Preoperative Radiotherapy + Mastectomy for Breast Cancer

Recruiting at 6 trial locations

Overseen By Atif Khan, MD

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Prior breast cancer, Pregnant, Stage IV, others

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

Compensation: Varies

Number of Visits: Unknown

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach to treating breast cancer by administering neoadjuvant radiotherapy (radiation therapy before surgery). The study evaluates the safety of receiving radiation before a mastectomy (breast removal surgery) followed by immediate breast reconstruction using tissue from another part of the body. It targets women with T4 breast cancer who have responded well to chemotherapy and seek immediate reconstruction. The trial aims to determine if this approach is feasible and safe compared to the usual treatment. Participants should have invasive breast cancer without metastasis. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this alternative treatment approach is safe?

Research has shown that radiation before surgery, known as neoadjuvant radiotherapy, is generally well-tolerated by breast cancer patients. Studies have found that while some patients may experience side effects like skin irritation or tiredness, these are usually mild and manageable. Another study confirmed that this treatment is safe for people with breast cancer, with most patients experiencing no major problems.

Overall, the treatment appears safe, with most side effects being mild and temporary. Participants should discuss any concerns with their doctors, who can provide personalized advice and support during treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the combination of preoperative radiotherapy and mastectomy for breast cancer because it offers a unique approach compared to the standard sequence of treatments. Typically, treatments involve surgery first, followed by radiotherapy, but this approach flips the order, potentially shrinking tumors more effectively before surgery. This could lead to better surgical outcomes and allow for immediate reconstruction options. Additionally, for patients showing a response to chemotherapy, this method might provide more tailored and effective treatment options, possibly improving recovery times and overall outcomes.

What evidence suggests that preoperative radiotherapy and mastectomy could be effective for breast cancer?

Studies have shown that neoadjuvant radiotherapy, which is radiation treatment given before surgery, can improve outcomes for people with breast cancer. Research indicates that this approach can lead to higher patient satisfaction and may reduce the chance of cancer returning in the treated area. One study found that this type of radiotherapy was linked to a better chance of staying cancer-free in the treated area. Another review suggests that this treatment can lead to shorter overall treatment times and fewer complications. These findings suggest that preoperative radiotherapy, which participants in this trial will receive, may be a promising option for effectively treating breast cancer. ^{1 2 6 7 8}

Who Is on the Research Team?

Audree Tadros, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for women over 18 with invasive breast cancer at a specific stage (cT3-4 cN0-3). They should have responded to initial chemotherapy, want reconstruction surgery using their own tissue, and be able to read English. It's not for those with unresectable disease, bilateral or previous same-side breast cancer, pregnancy, no change or worsening after chemo, prior chest radiotherapy, or BMI over 40.

Inclusion Criteria

I want and am deemed suitable for breast reconstruction using my own tissues.

My tumor is large or has spread to nearby tissues but not to distant parts of the body.

I am a woman over 18 with confirmed invasive breast cancer.

Exclusion Criteria

I have had radiation therapy to my chest area before.

You have a body mass index (BMI) higher than 40.

My breast cancer cannot be removed with surgery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Participants receive standard neoadjuvant chemotherapy to assess response before proceeding to radiotherapy

8-12 weeks

Preoperative Radiotherapy

Participants receive radiotherapy before their mastectomy

4-6 weeks

Surgery and Immediate Reconstruction

Participants undergo mastectomy followed by immediate autologous reconstruction

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on wound complications and surgical outcomes

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Neoadjuvant radiotherapy
• Pre-neoadjuvant radiotherapy (NART) biopsy
• Unilateral total mastectomy with axillary lymph node dissection

Trial Overview The study tests preoperative radiotherapy followed by mastectomy and immediate autologous reconstruction in T4 breast cancer patients. This means radiation treatment before surgery and using the patient's own tissue for breast reconstruction right after removing the cancer.

How Is the Trial Designed?

Group I: Participants with clinical T4 biopsy-proven breast cancer Experimental Treatment 3 Interventions

Participants with clinical T4 biopsy-proven breast cancer with no evidence of distant metastases who demonstrate a complete or partial response to standard neoadjuvant chemotherapy/NAC and desire immediate autologous reconstruction/IR will be eligible to enroll.

Neoadjuvant radiotherapy is already approved in United States, European Union, China for the following indications:

Approved in United States as Neoadjuvant radiotherapy for:

• Locally advanced breast cancer (LABC)
• T4 breast cancer

Approved in European Union as Preoperative radiotherapy for:

• Locally advanced breast cancer (LABC)
• T4 breast cancer

Approved in China as Neoadjuvant radiotherapy for:

• Locally advanced breast cancer (LABC)
• T4 breast cancer

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

Neoadjuvant chemotherapy or hormonal therapy allows more patients with locally advanced breast cancer (T2 and T3) to undergo breast-conserving surgery without significantly increasing the risk of cancer recurrence in the same breast.

Induction chemotherapy can enhance cosmetic outcomes post-surgery, but it is crucial to ensure clear surgical margins and to plan surgeries carefully, particularly in onco-plastic contexts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Breast conservative surgery for operable invasive ductal carcinoma after neoadjuvant chemotherapy or hormonal therapy- a challenge for breast surgeon: a review based on literature and experience. Bobin, JY., Al-Khaledi, K., Ahmad, J.[2014]

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]

Pre-operative 5-fraction breast radiotherapy followed by immediate breast-sparing surgery was feasible in 14 patients, but wound complications occurred in 5 patients, highlighting a significant risk of post-surgical issues.

The study emphasizes the importance of performing sentinel node procedures before pre-operative radiotherapy, as two patients had pathological lymph node involvement, which could affect treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-OPerative accelerated radiotherapy for early stage breast cancer patients (POPART): A feasibility study. Mulliez, T., Miedema, G., Van Parijs, H., et al.[2022]

Postmastectomy radiotherapy (PMRT) significantly reduces the risks of locoregional failure, recurrence, and breast cancer mortality in patients with T1-2 breast cancer who have one to three positive axillary nodes, based on a systematic review of recent literature.

The decision to use PMRT should be individualized, considering the patient's specific risk factors and potential toxicities, as some patients may have a low risk of locoregional failure that does not justify the treatment's risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postmastectomy Radiotherapy: An American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Focused Guideline Update. Recht, A., Comen, EA., Fine, RE., et al.[2022]

In a review of 100 patients with locally advanced breast cancer treated with preoperative radiotherapy, significant local postoperative complications were observed, including a 25% incidence of local wound infections and 63% seroma formation.

The study suggests that preoperative chemotherapy may be a better option than radiotherapy for these patients, as it could reduce local postoperative morbidity and improve their quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Morbidity of surgical treatment for advanced cancer of the breast after irradiation]. Guenier, C., Coibion, M., Badr el Din, A., et al.[2009]

Recent interest in preoperative breast radiation therapy (RT) is growing due to advancements in modern techniques, which may improve its effectiveness compared to older studies that did not change clinical practice.

Current clinical trials are exploring the combination of preoperative RT with novel drugs, aiming to enhance treatment outcomes and optimize translational research in breast cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative breast radiation therapy: Indications and perspectives. Lightowlers, SV., Boersma, LJ., Fourquet, A., et al.[2021]

In a study of 176 node-positive, ER+, HER2- breast cancer patients treated with neoadjuvant therapy, the overall rate of axillary pathologic complete response (pCR) was 12.3%, with higher rates observed in patients diagnosed at clinical stage II (20%) compared to stage III (8.4%).

Neoadjuvant chemotherapy (NCT) was associated with a higher pCR rate (13.9%) compared to neoadjuvant endocrine therapy (NET) (7.3%), and most patients achieving pCR after NCT were able to avoid axillary dissection, highlighting the potential of NAT to reduce surgical interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axillary Response to Neoadjuvant Therapy in Node-Positive, Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer Patients: Predictors and Oncologic Outcomes. Friedman-Eldar, O., Ozmen, T., El Haddi, SJ., et al.[2022]

In a study comparing three groups of breast cancer patients who underwent radical mastectomy, the ten-year survival rates were identical across all groups, indicating that the type of treatment (radical mastectomy alone, postoperative irradiation, or preoperative irradiation) did not significantly affect long-term survival.

The data showed that higher rates of positive axillary nodes were associated with lower survival rates, suggesting that irradiation (either pre- or post-surgery) may provide survival benefits, but there was no evidence that preoperative irradiation was more effective than postoperative irradiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative or postoperative irradiation as adjunctive treatment with radical mastectomy in breast cancer. Rodger, A., Montague, ED., Fletcher, G.[2019]

Modern neo-adjuvant therapies can effectively convert initially positive lymph nodes to negative in breast cancer patients, particularly those with HER2-positive disease, allowing for more accurate axillary staging.

Clinical trials are currently underway to identify which patients can safely forgo axillary dissection and/or radiation, potentially reducing the need for more invasive procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of the clinically positive axilla. Euhus, DM.[2020]

In a trial involving 67 breast cancer patients undergoing neo-adjuvant therapy, pre-operative chemotherapy showed low side effects, with 79% of patients experiencing no hair loss and 74% reporting no gastrointestinal issues, despite the use of five different cytotoxic agents.

Response rates to pre-operative chemotherapy included 4% complete remission and 38% partial remission, indicating that while the treatment was generally well-tolerated, the effectiveness varied, and the study aims to identify which patients would benefit most from subsequent post-operative treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective randomized clinical trial: protoadjuvant chemotherapy vs. protoadjuvant radiotherapy in breast cancer stages T3/4, N+/-, M0. Rainer, H.[2007]

Breast conservation surgery followed by radiation therapy is as effective as mastectomy for early-stage breast cancer, providing comparable local control and survival rates, based on various studies.

With proper patient selection and surgical techniques, 80-90% of patients achieve good to excellent cosmetic outcomes, which may encourage more women to seek early detection of breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Primary radiation therapy as an alternative to mastectomy for early-stage breast cancer. Ratanatharathorn, V., Powers, WE.[2006]

The increasing use of neoadjuvant chemotherapy in breast cancer patients with node-positive disease raises questions about the necessity of complete axillary lymph node dissection (ALND) after achieving a complete clinical response, highlighting a need for individualized treatment approaches.

The article emphasizes the importance of ongoing clinical trials to gather more evidence on optimal locoregional management, encouraging patient participation in trials and supporting informed decision-making based on personal values.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Debating the Optimal Approach to Nodal Management After Pathologic Complete Response to Neoadjuvant Chemotherapy in Patients With Breast Cancer. Carter, S., Neuman, H., Mamounas, EP., et al.[2019]

Preoperative radiotherapy for mastocarcinoma can effectively reduce tumor size, allowing for radical surgery, and is preferred over postoperative radiotherapy due to anatomical and radiobiological advantages.

The local control rate of the treatment is impressively high at 90-100%, and the cosmetic outcomes are generally excellent, making it a viable alternative to mastectomy for certain tumor sizes and conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Preoperative radiotherapy and curative radiotherapy without mastectomy in carcinoma of the breast (author's transl)]. Sauer, R.[2006]

In a clinical trial involving 250 patients per group, preoperative radiotherapy (RT) significantly reduced the incidence of locally recurrent breast cancer from 16% to 4% without affecting overall survival rates after two years.

The study found that preoperative RT did not increase mortality or metastasis, and the side effects were mild, suggesting that RT is a safe and effective option for reducing local recurrence in operable breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Preoperative radiotherapy in breast cancer. Description of a clinical trial record and first results]. de Schryver, A.[2009]

Citations

1. thegreenjournal.com thegreenjournal.com/article/S0167-8140(25)04495-0/fulltext

A systematic review of literature of the last decade This review indicates that NART followed by IBR may result in higher patient satisfaction, lower complication rates and shorter total treatment time compared ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12104955/

Radiotherapy in breast cancer patients achieving nodal ... The multivariate analysis showed that radiotherapy was associated with locoregional recurrence-free survival (HR: 0.61; 95% CI: 0.45–0.82; P= ...

3. nature.com nature.com/articles/s41598-024-59961-0

Neoadjuvant radiochemotherapy is safe and feasible for ... This study aimed to evaluate the survival outcomes of neoadjuvant radiochemotherapy (NARCT) for early breast cancer.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06313073

Neoadjuvant Radiotherapy for Breast Cancer Clinical or pathological stage T4 or M1 breast cancer;; Received preoperative neoadjuvant therapy;; Pathological confirmation shows that there is no invasive ...

5. breast-cancer-research.biomedcentral.com breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-017-0870-1

Neoadjuvant radiotherapy of early-stage breast cancer and ... Neoadjuvant RT may significantly improve disease-free survival without reducing overall survival, especially for estrogen receptor-positive patients with early ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11035569/

Neoadjuvant radiochemotherapy is safe and feasible for ... This study aimed to evaluate the survival outcomes of neoadjuvant radiochemotherapy (NARCT) for early breast cancer.

7. sciencedirect.com sciencedirect.com/science/article/pii/S0167814025044950

Review Article Neoadjuvant radiotherapy and immediate ... This comprehensive systematic review provides an overview of patient-reported, complications, and oncological outcomes of NART followed by IBR in breast cancer ...

8. ascopubs.org ascopubs.org/doi/10.1200/OP.21.00635

Advances in Breast Cancer Radiotherapy: Implications for ... The purpose of this clinical review is to provide an update on evolving RT techniques and to discuss future directions.