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

Breast Cancer Clinical Trial

Official title:

Changes in Breast Density and Plasma Hormone Levels After One Year of Aromatase Inhibitor Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00516698
• Other study ID #: NCCTG-N063I
• Secondary ID: NCI-2012-02719CD
• Status: Completed
• Phase: N/A
• First received: August 14, 2007
• Last updated: July 12, 2016
• Start date: September 2007
• Est. completion date: December 2009

Study information

• Verified date: July 2016
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 140
• Est. completion date: December 2009
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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)

Study Design

Observational Model: Case-Only, Time Perspective: Prospective

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Genetic:
• polymorphism analysis

Other:
• high performance liquid chromatography

• laboratory biomarker analysis

Procedure:
• radiomammography

Locations

Country	Name	City	State
United States	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan
United States	McFarland Clinic, PC	Ames	Iowa
United States	AnMed Cancer Center	Anderson	South Carolina
United States	MBCCOP - Medical College of Georgia Cancer Center	Augusta	Georgia
United States	Rush-Copley Cancer Care Center	Aurora	Illinois
United States	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana
United States	Mary Rutan Hospital	Bellefontaine	Ohio
United States	MeritCare Bemidji	Bemidji	Minnesota
United States	Billings Clinic - Downtown	Billings	Montana
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana
United States	Northern Rockies Radiation Oncology Center	Billings	Montana
United States	St. Vincent Healthcare Cancer Care Services	Billings	Montana
United States	Bismarck Cancer Center	Bismarck	North Dakota
United States	Medcenter One Hospital Cancer Care Center	Bismarck	North Dakota
United States	Mid Dakota Clinic, PC	Bismarck	North Dakota
United States	St. Alexius Medical Center Cancer Center	Bismarck	North Dakota
United States	St. Joseph Medical Center	Bloomington	Illinois
United States	Wood County Oncology Center	Bowling Green	Ohio
United States	Bozeman Deaconess Cancer Center	Bozeman	Montana
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	St. James Healthcare Cancer Care	Butte	Montana
United States	Graham Hospital	Canton	Illinois
United States	Memorial Hospital	Carthage	Illinois
United States	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	CCOP - Columbus	Columbus	Ohio
United States	Doctors Hospital at Ohio Health	Columbus	Ohio
United States	Grant Medical Center Cancer Care	Columbus	Ohio
United States	Mount Carmel Health - West Hospital	Columbus	Ohio
United States	Riverside Methodist Hospital Cancer Care	Columbus	Ohio
United States	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota
United States	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania
United States	CCOP - Dayton	Dayton	Ohio
United States	Good Samaritan Hospital	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Samaritan North Cancer Care Center	Dayton	Ohio
United States	Grady Memorial Hospital	Delaware	Ohio
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa
United States	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mercy Capitol Hospital	Des Moines	Iowa
United States	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas
United States	CCOP - Duluth	Duluth	Minnesota
United States	Duluth Clinic Cancer Center - Duluth	Duluth	Minnesota
United States	Miller - Dwan Medical Center	Duluth	Minnesota
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	St. Anthony's Memorial Hospital	Effingham	Illinois
United States	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas
United States	Hematology Oncology Center	Elyria	Ohio
United States	Eureka Community Hospital	Eureka	Illinois
United States	CCOP - MeritCare Hospital	Fargo	North Dakota
United States	MeritCare Broadway	Fargo	North Dakota
United States	Blanchard Valley Medical Associates	Findlay	Ohio
United States	Middletown Regional Hospital	Franklin	Ohio
United States	Fredericksburg Oncology, Incorporated	Fredericksburg	Virginia
United States	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota
United States	Galesburg Clinic, PC	Galesburg	Illinois
United States	Galesburg Cottage Hospital	Galesburg	Illinois
United States	Great Falls Clinic - Main Facility	Great Falls	Montana
United States	Mason District Hospital	Havana	Illinois
United States	Geisinger Hazleton Cancer Center	Hazleton	Pennsylvania
United States	St. Peter's Hospital	Helena	Montana
United States	Hopedale Medical Complex	Hopedale	Illinois
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois
United States	Glacier Oncology, PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology at KRMC	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Charles F. Kettering Memorial Hospital	Kettering	Ohio
United States	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas
United States	Cascade Cancer Center at Evergreen Hospital Medical Center	Kirkland	Washington
United States	Haematology-Oncology Associates of Ohio and Michigan, PC	Lambertville	Michigan
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Southwest Medical Center	Liberal	Kansas
United States	Meeker County Memorial Hospital	Lichfield	Minnesota
United States	Lima Memorial Hospital	Lima	Ohio
United States	McDonough District Hospital	Macomb	Illinois
United States	Immanuel St. Joseph's	Mankato	Minnesota
United States	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota
United States	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota
United States	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio
United States	Mercy Cancer Center at Mercy Medical Center - North Iowa	Mason City	Iowa
United States	Northwest Ohio Oncology Center	Maumee	Ohio
United States	St. Luke's Hospital	Maumee	Ohio
United States	Saint Anthony Memorial Health Centers	Michigan City	Indiana
United States	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota
United States	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota
United States	Community Medical Center	Missoula	Montana
United States	Guardian Oncology and Center for Wellness	Missoula	Montana
United States	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana
United States	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana
United States	Trinity Cancer Center at Trinity Medical Center - 7th Street Campus	Moline	Illinois
United States	Community Cancer Center of Monroe	Monroe	Michigan
United States	Mercy Memorial Hospital - Monroe	Monroe	Michigan
United States	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio
United States	Cancer Center of Kansas, PA - Newton	Newton	Kansas
United States	BroMenn Regional Medical Center	Normal	Illinois
United States	Community Cancer Center	Normal	Illinois
United States	St. Charles Mercy Hospital	Oregon	Ohio
United States	Toledo Clinic - Oregon	Oregon	Ohio
United States	Community Hospital of Ottawa	Ottawa	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois
United States	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas
United States	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois
United States	OSF St. Francis Medical Center	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois Valley Community Hospital	Peru	Illinois
United States	Olympic Medical Center	Port Angeles	Washington
United States	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas
United States	Perry Memorial Hospital	Princeton	Illinois
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Southlake Clinic	Renton	Washington
United States	Reid Hospital & Health Care Services	Richmond	Indiana
United States	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota
United States	Rutherford Hospital	Rutherfordton	North Carolina
United States	Arch Medical Services, Incorporated at Center for Cancer Care and Research	Saint Louis	Missouri
United States	Missouri Baptist Cancer Center	Saint Louis	Missouri
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Park Nicollet Cancer Center	Saint Louis Park	Minnesota
United States	HealthEast Cancer Care at St. Joseph's Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Cancer Center of Kansas, PA - Salina	Salina	Kansas
United States	Firelands Regional Medical Center	Sandusky	Ohio
United States	North Coast Cancer Care, Incorporated	Sandusky	Ohio
United States	CCOP - Virginia Mason Research Center	Seattle	Washington
United States	Virginia Mason Medical Center	Seattle	Washington
United States	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota
United States	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming
United States	Mercy Medical Center - Sioux City	Sioux City	Iowa
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa
United States	St. Luke's Regional Medical Center	Sioux City	Iowa
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Medical X-Ray Center, PC	Sioux Falls	South Dakota
United States	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	St. Margaret's Hospital	Spring Valley	Illinois
United States	Community Hospital of Springfield and Clark County	Springfield	Ohio
United States	Mercy Medical Center	Springfield	Ohio
United States	Regions Hospital Cancer Care Center	St. Paul	Minnesota
United States	Geisinger Medical Group - Scenery Park	State College	Pennsylvania
United States	Flower Hospital Cancer Center	Sylvania	Ohio
United States	Mercy Hospital of Tiffin	Tiffin	Ohio
United States	CCOP - Toledo Community Hospital	Toledo	Ohio
United States	Medical University of Ohio Cancer Center	Toledo	Ohio
United States	St. Vincent Mercy Medical Center	Toledo	Ohio
United States	Toledo Clinic, Incorporated - Main Clinic	Toledo	Ohio
United States	Toledo Hospital	Toledo	Ohio
United States	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio
United States	Natalie Warren Bryant Cancer Center at St. Francis Hospital	Tulsa	Oklahoma
United States	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Fulton County Health Center	Wauseon	Ohio
United States	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas
United States	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio
United States	Associates in Womens Health, PA - North Review	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas
United States	CCOP - Wichita	Wichita	Kansas
United States	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas
United States	Wesley Medical Center	Wichita	Kansas
United States	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania
United States	Mercy Hospital at Wilkes-Barre	Wilkes-Barre	Pennsylvania
United States	Clinton Memorial Hospital	Wilmington	Ohio
United States	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas
United States	HealthEast Cancer Care at Woodwinds Health Campus	Woodbury	Minnesota
United States	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota
United States	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio
United States	Genesis - Good Samaritan Hospital	Zanesville	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in percent breast density in response to 1 year of aromatase inhibitor therapy		Up to 12 months	No
Primary	Changes in dense area in response to 1 year of aromatase inhibitor therapy		Up to 12 months	No
Primary	Correlation of changes in percent breast density with changes in plasma hormone levels and drug levels		Up to 12 months	No
Primary	Correlation of changes in dense area with changes in plasma hormone levels and drug levels		Up to 12 months	No
Primary	Comparison of percent breast density in women with high pre-treatment percent density vs women with low pre-treatment percent density		Up to 12 months	No
Primary	Comparison of dense area in women with high pre-treatment dense area vs women with low pre-treatment dense area		Up to 12 months	No
Primary	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		Up to 12 months	No