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 this episode, Dr Nunnery sat down with MinhTri Nguyen, MD, a breast medical oncologist, assistant professor, and lead faculty for Health Equity at Rush MD Anderson Cancer Center in Chicago, Illinois.

They discussed the emergence of giredestrant, an investigational oral selective estrogen receptor degrader (SERD), across the hormone receptor–positive, HER2-negative breast cancer treatment paradigm. Unlike aromatase inhibitors, which lower estrogen levels, or tamoxifen, which blocks the estrogen receptor (ER), SERDs degrade the receptor entirely, Dr Nguyen explained. He noted that ESR1 mutations, an acquired resistance mechanism that renders the ER constitutively active, confer worse prognosis and appear to be where oral SERDs derive their strongest signal.

The conversation first addressed the phase 3 evERA Breast Cancer trial (NCT05306340), which randomly assigned patients with previously treated advanced disease to receive giredestrant plus everolimus (Afinitor) or standard-of-care endocrine therapy plus everolimus. Dr Nguyen emphasized the elegance of targeting 2 resistance pathways simultaneously: the endocrine pathway and the parallel mTOR/PI3K/AKT axis. The combination significantly improved median progression-free survival in both the population with ESR1-mutated disease and the intention-to-treat population, though the experts cautioned that the patients with ESR1-mutated disease likely drove the overall benefit, as wild-type outcomes mirrored those in the control arm. The experts characterized giredestrant-associated adverse effects as largely everolimus-driven, most notably stomatitis, and highlighted class-associated bradycardia. They also noted that no photopsia was reported.

They then turned to the phase 3 lidERA Breast Cancer trial (NCT04961996), in which patients with predominantly high-risk, early-stage disease received giredestrant or standard endocrine therapy. Giredestrant produced a reduction in the risk of invasive disease recurrence or death, with markedly lower discontinuation rates and consistent benefit across premenopausal and postmenopausal subgroups.

Finally, the experts contextualized findings from the negative first-line persevERA Breast Cancer trial (NCT04546009), concluding that a single negative readout does not close the oral SERD story, and that thoughtful patient selection will define giredestrant’s future role in the breast cancer treatment armamentarium.

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 this episode, Nunnery sat down with Annie Bond, a breast cancer survivor and patient advocate.

Diagnosed with breast cancer at age 26, Bond shared how her initial concerns about a breast lump were repeatedly dismissed by medical professionals who cited her youth and lack of a family history of breast cancer. It took months of persistence before she received a diagnosis, at which point the cancer had already spread to her liver.

Bond emphasizes the necessity of self-advocacy and the value of seeking second or third medical opinions. Regarding fertility preservation, her first oncologist discouraged her from freezing her eggs, but her third oncologist provided a more personalized approach, using CDK4/6 inhibitors rather than immediate chemotherapy based on her luminal A disease subtype.

A significant portion of the conversation focused on the mental health toll of cancer. Bond discusses the "warrior" stereotype, the guilt and shame she felt, and her struggle with post-traumatic stress disorder. She says she found critical support in community and support groups, which helped normalize her feelings and provided a sense of belonging.

Regarding physical adverse effects, Bond detailed the challenges of medical menopause, including "menopause brain" and joint pain, which she manages through walking and stretching. She expressed frustration with health education that focuses on diet or alcohol as "blame" factors, noting that cancer can often develop regardless of lifestyle.

Bond explained how she advocates for metastatic breast cancer research funding and the use of artificial intelligence risk assessment models to account for factors like breast density. Her mission is to increase early detection and ensure patients with metastatic disease are viewed with hope.

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.

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.

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 today's episode, 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 centered around lifestyle and medical interventions pertinent to breast cancer survivorship. Dr Iyengar explained that although endocrine therapies can be life-saving, they disrupt estrogen signaling, which can lead to cardiometabolic dysfunction, including increased risks for diabetes, heart disease, and bone health issues. He noted that weight gain associated with these treatments is often tied to the induction of a post-menopausal state, which disrupts energy homeostasis and promotes inflammation.

A key theme of the conversation was Dr Iyengar’s explanation of a "drug development paradigm" for lifestyle changes. Rather than offering generic advice, his research focuses on precision lifestyle interventions, treating diet and exercise as prescribed medical therapies with specific "doses". He highlighted that body mass index (BMI) is an insufficient tool for risk stratification, as high body fat despite a normal BMI is a significant risk factor for cancer recurrence.

The discussion also covered the rising use of GLP-1 receptor agonists to manage metabolic health. These drugs replicate natural hormones to maintain glycemic balance and reduce hunger. Dr Iyengar addressed the black box warning for thyroid cancer associated with this class of drugs, noting that although the data are mixed, the protective benefits against obesity-related cancers appear to outweigh the risks. Finally, he emphasized that exercise is a critical tool for managing treatment adverse effects like fatigue, noting that although starting is difficult, the "return on investment" for patient health is immense.

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 today's episode, filmed live onsite at the 43rd Annual Miami Breast Cancer Conference, Dr Nunnery sat down with Kelly E. McCann, MD, PhD, a breast medical oncologist in the University of California system.

Their conversation centered around the evolving HER2-positive breast cancer treatment paradigm. The experts highlighted that although this disease was once associated with a poor prognosis, targeted therapies like trastuzumab (Herceptin) have revolutionized management, making these cancers highly curable.

They noted the role of fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu), an antibody-drug conjugate (ADC) that delivers chemotherapy directly to cancer cells and uses a bystander effect to kill neighboring malignant cells. The phase 3 DESTINY-Breast11 trial (NCT05113251) evaluated T-DXd in the neoadjuvant setting for patients with high-risk, HER2-positive early breast cancer. Results showed significantly higher pathological complete response rates with T-DXd followed by docetaxel, trastuzumab, and pertuzumab (Perjeta) compared with standard chemotherapy. Responses were even more pronounced in patients with hormone receptor–negative disease.

Furthermore, they spotlighted the phase 3 DESTINY-Breast05 trial (NCT04622319), which examined T-DXd as adjuvant therapy for high-risk patients with residual HER2-positive disease. In this study, T-DXd generated an improvement in invasive disease–free survival compared with standard ado-trastuzumab emtansine (Kadcyla). They noted that a significant benefit of T-DXd is its ability to cross the blood-brain barrier, offering the potential for preventing brain metastases. However, the experts expressed caution regarding interstitial lung disease, a potentially fatal adverse effect associated with T-DXd. Because of this risk, patients who receive T-DXd require frequent, expensive CT monitoring, which Nunnery and McCann explained can pose logistical and insurance challenges in standard practice.

Although adjuvant T-DXd has been added to the National Comprehensive Cancer Network Clinical Practice Guidelines for HER2-positive breast cancer, the neoadjuvant regimen has not yet been included, likely awaiting more mature survival data. Both oncologists conclude that although ADC-associated toxicities require vigilant management, these treatment advancements provide powerful new tools for potentially curing high-risk patients with HER2-positive breast cancer.