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

• ClinicalTrials.gov Identifier: NCT00003771
• Recruitment Status: Completed
• First Posted: January 27, 2003
• Last Update Posted: September 20, 2013
• Sponsor: Regional Oncologic Center
• Collaborators: Scandinavian Breast Group; International Breast Cancer Study Group; European Organisation for Research and Treatment of Cancer - EORTC
• Information provided by: National Cancer Institute (NCI)

Study Description

Brief Summary:

RATIONALE: Hormone replacement therapy is effective for relieving symptoms of menopause. It is not yet known if hormone replacement therapy increases the risk of breast cancer recurrence in women previously treated for early stage breast cancer.

PURPOSE: Randomized phase III trial to determine the risk of breast cancer recurrence in women with previous early stage breast cancer who are receiving hormone replacement therapy for menopause symptoms.

Condition or disease	Intervention/treatment	Phase
Breast Cancer; Menopausal Symptoms	Biological: therapeutic estradiol; Drug: norethindrone acetate	Phase 3

Detailed Description:

OBJECTIVES:

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

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.

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 1300 participants
• Allocation: Randomized
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: Protocol for Randomized Clinical Study Concerning Hormonal Replacement Therapy (HRT) After Previous Radical Breast Cancer Treatment
• Study Start Date: September 1997
• Actual Study Completion Date: February 2004

Arms and Interventions

Outcome Measures

Eligibility Criteria

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

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

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

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

Contacts and Locations

Locations

Finland

Helsinki University Central Hospital

Helsinki, Finland, FIN-00029

Norway

Norwegian Radium Hospital

Oslo, Norway, N-0310

Poland

Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology

Warsaw, Poland, 02-781

Sweden

Karolinska Hospital

Stockholm, Sweden, S-171 76

Uppsala University Hospital

Uppsala, Sweden, S-75185

Switzerland

Breast Center

Zurich, Switzerland, CH-8008

Sponsors and Collaborators

Regional Oncologic Center

Scandinavian Breast Group

International Breast Cancer Study Group

European Organisation for Research and Treatment of Cancer - EORTC

Investigators

• Study Chair: Lars Holmberg, MD, PhD; Uppsala University Hospital
• Study Chair: Jonas Bergh, MD, PhD; Karolinska Institutet
• Study Chair: C. Rageth, MD, PD; Breast Center
• Study Chair: Janusz Jaskiewicz, MD; Maria Sklodowska-Curie Institute - Oncology Center

More Information

Publications of Results:

Holmberg L, Iversen OE, Rudenstam CM, Hammar M, Kumpulainen E, Jaskiewicz J, Jassem J, Dobaczewska D, Fjosne HE, Peralta O, Arriagada R, Holmqvist M, Maenpaa J; HABITS Study Group. Increased risk of recurrence after hormone replacement therapy in breast cancer survivors. J Natl Cancer Inst. 2008 Apr 2;100(7):475-82. doi: 10.1093/jnci/djn058. Epub 2008 Mar 25. Erratum in: J Natl Cancer Inst. 2008 May 7;100(9):685. Maenpa, Johanna [corrected to Maenpaa, Johanna].

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. 2004 Feb 7;363(9407):453-5.

Other Publications:

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

• ClinicalTrials.gov Identifier: NCT00003771 History of Changes
• Other Study ID Numbers: CDR0000066897; ROC-HABITS; EORTC-10992; IBCSG-17-98; SBG-HABITS; EU-98077
• First Posted: January 27, 2003
• Last Update Posted: September 20, 2013
• Last Verified: July 2001

Keywords provided by National Cancer Institute (NCI):

menopausal symptoms; stage I breast cancer; stage II breast cancer; breast cancer in situ

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Estradiol 3-benzoate; Estradiol 17 beta-cypionate; Norethindrone; Norethindrone Acetate; Estradiol; Polyestradiol phosphate; Estrogens; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral