S17 Ep9: Medical Crossfire®: Optimizing ESR1 Mutation Detection and Next-Generation Endocrine Therapy Integration in HR+/HER2– Breast Cancer

Dr Kruse discussed the evolving role of FES-PET/CT in breast cancer, particularly invasive lobular carcinoma. She explained that FES-PET/CT uses a radiotracer to map estrogen receptor–positive cancer sites, offering advantages over traditional imaging. FIndings from a study presented at the 2025 San Antonio Breast Cancer Symposium showed that many patients experienced treatment changes based on FES-PET/CT results. The National Comprehensive Cancer Network guidelines also now recommend FES-PET/CT for use in lobular breast cancer, enhancing its clinical utility. Dr Kruse concluded by emphasizing that future research is needed to explore its use in early-stage breast cancer and for monitoring endocrine therapy response.

In today’s episode, we spoke with Alissa Cooper, MD. Dr Cooper is a physician at Dana-Farber Cancer Institute and an instructor in medicine at Harvard Medical School in Boston, Massachusetts. In our exclusive interview, Dr Cooper discussed recent advances that have reshaped the treatment paradigm for small cell lung cancer (SCLC), particularly in the relapsed setting. She highlighted the FDA approval of tarlatamab-dlle (Imdelltra), a DLL3-targeting T-cell engager, as one of the most impactful developments in recent years. Despite this progress, Cooper emphasized that the frontline standard of care has remained largely unchanged, continuing to rely on platinum-based chemotherapy in combination with immunotherapy. She noted that, although ongoing clinical trials are exploring biomarker-driven strategies and novel combinations, a more personalized first-line approach has yet to be established.The conversation also explored real-world treatment sequencing and decision-making at the point of relapse. Cooper explained that, whenever feasible, oncologists aim to enroll patients in clinical trials or initiate treatment with tarlatamab. However, logistical barriers, including trial screening requirements and the need for monitored administration of T-cell engagers, can delay care. In cases of rapidly progressing disease, oncologists may instead turn to cytotoxic therapies such as lurbinectedin (Zepzelca) or use localized approaches like radiation to achieve faster disease control.The importance of multidisciplinary coordination was another key theme. Cooper underscored that SCLC management requires rapid collaboration among medical oncologists, radiation oncologists, pulmonologists, pathologists, and supportive care teams. Early involvement of palliative care is also critical, given the aggressive nature of the disease and high symptom burden.Additionally, she highlighted the essential role of oncology pharmacists, nursing teams, and structured patient education. Clear toxicity management protocols, dose-modification guidelines, and comprehensive patient education visits help ensure safe treatment delivery and empower patients to manage adverse effects.Looking ahead, Cooper described an “embarrassment of riches” in emerging therapies and targets under investigation. Beyond DLL3, novel approaches targeting markers such as SEZ6 and B7-H3, as well as next-generation antibody-drug conjugates and trispecific T-cell engagers, are showing early promise. However, key questions remain regarding biomarker selection, treatment sequencing, and real-world effectiveness, particularly for patients who would not meet clinical trial eligibility criteria.Finally, she emphasized that improving coordination between community and academic centers is essential to ensuring timely access to innovative therapies and clinical trials. Strengthening communication pathways and referral processes may help bridge gaps in care and improve outcomes for patients with this aggressive disease.

In this podcast, experts Neil Iyengar, MD; Kelly Elizabeth McCann, MD, PhD; and Wassim Mchayleh, MD, MBA, FACP, discuss the clinical applications and current evidence for using circulating tumor DNA (ctDNA) testing in early-stage and metastatic breast cancer.

Breast Cancer Briefing, hosted by Sara Nunnery, MD, MSCI, a breast medical oncologist and the director of Breast Cancer Research at Tennessee Oncology in Nashville, is a podcast series that breaks down the latest news in breast cancer research, one conversation at a time.In part 2 of this conversation, filmed live onsite at the 43rd Annual Miami Breast Cancer Conference, Dr Nunnery sat down with Irene Morae Kang, MD, an assistant professor in the Department of Medical Oncology & Therapeutics Research and the medical director of Women’s Health Medical Oncology at City of Hope Orange County in Irvine, California.Their discussion focuses on the rapidly evolving treatment paradigm for first-line metastatic triple-negative breast cancer (TNBC), including the emergence of new data that is shifting standards of care. Dr Kang explained that TNBC is defined by the absence of estrogen, progesterone, and HER2 receptors, which historically restricted treatment options to non-targeted chemotherapy. A primary focus of the conversation was the role of PD-L1 expression and the use of immunotherapy. Dr Kang described PD-L1 as a checkpoint inhibitor protein on cancer cells that shuts off the immune system. By blocking this protein, oncologists can keep the body’s T-cells vigilant to fight the cancer. However, she noted that immunotherapy is typically reserved for the approximately 40% of patients who express PD-L1 and may be contraindicated for those with active autoimmune diseases or a history of severe immune-related toxicities.The dialogue transitioned into the use of antibody-drug conjugates (ADCs). Dr Kang reviewed data from major trials using TROP2-targeting ADCs in the first-line setting. Dr Kang emphasized the importance of using these highly effective agents early, as many patients with TNBC do not survive to receive a second line of therapy.Finally, Dr Kang highlighted the distinct toxicity profiles and administration schedules that guide clinical decision-making. Although sacituzumab govitecan-hziy (Trodelvy) is frequently associated with neutropenia and alopecia, the primary toxicities associated with datopotamab deruxtecan-dlnk (Dato-DXd; Datroway) are stomatitis and ocular adverse effects like dry eye. Using Dato-DXd in practice requires a rigorous prophylactic regimen, including steroid mouthwash and lubricating eye drops. Ultimately, Dr Kang noted that because efficacy appears similar between the 2 ADCs, the choice often rests on the patient’s lifestyle, their ability to adhere to preventative AE protocols, and infusion schedule preference.

In this podcast, experts David S. Klimstra, MD; Danielle A. Hutchings, MD; Nancy M. Joseph, MD, PhD; and Jonathan Strosberg, MD; discuss how neuroendocrine neoplasms are defined, diagnosed, and treated and why distinguishing between tumor types is critical for prognosis and therapies.

Breast Cancer Briefing, hosted by Sara Nunnery, MD, MSCI, a breast medical oncologist and the director of Breast Cancer Research at Tennessee Oncology in Nashville, is a podcast series that breaks down the latest news in breast cancer research, one conversation at a time.In part 2 of this conversation, filmed live onsite at the 43rd Annual Miami Breast Cancer Conference, Dr Nunnery sat down with Neil M. Iyengar, MD, an associate professor and co-director of Breast Medical Oncology in the Department of Hematology and Medical Oncology at the Emory University School of Medicine, as well as the director of Survivorship Services at the Winship Cancer Institute of Emory University in Atlanta, Georgia.Their conversation highlighted the evolving integration of GLP-1 agonists into the breast cancer treatment armamentarium.

In this podcast, experts V.K. Gadi, MD, PhD; Neil M. Iyengar, MD; and Heather McArthur, MD; discuss advances in breast cancer treatment, endocrine resistance and mutations, and emerging targeted therapies for early-stage and metastatic disease.

In this podcast, experts Naval G. Daver, MD; Amir Fathi, MD; Guillermo Garcia-Manero, MD; and Aditi Shastri, MD, discuss current applications for menin inhibitors in patients with acute leukemia, combination approaches under investigation, and managing treatment-related adverse events with menin inhibitors.

From Discovery to Delivery: Charting Progress in Gynecologic Oncology, hosted by Ursula A. Matulonis, MD, brings expert insights into the most recent breakthroughs, evolving standards, and emerging therapies across gynecologic cancers. Dr Matulonis is chief of the Division of Gynecologic Oncology and the Brock-Wilcon Family Chair at the Dana-Farber Cancer Institute, as well as a professor of medicine at Harvard Medical School, both in Boston, Massachusetts. In this episode, Dr Matulonis was joined by Elizabeth H. Stover, MD, PhD, a physician at Dana-Farber Cancer Institute and an assistant professor of medicine at Harvard Medical School. Together, they explored the biology and therapeutic relevance of the RAS/MAP kinase pathway in gynecologic cancers. Dr Stover began by explaining that the RAS/MAP kinase pathway is a well-established oncogenic signaling cascade that regulates cancer cell proliferation, survival, and invasion. Advances in drug development are now making it possible to target multiple points along this pathway, including RAS itself, once considered “undruggable.”Drs Matulonis and Stover emphasized that RAS/MAP kinase pathway alterations are relatively common across gynecologic malignancies, occurring in at least 20% of cases overall. Certain disease subtypes have particularly high prevalence, including low-grade serous ovarian cancer, mucinous ovarian cancer, and subsets of endometrial and cervical cancers. Clinically, activation of this pathway is generally associated with more aggressive disease and reduced sensitivity to conventional chemotherapy, although nuances exist. The conversation also explored emerging therapeutic strategies targeting this pathway. Early developmental success with MEK inhibitors—such as trametinib (Mekinist), selumetinib (Koselugo), and binimetinib (Mektovi)—has translated to meaningful clinical benefit, particularly in low-grade serous ovarian cancer. More recently, combination approaches have shown promise, including the dual RAF/MEK inhibitor avutometinib paired with the FAK inhibitor defactinib (Avmapki Fakzynja Co-pack). This combination addresses adaptive resistance mechanisms and has generated improved response rates and disease control, leading to its May 2025 FDA approval in this setting.Looking ahead, Dr Stover highlighted the development of direct RAS inhibitors as one of the most exciting advances in oncology. Dr Stover concluded by outlining key areas of ongoing research, including understanding differential sensitivity across tumor subtypes, identifying mechanisms of resistance, and optimizing combination strategies. 

In this podcast, experts Adam Brufsky, MD, PhD; Kamel Abou Hussein, MD; and Priyanka Sharma, MD, FASCO, discuss personalizing care in early-stage triple-negative breast cancer (TNBC) and the evolving first-line strategies and their implications for downstream sequencing in metastatic TNBC.