Breast Cancer Clinical Trials: Current Options and How to Enroll
Written by North Editorial Staff | Clinically reviewed by Laura Morrissey, RN, BSN | Last reviewed: March 2026
Key Takeaways
Clinical trials are the source of every major breast cancer advancement in the past 30 years — from trastuzumab for HER2-positive disease to CDK4/6 inhibitors for metastatic HR+ cancer.
Trials exist at every stage and for every subtype of breast cancer: early-stage, locally advanced, metastatic, and even prevention and high-risk surveillance.
Participating in a trial does not mean giving up standard treatment. Most breast cancer trials compare a new approach against — or in addition to — current standard of care.
Clinical trials are not a last resort. Many are designed to enroll patients at or shortly after diagnosis, often as the first line of treatment.
The most common barrier to trial participation is not knowing trials exist or assuming you won’t qualify. Using a trial finder alongside your oncology team is the most effective way to identify options.
Triple-negative breast cancer (TNBC) and metastatic breast cancer patients particularly benefit from seeking trial options, as the landscape of active trials in these areas is rapidly evolving.
Why Clinical Trials Matter for Breast Cancer
Every standard breast cancer treatment in use today was once investigational, being tested in a clinical trial before it became routine care. Trastuzumab (Herceptin), which transformed HER2-positive breast cancer from a poor-prognosis subtype to a highly treatable one, was approved following Phase III trial evidence. CDK4/6 inhibitors — palbociclib, ribociclib, abemaciclib — which have extended progression-free and overall survival in metastatic hormone receptor-positive breast cancer, all followed the same path.
The trials running today represent the next generation of that progress: antibody-drug conjugates being tested in new settings, PARP inhibitors for BRCA-mutated disease, novel immunotherapy combinations, PI3K pathway inhibitors, and approaches to overcome resistance to existing treatments.
For patients, the practical implication is this: a clinical trial is not an alternative to good care, but rather it is often the best care available, particularly for metastatic disease or subtypes where standard options have limitations.
Types of Breast Cancer Clinical Trials
Treatment Trials
Treatment trials are the most common type of breast cancer clinical trials. Treatment trials test new drugs, drug combinations, surgical approaches, or radiation techniques against current standard of care. They are organized by phase:
Phase 1: Tests safety and dosing in small groups (typically 20–100 patients). The purpose is to determine whether a drug is safe enough to study further and what dose is appropriate.
Phase 2: Tests whether the treatment works — typically in a larger group (100–500 patients) with a defined tumor type. Look for signals of efficacy.
Phase 3: A large randomized trial comparing the new treatment head-to-head against current standard of care. This is the definitive test before FDA approval.
Phase 4: Post-approval studies that continue to monitor safety and effectiveness in broader populations.
Prevention Trials
Prevention trials study whether a drug, lifestyle intervention, or other approach can reduce the risk of breast cancer in high-risk individuals, particularly those with BRCA mutations, atypical hyperplasia, or elevated risk by validated models. The STAR trial, which compared tamoxifen and raloxifene in postmenopausal high-risk women, is a landmark example.
Screening and Detection Trials
These trials evaluate new screening technologies — AI-assisted mammogram interpretation, novel biomarker tests, or alternative imaging modalities — to determine whether they improve early detection outcomes.
Supportive Care Trials
Supportive care trials test interventions designed to reduce side effects, improve quality of life, or help patients manage the impact of treatment. They enroll patients who are already receiving standard or investigational cancer treatment.
The Current Trial Landscape by Subtype
HR-Positive, HER2-Negative Metastatic Breast Cancer
This is the largest subtype in metastatic disease, and the trial landscape is active. CDK4/6 inhibitors are now standard of care in combination with endocrine therapy as first-line treatment. Current trials are investigating:
PI3K/AKT/mTOR pathway inhibitors for patients who have progressed on CDK4/6 therapy (alpelisib, capivasertib, and similar agents)
Antibody-drug conjugates (ADCs) in later-line settings (sacituzumab govitecan, trastuzumab deruxtecan in HER2-low subtype)
Oral SERDs (selective estrogen receptor degraders) — next-generation endocrine agents
PARP inhibitors (olaparib, talazoparib) for patients with germline BRCA1/2 mutations
HER2-Positive Breast Cancer
HER2-positive breast cancer has one of the most active trial landscapes of any cancer type. Despite excellent outcomes with current HER2-directed therapy combinations, trials are investigating:
Trastuzumab deruxtecan (T-DXd) in earlier treatment settings (it is FDA-approved for later-line metastatic disease and in early-stage neoadjuvant/adjuvant settings)
Tucatinib combinations for brain metastases (a common complication in HER2-positive disease)
Bispecific antibodies that engage both HER2 and immune cells simultaneously
HER2-low disease — a newly defined subpopulation where HER2 expression is low but present; trastuzumab deruxtecan has demonstrated benefit and opened a new therapeutic category
Triple-Negative Breast Cancer (TNBC)
TNBC remains the subtype with the most urgent need for new treatment options and the most active trial landscape:
Immunotherapy combinations: Pembrolizumab is FDA-approved in combination with chemotherapy for high-risk early-stage and metastatic TNBC. Trials are exploring other checkpoint inhibitors and combinations.
Antibody-drug conjugates: Sacituzumab govitecan (Trodelvy) is FDA-approved for metastatic TNBC; trials are studying it in earlier settings and in combination.
PARP inhibitors: For patients with germline BRCA mutations.
TROP2-directed agents and other novel targeted approaches.
AKT pathway inhibitors: For TNBC with PI3K/AKT pathway alterations.
Patients with TNBC, particularly in the metastatic setting, should discuss trial options at every treatment decision point, as the landscape is evolving rapidly.
Early-Stage Breast Cancer
Trials for early-stage disease focus on:
De-escalation: Studying whether some patients can receive less chemotherapy, shorter radiation, or less extensive surgery without compromising outcomes (the IDEA trial in ER+ HER2-negative disease; the ACOSOG Z0011 trial on sentinel lymph node surgery are landmark examples).
Escalation in high-risk subgroups: Adding novel agents (immunotherapy, PARP inhibitors, CDK4/6 inhibitors) to standard regimens for high-risk early-stage patients to reduce recurrence risk.
Neoadjuvant approaches: Testing new agents given before surgery to reduce tumor size and assess treatment response.
BRCA-Mutated Breast Cancer
Patients with germline BRCA1 or BRCA2 mutations, whether early-stage or metastatic, have specific trial options:
PARP inhibitors (olaparib and talazoparib are FDA-approved for metastatic BRCA-mutated HER2-negative breast cancer; olaparib is also approved in the adjuvant early-stage setting for high-risk patients)
Platinum chemotherapy — cisplatin and carboplatin show elevated activity in BRCA-mutated TNBC
New combinations targeting DNA repair pathways
Who Is Eligible for Breast Cancer Trials?
Every trial has a specific set of inclusion and exclusion criteria — requirements that determine who can participate. Common factors include:
Diagnosis and subtype: Most trials enroll specific subtypes (e.g., HER2-positive only, or ER+ HER2-negative only)
Stage: Early-stage and metastatic trials are separate; some trials specify prior lines of treatment received
Prior treatment: Some trials require patients to have received — or not to have received — specific prior therapies
Biomarker status: Some trials require specific mutations (BRCA, PIK3CA) or expression levels (HER2-low)
Performance status: An assessment of overall health and ability to perform daily activities
Organ function: Adequate kidney, liver, and bone marrow function, typically assessed by blood tests
The best way to determine eligibility is to search for trials using a trial finder and then have your oncologist verify which ones fit your specific situation.
How to Find and Enroll in a Breast Cancer Clinical Trial
1. Start your search early. Many trials enroll patients at specific treatment windows — often at or shortly after diagnosis, or at first progression. Waiting until you’ve exhausted standard options may make you ineligible for some trials.
2. Search using a trial finder. North’s trial finder is designed to match your profile to currently enrolling trials. ClinicalTrials.gov is the comprehensive federal database with all registered trials.
3. Discuss options with your oncologist. Share the trials you’ve identified. Your oncologist can review the protocols, determine whether your tumor characteristics and prior treatment history match the eligibility criteria, and facilitate referral if needed.
4. Contact the trial site. Trial coordinators at the enrolling institution handle eligibility screening, consent, and logistics. Many trials are conducted at major cancer centers or NCI-designated cancer centers with dedicated research staff.
5. Ask about costs and coverage. Investigational treatment and research-related costs are typically covered by the trial sponsor. Routine care is covered by insurance under the Affordable Care Act. Some trials offer travel and lodging assistance.
6. Ask about second opinions. If your current oncologist is not affiliated with a trial site, a one-time consultation at a comprehensive cancer center can identify options you might otherwise miss.
What to Expect if You Join a Trial
Joining a clinical trial means:
Informed consent: Before enrolling, you will review and sign a detailed informed consent document explaining what the trial involves, its risks and potential benefits, your rights as a participant, and alternatives to participation.
Closer monitoring: Trial participants typically have more frequent visits, more lab tests, and more imaging than patients in standard care — the trial team is watching carefully for both efficacy and side effects.
The right to withdraw: You can leave a trial at any time without it affecting your access to standard care.
No guarantee of the experimental arm: Randomized trials assign participants to treatment arms. You may receive the experimental treatment or the standard-of-care comparison arm — both are medically appropriate.
Start Your Search
If you’ve been diagnosed with breast cancer — at any stage, at diagnosis or at progression — exploring trial options should be part of your conversation with your oncology team. Ready to see what’s available for your specific situation? Start your search with North’s trial finder, or explore our guide to breast cancer treatment options to understand the full landscape of options.
Frequently Asked Questions
Are clinical trials only for patients who have run out of options?
No — this is one of the most common and consequential misconceptions about clinical trials. Many breast cancer trials are designed for patients at or shortly after diagnosis, as first-line or adjuvant (post-surgery) therapy. Waiting until standard options are exhausted may make you ineligible for trials that could have been an option earlier. For metastatic disease, in particular, asking about trials at every treatment decision point is the standard of care at many major cancer centers.
Will I receive a placebo in a breast cancer clinical trial?
Breast cancer trials rarely use placebo alone. Most trials compare a new treatment (or the new treatment added to standard therapy) against current standard of care, so all participants receive an active treatment. When randomization occurs, you are comparing two active options, not treatment versus no treatment. The informed consent process will explain exactly what the treatment arms are before you agree to participate.
Do I have to travel to participate in a trial?
Trial sites vary. Many large Phase 3 trials enroll at hundreds of sites nationally, which means there may be a participating center near you. Some trials are available only at major cancer centers — if travel is required, trial sponsors often provide financial support for travel and lodging. Emerging “decentralized” trial designs are also allowing some elements (lab tests, imaging) to be conducted closer to home.
What happens if the experimental treatment doesn’t work for me?
You can withdraw from a trial at any time and transition to another standard treatment option. Your medical team remains involved throughout and will help determine next steps if the trial treatment isn’t working. Participation in a trial does not limit your future treatment options.
How do I know if a clinical trial is legitimate?
Legitimate clinical trials are registered on ClinicalTrials.gov, require FDA and institutional review board (IRB) oversight, and require informed consent. They are sponsored by academic medical centers, cooperative oncology groups (such as ECOG-ACRIN or SWOG), the NCI, or pharmaceutical companies. Trials accessed through ClinicalTrials.gov or a reputable trial matching service such as North are legitimate. Avoid any “trial” that asks you to pay for participation or that lacks proper registration.
References
National Cancer Institute. (2024). Breast Cancer Treatment — Health Professional Version. https://www.cancer.gov/types/breast/hp/breast-treatment-pdq
Gradishar, W. J., et al. (2024). NCCN Clinical Practice Guidelines in Oncology: Breast Cancer. National Comprehensive Cancer Network. https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1419
Cortés, J., et al. (2022). Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer (DESTINY-Breast03). New England Journal of Medicine. https://www.nejm.org/doi/full/10.1056/NEJMoa2115022
Schmid, P., et al. (2022). Pembrolizumab for Early Triple-Negative Breast Cancer (KEYNOTE-522). New England Journal of Medicine. https://www.nejm.org/doi/full/10.1056/NEJMoa1910549
Turner, N. C., et al. (2023). Capivasertib in Hormone Receptor-Positive Advanced Breast Cancer (CAPItello-291). New England Journal of Medicine. https://www.nejm.org/doi/10.1056/NEJMoa2214131
Modi, S., et al. (2022). Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer (DESTINY-Breast04). New England Journal of Medicine. https://www.nejm.org/doi/10.1056/NEJMoa2203690