Hypofractionated Radiation Therapy or Standard Radiation Therapy in Treating Patients With Ductal Breast Carcinoma In Situ or Early Invasive Breast Cancer

NCT ID: NCT01266642

Last Updated: 2025-08-17

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 301 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-02-08
• Study Completion Date: 2025-11-30

Brief Summary

This randomized phase II trial studies how well hypofractionated radiation therapy (RT) works compared to standard RT in treating patients with ductal breast carcinoma in situ (DCIS) or early invasive breast cancer. Radiation therapy (RT) uses high energy x-rays to kill tumor cells. Giving higher doses of RT over a shorter period of time may kill more tumor cells and have fewer side effects. It is not yet known if hypofractionated RT is more effective than standard RT in treating breast cancer.

Detailed Description

PRIMARY OBJECTIVES:

I. To compare patient-reported cosmetic outcome at 3 years using the Breast Cancer Treatment Outcomes Scale (BCTOS) for patients assigned to hypofractionated whole breast irradiation (HF-WBI) versus conventionally fractionated whole breast irradiation (CF-WBI).

SECONDARY OBJECTIVES:

I. To determine patient-reported cosmetic outcome using the BCTOS at 6 months, 1, 2, 4, and 5 years.

II. To determine physician-rated cosmetic outcome at 6 months, 1, 2, 3, 4, and 5 years using the Radiation Therapy and Oncology Group (RTOG) scale for physician assessment.

III. To determine the level of agreement between patient-rated cosmetic outcome and physician-rated cosmetic outcome at the various time points assessed.

IV. To determine the 5-year and risk of pathologically-confirmed invasive and/or in situ ipsilateral breast tumor recurrence (IBTR) for patients with ductal carcinoma in situ (DCIS) and early invasive breast cancer.

V. To determine patient-reported functional status and breast pain using the BCTOS at 6 months, 1, 2, 3, 4, and 5 years after treatment.

VI. To determine maximal acute (within 6 weeks of treatment) and late (more than 6 weeks after treatment) skin and soft tissue toxicities using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0 scale.

VII. To determine the relationship between the volume of breast tissue receiving excessive dose (defined as greater than 105% of the prescription dose) and the risk of adverse cosmesis.

VIII. To determine the relationship between bra cup size and the risk of adverse cosmesis.

IX. To determine whether there is a statistical interaction between breast volume and volume of tissue receiving greater than 105% of the prescription dose in predicting adverse cosmesis.

X. To determine in an exploratory analysis whether any other demographic, clinical, and pathologic factors correlate with risk of adverse cosmesis, quality of life, body image, image investment, and risk of IBTR.

XI. To determine if the C-509T variant allele of transforming growth factor-beta (TGF-beta) is associated with an increased risk of grade 2 or higher fibrosis (as determined by the Subjective, Objective, Medical Management, Analytic [SOMA] scale) three years after completion of radiation.

XII. To compare the cost of radiation for patients treated on the two treatment arms.

XIII. To compare patient quality of life, body image, and appearance investment for the two treatment arms using the Functional Assessment of Cancer Therapy-Breast (FACT-B), Appearance Schemas Inventory-Revised (ASI-R), and Body Image Scale, respectively.

XIV. To contribute additional blood samples to protocol LAB02-086 which is a case-control study investigating deoxyribonucleic acid (DNA) repair phenotypes and genotypes in breast cancer.

XV. To assess the psychometric profile of the Functional Assessment of Cancer Therapy-Breast (FACT-B) version 4 in collaboration with investigators from the Department of Medical Social Science, Northwestern University Feinberg School of Medicine.

XVI. To determine the influence of oncoplastic lumpectomy on the following outcomes: physician- and patient-reported cosmetic outcomes, other patient-reported health-related quality of life outcomes, and photographic measurements of breast cosmetic outcome.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients undergo HF-WBI comprising external beam RT 5 days a week for approximately 3 weeks.

ARM II: Patients undergo CF-WBI comprising external beam RT 5 days a week for approximately 5 weeks.

After completion of study treatment, patients are followed up at 6 months and then annually for 5 years.

Conditions

Ductal Breast Carcinoma In Situ; Invasive Breast Carcinoma; Stage I Breast Cancer AJCC v6; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage II Breast Cancer AJCC v6 and v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I (HF-WBI)

Patients undergo HF-WBI comprising external beam RT 5 days a week for approximately 3 weeks.

Group Type: EXPERIMENTAL

External Beam Radiation Therapy

Intervention Type: RADIATION

Undergo HF-WBI

Hypofractionated Radiation Therapy

Intervention Type: RADIATION

Undergo HF-WBI

Laboratory Biomarker Analysis

Intervention Type: OTHER

Optional correlative studies

Quality-of-Life Assessment

Intervention Type: OTHER

Ancillary studies

Questionnaire Administration

Intervention Type: OTHER

Ancillary studies

Whole Breast Irradiation

Intervention Type: RADIATION

Undergo HF-WBI

Arm II (CF-WBI)

Patients undergo CF-WBI comprising external beam RT 5 days a week for approximately 5 weeks.

Group Type: ACTIVE_COMPARATOR

External Beam Radiation Therapy

Intervention Type: RADIATION

Undergo CF-WBI

Laboratory Biomarker Analysis

Intervention Type: OTHER

Optional correlative studies

Quality-of-Life Assessment

Intervention Type: OTHER

Ancillary studies

Questionnaire Administration

Intervention Type: OTHER

Ancillary studies

Whole Breast Irradiation

Intervention Type: RADIATION

Undergo CF-WBI

Interventions

External Beam Radiation Therapy

Undergo HF-WBI

Intervention Type: RADIATION

External Beam Radiation Therapy

Undergo CF-WBI

Intervention Type: RADIATION

Hypofractionated Radiation Therapy

Undergo HF-WBI

Intervention Type: RADIATION

Laboratory Biomarker Analysis

Optional correlative studies

Intervention Type: OTHER

Quality-of-Life Assessment

Ancillary studies

Intervention Type: OTHER

Questionnaire Administration

Ancillary studies

Intervention Type: OTHER

Whole Breast Irradiation

Undergo HF-WBI

Intervention Type: RADIATION

Whole Breast Irradiation

Undergo CF-WBI

Intervention Type: RADIATION

Other Intervention Names

Definitive Radiation Therapy; EBRT; External Beam Radiation; External Beam Radiotherapy; External Beam RT; external radiation; External Radiation Therapy; external-beam radiation; Radiation, External Beam; Definitive Radiation Therapy; EBRT; External Beam Radiation; External Beam Radiotherapy; External Beam RT; external radiation; External Radiation Therapy; external-beam radiation; Radiation, External Beam; Hypofractionated Radiotherapy; hypofractionation; Quality of Life Assessment

Eligibility Criteria

Inclusion Criteria

• Pathologically confirmed ductal carcinoma in situ of the breast or early invasive breast cancer defined as pathologic stage Tis, T1, or T2, N0, N1mic, or N1a (pathologic staging of the axilla is required for all patients with invasive disease but is not required for patients with ductal carcinoma in situ [DCIS] only); (upfront pathologic stage cannot be assigned to patients treated with neoadjuvant chemotherapy; for such patients, the criteria for pathologic stage shall be applied to the initial clinical stage)
• Treatment with breast conserving surgery
• Final surgical margins must be negative, defined as no evidence for ductal carcinoma in situ or invasive breast cancer touching the inked surgical margin; if the invasive or in situ breast cancer approaches within less than 1 mm of the final surgical margin, then a re-excision is strongly encouraged; lobular carcinoma in situ at the final surgical margin will be disregarded
• 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.
• Female sex.
• Attending radiation oncologist declares intention to treat the whole breast only and that a third radiation field to treat regional lymph nodes is not planned (radiation of the undissected level I/II axilla with high tangents is allowed)
• 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
• Patients must be enrolled on the trial within 12 weeks of the later of two dates: the final breast conserving surgical procedure or administration of the last cycle of concurrent cytotoxic chemotherapy

Exclusion Criteria

• Pathologic or clinical evidence for a stage T3 or T4 breast cancer
• Pathologic evidence for involvement of 4 or more axillary lymph nodes, or imaging evidence of involvement of infraclavicular, supraclavicular, or internal mammary lymph nodes
• Clinical or pathologic evidence for distant metastases
• Any prior diagnosis of invasive or ductal carcinoma in situ breast cancer in either breast
• Current diagnosis of bilateral breast cancer
• History of therapeutic irradiation to the breast, lower neck, mediastinum or other area in which there could potentially be overlap with the affected breast
• Patients not fluent in English or Spanish (The BCTOS will be available in these two languages)
• Patient is pregnant

• Minimum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Benjamin D Smith

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

UF Cancer Center at Orlando Health

Orlando, Florida, United States

MD Anderson in The Woodlands

Conroe, Texas, United States

M D Anderson Cancer Center

Houston, Texas, United States

MD Anderson West Houston

Houston, Texas, United States

MD Anderson League City

League City, Texas, United States

MD Anderson in Sugar Land

Sugar Land, Texas, United States

Countries

United States

References

Weng JK, Lei X, Schlembach P, Bloom ES, Shaitelman SF, Arzu IY, Chronowski G, Dvorak T, Grade E, Hoffman K, Perkins G, Reed VK, Shah SJ, Stauder MC, Strom EA, Tereffe W, Woodward WA, Hortobagyi GN, Hunt KK, Buchholz TA, Smith BD. Five-Year Longitudinal Analysis of Patient-Reported Outcomes and Cosmesis in a Randomized Trial of Conventionally Fractionated Versus Hypofractionated Whole-Breast Irradiation. Int J Radiat Oncol Biol Phys. 2021 Oct 1;111(2):360-370. doi: 10.1016/j.ijrobp.2021.05.004. Epub 2021 May 13.

Reference Type: DERIVED

PMID: 33992718 (View on PubMed)

Grossberg AJ, Lei X, Xu T, Shaitelman SF, Hoffman KE, Bloom ES, Stauder MC, Tereffe W, Schlembach PJ, Woodward WA, Buchholz TA, Smith BD. Association of Transforming Growth Factor beta Polymorphism C-509T With Radiation-Induced Fibrosis Among Patients With Early-Stage Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial. JAMA Oncol. 2018 Dec 1;4(12):1751-1757. doi: 10.1001/jamaoncol.2018.2583.

Reference Type: DERIVED

PMID: 30027292 (View on PubMed)

Shaitelman SF, Schlembach PJ, Arzu I, Ballo M, Bloom ES, Buchholz D, Chronowski GM, Dvorak T, Grade E, Hoffman KE, Kelly P, Ludwig M, Perkins GH, Reed V, Shah S, Stauder MC, Strom EA, Tereffe W, Woodward WA, Ensor J, Baumann D, Thompson AM, Amaya D, Davis T, Guerra W, Hamblin L, Hortobagyi G, Hunt KK, Buchholz TA, Smith BD. Acute and Short-term Toxic Effects of Conventionally Fractionated vs Hypofractionated Whole-Breast Irradiation: A Randomized Clinical Trial. JAMA Oncol. 2015 Oct;1(7):931-41. doi: 10.1001/jamaoncol.2015.2666.

Reference Type: DERIVED

PMID: 26247543 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://www.mdanderson.org

University of Texas MD Anderson Cancer Center Website

Other Identifiers

NCI-2011-00253

Identifier Type: REGISTRY

Identifier Source: secondary_id

2010-0559

Identifier Type: OTHER

Identifier Source: secondary_id

2010-0559

Identifier Type: -

Identifier Source: org_study_id