Trial Outcomes & Findings for Tamoxifen or Letrozole in Treating Women With Ductal Carcinoma in Situ (NCT NCT00290745)

Last Updated: 2020-12-04

Results Overview

Change in size of Ductal Carcinoma in situ (DCIS) for participants on hormonal therapy, as determined by mammography are determined by (1) largest diameter of tumor, as visualized on mammography (2) extent of disease on mammography (3) quantification of mammographically-detected change from baseline to 6-month and used to generate the change in tumor volume of mammographic extent of disease from baseline. Since values were not normally distributed, the median change was calculated, and Wilcoxon sign rank tests were used to evaluate the significance of these changes

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

79 participants

Primary outcome timeframe

Baseline and 6 months

Results posted on

2020-12-04

Participant Flow

Patients seeking treatment at the University of California, San Francisco (UCSF) Breast Care Center and Kaiser Permanente for a diagnosis of DCIS were approached by their physicians at their discretion, and if fitting the eligibility criteria were asked to participate in the study.

Participant milestones

Participant milestones
Measure	Tamoxifen or Letrozole tamoxifen or letrozole work in treating women with ductal carcinoma in situ letrozole tamoxifen citrate conventional surgery neoadjuvant therapy
Overall Study STARTED	79
Overall Study COMPLETED	67
Overall Study NOT COMPLETED	12

Reasons for withdrawal

Reasons for withdrawal
Measure	Tamoxifen or Letrozole tamoxifen or letrozole work in treating women with ductal carcinoma in situ letrozole tamoxifen citrate conventional surgery neoadjuvant therapy
Overall Study Withdrawal by Subject	4
Overall Study Physician Decision	2
Overall Study Surgery after 3 months for progression	3
Overall Study Baseline MRI not available	3

Baseline Characteristics

Tamoxifen or Letrozole in Treating Women With Ductal Carcinoma in Situ

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tamoxifen or Letrozole n=67 Participants tamoxifen or letrozole work in treating women with ductal carcinoma in situ letrozole tamoxifen citrate conventional surgery neoadjuvant therapy
Age, Continuous	62.9 years n=5 Participants
Sex: Female, Male Female	67 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	64 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	10 Participants n=5 Participants
Race (NIH/OMB) White	54 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Region of Enrollment United States	67 participants n=5 Participants
Nuclear Grade Low (Grade 1)	8 Participants n=5 Participants
Nuclear Grade Intermediate (Grade 2)	31 Participants n=5 Participants
Nuclear Grade High (Grade 3)	27 Participants n=5 Participants
Nuclear Grade Indeterminate	1 Participants n=5 Participants
Hormone receptor status ER+ / PgR+	55 Participants n=5 Participants
Hormone receptor status ER+/(PgR- or PgR Unknown)	10 Participants n=5 Participants
Hormone receptor status ER-/PgR+	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 6 months

Population: Only 54 patients had evaluable mammograms at 6 months

Outcome measures

Outcome measures
Measure	Tamoxifen or Letrozole n=54 Participants tamoxifen or letrozole work in treating women with ductal carcinoma in situ letrozole tamoxifen citrate conventional surgery neoadjuvant therapy
Median Change in 6-month Tumor Volume Compared to Baseline Using Mammography	-5.0 change in tumor volume (mm) Interval -10.4 to 0.4

PRIMARY outcome

Timeframe: Baseline and 6 months

Change in size of Ductal Carcinoma in situ (DCIS) on hormonal therapy, as determined by MRI are determined by (1) largest diameter of tumor, as visualized on MRI (2) extent of disease on MRI (3) quantification of MR-detected change from baseline to 6-month and used to generate the change in tumor volume of MRI extent of disease from baseline. Since values were not normally distributed, the median change was calculated, and Wilcoxon sign rank tests were used to evaluate the significance of these changes.

Outcome measures

Outcome measures
Measure	Tamoxifen or Letrozole n=67 Participants tamoxifen or letrozole work in treating women with ductal carcinoma in situ letrozole tamoxifen citrate conventional surgery neoadjuvant therapy
Median Change in 6-month Tumor Volume Compared to Baseline Using Magnetic Resonance Imaging (MRI)	-0.8 change in tumor volume (cm3) Interval -1.95 to 0.35

SECONDARY outcome

Timeframe: 3 months

MRI volume response at each time point was classified as follows: 90% image-complete response (ICR90) is defined as a \>90% reduction in tumor volume, 80% image-complete response (ICR80) is defined as an 81-90% reduction in tumor volume , partial response (PR) is defined as a 20-80% reduction in tumor volume, and sustained disease or progressive disease (SD/PD) defined as a \<20% reduction or increase in volume.

Outcome measures

Outcome measures
Measure	Tamoxifen or Letrozole n=67 Participants tamoxifen or letrozole work in treating women with ductal carcinoma in situ letrozole tamoxifen citrate conventional surgery neoadjuvant therapy
Number of Responders to Neoadjuvant Therapy at Month 3 ICR90	13 Participants
Number of Responders to Neoadjuvant Therapy at Month 3 ICR80	10 Participants
Number of Responders to Neoadjuvant Therapy at Month 3 PR	27 Participants
Number of Responders to Neoadjuvant Therapy at Month 3 SD/PD	17 Participants

SECONDARY outcome

Timeframe: 6 months

Outcome measures

Outcome measures
Measure	Tamoxifen or Letrozole n=67 Participants tamoxifen or letrozole work in treating women with ductal carcinoma in situ letrozole tamoxifen citrate conventional surgery neoadjuvant therapy
Number of Responders to Neoadjuvant Therapy at Month 6 ICR90	22 Participants
Number of Responders to Neoadjuvant Therapy at Month 6 ICR80	7 Participants
Number of Responders to Neoadjuvant Therapy at Month 6 PR	26 Participants
Number of Responders to Neoadjuvant Therapy at Month 6 SD/PD	12 Participants

SECONDARY outcome

Timeframe: Baseline and 6 months

Population: Only 46 participants had both evaluable ER scores at baseline and evaluable month 6 scans

Tumor volume changes between baseline and surgery were calculated at month 6 and compared across baseline ER Hormone (H-) Score quartile. The ER H- scores are a percentage that tells you how many cells out of 100 stain positive for hormone receptors. Each participant is assigned an ER H- score at baseline with the full score range between 0 (none have receptors) and 100 (all have receptors). The participants were grouped into quartiles (four equal groups) based on their baseline ER H- score. ER H- score and the reduction in tumor volume from baseline to month 6 was measured for each quartile group.

Outcome measures

Outcome measures
Measure	Tamoxifen or Letrozole n=46 Participants tamoxifen or letrozole work in treating women with ductal carcinoma in situ letrozole tamoxifen citrate conventional surgery neoadjuvant therapy
Median Reduction in Tumor Volume by Estrogen Receptor Hormone (ER H-) Quartile Group Baseline ER Score quartile = 0-25	-58.8 decrease in tumor volume (cm^3) Interval -141.6 to 24.0
Median Reduction in Tumor Volume by Estrogen Receptor Hormone (ER H-) Quartile Group Baseline ER Score quartile = 26-50	-70.3 decrease in tumor volume (cm^3) Interval -91.2 to 49.4
Median Reduction in Tumor Volume by Estrogen Receptor Hormone (ER H-) Quartile Group Baseline ER Score quartile = 51-75	-80.3 decrease in tumor volume (cm^3) Interval -92.1 to -68.5
Median Reduction in Tumor Volume by Estrogen Receptor Hormone (ER H-) Quartile Group Baseline ER Score quartile = 76-100	-71.1 decrease in tumor volume (cm^3) Interval -85.75 to -56.45

SECONDARY outcome

Timeframe: Baseline and 6 months

Population: Only 45 participants had both evaluable PgR scores at baseline and evaluable month 6 scans

Tumor volume changes between baseline and surgery were calculated at month 6 and compared across baseline PgR Hormone (H-) Score quartile. The PgR H-scores are a percentage that tells you how many cells out of 100 stain positive for hormone receptors. Each participant is assigned a PgR H- score at baseline with the full PgR H score ranges between 0 (none have receptors) and 100 (all have receptors). The participants were grouped into quartiles (four equal groups) based on their baseline PgR H- score and the reduction in tumor volume from baseline to month 6 was measured for each quartile group. A wilcoxon sign rank tests were used to evaluate the significance of these changes

Outcome measures

Outcome measures
Measure	Tamoxifen or Letrozole n=45 Participants tamoxifen or letrozole work in treating women with ductal carcinoma in situ letrozole tamoxifen citrate conventional surgery neoadjuvant therapy
Median Reduction in Tumor Volume by PgR H-score by Quartile Group Baseline PgR Score Quartile = 0-25	-69.1 reduction in tumor volume (cm^3) Interval -103.7 to -34.5
Median Reduction in Tumor Volume by PgR H-score by Quartile Group Baseline PgR Score Quartile = 26-50	-45.8 reduction in tumor volume (cm^3) Interval -130.95 to 39.95
Median Reduction in Tumor Volume by PgR H-score by Quartile Group Baseline PgR Score Quartile = 51-75	-69.6 reduction in tumor volume (cm^3) Interval -85.65 to -56.65
Median Reduction in Tumor Volume by PgR H-score by Quartile Group Baseline PgR Score Quartile = 76-100	-96.2 reduction in tumor volume (cm^3) Interval -106.2 to -86.2

SECONDARY outcome

Timeframe: Baseline and 6 months

Population: Only 45 participants had both evaluable Ki-67 scores at baseline and evaluable month 6 scan

Tumor volume changes between baseline and surgery were calculated at month 6 by Baseline Ki-67 Average Score which is divided into 2 groups: (1) \<=10% or (2) \>10% to 100%. In est results, the Ki-67 findings expressed as a percentage with less than 10% considered low Ki-67 expression and \> than 10% or higher considered high. A "high" score means that the breast tumor is more likely to be aggressive and spread quickly. A wilcoxon sign rank tests were used to evaluate the significance of these changes

Outcome measures

Outcome measures
Measure	Tamoxifen or Letrozole n=45 Participants tamoxifen or letrozole work in treating women with ductal carcinoma in situ letrozole tamoxifen citrate conventional surgery neoadjuvant therapy
Median Reduction in Tumor Volume by Ki-67 Average Score Baseline Ki67 Average <=10%	-73.0 reduction in tumor volume (cm^3) Interval -98.45 to -47.55
Median Reduction in Tumor Volume by Ki-67 Average Score Baseline Ki67 Average > 10%	-70.3 reduction in tumor volume (cm^3) Interval -88.55 to -52.05

SECONDARY outcome

Timeframe: 6 months

Correlations between pathologic tumor size and maximum diameters of baseline and 6-month MRI extent of disease were evaluated using Spearman correlation coefficient measure of association. The Spearman's rank-order correlation (rs) measures the strength and direction of association between two variables. The Spearman correlation coefficient, rs, can take values from +1 to -1 where a value of +1 indicates a perfect association, an rs of 0 indicates no association and an rs of -1 indicates a perfect negative association. The closer rs is to 0, the weaker the association.

Outcome measures

Outcome measures
Measure	Tamoxifen or Letrozole n=67 Participants tamoxifen or letrozole work in treating women with ductal carcinoma in situ letrozole tamoxifen citrate conventional surgery neoadjuvant therapy
Correlation Between Pathologic Tumor Size at Radiographic (MRI) Tumor Size	0.46 Spearman correlation coefficient (rs)

SECONDARY outcome

Timeframe: 6 months

Population: Only 54 patients had evaluable mammograms at 6 months

Correlations between pathologic tumor size and maximum diameters of baseline and pre-surgical mammographic extent of disease were evaluated using Spearman correlation coefficient measure of association. The Spearman's rank-order correlation (rs) measures the strength and direction of association between two variables. The Spearman correlation coefficient, rs, can take values from +1 to -1 where a value of +1 indicates a perfect association, an rs of 0 indicates no association and an rs of -1 indicates a perfect negative association. The closer rs is to 0, the weaker the association.

Outcome measures

Outcome measures
Measure	Tamoxifen or Letrozole n=54 Participants tamoxifen or letrozole work in treating women with ductal carcinoma in situ letrozole tamoxifen citrate conventional surgery neoadjuvant therapy
Correlation Between Pathologic Tumor Size and Mammographic Tumor Size	0.02 Spearman correlation coefficient (rs)

Adverse Events

Tamoxifen or Letrozole

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. E. Shelly Hwang, MD, MPH

Duke University and Duke Cancer Institute

Phone: (919) 684-6849

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place