Trial Outcomes & Findings for Study of Breast Cancer Prevention by Letrozole in High Risk Women (NCT NCT00579826)
NCT ID: NCT00579826
Last Updated: 2023-06-12
Results Overview
Change in proliferation rate (percent positively stained cells for Ki-67 antigen by immunocytochemistry) in benign breast epithelial cells acquired by random periareolar fine needle aspiration (RPFNA) from women at high risk for the development of breast cancer.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
55 participants
Primary outcome timeframe
Baseline to 6 Months
Results posted on
2023-06-12
Participant Flow
Participant milestones
| Measure |
Letrozole
Letrozole, 2.5 mg daily for 6 months
Letrozole: Letrozole 2.5 mg tablet daily. Then optional open label letrozole for another 6 months.
|
Placebo
Placebo, daily for 6 months
Placebo: Placebo tablet daily for 6 months then optional open label letrozole for 6 months.
|
|---|---|---|
|
Overall Study
STARTED
|
29
|
26
|
|
Overall Study
6 Months
|
28
|
25
|
|
Overall Study
COMPLETED
|
24
|
23
|
|
Overall Study
NOT COMPLETED
|
5
|
3
|
Reasons for withdrawal
| Measure |
Letrozole
Letrozole, 2.5 mg daily for 6 months
Letrozole: Letrozole 2.5 mg tablet daily. Then optional open label letrozole for another 6 months.
|
Placebo
Placebo, daily for 6 months
Placebo: Placebo tablet daily for 6 months then optional open label letrozole for 6 months.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
5
|
3
|
Baseline Characteristics
Study of Breast Cancer Prevention by Letrozole in High Risk Women
Baseline characteristics by cohort
| Measure |
Letrozole
n=29 Participants
Letrozole, 2.5 mg daily for 6 months
Letrozole: Letrozole 2.5 mg tablet daily. Then optional open label letrozole for another 6 months.
|
Placebo
n=26 Participants
Placebo, daily for 6 months
Placebo: Placebo tablet daily for 6 months then optional open label letrozole for 6 months.
|
Total
n=55 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
58.2 years
STANDARD_DEVIATION 8.3 • n=5 Participants
|
44.7 years
STANDARD_DEVIATION 7.4 • n=7 Participants
|
57.0 years
STANDARD_DEVIATION 7.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
29 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
55 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
29 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
54 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
29 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
54 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
29 participants
n=5 Participants
|
26 participants
n=7 Participants
|
55 participants
n=5 Participants
|
|
Height
|
1.63 m
STANDARD_DEVIATION 0.09 • n=5 Participants
|
1.64 m
STANDARD_DEVIATION 0.08 • n=7 Participants
|
1.63 m
STANDARD_DEVIATION 0.08 • n=5 Participants
|
|
Weight
|
69.0 kg
STANDARD_DEVIATION 11.2 • n=5 Participants
|
73.6 kg
STANDARD_DEVIATION 15.9 • n=7 Participants
|
71.2 kg
STANDARD_DEVIATION 13.7 • n=5 Participants
|
|
Body Mass Index
|
26.3 kg/m^2
STANDARD_DEVIATION 5.0 • n=5 Participants
|
27.9 kg/m^2
STANDARD_DEVIATION 9.1 • n=7 Participants
|
27.0 kg/m^2
STANDARD_DEVIATION 7.2 • n=5 Participants
|
|
Age at menarche
|
12.6 years
STANDARD_DEVIATION 1.3 • n=5 Participants
|
12.6 years
STANDARD_DEVIATION 1.2 • n=7 Participants
|
12.6 years
STANDARD_DEVIATION 1.2 • n=5 Participants
|
|
Age at first live birth
|
20.5 years
STANDARD_DEVIATION 10.1 • n=5 Participants
|
21.7 years
STANDARD_DEVIATION 11.1 • n=7 Participants
|
21.4 years
STANDARD_DEVIATION 10.2 • n=5 Participants
|
|
History of prior breast biopsy
History of biopsy
|
19 participants
n=5 Participants
|
16 participants
n=7 Participants
|
35 participants
n=5 Participants
|
|
History of prior breast biopsy
No history of biopsy
|
10 participants
n=5 Participants
|
10 participants
n=7 Participants
|
20 participants
n=5 Participants
|
|
History of prior Ductal Carcinoma In Situ (DCIS) or Lobular Carcinoma in Situ (LCIS)
History
|
3 participants
n=5 Participants
|
1 participants
n=7 Participants
|
4 participants
n=5 Participants
|
|
History of prior Ductal Carcinoma In Situ (DCIS) or Lobular Carcinoma in Situ (LCIS)
No History
|
26 participants
n=5 Participants
|
25 participants
n=7 Participants
|
51 participants
n=5 Participants
|
|
Number of relatives with breast cancer
With relatives
|
18 participants
n=5 Participants
|
20 participants
n=7 Participants
|
38 participants
n=5 Participants
|
|
Number of relatives with breast cancer
No relatives
|
11 participants
n=5 Participants
|
6 participants
n=7 Participants
|
17 participants
n=5 Participants
|
|
Gail risk of developing breast cancer within 5 years
|
4.2 percent
STANDARD_DEVIATION 3.9 • n=5 Participants
|
3.4 percent
STANDARD_DEVIATION 1.8 • n=7 Participants
|
3.8 percent
STANDARD_DEVIATION 3.1 • n=5 Participants
|
|
Immunocytochemical expression of Ki-67
|
4.5 percent
STANDARD_DEVIATION 3.1 • n=5 Participants
|
4.0 percent
STANDARD_DEVIATION 2.8 • n=7 Participants
|
4.2 percent
STANDARD_DEVIATION 3.0 • n=5 Participants
|
|
Cytology
Hyperplasia
|
4 participants
n=5 Participants
|
4 participants
n=7 Participants
|
8 participants
n=5 Participants
|
|
Cytology
Hyperplasia with borderline atypia
|
5 participants
n=5 Participants
|
5 participants
n=7 Participants
|
10 participants
n=5 Participants
|
|
Cytology
Hyperplasia with Atypia
|
20 participants
n=5 Participants
|
17 participants
n=7 Participants
|
37 participants
n=5 Participants
|
|
Masood Score
|
15 units on a scale
STANDARD_DEVIATION 0.9 • n=5 Participants
|
15 units on a scale
STANDARD_DEVIATION 1.1 • n=7 Participants
|
15 units on a scale
STANDARD_DEVIATION 1.0 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to 6 MonthsPopulation: Subjects who complete initial 6-month period and have repeat RPFNA.
Change in proliferation rate (percent positively stained cells for Ki-67 antigen by immunocytochemistry) in benign breast epithelial cells acquired by random periareolar fine needle aspiration (RPFNA) from women at high risk for the development of breast cancer.
Outcome measures
| Measure |
Letrozole
n=28 Participants
Letrozole, 2.5 mg daily for 6 months
Letrozole: Letrozole 2.5 mg tablet daily. Then optional open label letrozole for another 6 months.
|
Placebo
n=25 Participants
Placebo, daily for 6 months
Placebo: Placebo tablet daily for 6 months then optional open label letrozole for 6 months.
|
|---|---|---|
|
Change in Proliferation Rate (Ki-67 by Immunocytochemistry) From Baseline to 6 Months
|
-1.5 percentage of cells stained positive
Standard Deviation 2.8
|
-1.1 percentage of cells stained positive
Standard Deviation 3.9
|
SECONDARY outcome
Timeframe: Baseline to 6 MonthsPopulation: Subjects who complete initial 6-month intervention and have a repeat RPFNA, thus a change from baseline to 6-months can be computed.
Masood score is a semi-quantitative index of increasing abnormality, thus higher values are worse. Range 6 to 24. Based on Masood S, Frykberg ER, McLellan GL, Scalapino MC, Mitchum DG, Bullard JB. Prospective evaluation of radiologically directed fine-needle aspiration biopsy of nonpalpable breast lesions. Cancer 1990; 66:1480-7.
Outcome measures
| Measure |
Letrozole
n=28 Participants
Letrozole, 2.5 mg daily for 6 months
Letrozole: Letrozole 2.5 mg tablet daily. Then optional open label letrozole for another 6 months.
|
Placebo
n=25 Participants
Placebo, daily for 6 months
Placebo: Placebo tablet daily for 6 months then optional open label letrozole for 6 months.
|
|---|---|---|
|
Assessment of Change in Morphology by the Masood Score.
|
-1.1 units on a scale
Standard Deviation 1.5
|
-1.1 units on a scale
Standard Deviation 1.8
|
SECONDARY outcome
Timeframe: Baseline to 6 MonthsPopulation: Subjects who complete the initial 6-months intervention and have mammograms available for analysis at baseline and 6 months, thus a change can be computed.
Percent area of the breast considered to be at increased density, as determined by the computer program Cumulus..
Outcome measures
| Measure |
Letrozole
n=23 Participants
Letrozole, 2.5 mg daily for 6 months
Letrozole: Letrozole 2.5 mg tablet daily. Then optional open label letrozole for another 6 months.
|
Placebo
n=24 Participants
Placebo, daily for 6 months
Placebo: Placebo tablet daily for 6 months then optional open label letrozole for 6 months.
|
|---|---|---|
|
Change in Mammographic Density From Baseline to 6 Months..
|
-3.8 percent of breast area at high density
Standard Deviation 12.8
|
0.2 percent of breast area at high density
Standard Deviation 11.8
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to 6 monthsPopulation: subjects who complete 6 month visit and provide a 6-month FIQ score, such that the change in score (6-month - baseline) can be computed.
Assessment of impact of fibromyalgia on everyday living activities. Composite score ranges from 0 (best, no interference or impact on activities) to 104 (worst, maximum interference with activities).
Outcome measures
| Measure |
Letrozole
n=25 Participants
Letrozole, 2.5 mg daily for 6 months
Letrozole: Letrozole 2.5 mg tablet daily. Then optional open label letrozole for another 6 months.
|
Placebo
n=24 Participants
Placebo, daily for 6 months
Placebo: Placebo tablet daily for 6 months then optional open label letrozole for 6 months.
|
|---|---|---|
|
Change in Fibromyalgia Impact Questionnaire (FIQ) Score.
|
3.7 score on scale
Standard Deviation 9.6
|
3.9 score on scale
Standard Deviation 10.3
|
OTHER_PRE_SPECIFIED outcome
Timeframe: baseline to 6 monthsPopulation: Subjects who complete a 6-months visit and a 6-months BFI questionnaire, such that change in score can be computed.
Assessment of the extent to which fatigue interferes in normal everyday living activities. Change over 6 months of treatment is assessed. Range from 0 (best, no fatigue) to 10 (worst). Increase in score indicates greater intensity of fatigue and/or greater interference with activities due to fatigue.
Outcome measures
| Measure |
Letrozole
n=26 Participants
Letrozole, 2.5 mg daily for 6 months
Letrozole: Letrozole 2.5 mg tablet daily. Then optional open label letrozole for another 6 months.
|
Placebo
n=25 Participants
Placebo, daily for 6 months
Placebo: Placebo tablet daily for 6 months then optional open label letrozole for 6 months.
|
|---|---|---|
|
Change in Brief Fatigue Inventory (BFI) Score.
|
0.6 score on a scale
Standard Deviation 1.9
|
0.4 score on a scale
Standard Deviation 1.6
|
Adverse Events
Letrozole, 2.5 mg Daily for 12 Months
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Placebo for 6 Months; Open Label Letrozole 2.5 mg Daily
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Letrozole, 2.5 mg Daily for 12 Months
n=29 participants at risk
Letrozole, 2.5 mg daily for 6 months
Letrozole: Letrozole 2.5 mg tablet daily. Then optional open label letrozole for another 6 months.
|
Placebo for 6 Months; Open Label Letrozole 2.5 mg Daily
n=26 participants at risk
Placebo, daily for 6 months
Placebo: Placebo tablet daily for 6 months then optional open label letrozole for 6 months.
|
|---|---|---|
|
Eye disorders
Cataract
|
3.4%
1/29 • Number of events 2 • 1 year
duration of study agent
|
0.00%
0/26 • 1 year
duration of study agent
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain
|
17.2%
5/29 • Number of events 5 • 1 year
duration of study agent
|
11.5%
3/26 • Number of events 3 • 1 year
duration of study agent
|
|
Cardiac disorders
Atrial Tachycardia
|
3.4%
1/29 • Number of events 1 • 1 year
duration of study agent
|
0.00%
0/26 • 1 year
duration of study agent
|
|
Skin and subcutaneous tissue disorders
Wound complication
|
3.4%
1/29 • Number of events 1 • 1 year
duration of study agent
|
0.00%
0/26 • 1 year
duration of study agent
|
|
Hepatobiliary disorders
Gallbladder necrosis
|
3.4%
1/29 • Number of events 1 • 1 year
duration of study agent
|
0.00%
0/26 • 1 year
duration of study agent
|
|
Renal and urinary disorders
Kidney pain
|
0.00%
0/29 • 1 year
duration of study agent
|
3.8%
1/26 • Number of events 1 • 1 year
duration of study agent
|
|
Nervous system disorders
Dizziness
|
3.4%
1/29 • Number of events 1 • 1 year
duration of study agent
|
0.00%
0/26 • 1 year
duration of study agent
|
|
Gastrointestinal disorders
Vomiting/nausea
|
3.4%
1/29 • Number of events 3 • 1 year
duration of study agent
|
0.00%
0/26 • 1 year
duration of study agent
|
|
Nervous system disorders
Headache
|
3.4%
1/29 • Number of events 2 • 1 year
duration of study agent
|
0.00%
0/26 • 1 year
duration of study agent
|
|
Reproductive system and breast disorders
Vaginal mucositis/ cervical infection
|
3.4%
1/29 • Number of events 2 • 1 year
duration of study agent
|
0.00%
0/26 • 1 year
duration of study agent
|
|
Skin and subcutaneous tissue disorders
Skin infection
|
3.4%
1/29 • Number of events 1 • 1 year
duration of study agent
|
0.00%
0/26 • 1 year
duration of study agent
|
Additional Information
Bruce F. Kimler, Ph.D.
University of Kansas Medical Center
Phone: 913-588-4523
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place