Genetic Susceptibility to Radiation-Induced Skin Reactions in Racial/Ethnic Groups of Patients With Breast Cancer

Breast Cancer Clinical Trial

Official title:

Impact of Genomics and Exposures on Disparities in Breast Cancer Radiosensitivity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01407770
• Other study ID #: IRB00011809
• Secondary ID: U10CA081851REBAC
• Status: Completed
• Start date: September 20, 2011
• Est. completion date: August 26, 2014

Study information

• Verified date: March 2023
• Source: Wake Forest University Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

RATIONALE: Radiation therapy uses high-energy x rays to kill tumor cells. Radiation therapy may cause skin reactions when patients are exposed to high-energy x rays. Studying the genetic pattern of patients before and after radiation therapy may help doctors prevent toxicity and plan the best treatment.

PURPOSE: This clinical trial studies genetic susceptibility to radiation-induced skin reactions in racial/ethnic groups of patients with breast cancer.

Description:

OBJECTIVES:

• To develop and validate prediction biomarkers for radiation therapy (RT)-induced acute and chronic skin reactions and quality of life in five racial/ethnic groups of breast cancer patients, Whites*, Black/African Americans, Hispanic/Latinos, Asians/Native Hawaiians/Pacific Islanders, and American Indians/Alaskan Natives. NOTE: *This stratum is closed as of April 25, 2012.

• To develop polygenic models of RT-induced skin reactions with a comprehensive evaluation of genome-wide nonsynonymous single nucleotide polymorphisms (nsSNPs).

• To evaluate the levels of DNA damage (Comet assay) and radiosensitivity (Cell Cycle G2 Delay assay) in lymphocytes before and after RT.

• To test the effect of gene-gene and gene-smoking interactions on RT-induced skin reactions.

• To assess race-ethnic differences in RT-induced skin reactions, DNA damage, and radiosensitivity and to determine if the gene effects are consistent across race-ethnicity (gene-race/ethnic interactions).

OUTLINE: This is a multicenter study. Patients are stratified according to race/ethnicity (Whites* vs Black/African Americans vs Hispanic/Latinos vs Asians/Native Hawaiians/Pacific Islanders vs American Indians/Alaskan Natives). NOTE: *This stratum is closed as of April 25, 2012.

Patients undergo adjuvant radiotherapy after breast-conserving surgery.

Blood and urine samples are collected at baseline and last day of radiotherapy for genotyping, DNA damage, cell cycle assays, urine cotinine, inflammatory immune response biomarkers, and tumor-killing activity by BeadArray System, Comet assay, flow cytometry-based assay, Cell-Cycle G2 Delay Assay, Oxygen Radical Absorbance Capacity (ORAC) assay, and ELISA.

Patients are assessed for acute toxicity by research staff using the ONS Criteria for Radiation-Induced Acute Skin Toxicity at baseline, week 3, and at 1 and 2 months after radiotherapy. Patients are also assessed for chronic toxicity by research staff using the Chronic skin toxicity questionnaire (RTOG SOMA Criteria for RT- Induced Breast/Chest Wall Late Skin Toxicity) at 6 and 12 months after completion of radiotherapy. Photographs of the breast, chest wall, and contralateral breast are also taken at baseline, week 3, last day of radiotherapy, and at 1, 2, 6, and 12 months after completion of radiotherapy.

Patients complete the Breast Cancer Risk Study Questionnaire, the Functional Assessment of Cancer Therapy Breast (FACT-B), the Modified Skindex, and the B39 Quality-of-Life (QOL) Questionnaire at baseline, last day of radiotherapy, and at 1, 2, 6, and 12 months after radiotherapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1000
• Est. completion date: August 26, 2014
• Est. primary completion date: August 26, 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Female patients newly diagnosed with breast carcinoma including ductal carcinoma in situ (DCIS)

• Stage 0-IIIA disease

• Status post-lumpectomy, -quadrantectomy, or -mastectomy

• Plan to receive adjuvant radiation to the whole breast or chest wall and/or regional lymph nodes

• No sites that cannot send blood/urine specimens to Wake Forest by overnight (next day) express shipping

PATIENT CHARACTERISTICS:

• *This stratum is closed as of April 25, 2012.

• No patients who do not understand English and are unable to complete form with assistance

PRIOR CONCURRENT THERAPY:

• Total dose > 40 Gy, dose per fraction > 1.8 - 2.0 Gy, use of 2D, 3D-conformal, or intensity-modulated radiation therapy (IMRT) treatment techniques allowed; a daily fraction of 2.7 Gy to the whole breast is suggested for hypofractionated regimens

• Concurrent and sequential boost techniques are allowed for both standard and hypofractionated regimens

• Adjuvant hormonal therapy will be allowed prior to, during, and/or after radiotherapy (RT) at the discretion of a medical oncologist

• Targeted therapies, such as Herceptin, will be allowed prior to, during, and/or after RT at the discretion of the medical oncologist

• No prior radiation to the involved breast or chest wall

• No concurrent chemotherapy

• No patients who underwent breast reconstruction following mastectomy

• Placement of tissue expanders and implants are not allowed

• No patients who have undergone MammoSite® or any other form of brachytherapy as well as those who will be treated with skin-sparing IMRT

• Patients may not be concurrently enrolled in a protocol that involves treatment of the skin, i.e., applying lotions/moisturizers

• Protocols that do not involve treatment of the skin are allowed

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Cognitive Ability, General
• Fatigue
• Pain
• Psychosocial Deprivation
• Radiation Toxicity
• Skin Abnormalities

Intervention

Genetic:
• DNA analysis
Genetic
• gene expression analysis
Genetic

Other:
• enzyme-linked immunosorbent assay
Genetic
• flow cytometry
Genetic
• laboratory biomarker analysis
Genetic
• questionnaire administration
Genetic

Procedure:
• adjuvant therapy
Genetic
• assessment of therapy complications
Genetic
• quality-of-life assessment
Genetic

Radiation:
• 3-dimensional conformal radiation therapy
Genetic
• breast irradiation
Genetic
• external beam radiation therapy
Genetic
• hypofractionated radiation therapy
Genetic
• intensity-modulated radiation therapy
Genetic
• whole breast irradiation
Genetic

Locations

Country	Name	City	State
United States	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Hu JJ, Urbanic JJ, Case LD, Takita C, Wright JL, Brown DR, Langefeld CD, Lively MO, Mitchell SE, Thakrar A, Bryant D, Baglan K, Strasser J, Baez-Diaz L, Lesser GJ, Shaw EG. Association Between Inflammatory Biomarker C-Reactive Protein and Radiotherapy-Induced Early Adverse Skin Reactions in a Multiracial/Ethnic Breast Cancer Population. J Clin Oncol. 2018 Aug 20;36(24):2473-2482. doi: 10.1200/JCO.2017.77.1790. Epub 2018 Jul 10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of RT-induced early adverse skin reaction (EASR)	The primary endpoint is RT-related skin reactions which for consistency and clarity across the study we will use the term "Early Adverse Skin Reaction" (EASR). Skin reactions will be assessed at 4 time points from the start of radiotherapy through 2 months of the post radiotherapy follow-up period. The Modified ONS Criteria for Radiation-Induced Acute Skin Toxicity will be used for classification of EASRs related to the skin. The primary outcome variable will be the occurrence (or not) of RT-induced EASR defined as a grade 4 or higher toxicity (based on the ONS criteria) during the 2 months of the follow-up period of the study.	2 months
Secondary	Quality of life as measured by FACT-B	Quality of life will be assessed using the FACT-B, a modification of the Skindex-16, and a modified version of the NSABP B39 Quality of Life metric.	12 months