Intestine Bacteria and Breast Cancer Risk
Condition: Breast Neoplasms
MeSH terms: Breast Neoplasms
Study type: Observational

Summary: 
      Background:

      - Some bacteria found in the large and small intestines help keep people healthy and aid
      digestion. They may also affect a person s risk of developing cancer. Researchers want to
      study the relationship between intestinal bacteria and breast cancer risk factors. They can
      do this by looking at stool and urine samples from postmenopausal women.

      Objectives:

      - To study intestinal bacteria and its relationship to urine-based markers of breast cancer
      risk in women.

      Eligibility:

      - Women between 55 and 69 years of age with a recent mammogram that showed no signs of
      cancer.

      Design:

        -  Participants will be screened with a medical history and basic health questionnaire.

        -  At home, participants will complete questionnaires about cancer risk factors and food
           consumption.

        -  Participants will also collect urine and stool samples. They will send the samples to
           the designated labs for study.

        -  No treatment will be provided as part of this protocol.
    

Detailed description: 
      Background/Significance: Commensal microbes (the microbiota), particularly in the gut, are
      required for human health and are postulated to affect cancer risk through several
      mechanisms. This proposed study builds upon a pilot within the NCI Division of Cancer
      Epidemiology and Genetics (DCEG) that identified highly acceptable methods for collecting
      fecal specimens and significant correlation between fecal microbial beta-glucuronidase
      activity and a marker of breast cancer risk, urine levels of estrogens. The proposed study
      will determine the correlation between levels of fecal enzyme activities and systemic
      estrogens in a random sample of postmenopausal women at Kaiser Permanente Colorado (KPCO).
      Demonstration of an association between the fecal microbiota and systemic estrogens would
      help to motivate future studies of how microbes affect cancer risk.

      Objectives: The main objective is to characterize the fecal microbiota and its association
      with levels of systemic estrogens among randomly sampled postmenopausal female members of a
      health maintenance organization (HMO). A secondary objective will determine the proportions
      of women who consent and then provide questionnaire data, a fecal specimen to characterize
      the microbiota, and a urine specimen to quantify systemic estrogens; and differences between
      participants (N=60) and non-participants. A third objective will determine whether
      consecutive, newly diagnosed postmenopausal breast cancer cases have similar participation
      rates, fecal microbiota characteristics and urine estrogen levels compared to the randomly
      sampled women.

      Methods: We will randomly sample from the KPCO population of approximately 50,000 women ages
      55-69 who have recently had a negative screening mammogram. An invitation packet (letter,
      information pamphlet, consent form, eligibility questionnaire, and opt-out postcard) will be
      sent in batches of 100, up to a maximum of 500 women. The consenting women will receive a
      second packet with a cancer risk-factor questionnaire, a link to the on-line Block brief food
      frequency questionnaire, and a specimen collection kit (with illustrated instructions) for
      collecting a fecal and urine specimen. Participants (minimum 60, maximum 80) will ship the
      specimens to the DCEG repository. As amended, consecutive newly diagnosed breast cancer cases
      (target N=60) will be enrolled in the oncology clinic prior to definitive surgery, with the
      same eligibility criteria as for the random sample. For contemporaneous controls,
      participants in the randomly sampled, mammogram-negative population will be recruited back
      (target N=60). Urine estrogens will be quantified by DCEG at NCI Frederick. Fecal microbial
      classification and enzymatic expression and activity will be performed at the University of
      Maryland Medical School (UMMS).

      Analyses: Data will be analyzed and summarized for publication with representatives from
      KPCO, DCEG and UMMS. Simple proportions will be used to estimate participation rates. Extant
      electronic records at KPCO will be used to compare participants to non-participants, overall
      and by pre-specified subgroups (5-year age groups, race/ethnicity, length of KPCO
      enrollment), with descriptive statistics and logistic regression. For the primary objective,
      fecal microbial 16S rRNA pyrosequences will be classified by phylogenetic and principal
      components analyses, while estrogen levels and Beta-glucuronidase RNA expression and
      enzymatic activity levels will be categorized using log standard deviations. The study will
      have 80% power to detect a 17% increase in estrogen level per 2.4-fold increase in
      glucuronidase activity and 80% power to detect a 3-fold case-control difference in
      above-median microbiome alpha diversity.
    

Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Probability Sample
Study population: 
        Examining fecal microbiota in women with breast cancer
      
Biospecimen description: 
      Feces and urine.
    
Keywords: Breast Cancer; Post Menopausal Estrogens; Fecal Microbes