Surgery vs Pre-Surgery Radiotherapy for Breast Cancer

(NORDIS Trial)

Overseen By Sinyoung Park

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: Stanford University

Must not be taking: Endocrine therapy

Disqualifiers: Invasive carcinoma, Pregnant, Breastfeeding, others

Stay on Your Current Meds You can continue your current medications while participating

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

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores two methods for treating ductal carcinoma in situ (DCIS), a non-invasive type of breast cancer. It compares removing the tumor through surgery alone (lumpectomy) to a combination of targeted radiation therapy (partial breast irradiation) before surgery, followed by the surgery itself. The goal is to determine which method is more effective based on tissue changes after treatment. Women diagnosed with DCIS through a biopsy and with specific imaging findings might be suitable candidates for this trial. As an unphased trial, it offers patients the opportunity to contribute to valuable research that could enhance future treatment options for DCIS.

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.

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

Research has shown that partial breast irradiation is generally safe and well-tolerated for treating early-stage breast cancer. Studies have found it causes fewer serious side effects compared to whole breast irradiation. For instance, a review of multiple studies found that partial breast irradiation significantly reduced early side effects, which occur soon after treatment. As a result, patients experienced fewer severe reactions during the treatment period.

Partial breast irradiation targets only the part of the breast where the cancer is located, helping to protect healthy tissues and lower the risk of side effects. The treatment typically concludes in five days, offering greater convenience for patients.

Overall, the safety data for partial breast irradiation is encouraging. It indicates that this treatment is not only effective but also has a lower risk of bothersome side effects compared to more extensive radiation methods. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the approach of using neoadjuvant partial breast irradiation because it offers a unique pre-surgical treatment for breast cancer. Unlike the standard of care, which typically involves surgery first, this method delivers radiation therapy before surgery, potentially shrinking the tumor and making surgical removal easier and less invasive. Additionally, this radiation is targeted specifically to the tumor site and is completed in just five days, offering a much shorter treatment period compared to traditional radiation schedules. This approach could lead to fewer side effects and a quicker recovery for patients, making it an appealing option for managing breast cancer.

What evidence suggests that this trial's treatments could be effective for breast cancer?

This trial will compare two treatment approaches for early-stage breast cancer, such as ductal carcinoma in situ (DCIS). One group of participants will receive neoadjuvant partial breast irradiation, where radiation targets only part of the breast before surgery. Research has shown that this method leads to excellent survival rates and effective cancer control while preserving the breast's appearance after treatment. One study found that this approach is safe and as effective as the traditional method of treating the whole breast with radiation. If successful, this method could offer a focused treatment option with potentially fewer side effects. Meanwhile, another group in this trial will undergo surgical excision without prior radiation. ^{1 5 6 7 8}

Who Is on the Research Team?

Irene Wapnir, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Lumpectomy
• Partial breast irradiation

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.

How Is the Trial Designed?

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 European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Lumpectomy for:

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

Approved in United States as Lumpectomy for:

• Early-stage breast cancer
• Low-risk breast cancer
• Ductal carcinoma in situ (DCIS)

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+

Published Research Related to This Trial

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]

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 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]

In a study of 190 women with breast cancer, segmental resection was found to be oncologically safe, showing no significant difference in positive resection margins compared to standard lumpectomy, indicating both techniques are effective for breast conservation.

Segmental resection can effectively treat larger tumors (average size 26.6 mm) while maintaining comparable cosmetic satisfaction to standard lumpectomy, which typically treats smaller tumors (average size 17.0 mm).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative study of surgical margins and cosmetic outcome in lumpectomy versus segmental resection in breast cancer. Eggemann, H., Ignatov, A., Krocker, J., et al.[2014]

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]

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]

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]

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]

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 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]

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]

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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4197356/

Accelerated Partial Breast Irradiation with Intensity- ... Accelerated partial breast irradiation is safe and effective using intensity-modulated radiation therapy in selected early-stage breast cancer. Int J Radiat ...

2. advancesradonc.org advancesradonc.org/article/S2452-1094(25)00079-X/fulltext

Long-Term Outcomes of Multimodality Accelerated Partial ... APBI as a component of breast-conserving therapy for pure ductal carcinoma in situ is associated with excellent survival rates, local control, and cosmetic ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6378667/

Effectiveness of different accelerated partial breast ... This systematic review was conducted to compare the effectiveness of different accelerated partial breast irradiation (APBI) techniques for the treatment of ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT00282035

RAPID: Randomized Trial of Accelerated Partial Breast ... To determine if Accelerated Partial Breast Irradiation, using 3D CRT, is as effective as Whole Breast Irradiation following breast conserving surgery in ...

5. practicalradonc.org practicalradonc.org/article/S1879-8500(23)00296-5/fulltext

Partial Breast Irradiation for Patients With Early-Stage ... Preoperative single-fraction partial breast radiation therapy: A novel phase 1, dose-escalation protocol with radiation response biomarkers.

6. sciencedirect.com sciencedirect.com/science/article/pii/S0959804915000027

Accelerated partial breast irradiation using intensity ... We present the results of a randomised trial comparing local recurrence and survival of APBI using the IMRT technique after BCS to conventional WBI in early ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7856797/

A meta-analysis of the efficacy and safety of accelerated ... Compared to whole breast irradiation, accelerated partial breast irradiation significantly reduced serious (≥ grade 2) early toxicities, ...

8. breastsurgeons.org breastsurgeons.org/docs/statements/Consensus-Statement-for-Accelerated-Partial-Breast-Irradiation.pdf

Resource Guide on Accelerated Partial Breast Irradiation APBI has been studied as an alternative to whole breast radiation to potentially increase the number of individuals eligible for breast conservation. APBI can ...