Eliminating surgery and radiation for certain breast cancer patients

Multicenter Trial for Eliminating Breast Cancer Surgery or Radiotherapy in Exceptional Responders to Neoadjuvant Systemic Therapy

This study is testing if some breast cancer patients can skip surgery and just use radiation therapy after their initial treatment to see how it affects their cancer and quality of life.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 30 Years and up
• Sex: Female
• Sponsor: M.D. Anderson Cancer Center (Academic / other)
• Drugs / interventions: radiation
• Locations: 8 sites (Gilbert, Arizona and 7 other locations)
• Trial ID: NCT02945579 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the possibility of forgoing surgery and assessing the effectiveness of radiation therapy in patients with HER2 positive or triple negative breast cancer who show no residual cancer after neoadjuvant systemic therapy. The study is divided into multiple cohorts, each focusing on different outcomes such as tumor recurrence rates and patient-reported quality of life over several years. Participants will undergo image-guided biopsies and receive standard breast radiotherapy if eligible. The trial aims to provide insights into the long-term effects of avoiding surgery in specific patient populations.

Who should consider this trial

Good fit: Ideal candidates are women aged 40 and older with HER2 positive or triple negative breast cancer who desire breast-conserving therapy and meet specific clinical criteria.

Not a fit: Patients with advanced breast cancer or those who do not meet the eligibility criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could reduce the need for invasive surgery and improve quality of life for patients with specific types of breast cancer.

How similar studies have performed: Other studies have explored similar approaches in breast cancer treatment, but this specific methodology of eliminating surgery in exceptional responders is relatively novel.

Eligibility criteria

Inclusion Criteria:

* Cohort A1 and A2

  • Conditions for patient eligibility: Patients on this portion of the study can receive radiation treatment at any MD Anderson Cancer Center or any outside hospital and may be enrolled prior to, during, or following neoadjuvant systemic therapy provided they meet the following eligibility and ineligibility requirements noted below:
  1. Pathologically confirmed unicentric invasive breast cancer defined as radiologic clinical stage T1 or T2 (≤ 5 cm), N0 or N1 (≤ 4 abnormal axillary nodes on initial ultrasound), clinical stage M0.
  2. HER2 positive (IHC 3+ and or FISH amplified) or triple receptor negative (TN, ER/PR\< 10% HER2 negative (IHC 1+ or 2+ FISH non-amplified) receiving any standard routine clinical NST regimen.
  3. Patient desires breast conserving therapy.
  4. Age 40 years or older. This age cutoff is justified because breast cancers in women under the age of 40 are known to have a significantly higher risk of IBTR presumably due to underlying biologic differences \[124, 125\].
  5. Female sex.
  6. If the patient has a history of a prior non-breast cancer, all treatment for this cancer must have been completed prior to study registration and the patient must have no evidence of disease for this prior non-breast cancer.
  7. Patient must have an initial nodal ultrasound that does not demonstrate more than four suspicious lymph nodes, any suspicious lymph nodes should be biopsied to determine if nodal metastatic disease present.
  8. Patient understands that the breast lesion size on final breast imaging must be less than or equal to 2 cm prior to the biopsy procedure being performed on study and if the biopsy shows residual carcinoma the patient will be taken off study.
* Cohort B1 and B2

  • Conditions for patient eligibility: Patients on this portion of the study will be limited to receive radiation treatment at MD Anderson Cancer Center or other approved locations and must be enrolled prior to any neoadjuvant systemic therapy provided they meet the following eligibility and ineligibility requirements noted below:
  1. ER and/or PR positive, HER2 negative
  2. Clinical stage T1N0M0, unicentric non-lobular breast cancer, no lymphovascular space invasion,
  3. At least 40 years of age.
  4. Oncotype ≤ 25 if age ≥ 50 years
  5. Oncotype 0-20 and tumor size ≤ 1.5cm if age 40-49 years.
  6. Patient agrees to take anti-estrogen therapy and is interested in breast conservation
  7. Female sex.
  8. If the patient has a history of a prior non-breast cancer, all treatment for this cancer must have been completed prior to study registration and the patient must have no evidence of disease for this prior non-breast cancer.
  9. No history of prior radiation to the area of the breast that would require protocol-mandated treatment
* Cohort C

  • Conditions for patient eligibility: Patients on this portion of the study can receive surgical treatment at any MD Anderson Cancer Center or any outside hospital and may be enrolled prior to or following neoadjuvant systemic therapy provided they meet the following eligibility and ineligibility requirements noted below:
  1. Pathologically confirmed invasive breast cancer defined as radiologic clinical stage T1 or T2 (≤ 5 cm), N0, clinical stage M0 and HER2 positive (IHC 3+ and or FISH amplified) receiving any standard routine clinical NST regimen containing her-2 directed therapy OR Pathologically confirmed invasive breast cancer defined as radiologic clinical stage T1 (≤ 2 cm), N0, clinical stage M0 and triple negative, receiving any standard routine clinical NST regimen.
  2. For cohort C patients participating in the optional pretreatment biopsy, the patient should be able undergo biopsy or surgery of the primary tumor site of suspected or proven invasive breast cancer and should be planned to receive neoadjuvant systemic therapy.
  3. Patient desires breast conserving therapy.
  4. Age 30 years or older if HER2 positive. Age 50 or older if HER2 negative (triple negative).
  5. Female sex.
  6. If the patient has a history of a prior non-breast cancer, all treatment for this cancer must have been completed prior to study registration and the patient must have no evidence of disease for this prior non-breast cancer.
  7. Patient must have an initial nodal ultrasound that does not demonstrate suspicious lymph nodes; any suspicious lymph nodes should be biopsied to determine if nodal metastatic disease present.
  8. Patient must have no evidence of residual invasive tumor or DCIS on pathologic review of the lumpectomy surgical specimen
  9. Patient must have no evidence of metastatic disease or isolated tumor cells involving the lymph nodes on pathologic review of the lymph node surgical specimen. If treatment effect in the nodes is noted on the pathology report, the investigators would generally discourage enrollment on this protocol.
  10. Unifocal disease or limited multifocal disease that can be excised in a single lumpectomy specimen
* Cohort D (MD Anderson Houston patients only)

  * Conditions for patient eligibility: Patients on this portion of the study meet all eligibility requirements for cohort C, but have not enrolled onto the study to omit radiation. Patients in Cohort D can be identified at the time of diagnosis or prior to lumpectomy. They are not required to participate in one of the treatment arms of the study, but can ultimately choose to move to an omission Cohort at a later time point.

3.5.1 Patients with triple negative or her-2 positive tumor who are amenable to breast conserving treatment and have received or are planned for neoadjuvant systemic therapy prior to surgery are eligible for Cohort D.

3.5.2 Eligible patients in cohort D who have undergone optional ARTIDIS biopsies of the primary breast tumor at the time of diagnosis, prior to starting neoadjuvant therapy, or following completion of systemic therapy, at the time of surgery, may later move to Cohort A or C if they meet all eligibility requirements and ultimately desire surgery or radiation omission

Exclusion Criteria:

1. Radiologic evidence for a stage T3 or clinical stage T4 breast cancer in Cohort A1/A2/C; radiologic evidence for a stage T2-T3 or clinical stage T4 breast cancer in Cohort B1/B2.
2. Clinical or pathologic evidence for distant metastases.
3. Prior diagnosis of invasive or ductal carcinoma in situ breast cancer in the ipsilateral breast.
4. Clinical evidence of progression of disease \>20% in the breast or new evidence of nodal metastases.
5. Patient is known to be pregnant.
6. Patient is participating in a NST protocol in which surgical excision of the breast and or lymph nodes are required in Cohort A1/A2/B1/B2.

Where this trial is running

Gilbert, Arizona and 7 other locations

• MD Anderson Cancer Center - Banner — Gilbert, Arizona, United States (Completed)
• Baptist MD Anderson Cancer Center — Jacksonville, Florida, United States (Recruiting)
• Queen's Medical Center — Honolulu, Hawaii, United States (Completed)
• Mayo Clinic — Rochester, Minnesota, United States (Recruiting)
• Cooper Hospital Univ Med Ctr, MD Anderson at Cooper Voorhees — Voorhees Township, New Jersey, United States (Recruiting)
• Carolinas Medical Center/Levine Cancer Institute — Charlotte, North Carolina, United States (Recruiting)
• University of Pittsburgh Cancer Institute (UPCI) — Pittsburgh, Pennsylvania, United States (Recruiting)
• M D Anderson Cancer Center — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Henry M Kuerer — M.D. Anderson Cancer Center
• Study coordinator: Henry Kuerer

Conditions Estrogen Receptor Negative; HER2 Positive Breast Carcinoma; HER2/Neu Negative; Invasive Breast Carcinoma; Progesterone Receptor Negative; Stage I Breast Cancer AJCC v7; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7