Breast Cancer
Conditions
Keywords
ductal breast carcinoma in situ, breast cancer in situ
Brief summary
RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using either tamoxifen or anastrozole may fight breast cancer by blocking the use of estrogen. It is not yet known whether tamoxifen is more effective than anastrozole in preventing breast cancer after surgery for ductal carcinoma in situ. PURPOSE: This randomized phase III trial is studying how well adjuvant tamoxifen works compared to anastrozole in treating postmenopausal women who have undergone surgery to remove ductal carcinoma in situ.
Detailed description
OBJECTIVES: Primary * Compare the efficacy of adjuvant tamoxifen vs anastrozole, in terms of local control and prevention of contralateral disease, in postmenopausal women with locally excised ductal carcinoma in situ. * Compare side effect profiles of these drugs in these patients. Secondary * Compare the efficacy of these drugs, according to the receptor status of the primary or recurrent cancer in these patients. * Compare the rate of breast cancer recurrence and growth of new contralateral tumors after cessation of treatment with these drugs in these patients. * Compare breast cancer mortality in patients treated with these drugs. * Compare the effect of these drugs on other cancers, cardiovascular disease, fracture rates, and non-breast cancer deaths in these patients. * Compare the tolerability and acceptability of side effects experienced by patients treated with these drugs. OUTLINE: This is a randomized, double-blind, multicentre study. Patients are stratified according to participating centre. Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive oral tamoxifen and oral placebo once daily. * Arm II: Patients receive oral anastrozole and oral placebo once daily. In both arms, treatment continues for 5 years in the absence of disease recurrence or unacceptable toxicity. Patients are followed annually for 5 years and a further 5 years (minimum) off treatment. Peer Reviewed and Funded by Cancer Research UK. Sponsored by Queen Mary University of London ACTUAL ACCRUAL: A total of 2,980 patients were accrued for this study over 9 years.
Interventions
DRUGtamoxifen citrate
Tamoxifen 20mg + Anastrozole placebo
DRUGAnastrozole
Anastrozole 1mg + Tamoxifen placebo
Sponsors
Cancer Research UK
Queen Mary University of London
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
40 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Diagnosis of ductal carcinoma in situ within the past 6 months * Locally excised with tumor-free margins at least 1 mm * Hormone receptor status: * Estrogen or progesterone receptor positive * Equal to or greater than 5% positive cells PATIENT CHARACTERISTICS: Age * 40 to 70 Sex * Female Menopausal status * Postmenopausal, defined as meeting at least 1 of the following criteria: * Over age 60 * Prior bilateral oophorectomy * Age 60 or under with a uterus AND amenorrhea for at least the past 12 months * Age 60 or under without a uterus AND follicle-stimulating hormone greater than 20 IU/L Performance status * Not specified Life expectancy * At least 10 years Hematopoietic * Not specified Hepatic * Not specified Renal * Not specified Cardiovascular * No prior deep vein thrombosis * No prior transient ischemic attack * No prior cerebrovascular accident Pulmonary * No prior pulmonary embolism Other * No unexplained postmenopausal bleeding * No other cancer within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix * No other concurrent medical condition that would preclude study therapy, place the patient at unusual risk, or confound study results * No evidence of osteoporosis * Fragility fractures within the spine allowed if T-score level is greater than -4 and consist of no more than 2 fractures * Psychologically and physically suitable for 5 years of study therapy PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * Not specified Endocrine therapy * No prior or concurrent tamoxifen use lasting more than 6 months unless treatment was completed more than 5 years ago. Women in IBIS-I can join if off trial therapy for at least 5 years. * No prior or concurrent raloxifene use lasting more than 6 months unless treatment was completed more than 5 years ago. * No other prior or concurrent selective estrogen-receptor modulator use lasting more than 6 months unless treatment was completed more than 5 years ago * No concurrent systemic estrogen-based hormone replacement therapy, including vaginal estrogen preparations Radiotherapy * Not specified Surgery * See Disease Characteristics * No prior mastectomy * No planned prophylactic mastectomy Other * At least 3 months since prior unapproved or experimental agents * No concurrent anticoagulants
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Breast Cancer Recurrence, Including Recurrent DCIS and New Contralateral Tumours | Date of the breast cancer occurrence is defined as the date of the confirmation of the specific event (from randomisation to date of occurrence). Data presented is from randomisation to study completion, median follow-up was 11.6 years (IQR: 9.9-13.5). |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants With ER+ Breast Cancer Recurrence, Including Recurrent DCIS and New Contralateral Tumours | Date of the breast cancer occurrence is defined as the date of the confirmation of the specific event (from randomisation to date of occurrence). Data presented is from randomisation to study completion, median follow-up was 11.6 years (IQR: 9.9-13.5). |
| Number of Participants With ER- Breast Cancer Recurrence | Date of the breast cancer occurrence is defined as the date of the confirmation of the specific event (from randomisation to date of occurrence). Data presented is from randomisation to study completion, median follow-up was 11.6 years (IQR: 9.9-13.5). |
| Number of Breast Cancer Deaths | Date of the death is defined as the date of the confirmation of the specific event (from randomisation to date of occurrence). Data presented is from randomisation to study completion, median follow-up was 11.6 years (IQR: 9.9-13.5). |
| Number of Non-breast Cancer Deaths | Date of the death is defined as the date of the confirmation of the specific event (from randomisation to date of occurrence). Data presented is from randomisation to study completion, median follow-up was 11.6 years (IQR: 9.9-13.5). |
Countries
Australia, Austria, Belgium, Chile, France, Germany, Hungary, Ireland, Italy, Malta, Sweden, Switzerland, Turkey (Türkiye), United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Anastrozole Anastrozole: Anastrozole 1mg + Tamoxifen placebo | 1,471 |
| Tamoxifen tamoxifen citrate: Tamoxifen 20mg + Anastrozole placebo | 1,509 |
| Total | 2,980 |
Baseline characteristics
| Characteristic | Total | Anastrozole | Tamoxifen |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 670 Participants | 332 Participants | 338 Participants |
| Age, Categorical Between 18 and 65 years | 2310 Participants | 1139 Participants | 1171 Participants |
| Age, Continuous | 60.3 years | 60.4 years | 60.3 years |
| Race and Ethnicity Not Collected | 0 Participants | — | — |
| Region of Enrollment Australia | 168 participants | 76 participants | 92 participants |
| Region of Enrollment Austria | 90 participants | 51 participants | 39 participants |
| Region of Enrollment Belgium | 104 participants | 54 participants | 50 participants |
| Region of Enrollment Chile | 17 participants | 9 participants | 8 participants |
| Region of Enrollment Finland | 7 participants | 4 participants | 3 participants |
| Region of Enrollment France | 426 participants | 211 participants | 215 participants |
| Region of Enrollment Germany | 779 participants | 386 participants | 393 participants |
| Region of Enrollment Hungary | 15 participants | 7 participants | 8 participants |
| Region of Enrollment India | 2 participants | 1 participants | 1 participants |
| Region of Enrollment Ireland | 78 participants | 42 participants | 36 participants |
| Region of Enrollment Italy | 323 participants | 165 participants | 158 participants |
| Region of Enrollment Malta | 4 participants | 2 participants | 2 participants |
| Region of Enrollment New Zealand | 10 participants | 4 participants | 6 participants |
| Region of Enrollment Sweden | 8 participants | 4 participants | 4 participants |
| Region of Enrollment Switzerland | 45 participants | 19 participants | 26 participants |
| Region of Enrollment Turkey | 15 participants | 7 participants | 8 participants |
| Region of Enrollment United Kingdom | 889 participants | 429 participants | 460 participants |
| Sex: Female, Male Female | 2980 Participants | 1471 Participants | 1509 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 62 / 1,449 | 69 / 1,489 |
| other Total, other adverse events | 1,323 / 1,449 | 1,380 / 1,489 |
| serious Total, serious adverse events | 333 / 1,449 | 371 / 1,489 |
Outcome results
Primary
Number of Participants With Breast Cancer Recurrence, Including Recurrent DCIS and New Contralateral Tumours
Time frame: Date of the breast cancer occurrence is defined as the date of the confirmation of the specific event (from randomisation to date of occurrence). Data presented is from randomisation to study completion, median follow-up was 11.6 years (IQR: 9.9-13.5).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Anastrozole | Number of Participants With Breast Cancer Recurrence, Including Recurrent DCIS and New Contralateral Tumours | 103 Participants |
| Tamoxifen | Number of Participants With Breast Cancer Recurrence, Including Recurrent DCIS and New Contralateral Tumours | 120 Participants |
p-value: 0.3395% CI: [0.67, 1.14]Regression, Cox
p-value: 0.3395% CI: [0.66, 1.15]Regression, Cox
Secondary
Number of Breast Cancer Deaths
Time frame: Date of the death is defined as the date of the confirmation of the specific event (from randomisation to date of occurrence). Data presented is from randomisation to study completion, median follow-up was 11.6 years (IQR: 9.9-13.5).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Anastrozole | Number of Breast Cancer Deaths | 3 Participants |
| Tamoxifen | Number of Breast Cancer Deaths | 3 Participants |
p-value: 0.9795% CI: [0.21, 5.11]Regression, Cox
p-value: 0.9395% CI: [0.22, 5.36]Regression, Cox
Secondary
Number of Non-breast Cancer Deaths
Time frame: Date of the death is defined as the date of the confirmation of the specific event (from randomisation to date of occurrence). Data presented is from randomisation to study completion, median follow-up was 11.6 years (IQR: 9.9-13.5).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Anastrozole | Number of Non-breast Cancer Deaths | 59 Participants |
| Tamoxifen | Number of Non-breast Cancer Deaths | 65 Participants |
p-value: 0.6795% CI: [0.65, 1.32]Regression, Cox
p-value: 0.3895% CI: [0.59, 1.22]Regression, Cox
Secondary
Number of Participants With ER- Breast Cancer Recurrence
Time frame: Date of the breast cancer occurrence is defined as the date of the confirmation of the specific event (from randomisation to date of occurrence). Data presented is from randomisation to study completion, median follow-up was 11.6 years (IQR: 9.9-13.5).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Anastrozole | Number of Participants With ER- Breast Cancer Recurrence | 24 Participants |
| Tamoxifen | Number of Participants With ER- Breast Cancer Recurrence | 15 Participants |
p-value: 0.1395% CI: [0.75, 2.84]Regression, Cox
p-value: 0.2695% CI: [0.75, 2.84]Regression, Cox
Secondary
Number of Participants With ER+ Breast Cancer Recurrence, Including Recurrent DCIS and New Contralateral Tumours
Time frame: Date of the breast cancer occurrence is defined as the date of the confirmation of the specific event (from randomisation to date of occurrence). Data presented is from randomisation to study completion, median follow-up was 11.6 years (IQR: 9.9-13.5).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Anastrozole | Number of Participants With ER+ Breast Cancer Recurrence, Including Recurrent DCIS and New Contralateral Tumours | 58 Participants |
| Tamoxifen | Number of Participants With ER+ Breast Cancer Recurrence, Including Recurrent DCIS and New Contralateral Tumours | 82 Participants |
p-value: 0.0695% CI: [0.52, 1.01]Regression, Cox
p-value: 0.0995% CI: [0.52, 1.05]Regression, Cox