Radiation Omission for Breast Cancer

Overseen By Michelle Faucheux, RN

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: University of Kansas Medical Center

Must be taking: Trastuzumab

Disqualifiers: Inflammatory breast cancer, metastatic, others

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

Compensation: Varies

Number of Visits: 3

Duration: 1 year

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates whether skipping radiation therapy is effective for certain early-stage breast cancer patients with HER-2 positive tumors. The researchers aim to determine if patients who have had a complete response to chemotherapy and a lumpectomy can maintain local control without radiation. Participants will either skip radiation after surgery or follow standard care, which includes radiation. This trial targets postmenopausal women diagnosed with HER-2 positive breast cancer who have undergone chemotherapy and surgery, with no remaining cancer in the tumor area. As an unphased trial, it offers the opportunity to contribute to research that could change future treatment approaches for similar patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since the trial involves chemotherapy and trastuzumab, it's best to discuss your current medications with the trial team to ensure there are no interactions.

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

Research has shown that skipping radiation in breast cancer treatment can be risky. A study from Scotland found a 10% chance of cancer returning in the same breast within 10 years if radiation is not used. Other studies suggest that omitting radiation might lower overall survival rates for individuals with early-stage HER2-positive breast cancer.

While some older patients (aged 65–70 and above) face a low risk of recurrence without radiation, these findings require careful consideration. The evidence indicates that for younger patients or those with early-stage cancer, skipping radiation might not be the safest option. Consulting a doctor is crucial to understand the implications of these findings. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Radiation Omission for Breast Cancer trial because it explores the possibility of safely skipping radiation therapy for certain breast cancer patients. Typically, HER2-positive breast cancer patients undergo surgery and radiation as part of their treatment. However, this trial investigates whether patients with a complete response after surgery and chemotherapy can avoid radiation altogether. Skipping radiation could spare patients from potential side effects, reduce treatment burdens, and improve quality of life. If successful, this approach could lead to a more tailored and less invasive treatment option for breast cancer patients.

What evidence suggests that the omission of radiation could be effective for early-stage HER2-positive breast cancer?

This trial will compare the outcomes of omitting radiation with standard radiation treatment for early-stage HER2-positive breast cancer. Research has shown that in some cases, skipping radiation might be just as effective for overall survival. One study found that not having radiation did not increase the risk of dying from this type of breast cancer. However, other studies have found that skipping radiation could lead to a higher chance of the cancer returning in the same area. Considering these potential risks and benefits is important when evaluating treatment options. ^{1 4 6 7 8}

Who Is on the Research Team?

Shane Stecklein, MD, PhD

Principal Investigator

University of Kansas Medical Center

Are You a Good Fit for This Trial?

This trial is for postmenopausal women aged 40 or older with early-stage HER-2 positive breast cancer who've had a complete response to chemotherapy and lumpectomy. Participants must have no evidence of residual disease, be in good health (Karnofsky Performance Status 50% to 100%), and agree to sign informed consent.

Inclusion Criteria

Your Her-2 test results show a high level of a specific protein or gene.

Only women who have gone through menopause will be eligible. This means they have not had a period for at least one year, have had both ovaries removed, or have specific hormone levels as per the clinic's standards.

Ability to understand and the willingness to sign a written informed consent

Exclusion Criteria

You have been diagnosed with a disease that has spread to other parts of your body.

You have had a cancer diagnosis, except for certain types of skin cancer, and have been cancer-free for at least 5 years.

You have been diagnosed with inflammatory breast cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Participants receive neoadjuvant chemotherapy as per medical oncologist's plan

Varies

Surgery

Participants undergo lumpectomy with sentinel lymph node biopsy

1 day

Treatment

Participants continue trastuzumab +/- pertuzumab therapy to complete a full year of therapy

1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up assessments every 3 months up to 5 years post-op

5 years

Every 3 months (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Omission of Radiation

Trial Overview The study aims to see if omitting radiation therapy after successful chemotherapy and lumpectomy can still maintain local control of the cancer in patients with HER-2 positive early-stage breast cancer.

How Is the Trial Designed?

Group I: Arm A Experimental Treatment 1 Intervention

Patient is required to have lumpectomy with sentinel lymph node biopsy shows pCR and will complete 1 year of trastuzumab +/- pertuzumab treatment. No radiation, or an omission of radiation, will be given on this arm, including external beam, brachytherapy or intraoperative radiation. Patients will be required to follow up with a medical, surgical, or radiation oncologist every 3 months for 5 years. At these follow up visits, a physical exam will be performed to assess for any disease recurrence. Screening mammogram or MRI is recommended every 6 months for patients on this arm.

Group II: Arm B Active Control 1 Intervention

Patient is required to have her-2 positive breast cancer, clinically node negative from exam. Patient will complete neoadjuvant chemotherapy per Medical Oncologist. This arm will undergo lumpectomy with sentinel lymph node biopsy shows pCR. The patient will proceed with radiation as standard of care. This arm includes a review of outcomes in the patient's medical chart as well as a collection of biospecimens such as blood and urine, for correlative studies.

Group III: Arm C Active Control 1 Intervention

Patient is required to have her-2 positive breast cancer, clinically node negative from exam. patient will complete neoadjuvant chemotherapy per Medical Oncologist. This arm will not undergo lumpectomy with sentinel lymph node biopsy shows pCR. The patient will proceed with radiation as standard of care. This arm includes a review of outcomes in the patient's medical chart as well as a collection of biospecimens, such as blood and urine, for correlative studies.

Who Is Running the Clinical Trial?

University of Kansas Medical Center

Lead Sponsor

Trials

527

Recruited

181,000+

Published Research Related to This Trial

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]

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]

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]

Citations

1. nature.com nature.com/articles/s41523-021-00242-8

De-escalation of radiation therapy in patients with stage I, ... We used the National Cancer Database (NCDB) to test the hypothesis that RT omission results in equivalent overall survival (OS) in stage 1 (T1N0) HER2+ breast ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2207586

Breast-Conserving Surgery with or without Irradiation in ... Omission of radiotherapy was associated with an increased incidence of local recurrence but had no detrimental effect on distant recurrence as the first event ...

3. clinical-breast-cancer.com clinical-breast-cancer.com/article/S1526-8209(24)00205-2/fulltext

Re-Evaluating the Omission of Radiation Therapy in Low ... The Early Breast Cancer Trialists' Collaborative Group (EBCTCG) analyzed these trials and found that RT reduced the absolute 10 year risk of ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12269788/

Omitting Regional Nodal Irradiation in Responders to ... The addition of adjuvant regional nodal irradiation did not decrease the risk of invasive breast cancer recurrence or death from breast cancer ...

5. nrgoncology.org nrgoncology.org/Home/News/Post/nrg-br008-hero-a-phase-iii-randomized-trial-seeking-to-optimize-use-of-radiotherapy-in-patients-with-early-stage-low-risk-her2-positive-breast-cancer-1

NRG-BR008 (“HERO”): A Phase III Randomized Trial ... A large randomized trial that is comparing the recurrence-free interval (RFI) among patients with early-stage, low risk HER2+ breast cancer.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11846025/

Omission of radiotherapy after breast-conserving surgery ... Multiple studies have shown a low risk of ipsilateral breast events (IBE) or other recurrences for selected patients aged 65–70 or older ...

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa2302344

Omitting Radiotherapy after Breast-Conserving Surgery in ... A recent Scottish trial reported a risk of local recurrence of approximately 10% at 10 years with the omission of radiotherapy, findings that ...

8. cancernetwork.com cancernetwork.com/view/radiation-therapy-omission-not-advised-in-early-stage-her2-breast-cancer

Radiation Therapy Omission Not Advised in Early-Stage ... Data indicate that omitting radiation therapy results in decreased overall survival in patients with stage I HER2-positive breast cancer.