2. Prevention, DCIS

2.1 Study of Tamoxifen and Raloxifene (STAR) for the Prevention of Breast Cancer

Objectives

I. Determine whether raloxifene is more or less effective than tamoxifen in significantly reducing the incidence rate of invasive breast cancer in postmenopausal women.

II. Evaluate the effects of tamoxifen and raloxifene on the incidence of intraductal carcinoma in situ, lobular carcinoma in situ, endometrial cancer, ischemic heart disease, fractures of the hip and spine, or Colles' fractures of the wrist.

III. Evaluate the toxic effects of these regimens in these participants.

IV. Determine the effect of these regimens on the quality of life of these participants.

Participation Criteria

• Age Range: 35 and over.
  
  
• Postmenopausal women with: histologically confirmed lobular carcinoma in situ treated by local excision only
  OR
  at least 1.66% probability of invasive breast cancer within 5 years using Breast Cancer Risk Assessment Profile.
  
  
• Endocrine therapy: At least 3 months since prior estrogen or progesterone replacement therapy, oral contraceptives, androgens, luteinizing hormone releasing hormone analogs, prolactin inhibitors, or antiandrogens. At least 3 months since prior tamoxifen, raloxifene, or other SERM therapy of less than 3 months duration. Concurrent Estring¨ (estradiol vaginal ring) allowed.

Randomization

Arm I:
Patients receive oral tamoxifen plus placebo daily for 5 years.

Arm II:
Patients receive oral raloxifene plus placebo daily for 5 years.

Norman Wolmark, Chair
Ph: 412-359-3336 National Surgical Adjuvant Breast and Bowel Project

2.2 Randomized, Double-Blind, Placebo-Controlled Study of Tamoxifen for the Prevention of Breast Cancer in High-Risk Women: International Breast Cancer Intervention Study

Objectives

I. Evaluate whether tamoxifen taken daily for 5 years reduces the incidence of and mortality from breast cancer in high-risk women.

II. Assess the risks and benefits of this intervention.

Participation Criteria

• Age Range: 35 to 70
  
  
• Menopausal status: Pre-, peri-, or postmenopausal
  
  
• No malignant disease on mammogram with, as indicated, fine-needle biopsy or cytology within 1 year prior to entry.
  
  Women with at least 1 risk factor for developing breast cancer, as follows: Ages 45-70 (with at least a 2-fold risk):
  
  
• First-degree relative developed breast cancer at age 50 or less.
  
  
• First-degree relative developed bilateral breast cancer
  
  
• 2 or more first- or second-degree relatives developed breast cancer.
  
  
• Nulliparous and a first-degree relative developed breast cancer.
  
  
• Benign biopsy with proliferative disease and a first-degree relative developed breast cancer.
  
  
• Lobular carcinoma in situ.
  
  
• Atypical ductal or lobular hyperplasia in a benign lesion.
  Ages 40-44 (with at least a 4-fold risk)*:
  
  
• 2 or more first- or second-degree relatives developed breast cancer at age 50 or less.
  
  
• First-degree relative with bilateral breast cancer developed the first breast cancer at age 50 or less.
  
  
• Nulliparous and a first-degree relative developed breast cancer at age 40 or less.
  
  
• Benign biopsy with proliferative disease and a first-degree relative developed breast cancer at age 40 or less.
  
  
• Lobular carcinoma in situ.
  
  
• Atypical ductal or lobular hyperplasia in a benign lesion. Ages 35-39 (with at least a 10-fold risk)*:
  
  
• 2 or more first-degree relatives developed breast cancer at age 50 or less.
  
  
• First-degree relative with bilateral breast cancer developed the first breast cancer at age 40 or less.
  
  
• Lobular carcinoma in situ.

* Entry of women who do not fit into these categories but with a clearly apparent family history indicating appropriate risk requires approval of the Working Party Chairman.

Randomization

Principal Investigator

Jack Cuzick, Ph: 44 207 269 3006 Imperial Cancer Research Fund London, England, United Kingdom

2.3 Phase III Randomized Study of Tamoxifen with or without Radiotherapy in Women with Ductal Carcinoma In Situ (DCIS) of the Breast

Objectives

I. Compare the efficacy of tamoxifen with or without whole breast radiation, in decreasing or delaying the appearance of local failure, both invasive and in situ, and preventing the need for mastectomy in women with ductal carcinoma in situ (DCIS) of the breast.

II. Compare distant disease-free survival of these patients in these treatment arms.

Participation Criteria

• Ductal carcinoma in situ of the breast detected by mammogram at the time of diagnosis.
  
  
• Unicentric.
  
  
• Lesions no greater than 2.5 cm.
  
  
• Low or intermediate grade.
  
  
• Inked margins at least 3 mm.
  
  
• Clinically node-negative.
  
  
• No suspicious areas on post-operative mammogram taken within 12 weeks after final surgery.
  
  
• Concurrent tamoxifen required, but must have begun no more than 4 weeks prior to diagnosis.

Randomization

Arm I:
Patients receive oral tamoxifen 1-2 times daily for 5 years.

Arm II:
Patients receive tamoxifen as in Arm I. Concurrent radiotherapy is given once daily 5 times a week for 5.5 weeks.

Participating Organizations/Investigators
Beryl McCormick, Chair, Ph: 212-639-6828
Radiation Therapy Oncology Group

Barbara L. Smith, Chair, Ph: 617-724-4800 Cancer and Leukemia Group B