Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information
Registry Information

Alternate Title

Hormone Replacement Therapy and the Risk of Breast Cancer Recurrence in Women With Previous Early Stage Breast Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Supportive care, Treatment	Closed	Not specified	Other	ROC-HABITS EORTC-10992, IBCSG-17-98, SBG-HABITS, EU-98077, NCT00003771

Objectives

1. Evaluate the safety of hormone replacement therapy, in terms of risk of recurrence, in women with previously treated, nonrecurrent stage 0-II breast cancer.
2. Compare this regimen vs non-hormonal symptomatic treatment, in terms of quality of life and risk of death, in this patient population.

Entry Criteria

Disease Characteristics:

• History of stage 0-II breast cancer with no more than 4 involved axillary nodes if nodal status and number of nodes investigated is known



• No current evidence of disease



• Hormone receptor status:
  • Positive, negative, or unknown

Prior/Concurrent Therapy:

Biologic therapy:

• Not specified

Chemotherapy:

• No concurrent chemotherapy

Endocrine therapy:

• 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 initiated after breast cancer diagnosis
• No concurrent hormonal therapy for breast cancer except tamoxifen or toremifene

Radiotherapy:

• No concurrent radiotherapy

Surgery:

• Not specified

Other:

• No prior randomization into trials comparing effects of chemotherapy and bilateral oophorectomy in premenopausal women

Patient Characteristics:

Age:

• Not specified

Sex:

• Female

Menopausal status:

• Menopausal or perimenopausal

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• No active liver disease

Renal:

• Not specified

Cardiovascular:

• No prior or concurrent deep vein thrombosis
• No hereditary traits for deep vein thrombosis
• No prior or concurrent cerebral stroke
• No prior or concurrent coronary disease

Other:

• No prior malignancy except basal cell skin cancer or carcinoma in situ of the cervix
• No porphyria
• No other serious disease that would prevent compliance or greatly limit life expectancy

Expected Enrollment

A total of 1,300 patients will be accrued for this study within 5-6 years.

Outline

This is a randomized, open-label, multicenter study. Patients are stratified by center, prior hormone replacement therapy before diagnosis, and concurrent tamoxifen therapy. Patients are randomized to one of two treatment arms.

• Arm I: Patients receive one of the following: Women with an intact uterus whose last menstrual bleeding has occurred within 2 years receive continuous oral cyclic estradiol-norethindrone combination comprising estradiol only on days 1-12, estradiol plus norethindrone on days 13-22, and then estradiol only on days 22-28. Women with an intact uterus whose last menstrual bleeding occurred more than 2 years prior to study receive continuous daily oral estradiol-norethindrone combination. Women who have had a hysterectomy receive continuous daily oral estradiol only.



• Arm II: Patients receive one or more non-hormonal therapies (e.g., clonidine, beta blockers, psychological support, physical exercise, acupuncture).

Treatment in both arms continues for 2 years in the absence of disease progression. Patients may continue their randomized treatment regimen at the discretion of the treating physician.

Quality of life is assessed 3 times during the study and then every two years thereafter. Gynecological health is assessed at 3 months, 6 months, and one year during the study and then annually for at least 5 years. Breast cancer is assessed every 6 months for 3 years and then annually thereafter or at the discretion of the treating physician.

Holmberg L, Iversen OE, Rudenstam CM, et al.: Increased risk of recurrence after hormone replacement therapy in breast cancer survivors. J Natl Cancer Inst 100 (7): 475-82, 2008.[PUBMED Abstract]

Holmberg L, Anderson H; HABITS steering and data monitoring committees.: HABITS (hormonal replacement therapy after breast cancer--is it safe?), a randomised comparison: trial stopped. Lancet 363 (9407): 453-5, 2004.[PUBMED Abstract]

Brincat M, Muscat Baron Y, Ciantar E: Hormone replacement in women with breast cancer: the HABITS study. Endocrine 24 (3): 255-7, 2004.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Regional Oncologic Center

Lars Holmberg, MD, PhD, Protocol chair		Ph: 46-18-151-910 Email: Lars.Holmberg@akademiska.se

Scandinavian Breast Group

Jonas Bergh, MD, PhD, Protocol chair		Ph: 46-8-517-762-79

International Breast Cancer Study Group

C. Rageth, MD, PD, Protocol chair		Ph: 41-44-380-76-60 Email: c.rageth@brust-zentrum.ch

European Organization for Research and Treatment of Cancer

Janusz Jaskiewicz, MD, Protocol chair		Ph: 48-22-644-0024

Registry Information
Official Title		Protocol for Randomized Clinical Study Concerning Hormonal Replacement Therapy (HRT) After Previous Radical Breast Cancer Treatment
Trial Start Date		1997-09-17
Registered in ClinicalTrials.gov		NCT00003771
Date Submitted to PDQ		1999-02-05
Information Last Verified		2001-07-06