. Highlights include:
Expression of the 2 hormone receptors—estrogen receptor (ER) and progesterone receptor (PR)—along with expression and/or amplification of the HER2 receptor, are well-established standards in the initial characterization of breast cancers, based on their utility for identifying patients who may benefit from endocrine therapies and HER2-targeted agents, respectively.
Determination of BRCA1/2 status has been a standard component of risk assessment protocols in women with a potential genetic predisposition to the development of ovarian and breast cancers, to guide screening and prevention strategies. However, the emergence of data demonstrating the efficacy of poly (ADP-ribose) polymerase (PARP) inhibitors for the treatment of germline BRCA1/2-mutated metastatic breast cancer (MBC), and the approval of the first agent in this class for this use by the US Food and Drug Administration (FDA), have made BRCA1/2 mutations another important biomarker for guiding treatment in patients diagnosed with breast cancer.
Olaparib was the first PARP inhibitor to receive FDA approval, based on the results of the phase III OlympiAD trial, which showed a significant improvement in progression-free survival (PFS) for single-agent olaparib compared with physician’s choice of chemotherapy (7.0 months vs 4.2 months; hazard ratio [HR], 0.58; P <.001) in patients with germline BRCA1/2-mutated, anthracycline- and taxane-pretreated MBC. Regulatory review by the European Medicines Agency is underway.
A second PARP inhibitor, talazoparib, has also demonstrated the ability to improve outcomes when compared with chemotherapy in a similar patient population in the phase III EMBRACA trial (median PFS: 8.6 months vs 5.6 months; HR, 0.54; P <.0001); regulatory consideration is ongoing.
PER Pulse Recap (2 of 3)
This second of 3 PER Pulse™ Recaps focuses on currently available multigene assays that have been validated for their prognostic and/or predictive utility in guiding adjuvant treatment decisions for patients with node-negative, HER2-negative breast cancers. Highlights include:
The Oncotype DX® (21-gene Recurrence Score) assay has been validated as a prognostic tool for node-negative, hormone receptor‒positive (HR+)/HER2-negative, early-stage breast cancer.
Oncotype DX is the only molecular assay to date that has demonstrated the ability to predict whether or not a patient is likely to benefit from adjuvant chemotherapy. A retrospective analysis of patients with HR+, node-negative breast cancer enrolled in the NSABP B-20 trial showed that patients with a high-risk recurrence score derived the greatest benefit when they received adjuvant chemotherapy as well as endocrine therapy, whereas patients classified as low risk appeared to derive little or no benefit from treatment with a cytotoxic regimen.
In the TAILORx trial, a low-risk Oncotype DX score was associated with an invasive disease-free survival (iDFS) rate of 94% at 5 years in patients with HR+, node-negative breast cancer treated with endocrine adjuvant therapy alone.
The TAILORx trial also addressed the question of how to best manage patients with an intermediate recurrence score. Recently published results indicated that endocrine therapy alone was statistically noninferior to chemotherapy plus endocrine therapy in the intent-to-treat population of patients (n=6711) with a recurrence score of 11-25; 9-year iDFS rates were similar between arms (83% vs 84%; HR, 1.08; P =.26). However, subset analysis suggested that chemotherapy may benefit some patients, such as those age ≤50 years with a recurrence score of 16-25.
MammaPrint® (70-gene signature) has demonstrated prognostic utility in both HR+ and HR-negative, HER2-negative, node-negative breast cancer.
The MammaPrint assay has demonstrated the ability to identify a subpopulation of node-negative breast cancers with an ultralow risk of disease recurrence or death; the 20-year disease-specific survival rate was 97% for tamoxifen-treated patients meeting the ultralow-risk threshold, and 94% for those who received no postsurgical systemic therapy at all.
In the MINDACT trial, patients with HR+/HER2-negative, early-stage breast cancer who were classified as high clinical risk and low genomic risk using the MammaPrint assay were randomized to receive adjuvant endocrine therapy with or without chemotherapy. The 5-year rate of distant metastasis-free survival was 95% with endocrine therapy alone compared with 96% for those who received adjuvant chemotherapy (P =.267). Similar results were observed in both node-negative and node-positive subsets.
EPclin® integrates the molecular information from an 8-gene signature (EndoPredict®) with clinical characteristics (tumor size and nodal status) to derive a prognostic algorithm that has been validated in HR+, HER2-negative, early-stage breast cancer, and can be used for both node-negative and node-positive disease.
The Breast Cancer Index (BCI) combines 2 independently developed prognostic tests, the molecular grade index (MGI) and HOXB13/IL17BR (H/I), to produce a continuous-risk model that is prognostic for both early and late distant recurrence in ER+, node-negative breast cancer.
The Prosigna (PAM50) Risk of Recurrence (ROR) Score is a gene expression‒based assay that first categorizes breast cancers according to intrinsic subtype, and then combines this information into an algorithm that incorporates a proliferation score, as well as tumor size, to estimate the probability of 10-year distant recurrence. It has been validated in postmenopausal patients with HR+, node-negative breast cancer.
PER Pulse Recap (3 of 3)
This third of 3 PER Pulse™ Recaps focuses on emerging or investigational settings for multigene signatures and NGS in early-stage or MBC. Highlights include:
Multigene assays are also being investigated for their prognostic utility in node-positive breast cancer. Based on the results of the MINDACT trial, which included patients with node-positive disease, the American Society of Clinical Oncology (ASCO) recently updated its guidelines to indicate that results of the MammaPrint test may be used to guide treatment in select patients with 1 to 3 positive nodes who have a high-clinical-risk profile, although these patients should be informed that the potential for benefit from adjuvant chemotherapy cannot be excluded in the event of a low-risk molecular signature.
Retrospective analysis of the SWOG 8814 trial, as well as a Surveillance, Epidemiology, and End Results (SEER) population-based study, suggest that the Oncotype DX assay may also be able to identify a low-risk population of patients with node-positive disease. The ongoing RxPONDER trial is prospectively addressing whether Oncotype DX can be used to identify patients with node-positive breast cancer who can avoid adjuvant chemotherapy, by randomizing patients with 1 to 3 positive nodes and a recurrence score ≤25 to endocrine therapy alone or with chemotherapy.
Data are also emerging that suggest the PAM50 ROR Score also has the ability to identify distinct prognostic subgroups in patients with 1 to 3 positive nodes, identifying low-, intermediate-, and high-risk groups.
Another potential setting for the use of multigene assays is in the prediction of late risk of recurrence in patients with HR+ breast cancer, who may benefit from extended adjuvant endocrine therapy. A recent retrospective study comparing the prognostic ability of 4 multigene signatures found that ROR, BCI, and EPclin provided the most robust prognostic information with regard to predicting late distant recurrence in postmenopausal patients with HR+, HER2-negative, node-negative breast cancer treated with 5 years of endocrine therapy. However, none of the available prognostic assays has yet been validated for the prediction of benefit from extended adjuvant endocrine therapy.
The utility of NGS in breast cancer is currently limited to the identification of patients for potential enrollment in clinical trials investigating novel targeted agents. To fully optimize the use of this emerging technology, it will be necessary to identify and validate genomic aberrations that predict for responsiveness to specific targeted therapies.
For additional commentary about this topic and others, please visit www.gotoper.com.