Case 3: Metastatic HR-Positive/HER2-Negative Breast Cancer With PTEN Loss and Emergent ESR1 Mutation
This is Part 3 of Balancing Benefit and Burden: Managing Toxicities in HR-Positive/HER2-Negative Metastatic Breast Cancer, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Neil Iyengar, Sara Tolaney, and William Gradishar discuss the treatment of a patient with metastatic hormone receptor–positive/HER2-negative breast cancer with PTEN loss and emergent ESR1 mutation. The patient is a 61-year-old woman with a history of primary HR-positive/HER2-negative invasive lobular carcinoma who presents 7 years post-treatment with metastatic disease involving bone and colon. Her treatment course is complicated by baseline gastrointestinal symptoms from colonic involvement, and her baseline IBS-like symptoms require careful consideration when selecting therapies, particularly those with gastrointestinal toxicity profiles. In the conversation that follows, the faculty emphasize the superiority of FES PET for lobular carcinoma imaging and the importance of integrating multiple monitoring tools in bone-predominant disease. They highlight the role of serial molecular profiling to identify emergent alterations like ESR1 mutations and PTEN loss that create new therapeutic opportunities. The case underscores the importance of selecting treatments that balance efficacy against patient-specific tolerability factors.
Case 2: De Novo Metastatic PIK3CA-Altered HR-Positive/HER2-Negative Breast Cancer and Non–Insulin-Dependent Diabetes
This is Part 2 of Balancing Benefit and Burden: Managing Toxicities in HR-Positive/HER2-Negative Metastatic Breast Cancer, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Neil Iyengar, Sara Tolaney, and William Gradishar discuss the treatment of a patient with PIK3CA-altered hormone receptor (HR)-positive/HER2-negative metastatic breast cancer and non–insulin-dependent diabetes. The patient is a 58-year-old postmenopausal woman presenting with de novo metastatic HR-positive/HER2-negative breast cancer involving the lungs and liver. Next-generation sequencing reveals a PIK3CA E542K mutation. She has a high-risk metabolic profile including pre-existing diabetes and obesity, and she was already receiving metformin therapy. As her disease progresses, she experiences severe hyperglycemia and a concurrent urinary tract infection. Patients with high-risk metabolic features require early endocrinology involvement and heightened vigilance when initiating PI3K pathway inhibitors. The faculty discuss the optimal treatment sequencing for this patient, the importance of risk stratification, prophylactic strategies such as metformin optimization and early SGLT2 inhibitor use, and the crucial role of intensive glucose monitoring for high-risk patients.
Case 1: PIK3CA-Altered HR-Positive/HER2-Negative Metastatic Breast Cancer
This is Part 1 of Balancing Benefit and Burden: Managing Toxicities in HR-Positive/HER2-Negative Metastatic Breast Cancer, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Neil Iyengar, Sara Tolaney, and William Gradishar discuss the treatment of a patient with PIK3CA-altered hormone receptor (HR)-positive/HER2-negative metastatic breast cancer. The patient is a 64-year-old postmenopausal woman with a history of early-stage HR-positive/HER2-negative breast cancer that was originally treated with lumpectomy, chemotherapy, radiation, and 10 years of endocrine therapy. Two years post-treatment, she presents with metastatic disease to her bone and liver, and next-generation sequencing reveals a PIK3CA H1047R mutation. As her disease progresses, the patient requires glucose monitoring and management due to capivasertib-associated hyperglycemia. In the conversation that follows, the faculty review treatment options for patients with PIK3CA-altered disease, the role of early genomic testing, and the nuances of AKT vs PI3K inhibitor selection. They emphasize the importance of proactive toxicity management for high-risk patients, including glucometer education for hyperglycemia and multidisciplinary collaboration to ensure that patients are able to continue treatment.
Most Patients Support Use of AI in Mammogram Readings, Survey Reveals
The results of a recent survey showed that patients largely support the use of artificial intelligence (AI) to aid radiologists in reading mammograms. The findings, which were published in Breast Cancer Research and Treatment, also indicated acceptance varied in association with factors such as...
Axillary Recurrence With or Without ALND in Patients With Residual Micrometastases After Neoadjuvant Chemotherapy for Breast Cancer
In an initial analysis of a retrospective cohort study (OPBC-07/microNAC) reported in The Lancet Oncology, Montagna et al found that available evidence did not provide support for axillary lymph node dissection (ALND) in all patients with ypN1mi disease in sentinel lymph nodes after neoadjuvant...
Breast Cancer Risk May Be Linked to Physical Activity Levels in Adolescence
Recreational physical activity may be associated with breast tissue composition and oxidative stress levels in adolescent girls, independent of body fat percentages, according to research findings published in Breast Cancer Research. “The importance and urgency of this research are underscored by...
ctDNA Positivity After Neoadjuvant T-DM1 May Predict HER2-Positive Breast Cancer Recurrence
Excluding skin cancers, breast cancer is the most commonly diagnosed cancer among women in the United States, accounting for about 30% of all new female cancers each year. In 2026, the American Cancer Society estimates that 322,000 new cases of invasive breast cancer and about 61,000 new cases of...
Genetic Predisposition to Higher Body Mass Index Linked to Mortality After Breast Cancer
In an observational cohort study published in JAMA Network Open, Bodelon et al examined whether inherited susceptibility to excess body weight influences long-term survival among breast cancer survivors. Using a polygenic score for body mass index (BMI), the investigators sought to determine...
Improved Contralateral Breast Cancer Risk Knowledge With Personalized Counseling Tool
Patients with unilateral breast cancer who underwent quantitative counseling with a personalized tool incorporating genetic testing results were better informed of their contralateral breast cancer risk compared with those who received standard counseling, according to results from the GET FACTS...
Machine Learning Approach Accelerates Discovery of Novel CDK9 Inhibitors
A virtual screening campaign using machine learning identified molecules with potential for development as novel CDK9 inhibitors for the treatment of cancer, according to early research findings published in Biomolecules. Integration of artificial intelligence (AI) into the drug discovery phase...
Breast Cancer Recurrence Risk Determined by Deep Learning Model Trained on Histopathologic Slides
A deep learning model demonstrated the ability to predict breast cancer recurrence risk and possible benefit from the addition of chemotherapy based on histopathologic images rather than genomic testing in patients with hormone receptor–positive, HER2-negative breast cancer, according to findings...
Novel Endocrine Therapy, Giredestrant, Improves Invasive Disease–Free Survival in Estrogen Receptor–Positive, HER2-Negative Early Breast Cancer
Giredestrant, a next-generation oral selective estrogen receptor degrader (SERD) and full antagonist, significantly improved invasive disease–free survival as adjuvant treatment for patients with estrogen receptor–positive, HER2-negative early breast cancer compared with standard-of-care endocrine...
Adjuvant Epirubicin Plus Cyclophosphamide Followed by Taxane With or Without Carboplatin in Early-Stage Triple-Negative Breast Cancer
In a Chinese phase III trial (RJBC 1501) reported in the Journal of Clinical Oncology, Chen et al found that the addition of carboplatin to adjuvant epirubicin plus cyclophosphamide followed by taxane chemotherapy significantly improved disease-free survival in patients with early-stage...
10-Year Outcomes With Adjuvant Metronomic Capecitabine in Early Triple-Negative Breast Cancer
In a 10-year update of a Chinese phase III trial (SYSUCC-001) reported in The Lancet Oncology, Yuan et al found that the sequential addition of metronomic capecitabine to standard adjuvant therapy continued to be associated with significant benefits in patients who had undergone surgery for early...
Distant Disease–Free Survival as a Surrogate for Overall Survival in Trials of Neoadjuvant Therapy in Early Breast Cancer
In a pooled analysis of randomized neoadjuvant trials reported in The Lancet Oncology, Conforti et al found that distant disease–free survival was a “robust” surrogate endpoint for overall survival in many patients with early breast cancer. Study Details The analysis included individual patient...
HER2-Positive Breast Cancer: FDA Approves T-DXd Plus Pertuzumab
On December 15, the U.S. Food and Drug Administration (FDA) approved fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) in combination with pertuzumab for the first-line treatment of adults with unresectable or metastatic HER2-positive (IHC 3+ or ISH+) breast cancer, as determined by an FDA-approved...
AI Models Advance Individualized Breast Cancer Recurrence Risk Assessments
Two presentations at the 2025 San Antonio Breast Cancer Symposium (SABCS) highlighted new artificial intelligence (AI) tools and systems for improving distant recurrence risk stratification among patients with early-stage breast cancer. The first tested multimodal AI models with imaging, clinical,...
Is Menopausal Hormone Therapy Associated With Increased Breast Cancer Risk?
Using menopausal hormone therapy was not associated with an increased risk of breast cancer in women with inherited mutations in the BRCA1 or BRCA2 genes, according to the results of a matched prospective analysis presented at the 2025 San Antonio Breast Cancer Symposium (SABCS; Abstract GS3-01)....
Mobile Health Intervention Offers Tailored Support for Adolescent and Young Adult Breast Cancer Survivors
A mobile health tool designed specifically for adolescent and young adult (AYA) breast cancer survivors significantly improved overall quality of life and reduced symptoms related to vaginal and arm problems when compared with usual care, according to the results of a multicenter randomized trial...
Can Multimodal AI Models Predict Distant Recurrence Risk in Patients With Early Breast Cancer?
Multimodal artificial intelligence (AI) models using a combination of molecular, imaging, and clinical features improved the individual prognostic assessment of patients with early breast cancer's risk of distant recurrence, according to an analysis presented at the 2025 San Antonio Breast Cancer...
Acupuncture May Improve Perceived Cognitive Difficulties in Breast Cancer Survivors
New findings from the phase II ENHANCE clinical trial indicate that both real and sham acupuncture improve breast cancer survivors’ perceived cognitive impairment more effectively than usual care alone, while real acupuncture improves objective measures of cognitive performance better than sham...
Regional Control Unchanged by Avoiding Sentinel Lymph Node Biopsy in Early Node-Negative Breast Cancer
Similar recurrence and regional recurrence-free survival rates were observed at 5 years with or without a sentinel lymph node biopsy in patients with clinically node-negative cT1-2 breast cancer treated with breast-conserving therapy, according to findings from the phase III BOOG 2013-08 trial...
Sacituzumab Govitecan vs Standard of Care for Certain Endocrine Therapy–Refractory Advanced Breast Cancers
Patients with hormone receptor–positive, HER2-negative advanced breast cancers had similar progression-free survival whether they were treated with sacituzumab govitecan-hziy or standard-of-care chemotherapy as the first treatment after endocrine therapy, according to results from the phase III...
Oral SERD Improves Disease-Free Survival Over Standard of Care for Patients With Early-Stage Breast Cancer
The investigational oral selective estrogen receptor degrader (SERD) giredestrant given as an adjuvant therapy showed significant improvement in invasive disease–free survival compared with the current standard-of-care endocrine therapy in patients with early-stage, hormone receptor-positive,...
Phase III Trial Shows No Oncologic Benefit From Routine Preoperative MRI for Some Early Breast Cancers
Rates of local regional recurrence were very low for patients with early-stage triple-negative or HER2-positive breast cancer regardless of whether or not they received a breast MRI for staging and surgical planning, according to findings from the phase III Alliance A011104/ACRIN 6694 trial...
Adding Tucatinib to First-Line Maintenance Therapy Delays Disease Progression in HER2-Positive Metastatic Breast Cancer
Adding the selective HER2 inhibitor tucatinib to first-line maintenance therapy with trastuzumab and pertuzumab delayed disease progression in patients with HER2-positive metastatic breast cancer, potentially extending time off chemotherapy, according to results from the phase III HER2CLIMB-05...
P-RAD Trial Shows Increased T-Cell Infiltration With Preoperative Radiation Added to Anti–PD-1 Therapy in Early Breast Cancer
Preoperative radiation therapy added to anti–PD-1 immune checkpoint inhibition led to a significant increase in T-cell infiltration in patients with hormone receptor–positive/HER2-negative early-stage breast cancer, according to findings from the phase II P-RAD trial presented at the 2025 San...
AI Tops Density in Predicting Breast Cancer Risk
An image-only artificial intelligence (AI) model for predicting the 5-year risk of breast cancer provided stronger and more precise risk stratification than breast density assessment, according to a news statement issued about a study presented at the annual meeting of the Radiological Society of...
Toxicity Concerns for PARP Inhibition Given Concurrently With Adjuvant Radiotherapy for Breast Cancer
Rates of radiotherapy-associated adverse events were considerably higher with the concurrent addition of low doses of the PARP inhibitor olaparib compared with radiotherapy alone in patients with inflammatory breast cancer in the adjuvant setting, according to the results of a toxicity analysis...
Benefits Mount for TROP2-Directed Antibody-Drug Conjugates in Triple-Negative Breast Cancer
Two randomized phase III trials presented at the European Society for Medical Oncology (ESMO) Congress 2025 bolster support for the use of antibody–drug conjugates—in particular, trophoblast cell surface antigen 2 (TROP2)-targeted agents—as first-line treatments for patients with triple-negative...
Fuzuloparib in HER2-Negative Metastatic Breast Cancer With Germline BRCA1/2 Mutations
In an interim analysis of a Chinese phase III trial (FABULOUS) reported in The Lancet Oncology, Li et al found that the addition of the PARP inhibitor fuzuloparib to apatinib and fuzuloparib alone improved progression-free survival vs chemotherapy in patients with HER2-negative metastatic breast...
Mammography-Based Outreach Increases Lung Cancer Screening Enrollment in Eligible Women
Women who undergo mammography to screen for breast cancer can be reviewed and recommended for additional lung cancer screening, thereby increasing enrollment, according to the results of a study published in the Journal of the American College of Radiology. The study, called Coordinate a Lung...
Retrospective Review Shows Persistent Breast Cancer Burden in Younger Women
Up to 24% of breast cancers diagnosed in an 11-year period between seven outpatient facilities around New York were found in women aged 18 to 49 years, according to findings presented during the 2025 Annual Meeting of the Radiological Society of North America (RSNA; Abstract S5-SSBR02-1). “This...
Image-Only AI Model Outperforms Breast Density Assessment for 5-Year Breast Cancer Risk Stratification
An image-only artificial intelligence (AI) model demonstrated stronger and more precise risk stratification than breast density assessment for predicting 5-year risk for developing breast cancer, according to findings from a study presented at the 2025 Annual Meeting of the Radiological Society of...
ADCs vs Standard Chemotherapy: Cardiotoxicity in HER2-Positive Advanced Breast Cancer
A systematic review and meta-analysis published in JAMA Network Open compared the cardiotoxicity of novel antibody-drug conjugates (ADCs) with that of standard trastuzumab-containing chemotherapy in patients with HER2-positive locally advanced or metastatic breast cancer, finding that treatment...
Proton vs Photon Radiation Therapy for Nonmetastatic Breast Cancer: Focus on Patient Perspective and Satisfaction
Health-related quality-of-life analyses for proton radiation therapy and photon radiation therapy in patients with nonmetastatic breast cancer showed similar impacts on quality of life with both treatments, according to findings from the phase III RadComp consortium trial. Shannon M. MacDonald, MD, ...
HER2-Positive Early Breast Cancer: Trastuzumab Deruxtecan Moves Into Earlier Clinical Settings
Two pivotal studies of fam-trastuzumab deruxtecan-nxki (T-DXd) in early HER2-positive breast cancer suggest this antibody-drug conjugate (targeting the HER2 protein) may be moving into the curative setting after having shown benefit in metastatic disease in multiple previous trials. The new...
Large AI Breast Cancer Screening Trial Increases Detection Rate by 20%
Using an artificial intelligence (AI)–integrated workflow, DeepHealth, in computer-aided detection of breast cancer from digital breast tomosynthesis exams found 21.6% more cases than the usual standard of care, according to findings from the AI-Supported Safeguard Review Evaluation (ASSURE) study...
ASTRO Experts Comment on the Results of the SUPREMO Trial
A large international study published by Kunkler et al in The New England Journal of Medicine examined whether chest wall radiation therapy after mastectomy improves survival for patients with early-stage breast cancer. The study, known as the SUPREMO trial, found no overall survival difference...
Long-Term Survival With vs Without Postmastectomy Chest Wall Irradiation in Breast Cancer
As reported in the The New England Journal of Medicine by Kunkler et al, the phase III SUPREMO trial showed no significant difference in 10-year overall survival in women with breast cancer receiving vs not receiving postmastectomy chest-wall irradiation. Study Details In the international trial...
FDA Approves New Interchangeable Biosimilar to Pertuzumab
The U.S. Food and Drug Administration (FDA) has approved pertuzumab-dpzb (Poherdy) as an interchangeable biosimilar to pertuzumab (Perjeta). This is the first approval of a biosimilar for pertuzumab. Pertuzumab-dpzb is a HER2/neu receptor antagonist indicated for the following: Use in combination...
Exercise Training Improves Strength and Quality of Life for Patients With Metastatic Breast Cancer
Supervised aerobic and resistance exercise can improve the physical performance and strength of patients living with metastatic breast cancer, according to new data from the PREFERABLE-EFFECT study that was presented by Anne May, PhD, during the Advanced Breast Cancer Eighth International Consensus ...
T-DXd Plus Pertuzumab in HER2-Positive Advanced or Metastatic Breast Cancer
As reported in The New England Journal of Medicine by Tolaney et al, interim analysis of the phase III DESTINY-Breast09 trial has shown significantly improved progression-free survival with fam-trastuzumab deruxtecan-nxki (T-DXd) plus pertuzumab vs a taxane (paclitaxel or docetaxel), trastuzumab,...
Survey Highlights Unmet Needs Among Young Women With Advanced Breast Cancer
Almost half of all women (48%) under the age of 40 who are living with advanced breast cancer have children under the age of 18, and 64% of these young patients also experience employment disruptions after they are diagnosed, according to findings from a survey conducted by the Young Survival...
Global Report Highlights Decade of Uneven Progress in Advanced Breast Cancer Care
ABC Global Alliance's landmark Advanced Breast Cancer Global Decade Report 2015–2025 was recently released and published in The Breast. The report highlights significant advancements made over the past decade that have transformed care for patients with advanced breast cancer, but also reveals gaps ...
Model for Predicting Risk of Heart Failure or Cardiomyopathy After Breast Cancer Treatment
In a study reported in JAMA Oncology, Barac et al developed a risk prediction model for heart failure or cardiomyopathy (HF/CM) after breast cancer treatment. Study Details The aim of the study was to construct a model predicting the 10-year risk of developing HF/CM in women receiving systemic...
HER3-DXd in Patients With Active Brain Metastases From NSCLC and Breast Cancer
In the phase II TUXEDO-3 trial—reported in two articles in The Lancet Oncology—Fuereder et al and Bartsch et al found that the topoisomerase-1 HER3-targeting antibody-drug conjugate patritumab deruxtecan (HER3-DXd) was active in cohorts of patients with active brain metastases from advanced...
Impact of Concomitant Noncancer Medications on Outcomes in Breast Cancer
An evaluation of noncancer medications used concomitantly with cancer therapies for patients with breast cancer showed that proton pump inhibitors specifically were associated with worse survival outcomes and with an increased risk of grade 3 or higher adverse events than other classes of therapy....
Basser Center for BRCA Announces Two Award Winners
The Basser Center for BRCA at the Abramson Cancer Center of the University of Pennsylvania, the world’s first comprehensive center aimed at advancing research, treatment, and prevention of BRCA-related cancers, is honoring Alan D. D'Andrea, MD, of Dana-Farber Cancer Institute, with the 2025 BRCA...
Study Finds Breast Cancer Risk Varies Between Different Hormonal Contraceptives
Some common hormonal contraceptives are linked to a slightly higher risk of breast cancer than others. This is shown by a new study from Uppsala University, in which researchers followed more than 2 million women and teenage girls in Sweden to identify how different hormonal contraceptives affect...
