Eliminating Surgery or Radiotherapy After Systemic Therapy in Treating Patients With HER2 Positive or Triple Negative Breast Cancer
Study Details
Study Description
Brief Summary
This clinical trial studies eliminating surgery and how well radiation therapy after systemic therapy works in treating patients with HER2 positive or triple negative breast cancer when image-guided biopsy shows no residual cancer. Patients then receive standard breast radiotherapy.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
Detailed Description
PRIMARY OBJECTIVES:
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To determine the 6 months (mo), 1, 2, 3, and 5-year biopsy confirmed ipsilateral breast tumor recurrence rate (IBTR, invasive, and/or in situ) among patients who do not undergo surgery (cohort A).
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To determine the pCR rate 6 months after radiation therapy based on image- guided biopsy (cohort B).
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To determine the 6 months, 1, 2, 3, and 5-year ipsilateral breast tumor recurrence rate among patients who undergo surgery alone without radiation (cohort C).
SECONDARY OBJECTIVES:
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To determine the 6 months, 1, 2, 3, and 5-year biopsy confirmed ipsilateral breast tumor recurrence rate (IBTR, invasive and/or in situ) among patients who do not undergo surgery (cohort C).
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To determine the number (%) of patients where final biopsy reveals residual disease and quantify the residual disease (residual cancer burden, RCB) determined by routine pathologic examination of surgery specimens.
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To assess baseline, 6 months, 1, 3, and 5 years decisional comfort of clinical trial participation using the Decisional Regret Scale (DRS).
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To determine patient-reported cosmetic outcome, breast pain, and functional status using the Breast Cancer Treatment Outcomes Scale (BCTOS) at baseline, 6 months, 1, 3, and 5 years.
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To determine the 6 mo, 1, 2, 3, and 5-year incidence of ipsilateral breast and nodal recommendation and performance of biopsy based on breast imaging follow-up.
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Correlate "liquid biopsy" analyses (after neoadjuvant systemic therapy [NST], 6 months and one year postradiotherapy or surgery) among protocol participants with pathologic complete response (pCR), utilizing circulating tumor cells (CTCs) and circulating tumor-deoxyribonucleic acid (DNA) (ctDNA).
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Among patients who decide to proceed with routine surgery, record the results of final biopsy compared with routine pathologic examination of surgery specimens.
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To determine patient-reported quality of life using the Functional Assessment of Cancer Therapy-Breast version 4 (FACT B+4) instrument at baseline, 6 months, 1, 3, and 5 years after treatment.
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To explore if radiation genomic sensitivity scores and Oncotype performed on the initial diagnostic core biopsy specimen correlate with pCR rates in Cohort B.
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To determine if changes in blood-based RNA Sequencing are elicited with radiation in Cohort B, measured at baseline, at the first 4-6 week follow-up after radiation, and at the 6 month post-radiation follow-up.
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In Cohort B to determine the 3 year rate of tumor control/progression free survival (PFS).
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In Cohort C to determine whether nanomechanical biomarkers or quantification of stromal and tumor TILS can predict for low risk of local recurrence in exceptional responders who omit radiation therapy.
OUTLINE:
For Cohorts A and B, within 12 weeks of completing neoadjuvant systemic therapy, patients undergo whole breast irradiation over 15-25 fractions on consecutive days. Patients then undergo external beam radiation therapy (EBRT) boost over 7 fractions on consecutive days beginning the day following completion of whole breast irradiation.
After completion of study treatment, patients are followed up every 6 months for 5 years.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort A Neoadjuvant chemotherapy therapy Biopsy: if no disease remaining - stay on the study and receive radiation (skip breast surgery) H&P and Imaging every 6 months Treatment (whole breast irradiation, EBRT) Within 12 weeks of completing neoadjuvant systemic therapy, patients undergo whole breast irradiation over 15-25 fractions on consecutive days. Patients then undergo EBRT boost over 7 fractions on consecutive days beginning the day following completion of whole breast irradiation. |
Radiation: External Beam Radiation Therapy
Undergo EBRT
Other Names:
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
Other: Questionnaire Administration
Ancillary studies
Radiation: Whole Breast Irradiation
Undergo whole breast irradiation
|
| Experimental: Cohort B Neoadjuvant endocrine therapy for 6 months Radiation if there is less than 25% tumor increase Biopsy: if negative - additional endocrine therapy under the guidance of medical oncologist (skip breast surgery) H&P and Imaging every 6 months Cohort B Radiation: Treatment (Stereotactic ablative radiotherapy -SABR) Following 3-6 months of endocrine therapy, if less than 25% tumor increase, patients undergo SABR irradiation over 10 fractions every other business day. |
Radiation: External Beam Radiation Therapy
Undergo EBRT
Other Names:
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
Other: Questionnaire Administration
Ancillary studies
Radiation: Whole Breast Irradiation
Undergo whole breast irradiation
|
| Experimental: Cohort C Optional biopsy for nanomechanical biomarker assessment Neoadjuvant chemotherapy therapy Surgery (& optional biopsy nanomechanical biomarker assessment): if no disease remaining - stay on the study and skip radiation H&P and Imaging every 6 months |
Radiation: External Beam Radiation Therapy
Undergo EBRT
Other Names:
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
Other: Questionnaire Administration
Ancillary studies
Radiation: Whole Breast Irradiation
Undergo whole breast irradiation
|
Outcome Measures
Primary Outcome Measures
- Ipsilateral breast tumor recurrence-free survival (IBT-RFS) [From confirmation of pathologic complete response (pCR) to the time of ipsilateral breast tumor recurrence or death, whichever occurs first or the time of last contact, assessed for up to 5 years]
Will monitor IBT-RFS using the method of Thall et al. Will be estimated using the Kaplan-Meier method log-rank test will be performed to test the difference in time-to-event distributions between patient groups. Cox proportional hazards model will be used to include multiple covariates in the time-to-event analysis.
- Overall survival [Up to 5 years]
Will be estimated using the Kaplan-Meier method log-rank test will be performed to test the difference in time-to-event distributions between patient groups. Cox proportional hazards model will be used to include multiple covariates in the time-to-event analysis.
Other Outcome Measures
- Change in biomarkers in blood and plasma [Baseline, 6 months, 12 months]
Biomarkers in blood and plasma, specifically CTC and cDNA, will be assessed by exploratory data analysis and graphical methods, which will be applied to examine distributions and to identify data errors and outliers. Linear mixed effect models for repeated measures analysis will be employed to assess the change of the data over time with multi-covariates including disease characteristics (tumor stage, site, pathology), and other patient prognostic factors.
- Quality of Life measured by FACT-B+4 questionnaire [Baseline, 6 months, 12 months, 36 months, 60 months]
The FACT-B+4 will assess the general quality of life of the patient.
- Quality of Life measured by BCTOS questionnaire [Baseline, 6 months, 12 months, 36 months, 60 months]
The Breast Cancer Treatment Outcome Scale (BCTOS) will assess patient-reported cosmetic outcome, breast pain, and functional status by comparing the affected breast with her unaffected breast.
- Quality of Life measured by DRS questionnaire [Baseline, 6 months, 12 months, 36 months, 60 months]
The Decisional Regret Scale (DRS) questionnaire will assess the decisional comfort of the clinical trial participant. Question answers range : Strongly Agree, Agree, Neither Agree Nor Disagree, Disagree, or Strongly Agree
- Incidence of ipsilateral breast and nodal recommendation and performance of biopsy based on breast imaging follow-up [Up to 5 years]
Multivariable logistic regression analysis using generalized estimating equations to take the intra-patient correlation into account will be used to determine factors significantly associated with the outcome.
- Residual cancer burden (RCB) [Up to 5 years]
Will be assessed by biopsy and routine surgery. Descriptive statistics will be used. The final biopsy will be compared with the response status determined by routine pathologic examination of surgery specimens using McNemar test.
Eligibility Criteria
Criteria
Inclusion Criteria:
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(Cohort A) 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
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(Cohort A) HER2 positive (immunohistochemistry [IHC] 3+ and or fluorescence in situ hybridization [FISH] amplified) or triple receptor negative (triple negative [TN], estrogen receptor [ER]/progesterone receptor [PR] < 10% HER2 negative [IHC 1+ or 2+ FISH non-amplified]) receiving any standard routine clinical NST regimen
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(Cohort A) Patient desires breast conserving therapy
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(Cohort A) 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
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(Cohort A) Female sex
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(Cohort A) 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
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(Cohort A) 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
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(Cohort B) ER and/or PR positive, HER2 negative
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(Cohort B) Clinical stage T1N0M0, unicentric non-lobular breast cancer, no lymphovascular space invasion,
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(Cohort B) At least 40 years of age.
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(Cohort B) Oncotype ≤ 25 if age ≥ 50 years
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(Cohort B) Oncotype 0-20 and tumor size ≤ 1.5cm if age 40-49 years.
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(Cohort B) Patient agrees to take anti-estrogen therapy and is interested in breast conservation
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(Cohort B) Female sex.
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(Cohort B) 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.
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(Cohort B) No history of prior radiation to the area of the breast that would require protocol-mandated treatment
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(Cohort C) Pathologically confirmed invasive breast cancer defined as radiologic clinical stage T1 or T2 (≤ 5 cm), N0, clinical stage M0.
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(Cohort C) HER2 positive (IHC 3+ and or FISH amplified) receiving any standard routine clinical NST regimen.
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(Cohort C) Patient desires breast conserving therapy.
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(Cohort C) Age 30 years or older.
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(Cohort C) Female sex.
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(Cohort C) 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.
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(Cohort C) 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.
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(Cohort C) Patient must have no evidence of residual invasive tumor or DCIS on pathologic review of the lumpectomy surgical specimen
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(Cohort C) Patient must have no evidence of metastatic disease involving the lymph nodes on pathologic review of the lymph node surgical specimen.
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(Cohort C) Unifocal disease or limited multifocal disease that can be excised in a single lumpectomy specimen
Exclusion Criteria:
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Radiologic evidence for a stage T3 or clinical stage T4 breast cancer in Cohort A/C; radiologic evidence for a stage T2-T3 or clinical stage T4 breast cancer in Cohort B.
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Clinical or pathologic evidence for distant metastases
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Prior diagnosis of invasive or ductal carcinoma in situ breast cancer in the ipsilateral breast
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Clinical evidence of progression of disease > 20% in the breast or new evidence of nodal metastases
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Patient is known to be pregnant
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Patient is participating in a NST protocol in which surgical excision of the breast and or lymph nodes are required in Cohort A/B.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Banner Health/Banner Research | Phoenix | Arizona | United States | 85006 |
| 2 | Baptist MD Anderson Cancer Center | Jacksonville | Florida | United States | 32207 |
| 3 | Queen's Medical Center | Honolulu | Hawaii | United States | 96813 |
| 4 | Mayo Clinic | Rochester | Minnesota | United States | 55905 |
| 5 | MD Anderson Cancer Center at Cooper-Voorhees | Voorhees | New Jersey | United States | 08043 |
| 6 | Carolinas Medical Center/Levine Cancer Institute | Charlotte | North Carolina | United States | 28203 |
| 7 | University of Pittsburgh Cancer Institute (UPCI) | Pittsburgh | Pennsylvania | United States | 15232 |
| 8 | M D Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- M.D. Anderson Cancer Center
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Henry M Kuerer, M.D. Anderson Cancer Center
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 2016-0046
- NCI-2016-01929
- 2016-0046