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Changes in Breast Density and Blood Hormone Levels in Postmenopausal Women Receiving Anastrozole or Exemestane for Breast Cancer

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2008 by National Cancer Institute (NCI).
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00516698
First received: August 14, 2007
Last updated: May 9, 2009
Last verified: November 2008
  Purpose

RATIONALE: Studying changes in breast density and blood hormone levels in women receiving anastrozole or exemestane for breast cancer may help doctors learn more about the long-term effects of treatment and may help the study of breast cancer in the future.

PURPOSE: This clinical trial is studying changes in breast density and blood hormone levels in postmenopausal women receiving anastrozole or exemestane for breast cancer.


Condition Intervention
Breast Cancer
Drug: anastrozole
Drug: exemestane
Genetic: polymorphism analysis
Other: high performance liquid chromatography
Other: laboratory biomarker analysis
Other: pharmacological study
Procedure: adjuvant therapy
Procedure: radiomammography

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: Changes in Breast Density and Plasma Hormone Levels After One Year of Aromatase Inhibitor Therapy

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Changes in percent breast density in response to 1 year of aromatase inhibitor therapy [ Designated as safety issue: No ]
  • Changes in dense area in response to 1 year of aromatase inhibitor therapy [ Designated as safety issue: No ]
  • Correlation of changes in percent breast density with changes in plasma hormone levels and drug levels [ Designated as safety issue: No ]
  • Correlation of changes in dense area with changes in plasma hormone levels and drug levels [ Designated as safety issue: No ]
  • Comparison of percent breast density in women with high pre-treatment percent density vs women with low pre-treatment percent density [ Designated as safety issue: No ]
  • Comparison of dense area in women with high pre-treatment dense area vs women with low pre-treatment dense area [ Designated as safety issue: No ]
  • Associations of haplotype-tagged single nucleotide polymorphisms in genes in the aromatase pathway with changes in percent and area density, plasma hormone levels, and drug levels after 1 year of aromatase inhibitor therapy [ Designated as safety issue: No ]

Estimated Enrollment: 500
Study Start Date: September 2007
Detailed Description:

OBJECTIVES:

  • To assess the changes in percent breast density (in response to 1 year of aromatase inhibitor therapy) from levels prior to the initiation of treatment.
  • To assess the changes in dense area (in response to 1 year of aromatase inhibitor therapy) from levels prior to the initiation of treatment.
  • To examine whether changes in percent breast density (in response to 1 year of aromatase inhibitor therapy) from pre-treatment levels correlate with changes in plasma hormone levels (estrone, estrone-sulfate, estradiol, and SHBG) and drug levels (anastrozole or exemestane) over the same time period.
  • To examine whether changes in dense area (in response to 1 year of aromatase inhibitor therapy) from pre-treatment mammogram correlate with changes in plasma hormone levels (estrone, estrone-sulfate, estradiol, and SHBG) and drug levels (anastrozole or exemestane) over the same time period.
  • To assess whether women with high pre-treatment percent density (upper tertile) experience greater decreases in percent breast density after 1 year of aromatase inhibitor therapy than women with low pre-treatment percent density (lower tertile).
  • To assess whether women with high pre-treatment dense area (upper tertile) experience greater decreases in dense area after 1 year of aromatase inhibitor therapy than women with low pre-treatment dense area (lower tertile).
  • To examine the associations of haplotype-tagged single nucleotide polymorphisms in genes in the aromatase pathway identified through the Mayo Clinic and Indiana University Pharmacogenomics Research Network Projects, with changes in percent and area density, plasma hormone levels, and drug levels after 1 year of aromatase inhibitor therapy.

OUTLINE: This is a multicenter study.

Patients undergo blood sample collection at baseline and at 1 year after initiation of aromatase inhibitor therapy (anastrozole or exemestane). Samples are analyzed for estrogen and testosterone levels and additional hormone levels and growth factors that have been previously linked with breast density and that could be altered by aromatase inhibitor use (i.e., sex hormone-binding globulin [SHBG], DHEA, DHEA sulfate, progesterone, prolactin, insulin-like growth factor-1 [IGF-1], and insulin-like growth factor binding protein 3 [IGF BP3]). Samples are also analyzed for anastrozole and exemestane levels by HPLC. Pharmacogenetic studies are also performed. Haplotype-tagged single nucleotide polymorphisms in genes in the aromatase pathway are examined.

Patients also undergo mammogram at baseline (≤ 6 months prior to study registration) and at 1 year after initiation of aromatase inhibitor therapy.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

Inclusion criteria:

  • Must have histologically confirmed invasive breast cancer, as defined by the following TNM staging criteria:

    • pT1, pT2, or pT3
    • pNx, pN0, pN1, pN2, or pN3*

      • Patients with positive sentinel node biopsies (pN1) must have subsequent axillary dissection to be eligible
      • Patients with negative sentinel node biopsies (pN0) do not require axillary surgery for study eligibility
    • M0, according to the following radiologic studies:

      • Bone scan (required only if alkaline phosphatase is > 2 x institutional upper limit of normal [ULN] and/or there are symptoms of metastatic disease)

        • A confirmatory x-ray or other imaging study, such as CT scan or MRI, is required if the results from the bone scan are questionable
      • Abdominal ultrasound or CT scan of the abdomen (required only if AST/ALT or alkaline phosphatase is > 2 x ULN unless the elevation is in the bone fraction)
      • Chest x-ray NOTE: *Only when the sole basis for this classification is the presence of 10 or more involved axillary nodes
  • Completely resected disease

    • Surgical margins must be clear of invasive carcinoma and ductal carcinoma in situ or lobular carcinoma in situ
  • Must have one intact, noncancerous breast with no history of previous breast surgery in that breast (other than a breast biopsy)

    • Mammogram of the intact, noncancerous breast required ≤ 6 months prior to study registration (both a craniocaudal [top down] and mediolateral oblique view [side view] must be available)
  • Must be registered on this study ≥ 3 weeks but ≤ 3 months after completion of chemotherapy OR primary surgery*

    • Adjuvant chemotherapy and radiation therapy as prescribed by the local institution is allowed provided patient is registered on this study and hormonal treatment is begun as soon as patient has sufficiently recovered from chemotherapy NOTE: *Primary surgery is defined as the last surgical procedure to remove invasive or in situ disease
  • Planning to receive anastrozole or exemestane for ≥ 1 year for treatment of breast cancer
  • Hormone receptor status:

    • Estrogen receptor- and/or progesterone receptor-positive (defined as a tumor receptor content of > 10 fmol/mg protein OR receptor-positive by immunohistochemistry [ERICA or PgRICA])

PATIENT CHARACTERISTICS:

Inclusion criteria:

  • Female
  • Postmenopausal, defined by one of the following:

    • Age > 60 years
    • Age 45-59 years with spontaneous cessation of menses > 12 months prior to chemotherapy (if no chemotherapy was given, then prior to study registration)
    • Age 45-59 years with cessation of menses for a duration of < 12 months or secondary to hysterectomy AND an FSH level in the postmenopausal range (or ≥ 34.4 IU/L, if institutional range is not available) prior to chemotherapy (if no chemotherapy was given, then prior to study registration)
    • Age 45-59 years with an FSH level in the postmenopausal range according to institutional laboratory standards (or > 34.4 IU/L, if the institutional range is not available) prior to chemotherapy (if no chemotherapy was given, then prior to study registration)
    • Bilateral oophorectomy
  • ECOG performance status 0, 1, or 2
  • Life expectancy ≥ 5 years

Exclusion criteria:

  • History of other (non-breast) malignancies, except adequately treated nonmelanoma skin cancer, curatively treated in situ cancer of the cervix, or other curatively treated solid tumors with no evidence of disease for > 5 years
  • Any co-existing medical or psychiatric condition that is likely to interfere with study procedures and/or results

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

  • See Disease Characteristics

Exclusion criteria:

  • Hormone replacement therapy, oral contraceptives, tamoxifen, raloxifene, other selective estrogen-receptor modulators, or gonadotropin releasing-hormone analogues ≤ 6 months prior to the pre-registration mammogram
  • Prior treatment with an aromatase inhibitor (e.g., anastrozole, exemestane, letrozole)
  • Planned surgery (other than core needle biopsy) to intact non-cancerous breast (e.g., preventive/prophylactic mastectomy)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00516698

  Show 180 Study Locations
Sponsors and Collaborators
North Central Cancer Treatment Group
Investigators
Study Chair: James N. Ingle, MD Mayo Clinic
Investigator: Wilma Lingle, PhD Mayo Clinic
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00516698     History of Changes
Other Study ID Numbers: CDR0000560200, NCCTG-N063I
Study First Received: August 14, 2007
Last Updated: May 9, 2009
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
stage I breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIC breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Anastrozole
Exemestane
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014