Anatomic Stage IA Breast Cancer AJCC v8, Anatomic Stage IB Breast Cancer AJCC v8, Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage IIA Breast Cancer AJCC v8, Anatomic Stage IIB Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8, Anatomic Stage IIIB Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IIIC Breast Cancer AJCC v8, Early-Stage Breast Carcinoma, Invasive Breast Carcinoma, Prognostic Stage IA Breast Cancer AJCC v8, Prognostic Stage IB Breast Cancer AJCC v8, Prognostic Stage I Breast Cancer AJCC v8, Prognostic Stage IIA Breast Cancer AJCC v8, Prognostic Stage IIB Breast Cancer AJCC v8, Prognostic Stage II Breast Cancer AJCC v8, Prognostic Stage IIIA Breast Cancer AJCC v8, Prognostic Stage IIIB Breast Cancer AJCC v8, Prognostic Stage III Breast Cancer AJCC v8, Prognostic Stage IIIC Breast Cancer AJCC v8
Conditions
Brief summary
This phase II trial studies how well anastrozole and letrozole after surgery work in treating patients with stage I-III breast cancer. Drugs, such as anastrozole and letrozole, may stop the growth of tumor cells by decreasing the amount of estrogen made by the body. Giving anastrozole and letrozole after surgery may prevent breast cancer from coming back (recurrence).
Detailed description
PRIMARY OBJECTIVE: I. To estimate the proportion of women who have adequate estrone (E1) and estradiol (E2) suppression after 8-10 weeks of adjuvant anastrozole 10 mg once daily (ANA10) having had inadequate E1 and E2 suppression after 8-10 weeks of standard dose anastrozole 1 mg once daily (ANA1). SECONDARY OBJECTIVES: I. To estimate the proportion of women with elevated E1 and E2 levels after 8-10 weeks of adjuvant ANA1. II. To estimate the proportion of women with elevated E1 and E2 levels after 8-10 weeks of adjuvant ANA1 whose E1 and E2 levels remain elevated after 8-10 weeks of adjuvant ANA10. III. To examine the toxicity profile of ANA1 over the 8-10 weeks of treatment, ANA10 over the 8-10 weeks of treatment, and letrozole over the 8-10 weeks of treatment. IV. To examine concentrations of anastrozole at both the ANA1 and ANA10 dose levels. V. To examine E1 and E2 concentrations, as well as letrozole drug levels, in patients receiving letrozole (following ANA10). VI. To bank deoxyribonucleic acid (DNA) for examination of single-nucleotide polymorphism (SNP)-set(s) determined in the ongoing Mayo Clinic Breast Cancer Specialized Program of Research Excellence (SPORE) Project 4. EXPLORATORY OBJECTIVE: I. To examine association between clinical variables such as age, age at menopause, body mass index (BMI), receipt of chemotherapy, chemotherapy regimen, and dose on E1 and E2 levels after 8-10 weeks of ANA10. OUTLINE: Patients receive anastrozole orally (PO) once daily (QD) for 56-70 days (8-10 weeks). Patients with E1 \>= 1.3 pg/ml and E2 \>= 0.5 pg/ml continue to receive anastrozole PO QD for another 56-70 days (8-10 weeks). Patients then receive letrozole PO QD for 8-10 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
Interventions
Given PO
Given PO
Sponsors
Study design
Eligibility
Inclusion criteria
* REGISTRATION-INCLUSION CRITERIA * Disease characteristics: * Histological confirmation of invasive breast carcinoma * Stage I-III breast cancer * Estrogen receptor (ER) positive disease according to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines as ER \>= 1% positive nuclear staining * Completion of all planned cancer treatments prior to registration: * Surgical resection of breast and nodal surgery; (NOTE: Reconstructive surgery does not have to be completed) * Adjuvant radiation therapy, if needed * Neoadjuvant and/or adjuvant chemotherapy, if needed * Post-menopausal defined as * Age \>= 60 and amenorrhea \> 12 consecutive months OR * Previous bilateral oophorectomy OR * Age \< 60 and amenorrhea \> 12 consecutive months and documented follicle stimulating hormone (FSH) level within post-menopausal range according to institutional standard * NOTE: Patients who did not meet these criteria at time of diagnosis and received pre-operative (neoadjuvant) or post-operative (adjuvant) chemotherapy will not be allowed to participate * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2 * Hemoglobin \>= 8.0 g/dL (obtained =\< 14 days prior to registration) * Absolute neutrophil count (ANC) \>= 1500/mm\^3 (obtained =\< 14 days prior to registration) * Platelet count \>= 70,000/mm\^3 (obtained =\< 14 days prior to registration) * Total bilirubin =\< 1.5 x upper limit of normal (ULN) (obtained =\< 14 days prior to registration) * Alanine aminotransferase (ALT) and aspartate transaminase (AST) =\< 3 x ULN (obtained =\< 14 days prior to registration) * Ability to swallow oral medication * Provide written informed consent * Willingness to provide mandatory blood specimens for correlative research * Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study) * RE-REGISTRATION-INCLUSION CRITERIA * Confirmation that baseline blood sample was drawn and submitted * Blood estrogen levels after cycle 1 anastrozole (ANA1) must meet the following criteria: * E1 \>= 1.3 pg/ml, AND * E2 \>= 0.5 pg/ml
Exclusion criteria
* REGISTRATION-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Adequate Estrogen Suppression After 8 Weeks of Adjuvant Anastrozole 10 mg Daily | 24 weeks | Percentage of women who have adequate E1 and E2 suppression (E1 \< 1.3 pg/ml and/or E2 \< 0.5) after 8-10 weeks of adjuvant anastrozole 10 mg daily having had inadequate E1 and E2 (E1 \>= 1.3 pg/ml and E2 \>= 0.5) after 8-10 weeks of adjuvant anastrozole 1 mg daily. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing a Grade 3 or Greater Adverse Event | 24 weeks | Patients will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Patients were to receive anastrozole 1 mg daily for 8 weeks (ANA1). After 8 weeks of ANA1, patients with E1 \< 1.3 pg/ml and/or E2 \< 0.5 pg/ml completed study and patients with E1 \>= 1.3 pg/ml and E2 \>= 0.5 pg/ml were to switch to anastrozole 10 mg daily (ANA10) for 8 weeks. After 8 weeks of ANA10, patients were to switch to letrozole 2.5 mg daily for 8 weeks. E1 and E2 levels were measured after this 8 week period. Patients were then go off study |
| Percent Change in Estrone (E1) and Estradiol (E2) Concentrations | 24 weeks | Descriptive statistics will be used. The median percent change in E1 and E2 concentrations from pre-AI levels will be presented. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Anastrozole, Letrozole) Patients were to receive anastrozole 1 mg daily for 8 weeks (ANA1). After 8 weeks of ANA1, patients with E1 \< 1.3 pg/ml and/or E2 \< 0.5 pg/ml completed study and patients with E1 \>= 1.3 pg/ml and E2 \>= 0.5 pg/ml were to switch to anastrozole 10 mg daily (ANA10) for 8 weeks. After 8 weeks of ANA10, patients were to switch to letrozole 2.5 mg daily for 8 weeks. E1 and E2 levels were measured after this 8 week period. Patients were then go off study | 156 |
| Total | 156 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Anastrozole 10 mg/Day | Withdrawal by Subject | 1 |
| Anastrozole 1 mg/Day | Discontinued due to adverse events | 3 |
| Anastrozole 1 mg/Day | Discontinued due to COVID | 1 |
| Anastrozole 1 mg/Day | Ineligible | 2 |
| Anastrozole 1 mg/Day | Withdrawal by Subject | 5 |
Baseline characteristics
| Characteristic | Treatment (Anastrozole, Letrozole) |
|---|---|
| Age, Customized Age at registration (years) 40-49 | 5 Participants |
| Age, Customized Age at registration (years) 50-59 | 46 Participants |
| Age, Customized Age at registration (years) 60-69 | 62 Participants |
| Age, Customized Age at registration (years) 70-79 | 35 Participants |
| Age, Customized Age at registration (years) 80-89 | 8 Participants |
| BMI Obese | 62 Participants |
| BMI Overweight | 54 Participants |
| BMI Underweight/Normal | 36 Participants |
| BMI Unknown | 4 Participants |
| ECOG Performance Status 0 | 148 Participants |
| ECOG Performance Status 1 | 8 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 149 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 146 Participants |
| Region of Enrollment United States | 156 participants |
| Sex: Female, Male Female | 156 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 156 | 0 / 33 | 0 / 24 |
| other Total, other adverse events | 120 / 156 | 26 / 33 | 20 / 24 |
| serious Total, serious adverse events | 4 / 156 | 1 / 33 | 0 / 24 |
Outcome results
Percentage of Participants With Adequate Estrogen Suppression After 8 Weeks of Adjuvant Anastrozole 10 mg Daily
Percentage of women who have adequate E1 and E2 suppression (E1 \< 1.3 pg/ml and/or E2 \< 0.5) after 8-10 weeks of adjuvant anastrozole 10 mg daily having had inadequate E1 and E2 (E1 \>= 1.3 pg/ml and E2 \>= 0.5) after 8-10 weeks of adjuvant anastrozole 1 mg daily.
Time frame: 24 weeks
Population: Only participants that received anastrozole 10 mg daily (ANA10) and were adherent (reported taking ANA10 for 45-84 days) to treatment were analyzed
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Anastrozole, Letrozole) | Percentage of Participants With Adequate Estrogen Suppression After 8 Weeks of Adjuvant Anastrozole 10 mg Daily | 76.0 percentage of participants |
Number of Participants Experiencing a Grade 3 or Greater Adverse Event
Patients will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Patients were to receive anastrozole 1 mg daily for 8 weeks (ANA1). After 8 weeks of ANA1, patients with E1 \< 1.3 pg/ml and/or E2 \< 0.5 pg/ml completed study and patients with E1 \>= 1.3 pg/ml and E2 \>= 0.5 pg/ml were to switch to anastrozole 10 mg daily (ANA10) for 8 weeks. After 8 weeks of ANA10, patients were to switch to letrozole 2.5 mg daily for 8 weeks. E1 and E2 levels were measured after this 8 week period. Patients were then go off study
Time frame: 24 weeks
Population: Only participants that received treatment and were eligible were analyzed
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Anastrozole, Letrozole) | Number of Participants Experiencing a Grade 3 or Greater Adverse Event | 6 Participants |
| Anastrozolem10mg Daily | Number of Participants Experiencing a Grade 3 or Greater Adverse Event | 0 Participants |
| Letrozole 2.5 mg Daily | Number of Participants Experiencing a Grade 3 or Greater Adverse Event | 0 Participants |
Percent Change in Estrone (E1) and Estradiol (E2) Concentrations
Descriptive statistics will be used. The median percent change in E1 and E2 concentrations from pre-AI levels will be presented.
Time frame: 24 weeks
Population: Patients that received anastrozole 10 mg daily (ANA10) and were adherent to treatment were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment (Anastrozole, Letrozole) | Percent Change in Estrone (E1) and Estradiol (E2) Concentrations | E1 levels | -97.0 percent change |
| Treatment (Anastrozole, Letrozole) | Percent Change in Estrone (E1) and Estradiol (E2) Concentrations | E2 levels | -94.6 percent change |