Hadeel Assad, MD, is an associate professor, clinician educator, and medical oncologist at Wayne State University and Karmanos Cancer Institute

Breast cancer remains the most prevalent cancer among women in the US. In 2024, approximately 310,720 new cases of invasive breast cancer and 56,500 cases of ductal carcinoma in situ were diagnosed among women across the country. Additionally, approximately 42,250 women died from this disease.

Metastatic breast cancer poses significant treatment challenges. Approximately 15% to 20% of cases of metastatic disease are HER2 positive, which promotes cancer cell growth.

The treatment paradigm for metastatic HER2-positive breast cancer typically involves targeted therapies such as trastuzumab (Herceptin) and pertuzumab (Perjeta), often in combination with chemotherapy, to inhibit the HER2 protein and slow disease progression.

 The antibody-drug conjugate fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) displayed a high response rate of 79.7% (95% CI, 74.3%-84.4%) and a median investigator-assessed progression-free survival of 25.1 months (95% CI, 22.1-not estimable) in patients with HER2-positive metastatic breast cancer in the second-line setting (n = 261), according to data from the phase 3 DESTINY-Breast03 trial (NCT03529110).

Small-molecule HER2 inhibitors, such as tucatinib (Tukysa), neratinib (Nerlynx), and lapatinib (Tykerb), have also shown positive results and intracranial responses when combined with chemotherapy (with/without trastuzumab) or endocrine therapy.

 Despite these advances, the response to treatment tends to be limited, and disease progression is inevitable. In addition, both the response rates and duration of response decrease as patients cycle through the lines of therapy. There remains a significant unmet need for better treatments that not only prolong life but also preserve the quality of life in women with metastatic disease.

Developing a Potential New Treatment Option for Patients With Breast Cancer

At the Barbara Ann Karmanos Cancer Institute, a National Cancer Institute–Designated Comprehensive Cancer Center in Detroit, Michigan, the Bone Marrow and Stem Cell Transplant, Hematologic Oncology, and Multiple Myeloma and Amyloidosis Multidisciplinary Teams (MDTs) have helped drive many treatment advancements in cellular immune therapies for cancers. This includes chimeric antigen receptor (CAR) T-cell therapy, which has revolutionized the treatment of certain hematologic malignancies, including specific types of leukemia and lymphoma, and has significantly improved response rates for these diseases.

 This personalized immunotherapy involves modifying a patient’s T cells, which are an integral part of the immune system, to recognize and attack cancer cells.

Karmanos Cancer Institute offers all approved CAR T-cell therapies for non-Hodgkin lymphoma, acute lymphoblastic leukemia, and multiple myeloma. The institute also supports research into new treatment indications for which CAR T-cell therapy could be used. I, along with other principal investigators at Karmanos, am now exploring the application of CAR T-cell therapy for solid tumors, including breast cancer, which presents a set of new challenges due to tumor microenvironment and antigen heterogeneity.

One such clinical study open at Karmanos is investigating the safety and efficacy of cellular immunotherapy in combination with targeted therapy for the treatment of solid tumors. In a phase 1 trial (NCT06241456), we are evaluating FT825/ONO-8250, an induced pluripotent stem cell–derived off-the-shelf CAR T-cell product targeting HER2-positive and other advanced solid tumors in combination with trastuzumab or cetuximab (Erbitux). Early data from this trial indicate no dose-limiting toxicities and no significant adverse effects, such as cytokine release syndrome, immune effector cell–associated neurotoxicity syndrome, or graft-vs-host disease. These findings suggest a promising avenue for developing effective cellular therapies for solid tumors, including HER2-positive breast cancer. The ongoing study enrolls participants with advanced HER2- and EGFR-expressing solid tumors such as breast, gastrointestinal, gynecologic, and head and neck cancers.

Karmanos specialists have experience in providing commercially approved and investigational cellular therapies. We work closely with investigators, developing novel strategies to make this therapy safer, developing pathways toward new indications, and ensuring more accessibility to CAR T-cell therapy. With our robust clinical trials program and experienced team, we are committed to further improving outcomes for patients who are candidates for these therapies and overcoming associated challenges. We look forward to witnessing how this therapy can transform the standard of care for many of our patients in the future.

Hadeel Assad, MD, is a medical oncologist specializing in breast cancer. She is the co-leader of the Breast Cancer Multidisciplinary Team (MDT), a member of the Phase I Clinical Trials MDT, and a scientific member of the Population Studies and Disparities and the Molecular Therapeutics Research Programs at Karmanos Cancer Institute in Detroit, Michigan.

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Fate Therapeutics highlights cancer-selective, HER2-targeting profile of FT825 / ONO-8250 CAR T-cell product candidate for treatment of advanced solid tumors at 2024 SITC Annual Meeting. News release. Fate Therapeutics. November 9, 2024. Accessed March 28, 2025. https://ir.fatetherapeutics.com/news-releases/news-release-details/fate-therapeutics-highlights-cancer-selective-her2-targeting

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There remains a significant unmet need for better treatments that prolong life and preserve the quality of life in women with metastatic breast cancer.

Hadeel Assad, MD

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