9. Other Endocrine Interventions

9.1 Phase III Randomized Study of Hormone Replacement Therapy in Menopausal or Perimenopausal Women with Prior Stage O-II Breast Cancer 

Objectives

I. Evaluate the safety of hormone replacement therapy in terms of risk of recurrence in women with previously treated, nonrecurrent stage 0-II breast cancer.

II. Compare this regimen with non-hormonal symptomatic treatment in terms of quality of life and risk of death in this patient population.

Participation Criteria

• Menopausal status: menopausal or perimenopausal.
  
• Hormone receptor status: positive, negative, or unknown.
  
• History of stage 0-II breast cancer with no more than four involved axillary nodes if nodal status and number of nodes investigated is known.
  
• Currently without evidence of disease.
  
• No concurrent chemotherapy.
  
• Prior hormone replacement therapy (HRT) allowed if stopped no more than 4 weeks after breast cancer diagnosis and at least 3 months prior to study.
  
• No prior HRT begun after breast cancer diagnosis.
  
• No concurrent hormonal therapy for breast cancer except tamoxifen or Toremifene.
  
• No concurrent radiotherapy.

Randomization

C. Rageth, Chair Principal Investigator
Ph: 0041 1 733 21 76 International Breast Cancer Study GroupSpital Limmattal Schlieren, Switzerland

9.2 Phase IB Randomized, Multiple-Dose Pharmacodynamic (Biomarker Modulation) Study of LY353381.HCl, Tamoxifen, and Placebo in Women with Newly Diagnosed Breast Cancer 

Objectives

I. Evaluate the ability of tamoxifen or LY353381.HCl to favorably modulate one or more biomarkers associated with breast cancer progression in patients with newly diagnosed breast cancer.
II. Validate a short-term tissue and serum biomarker modulation model as a means of predicting efficacy of these agents as preventive agents.

Participation Criteria

• Age: 18 and over.
• Menopausal status: Postmenopausal.
• Histologically confirmed noninvasive or small invasive breast cancer.
• Low or intermediate grade (ductal carcinoma in situ, T1, or T2) OR estrogen and/or progesterone receptor-positive.
• Largest mass no greater than 5 cm.
• Clustered microcalcifications as only abnormality allowed with no upper size limit.
• If no distinction between mass and microcalcifications, size as one lesion.
• No evidence of metastases from any malignancy.
• Hormone receptor status: estrogen and progesterone receptor-positive (unless low 
  or intermediate grade tumor).
• At least 1 year since prior chemotherapy.
• At least 30 days since prior hormone replacement therapy or oral contraceptives.
• At least 1 year since prior aromatase inhibitors, antiestrogens, or LH agonists/antagonists.
• Lumpectomy or mastectomy must be planned for 2-6 weeks from start of study.

Randomization

Treatment continues for 2-6 weeks (until scheduled lumpectomy or mastectomy) in the absence of disease progression or unacceptable toxicity.

Carol J. Fabian, Chair Principal Investigator 
Ph: 913-588-7791 University of Kansas Medical Center Kansas City, Kansas

9.3 Phase III Study of the Effect of Menstrual Cycle Timing with Breast Surgery on Prognosis in Premenopausal Women With Stage I, II, or III Breast Cancer

Objectives

I. Determine if the timing of breast surgery during the menstrual cycle impacts disease recurrence, progression, or death among different racial groups in premenopausal women with stage I, II, or III breast cancer.

II. Determine if definitive breast cancer surgeries (e.g., lumpectomy or mastectomy) performed during the follicular phase result in poorer prognosis (recurrence, disease progression, or death) compared with surgeries performed during the midcycle or luteal phases in this patient population.

Participation Criteria

• Age: Any age.
• Menopausal status: Premenopausal.
• Hormone receptor status: Not specified.
• Histologically confirmed stage I, II, or III primary breast cancer undergoing breast surgery.
• Invasive disease (e.g., lobular or ductal).
• Regular menses (no amenorrhea of greater than 90 days) without hormone replacement.
• Documented last menstrual period.
• No preoperative chemotherapy.
• No concurrent hormonal replacement therapy.
• No concurrent interruptive oral contraceptive use of less than 3 months.

Protocol

Patients undergo either fine needle aspiration concurrently with definitive breast surgery (mastectomy or lumpectomy) or needle-directed excisional biopsy followed by definitive breast surgery.

Patients undergo serum collection for hormonal analysis preoperatively, 24 hours post-operatively, at days 7 and 14, and at 3 months and urine collection for hormonal analysis beginning 24 hours prior to surgery and continuing daily until the onset of the next menses.

Patients complete a 30-minute telephone interview regarding medical, family, occupational and reproductive history, and lifestyle habits (e.g., diet, exercise, environmental exposures). Beginning 24 hours prior to surgery and continuing until the onset of the next menses, patients complete a menstrual cycle journal indicating the start and length of menses.

Patients undergoing mastectomy are followed every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter. Patients undergoing adjuvant therapy are followed every 3 months for 3 years, and then every 6 months thereafter or every 4 months for 2 years and then every 6 months thereafter.

Helena R. Chang, Chair Principal Investigator
Ph: 310-794-5624 Jonsson Comprehensive Cancer Center, UCLA Los Angeles, California

9.4 Correlation of Menstrual Cycle Phase at the Time of Surgery with Disease-Free Survival in Women with Stage I/II Breast Cancer 

Objectives

I. Document menstrual phase (follicular vs luteal) by circulating hormones and menstrual history in premenopausal women at the time of primary surgery for stage I/II breast cancer.

II. Correlate menstrual phase at primary surgery with 5-year disease-free survival in these patients.

III. Compare the menstrual cycle data obtained by hormone levels and study-specific menstrual cycle history with information recorded in the general written record.

IV. Compare the menstrual cycle data for these women (i.e., hormone levels and cycle history) with the data for the general population.

V. Estimate the disease-free survival of women who undergo a 2-stage surgical procedure with cancer found at both stages when the surgery is not confined to the same menstrual cycle phase.

Participation Criteria

• Age: 18 to 55.
• Menopausal status: Premenopausal.
• Hormone receptor status: Not specified.
• Pathologically confirmed stage I/II breast cancer.
• No prior neoadjuvant therapy.
• Concurrent chemotherapy allowed.
• At least 3 months since oral contraceptives.
• Concurrent radiotherapy allowed.
• Complete surgical resection required prior to entry. One or two stage procedure (i.e., open biopsy followed immediately or later by mastectomy or breast-conserving approach). Two-step registration required for patients undergoing two-stage procedure.
• Fine needle aspiration (FNA), stereotactic, or core needle biopsy is allowed at any time prior to open biopsy.
• Sentinel node dissection/axillary node dissection allowed.

Protocol

Hormone levels and menstrual history are obtained within one calendar day to surgery.

Patients undergo either one-stage surgery (open biopsy followed by mastectomy or breast-conserving surgery) or two-stage surgery.

Patients complete a questionnaire 6 months after surgery to assess the extent of adjuvant therapy received (if any), and a questionnaire 12 months after surgery to assess recurrence of breast cancer and vital status.

Clive S. Grant, Chair 
Ph: 507-284-2644 North Central Cancer Treatment Group

D. Lawrence Wickerham, Chair 
Ph: 412-330-4600 National Surgical Adjuvant Breast and Bowel Project