Optimizing Biomarker Assessment and Related Treatment Decision-Making for Patients with HR-Positive Metastatic Breast Cancer — Video Lecture: Seth Wander, MD, PhD

Faculty

TARGET AUDIENCE
This activity is intended for medical oncologists, hematology-oncology fellows and other healthcare providers involved in the treatment of breast cancer.

LEARNING OBJECTIVES

• Review available research findings documenting the correlation between the presence of various biomarkers (eg, PIK3CA/AKT1/PTEN alterations, ESR1 mutations) and response to specific therapies, and develop optimal testing algorithms for patients with HR-positive, HER2-negative metastatic breast cancer (mBC).
• Appreciate the incidence and clinical implications of ESR1 mutations in endocrine-resistant mBC and determine the appropriate timing of and platforms to test for these abnormalities.
• Recognize the frequency of PIK3CA/AKT/PTEN pathway abnormalities in patients with HR-positive mBC, and employ evidence-based approaches designed to document and subsequently target these aberrations in individuals with newly diagnosed and relapsed/refractory disease.
• Interrogate published research findings documenting the efficacy of oral selective estrogen receptor degraders for patients with ER-positive, HER2-negative, ESR1 mutation-positive mBC experiencing disease progression on standard endocrine therapy in combination with a CDK4/6 inhibitor in order to optimally integrate these agents into the care of appropriately selected individuals.
• Review available and emerging research data evaluating the role of serial ESR1 testing using circulating tumor DNA to inform early therapeutic switching in patients with HR-positive mBC receiving CDK4/6 inhibitor-based first-line therapy, and consider the potential role of this novel strategy.

ACCREDITATION STATEMENT
Research To Practice is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT

Video Lecture: Research To Practice designates this enduring material for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

AMERICAN BOARD OF INTERNAL MEDICINE (ABIM) — MAINTENANCE OF CERTIFICATION (MOC)
Successful completion of these CME activities, which includes participation in the evaluation components and post-tests, enables the participant to earn up to 1 Medical Knowledge MOC points in the American Board of Internal Medicine’s (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for each activity. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.

Please note, these programs have been specifically designed for the following ABIM specialty: medical oncology. 

AMERICAN BOARD OF SURGERY (ABS) — CONTINUOUS CERTIFICATION (CC)
Successful completion of these CME activities, which includes participation in the evaluation components and post-tests, enables the learner to earn credit toward the CME and Self-Assessment requirement(s) of the American Board of Surgery’s Continuous Certification program. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABS credit.

Please note, these programs have been specifically designed for the following ABS practice area: complex general surgical oncology. 

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HOW TO USE THIS CME ACTIVITY
Video Lecture: ResearchToPractice.com/OncologyTodayBiomarkersHRPosmBC25/Presentation and evaluation ResearchToPractice.com/OncologyTodayBiomarkersHRPosmBC25/Presentation/CME.

CONTENT VALIDATION AND DISCLOSURES
Research To Practice (RTP) is committed to providing its participants with high-quality, unbiased and state-of-the-art education and adheres to the ACCME’s Standards for Integrity and Independence in Accredited Continuing Education. Any individuals in a position to control the content of an accredited continuing education activity, including faculty, planners, reviewers and others, are required to disclose all relevant financial relationships with ineligible entities (commercial interests). All relevant financial relationships have been mitigated prior to the commencement of these activities. In addition, all activity content is reviewed by RTP scientific staff and an external, independent physician reviewer for fair balance, scientific objectivity of studies referenced and patient care recommendations.

FACULTY — The following faculty reported relevant financial relationships with ineligible entities:

Seth Wander, MD, PhD
Director of Precision Medicine
Termeer Center for Targeted Therapies
Director of Translational Research
Breast Oncology Program
Massachusetts General Hospital
Assistant Professor of Medicine
Harvard Medical School
Boston, Massachusetts

Consulting Agreements: Arvinas, AstraZeneca Pharmaceuticals LP, Biotheranostics Inc, A Hologic Company, Biovica International AB, Foundation Medicine, Genentech, a member of the Roche Group, Gilead Sciences Inc, Lilly, Menarini Group, Novartis, Pfizer Inc, Puma Biotechnology Inc, Regor Therapeutics, Stemline Therapeutics Inc, Veracyte Inc; Contracted Research: Arvinas, Genentech, a member of the Roche Group, Lilly, Menarini Group, Nuvation Bio Inc, Pfizer Inc, Phoenix Molecular Designs, Puma Biotechnology Inc, Regor Therapeutics, Sermonix Pharmaceuticals, Stemline Therapeutics Inc.

EDITOR — Dr Love is president and CEO of Research To Practice. Research To Practice receives funds in the form of educational grants to develop CME activities from the following companies: Aadi Bioscience, AbbVie Inc, ADC Therapeutics, Agendia Inc, Alexion Pharmaceuticals, Amgen Inc, Array BioPharma Inc, a subsidiary of Pfizer Inc, Arvinas, Astellas, AstraZeneca Pharmaceuticals LP, Aveo Pharmaceuticals, Bayer HealthCare Pharmaceuticals, BeOne, Biotheranostics Inc, A Hologic Company, Black Diamond Therapeutics Inc, Blueprint Medicines, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Celcuity, Clovis Oncology, Coherus BioSciences, Corcept Therapeutics Inc, CTI BioPharma, a Sobi Company, Daiichi Sankyo Inc, Eisai Inc, Elevation Oncology Inc, Exact Sciences Corporation, Exelixis Inc, Genentech, a member of the Roche Group, Genmab US Inc, Geron Corporation, Gilead Sciences Inc, GSK, Helsinn Therapeutics (US) Inc, ImmunoGen Inc, Incyte Corporation, Ipsen Biopharmaceuticals Inc, Jazz Pharmaceuticals Inc, Johnson & Johnson, Karyopharm Therapeutics, Kite, A Gilead Company, Kura Oncology, Legend Biotech, Lilly, MEI Pharma Inc, Merck, Mersana Therapeutics Inc, Mirati Therapeutics Inc, Mural Oncology Inc, Natera Inc, Novartis, Novartis Pharmaceuticals Corporation on behalf of Advanced Accelerator Applications, Novocure Inc, Nuvalent, Nuvation Bio Inc, Pfizer Inc, Pharmacyclics LLC, an AbbVie Company, Puma Biotechnology Inc, Regeneron Pharmaceuticals Inc, Revolution Medicines Inc, Rigel Pharmaceuticals Inc, R-Pharm US, Sanofi, Seagen Inc, Servier Pharmaceuticals LLC, SpringWorks Therapeutics Inc, Stemline Therapeutics Inc, Sumitomo Pharma America, Summit Therapeutics, Syndax Pharmaceuticals, Taiho Oncology Inc, Takeda Pharmaceuticals USA Inc, TerSera Therapeutics LLC, and Tesaro, A GSK Company.

RESEARCH TO PRACTICE CME PLANNING COMMITTEE MEMBERS, STAFF AND REVIEWERS — Planners, scientific staff and independent reviewers for Research To Practice have no relevant financial relationships to disclose.

These educational activities contain discussion of published and/or investigational uses of agents that are not indicated by the Food and Drug Administration. Research To Practice does not recommend the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications and warnings. The opinions expressed are those of the presenters and are not to be construed as those of the publisher or grantors.

These activities are supported by educational grants from AstraZeneca Pharmaceuticals LP, Lilly, and Stemline Therapeutics Inc. 

Release date: April 2026
Expiration date: April 2027

After completing the post-test, learners may download and review the answers here in order to identify further areas of study.

Bidard FC et al. First-line camizestrant for emerging ESR1-mutated advanced breast cancer. N Engl J Med 2025;393(6):569-80. Abstract

Bidard F et al. Updated results and an exploratory analysis of ESR1m circulating tumor DNA (ctDNA) dynamics from SERENA-6, a phase 3 trial of camizestrant (CAMI) + CDK4/6 inhibitor (CDK4/6i) for emergent ESR1 mutations (ESR1m) during first-line (1L) endocrine-based therapy and ahead of disease progression in patients (pts) with HR+/HER2- advanced breast cancer (ABC). San Antonio Breast Cancer Symposium 2025;Abstract RF7-03.

Brett JO et al. ESR1 mutation as an emerging clinical biomarker in metastatic hormone receptor-positive breast cancer. Breast Cancer Res 2021;23(1):85. Abstract

Burstein HJ et al. Testing for ESR1 mutations to guide therapy for hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer: ASCO guideline rapid recommendation update. J Clin Oncol 2023;41(18):3423-5. Abstract

Cortes J et al. Phase III study of first-line (1L) inavolisib/placebo + a CDK4/6 inhibitor + letrozole (INAVO/PBO + CDK4/6i + LET) in participants (pts) with PIK3CA-mutated (mut), hormone receptor-positive (HR+), HER2-negative (HER2–), endocrine-sensitive advanced breast cancer (aBC). ESMO 2025;Abstract 408TiP.

Iams WT et al. Concurrent tissue and circulating tumor DNA molecular profiling to detect guideline-based targeted mutations in a multicancer cohort. JAMA Netw Open 2024;7(1):e2351700. Abstract

Jeselsohn R et al. ESR1 mutations — A mechanism for acquired endocrine resistance in breast cancer.Nat Rev Clin Oncol 2015;12(10):573-83. Abstract

Malorni L et al. Serum thymidine kinase activity in patients with HR-positive/HER2-negative advanced breast cancer treated with ribociclib plus letrozole: Results from the prospective BioItaLEE trial. Eur J Cancer 2023;186:1-11. Abstract

Malorni L et al. Serum thymidine kinase 1 activity in patients with hormone receptor positive (HR+)/HER2 negative (HER2-) advanced breast cancer (aBC) treated in first-line with ribociclib (R) and letrozole (L) in the BioItaLEE trial. ESMO 2021;Abstract 292P.

Mayer E et al. Giredestrant (GIRE), an oral selective oestrogen receptor (ER) antagonist and degrader, + everolimus (E) in patients (pts) with ER-positive, HER2-negative advanced breast cancer (ER+, HER2– aBC) previously treated with a CDK4/6 inhibitor (i): Primary results of the phase III evERA BC trial. ESMO 2025;Abstract LBA16.

Michaels EM et al. Associations between circulating tumor DNA genomic profiles and serum thymidine kinase patterns in patients with advanced, hormone receptor-positive, HER2-negative (HR+/HER-) breast cancer initiating treatment with a CDK4/6 inhibitor (CDK4/6i). San Antonio Breast Cancer Symposium 2025;Abstract PS2-10-21.

Saura C et al. Efficacy of RLY-2608, a mutant-selective PI3Kα inhibitor in patients with PIK3CA-mutant HR+HER2- advanced breast cancer: ReDiscover trial. San Antonio Breast Cancer Symposium 2024;Abstract PS7-01.

Turner NC et al. Capivasertib plus fulvestrant in hormone receptor-positive (HR+) advanced breast cancer (ABC): Exploratory ctDNA analyses from the phase 3 CAPItello-291 trial. San Antonio Breast Cancer Symposium 2025;Abstract RF7-05.

Turner NC et al. Inavolisib-based therapy in PIK3CA-mutated advanced breast cancer. N Engl J Med2024;391(17):1584-96. Abstract

Turner NC et al. Design of SERENA-6, a phase III switching trial of camizestrant in ESR1-mutant breast cancer during first-line treatment. Future Oncol 2023;19(8):559-73. Abstract

Turner NC et al. Circulating tumour DNA analysis to direct therapy in advanced breast cancer (plasmaMATCH): A multicentre, multicohort, phase 2a, platform trial. Lancet Oncol 2020;21(10):1296-308. Abstract

Vasan N, Cantley LC. At a crossroads: How to translate the roles of PI3K in oncogenic and metabolic signalling into improvements in cancer therapy. Nat Rev Clin Oncol 2022;19(7):471-85. Abstract