Preoperative Radiation Therapy for Early-Stage Breast Cancer

Overseen By Brieana Marino, MS

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: Parul Barry

Must not be taking: Chemotherapy

Disqualifiers: Prior malignancy, Male breast cancer, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

24 Participants Needed

Trial Summary

What is the purpose of this trial?

The novel use of preoperative RT will have broad implications for breast cancer patients, most of whom present with early-stage disease. In the era of reduced chemotherapy delivery, preoperative RT will allow oncologists to assess radiologic and biologic tumor response and correlate it to outcomes. Underutilization of RT negatively affects mortality. This trial aims to further evaluate pre-operative radiation therapy in patients with early stage, biologically favorable breast cancer, with improved access to RT.

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, it does mention that concurrent chemotherapy for current breast cancer is not allowed.

What data supports the effectiveness of the treatment Preoperative Radiation Therapy for Early-Stage Breast Cancer?

Research shows that preoperative radiation therapy can significantly reduce the chance of cancer returning in the same area, lowering local recurrence from 16% to 4%, without increasing the risk of death or spread of cancer. Additionally, it may help shrink tumors before surgery, potentially leading to better surgical outcomes. ^{1 2 3 4 5}

Is preoperative radiation therapy for early-stage breast cancer safe?

Preoperative radiation therapy for early-stage breast cancer has been studied and found to have mild side effects that do not require stopping the treatment. No increase in mortality or spread of cancer was noted, suggesting it is generally safe for humans. ^{1 3 6 7 8}

How is preoperative radiation therapy different from other treatments for early-stage breast cancer?

Preoperative radiation therapy for early-stage breast cancer is unique because it is given before surgery, which may help shrink the tumor and improve surgical outcomes. This approach can also help identify the exact tumor location and potentially reduce the need for additional treatments if the tumor responds well. ^{1 2 4 5 9}

Research Team

Parul N. Barry

Principal Investigator

UPMC Hillman Cancer Center

Eligibility Criteria

This trial is for women over 50 with early-stage, hormone-positive, HER2-negative breast cancer that's ≤2 cm in size and not spread to lymph nodes. Participants should be generally healthy (ECOG ≤ 2), not pregnant or breastfeeding, willing to use contraception during treatment, and have no severe illnesses or prior invasive cancers (except certain skin cancers) within the last 5 years.

Inclusion Criteria

My breast cancer includes all types and DCIS.

Your breast imaging shows no signs of lymph node involvement.

I have been active and mostly self-sufficient in the last 3 months.

Exclusion Criteria

I have had radiation therapy in the same breast area before.

My cancer has spread to nearby lymph nodes.

I have had breast cancer in both breasts or twice in the same breast.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Preoperative radiation therapy with dose escalation to determine the maximum tolerated dose (MTD)

Up to 18 months

Multiple visits for radiation therapy and monitoring

Dose Expansion

Additional 6 patients studied at the MTD for further experience with safety and efficacy

Varies based on cohort completion

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Regular follow-up visits at 1 month, 6 months, 1 year, 2 years, and 3 years after RT

Treatment Details

Interventions

• Preoperative Irradiation

Trial Overview The study tests preoperative radiation therapy in patients with favorable early-stage breast cancer. It aims to improve outcomes by allowing doctors to assess tumor response before surgery. The goal is also to increase access to radiation therapy which has been underused.

Participant Groups

Group I: Radiation Therapy (RT) Experimental Treatment 1 Intervention

Preoperative Dose-escalated RT (4 Cohorts): Cohort 1: standard dose of 30 Gy in 5 fractions to the planning target volume (PTV) and 30 GY in 5 fractions to the gross target volume (GTV) Cohort 2: 30 Gy in 5 fractions to the PTV with dose-escalation of the GTV to 35 Gy Cohort 3: 30 Gy in 5 fractions to the PTV with dose-escalation of the GTV to 40 Gy Cohort 4: 30 Gy in 5 fractions to the PTV with dose-escalation of the GTV to 50 Gy

Preoperative Irradiation is already approved in United States, European Union for the following indications:

Approved in United States as Preoperative Radiation Therapy for:

• Early-stage breast cancer
• Locally advanced breast cancer

Approved in European Union as Preoperative Radiotherapy for:

• Breast cancer
• Esophageal carcinoma
• Rectal carcinoma

Who Is Running the Clinical Trial?

Parul Barry

Lead Sponsor

Trials

2

Recruited

40+

Findings from Research

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]

Neoadjuvant radiotherapy (RT) in early-stage breast cancer patients significantly improves disease-free survival, particularly in estrogen receptor-positive patients, without negatively impacting overall survival rates.

In a large analysis of 250,195 patients, those receiving neoadjuvant RT had a lower risk (HR 0.64) of developing a second primary tumor compared to those who received adjuvant RT, suggesting potential long-term benefits that need further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant radiotherapy of early-stage breast cancer and long-term disease-free survival. Poleszczuk, J., Luddy, K., Chen, L., et al.[2018]

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]

In a study of 9,605 patients with stage III breast cancer, preoperative radiotherapy (RT) was found to be less effective than postoperative RT, leading to a higher risk of overall mortality.

After a median follow-up of 72 months, the results indicated that preoperative RT does not improve overall survival compared to postoperative RT, reinforcing the current treatment approach for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative radiotherapy does not change the existing treatment paradigm in stage III breast cancer. He, Y., Chen, Q., Zhu, F., et al.[2023]

Preoperative radiation therapy (RT) for early-stage breast cancer may offer benefits such as tumor downstaging and improved surgical outcomes, although the current evidence is mostly from retrospective studies.

Despite the limited data, the reviewed studies indicate that preoperative RT is feasible and effective, especially when combined with systemic therapy or higher radiation doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative radiotherapy: A paradigm shift in the treatment of breast cancer? A review of literature. Corradini, S., Krug, D., Meattini, I., et al.[2019]

This phase I/II clinical trial is investigating the feasibility, safety, and efficacy of preoperative accelerated partial breast irradiation (APBI) in early-stage breast cancer patients, aiming to identify the maximum tolerated dose without severe toxicity.

The study may provide insights into whether preoperative APBI can effectively replace surgery for certain patients, particularly those who are older or have significant health issues, while also exploring its impact on tumor response and local control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single fraction ablative preoperative radiation treatment for early-stage breast cancer: the CRYSTAL study - a phase I/II clinical trial protocol. Zerella, MA., Zaffaroni, M., Ronci, G., et al.[2022]

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]

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 1029 breast cancer patients, starting radiation therapy (RT) within 8 weeks after surgery was linked to improved locoregional recurrence-free survival (LRRFS) for those with luminal subtype breast cancer.

No significant differences in disease-free survival (DFS) or overall survival were found based on the timing of RT initiation, suggesting that while early RT may benefit certain patients, it does not universally affect all outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact on clinical outcomes of post-operative radiation therapy delay after neoadjuvant chemotherapy in patients with breast cancer: A multicentric international study. Marta, GN., AlBeesh, R., Pereira, AAL., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Preoperative breast radiation therapy: Indications and perspectives. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Neoadjuvant radiotherapy of early-stage breast cancer and long-term disease-free survival. [2018]

3. France pubmed.ncbi.nlm.nih.gov

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

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

Preoperative radiotherapy does not change the existing treatment paradigm in stage III breast cancer. [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Preoperative radiotherapy: A paradigm shift in the treatment of breast cancer? A review of literature. [2019]

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

Single fraction ablative preoperative radiation treatment for early-stage breast cancer: the CRYSTAL study - a phase I/II clinical trial protocol. [2022]

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

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

8. United States 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. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

The impact on clinical outcomes of post-operative radiation therapy delay after neoadjuvant chemotherapy in patients with breast cancer: A multicentric international study. [2021]