Cytokine Expression During Radiation for Breast Cancer
18 Years
N/A
Female
Breast Cancer
Trial Information
Cytokine Expression During Radiation for Breast Cancer
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.(1-5) These differences in outcome persist even when controlling for
age, and stage at presentation.(1, 6, 7) 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.(5, 8) Controlling for
socioeconomic factors decreases the severity of these disparities, but it does not
completely explain them.(4) 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.(9) There has been substantial research linking some of these chemo/cytokines
(TNFα, PDGF, TGFβ, 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.(10) Blocking the receptor for PDGF appears to decrease
the metastatic potential of breast cancer cell lines.(11, 12) TGFβ inhibits T cell and B
cell lymphocytes and natural killer cell cytotoxicity.(13) This immuno-suppression has been
shown to promote tumor progression in mammary cancer cells lines.(13, 14) The ability of
TGFβ to promote tumor progression is so well recognized that it has become a therapeutic
target by some researchers.(15, 16) IFNγ has been shown to inhibit mammary cancer cell
proliferation and angiogenesis in vitro and in vivo.(17) 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.(18) Additionally, researchers have
directly correlated increased levels of IL-6 with the development and progression of breast
cancer, and decreased overall survival (OAS).(19) Conclusion: Expression of certain
chemokines and cytokines is associated with development and progression of breast cancer.
Inclusion Criteria
- Patient must be 18 years of age or older
- Patients must have histologically confirmed (by routine H&E staining) adenocarcinoma
of the breast any T or N No M disease Patients with squamous carcinomas or sarcomas
of the breast cancer are NOT eligible
- Patients must have undergone a segmental mastectomy SM with a level I and ll axillary
dissection or sentinel lymph node biopsy Surgical margins at time of local surgery
must be negative greater or equal to 2mm for both invasive carcinoma and for
non-invasive ductal carcinoma Patients who have post-operative margins which are
negative but less than 2mm will be considered eligible if the surgeon states that the
margin in question cannot be improved. Patients treated with a mastectomy are NOT
eligible
- Patients must be registered such that radiation therapy begins within 10 weeks of
last surgery
- Patients must have a performance status 0 or 1 by ECOG criteria or a 80-100 Karnofsky
Performance Scale at time of consult
- Patients must not have received prior radiation therapy to the breast at any time for
any reason
- Any patient with active local-regional disease prior to registration is not eligible
- No other prior malignancy is allowed except for adequately treated basal cell or
squamous cell skin cancer, in situ cervical cancer, or any other cancer from which
the patient has been disease-free for at least 5 years
- Patients must not be pregnant due to the potential for fetal harm as a result of this
treatment regimen. Women of child-bearing potential must use effective non hormonal
contraception while undergoing radiation therapy
- Patients must not have a serious medical or psychiatric illness which prevents
informed consent or compliance with treatment
- All patients must be informed of the investigational nature of this study and give
written informed consent in accordance with institutional and federal guidelines
- Women of all races and ethnic groups are eligible for this trial
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention
Outcome Measure:
To systematically and quantitatively assess the magnitude and frequency (increases/decreases) of changes in chemo/cytokine (TNFα, PDGF, TGFβ, IL-1, IL-6, IL-8) expression in women receiving radiation therapy for breast cancer.
Outcome Time Frame:
7 years
Safety Issue:
No
Principal Investigator
Richard Zellars, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
The Johns Hopkins University School of Medicine
Authority:
United States: Institutional Review Board
Study ID:
J08130
NCT ID:
NCT00836186
Start Date:
March 2009
Completion Date:
March 2016
Related Keywords:
- Breast Cancer
- Breast Neoplasms
Name | Location |
|---|---|
| The Johns Hopkins University School of Medicne | Baltimore, Maryland 21231 |
