A Pilot Trial of Tamoxifen and 4-HPR (4-N-Hydroxyphenyl Retinamide) in Persons at High Risk for Developing Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00001378
Recruitment Status : Completed
First Posted : December 10, 2002
Last Update Posted : March 4, 2008
Information provided by:
National Institutes of Health Clinical Center (CC)

Brief Summary:

This is a pilot, chemoprevention study. Patients receive fenretinide daily for 25 of every 28 days for 4 months and tamoxifen daily for 23 months, beginning the second month of fenretinide.

Patients are removed from study for unacceptable toxicity, the development of invasive breast cancer, or for dysfunctional uterine bleeding.

Condition or disease Intervention/treatment Phase
Breast Cancer Breast Neoplasms Drug: fenretinide Phase 1

Detailed Description:
This is a pilot chemo-prevention study of the combination tamoxifen and 4-HPR in persons at increased risk of developing invasive breast cancer. The objectives of the study are to determine the acute and cumulative toxicity of tamoxifen and 4-HPR in high risk persons; to assess the feasibility of obtaining adequate tissue to study potential intermediate biomarkers of proliferative disease and malignancy using nipple aspiration, four quadrant fine needle aspirates, and breast core needle biopsies; and to study the effects of tamoxifen and 4-HPR on TGF-beta isoforms and the proliferative markers ki67 and PCNA pre- and post-therapy.

Study Type : Interventional  (Clinical Trial)
Enrollment : 75 participants
Primary Purpose: Treatment
Official Title: A Pilot Trial of Tamoxifen and 4-HPR (4-N-Hydroxyphenyl Retinamide) in Persons at High Risk for Developing Breast Cancer
Study Start Date : January 1994
Study Completion Date : November 2000

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Tamoxifen

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


Women and men at increased risk for the development of breast cancer by at least one of the following criteria:

Histologically documented ductal carcinoma in situ (DCIS), including DCIS with minimal invasion or microinvasion.

Histologically documented lobular neoplasia, including lobular hyperplasia and lobular carcinoma in situ (LCIS).

Histologically documented atypical ductal hyperplasia in postmenopausal women.

Histologically documented atypical ductal hyperplasia in premenopausal women with 1 first-degree relative (mother or sister) diagnosed with breast cancer.

Histologically documented atypical ductal hyperplasia in premenopausal women with 3 or more relatives diagnosed with breast cancer provided at least 1 is a second-degree relative.

3 or more first- or second-degree relatives diagnosed with breast or ovarian cancer with at least 1 diagnosed with breast cancer.

2 or more premenopausal (under age 50) first-degree relatives diagnosed with breast cancer.

1 or more first-degree relatives diagnosed with breast cancer if at least 1 relative in the extended pedigree had ovarian cancer.

3 or more relatives with breast cancer with at least 1 first-degree relative diagnosed with premenopausal breast cancer.

Previously diagnosed Stage I breast cancer with surgery and/or radiotherapy only (without prior adjuvant chemo- or hormonal therapy).

Positive for the BRCA1/BRCA2 gene.

No history of other invasive breast cancer.

No evidence of malignancy on breast and gynecologic exams.

Participants with a family history of breast cancer will be seen in consultation by the Family Studies Branch, NCI.


Mastectomy or lumpectomy plus radiotherapy required prior to entry for patients with DCIS. Patients with DCIS who have participated in protocol NCI-MB-348 eligible.

No participation in any other breast cancer prevention study involving pharmacologic intervention.

No prior chemotherapy or hormonal therapy for invasive breast cancer.

At least 3 months since estrogen or progesterone replacement therapy or hormonal contraceptives.


Age: 35 and over.

Performance status: Ambulatory.

Life expectancy: At least 10 years.

Hematopoietic: Complete blood count normal.


Bilirubin normal.

Alkaline phosphate normal.

AST normal.

PT, PTT normal.

No history of bleeding disorder.

No history of chronic hepatitis or cirrhosis.

Renal:Creatinine less than 1.5 mg/dL.


No history of deep venous thrombosis.

No history of pulmonary embolus.


No allergy to any study medication.

Capable of tolerating multiple diagnostic procedures.

No history of abnormal vaginal bleeding. Hysterectomy for vaginal bleeding of benign etiology allowed.

No history of retinal disease, macular degeneration, or night blindness.

No medical or psychiatric risk due to nonmalignant systemic disease that would preclude study participation.

No history of malignancy except: Curatively treated nonmelanomatous skin cancer. Curatively treated in situ cervical carcinoma. Hodgkin's disease treated more than 5 years ago.

No pregnant women.

Adequate contraception required of fertile patients during and for 12 months after fenretinide and for 2 months after tamoxifen.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00001378

United States, Maryland
National Cancer Institute (NCI)
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Cancer Institute (NCI)

Publications: Identifier: NCT00001378     History of Changes
Other Study ID Numbers: 940056
First Posted: December 10, 2002    Key Record Dates
Last Update Posted: March 4, 2008
Last Verified: November 1999

Keywords provided by National Institutes of Health Clinical Center (CC):
4-Quadrant Fine Needle Aspiration
Nipple Suction Aspirates
TGF Beta

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Bone Density Conservation Agents