Invasive Breast Cancer
Conditions
Keywords
Invasive Breast Cancer, Metastatic Breast Cancer, PR Positive Breast Cancer
Brief summary
The goal of this research is to test the accuracy of PET/MRI imaging with 18F-fluorofuranylnorprogesterone (FFNP) for measuring progesterone receptor (PR) expression in patients with invasive breast cancer. The hypothesis is that FFNP SUVmax from PET/MRI will correlate well against the semi-quantitative PR immunohistochemistry score.
Detailed description
Integrated whole-body magnetic resonance imaging (MRI)-positron emission tomography (PET) scanners have recently been introduced for clinical use. This technology combines the anatomic and perfusion data obtained with dynamic contrast enhanced (DCE) MRI with functional imaging data obtained from PET. For breast imaging, the combination of MRI and PET has important potential to improve diagnostic accuracy and provide molecular characterization of breast cancer. The overall purpose of this research is to test the accuracy of PET/MRI imaging with 18F-fluorofuranylnorprogesterone (FFNP) for measuring progesterone receptor (PR) expression in patients with invasive breast cancer. This is a prospective, one-arm, study which will enroll patients with newly diagnosed breast cancer scheduled for diagnostic breast MRI for preoperative staging/extent of disease evaluation as part of standard of care. Participation in this research study includes a directed breast PET/MRI with the investigational radiopharmaceutical, FFNP. FFNP uptake of the known, biopsy-proven malignancy will be measured on the PET/MRI examinations using standardized uptake values (SUV) and tumor-to-normal tissue ratios.
Interventions
DRUG[18F]Fluorofuranylnorprogesterone (FFNP) PET/MR Imaging
18F-Fluorofuranylnorprogesterone (FFNP) PET/MR Imaging tracer
Sponsors
National Center for Advancing Translational Sciences (NCATS)
University of Wisconsin, Madison
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
Single Group Assignment
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Women 18 years of age or older * Diagnosis of biopsy-proven invasive breast cancer measuring at least 1.0 cm in diameter by any imaging modality * Biopsy-proven PR-positive or PR-negative invasive breast cancer * Undergoing diagnostic breast MRI ordered by the referring clinician for staging and extent of disease
Exclusion criteria
* Inability or unwillingness to provide informed consent to the study * Participants currently undergoing neoadjuvant chemotherapy/endocrine therapy or those who have received chemotherapy/endocrine therapy within 6 months prior to the MRI * Participants who have had neoadjuvant chemotherapy/endocrine therapy, surgical intervention, or radiation for the current biopsy-proven malignancy * Participants with breast expanders * Participants who are or might be pregnant or lactating * Participants with a contraindication to gadolinium based contrast agents, including allergy or impaired renal function (per University of Wisconsin Health Guidelines) * Participants with a history of allergic reaction attributable to compounds of similar chemical or biologic composition to FFNP * Participants in liver failure as judged by the patient's physician * Participants with standard contraindications to MRI, including claustrophobia and metallic implants incompatible with MRI * Participants requiring intravenous (IV) conscious sedation for imaging are not eligible; participants requiring mild, oral anxiolytics for the clinical MRI will be allowed to participate as long as the following criteria are met: * The subject has their own prescription for the medication * The informed consent process is conducted prior to the self-administration of this medication * They come to the research visit with a driver * Participants unable to lie prone for 30 minutes for imaging
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Correlation Coefficient Between FFNP Uptake and Allred Score | Up to 1 day | To compare FFNP uptake of biopsy-proven primary PR+ breast malignancies measured using PET/MRI with the reference standard of PR immunohistochemistry (IHC) using a semi-quantitative score obtained by using the Allred score (0-8; the higher the score, the more receptors were found). The correlation of the two measures will be evaluated with Pearson's correlation coefficient. The null hypothesis is H0: p0=0.50 and the alternative hypothesis is H1: p1 =0.75. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Test-Retest Reproducibility | Up to 4 weeks | Tumor uptake of FFNP and the ability to reproduce this measure, will be quantified in the 5 subjects who elect to undergo a second imaging session, using summary statistics of tumor FFNP uptake for each reading for PET/MRI. The analysis will be done separately for each reader. |
| Intra and Inter-Observer Assessment | Up to 4 weeks | The variability of observer assessment of tumor FFNP uptake will be measured. The intra- and inter-reader agreement of SUV values for tumor FFNP uptake will be analyzed with Bland-Altman plots and 95% limits of agreement. Analyses will be conducted on a per-lesion basis, and repeat tumors within the same patient will be assumed to be independent. |
| Correlation Coefficient Between Tumor FFNP Uptake With Oncotype DX Score | Up to 4 weeks | Estimate the association of tumor FFNP uptake (continuous SUVmax) with research-based Oncotype DX scores (0-100). The risk score (0-100) is generated from expression levels of sixteen cancer related genes and five reference genes. Scores are further categorized as low-risk (0-17), intermediate-risk (18-30), and high-risk (31-100). Pearson's or Spearman's rank correlation will be used to evaluate the association between FFNP uptake and research-based Oncotype DX score. The correlation coefficient (rho) and 95% confidence interval will be reported. |
| Distinguishing Between PR Negative and PR Positive Breast Cancer Reported as Area Under the Curve (AUC) | up to 4 weeks | To evaluate the optimal cut-point of FFNP uptake for distinguishing between PR-negative and PR-positive invasive breast cancer. Receiver operating characteristic (ROC) curve analysis will be performed to determine the optimal cut-point for FFNP uptake to distinguish PR-positive from PR-negative invasive breast cancer, as defined by the clinical pathology report. The AUC for the ROCs and their respective two-sided 95% confidence intervals will be calculated using logistic regression. The optimal cut-off point will be determined by considering the FFNP uptake value with the maximum sensitivity and specificity. The analysis will be done separately for each reader, AUC is reported here. |
| Distinguishing Between PR Negative and PR Positive Breast Cancer Reported as Optimal Cut Point | up to 4 weeks | To evaluate the optimal cut-point of FFNP uptake for distinguishing between PR-negative and PR-positive invasive breast cancer. Receiver operating characteristic (ROC) curve analysis will be performed to determine the optimal cut-point for FFNP uptake to distinguish PR-positive from PR-negative invasive breast cancer, as defined by the clinical pathology report. The AUC for the ROCs and their respective two-sided 95% confidence intervals will be calculated using logistic regression. The optimal cut-off point will be determined by considering the FFNP uptake value with the maximum sensitivity and specificity. The analysis will be done separately for each reader, optimal cut point is reported here. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled from December 2017 to November 2024.
Participants by arm
| Arm | Count |
|---|---|
| FFNP PET/MRI 18F-Fluorofuranylnorprogesterone (FFNP) administration for PET/MRI imaging to assess biopsy-proven primary PR+ breast malignancies.
\[18F\]Fluorofuranylnorprogesterone (FFNP) PET/MR Imaging: 18F-Fluorofuranylnorprogesterone (FFNP) PET/MR Imaging tracer | 21 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | FFNP PET/MRI |
|---|---|
| Age, Customized 30-39 years | 1 Participants |
| Age, Customized 40-49 years | 3 Participants |
| Age, Customized 50-59 years | 12 Participants |
| Age, Customized 60-69 years | 4 Participants |
| Age, Customized 70-79 years | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 21 Participants |
| Region of Enrollment United States | 21 participants |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 20 |
| other Total, other adverse events | 2 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
Primary
Correlation Coefficient Between FFNP Uptake and Allred Score
To compare FFNP uptake of biopsy-proven primary PR+ breast malignancies measured using PET/MRI with the reference standard of PR immunohistochemistry (IHC) using a semi-quantitative score obtained by using the Allred score (0-8; the higher the score, the more receptors were found). The correlation of the two measures will be evaluated with Pearson's correlation coefficient. The null hypothesis is H0: p0=0.50 and the alternative hypothesis is H1: p1 =0.75.
Time frame: Up to 1 day
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FFNP PET/MRI | Correlation Coefficient Between FFNP Uptake and Allred Score | 0.3215 correlation coefficient (rho) |
p-value: 0.1347two-sided hypothesis test
Secondary
Correlation Coefficient Between Tumor FFNP Uptake With Oncotype DX Score
Estimate the association of tumor FFNP uptake (continuous SUVmax) with research-based Oncotype DX scores (0-100). The risk score (0-100) is generated from expression levels of sixteen cancer related genes and five reference genes. Scores are further categorized as low-risk (0-17), intermediate-risk (18-30), and high-risk (31-100). Pearson's or Spearman's rank correlation will be used to evaluate the association between FFNP uptake and research-based Oncotype DX score. The correlation coefficient (rho) and 95% confidence interval will be reported.
Time frame: Up to 4 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FFNP PET/MRI | Correlation Coefficient Between Tumor FFNP Uptake With Oncotype DX Score | -0.377 correlation coefficient (rho) |
p-value: 0.2521Pearson Correlation Statistical Test
Secondary
Distinguishing Between PR Negative and PR Positive Breast Cancer Reported as Area Under the Curve (AUC)
To evaluate the optimal cut-point of FFNP uptake for distinguishing between PR-negative and PR-positive invasive breast cancer. Receiver operating characteristic (ROC) curve analysis will be performed to determine the optimal cut-point for FFNP uptake to distinguish PR-positive from PR-negative invasive breast cancer, as defined by the clinical pathology report. The AUC for the ROCs and their respective two-sided 95% confidence intervals will be calculated using logistic regression. The optimal cut-off point will be determined by considering the FFNP uptake value with the maximum sensitivity and specificity. The analysis will be done separately for each reader, AUC is reported here.
Time frame: up to 4 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FFNP PET/MRI | Distinguishing Between PR Negative and PR Positive Breast Cancer Reported as Area Under the Curve (AUC) | 0.80 probability |
| FFNP PET/MRI (Re-test) | Distinguishing Between PR Negative and PR Positive Breast Cancer Reported as Area Under the Curve (AUC) | 0.70 probability |
Secondary
Distinguishing Between PR Negative and PR Positive Breast Cancer Reported as Optimal Cut Point
To evaluate the optimal cut-point of FFNP uptake for distinguishing between PR-negative and PR-positive invasive breast cancer. Receiver operating characteristic (ROC) curve analysis will be performed to determine the optimal cut-point for FFNP uptake to distinguish PR-positive from PR-negative invasive breast cancer, as defined by the clinical pathology report. The AUC for the ROCs and their respective two-sided 95% confidence intervals will be calculated using logistic regression. The optimal cut-off point will be determined by considering the FFNP uptake value with the maximum sensitivity and specificity. The analysis will be done separately for each reader, optimal cut point is reported here.
Time frame: up to 4 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FFNP PET/MRI | Distinguishing Between PR Negative and PR Positive Breast Cancer Reported as Optimal Cut Point | 1.96 SUVmax |
| FFNP PET/MRI (Re-test) | Distinguishing Between PR Negative and PR Positive Breast Cancer Reported as Optimal Cut Point | 1.96 SUVmax |
Secondary
Intra and Inter-Observer Assessment
The variability of observer assessment of tumor FFNP uptake will be measured. The intra- and inter-reader agreement of SUV values for tumor FFNP uptake will be analyzed with Bland-Altman plots and 95% limits of agreement. Analyses will be conducted on a per-lesion basis, and repeat tumors within the same patient will be assumed to be independent.
Time frame: Up to 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FFNP PET/MRI | Intra and Inter-Observer Assessment | 2.76 SUVmax | Standard Deviation 1.536 |
| FFNP PET/MRI (Re-test) | Intra and Inter-Observer Assessment | 2.629 SUVmax | Standard Deviation 1.568 |
95% CI: [-0.282, 0.544]
Secondary
Test-Retest Reproducibility
Tumor uptake of FFNP and the ability to reproduce this measure, will be quantified in the 5 subjects who elect to undergo a second imaging session, using summary statistics of tumor FFNP uptake for each reading for PET/MRI. The analysis will be done separately for each reader.
Time frame: Up to 4 weeks
Population: test-retest completed on a subset of the population, only 1 participant volunteered
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FFNP PET/MRI | Test-Retest Reproducibility | NA SUVmax |
| FFNP PET/MRI (Re-test) | Test-Retest Reproducibility | NA SUVmax |