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

Launched by NATIONAL CANCER INSTITUTE (NCI) · Dec 9, 2002

Keywords

ClinConnect Summary

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 mark...

Gender

ALL

Eligibility criteria

• POPULATION CHARACTERISTICS:
• 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.
• PRIOR/CONCURRENT THERAPY:
• • 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.
• PATIENT CHARACTERISTICS:
• • Age: 35 and over.
• • Performance status: Ambulatory.
• • Life expectancy: At least 10 years.
• • Hematopoietic: Complete blood count normal.
• Hepatic:
• • 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.
• Cardiovascular:
• • No history of deep venous thrombosis.
• • No history of pulmonary embolus.
• Other:
• • 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.