Surgery vs Pre-Surgery Radiotherapy for Breast Cancer

(NORDIS Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Irene Wapnir, MD

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Stanford University

Must not be taking: Endocrine therapy

Disqualifiers: Invasive carcinoma, Pregnant, Breastfeeding, others

Stay on Your Current Meds

No Placebo Group

Approved in 5 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial compares two treatments for a type of breast cancer called DCIS. One group will have surgery, while the other will have radiation followed by surgery. The goal is to see if radiation before surgery improves treatment outcomes.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that endocrine therapy (hormone treatment) is not allowed from the time of study randomization to the completion of surgery, unless it's for a cancer in the opposite breast.

What data supports the effectiveness of the treatment involving surgery and pre-surgery radiotherapy for breast cancer?

Research shows that lumpectomy followed by breast irradiation is effective for early-stage breast cancer, with high survival rates and reduced local recurrence. Additionally, preoperative radiotherapy is being explored to enhance treatment effectiveness and allow for more conservative surgeries. ^{1 2 3 4 5}

Is breast-conserving surgery with radiotherapy generally safe for humans?

Breast-conserving surgery with radiotherapy is considered a safe option for most women with early breast cancer, with studies showing good long-term outcomes and patient satisfaction. ^{6 7 8 9 10}

How does the treatment of lumpectomy with pre-surgery radiotherapy differ from other breast cancer treatments?

Lumpectomy, also known as breast-conserving surgery, is unique because it removes only the cancerous part of the breast, preserving most of the breast tissue, and is often combined with radiotherapy to prevent cancer recurrence. This approach contrasts with mastectomy, which involves removing the entire breast, and offers similar survival rates while maintaining the breast's appearance. ^{11 12 13 14 15}

Research Team

Irene Wapnir, MD

Principal Investigator

Stanford University

Eligibility Criteria

This trial is for individuals with non-palpable, image-detected ductal carcinoma in situ (DCIS) of the breast measuring up to 4 cm. Participants must have a biopsy marker placed and an ECOG performance status of 0-2. Prior contralateral breast cancer is okay, but not ipsilateral cancer or multicentric/multifocal DCIS, Paget's disease, invasive carcinoma on biopsy, mass lesions/palpable tumors over 4 cm, or positive lymph nodes.

Inclusion Criteria

My breast scan shows a non-mass lesion 4 cm or smaller.

I can take care of myself and perform daily activities.

I may have abnormal cells or lobular carcinoma in either breast.

Exclusion Criteria

Pregnant or breastfeeding

I have no remaining signs of the lesion after my biopsy.

My breast cancer is larger than 4 cm on imaging tests.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Radiotherapy

Participants receive partial breast irradiation once a day for 5 days before surgery

1 week

5 visits (in-person)

Surgical Excision

Participants undergo surgical excision of ductal carcinoma

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• Lumpectomy (Surgery)
• Partial breast irradiation (Radiation)

Trial Overview The study compares immediate surgical removal (lumpectomy) versus radiation therapy followed by delayed surgery for treating DCIS. The goal is to assess which method is more effective based on pathological findings from the excised tissue.

Participant Groups

Group I: Neoadjuvant partial breast irradiation Experimental Treatment 2 Interventions

Partial breast irradiation will be delivered once a day for 5 days before surgery. The planned daily dose is 6 Gy.

Group II: Surgical Excision Active Control 1 Intervention

Surgical excision of ductal carcinoma

Lumpectomy is already approved in Canada, Japan for the following indications:

Approved in Canada as Lumpectomy for:

• Early-stage breast cancer
• Low-risk breast cancer

Approved in Japan as Lumpectomy for:

• Early-stage breast cancer
• Low-risk breast cancer

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Dr. Richard A. Miller

Stanford University

Chief Executive Officer since 2023

Stanford University, MD

Dr. Robert Schott

Stanford University

Chief Medical Officer since 2021

University of Michigan, MD

Findings from Research

In a study of 1843 women with Stage I or II breast cancer, lumpectomy followed by breast irradiation resulted in a significantly lower rate of local tumor recurrence (90% remained free of ipsilateral breast tumor) compared to those who did not receive irradiation (61%).

After eight years of follow-up, the overall survival rates and distant-disease-free survival rates were similar between women who underwent lumpectomy (with or without irradiation) and those who had total mastectomy, indicating that lumpectomy is a viable treatment option for early-stage breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eight-year results of a randomized clinical trial comparing total mastectomy and lumpectomy with or without irradiation in the treatment of breast cancer. Fisher, B., Redmond, C., Poisson, R., et al.[2022]

Accelerated partial breast irradiation (APBI) offers a shorter treatment option compared to traditional whole breast irradiation (WBI), potentially increasing access to breast-conserving therapy for women with early-stage breast cancer.

While APBI techniques show similar local control rates to WBI in selected patients, the follow-up data on their long-term efficacy is limited, necessitating careful patient selection based on evidence-based criteria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated partial breast irradiation: potential roles following breast-conserving surgery. Biagioli, MC., Harris, EE.[2017]

Recent advancements in breast cancer treatment are shifting towards administering systemic therapy before surgery, which can lead to more effective treatment outcomes and potentially higher rates of disease-free and overall survival.

The evolving approach to radiotherapy includes considering its use before surgery, supported by improved radiobiological knowledge and technology, allowing for safer and more effective combinations with other treatments like antitumor drugs or immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative Radio(Chemo)Therapy in Breast Cancer: Time to Switch the Perspective? Montero, A., Ciérvide, R.[2023]

Breast-conserving treatment, which includes lumpectomy followed by radiotherapy, has become a successful alternative to mastectomy for early-stage breast cancer, offering effective tumor control and better cosmetic outcomes.

Recent advancements in radiotherapy methods allow for shorter treatment schedules that are just as effective as traditional longer courses, leading to improved convenience and potential cost savings for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frontiers in radiotherapy for early-stage invasive breast cancer. Fisher, CM., Rabinovitch, R.[2021]

In a study of 18 patients who underwent reduction mammaplasties and mastopexies on previously irradiated breasts, 94% achieved successful outcomes with their preoperative goals, indicating that these surgeries can be effective even after breast conservation therapy.

While there were some minor complications (22% of patients), only one major complication occurred (6%), suggesting that with careful consideration, elective breast surgeries can be performed safely in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduction mammaplasty and mastopexy in previously irradiated breasts. Spear, SL., Rao, SS., Patel, KM., et al.[2016]

Breast-conserving treatment is recognized as the standard surgical option for primary breast cancer, providing a balance of oncological safety and aesthetic satisfaction for most patients.

While breast-conserving surgery is deemed safe, it is important to consider individual patient preferences when deciding between breast conservation and mastectomy in treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is Mastectomy Oncologically Safer than Breast-Conserving Treatment in Early Breast Cancer? Riedel, F., Hennigs, A., Hug, S., et al.[2022]

Breast conserving surgery is safe for patients with breast tumors that have been effectively downstaged after neoadjuvant therapy, showing a similar recurrence rate (7.9%) to those with early breast cancer who underwent primary surgery (7.8%).

The study involved 88 patients in the neoadjuvant therapy group and 191 patients in the early breast cancer group, with a mean follow-up of over 61 months, indicating that age was the most significant predictor of recurrence in the neoadjuvant group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Breast conserving surgery after neoadjuvant therapy for large primary breast cancer. Tiezzi, DG., Andrade, JM., Marana, HRC., et al.[2021]

Partial breast reconstructive techniques can enhance cosmetic outcomes and patient satisfaction after breast-conserving surgery, but studies often lack comprehensive oncological outcomes and long-term data.

Local recurrence rates for these techniques are low, ranging from 0 to 1.8% per year, while cosmetic failure rates can vary significantly from 0 to 18%, indicating a need for more standardized assessments of both oncological and cosmetic results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oncological and cosmetic outcomes of oncoplastic breast conserving surgery. Asgeirsson, KS., Rasheed, T., McCulley, SJ., et al.[2007]

In a study of 438 patients with early-stage breast cancer treated with conservative surgery and radiation therapy, the long-term outcomes showed a low local recurrence rate of 6% at 5 years and 10% at 10 years, indicating the efficacy of this treatment approach.

Younger patients (under 35 years) had a higher local recurrence rate of 13% compared to older patients, suggesting that age at diagnosis may influence treatment outcomes, while the radiation dose and boost technique did not affect recurrence rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Breast conservation: long-term results from Westmead Hospital. Zissiadis, Y., Langlands, AO., Barraclough, B., et al.[2019]

In a study of 13,914 female patients with breast cancer, those who underwent breast-conserving surgery combined with radiotherapy (BCT) had significantly better overall survival (OS) and breast cancer-specific survival (BCSS) compared to those who had mastectomy, regardless of whether they were clinically node-positive or node-negative.

The risk of locoregional recurrence (LRR) was similar between the BCT and mastectomy groups, suggesting that BCT is a safe and effective treatment option that does not compromise local control of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Breast-Conserving Therapy is Associated with Improved Survival Without an Increased Risk of Locoregional Recurrence Compared with Mastectomy in Both Clinically Node-Positive and Node-Negative Breast Cancer Patients. Vasilyeva, E., Hamm, J., Nichol, A., et al.[2023]

The modified radical mastectomy remains the standard surgical treatment for breast cancer, but adjuvant radiation therapy after this procedure does not improve overall survival rates for patients.

Breast-conserving surgical procedures are gaining interest among patients, and radiation therapy is essential in these cases as part of the primary treatment alongside surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Established and new surgical procedures in the therapy of breast cancer]. Steindorfer, P., Pierer, G., Rabl, H., et al.[2006]

In a study of 68 patients with Stage III breast cancer, preoperative radiotherapy was found to delay the time until the first local recurrence of cancer, compared to conventional treatment methods.

However, this approach did not lead to an improvement in overall survival rates, suggesting that while it may help manage local disease, it does not enhance control over systemic recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The dilemma of stage III breast cancer: a study of preoperative radiotherapy. Whitaker, SV., Battersby, C.[2019]

In a study of 162 patients with favorable breast cancer, conservation surgery combined with radiation therapy achieved an impressive 96% control rate of local and regional tumors.

The results support the effectiveness of breast-conserving treatments, allowing for successful tumor management without the need for complete breast removal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conservation surgery and irradiation for the treatment of favorable breast cancer. Montague, ED., Gutierrez, AE., Barker, JL., et al.[2019]

In a clinical audit of 1252 patients treated with adjuvant radiation for early-stage breast cancer, the ipsilateral breast tumor recurrence rate was only 0.56%, indicating effective treatment outcomes that align with international standards.

The study reported low rates of late toxicity, with only 6.8% of patients experiencing grade 1 toxicity and 1.6% experiencing grade 2-3 toxicity, suggesting that adjuvant radiotherapy is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benchmarking clinical practice quality: an audit of ipsilateral breast tumor recurrence in patients managed for T1/T2 breast carcinoma. Suttie, C., Back, M., Donovan, J., et al.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Eight-year results of a randomized clinical trial comparing total mastectomy and lumpectomy with or without irradiation in the treatment of breast cancer. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Comparative study of surgical margins and cosmetic outcome in lumpectomy versus segmental resection in breast cancer. [2014]

3. United States pubmed.ncbi.nlm.nih.gov

Accelerated partial breast irradiation: potential roles following breast-conserving surgery. [2017]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Preoperative Radio(Chemo)Therapy in Breast Cancer: Time to Switch the Perspective? [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Frontiers in radiotherapy for early-stage invasive breast cancer. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Reduction mammaplasty and mastopexy in previously irradiated breasts. [2016]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Is Mastectomy Oncologically Safer than Breast-Conserving Treatment in Early Breast Cancer? [2022]

8. England pubmed.ncbi.nlm.nih.gov

Breast conserving surgery after neoadjuvant therapy for large primary breast cancer. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Oncological and cosmetic outcomes of oncoplastic breast conserving surgery. [2007]

10. Australia pubmed.ncbi.nlm.nih.gov

Breast conservation: long-term results from Westmead Hospital. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Breast-Conserving Therapy is Associated with Improved Survival Without an Increased Risk of Locoregional Recurrence Compared with Mastectomy in Both Clinically Node-Positive and Node-Negative Breast Cancer Patients. [2023]

12. Austria pubmed.ncbi.nlm.nih.gov

[Established and new surgical procedures in the therapy of breast cancer]. [2006]

13. Australia pubmed.ncbi.nlm.nih.gov

The dilemma of stage III breast cancer: a study of preoperative radiotherapy. [2019]

14. United States pubmed.ncbi.nlm.nih.gov

Conservation surgery and irradiation for the treatment of favorable breast cancer. [2019]

15. Australia pubmed.ncbi.nlm.nih.gov

Benchmarking clinical practice quality: an audit of ipsilateral breast tumor recurrence in patients managed for T1/T2 breast carcinoma. [2018]