Omitting Radiation Therapy for Breast Cancer

(TAILOR RT Trial)

Recruiting at 517 trial locations

Overseen By Wendy Parulekar

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: Canadian Cancer Trials Group

Must be taking: Endocrine therapy

Disqualifiers: Pregnancy, Prior chest radiation, Others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 weeks

2140 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether women with low-risk breast cancer can safely skip regional radiation therapy without increasing the risk of recurrence. It compares the usual care, which includes radiation, to a treatment plan without it. Women diagnosed with breast cancer who have undergone surgery and meet specific cancer characteristics may be suitable candidates. The study aims to determine if omitting radiation can be equally effective, potentially reducing treatment side effects. As a Phase 3 trial, this research represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that endocrine therapy should be initiated or planned for at least 5 years, and it can be given concurrently or following radiation therapy.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that regional radiotherapy, which targets specific areas, is usually well-tolerated and causes few immediate side effects. For instance, a large study involving over 12,000 women found that this treatment significantly reduces the risk of breast cancer recurrence. However, some patients reported increased fatigue and nausea during treatment.

Opting out of regional radiotherapy avoids these potential side effects. This choice might still involve whole breast irradiation, a more focused type of radiation therapy, which generally has fewer side effects. The main goal is to determine if skipping regional radiotherapy is equally effective in preventing cancer recurrence without adding extra side effects.

Both treatment options have demonstrated safety. The decision may involve weighing the potential benefits and side effects of each choice. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about omitting radiation therapy for breast cancer because it could significantly reduce the side effects and burdens associated with radiation. The standard of care typically involves radiation therapy, which, while effective, can lead to fatigue, skin changes, and other long-term complications. By exploring the option of skipping radiation, especially after surgeries like mastectomy, patients might experience quicker recovery times and improved quality of life. This approach aims to maintain effective cancer control while minimizing the physical and emotional toll of treatment.

What evidence suggests that omitting radiation therapy might be effective for low risk breast cancer?

Research has shown that regional radiotherapy can significantly reduce the chances of breast cancer returning and lower the risk of mortality. A large study involving over 12,000 women demonstrated that adding radiation to areas near the breast decreased cancer recurrence and improved survival rates. Another study found that 97.3% of women who received regional radiation were still alive after five years. In this trial, some participants will receive regional radiotherapy, while others will not, to assess its necessity for women with low-risk breast cancer. While radiation is effective, uncertainty remains about its necessity for women with low-risk breast cancer. Some evidence suggests it might be beneficial, but more long-term results are needed to confirm this. ^{1 4 6 7 8}

Who Is on the Research Team?

Timothy Whelan

Principal Investigator

Juravinski Cancer Centre at Hamilton Health Sciences, Ontario Canada

Are You a Good Fit for This Trial?

This trial is for women over 35 with early-stage breast cancer that hasn't spread, specifically T3N0 or limited nodal micrometastases. They should have an Oncotype DX score ≤25, be ER ≥1% and HER2 negative, and can start treatment within 6 weeks of joining the study. Participants must not be pregnant, have serious illnesses preventing protocol adherence, or a history of certain cancers within the last 5 years.

Inclusion Criteria

My breast cancer recurrence score is 25 or less.

I agree to provide a tumor tissue sample for research.

I am a woman newly diagnosed with invasive breast cancer without spread beyond the breast.

Exclusion Criteria

I have had cancer other than breast cancer, but it was treated over 5 years ago with no current signs of the disease.

I have had radiation therapy on the same side of my chest before.

I have had breast cancer or DCIS on the same side treated with radiation before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either regional radiotherapy or no regional radiotherapy, along with standard care including endocrine therapy and possibly chemotherapy

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of arm volume, mobility, and quality of life

9.5 years

What Are the Treatments Tested in This Trial?

Interventions

• No Radiation
• Radiation

Trial Overview

The study is examining if skipping regional radiation therapy after usual care (like surgery) prevents breast cancer from returning in low-risk patients as effectively as including it. Women will either receive no radiation or the standard regional radiation to see which approach works best.

How Is the Trial Designed?

Group I: Regional Radiotherapy Active Control 1 Intervention

A. WBI plus RT to the regional nodes (supraclavicular, non-dissected axillary, and internal mammary) following BCS or; B. RT to the chestwall and regional nodes (supraclavicular, non-dissected axillary, and internal mammary) following mastectomy

Group II: No Regional Radiotherapy Active Control 2 Interventions

A. Whole Breast Irradiation (WBI) following BCS or; B. No Radiotherapy (RT) following mastectomy

No Radiation is already approved in European Union, United States for the following indications:

Approved in European Union as No Radiation Therapy for:

• Early-stage breast cancer with specific criteria (e.g., T1N0, grade 1-2 tumors, estrogen receptor-positive)

Approved in United States as No Radiation Therapy for:

• Early-stage breast cancer with specific criteria (e.g., T1N0, grade 1-2 tumors, estrogen receptor-positive), particularly in older women or those with low-risk features

Who Is Running the Clinical Trial?

Canadian Cancer Trials Group

Lead Sponsor

Trials

135

Recruited

70,300+

Alliance for Clinical Trials in Oncology

Collaborator

Trials

521

Recruited

224,000+

SWOG Cancer Research Network

Collaborator

Trials

403

Recruited

267,000+

Southwest Oncology Group

Collaborator

Trials

389

Recruited

260,000+

Eastern Cooperative Oncology Group

Collaborator

Trials

272

Recruited

153,000+

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

Published Research Related to This Trial

Radiation therapy (RT) is crucial in breast cancer treatment as it helps eliminate remaining cancer cells after surgery, significantly lowering the chances of local recurrence and improving survival rates for early-stage patients.

The article discusses various RT techniques, including hypofractionated RT and partial breast irradiation, highlighting their effectiveness in both noninvasive and invasive breast cancer cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation therapy in the management of breast cancer. Yang, TJ., Ho, AY.[2018]

In a study of 13,321 older women with stage I ER+ breast cancer, those who did not receive any treatment (neither radiation therapy nor endocrine therapy) had a significantly higher risk of developing second breast cancer events compared to those who received both treatments.

Radiation therapy alone did not increase the risk of second breast cancer events, suggesting it may be a safe option for older patients, while the omission of endocrine therapy was linked to a higher risk of recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation Without Endocrine Therapy in Older Women With Stage I Estrogen-Receptor-Positive Breast Cancer is Not Associated With a Higher Risk of Second Breast Cancer Events. Gerber, NK., Shao, H., Chadha, M., et al.[2022]

Postmastectomy irradiation significantly reduces the locoregional recurrence rate of breast cancer by a factor of 3, but this does not necessarily translate into improved long-term survival for all patients.

Recent studies indicate that high-risk premenopausal patients receiving both postmastectomy radiotherapy and adjuvant chemotherapy may experience a clinically relevant survival benefit, highlighting the importance of systemic therapy in conjunction with radiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of randomized trials in high risk breast cancer patients treated with adjuvant systemic therapy with or without postmastectomy irradiation. Overgaard, M.[2019]

Radiation therapy (RT) is crucial in breast cancer treatment, effectively reducing local recurrence and mortality, with short courses of RT (3-4 weeks) being as effective as longer ones.

Certain patients, particularly older individuals with good prognosis tumors and clear margins, may safely omit radiation boosts, while untreated regional nodes can lead to reduced survival, highlighting the need for tailored treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation therapy and early breast cancer: current controversies. Boyages, J.[2019]

Radiation therapy is crucial in breast cancer treatment, significantly reducing local recurrence and improving survival rates, especially with advancements in techniques since the late 1980s.

Shorter courses of radiation therapy (3-4 weeks) are generally as effective as longer ones, and modern techniques like volumetric modulated arc therapy (VMAT) help minimize complications while enhancing treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolution of radiotherapy techniques in breast conservation treatment. Boyages, J., Baker, L.[2020]

In a study of 1105 older women with low-risk breast cancer, omitting adjuvant radiation treatment after breast-conserving surgery did not increase the risk of cancer-specific death in the short term (5- and 10-year follow-up) for those with moderate to high comorbidity burden.

However, for women with low comorbidity burden, omitting radiation treatment may double the risk of long-term cancer-specific death, indicating that further research is needed to understand the implications of this treatment choice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between adjuvant radiation treatment and breast cancer-specific mortality among older women with comorbidity burden: A comparative effectiveness analysis of SEER-MHOS. Lee, E., Hines, RB., Zhu, J., et al.[2023]

Radiotherapy can be an effective alternative to surgery for breast cancer treatment, especially in cases where surgery is not possible or when it can provide similar outcomes in terms of cancer control and aesthetic results, particularly for larger tumors (T > 3 cm).

Recent studies indicate that the type of treatment (conservative vs. radical) does not significantly affect survival rates, and advancements in radiotherapy have improved its tolerability, allowing for lower doses and making it a viable option for patients who may eventually require surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Radiotherapy--an alternative to surgery in the treatment of breast cancer]. Baillet, F.[2006]

Omitting endocrine therapy in older women receiving adjuvant radiation after breast-conserving surgery may provide similar local control and survival rates, suggesting a potential alternative treatment strategy for those who struggle with endocrine therapy side effects.

Current evidence on this approach is limited, highlighting the necessity for future prospective, randomized studies to better understand the outcomes of omitting endocrine therapy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing Adjuvant Treatment Recommendations for Older Women with Biologically Favorable Breast Cancer: Short-Course Radiation or Long-Course Endocrine Therapy? McDuff, SGR., Blitzblau, RC.[2023]

Radiation therapy is an effective and safe option for breast conservation therapy in localized breast cancer, with careful consideration of factors like patient history and breast size.

Acute skin reactions during treatment do not predict long-term complications, suggesting that with proper techniques, most patients can achieve good outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conservation Therapy of the Breast: Optimizing Long-term Results. Greenberg, HM.[2019]

Breast conservation, combined with adjuvant radiation therapy, is a safe and effective treatment for most women with early-stage breast cancer, significantly reducing the risk of recurrence and improving survival rates.

Current research is focused on minimizing long-term side effects of radiation, such as heart disease, and exploring shorter treatment options like accelerated hypofractionated irradiation, especially for elderly patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ACR Appropriateness Criteria® conservative surgery and radiation--stage I and II breast carcinoma: expert panel on radiation oncology: breast. Bellon, JR., Harris, EE., Arthur, DW., et al.[2017]

A study of 1,292 elderly women with stage I, estrogen receptor-positive breast cancer showed that after 2004, when new guidelines were introduced, there was a significant decrease in the use of radiation therapy (RT), particularly among women aged 80 and older, where RT use dropped from 80% to 41%.

Factors influencing the omission of RT included older age, higher comorbidity scores, smaller tumor sizes, and the absence of axillary surgery, indicating that patient and tumor characteristics, along with institutional practices, play a crucial role in the adoption of treatment guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of guideline changes on use or omission of radiation in the elderly with early breast cancer: practice patterns at National Comprehensive Cancer Network institutions. McCormick, B., Ottesen, RA., Hughes, ME., et al.[2022]

In a study of 657 patients with T1 to T2N0 breast cancer who underwent mastectomy and received systemic therapy, the locoregional disease recurrence (LRR) rate was low at 4.7%, suggesting that many patients may not require postmastectomy radiotherapy (PMRT).

The study found that while larger tumor size was associated with a higher risk of recurrence, other high-risk features did not significantly impact LRR, indicating that PMRT may not be necessary solely based on these features in patients receiving modern systemic therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are there patients with T1 to T2, lymph node-negative breast cancer who are "high-risk" for locoregional disease recurrence? Mamtani, A., Patil, S., Stempel, MM., et al.[2018]

In a study of 2618 older women with early-stage, hormone-receptor-positive breast cancer who omitted radiation therapy, 30.9% did not receive endocrine therapy (ET), highlighting a significant gap in treatment.

Receiving endocrine therapy was linked to improved overall survival, indicating its importance for patients who forgo radiation; however, older patients were less likely to initiate ET, suggesting a need for targeted interventions in this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endocrine therapy initiation and overall survival outcomes with omission of radiation therapy in older Medicare patients with early-stage hormone-receptor-positive breast cancer. Shen, C., Li, N., Zhou, S., et al.[2023]

Citations

1.

thelancet.com

thelancet.com/journals/lancet/article/PIIS0140-6736(23)01082-6/fulltext

Radiotherapy to regional nodes in early breast cancer

In analyses of data on 12 167 women, regional node radiotherapy significantly reduced breast cancer recurrence, breast cancer mortality, and all ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9954587/

Recent Advances in Optimizing Radiation Therapy Decisions ...

Moreover, the 5-year rates for contralateral breast cancer, relapse-free, disease-free, and overall survival are 1.9% (90% CI 1.1–3.2), 97.3% (90% CI 95.9–98.4) ...

3.

cancer.gov

cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2017-02047

Regional Radiation Therapy with or without Whole Breast ...

Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. It is not known whether patients with low risk breast cancer need to receive ...

4.

practicalradonc.org

practicalradonc.org/article/S1879-8500(25)00108-0/fulltext

The Efficacy and Toxicity of Hypofractionated Regional ...

Although these studies have demonstrated promising results in terms of disease outcomes and toxicities, long-term outcome data are necessary.

5.

clinicaltrials.gov

clinicaltrials.gov/study/NCT00005957

NCT00005957 | Radiation Therapy in Treating Women ...

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Radiation to the tumor site and surrounding area may kill more tumor cells.

6.

jamanetwork.com

jamanetwork.com/journals/jamanetworkopen/fullarticle/2839036

Adjuvant Radiation and Endocrine Therapy in Early-Stage ...

Meaning These findings suggest that adjuvant RT or ET can significantly reduce the risk of LRR among patients with early-stage breast cancer and ...

7.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39326505/

A Randomized Phase 3 Clinical Trial (KROG 17-01)

All PRO domains showed improvements over time (P < .001). During radiation therapy, the WBI+RNI group reported greater fatigue and nausea.

8.

sciencedirect.com

sciencedirect.com/science/article/pii/S0360301623043419

104 Largest Real-World Data of Regional Nodal Irradiation ...

Conclusion. Five-fraction adjuvant breast cancer RT is well tolerated with low acute toxicity burden even among patients requiring regional nodal irradiation.