© 2025 HSP News Service, L.L.C.
This is Part 1 of PI3K Inhibition Strategies for 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. Adam Brufsky, Heather McArthur, and Seth Wander discuss the first-line treatment of hormone receptor (HR)-positive metastatic breast cancer. The patient is a 64-year-old postmenopausal woman with a history of asymptomatic left bundle branch block and irritable bowel syndrome. In 2015, she was diagnosed with a 3.5-cm invasive ductal carcinoma of the left breast with 3 positive axillary lymph nodes. She was treated with dose-dense doxorubicin, cyclophosphamide, and paclitaxel and postmastectomy radiation therapy, and then received anastrozole for 5 years, completing therapy in 2021. In 2024, she complains of worsening back pain, and PET-CT scan reveals multiple lytic lesions of the thoracic and lumbar spine, as well as a 3-cm lesion in the liver. In the conversation that follows, the faculty discuss how the treatment of HR-positive breast cancer has changed over the past decade, the appropriate duration of adjuvant endocrine therapy, what blood or biomarker tests to perform, and how to choose between doublet and triplet therapy with PI3K inhibitors.
This is Part 3 of Evolving Paradigms in the Treatment of HR-Positive/HER2-Positive Metastatic Breast Cancer, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Sara Tolaney, Ian Krop, and Mark Pegram discuss second-line therapy for hormone receptor (HR)-positive/HER2-positive metastatic breast cancer. The patient is a 62-year-old woman who received first-line paclitaxel plus trastuzumab for de novo metastatic HR-positive/HER2-positive breast cancer. After seven cycles, she stopped paclitaxel and initiated an aromatase inhibitor plus trastuzumab plus pertuzumab plus palbociclib. She remained on therapy for approximately 3 years and then developed new liver metastases and a single brain metastasis, for which she was asymptomatic. In the conversation that follows, the faculty discuss the role of screening brain MRIs for patients with metastatic HER2-positive breast cancer, local vs systemic treatment for brain metastases, and how to approach the timing of systemic therapy with radiation.
This is Part 2 of Evolving Paradigms in the Treatment of HR-Positive/HER2-Positive Metastatic Breast Cancer, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Sara Tolaney, Ian Krop, and Mark Pegram discuss how to manage a patient following first-line induction therapy for metastatic hormone receptor (HR)-positive/HER2-positive breast cancer. The patient is a 62-year-old woman who had initiated therapy with weekly paclitaxel plus trastuzumab and pertuzumab for her de novo metastatic disease. She had resolution of her liver metastasis and reduction in her breast mass. After seven cycles of therapy, however, she began to experience worsening neuropathy. In the conversation that follows, the faculty discuss when to discontinue paclitaxel, clinical implications of the recently presented PATINA trial, whether palbociclib should be a standard addition to maintenance for all patients with HR-positive/HER2-positive metastatic breast cancer, and more.
This is Part 1 of Evolving Paradigms in the Treatment of HR-Positive/HER2-Positive Metastatic Breast Cancer, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Sara Tolaney, Ian Krop, and Mark Pegram discuss the treatment of de novo metastatic hormone receptor (HR)-positive/HER2-positive breast cancer. The patient is a 62-year-old woman who presented with a palpable right breast mass and ipsilateral axillary lymph node. Biopsy confirmed the breast mass as a high-grade invasive ductal carcinoma that was strongly hormone receptor–positive and HER2 IHC 3+. Fine-needle aspiration of the axillary node was positive, and staging studies revealed a single liver metastasis consistent with her breast primary tumor. In the conversation that follows, the faculty discuss whether there is a role for surgery or locoregional therapy in patients with de novo metastatic HR-positive/HER2-positive disease, what systemic treatment options would be appropriate, and endocrine-based options for patients with contraindications to chemotherapy.
Andrew Tutt, MB ChB, PhD, FMedSci, Director of The Breast Cancer Now Toby Robins Research Centre and the Institute of Cancer Research (ICR) and Guy’s Hospital King’s College, London, discusses longer-term follow-up of OlympiA, a phase III, multicenter, randomized, placebo-controlled trial of adjuvant olaparib after (neo)adjuvant chemotherapy in patients with germline BRCA1/BRCA2 pathogenic variants and high-risk HER2-negative primary breast cancer (Abstract GS1-09).
Nan Chen, MD, of the University of Chicago Medicine, Chicago, discusses the impact of anthracyclines in high genomic risk node-negative HR-positive/HER2-negative breast cancer (Abstract GS3-03).
Kathryn Newlin, RN, MSN, ANP-BC, of Washington University in St. Louis, discusses her presentation on HR+ HER2- metastatic breast cancer from the JADPRO Live conference recently held in Grapevine, Texas. Kathryn covers factors involved in treatment selection for this patient population, including key agents in the armamentarium, relevant biomarkers and the emergence of HER2 low as a factor in added treatment options, and the management of adverse effects.
Adrienne Waks, MD, of Dana-Farber Cancer Institute, Boston, discusses the randomized phase II trial comparing neoadjuvant paclitaxel/margetuximab/pertuzumab vs paclitaxel/trastuzumab/pertuzumab in patients with stage II-III HER2-positive breast cancer. This trial is being done to determine how well HER2-positive breast cancer responds to preoperative treatment using one of two different combinations of drugs as a treatment for this diagnosis (Abstract LB1-02).
Aditya Bardia, MD, of UCLA David Geffen School of Medicine, Los Angeles, presents the additional analysis of the efficacy and safety of trastuzumab deruxtecan vs physician’s choice of chemotherapy by pace of disease progression on prior endocrine-based therapy from DESTINY-Breast06 (Abstract LB1-04).
Mafalda Oliveira, MD, PhD, of Vall d’Hebron Institute of Oncology, Spain, presented the primary results of SOLTI VALENTINE, a neoadjuvant randomized phase II trial of HER3-DXd alone or in combination with letrozole for high-risk hormone receptor–positive/HER2-negative early breast cancer (Abstract LB1-06).
Sibylle Loibl, MD, PhD, of the German Breast Group, Neu-Isenburg, Germany, presented primary results of the randomized phase III PADMA trial comparing first-line endocrine therapy plus palbociclib vs standard mono-chemotherapy in women with high-risk HER2-negative/HR-positive metastatic breast cancer and indication for chemotherapy (Abstract LB1-03).
Tiffany Traina, MD, FASCO, is Vice Chair of the Department of Medicine at Memorial Sloan Kettering Cancer Center, where she has been a medical oncologist on the Breast Medicine Service since 2006. Dr. Traina is also the Section Head of the Triple Negative Breast Cancer Clinical Research Program. In this video, Dr. Traina speaks with The ASCO Post about management options and advances in the treatment of HR-positive breast cancer. Dr. Traina was co-Program Chair of the recent Chemotherapy Foundation Symposium.
Komal Jhaveri, MD, FACP, is an Associate Professor of Clinical Medicine at Weill Cornell Medical College and a Breast Medical Oncologist & Early Drug Development Specialist at Memorial Sloan Kettering Cancer Center in New York. In this video from The ASCO Post Newreels, Dr. Jhaveri shares a summary of her talk presented recently at the Chemotherapy Foundation Symposium. Dr. Jhaveri discusses important data about the activity of antibody-drug conjugates in patients with breast cancer, including breast cancer that is HER2-positive, HER2-low, and HER2-ultralow.
Vered Stearns, MD, is the Director for Translational Breast Cancer Research in the Department of Hematology and Medical Oncology at Sandra and Edward Meyer Cancer Center and Weill Cornell Medical School. Dr. Stearns talks about updates in the management of patients with triple-negative breast cancer. Triple-negative breast cancer affects a small portion of all breast cancer subtypes, representing about 15% of tumors. It is more common in younger women, in black African American women, and those who are BRCA mutation carriers. Dr. Stearns shares her expertise on the management of patients with triple-negative breast cancer and some of the advances made in treatment.
William Gradishar, MD, discusses advances in endocrine therapeutic options for patients with estrogen receptor–positive, HER2-negative breast cancer, in follow-up to his presentation at the Lynn Sage Breast Cancer Symposium, October 2024. Dr. Gradishar is the Betsy Bramsen Professor of Breast Oncology; Professor, Medicine (Hematology and Oncology), at the Robert H. Lurie Comprehensive Cancer Center at Northwestern University, Chicago. Presented at the Lynn Sage Breast Cancer Symposium, hosted by the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago. Filmed November 1, 2024.
Sunil S. Badve, MD, FRCPath, discusses research on tumor-infiltrating lymphocytes in the patient with breast cancer, based in part on his presentation at the Lynn Sage Breast Cancer Symposium, October 2024. Dr. Badve is Professor, Department of Pathology and Laboratory Medicine, and Vice Chair, Pathology Cancer Programs, at Emory University School of Medicine in Atlanta. Presented at the Lynn Sage Breast Cancer Symposium, hosted by the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago. Filmed October 31, 2024.
Charles E. Geyer, Jr, MD, FACP, discusses the management of patients with HER2-positive breast cancer in 2024, based in part on his presentation at the Lynn Sage Breast Cancer Symposium, October 2024. Dr. Geyer is Professor of Medicine and Interim Division Chief of Malignant Hematology and Medical Oncology at the University of Pittsburgh Medical Center (UPMC/Hillman Cancer Center; Dr. Geyer is also Chief Scientific Officer, National Surgical Adiuvant Breast and Bowel Project (NSABP) Foundation. Presented at the Lynn Sage Breast Cancer Symposium, hosted by the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago. Filmed October 25, 2024.
Frederick Howard, MD, discusses the role of targeted therapy and endocrine therapy in the patient with breast cancer, based in part on his presentation at the Lynn Sage Breast Cancer Symposium, October 2024. Dr. Howard is Assistant Professor of Medicine in the section of Hematology/Oncology at the University of Chicago. Presented at the Lynn Sage Breast Cancer Symposium, hosted by the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago.
This is Part 3 of Next-Generation Therapies for Metastatic Hormone Receptor–Positive Breast Cancer: Where Are We Headed?, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Virginia Kaklamani, William Gradishar, and Komal Jhaveri discuss the management of endocrine-resistant metastatic breast cancer. The patient is a 66-year-old postmenopausal woman who was originally diagnosed with a right ER 30% PR 20% HER2 2+ breast cancer. She underwent a partial mastectomy showing a 2.1-cm tumor and one positive lymph node; her Oncotype recurrence score was 35. She received adjuvant chemotherapy and radiation therapy and then started treatment with aromatase inhibitor (AI) and abemaciclib. While on abemaciclib, she presents with shortness of breath, and imaging shows a pleural effusion and lung nodules. A lung biopsy confirms ER 20% PR 0% HER2 1+ breast cancer. In the conversation that follows, the faculty discuss whether antibody-drug conjugates are an option in the first-line setting for endocrine-resistant disease; how to approach sequencing of antibody-drug conjugates; and the appropriate management of toxicities associated with these agents.
This is Part 2 of Next-Generation Therapies for Metastatic HR-Positive Breast Cancer: Where Are We Headed?, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Virginia Kaklamani, William Gradishar, and Komal Jhaveri discuss the management of PIK3CA-mutated metastatic breast cancer. The patient is a 45-year-old premenopausal woman who was originally diagnosed with a right ER 90% PR 80% HER2 1+ breast cancer. She underwent a partial mastectomy, which revealed a 1.5-cm tumor with one positive lymph node. After receiving adjuvant chemotherapy followed by radiation therapy, she began treatment with ovarian function suppression (OFS), an aromatase inhibitor (AI), and abemaciclib. She completed 2 years of abemaciclib and continued OFS and AI. Now, 2 years later, she presents with increased fatigue and weight loss. Imaging shows two liver lesions and multiple bone metastases, and a liver biopsy confirms ER 50% PR 40% HER2 1+ breast cancer. In the conversation that follows, the faculty discuss combination treatment options for PIK3CA-mutated metastatic breast cancer; the importance of clinical trials; adverse events associated with PI3K inhibitors; and more.
This is Part 1 of Next-Generation Therapies for Metastatic HR-Positive Breast Cancer: Where Are We Headed?, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Virginia Kaklamani, William Gradishar, and Komal Jhaveri discuss the management of ESR1-mutated metastatic breast cancer. The patient is a 54-year-old postmenopausal woman who was initially diagnosed with a left ER 90% PR 30% HER2 1+ breast cancer. She underwent a partial mastectomy, revealing a 2.3-cm tumor that was lymph node negative. Her Oncotype recurrence score was 21. After receiving radiation therapy, she completed 5 years of treatment with an aromatase inhibitor, but now 2 years later presents with back pain. Imaging shows three lesions in the lumbar spine, and a biopsy confirms ER 80% PR 40% HER2 1+ breast cancer. In the conversation that follows, the faculty discuss the utility of next-generation sequencing in the first-line setting; patient considerations when deciding on treatment after disease progression; the role of oral SERDs in ESR1-mutated metastatic breast cancer; and more.
Sara A. Hurvitz, MD, FACP, of Fred Hutch Cancer Center, discusses her presentation on new therapeutic strategies for HER2-positive metastatic disease including brain metastases. Dr. Hurvitz is Senior Vice President and Director, Clinical Research Division, Fred Hutch Cancer Center, and Professor, Clinical Research Division, Fred Hutch.
Kristin Rojas, MD, FACS, of the University of Miami, shares key points from her discussion on improving sexual health during breast cancer treatment. Dr. Rojas is an Associate Professor of Surgery in the DeWitt Daughtry Family Department of Surgery, Division of Surgery, Miller School of Medicine at University of Miami Health System. She presented her talk at the Annual International Congress on the Future of Breast Cancer East.
Joseph A. Sparano, MD, FACP, of Icahn School of Medicine at Mount Sinai, discusses his presentation on premenopausal patients with hormone receptor–positive early breast cancer. Dr. Sparano is the Ezra M. Greenspan, MD, Professor in Clinical Cancer Therapeutics, Chief of the Division of Hematology Oncology, and Deputy Director of the Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai in New York. He presented his talk at the Annual International Congress on the Future of Breast Cancer East.
Paolo Tarantino, MD, of Dana-Farber Cancer Institute and Harvard Medical School, shares key points from his discussion on the current and future landscape of antibody-drug conjugates. Dr. Tarantino is an Advanced Research Fellow in the Breast Oncology Program at Dana-Farber Cancer Institute and Harvard Medical School. He is also affiliated with the European Institute of Oncology. Dr. Tarantino presented his talk at the Annual International Congress on the Future of Breast Cancer East.
Aditya Bardia, MD, MPH, FASCO, of UCLA Health/Jonsson Comprehensive Cancer Center, shares key points from his discussion on novel therapies targeting the estrogen receptor. Dr. Bardia is Professor, Department of Medicine, Division of Hematology/Oncology, and Director of Translational Research Integration. He presented his talk at the Annual International Congress on the Future of Breast Cancer West.
Heather McArthur, MD, MPH, talks about immunotherapy for high-risk, early-stage breast cancer. Dr. McArthur is Associate Professor in the Department of Internal Medicine and Clinical Director of the Breast Cancer Program at Simmons Cancer Center at UT Southwestern Medical Center, Houston. She presented her talk at the Annual International Congress on the Future of Breast Cancer West.
Aditya Bardia, MD, MPH, FASCO, of UCLA Health/Jonsson Comprehensive Cancer Center, shares key points from his discussion on the current and future landscape of antibody-drug conjugates. Dr. Bardia is Professor, Department of Medicine, Division of Hematology/Oncology, and Director of Translational Research Integration. He presented his talk at the Annual International Congress on the Future of Breast Cancer West.
Milana Bergamino Sirvén, MD, PhD, of Spain’s Institute of Cancer Research, discusses her findings on molecular profiling of patients with estrogen receptor–positive, HER2-positive early-stage breast tumors after short-term preoperative endocrine therapy. This study suggests that such profiling may help clinicians identify those patients with a favorable prognosis for adjuvant endocrine therapy and those who may require additional treatment (Abstract 560).
Ciara C. O’Sullivan, MD, MBBCh, of Mayo Clinic, discusses three studies of treatment for patients with HER2-positive metastatic breast cancer and their clinical implications: the EMERALD trial of eribulin and taxane; the Patricia Cohort C trial of palbociclib plus trastuzumab and endocrine therapy; and DB07 on trastuzumab deruxtecan with or without palbociclib.
Yeon Hee Park, MD, PhD, of South Korea’s Samsung Medical Center and Sungkyunkwan University, discusses phase II findings on palbociclib plus exemestane with a GnRH agonist vs capecitabine in premenopausal patients with hormone receptor–positive, HER2-negative metastatic breast cancer (LBA1002).
Reshma Jagsi, MD, DPhil, of Emory University Winship Cancer Institute, and Tarah J. Ballinger, MD, of Indiana University Simon Comprehensive Cancer Center, discuss the disparate burden of taxane-induced peripheral neuropathy in Black women with early-stage breast cancer and how a tailored trial for this population showed that using docetaxel as the preferred taxane may be beneficial (LBA503).
Pierfranco Conte, MD, of the University of Padua, discusses phase III findings from the A-BRAVE trial, which was designed to evaluate the efficacy of avelumab, an anti–PD-L1 antibody, as adjuvant treatment for patients with early-stage triple-negative breast cancer who are at high risk (LBA500).
Sherene Loi, MD, PhD, of Peter MacCallum Cancer Centre, discusses a circulating tumor DNA (ctDNA) analysis from a cohort of patients with early-stage breast cancer who were enrolled in the monarchE trial. This large cohort was studied to look at the usefulness of a personalized tumor-informed assay for ctDNA detection in early stage high-risk patients (LBA507).
Emily L. Podany, MD, of Washington University, St. Louis, discusses disparities in the use of PI3K inhibitors for Black patients with estrogen receptor–positive, HER2-negative metastatic breast cancer while other drugs that do not require genomic profiling were similarly used (Abstract 1017).
Eva M. Ciruelos, MD, PhD, of Spain’s Hospital 12 de Octubre and the Instituto de Investigación Sanitaria Hospital 12 de Octubre, discusses phase II data showing that the combination of palbociclib, trastuzumab, and endocrine therapy improved progression-free survival in patients with previously treated PAM50 luminal A or B, HER2-positive advanced breast cancer, as compared with treatment of physicians’ choice (Abstract 1008).
Reshma Jagsi, MD, DPhil, of Emory University Winship Cancer Institute, and Christian F. Singer, MD, MPH, of the Medical University of Vienna, discuss the MUC-1 vaccine tecemotide. When added to standard neoadjuvant systemic therapy for patients with early-stage breast cancer, this vaccine improved distant relapse–free and overall survival rates. Despite the exploratory nature of this observation, says Dr. Singer, this is the first long-term survival benefit of an anticancer vaccine in breast disease reported to date (Abstract 587).
Lisa A. Carey, MD, of the University of North Carolina, Chapel Hill and UNC Lineberger Comprehensive Cancer Center, and Dejan Juric, MD, of the Massachusetts General Hospital Cancer Center, discuss phase III findings on first-line use of inavolisib or placebo plus palbociclib and fulvestrant in patients with PIK3CA-mutated, hormone receptor–positive, HER2-negative locally advanced or metastatic breast cancer who relapsed within 12 months of completing adjuvant endocrine therapy (Abstract 1003).
Lisa A. Carey, MD, of University of North Carolina, Chapel Hill and UNC Lineberger Comprehensive Cancer Center, and Kevin Kalinsky, MD, of the Winship Cancer Institute of Emory University, discuss the first phase III findings showing a benefit of continued CDK4/6 inhibition with abemaciclib plus fulvestrant, following disease progression in patients with hormone receptor–positive, HER2-negative advanced breast cancer (LBA1001).
Denise A. Yardley, MD, of the Sarah Cannon Research Institute, discusses the NATALEE trial, which assessed ribociclib plus a nonsteroidal aromatase inhibitor (NSAI) vs an NSAI alone in patients with hormone receptor–positive/HER2-negative early breast cancer at increased risk of recurrence, including patients with node-negative disease, and showed a benefit in invasive disease–free survival (Abstract 512).
Ana C. Garrido-Castro, MD, of Dana-Farber Cancer Institute, discusses recent approvals of multiple novel therapies for metastatic breast cancer, weighing their potential benefits and risks, understanding the mechanisms that drive response and resistance, and exploring how to optimally sequence them to enhance survival and quality of life.
Ana C. Garrido-Castro, MD, of Dana-Farber Cancer Institute, reports the results from the phase II SACI-IO trial in patients with hormone receptor–positive/HER2-negative metastatic breast cancer who received sacituzumab govitecan-hziy with or without pembrolizumab (LBA1004).
Fabrice Andre, MD, PhD, of Gustave Roussy and the Université Paris-Saclay, discusses a dose-expansion interim analysis of trastuzumab deruxtecan (T-DXd) monotherapy and T-DXd plus pertuzumab in patients with previously untreated HER2-positive metastatic breast cancer (Abstract 1009).
Kelly K. Hunt, MD, of The University of Texas MD Anderson Cancer Center, discusses the benefits to patients with neoadjuvant therapy in advanced, inoperable breast cancer, for whom this treatment works best, and novel approaches currently under investigation.
William J. Gradishar, MD, of Robert H. Lurie Comprehensive Cancer Center of Northwestern University, details the fundamental shift in how clinicians now treat patients with endocrine-sensitive breast cancer, both advanced and early stage, by pairing antihormonal therapy with targeted treatment.
Judy C. Boughey, MD, of the Mayo Clinic, discusses findings from the I-SPY2 trial, which show that although the extent of residual disease and tumor biology in patients with breast cancer may impact outcomes, the type of axillary surgery after neoadjuvant chemotherapy does not (Abstract 3).
Kerollos N. Wanis, MD, PhD, of The University of Texas MD Anderson Cancer Center, discusses a study in which he evaluated the risk of future ipsilateral and contralateral breast cancer events in a large cohort of patients with BRCA1 or BRCA2 mutations who chose breast conservation (Abstract 12).
Heather McArthur, MD, MPH, of UT Southwestern Medical Center, discusses phase III findings from the KEYNOTE-756 trial, which shows that adding pembrolizumab to neoadjuvant chemotherapy increases pathologic complete response (pCR) rates in patients with early-stage, high-risk, estrogen receptor–positive or HER2-negative breast cancer. (ER+/HER2−). The regimen shifted more patients to lower residual cancer burden categories (Abstract 2).
Natália Polidorio, MD, PhD, of Memorial Sloan Kettering Cancer Center, discusses findings on the impact of race on pathologic complete response in patients with early-stage triple-negative breast cancer who received neoadjuvant chemoimmunotherapy vs chemotherapy alone. Such targeted research may potentially result in more informed treatment strategies and improved identification of those most likely to benefit (Abstract 15).
This is Part 3 of Targeting Endocrine Resistance 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. Kevin Kalinsky, Manali Bhave, and Ruth O’Regan discuss the treatment of endocrine-resistant hormone receptor–positive, HER2-negative metastatic breast cancer. The patient is a 61-year-old postmenopausal female who was initially diagnosed with stage IB, ER-positive, PR-positive, HER2 IHC 1+, histologic grade 3 invasive ductal carcinoma. She was treated with lumpectomy and radiotherapy followed by nonsteroidal aromatase inhibitor for 4.5 years of therapy, during which her disease progressed. Further imaging reveals multiple bone and liver lesions. Her liver lesion is biopsied and found to be invasive ductal carcinoma, ER/PR 50%, and HER2 IHC 1+. She receives fulvestrant and ribociclib for 4 months, and then experiences new shortness of breath due to lymphangitic spread. A ctDNA reveals a pathogenic PIK3CA H1047R mutation and ESR1 D538G mutation. The faculty discuss next steps for a symptomatic patient such as this with pathogenic mutations, sequencing of antibody-drug conjugates, and how best to manage and monitor for toxicities.