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Live from Stage 4 | Episode #050| 10/27/2026 | Developing Story
GUESTS
Dr. Nour Abuhadra, MD, is a board-certified breast medical oncologist at the Evelyn H. Lauder Breast Center at Memorial Sloan Kettering Cancer Center (MSK). She serves as the Director of the Rare Breast Cancer Program and the Co-Section Head of the Triple Negative Breast Cancer Clinical Research Program. Dr. Abuhadra specializes in treating all stages of breast cancer, with a particular research and clinical focus on triple-negative breast cancer (TNBC), metaplastic carcinoma, and tumor immune microenvironments.
She earned her medical degree from Weill Cornell Medicine, completed her internal medicine residency at the Cleveland Clinic, and fulfilled her hematology/oncology fellowship at MD Anderson Cancer Center. A dedicated clinical researcher and patient advocate, she has been recognized with prestigious honors, including the Conquer Cancer Foundation Career Development Award.
Quick Summary
Dr. Nour Abuhadra, a breast medical oncologist at Memorial Sloan Kettering (MSKCC), explains why triple negative breast cancer (TNBC) is a group of different diseases and not a single one. She covers how pathologists classify tumors by how the cells look under the microscope, and how rare subtypes like metaplastic and adenoid cystic carcinoma differ from common ductal TNBC. She also discusses second pathology opinions, genomic testing, clinical trials, and the antibody drug conjugates (ADCs) that are changing treatment. She ends on an optimistic note about the next five years.
Key Takeaways
TNBC is not one disease. It means the cancer has no estrogen, progesterone, or HER2 receptors. Within that group, biology and prognosis vary widely.
Morphology drives classification. Pathologists look at how the cells appear and then confirm with stains and markers. Rare subtypes are often TNBC, but not always, so receptor status is still checked every time.
Rare doesn't mean the same. Metaplastic breast cancer is often chemo-resistant and aggressive. Classic adenoid cystic carcinoma usually grows slowly and rarely spreads.
Ask for a second pathology review. You can request one yourself. It doesn't change the diagnosis often (roughly under 5–10% of the time), but it's worth doing before you start treatment, especially for a rare subtype.
Test the tumor's genes early. For metastatic disease, next generation sequencing can reveal targets, such as PI3K pathway changes in many metaplastic tumors. Targeted drugs may then be available through off-label prescribing, insurance appeals, compassionate use, or trials.
ADCs are changing first-line care. These drugs act like targeted chemo delivery. Datopotamab deruxtecan and sacituzumab govitecan have both beaten chemotherapy in studies. For PD-L1 positive disease, sacituzumab plus immunotherapy beat chemo plus immunotherapy.
Choosing an ADC is personal. Side effects (pneumonitis, eye problems, skin and GI effects), dosing schedule, travel burden, cost, and how quickly a response is needed all factor in. Report new symptoms like a dry cough or shortness of breath right away.
Check PD-L1 status. Everyone with metastatic TNBC should have it tested. Immunotherapy only helps when it is expressed.
Rare subtype research is growing. Expert networks are forming, and trials are starting to include rare-subtype groups. The goal is dedicated studies and approvals so rare cancers feel less isolated.
Cause for optimism. Drug approvals are coming at a fast pace, and ADCs weren't on the map 10 years ago.
Researchers and clinicians named
Dr. Jacqueline F. Bromberg, MD, PhD is an MSK colleague who does a lot of work on inflammatory breast cancer.
Audree B. Tadros, MD is a surgeon who partnered on inflammatory breast cancer work.
Mahmoud B. El-Tamer, MD is a surgeon with a dedicated interest in inflammatory breast cancer.
Alan L. Ho, MD, PhD is an MSKCC medical oncologist who specializes in the treatment of head and neck cancers, including head and neck squamous cell carcinoma, salivary gland cancer, thyroid cancer, and skin cancers other than melanoma.
Studies, trials, and research referenced
B7-H4 Emiltatug ledadotin (Emi-Le / XMT-1660) is a B7-H4-directed ADC investigated in early-phase trials across multiple solid tumor types, showing notable clinical activity and FDA fast-track designations in heavily pretreated triple-negative breast cancer, endometrial carcinoma, and adenoid cystic carcinoma (ACC) NCT05377996.
Trials of targeted drugs for metaplastic breast cancer looked at PIK3CA, AKT, and mTOR pathway alterations. Dr. Abuhadra says "smaller studies" showed efficacy and she shares them with insurers for approval. She names alpelisib and capivasertib as example drugs.
Comparison of the two TROP2 ADC studies in the PD-L1 negative group found a higher objective response rate with Dato-DXd. This is her read of the two trials side by side, not one head-to-head study.
Retrospective studies on sequencing ADCs found a second ADC still produces a response, but a shorter one. She also mentions data that "sandwiching" chemo between ADCs may extend efficacy.
ENCORE (TBCRC-067 / NCT06774027) Study - TReatment of ADC-Refractory Breast CancEr With Dato-DXd or T-DXd: TRADE DXd (TRADE DXd). This is a multi-institutional, open-label, phase 2 trial assessing the efficacy of sequential antibody drug conjugate (ADC) treatment with Dato-DXd or T-DXd in patients with HER2-negative (HER2-low and HER2-0) locally advanced unresectable or metastatic breast cancer (MBC).
Immunotherapy timing data show more benefit the earlier it is given. She says no dedicated study has asked whether to continue immunotherapy after switching the treatment backbone, though some groups are starting to look into it.
Statistic on TNBC patients not reaching later lines: about 50% don't make it to second- or third-line therapy, from "very sad data that came out a few months ago." No source is named.
Estimated frequencies, mostly her own estimates:
Ductal carcinoma is about 70% of breast cancers.
Lobular carcinoma is about 20%.
Rare types are about 10%.
Metaplastic is under 2%.
Adenoid cystic is under 1.5%.
PI3K is mutated in about 60% of metaplastic cases.
PD-L1 is expressed in 20–40% of TNBC.
A second pathology opinion changes the diagnosis under 5–10% of the time.
Cancer that spreads to the breast is under 1% ("don't quote me").
Glossary
Types of cancer
Carcinoma is a cancer that begins in epithelial cells, the cells that line the surface and passages of the body, including the ducts and glands of the breast. Most breast cancers are carcinomas.
Ductal carcinoma starts in the milk ducts and is the most common type of breast cancer.
Lobular carcinoma starts in the lobules, the small glands where milk is made. It is the second most common type.
Triple negative breast cancer (TNBC) means the cancer cells have no estrogen receptors, no progesterone receptors, and no excess HER2 protein. Dr. Abuhadra calls it "the absence of three answers," and it includes many different biologies.
Metaplastic breast cancer is a rare type whose cells change into forms not normally found in the breast. It is often chemo-resistant.
Adenoid cystic carcinoma is a rare, usually triple negative cancer. The classic type is slow-growing. The basaloid type is aggressive.
Secretory carcinoma is very rare and often has a distinct genetic change that can be tested for.
Medullary carcinoma looks aggressive under the microscope but often has a better outlook.
Neuroendocrine breast cancer is a rare subtype.
Inflammatory breast cancer is diagnosed by how it looks and behaves: a red, enlarged, inflamed breast. It is not always triple negative.
Pathology and testing
Histology is the study of tissue under the microscope. A histologic subtype is a cancer type defined by how its tissue looks.
Morphology is how cells look under the microscope.
Pathologist is the doctor who examines tissue samples to diagnose cancer.
Second opinion pathology review is when a different expert re-examines your slides to confirm the diagnosis.
Estrogen receptor, progesterone receptor, and HER2 are proteins on cancer cells that act like locks, and they guide treatment choices.
GATA3 is a marker pathologists check to confirm a tumor is of breast origin.
PD-L1 is a protein found on some triple negative tumors, in roughly 20–40% of cases. When it is present, immunotherapy can help.
Next generation sequencing (genomic testing) reads the tumor's DNA to find mutations that could be treatment targets.
Treatments
Chemotherapy is a drug treatment that kills fast-growing cells throughout the body.
Immunotherapy helps the immune system attack the cancer. It is used in PD-L1 positive TNBC.
Antibody drug conjugate (ADC) is a drug that attaches to a protein on cancer cells and delivers chemotherapy directly into them. Dr. Abuhadra describes it as targeted chemo delivery, and her co-host calls it "fancy chemo."
TROP2 is the protein targeted by two ADCs discussed in the episode, datopotamab deruxtecan (Dato-DXd) and sacituzumab govitecan.
B7-H4 is a protein found on triple negative and adenoid cystic tumors. It is the target of an ADC in an ongoing trial.
Targeted therapy is a drug aimed at a specific mutation or pathway. Alpelisib and capivasertib are examples mentioned for PI3K/AKT pathway changes.
PIK3CA, AKT, and mTOR are genes and proteins in the same growth pathway. Changes in them are common in metaplastic breast cancer.
Pneumonitis is lung inflammation. It is a rare but serious ADC side effect, and the warning signs are a dry cough or shortness of breath.
Bystander effect is when an ADC's chemo also affects nearby cancer cells.
Access and trials
Off-label use is prescribing an FDA-approved drug for a different cancer or patient type than it was approved for. It is legal and common in oncology.
Compassionate use is access to a drug that isn't yet approved, or is otherwise hard to get, when other options are limited.
Peer-to-peer review is a call between your doctor and an insurance reviewer to appeal a denial.
Clinical trial is a research study testing a treatment.
Progression-free survival is how long a patient lives without the cancer growing.
Objective response rate is the percentage of patients whose tumors shrink.
Sequencing is the order in which treatments are given.
