Breast Cancer, Breast Neoplasms
Conditions
Keywords
Breast neoplasms, Breast cancer, Locally advanced breast cancer, Neoadjuvant endocrine therapy, Tamoxifen, Low and middle income country
Brief summary
This study evaluates the feasibility and efficacy of neoadjuvant tamoxifen for patients with locally advanced hormone receptor positive breast cancer in a low/middle income country.
Detailed description
This is a single arm feasibility study of neoadjuvant tamoxifen for locally advanced hormone receptor positive breast cancer in a low-resource setting in a middle-income country (Guatemala). Patients will be treated with tamoxifen for four to six weeks, then have an on-treatment biopsy to assess Ki-67. If Ki-67 is less than or equal to 10%, the patient will continue on tamoxifen for a total of 4 months; if Ki-67 is greater than 10% or there is clinical progression, patients will be taken off study. The study will evaluate the proportion of patients treated with four months of tamoxifen who undergo definitive surgery and the clinical and pathologic response rates.
Interventions
DRUGTamoxifen
Tamoxifen 20mg by mouth daily
Sponsors
Washington University School of Medicine
Instituto National de Cancerologia, Guatemala
Vanderbilt University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient evaluated and treated at INCAN * Patients must provide informed consent * Patient must be ≥ 18 years of age. * Life expectancy ≥ 6 months * Clinical locally advance breast cancer (Stage IIB or III) * Pathologically confirmed diagnosis of estrogen receptor (ER)-positive or progesterone receptor (PR)-positive breast cancer with ER or PR Allred Score \> 4 * Patient must have an ECOG Performance Status of 0-2 * Patients must be able to swallow and retain oral medication
Exclusion criteria
* Patient must not have received any prior chemotherapy, radiation therapy, or biologic therapy for invasive breast cancer within the past five years * Patient must not be pregnant or nursing * Patient must not have had any prior malignancy except for adequately treated basal cell (or squamous cell) skin cancer, in situ cervical cancer or other cancer for which the patient has been disease-free for five years. * Women of childbearing age unable or unwilling to use contraception
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Were Successfully Accrued in the Study, as a Measure of Feasibility | 4-6 months | Feasibility is defined as the ability to recruit the stated number of patients and fifty percent of participants completing the trial. Completing the trial is defined as reaching surgery if they are a responder to tamoxifen or obtaining the six week biopsy specimen if they are a non-responder. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Definitive Surgery in Responders to Neoadjuvant Tamoxifen | 4-6 months | Rate of definitive surgery after 4 months of neoadjuvant tamoxifen therapy in patients who were deemed to be responders to neoadjuvant tamoxifen (Ki67 \< or = 10% after 4-6 weeks on neoadjuvant tamoxifen therapy) |
| Ki67 Suppression Rate at 4-6 Weeks in Patients Who Underwent an On-treatment Biopsy | 4-6 weeks | Result is the number of participants who had Ki67 suppression (\< or = 10%) after 4-6 weeks of neoadjuvant tamoxifen out of patients who underwent an on-treatment biopsy. |
| Overall Clinical Response Rate | 4-6 months | Clinical response rate was assessed by palpation after 4 months of tamoxifen. Complete response was defined as no palpable primary tumor on clinical examination and lymph nodes \< 10 mm. Partial response was defined as at least 30% decrease in the sum of the diameters compared to baseline sum of diameters. The overall clinical response was the sum of the complete clinical response and partial clinical response. |
| Pathologic Complete Response | 4-6 months | Pathologic complete response was defined as no residual tumor at the primary site or the axillary lymph nodes at the time of surgery. |
| Breast Conserving Therapy | 4-6 months | The rate of breast conservation surgery (as opposed to mastectomy) after 4 months of neoadjuvant tamoxifen therapy in patients who were deemed to be responders to neoadjuvant tamoxifen (Ki67 \< or = 10% after 4-6 weeks on neoadjuvant tamoxifen therapy). |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tamoxifen Tamoxifen 20mg by mouth daily
Tamoxifen: Tamoxifen 20mg by mouth daily | 35 |
| Total | 35 |
Baseline characteristics
| Characteristic | Tamoxifen |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 12 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants |
| Age, Continuous | 59.1 years |
| Gender Female | 35 Participants |
| Gender Male | 0 Participants |
| Region of Enrollment Guatemala | 35 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 35 |
| serious Total, serious adverse events | 0 / 35 |
Outcome results
Primary
Number of Participants Who Were Successfully Accrued in the Study, as a Measure of Feasibility
Feasibility is defined as the ability to recruit the stated number of patients and fifty percent of participants completing the trial. Completing the trial is defined as reaching surgery if they are a responder to tamoxifen or obtaining the six week biopsy specimen if they are a non-responder.
Time frame: 4-6 months
Population: The number of patients analyzed was the accrual goal for number of participants and the outcome measure was the actual number of participants accrued. The outcome measure time frame is the maximum time each participant would be on study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tamoxifen | Number of Participants Who Were Successfully Accrued in the Study, as a Measure of Feasibility | 35 participants |
Secondary
Breast Conserving Therapy
The rate of breast conservation surgery (as opposed to mastectomy) after 4 months of neoadjuvant tamoxifen therapy in patients who were deemed to be responders to neoadjuvant tamoxifen (Ki67 \< or = 10% after 4-6 weeks on neoadjuvant tamoxifen therapy).
Time frame: 4-6 months
Population: This outcome measure was analyzed in patients who were treated with 4 months of neoadjuvant tamoxifen
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tamoxifen | Breast Conserving Therapy | 0 participants |
Secondary
Ki67 Suppression Rate at 4-6 Weeks in Patients Who Underwent an On-treatment Biopsy
Result is the number of participants who had Ki67 suppression (\< or = 10%) after 4-6 weeks of neoadjuvant tamoxifen out of patients who underwent an on-treatment biopsy.
Time frame: 4-6 weeks
Population: 32 of the 35 patients underwent an on-treatment biopsy; 3 patients did not follow-up and were not included in the number of participants analyzed for this measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tamoxifen | Ki67 Suppression Rate at 4-6 Weeks in Patients Who Underwent an On-treatment Biopsy | 15 participants |
Secondary
Number of Participants With Definitive Surgery in Responders to Neoadjuvant Tamoxifen
Rate of definitive surgery after 4 months of neoadjuvant tamoxifen therapy in patients who were deemed to be responders to neoadjuvant tamoxifen (Ki67 \< or = 10% after 4-6 weeks on neoadjuvant tamoxifen therapy)
Time frame: 4-6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tamoxifen | Number of Participants With Definitive Surgery in Responders to Neoadjuvant Tamoxifen | 13 participants |
Secondary
Overall Clinical Response Rate
Clinical response rate was assessed by palpation after 4 months of tamoxifen. Complete response was defined as no palpable primary tumor on clinical examination and lymph nodes \< 10 mm. Partial response was defined as at least 30% decrease in the sum of the diameters compared to baseline sum of diameters. The overall clinical response was the sum of the complete clinical response and partial clinical response.
Time frame: 4-6 months
Population: This Outcome Measure was only assessed among patients undergoing surgery and is a unique outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tamoxifen | Overall Clinical Response Rate | 13 participants |
Secondary
Pathologic Complete Response
Pathologic complete response was defined as no residual tumor at the primary site or the axillary lymph nodes at the time of surgery.
Time frame: 4-6 months
Population: This Outcome Measure was only assessed among patients who had undergone surgery.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tamoxifen | Pathologic Complete Response | 1 participants |