Newly Diagnosed Hormone Positive Clinical Stage 1 or 2 Breast Cancer
Conditions
Brief summary
The purpose of the study is to see if tumors respond to endocrine therapy by taking a total of 21 doses of Tamoxifen before and after surgery. Tamoxifen is currently approved by the FDA (Food and Drug Administration) for use in the treatment of hormone positive breast cancer.
Detailed description
Patients who are eligible (newly diagnosed hormone positive clinical stage 1 or 2 breast cancer) will be approached about the study. If they sign informed consent a prescription for 21 doses of Tamoxifen will be provided. The patient's surgery will be scheduled at a time convenient for the patient and the surgeon. Once the surgery has been scheduled, a medication calendar will be completed that allows the patient to take tamoxifen for 7 days preoperatively with the 7th dose of tamoxifen to coincide with the day before surgery. The patient will continue to take tamoxifen for 2 weeks (14 days) after surgery. Patients will then proceed along normal treatment guidelines. For those needing chemotherapy or radiation therapy, we recommend the long term endocrine therapy start at the conclusion of chemo and/or radiation treatments. For those not going on to any additional therapy, the prescription for endocrine therapy will be written at the initial post-operative visit. Unstained slides from the formalin-fixed, paraffin-embedded tissue blocks from the patient's breast tissue from which the original diagnosis of breast cancer was made by H&E will be stained for Ki67. After endocrine therapy and subsequent resection, carcinoma will be confirmed by the participating pathologist on H&E, and Ki67 will be performed on unstained slides from a representative tissue block containing invasive carcinoma. The pathologist will circle a designated area of tumor on the H&E slide and both the H&E and immunostained (Ki67) slides will be scanned in a digital imaging device (Aperio XT Scanscope), which quantitatively analyzes the tumor designated by the pathologist with image analysis algorithms. The algorithm accurately detects regions of interest and distinguishes cells and sub-cellular objects within these target regions. It determines morphology and expression profiles per individual cell or cell compartment. For Ki67 analysis, a nuclear Immunohistochemistry (IHC) algorithm will be used.
Interventions
DRUGTamoxifen
All patients will take tamoxifen 20 mg po daily for 7 days prior to surgery and for 14 days after surgery.
PROCEDUREBreast cancer surgery
Breast cancer surgery
Sponsors
University of Utah
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \> 18 years old * Diagnosed with hormone receptor positive invasive breast cancer (estrogen receptor (ER) or progesterone receptor (PR) or both \>1%) by core needle biopsy * Clinical American Joint Committee on Cancer (AJCC) 7th edition Stage 1 or 2 * Candidate for surgical therapy * Eastern Cooperative Oncology Group (ECOG) performance status 0,1, or 2 * No chemotherapy or endocrine therapy for breast cancer in last 5 years * Paraffin fixed core needle tissue block, or biopsy punch available for central analysis for proliferative markers * Not pregnant or lactating and practicing adequate birth control if premenopausal * Able and willing to provide informed consent
Exclusion criteria
* Prior personal history of uterine cancer * Prior personal history of stroke or deep vein thrombosis (DVT) * Current therapy with strong CYP2D6 inhibitors The following medications should not be administered with tamoxifen (21 day treatment period) and will need to be stopped for the designated period of time prior to starting the study tamoxifen. No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage 0, I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years Fluoxetine - should be discontinued 30 days prior to starting tamoxifen Paroxetine - should be discontinued 5 days prior to starting tamoxifen Sertraline - should be discontinued 5 days prior to starting tamoxifen Bupropion - should be discontinued 5 days prior to starting tamoxifen * Concurrent coumarin-type anticoagulation therapy * Any other contraindications to tamoxifen therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Ki67 Expression in Tumors | 7 days | Demonstrate a significant change in Ki67 expression in tumors with 7 days of pre-surgical tamoxifen. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in FACT-ES Symptom Scores | 18 months | Patients were given the Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) quality of life assessment at baseline (prior to tamoxifen administration) and again 18 months following breast surgery to assess quality of life. The difference in total score from baseline to 18 months was calculated. The FACT-ES total score ranges from 0-180, with higher scores indicating higher quality of life. |
| Number of Participants With Long Term Endocrine Therapy Adherence | 18 months | For the patient population on this study, endocrine therapy was indicated for 5 years post-surgery according to the current standard of care recommendations for hormone positive breast cancer. Endocrine therapy was prescribed as standard of care as appropriate for each patient's situation. At 18 months post-surgery, patients were evaluated to determine if they were taking their endocrine therapy as prescribed. |
| Correlation Between Changes in Ki67 and Symptoms | 7 days | Evaluate correlation between changes in Ki67 expression and symptom scores. Differences between changes in FACT-ES total score were correlated with changes in Ki67 expression using a the Spearman correlation method and results are expressed as the correlation coefficient. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in FACT-ES Symptom Scores | 7 days | Patients were given the Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) quality of life assessment at baseline (prior to tamoxifen administration) and again 7 days following start of tamoxifen to assess quality of life while on tamoxifen. The difference in total score from baseline to 7 days was calculated. The FACT-ES total score ranges from 0-180, with higher scores indicating higher quality of life. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tamoxifen Pre and Post Breast Surgery All patients enrolled in the study.
Tamoxifen: All patients will take tamoxifen 20 mg po daily for 7 days prior to surgery and for 14 days after surgery.
Breast cancer surgery: Breast cancer surgery | 52 |
| Total | 52 |
Baseline characteristics
| Characteristic | Tamoxifen Pre and Post Breast Surgery |
|---|---|
| Age, Continuous | 58.5 years |
| Region of Enrollment United States | 52 Participants |
| Sex: Female, Male Female | 52 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 42 / 52 |
| serious Total, serious adverse events | 1 / 52 |
Outcome results
Primary
Change in Ki67 Expression in Tumors
Demonstrate a significant change in Ki67 expression in tumors with 7 days of pre-surgical tamoxifen.
Time frame: 7 days
Population: 3 were not evaluable due to rescheduling of surgery; 1 not evaluable due to pharmacy error. 2 patients had no invasive tumor on Ki-67 slides from pretreatment biopsy, and 2 patients had no invasive tumor on post-treatment surgery and were not evaluable.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Tamoxifen Pre and Post Breast Surgery | Change in Ki67 Expression in Tumors | -40 percentage change in Ki67 |
p-value: 0.0001t-test, 1 sided
Secondary
Change in FACT-ES Symptom Scores
Patients were given the Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) quality of life assessment at baseline (prior to tamoxifen administration) and again 18 months following breast surgery to assess quality of life. The difference in total score from baseline to 18 months was calculated. The FACT-ES total score ranges from 0-180, with higher scores indicating higher quality of life.
Time frame: 18 months
Population: Of the 44 patients evaluable for the primary outcome measure, 35 completed both baseline and 18 month FACT-ES assessments
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Tamoxifen Pre and Post Breast Surgery | Change in FACT-ES Symptom Scores | -4.53 change in units on a scale |
Secondary
Correlation Between Changes in Ki67 and Symptoms
Evaluate correlation between changes in Ki67 expression and symptom scores. Differences between changes in FACT-ES total score were correlated with changes in Ki67 expression using a the Spearman correlation method and results are expressed as the correlation coefficient.
Time frame: 7 days
Population: Of the 50 patients enrolled Ki67 measurements were obtained for 44. Of the 44 patients which had a Ki67 result, 43 had both a pre and post symptom score.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tamoxifen Pre and Post Breast Surgery | Correlation Between Changes in Ki67 and Symptoms | -0.02 spearman correlation coefficient |
Secondary
Number of Participants With Long Term Endocrine Therapy Adherence
For the patient population on this study, endocrine therapy was indicated for 5 years post-surgery according to the current standard of care recommendations for hormone positive breast cancer. Endocrine therapy was prescribed as standard of care as appropriate for each patient's situation. At 18 months post-surgery, patients were evaluated to determine if they were taking their endocrine therapy as prescribed.
Time frame: 18 months
Population: Of the 52 patients enrolled on the study, 38 patients had data regarding long term endocrine therapy at 18 months post-surgery.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tamoxifen Pre and Post Breast Surgery | Number of Participants With Long Term Endocrine Therapy Adherence | 33 participants adhering to therapy |
Other Pre-specified
Change in FACT-ES Symptom Scores
Patients were given the Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) quality of life assessment at baseline (prior to tamoxifen administration) and again 7 days following start of tamoxifen to assess quality of life while on tamoxifen. The difference in total score from baseline to 7 days was calculated. The FACT-ES total score ranges from 0-180, with higher scores indicating higher quality of life.
Time frame: 7 days
Population: Of the 50 patients enrolled, 46 had both pre and post FACT-ES total scores.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tamoxifen Pre and Post Breast Surgery | Change in FACT-ES Symptom Scores | 1.5 change in units on a scale |