Clinical trial NCT01407770: Genetic Susceptibility to Radiation-Induced Skin Reactions in Racial/Ethnic Groups of Patients With Breast Cancer
Official title: Impact of Genomics and Exposures on Disparities in Breast Cancer Radiosensitivity
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Breast Cancer
Cognitive Ability, General
Fatigue
Pain
Psychosocial Deprivation
Radiation Toxicity
Skin Abnormalities
Keywords: radiation toxicity
skin reactions secondary to radiation therapy
pain
fatigue
psychosocial effects of cancer and its treatment
depression
cognitive/functional effects
stage IA breast cancer
stage IB breast cancer
stage II breast cancer
stage IIIA breast cancer
ductal breast carcinoma in situ
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2011-08-02
Enrollment: 1000
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Race/ethnicity to include Whites\*, Black/African Americans (AA), Hispanic/Latinos, Asians/Native Hawaiians/Pacific Islanders, and Native American or Alaskan

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Occurrence of RT-induced early adverse skin reaction (EASR)
timeFrame: 2 months
Secondary outcomes:
measure: Quality of life as measured by FACT-B
timeFrame: 12 months
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest University Comprehensive Cancer Center
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: James J. Urbanic, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.