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An Exploratory Study to Identify Potential Surrogate Endpoint Biomarkers That Are Modulated by Tamoxifen vs. Placebo in Women With an Increased Risk for Breast Cancer

Phase 2
35 Years
Open (Enrolling)
Breast Cancer

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Trial Information

An Exploratory Study to Identify Potential Surrogate Endpoint Biomarkers That Are Modulated by Tamoxifen vs. Placebo in Women With an Increased Risk for Breast Cancer


- Compare molecular markers of proliferation and apoptosis in breast epithelial tissue of
women at increased risk for breast cancer treated with tamoxifen vs placebo.

- Compare the modulation of markers of genomic instability in breast epithelial tissue of
patients treated with these drugs.

- Compare serum levels of IGF-1, IGF-2, and IGFBP-3 of these patients at baseline and
after treatment with these drugs.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients
are stratified according to estimated 5-year breast cancer risk (1.67-5% vs ≥ 5%), presence
of atypical ductal hyperplasia (yes vs no), and menopausal status (premenopausal vs
postmenopausal). Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive oral tamoxifen once daily.

- Arm I: Patients receive oral placebo once daily. Treatment in both arms continues for 3
months in the absence of invasive breast cancer or unacceptable toxicity.

Patients undergo core needle biopsy and fine needle aspiration biopsy at baseline and then
at the completion of study treatment (for premenopausal patients); exactly 84 days after the
first biopsy (for postmenopausal patients); or on the first or second day of the menstrual
cycle on or after 84 days (during the third menstrual cycle) after the first dose of study
medication (for patients with irregular menses).

Patients are followed at 30 days.

PROJECTED ACCRUAL: A total of 130 patients (65 per arm) will be accrued for this study
within 30 months.

Inclusion Criteria


- At increased risk for breast cancer, as defined by 1 of the following criteria:

- Histologically confirmed lobular carcinoma in situ (LCIS) treated by local
excision only

- Composite increased breast cancer risk of ≥ 1.67% over 5 years, based on the
following criteria:

- Age

- Number of first-degree female relatives with breast cancer

- One or more prior breast biopsies

- Fine-needle aspiration cytology of a non-cystic lesion in lieu of an
open biopsy is considered a biopsy

- Prior diagnosis of atypical hyperplasia of the breast

- Age at first live birth

- Nulliparity

- Race

- Age at onset of menarche

- No prior or suspected invasive breast cancer or ductal carcinoma in situ

- No clinical evidence of malignancy by physical examination, including a breast
examination within the past 3 months

- No evidence of suspicious or malignant disease or uncharacterized lesions on
bilateral mammogram within the past 6 months

- Normal gynecologic examination, including a bimanual pelvic examination and, if
indicated, pap smear within the past 12 months

- Hormone receptor status:

- Not specified



- 35 and over


- Female

Menopausal status

- Premenopausal and ovulating*, defined as having regular menses for the past 6 months
OR irregular menses with follicular phase (i.e., day 3) follicle-stimulating hormone
level < 20 mIU/mL OR

- Postmenopausal NOTE: * Ovulation is determined by day 21 progesterone level > 3 ng/mL

Performance status

- ECOG 0-2

Life expectancy

- Not specified


- Complete blood count normal

- No active bleeding disorder (e.g., qualitative or quantitative platelet abnormality,
hemophilia, or von Willebrand's disease)


- Liver function tests normal


- Not specified


- No prior deep-vein thrombosis except a single occurrence related to lower extremity

- No prior cerebral vascular accident

- No prior transient ischemic attack


- No prior pulmonary embolus except a single occurrence related to lower extremity


- No saline or silicone breast implants

- No known allergy to tamoxifen

- No macular degeneration

- No malignancy within the past 5 years except basal cell or squamous cell skin cancer
or carcinoma in situ of the cervix

- No nonmalignant disease that would preclude administration of tamoxifen

- No psychiatric condition, including a history of clinical depression or addictive
disorder, that would preclude giving informed consent or study compliance

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective nonhormonal contraception during and for 3 months
after study participation


Biologic therapy

- Not specified


- No prior systemic adjuvant chemotherapy for LCIS

Endocrine therapy

- No prior tamoxifen, raloxifene, or other selective estrogen-receptor modulators

- At least 3 months since prior and no concurrent use of any of the following drugs:

- Estrogen or progesterone replacement therapy

- Oral contraceptives

- Androgens

- Luteinizing hormone-releasing hormone analogs

- Prolactin inhibitors

- Antiandrogens

- Steroids

- No concurrent steroids for asthma


- No prior radiotherapy for LCIS


- No prior bilateral prophylactic mastectomy

- No prior mastectomy for LCIS


- Concurrent nonhormonal medications allowed

- No concurrent warfarin or cholestyramine

- No prior or concurrent participation in any other cancer prevention study

- Patients treated with placebo on protocol NSABP-P-1 are eligible

Type of Study:


Study Design:

Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Prevention

Outcome Measure:

Plasma levels of hormones and binding proteins as measured by ELISA, IHC, and TUNEL at baseline and 3 months

Safety Issue:


Principal Investigator

David M. Euhus, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Simmons Cancer Center


United States: Federal Government

Study ID:




Start Date:

February 2002

Completion Date:

Related Keywords:

  • Breast Cancer
  • breast cancer
  • lobular breast carcinoma in situ
  • breast cancer in situ
  • Breast Neoplasms



M.D. Anderson Cancer Center at University of Texas Houston, Texas  77030
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas Dallas, Texas  75390
Oklahoma University Cancer Institute Oklahoma City, Oklahoma  73104
Cancer Therapy and Research Center San Antonio, Texas  78229