Cytokine Expression During Radiation for Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Study type: Interventional

Summary: 
      To assess the magnitude and frequency of changes in chemo/cytokine expression in women
      receiving radiation treatment. To asses the impact of race/ethnicity on the magnitude and
      frequency of changes in chemo/cytokine expression during radiation therapy for breast cancer.
      And finally to assess the interaction between radiation-induced chemo/cytokine expression
      changes, and race/ethnicity, with respect to normal tissue reactions to radiation and
      tumor-associated outcomes.
    

Detailed description: 
      It is well recognized that the diagnostic and therapeutic gains made in the management of
      breast cancer over the last 2 decades are not fully realized by all groups. African American
      women with breast cancer have greater risk of recurrence, shorter overall survival, shorter
      survival after relapse, worse toxicity and worse cosmetic outcome than their Caucasian
      counterparts. These differences in outcome persist even when controlling for age, and stage
      at presentation. Being similarly treated with modern breast conserving therapy (lumpectomy
      and adjuvant whole breast irradiation) at recognized centers of excellence does little to
      alleviate the disparities in outcomes. Controlling for socioeconomic factors decreases the
      severity of these disparities, but it does not completely explain them. Theories abound as to
      the cause of outcome inequality. Many of these theories take either a psychosocial, or
      biologic bent. One potential biologic cause may be chemokine and cytokine expression.

      Chemokines and cytokines (chemo/cytokines) are proteins and peptides used for cell signaling.
      Primarily secreted by T cells and macrophages, they influence cellular activation,
      differentiation, and function and act as mediators for inflammatory and immune responses.
      There has been substantial research linking some of these chemo/cytokines [Tumor necrosis
      factor alpha (TNFα), platelet derived growth factor (PDGF), Transforming growth factor beta
      (TGFβ), interleukin (IL)-6,and IL-8] to tumor promotion and progression. For example, TNFα
      has been linked to greater cell survival despite genomic injury which in turn leads to
      greater genetic alterations and malignant transformation. TNFα has been associated with
      breast cancer progression and metastases. Blocking the receptor for PDGF appears to decrease
      the metastatic potential of breast cancer cell lines. TGFβ inhibits T cell and B cell
      lymphocytes and natural killer cell cytotoxicity. This immuno-suppression has been shown to
      promote tumor progression in mammary cancer cells lines. The ability of TGFβ to promote tumor
      progression is so well recognized that it has become a therapeutic target by some
      researchers. Interferon gamma (IFNγ) has been shown to inhibit mammary cancer cell
      proliferation and angiogenesis in vitro and in vivo. Clinically, Lyon et al reported
      significantly higher circulating levels of TNFα, IL-6, and IL-8 in women with breast cancer
      compared to women with a negative breast biopsy. Additionally, researchers have directly
      correlated increased levels of IL-6 with the development and progression of breast cancer,
      and decreased overall survival (OAS). Conclusion: Expression of certain chemokines and
      cytokines is associated with development and progression of breast cancer.
    

Intervention name(s): Radiation therapy
Intervention type(s): Radiation
Intervention description(s): Patients will receive whole breast radiation therapy at a dose of 180-200 centigray (cGy) per fraction for 23-27 fractions to a total dose of 4600 - 4860 cGy. Additional radiation to the lumpectomy bed (Boost) is at the discretion of the treating physician. The total dose to the tumor bed cannot exceed 6600 cGy.
Intervention model: Single Group Assignment
Intervention model description: This is a prospective study designed to analyze tumor markers and pathologic data in order to examine the prediction of tumor response to radiation therapy.
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Cytokine; Tumor Marker; Disparities