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

Phase 2

Active, not recruiting

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

Interventions: Radiation: External Beam Radiation Therapy
Radiation: Hypofractionated Radiation Therapy
Other: Laboratory Biomarker Analysis
Other: Quality-of-Life Assessment
Other: Questionnaire Administration
Radiation: Whole Breast Irradiation

Registration Number: NCT01266642

Lead Sponsor: M.D. Anderson Cancer Center

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.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: Female

Target Recruitment: 301

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (HF-WBI)	Hypofractionated Radiation Therapy	Patients undergo HF-WBI comprising external beam RT 5 days a week for approximately 3 weeks.
Arm I (HF-WBI)	Quality-of-Life Assessment	Patients undergo HF-WBI comprising external beam RT 5 days a week for approximately 3 weeks.
Arm I (HF-WBI)	Questionnaire Administration	Patients undergo HF-WBI comprising external beam RT 5 days a week for approximately 3 weeks.
Arm I (HF-WBI)	External Beam Radiation Therapy	Patients undergo HF-WBI comprising external beam RT 5 days a week for approximately 3 weeks.
Arm II (CF-WBI)	Whole Breast Irradiation	Patients undergo CF-WBI comprising external beam RT 5 days a week for approximately 5 weeks.
Arm I (HF-WBI)	Laboratory Biomarker Analysis	Patients undergo HF-WBI comprising external beam RT 5 days a week for approximately 3 weeks.
Arm II (CF-WBI)	Quality-of-Life Assessment	Patients undergo CF-WBI comprising external beam RT 5 days a week for approximately 5 weeks.
Arm I (HF-WBI)	Whole Breast Irradiation	Patients undergo HF-WBI comprising external beam RT 5 days a week for approximately 3 weeks.
Arm II (CF-WBI)	Laboratory Biomarker Analysis	Patients undergo CF-WBI comprising external beam RT 5 days a week for approximately 5 weeks.
Arm II (CF-WBI)	External Beam Radiation Therapy	Patients undergo CF-WBI comprising external beam RT 5 days a week for approximately 5 weeks.
Arm II (CF-WBI)	Questionnaire Administration	Patients undergo CF-WBI comprising external beam RT 5 days a week for approximately 5 weeks.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Scores of Either <2.5 or >=2.5 on the Breast Cancer Treatment Outcome Scale (BCTOS) Cosmesis	3 years after completing radiation therapy	BCTOS cosmesis score range from 1 to 4, and scores of 2.5 or more indicate adverse cosmetic outcomes.

Secondary Outcome Measures

Name	Time	Method
Panel Physicians Rated Cosmesis	3 years after completing radiation therapy.	A group of three attending physicians blinded to the treatment scored the photographs using the Radiation Therapy and Oncology Group (RTOG) criteria. RTOG scale range from 1 (excellent), 2 (good), 3 (fair), and 4 (poor).

Trial Locations

Locations (7): Banner MD Anderson Cancer Center
🇺🇸
Gilbert, Arizona, United States
M D Anderson Cancer Center
🇺🇸
Houston, Texas, United States
MD Anderson West Houston
🇺🇸
Houston, Texas, United States
UF Cancer Center at Orlando Health
🇺🇸
Orlando, Florida, United States
MD Anderson in Sugar Land
🇺🇸
Sugar Land, Texas, United States
MD Anderson in The Woodlands
🇺🇸
Conroe, Texas, United States
MD Anderson League City
🇺🇸
League City, Texas, United States