
In their concluding remarks, Virginia Kaklamani, MD, DSc, and Heather McArthur, MD, summarize their key insights and perspectives on the management of HR+ breast cancer.

Heather McArthur, MD, MPH, FASCO, is the Clinical Director of Breast Cancer and Komen Distinguished Chair in Clinical Breast Cancer Research at University of Texas Southwestern (UTSW) Medical Center.

In their concluding remarks, Virginia Kaklamani, MD, DSc, and Heather McArthur, MD, summarize their key insights and perspectives on the management of HR+ breast cancer.

The key opinion leaders discuss the current unmet needs in the management of HR+/HER2- metastatic breast cancer and explore potential future directions and strategies that may lead to improved patient outcomes.

In their discussion, the key opinion leaders explore the potential of combination therapies in HR+/HER2- metastatic breast cancer, with a specific focus on the ELECTRA study, which investigated the combination of elacestrant and abemaciclib.

The expert panel examines the subgroup data from the postMONARCH study, focusing on patients with ESR1 and PIK3CA mutations, and emphasizes the important role of CDK4/6 inhibitors in the treatment of these specific patient populations with HR+/HER2- metastatic breast cancer.

In their discussion, the key opinion leaders explore the significance of PIK3CA mutations in HR+/HER2- metastatic breast cancer and review the findings from two pivotal clinical trials, SOLAR-1 and CAPItello-291, which investigated the efficacy of targeted therapies in patients harboring these mutations.

Virginia Kaklamani, MD, DSc, and Heather McArthur, MD, discuss the clinical presentation and management of a 64-year-old postmenopausal female with a history of rheumatoid arthritis who was diagnosed with stage IV, grade 3, invasive ductal carcinoma in her left breast, taking into account her comorbidities and the advanced stage of her breast cancer.

The breast cancer experts share their clinical experiences and strategies regarding the optimal timing for testing ESR1 mutations in patients with HR+/HER2- metastatic breast cancer, elaborating on how the specific points in the treatment journey at which they recommend testing influence their subsequent treatment decisions and overall approach to patient management.

Key opinion leaders examine the EMERALD trial, which evaluates the efficacy of elacestrant in patients with HR+ HER2- metastatic breast cancer, focusing on the subgroup analysis of patients with visceral metastases, and explore how the trial's design and results have influenced their clinical practice.

Virginia Kaklamani, MD, DSc, and Heather McArthur, MD, present a patient case involving a 54-year-old postmenopausal woman diagnosed with a 2.1cm estrogen receptor positive (ER+), HER2 negative breast cancer, and discuss the clinical implications and management strategies for this specific patient scenario.

In their discussion, medical experts in the field of breast cancer explore the role of liquid biopsies and compare the significance of ESR1 mutations to other biomarkers, such as PIK3CA, in terms of their driver versus passenger status in the context of HR+/HER2- breast cancer.

The key opinion leaders (KOLs) review the current testing methods for detecting ESR1 mutations and explore the existing strategies employed to overcome or delay the development of these mutations and the associated endocrine resistance in patients with HR+/HER2- metastatic breast cancer.

Virginia Kaklamani, MD, DSc, and Heather McArthur, MD, explore the clinical significance of *ESR1* mutations in HR+/HER2- metastatic breast cancer patients, including their impact on disease prognosis, treatment outcomes, and the increasing prevalence of these mutations with each line of endocrine therapy, ultimately informing their therapeutic approach.

Key opinion leaders anticipate future developments in HER2-positive breast cancer, and on the potential for translating therapeutic advances from the metastatic landscape into early-stage disease management.

Medical experts delve into the challenges of brain metastases in HER2-positive breast cancer, exploring local therapies for targeting central nervous system metastases and emphasizing the crucial role of multidisciplinary tumor boards, collaboration with colleagues, and referrals to specialized providers in optimizing patient outcomes.

Key opinion leaders revisit the HER2CLIMB trial, providing an in-depth analysis of the latest updates and their implications for the management of HER2-positive metastatic breast cancer.

Vijayakrishna Gadi, MD, PhD, presents the case of a 54-year-old woman with HER2-positive metastatic breast cancer exhibiting bone, liver, and brain lesions, and key opinion leaders share their perspectives on the most appropriate treatment approaches tailored to the patient's specific disease characteristics and metastatic sites.

Vijayakrishna Gadi, MD, PhD, shares his insights on managing patients with HER2-positive metastatic breast cancer who have progressed on second and third-line treatments, stressing the potential benefits of incorporating small molecules, tyrosine kinase inhibitors (TKIs), chemotherapy, and enrolling patients in clinical trials to optimize outcomes.

Tiffany A. Traina, MD, addresses adverse event monitoring and the range of adverse events patients may experience with front-line treatments for HER2-positive metastatic breast cancer, particularly highlighting alopecia and diarrhea as common side effects.

Key opinion leaders explore various therapeutic options for later-line treatment of HER2-positive metastatic breast cancer, emphasizing the significance of the HER2CLIMB and CLEOPATRA trials, while also drawing comparisons to real-world data to inform clinical decision-making.

Tiffany A. Traina, MD, presents a patient case involving a woman diagnosed with HR-negative, HER2 3+ invasive ductal adenocarcinoma and elaborates on the clinical management approaches employed in her treatment sequencing.

Heather McArthur, MD, emphasizes the influence of recent and ongoing clinical trials, specifically DESTINY-Breast09 and HER2CLIMB-05, in steering the treatment paradigm in 1st-line HER2-positive metastatic breast cancer.

Medical experts examine the current standards of care and successive lines of treatment for HER2-positive metastatic breast cancer, while also addressing the challenges encountered in managing this complex disease.

Tiffany A. Traina, MD; Vijayakrishna Gadi, MD, PhD, and Heather McArthur, MD, underscore the importance of testing all early-stage and breast cancer patients for HER2 positivity to inform and guide optimal therapeutic decision-making.

Heather Lynn McArthur, MD, MPH, discusses the primary results from the phase 3 KEYNOTE-756 study of neoadjuvant pembrolizumab plus chemotherapy in early-stage, high-risk, estrogen receptor–positive, HER2-negative breast cancer.

Panelists wrap up their discussion on HER2+ breast cancer by summarizing the most exciting recent advances in the field and their hopes for the future of treatment.

Dr Kaklamani presents a profile of a patient with HER2+ breast cancer and liver metastases who had disease progression after first-line chemotherapy and a solitary new brain metastasis after second-line T-DM1.

Melinda L. Telli, MD, presents a profile of a patient with early stage breast cancer with residual nodal disease after neoadjuvant chemotherapy and surgery, whose tumor was initially HER2+ but became triple-negative after treatment.

Virginia G. Kaklamani, MD, DSc, presents a patient profile of early stage HER2+ breast cancer with residual nodal disease after neoadjuvant chemotherapy and surgery.

Experts share their go-to regimens in the third-line and higher setting of HER2+ metastatic breast cancer, and touch on the factors that support their decision-making.

Debu Tripathy, MD, discusses novel therapies being developed for later-line treatment of HER2+ mBC.