Stage 0 Breast Cancer AJCC v6 and v7, Stage IA Breast Cancer AJCC v7, Stage IB Breast Cancer AJCC v7, Stage I Breast Cancer AJCC v7, Stage IIA Breast Cancer AJCC v6 and v7, Stage IIB Breast Cancer AJCC v6 and v7, Stage II Breast Cancer AJCC v6 and v7
Conditions
Brief summary
This phase IIb trial studies how well alternative dosing of exemestane before surgery works in treating in postmenopausal patients with stage 0-II estrogen positive breast cancer. Chemoprevention is the use of drugs to keep breast cancer from forming or coming back. The use of exemestane may treat early stage (stage 0-II) breast cancer. Comparing the exemestane standard dose regimen versus two alternative, less frequent dose regimens may decrease undesirable symptoms and have similar efficacy in reducing serum estradiol.
Detailed description
We have conducted an international, multicenter, pre-surgical double-blind non-inferiority phase IIb study in which a total of 180 participants have been randomized to receive either exemestane 25 mg/day (Exemestane 25 mg QD) or 25 mg/ three times a week (Exemestane 25 mg TIW) or a single dose of 25 mg/week (Exemestane 25 mg QW) for a minimum of 4 up to 6 weeks. Participants were stratified by center and BMI (\<25 kg/m2 vs \>25 kg/m2). Participants were histologically confirmed ER-positive (ER \>10%) primary breast cancer patients who were candidates for breast surgery. Postmenopausal women younger than 76 years of age with cT0-2, cN0-1, Mx or women with larger tumors who refuse neo-adjuvant therapy before surgery were eligible. No previous treatment for breast cancer was allowed. Complete physical exam and safety lab tests have been performed at baseline and at the end of treatment (28+1, 35+1, 42+1 days). Phone contact occurred on day 1 and a week before surgery (+3 days). Participants experiencing persistent adverse events (certainly, probably, and possibly treatment-related) have been monitored 20-30 days after study completion. Biomarkers: blood samples were collected at baseline and the end of treatment (fasting blood for biomarkers collected prior to randomization and either on the day of surgery or the day before; fasting strongly recommended but not mandated), tissue samples collected from the diagnostic or research biopsy and at the time of surgery.
Interventions
DRUGExemestane
Given PO
OTHERLaboratory Biomarker Analysis
Correlative studies
OTHERPharmacological Study
Correlative studies
OTHERPlacebo Administration
Given PO
OTHERQuality-of-Life Assessment
Ancillary studies
OTHERQuestionnaire Administration
Ancillary studies
PROCEDURETherapeutic Conventional Surgery
Undergo surgery
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
No minimum to 75 Years
Healthy volunteers
No
Inclusion criteria
* Postmenopausal women (postmenopausal: age \>= 60 years, or amenorrhea \>= 12 months, or bilateral oophorectomy, or - in women with hysterectomy only - follicle stimulating hormone \[FSH\] in the menopausal levels as per local institutional guidelines if \< 60 years old) with histologically-confirmed estrogen receptor (ER)-positive (\>= 10%) primary breast cancer stage cT0-2, cN0-1, Mx; women with larger tumors who refuse chemotherapy (chemo) and/or endocrine neoadjuvant therapy can be eligible * Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%) * Leukocytes \>= 3,000/microliter * Absolute neutrophil count \>= 1,500/microliter * Platelets \>= 100,000/microliter * Total bilirubin =\< 2 x institutional upper limit of normal (ULN) * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 1.5 x institutional ULN * Serum creatinine =\< 1.5 times institutional ULN * Ability to understand and the willingness to sign a written informed consent document
Exclusion criteria
* Body mass index (BMI) \< 18.5 Kg/m\^2 * Previous treatment for breast cancer including chemotherapy, endocrine therapy and radiotherapy; women with prior ductal breast carcinoma in situ (DCIS) who were treated with surgery only and whose treatment ended \>= 2 years prior to enrollment are eligible for the trial * Women who are planned to receive neoadjuvant therapy * Participants may not be receiving investigational agents * History of allergic reactions attributed to compounds of similar chemical or biologic composition to exemestane * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * Other co-existing invasive malignancies (with the exclusion of basal cell carcinoma or skin squamous cell carcinoma) diagnosed during the last 2 years before randomization * History of severe osteoporosis (T score =\< -4 either spine or hip), or presence of vertebral fracture * Use of systemic hormone replacement therapy (HRT) in the last 30 days prior to the randomization; the use of non-systemic estrogen (such as vaginal estrogen use) is allowed * Use of any chemopreventive agents (selective estrogen receptor modulators \[SERM\]) in the last 3 months * Concomitant use of CYP3A4 inducer medication (rifampicin, phenytoin, carbamazepine, phenobarbital, and St. John's wort)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Time of Circulating Estradiol SPE in Each Arm | baseline and 4-6 weeks | LS means of percent change |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change of Circulating Androstenedione | baseline and 4-6 weeks | \[(Final levels-baseline levels)/baseline levels\]\*100 |
| Percent Change of Circulating Testosterone | baseline and 4-6 weeks | \[(Final levels-baseline levels)/baseline levels\]\*100 |
| Percent Change of Circulating Testosterone CLIA | baseline and 4-6 weeks | \[(Final levels-baseline levels)/baseline levels\]\*100 |
| Percent Change of Circulating SHBG | baseline and 4-6 weeks | \[(Final levels-baseline levels)/baseline levels\]\*100 |
| Percent Change of Circulating Estrone LLE | baseline and 4-6 weeks | \[(Final levels-baseline levels)/baseline levels\]\*100 |
| Percent Change of Circulating Total Estrone | baseline and 4-6 weeks | \[(Final levels-baseline levels)/baseline levels\]\*100 |
| Percent Change in Time of Circulating Estradiol LLE in Each Arm | baseline and 4-6 weeks | LS means of percent change |
| Percent Change of Circulating Estrone SPE | baseline and 4-6 weeks | \[(Final levels-baseline levels)/baseline levels\]\*100 |
| Percent Change of Circulating Total Cholesterol | baseline and 4-6 weeks | \[(Final levels-baseline levels)/baseline levels\]\*100 |
| Percent Change of Circulating HDL Cholesterol | baseline and 4-6 weeks | \[(Final levels-baseline levels)/baseline levels\]\*100 |
| Percent Change of Circulating LDL Cholesterol | baseline and 4-6 weeks | \[(Final levels-baseline levels)/baseline levels\]\*100 |
| Percent Change of Circulating Triglycerides | baseline and 4-6 weeks | \[(Final levels-baseline levels)/baseline levels\]\*100 |
| Percent Change of Circulating Insulin | baseline and 4-6 weeks | \[(Final levels-baseline levels)/baseline levels\]\*100 |
| Percent Change of Serum Glucose | baseline and 4-6 weeks | \[(Final levels-baseline levels)/baseline levels\]\*100 |
| Percent Change of Circulating Estrone Sulfate | baseline and 4-6 weeks | \[(Final levels-baseline levels)/baseline levels\]\*100 |
| Percent Change of Circulating Adiponectin | baseline and 4-6 weeks | \[(Final levels-baseline levels)/baseline levels\]\*100 |
| Percent Change of Circulating Leptin | baseline and 4-6 weeks | \[(Final levels-baseline levels)/baseline levels\]\*100 |
| Exemestane Blood Concentration at Surgery | at surgery | Final drug concentration |
| 17-OH Exemestane Blood Concentration at Surgery | at surgery | Final drug concentration |
| Change of ER Expression (Cancer Tissue), Central Review | 4-6 weeks | Surgery level-biopsy level. |
| Change of PgR Expression (Cancer Tissue), Central Review | 4-6 weeks | Surgery level-biopsy level. |
| Change of Ki67% Expression (Cancer Tissue), Central Review | 4-6 weeks | Surgery level-biopsy level. |
| Change of Ki67% Expression (Adjacent Non Cancer Tissue), Central Review | 4-6 weeks | Surgery level-biopsy level. |
| Estradiol Tissue Concentration at Surgery | 4-6 weeks | Final biomarker concentration |
| Estrone Tissue Concentration at Surgery | 4-6 weeks | Final biomarker concentration |
| Androstenedione Tissue Concentration at Surgery | 4-6 weeks | Final biomarker concentration. |
| Testosterone Tissue Concentration at Surgery | 4-6 weeks | Final biomarker concentration |
| Exemestane Tissue Concentration at Surgery | 4-6 weeks | Final drug concentration |
| 17 OH Exemestane Tissue Concentration at Surgery | 4-6 weeks | Final drug concentration |
| Change in MenQoL Questionnaire Score | baseline and 4-6 weeks | MenQOL questionnaire assessed how bothered participants were with 31 symptoms. It contains domains: vasomotor (items 1-3); psychosocial (items 4-10); physical (items 11-26); sexual (items 27-29); in addition to nausea and indigestion. 31 individual symptoms are rated on a scale of 0 (not at all bothered) to 6 (extremely bothered). Total possible score ranged from 0 to 186. MenQOL summary score was calculated as mean of four domain scores (Physical function, Psychosocial function, Sexual function and Vasomotor function) ranging from 1 to 8, with higher scores indicating worse quality of life. Final score-baseline score |
| Percent Change of HOMA IR | baseline and 4-6 weeks | Insulin Resistance Index (HOMA-IR) measures insulin resistance, calculated by fasting insulin (mU/L) multiplied by fasting glucose (mmol/L), and divided by a constant (22.5). A higher score indicates higher insulin resistance. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Proteomic Analysis | 4-6 weeks | The Proteomic Analysis was not performed. |
Countries
Italy, United States
Participant flow
Pre-assignment details
50 participants were not randomized (25 not eligible, 20 withdrew consent, 5 other reasons)
Participants by arm
| Arm | Count |
|---|---|
| Exemestane 25 mg QD 1 tablet of exemestane 25 mg a day for up to 6 weeks | 57 |
| Exemestane 25 mg TIW 1 tablet of exemestane 25 mg a day (on days 1, 3, 5) and 1 tablet of placebo on days 2, 4, 6, 7 for up to 6 weeks | 57 |
| Exemestane 25 mg QW 1 tablet of exemestane 25 mg a day (on day 1) and 1 tablet of placebo on days 2 to 7 for up to 6 weeks | 62 |
| Total | 176 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 0 |
| Overall Study | Participant did not start treatment | 2 | 1 | 1 |
| Overall Study | Unavailable specimen for endpoint evaluations | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Exemestane 25 mg QD | Total | Exemestane 25 mg QW | Exemestane 25 mg TIW |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 32 Participants | 90 Participants | 33 Participants | 25 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants | 86 Participants | 29 Participants | 32 Participants |
| Age, Continuous | 66 years | 64 years | 65 years | 63 years |
| Baseline levels of serum glucose | 96 mg/dL | 97 mg/dL | 95 mg/dL | 98 mg/dL |
| Circulating levels of adiponectin | 10.99 µg/mL | 9.5 µg/mL | 8.99 µg/mL | 8.82 µg/mL |
| Circulating levels of androstenedione | 1.5 nmol/L | 1.5 nmol/L | 1.4 nmol/L | 1.7 nmol/L |
| Circulating levels of estrone sulfate | 581.9 pmol/L | 560.4 pmol/L | 452.3 pmol/L | 625.8 pmol/L |
| Circulating levels of High density lipoprotein (HDL) cholesterol | 62 mg/dL | 59 mg/dL | 57 mg/dL | 59 mg/dL |
| Circulating levels of insulin | 7.6 uU/mL | 8.0 uU/mL | 7.9 uU/mL | 8.1 uU/mL |
| Circulating levels of leptin | 35.1 ng/mL | 36.6 ng/mL | 38.5 ng/mL | 41.7 ng/mL |
| Circulating levels of Low density lipoprotein (LDL) cholesterol | 122.7 mg/dL | 123.6 mg/dL | 132.3 mg/dL | 120.4 mg/dL |
| Circulating levels of SHBG (Sex Hormone-Binding Globulin) | 53.4 nmol/L | 50.6 nmol/L | 50.1 nmol/L | 47.9 nmol/L |
| Circulating levels of testosterone | 0.6 nmol/L | 0.6 nmol/L | 0.6 nmol/L | 0.7 nmol/L |
| Circulating levels of testosterone CLIA (Chemiluminescent immunoassay) | 0.447 nmol/L | 0.477 nmol/L | 0.425 nmol/L | 0.512 nmol/L |
| Circulating levels of total cholesterol | 205 mg/dL | 213 mg/dL | 220 mg/dL | 208 mg/dL |
| Circulating levels of total estrone | 294.7 pmol/L | 279.9 pmol/L | 246.1 pmol/L | 302.2 pmol/L |
| Circulating levels of triglycerides | 104 mg/dL | 108 mg/dL | 119 mg/dL | 92 mg/dL |
| Circulating levels of unconjugated estradiol LLE (Liquid liquid extraction) | 21.2 pmol/L | 20.5 pmol/L | 19.7 pmol/L | 20.9 pmol/L |
| Circulating levels of unconjugated estradiol SPE (Solid phase extraction) | 21.6 pmol/L | 21.3 pmol/L | 20.6 pmol/L | 22.4 pmol/L |
| Circulating levels of unconjugated estrone LLE (Liquid liquid extraction) | 101.0 pmol/L | 98.3 pmol/L | 93.4 pmol/L | 96.2 pmol/L |
| Circulating levels of unconjugated estrone SPE(Solid phase extraction) | 104.3 pmol/L | 98.7 pmol/L | 92.2 pmol/L | 99.4 pmol/L |
| CYP19A1 rs10046 distribution by arm v/v | 11 Participants | 31 Participants | 12 Participants | 8 Participants |
| CYP19A1 rs10046 distribution by arm wt/v | 31 Participants | 95 Participants | 33 Participants | 31 Participants |
| CYP19A1 rs10046 distribution by arm wt/wt | 11 Participants | 38 Participants | 12 Participants | 15 Participants |
| CYP19A1 rs4646 distribution by arm v/v | 6 Participants | 15 Participants | 5 Participants | 4 Participants |
| CYP19A1 rs4646 distribution by arm wt/v | 18 Participants | 60 Participants | 17 Participants | 25 Participants |
| CYP19A1 rs4646 distribution by arm wt/wt | 29 Participants | 89 Participants | 35 Participants | 25 Participants |
| CYP3A4*22 rs35599367 distribution by arm v/v | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| CYP3A4*22 rs35599367 distribution by arm wt/v | 4 Participants | 8 Participants | 1 Participants | 3 Participants |
| CYP3A4*22 rs35599367 distribution by arm wt/wt | 49 Participants | 156 Participants | 56 Participants | 51 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 20 Participants | 10 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 52 Participants | 152 Participants | 51 Participants | 49 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 4 Participants | 1 Participants | 1 Participants |
| HOMA IR | 1.76 HOMA IR Index | 1.94 HOMA IR Index | 1.96 HOMA IR Index | 1.99 HOMA IR Index |
| Menopause specific quality of life questionnaire mean score Overall | 2.3 score on a scale STANDARD_DEVIATION 0.9 | 2.4 score on a scale STANDARD_DEVIATION 1 | 2.5 score on a scale STANDARD_DEVIATION 1.1 | 2.2 score on a scale STANDARD_DEVIATION 1 |
| Menopause specific quality of life questionnaire mean score Physical domain | 2.5 score on a scale STANDARD_DEVIATION 1.1 | 2.5 score on a scale STANDARD_DEVIATION 1.2 | 2.6 score on a scale STANDARD_DEVIATION 1.4 | 2.3 score on a scale STANDARD_DEVIATION 0.9 |
| Menopause specific quality of life questionnaire mean score Psychosocial domain | 2.5 score on a scale STANDARD_DEVIATION 1.3 | 2.5 score on a scale STANDARD_DEVIATION 1.4 | 2.6 score on a scale STANDARD_DEVIATION 1.5 | 2.3 score on a scale STANDARD_DEVIATION 1.2 |
| Menopause specific quality of life questionnaire mean score Sexual domain | 2.0 score on a scale STANDARD_DEVIATION 1.4 | 2.1 score on a scale STANDARD_DEVIATION 1.6 | 2.2 score on a scale STANDARD_DEVIATION 1.8 | 1.9 score on a scale STANDARD_DEVIATION 1.9 |
| Menopause specific quality of life questionnaire mean score Vasomotor domain | 2.2 score on a scale STANDARD_DEVIATION 1.9 | 2.4 score on a scale STANDARD_DEVIATION 1.8 | 2.6 score on a scale STANDARD_DEVIATION 1.9 | 2.5 score on a scale STANDARD_DEVIATION 1.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 6 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 8 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 5 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) White | 49 Participants | 155 Participants | 55 Participants | 51 Participants |
| Region of Enrollment Italy | 29 participants | 83 participants | 28 participants | 26 participants |
| Region of Enrollment United States | 28 participants | 93 participants | 34 participants | 31 participants |
| Sex: Female, Male Female | 57 Participants | 176 Participants | 62 Participants | 57 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| SLCO1B1 rs10841753 distribution by arm v/v | 2 Participants | 6 Participants | 2 Participants | 2 Participants |
| SLCO1B1 rs10841753 distribution by arm wt/v | 13 Participants | 46 Participants | 17 Participants | 16 Participants |
| SLCO1B1 rs10841753 distribution by arm wt/wt | 38 Participants | 112 Participants | 38 Participants | 36 Participants |
| SLCO1B1 rs4149056 distribution by arm v/v | 3 Participants | 6 Participants | 0 Participants | 3 Participants |
| SLCO1B1 rs4149056 distribution by arm wt/v | 13 Participants | 42 Participants | 16 Participants | 13 Participants |
| SLCO1B1 rs4149056 distribution by arm wt/wt | 37 Participants | 116 Participants | 41 Participants | 38 Participants |
| Tissue biopsy estrogen receptor level (centralized evaluation) | 99 Percentage of positive tumor cells | 99 Percentage of positive tumor cells | 99 Percentage of positive tumor cells | 99 Percentage of positive tumor cells |
| Tissue biopsy Ki-67 adjacent non cancer tissue (centralized evaluation) | 1 Percentage of positive tumor cells | 1 Percentage of positive tumor cells | 1 Percentage of positive tumor cells | 1 Percentage of positive tumor cells |
| Tissue biopsy Ki-67 cancer tissue (centralized evaluation) | 13 Percentage of positive tumor cells | 12 Percentage of positive tumor cells | 12 Percentage of positive tumor cells | 13 Percentage of positive tumor cells |
| Tissue biopsy progesteron receptor level (centralized evaluation) | 65 Percentage of positive tumor cells | 70 Percentage of positive tumor cells | 70 Percentage of positive tumor cells | 70 Percentage of positive tumor cells |
| UGT2B17 Copy number variation distribution by arm 0 | 9 count | 22 count | 8 count | 5 count |
| UGT2B17 Copy number variation distribution by arm 1 | 22 count | 78 count | 30 count | 26 count |
| UGT2B17 Copy number variation distribution by arm 2 | 22 count | 64 count | 19 count | 23 count |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 57 | 0 / 57 | 0 / 62 |
| other Total, other adverse events | 36 / 57 | 40 / 57 | 37 / 62 |
| serious Total, serious adverse events | 1 / 57 | 0 / 57 | 0 / 62 |
Outcome results
Primary
Percent Change in Time of Circulating Estradiol SPE in Each Arm
LS means of percent change
Time frame: baseline and 4-6 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Exemestane 25 mg QD | Percent Change in Time of Circulating Estradiol SPE in Each Arm | -89 percent change |
| Exemestane 25 mg TIW | Percent Change in Time of Circulating Estradiol SPE in Each Arm | -85 percent change |
| Exemestane 25 mg QW | Percent Change in Time of Circulating Estradiol SPE in Each Arm | -60 percent change |
Secondary
17-OH Exemestane Blood Concentration at Surgery
Final drug concentration
Time frame: at surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exemestane 25 mg QD | 17-OH Exemestane Blood Concentration at Surgery | 1069 pmol/L |
| Exemestane 25 mg TIW | 17-OH Exemestane Blood Concentration at Surgery | 196 pmol/L |
| Exemestane 25 mg QW | 17-OH Exemestane Blood Concentration at Surgery | 4 pmol/L |
Secondary
17 OH Exemestane Tissue Concentration at Surgery
Final drug concentration
Time frame: 4-6 weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Exemestane 25 mg QD | 17 OH Exemestane Tissue Concentration at Surgery | cancer tissue | 338 fmol/g wet weight |
| Exemestane 25 mg QD | 17 OH Exemestane Tissue Concentration at Surgery | non cancer adjacent tissue | 1343 fmol/g wet weight |
| Exemestane 25 mg TIW | 17 OH Exemestane Tissue Concentration at Surgery | cancer tissue | 65 fmol/g wet weight |
| Exemestane 25 mg TIW | 17 OH Exemestane Tissue Concentration at Surgery | non cancer adjacent tissue | 65 fmol/g wet weight |
| Exemestane 25 mg QW | 17 OH Exemestane Tissue Concentration at Surgery | cancer tissue | 65 fmol/g wet weight |
| Exemestane 25 mg QW | 17 OH Exemestane Tissue Concentration at Surgery | non cancer adjacent tissue | 65 fmol/g wet weight |
Secondary
Androstenedione Tissue Concentration at Surgery
Final biomarker concentration.
Time frame: 4-6 weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Exemestane 25 mg QD | Androstenedione Tissue Concentration at Surgery | cancer tissue | 6864 fmol/g wet weight |
| Exemestane 25 mg QD | Androstenedione Tissue Concentration at Surgery | non cancer adjacent tissue | 10251 fmol/g wet weight |
| Exemestane 25 mg TIW | Androstenedione Tissue Concentration at Surgery | cancer tissue | 5314 fmol/g wet weight |
| Exemestane 25 mg TIW | Androstenedione Tissue Concentration at Surgery | non cancer adjacent tissue | 12366 fmol/g wet weight |
| Exemestane 25 mg QW | Androstenedione Tissue Concentration at Surgery | cancer tissue | 5564 fmol/g wet weight |
| Exemestane 25 mg QW | Androstenedione Tissue Concentration at Surgery | non cancer adjacent tissue | 10580 fmol/g wet weight |
Secondary
Change in MenQoL Questionnaire Score
MenQOL questionnaire assessed how bothered participants were with 31 symptoms. It contains domains: vasomotor (items 1-3); psychosocial (items 4-10); physical (items 11-26); sexual (items 27-29); in addition to nausea and indigestion. 31 individual symptoms are rated on a scale of 0 (not at all bothered) to 6 (extremely bothered). Total possible score ranged from 0 to 186. MenQOL summary score was calculated as mean of four domain scores (Physical function, Psychosocial function, Sexual function and Vasomotor function) ranging from 1 to 8, with higher scores indicating worse quality of life. Final score-baseline score
Time frame: baseline and 4-6 weeks
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Exemestane 25 mg QD | Change in MenQoL Questionnaire Score | Vasomotor domain | 0.41 score on a scale | Standard Deviation 1.2 |
| Exemestane 25 mg QD | Change in MenQoL Questionnaire Score | Sexual domain | -0.45 score on a scale | Standard Deviation 1 |
| Exemestane 25 mg QD | Change in MenQoL Questionnaire Score | Physical domain | -0.37 score on a scale | Standard Deviation 0.77 |
| Exemestane 25 mg QD | Change in MenQoL Questionnaire Score | Overall | -0.15 score on a scale | Standard Deviation 0.58 |
| Exemestane 25 mg QD | Change in MenQoL Questionnaire Score | Psychosocial domain | -0.19 score on a scale | Standard Deviation 0.98 |
| Exemestane 25 mg TIW | Change in MenQoL Questionnaire Score | Overall | 0.05 score on a scale | Standard Deviation 0.79 |
| Exemestane 25 mg TIW | Change in MenQoL Questionnaire Score | Vasomotor domain | 0.28 score on a scale | Standard Deviation 1.4 |
| Exemestane 25 mg TIW | Change in MenQoL Questionnaire Score | Psychosocial domain | 0.06 score on a scale | Standard Deviation 1.2 |
| Exemestane 25 mg TIW | Change in MenQoL Questionnaire Score | Physical domain | 0.07 score on a scale | Standard Deviation 0.86 |
| Exemestane 25 mg TIW | Change in MenQoL Questionnaire Score | Sexual domain | -0.2 score on a scale | Standard Deviation 1.7 |
| Exemestane 25 mg QW | Change in MenQoL Questionnaire Score | Physical domain | -0.09 score on a scale | Standard Deviation 0.67 |
| Exemestane 25 mg QW | Change in MenQoL Questionnaire Score | Psychosocial domain | -0.06 score on a scale | Standard Deviation 1.1 |
| Exemestane 25 mg QW | Change in MenQoL Questionnaire Score | Sexual domain | -0.52 score on a scale | Standard Deviation 1.7 |
| Exemestane 25 mg QW | Change in MenQoL Questionnaire Score | Vasomotor domain | 0.51 score on a scale | Standard Deviation 1.5 |
| Exemestane 25 mg QW | Change in MenQoL Questionnaire Score | Overall | -0.06 score on a scale | Standard Deviation 0.71 |
Secondary
Change of ER Expression (Cancer Tissue), Central Review
Surgery level-biopsy level.
Time frame: 4-6 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exemestane 25 mg QD | Change of ER Expression (Cancer Tissue), Central Review | 0 Abs change of % of positive tumor cells |
| Exemestane 25 mg TIW | Change of ER Expression (Cancer Tissue), Central Review | 0 Abs change of % of positive tumor cells |
| Exemestane 25 mg QW | Change of ER Expression (Cancer Tissue), Central Review | 0 Abs change of % of positive tumor cells |
Secondary
Change of Ki67% Expression (Adjacent Non Cancer Tissue), Central Review
Surgery level-biopsy level.
Time frame: 4-6 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exemestane 25 mg QD | Change of Ki67% Expression (Adjacent Non Cancer Tissue), Central Review | 0 Absolute change of % of positive cells |
| Exemestane 25 mg TIW | Change of Ki67% Expression (Adjacent Non Cancer Tissue), Central Review | 0 Absolute change of % of positive cells |
| Exemestane 25 mg QW | Change of Ki67% Expression (Adjacent Non Cancer Tissue), Central Review | 0 Absolute change of % of positive cells |
Secondary
Change of Ki67% Expression (Cancer Tissue), Central Review
Surgery level-biopsy level.
Time frame: 4-6 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exemestane 25 mg QD | Change of Ki67% Expression (Cancer Tissue), Central Review | -7.5 Abs change of % of positive tumor cells |
| Exemestane 25 mg TIW | Change of Ki67% Expression (Cancer Tissue), Central Review | -5 Abs change of % of positive tumor cells |
| Exemestane 25 mg QW | Change of Ki67% Expression (Cancer Tissue), Central Review | -4 Abs change of % of positive tumor cells |
Secondary
Change of PgR Expression (Cancer Tissue), Central Review
Surgery level-biopsy level.
Time frame: 4-6 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exemestane 25 mg QD | Change of PgR Expression (Cancer Tissue), Central Review | -17 Abs change of % of positive tumor cells |
| Exemestane 25 mg TIW | Change of PgR Expression (Cancer Tissue), Central Review | -9 Abs change of % of positive tumor cells |
| Exemestane 25 mg QW | Change of PgR Expression (Cancer Tissue), Central Review | -7 Abs change of % of positive tumor cells |
Secondary
Estradiol Tissue Concentration at Surgery
Final biomarker concentration
Time frame: 4-6 weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Exemestane 25 mg QD | Estradiol Tissue Concentration at Surgery | cancer tissue | 15.5 fmol/g wet weight |
| Exemestane 25 mg QD | Estradiol Tissue Concentration at Surgery | non cancer adjacent tissue | 15.5 fmol/g wet weight |
| Exemestane 25 mg TIW | Estradiol Tissue Concentration at Surgery | cancer tissue | 17.1 fmol/g wet weight |
| Exemestane 25 mg TIW | Estradiol Tissue Concentration at Surgery | non cancer adjacent tissue | 15.5 fmol/g wet weight |
| Exemestane 25 mg QW | Estradiol Tissue Concentration at Surgery | cancer tissue | 128.8 fmol/g wet weight |
| Exemestane 25 mg QW | Estradiol Tissue Concentration at Surgery | non cancer adjacent tissue | 15.5 fmol/g wet weight |
Secondary
Estrone Tissue Concentration at Surgery
Final biomarker concentration
Time frame: 4-6 weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Exemestane 25 mg QD | Estrone Tissue Concentration at Surgery | cancer tissue | 8.7 fmol/g wet weight |
| Exemestane 25 mg QD | Estrone Tissue Concentration at Surgery | non cancer adjacent tissue | 17.4 fmol/g wet weight |
| Exemestane 25 mg TIW | Estrone Tissue Concentration at Surgery | cancer tissue | 28.1 fmol/g wet weight |
| Exemestane 25 mg TIW | Estrone Tissue Concentration at Surgery | non cancer adjacent tissue | 37.8 fmol/g wet weight |
| Exemestane 25 mg QW | Estrone Tissue Concentration at Surgery | cancer tissue | 138.9 fmol/g wet weight |
| Exemestane 25 mg QW | Estrone Tissue Concentration at Surgery | non cancer adjacent tissue | 140.5 fmol/g wet weight |
Secondary
Exemestane Blood Concentration at Surgery
Final drug concentration
Time frame: at surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exemestane 25 mg QD | Exemestane Blood Concentration at Surgery | 3217 pmol/L |
| Exemestane 25 mg TIW | Exemestane Blood Concentration at Surgery | 513 pmol/L |
| Exemestane 25 mg QW | Exemestane Blood Concentration at Surgery | 24 pmol/L |
Secondary
Exemestane Tissue Concentration at Surgery
Final drug concentration
Time frame: 4-6 weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Exemestane 25 mg QD | Exemestane Tissue Concentration at Surgery | non cancer adjacent tissue | 17485 fmol/g wet weight |
| Exemestane 25 mg QD | Exemestane Tissue Concentration at Surgery | cancer tissue | 3807 fmol/g wet weight |
| Exemestane 25 mg TIW | Exemestane Tissue Concentration at Surgery | cancer tissue | 44 fmol/g wet weight |
| Exemestane 25 mg TIW | Exemestane Tissue Concentration at Surgery | non cancer adjacent tissue | 435 fmol/g wet weight |
| Exemestane 25 mg QW | Exemestane Tissue Concentration at Surgery | cancer tissue | 44 fmol/g wet weight |
| Exemestane 25 mg QW | Exemestane Tissue Concentration at Surgery | non cancer adjacent tissue | 44 fmol/g wet weight |
Secondary
Percent Change in Time of Circulating Estradiol LLE in Each Arm
LS means of percent change
Time frame: baseline and 4-6 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exemestane 25 mg QD | Percent Change in Time of Circulating Estradiol LLE in Each Arm | -96 percent change |
| Exemestane 25 mg TIW | Percent Change in Time of Circulating Estradiol LLE in Each Arm | -91 percent change |
| Exemestane 25 mg QW | Percent Change in Time of Circulating Estradiol LLE in Each Arm | -72 percent change |
Secondary
Percent Change of Circulating Adiponectin
\[(Final levels-baseline levels)/baseline levels\]\*100
Time frame: baseline and 4-6 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exemestane 25 mg QD | Percent Change of Circulating Adiponectin | -12 percent change |
| Exemestane 25 mg TIW | Percent Change of Circulating Adiponectin | -3 percent change |
| Exemestane 25 mg QW | Percent Change of Circulating Adiponectin | -1 percent change |
Secondary
Percent Change of Circulating Androstenedione
\[(Final levels-baseline levels)/baseline levels\]\*100
Time frame: baseline and 4-6 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exemestane 25 mg QD | Percent Change of Circulating Androstenedione | 0 percent change |
| Exemestane 25 mg TIW | Percent Change of Circulating Androstenedione | 11 percent change |
| Exemestane 25 mg QW | Percent Change of Circulating Androstenedione | 11 percent change |
Secondary
Percent Change of Circulating Estrone LLE
\[(Final levels-baseline levels)/baseline levels\]\*100
Time frame: baseline and 4-6 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exemestane 25 mg QD | Percent Change of Circulating Estrone LLE | -99 percent change |
| Exemestane 25 mg TIW | Percent Change of Circulating Estrone LLE | -96 percent change |
| Exemestane 25 mg QW | Percent Change of Circulating Estrone LLE | -78 percent change |
Secondary
Percent Change of Circulating Estrone SPE
\[(Final levels-baseline levels)/baseline levels\]\*100
Time frame: baseline and 4-6 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exemestane 25 mg QD | Percent Change of Circulating Estrone SPE | -93 percent change |
| Exemestane 25 mg TIW | Percent Change of Circulating Estrone SPE | -89 percent change |
| Exemestane 25 mg QW | Percent Change of Circulating Estrone SPE | -73 percent change |
Secondary
Percent Change of Circulating Estrone Sulfate
\[(Final levels-baseline levels)/baseline levels\]\*100
Time frame: baseline and 4-6 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exemestane 25 mg QD | Percent Change of Circulating Estrone Sulfate | -96 percent change |
| Exemestane 25 mg TIW | Percent Change of Circulating Estrone Sulfate | -95 percent change |
| Exemestane 25 mg QW | Percent Change of Circulating Estrone Sulfate | -75 percent change |
Secondary
Percent Change of Circulating HDL Cholesterol
\[(Final levels-baseline levels)/baseline levels\]\*100
Time frame: baseline and 4-6 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exemestane 25 mg QD | Percent Change of Circulating HDL Cholesterol | -14 percent change |
| Exemestane 25 mg TIW | Percent Change of Circulating HDL Cholesterol | -3 percent change |
| Exemestane 25 mg QW | Percent Change of Circulating HDL Cholesterol | -2 percent change |
Secondary
Percent Change of Circulating Insulin
\[(Final levels-baseline levels)/baseline levels\]\*100
Time frame: baseline and 4-6 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exemestane 25 mg QD | Percent Change of Circulating Insulin | 3 percent change |
| Exemestane 25 mg TIW | Percent Change of Circulating Insulin | 9 percent change |
| Exemestane 25 mg QW | Percent Change of Circulating Insulin | 4 percent change |
Secondary
Percent Change of Circulating LDL Cholesterol
\[(Final levels-baseline levels)/baseline levels\]\*100
Time frame: baseline and 4-6 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exemestane 25 mg QD | Percent Change of Circulating LDL Cholesterol | -1 percent change |
| Exemestane 25 mg TIW | Percent Change of Circulating LDL Cholesterol | 0 percent change |
| Exemestane 25 mg QW | Percent Change of Circulating LDL Cholesterol | 0 percent change |
Secondary
Percent Change of Circulating Leptin
\[(Final levels-baseline levels)/baseline levels\]\*100
Time frame: baseline and 4-6 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exemestane 25 mg QD | Percent Change of Circulating Leptin | -16 percent change |
| Exemestane 25 mg TIW | Percent Change of Circulating Leptin | -5 percent change |
| Exemestane 25 mg QW | Percent Change of Circulating Leptin | -4 percent change |
Secondary
Percent Change of Circulating SHBG
\[(Final levels-baseline levels)/baseline levels\]\*100
Time frame: baseline and 4-6 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exemestane 25 mg QD | Percent Change of Circulating SHBG | -29 percent change |
| Exemestane 25 mg TIW | Percent Change of Circulating SHBG | -15 percent change |
| Exemestane 25 mg QW | Percent Change of Circulating SHBG | -5.5 percent change |
Secondary
Percent Change of Circulating Testosterone
\[(Final levels-baseline levels)/baseline levels\]\*100
Time frame: baseline and 4-6 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exemestane 25 mg QD | Percent Change of Circulating Testosterone | -19 percent change |
| Exemestane 25 mg TIW | Percent Change of Circulating Testosterone | 0 percent change |
| Exemestane 25 mg QW | Percent Change of Circulating Testosterone | 0 percent change |
Secondary
Percent Change of Circulating Testosterone CLIA
\[(Final levels-baseline levels)/baseline levels\]\*100
Time frame: baseline and 4-6 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exemestane 25 mg QD | Percent Change of Circulating Testosterone CLIA | 10 percent change |
| Exemestane 25 mg TIW | Percent Change of Circulating Testosterone CLIA | 0 percent change |
| Exemestane 25 mg QW | Percent Change of Circulating Testosterone CLIA | 6 percent change |
Secondary
Percent Change of Circulating Total Cholesterol
\[(Final levels-baseline levels)/baseline levels\]\*100
Time frame: baseline and 4-6 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exemestane 25 mg QD | Percent Change of Circulating Total Cholesterol | -4 percent change |
| Exemestane 25 mg TIW | Percent Change of Circulating Total Cholesterol | -5 percent change |
| Exemestane 25 mg QW | Percent Change of Circulating Total Cholesterol | -1 percent change |
Secondary
Percent Change of Circulating Total Estrone
\[(Final levels-baseline levels)/baseline levels\]\*100
Time frame: baseline and 4-6 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exemestane 25 mg QD | Percent Change of Circulating Total Estrone | -95 percent change |
| Exemestane 25 mg TIW | Percent Change of Circulating Total Estrone | -94 percent change |
| Exemestane 25 mg QW | Percent Change of Circulating Total Estrone | -76 percent change |
Secondary
Percent Change of Circulating Triglycerides
\[(Final levels-baseline levels)/baseline levels\]\*100
Time frame: baseline and 4-6 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exemestane 25 mg QD | Percent Change of Circulating Triglycerides | -7 percent change |
| Exemestane 25 mg TIW | Percent Change of Circulating Triglycerides | -1 percent change |
| Exemestane 25 mg QW | Percent Change of Circulating Triglycerides | 5 percent change |
Secondary
Percent Change of HOMA IR
Insulin Resistance Index (HOMA-IR) measures insulin resistance, calculated by fasting insulin (mU/L) multiplied by fasting glucose (mmol/L), and divided by a constant (22.5). A higher score indicates higher insulin resistance.
Time frame: baseline and 4-6 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exemestane 25 mg QD | Percent Change of HOMA IR | 8 percent change |
| Exemestane 25 mg TIW | Percent Change of HOMA IR | 15 percent change |
| Exemestane 25 mg QW | Percent Change of HOMA IR | 6 percent change |
Secondary
Percent Change of Serum Glucose
\[(Final levels-baseline levels)/baseline levels\]\*100
Time frame: baseline and 4-6 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exemestane 25 mg QD | Percent Change of Serum Glucose | -1 percent change |
| Exemestane 25 mg TIW | Percent Change of Serum Glucose | 1 percent change |
| Exemestane 25 mg QW | Percent Change of Serum Glucose | -2 percent change |
Secondary
Testosterone Tissue Concentration at Surgery
Final biomarker concentration
Time frame: 4-6 weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Exemestane 25 mg QD | Testosterone Tissue Concentration at Surgery | cancer tissue | 395 fmol/g wet weight |
| Exemestane 25 mg QD | Testosterone Tissue Concentration at Surgery | non cancer adjacent tissue | 436 fmol/g wet weight |
| Exemestane 25 mg TIW | Testosterone Tissue Concentration at Surgery | cancer tissue | 396 fmol/g wet weight |
| Exemestane 25 mg TIW | Testosterone Tissue Concentration at Surgery | non cancer adjacent tissue | 464 fmol/g wet weight |
| Exemestane 25 mg QW | Testosterone Tissue Concentration at Surgery | cancer tissue | 453 fmol/g wet weight |
| Exemestane 25 mg QW | Testosterone Tissue Concentration at Surgery | non cancer adjacent tissue | 399 fmol/g wet weight |
Other Pre-specified
Proteomic Analysis
The Proteomic Analysis was not performed.
Time frame: 4-6 weeks