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Estrogen Receptor NegativeNCT02945579

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

A study testing Undergo EBRT, Laboratory Biomarker Analysis and Quality-of-Life Assessment in people with Estrogen Receptor Negative and HER2 Positive Breast Carcinoma, run by M.D. Anderson Cancer Center at 8 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record

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Trial summary

This clinical trial studies eliminating surgery and/or radiation therapy in treating breast cancer patients. In HER2 positive and triple negative breast cancers, after systemic therapy, when image-guided biopsy shows no residual cancer, patients then receive standard breast radiotherapy with no surgery. Read more about this study

Who is it for?
Ages 30 years and older, women only
What is being tested?
Undergo EBRT, Laboratory Biomarker Analysis and Quality-of-Life Assessment
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
120 participants
Where
8 sitesUnited States
Study dates
20 Jan 2017to 31 Jan 2028
Phase
Interventional

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 30 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
  • 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.
  • 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.
  • Patient desires breast conserving therapy.
  • 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].
Show all 37Show fewer
  • Female sex.
  • 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.
  • 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.
  • 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:
  • ER and/or PR positive, HER2 negative
  • Clinical stage T1N0M0, unicentric non-lobular breast cancer, no lymphovascular space invasion,
  • At least 40 years of age.
  • Oncotype ≤ 25 if age ≥ 50 years
  • Oncotype 0-20 and tumor size ≤ 1.5cm if age 40-49 years.
  • Patient agrees to take anti-estrogen therapy and is interested in breast conservation
  • Female sex.
  • 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.
  • 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:
  • 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.
  • 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.
  • Patient desires breast conserving therapy.
  • Age 30 years or older if HER2 positive. Age 50 or older if HER2 negative (triple negative).
  • Female sex.
  • 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.
  • 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.
  • Patient must have no evidence of residual invasive tumor or DCIS on pathologic review of the lumpectomy surgical specimen
  • 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.
  • 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

Who cannot join

  • 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.
  • Clinical or pathologic evidence for distant metastases.
  • Prior diagnosis of invasive or ductal carcinoma in situ breast cancer in the ipsilateral breast.
  • Clinical evidence of progression of disease \>20% in the breast or new evidence of nodal metastases.
  • Patient is known to be pregnant.
  • 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.

Trial locations and contacts

8 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Henry Kuerer contact

713-745-5043

hkuerer@mdanderson.org

8 sites in 1 country

United States8 sites, 6 recruiting

  • Carolinas Medical Center/Levine Cancer Institute

    Charlotte, North Carolina, 28203

    Richard L. White, 980-442-6358, Richard.White@atriumhealth.org

    Richard L. White

    Recruiting

  • MD Anderson Cancer Center - Banner

    Gilbert, Arizona, 85234

    Completed

  • Queen's Medical Center

    Honolulu, Hawaii, 96813

    Completed

  • M D Anderson Cancer Center

    Houston, Texas, 77030

    Henry M. Kuerer, 713-745-5043, hkuerer@mdanderson.org

    Henry M. Kuerer

    Recruiting

  • Baptist MD Anderson Cancer Center

    Jacksonville, Florida, 32207

    Laila Samiian, laila.samiian@bmcjax.com

    Beth A. Lesnikoski

    Recruiting

  • University of Pittsburgh Cancer Institute (UPCI)

    Pittsburgh, Pennsylvania, 15232

    Emilia J. Diego, 412-641-3083, diegoe@upmc.edu

    Emilia J. Diego

    Recruiting

  • Mayo Clinic

    Rochester, Minnesota, 55905

    Judy C. Boughey, 507-284-2511, boughey.judy@mayo.edu

    Judy C. Boughey

    Recruiting

  • Cooper Hospital Univ Med Ctr, MD Anderson at Cooper Voorhees

    Voorhees Township, New Jersey, 08103

    Catherine E. Loveland-Jones, 856-135-6207, loveland-jones-catherine@CooperHealth.edu

    Catherine E. Loveland-Jones

    Recruiting

Other trials in United States

About this study

This clinical trial studies eliminating surgery and/or radiation therapy in treating breast cancer patients. In HER2 positive and triple negative breast cancers, after systemic therapy, when image-guided biopsy shows no residual cancer, patients then receive standard breast radiotherapy with no surgery. In ER positive/HER2 negative breast cancers, after endocrine therapy and ablative radiotherapy, when image-guided biopsy shows no residual cancer, patients then receive standard endocrine therapy with no surgery. For patients who have HER2 positive and triple negative breast cancers and standard surgery, after systemic therapy, breast radiotherapy is being eliminated when the pathology from surgery shows no residual cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Cohort A1 and A2: To determine the 6 mo, 1, 2, 3, 5, 7, and 10 year biopsy confirmed ipsilateral breast tumor recurrence rate (IBTR, invasive and/or in situ) among patients who do not undergo surgery.

II. Cohort B: To determine the pCR rate 6 or 12 months after radiation therapy based on image-guided biopsy.

III. Cohort C: To determine the 6 mo, 1, 2, 3, 5, 7 and 10-year ipsilateral breast tumor recurrence rate among patients who undergo surgery alone without radiation.

SECONDARY OBJECTIVES:

  1. Cohort B: To determine the 6 mo, 1, 2, 3, 5, 7 and 10--year biopsy confirmed ipsilateral breast tumor recurrence rate (IBTR, invasive and/or in situ) among patients who do not undergo surgery.

II. 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.

III. To assess baseline, 6 months, 1, 3, 5, 7, and 10 years decisional comfort of clinical trial participation using the Decisional Regret Scale (DRS).

IV. 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, 5, 7, and 10 years.

  1. To determine the 6 mo, 1, 2, 3, 5, 7, and 10 years incidence of ipsilateral breast and nodal recommendation and performance of biopsy based on breast imaging follow-up.

VI. Correlate "liquid biopsy" analyses (after standard routine NST, 6 months and one year post-radiotherapy or surgery) among protocol participants with pCR, utilizing circulating tumor cells (CTCs) and circulating tumor-DNA (ctDNA).

VII. Among patients who decide to proceed with routine surgery, record the results of final biopsy compared with routine pathologic examination of surgery specimens.

VIII. To determine patient-reported quality of life using the FACT B+4 instrument at baseline, 6 months, 1, 3, 5, 7, and 10 years after treatment.

IX. To explore if radiation genomic sensitivity scores and Oncotype performed on the initial diagnostic core biopsy specimen correlate with pCR rates in Cohort B.

  1. 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.

XI. In Cohort B to determine the 3-year rate of tumor control/ progression free survival (PFS).

XII. In Cohort C/D 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.

XIII. In Cohorts A/B/C/D: To record 6 mo, 1, 2, 3, 5, 7, and 10 year breast cancer disease-free and overall survival.

XIV. In Cohort D: Correlate nanomechanical biomarker analyses with pCR and/or local recurrence in patients with triple negative or her-2 positive breast cancer treated with lumpectomy +/- radiation.

OUTLINE:

For Cohorts A, 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.

For Cohort B, patients will receive 3 months of neoadjuvant endocrine therapy, after which they will receive ablative partial breast irradiation over 5 fractions. Patients will then continue with endocrine therapy.

After completion of study treatment, patients are followed up every 6 months for 10 years.

Being tested
Undergo EBRT, Laboratory Biomarker Analysis, Quality-of-Life Assessment, Questionnaire Administration, Partial Breast Irradiation
Medical subject headings
Breast Neoplasms, Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Undergo EBRTRadiation

    Also called Definitive Radiation Therapy, SABR, External Beam Radiation Therapy, External Beam Radiotherapy

    Undergo EBRT

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • Questionnaire AdministrationOther

    Ancillary studies

  • Partial Breast IrradiationRadiation

    Undergo partial breast irradiation

Study groups in NCT02945579
Study groupRoleWhat they receive
Cohort AExperimental* 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.
Receives: Radiation: Undergo EBRT; Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Radiation: Partial Breast Irradiation
Cohort BExperimental• Neoadjuvant endocrine therapy for 3 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 5 fractions * Continued endocrine therapy for total of 5 years Biopsy 6-12months after radiation: if negative - additional endocrine therapy under the guidance of medical oncologist (skip breast surgery) * H\&P and Imaging every 6 months
Receives: Radiation: Undergo EBRT; Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Radiation: Partial Breast Irradiation
Cohort CExperimental* 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
Receives: Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Other: Questionnaire Administration
Cohort DExperimental* Optional biopsy for nanomechanical biomarker assessment * Chart review every year after surgery for 5 years * Eligible patients who have undergone the optional biopsy may later move to Cohort A or C if they meet all eligibility requirements and desire radiation omission.
Receives: Other: Questionnaire Administration

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Ipsilateral breast tumor recurrence-free survival (IBT-RFS)

    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.

    Measured: 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 10 years

  2. Overall survival

    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.

    Measured: Up to 10 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Oct 2016 (estimated)
  2. Study start20 Jan 2017
  3. Primary completion31 Jan 2028 (estimated)
  4. Study completion31 Jan 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
120 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02945579
Sponsor's protocol ID
2016-0046
Other IDs
NCI-2016-01929, 2016-0046
Status last verified
Sep 2026
First submitted
24 Oct 2016
Last updated
25 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Kuerer HM, Valero V, Smith BD, Krishnamurthy S, Diego EJ, Johnson HM, Lin H, Shen Y, Lucci A, Shaitelman SF, Mitchell MP, Boughey JC, White RL, Hunt KK, Yang WT, Rauch GM; Exceptional Responders Study Group. Selective Elimination of Breast Surgery for Invasive Breast Cancer: A Nonrandomized Clinical Trial. JAMA Oncol. 2025 May 1;11(5):529-534. doi: 10.1001/jamaoncol.2025.0207.

    PubMed 40152443

  • Johnson HM, Lin H, Shen Y, Diego EJ, Krishnamurthy S, Yang WT, Smith BD, Valero V, Lucci A, Sun SX, Shaitelman SF, Mitchell MP, Boughey JC, White RL, Rauch GM, Kuerer HM; Exceptional Responders Study Group. Patient-Reported Outcomes of Omission of Breast Surgery Following Neoadjuvant Systemic Therapy: A Nonrandomized Clinical Trial. JAMA Netw Open. 2023 Sep 5;6(9):e2333933. doi: 10.1001/jamanetworkopen.2023.33933.

    PubMed 37707811

  • Kuerer HM, Smith BD, Krishnamurthy S, Yang WT, Valero V, Shen Y, Lin H, Lucci A, Boughey JC, White RL, Diego EJ, Rauch GM; Exceptional Responders Clinical Trials Group. Eliminating breast surgery for invasive breast cancer in exceptional responders to neoadjuvant systemic therapy: a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2022 Dec;23(12):1517-1524. doi: 10.1016/S1470-2045(22)00613-1. Epub 2022 Oct 25.

    PubMed 36306810

  • Hariharan N, Rao TS, Rajappa S, Naidu CCK. Precision medicine - A new era in multidisciplinary care. Cancer Treat Res Commun. 2022;32:100577. doi: 10.1016/j.ctarc.2022.100577. Epub 2022 May 17. No abstract available.

    PubMed 35617923

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