This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for ER Reactivation Therapy for Breast Cancer (NCT02188745), a na phase 2 study. The primary outcome is Clinical Benefit.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02188745 |
| Phase | Phase 2 |
| Condition | Metastatic Breast Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 20 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Dartmouth-Hitchcock Medical Center |
| Results posted | Yes |
2. Clinical Question
Population
The registry identifies metastatic breast cancer. The official title specifies ER-positive, HER2-negative metastatic or advanced breast cancer, while the stated hypothesis concerns metastatic ER-positive cancer resistant to anti-estrogen therapy. The record says 20 people were enrolled at 3 sites. Patient #10 withdrew without completing cycle 1 and was not evaluable for analysis.
Intervention
The study used an alternating 17B-estradiol and aromatase inhibitor regimen, described as an 8-week/16-week schedule. The listed aromatase inhibitors are letrozole, anastrozole and exemestane, with use of only one aromatase inhibitor throughout the study preferred. The regimen description specifies a 2 mg 17B-estradiol tablet taken orally three times daily, for a total dose of 6 mg/day.
Comparator
There was no randomized comparison or separate control arm: the trial model is single group, and allocation is listed as not applicable. The registry summary frames continuous treatment with either therapy type as the contrast motivating the hypothesis, but it does not describe a concurrent continuous-treatment group in this study. The alternating regimen therefore cannot be interpreted as a randomized comparison against continuous therapy.
Primary question
The primary question was whether participants receiving alternating 17B-estradiol/aromatase inhibitor therapy had clinical benefit at 24 weeks. Clinical benefit was defined as complete response, partial response or stable disease at that time, per RECIST criteria. The registry record does not report the number of participants meeting this definition or the resulting rate, so the primary question cannot be answered from the posted outcome information.
3. Trial Design
This was a Phase II, single-group trial titled ER Reactivation Therapy for Breast Cancer. The registry lists allocation as not applicable and masking as none. The study status is completed, with 20 participants enrolled at 3 sites. The recorded start date is 2016-03-11 and the primary completion date is 2024-01-05. These design features describe a study of one treatment strategy, not a randomized test against a concurrent control.
The treatment strategy alternated 17B-estradiol and an aromatase inhibitor on an 8-week/16-week schedule. The listed aromatase inhibitors were letrozole, anastrozole and exemestane; the treatment description says that use of only one aromatase inhibitor throughout the study is preferred. The 17B-estradiol instructions specify one 2 mg tablet taken orally three times daily, for a total dose of 6 mg/day.
The registry summary gives the biological rationale: tumors may change between sensitivity to anti-estrogen treatment and sensitivity to 17B-estradiol. It proposes that alternating therapies could prevent cancer growth more effectively than continuous treatment with either type of therapy. That is the study hypothesis, not a result. Because the design has no concurrent comparison group, the trial's posted results cannot by themselves establish how outcomes would have differed under continuous therapy.
The registry identifies metastatic breast cancer as a condition. The official title further describes ER-positive, HER2-negative metastatic or advanced breast cancer, while the summary focuses on metastatic anti-estrogen-resistant ER-positive disease. The record does not report additional eligibility details, the planned sample-size justification, or a full statistical analysis plan. Patient #10 withdrew before completing cycle 1 and was not evaluable for analysis; the record does not give further details about the analysis population.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: 20 were enrolled.
Overall Study
| Stage | Alternating Therapy |
|---|---|
| STARTED | 20 |
| COMPLETED | 19 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | Alternating Therapy |
|---|---|
| Withdrawal by Subject | 1 |
Analysis population for the primary outcome, as defined in the registry: 20 people were enrolled at 3 sites. Patient #10 withdrew without completing cycle 1 and was not evaluable for analysis.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | Alternating Therapy |
|---|---|---|
| Participants analysed | 20 | |
| Age, Customized: Median Age of Participants | years | 61 (SD 61) |
| Sex: Female, Male: Female | Participants | 20 |
| Sex: Female, Male: Male | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 20 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States – Massachusetts | Participants | 1 |
| Region of Enrollment: United States – New Hampshire | Participants | 13 |
| Region of Enrollment: United States – Minnesota | Participants | 6 |
6. Primary Endpoint
The registry lists the primary outcome as Clinical Benefit, measured over 24 weeks.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is clinical benefit at 24 weeks. The registry defines clinical benefit as complete response, partial response or stable disease at that time according to RECIST criteria. The endpoint is a participant count, and its intended interpretation is the number meeting at least one of those response or disease-control categories at the stated assessment time.
A composite endpoint of this kind can capture more than tumor shrinkage alone: stable disease qualifies alongside complete and partial response. That makes it relevant to a study hypothesis about preventing cancer growth, but it also means the endpoint combines distinct clinical states. The registry does not report separate counts for the component categories or the total meeting the composite definition.
The record says 20 people were enrolled at 3 sites and identifies patient #10 as having withdrawn without completing cycle 1 and as not evaluable for analysis. It does not report the number evaluable at 24 weeks, the number with clinical benefit, or the primary endpoint rate. The endpoint definition is therefore available, but the posted record does not allow readers to quantify the observed clinical benefit or its precision.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive point is that the registry record describes the primary endpoint but does not report its result. Clinical benefit was defined as complete response, partial response or stable disease at 24 weeks per RECIST criteria. No count meeting that definition, rate, or uncertainty interval is reported in the record. Consequently, the direction and precision of the primary endpoint estimate cannot be assessed from the posted information.
This is a single-group study of an alternating treatment strategy. Its design can describe outcomes among participants receiving that regimen, but it does not provide a randomized concurrent comparison with continuous 17B-estradiol, continuous aromatase inhibitor therapy, or another control. The registry summary presents those continuous approaches as the conceptual contrast behind the hypothesis. They are not listed as study arms. Any causal comparison with those alternatives would require evidence beyond this single-group record.
The enrollment was 20 participants at 3 sites. Patient #10 withdrew without completing cycle 1 and was not evaluable for analysis. The registry does not report the endpoint analysis population, how missing endpoint information was handled, or whether any other participants lacked a 24-week assessment. Without those details and the outcome count, it is not possible to judge how much the observed estimate might depend on evaluability or missing information.
The listed secondary outcomes are objective response rate, progression-free survival, adverse event profiles and predictive tumor genetic lesions. Their presence identifies other intended areas of assessment, but results for them are not reported in the registry record. The record lists 5 outcome measures and 0 analyses. The absence of posted analysis results is distinct from evidence that an outcome was absent or that no analysis was conducted outside the registry.
The posted safety figures indicate 0 serious adverse events among 20 at risk, 1 other adverse event among 20 at risk, and 0 deaths. These counts should be read as the registry's reported event summaries, not as a complete characterization of safety. The record does not list serious adverse event terms, and the single other adverse event is not identified by type in the information.
Overall, the registry supports description of the planned treatment sequence, endpoint definition, enrollment and limited event counts. It does not support a numerical conclusion about the primary clinical-benefit outcome, the secondary outcomes, or comparative effectiveness. The proposed biological rationale and hypothesis remain distinct from an observed result.
9. Statistical Methods Explained
The registry describes a single-group Phase II study with clinical benefit as the primary endpoint. Interpreting such an endpoint requires separating its definition, observed count, denominator and uncertainty. The definition and enrollment are recorded, but the primary outcome count and rate are not reported in the registry record.
What does a binary endpoint represent?
Clinical benefit is defined as whether a participant had complete response, partial response or stable disease at 24 weeks according to RECIST criteria. In statistical terms, this is a binary classification: a participant either meets the composite definition at the assessment time or does not. A count is the number meeting the definition; a rate expresses that count relative to a stated analysis population. The registry gives neither the count nor the rate. It also does not report counts for the individual response categories, so the contribution of each category cannot be distinguished.
Why does the analysis population matter?
An outcome rate depends on which participants are included in its denominator. The record says 20 people enrolled at 3 sites and notes that patient #10 withdrew without completing cycle 1 and was not evaluable for analysis. It does not specify the complete analysis population for the 24-week endpoint or how endpoint information was handled when unavailable. That information matters because an enrolled population and an evaluable population need not be identical. No evaluable total should be inferred from the available record.
What would an uncertainty interval communicate?
General statistical explanation: a confidence interval describes the uncertainty around an estimated quantity under the assumptions of the statistical method. For a binary outcome, the estimate is based on the observed count and its denominator. Wider intervals generally indicate less precision, while narrower intervals indicate greater precision under that method. No confidence interval for clinical benefit is reported in the registry record, and the missing outcome count and analysis denominator prevent readers from assessing precision from the posted information.
Why is the single-group design important?
The trial's model is single group, with allocation listed as not applicable and masking as none. The registry summary proposes alternating therapy as a strategy to prevent cancer growth and contrasts it conceptually with continuous treatment. However, no randomized control group is described. General statistical explanation: a concurrent comparison helps distinguish treatment-associated outcomes from changes that could occur because of participant characteristics, disease course, or other influences. A single-group outcome can describe what happened in the group, but it does not directly estimate a randomized between-group treatment effect.
What do planning assumptions mean?
The registry's sample-size assumptions describe an illustration based on the observed effect, rather than the trial's own design. They specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect defined as a stated fraction of the observed effect. These are hypothetical planning conditions, not the design recorded for this single-group trial. Sample-size illustrations are planning quantities, not observed power. The registry does not report a sample-size justification for the trial itself, and it does not report the primary outcome result needed to assess the stated observed-effect basis.
How should secondary outcomes and multiplicity be understood?
The registry names objective response rate, progression-free survival, adverse event profiles and predictive tumor genetic lesions as secondary outcomes. When a study assesses multiple outcomes, general statistical explanation: the chance of at least one apparently notable finding can depend on how many comparisons are made and how they are interpreted. A prespecified approach to multiplicity can clarify which findings are confirmatory and how uncertainty is controlled. The registry record does not report a multiplicity strategy, an analysis plan, or analysis results for these outcomes. The record lists 0 analyses, which means no analysis entries are posted there; it does not establish what analyses may have been conducted elsewhere.
Why can over-dispersion matter?
General statistical explanation: over-dispersion occurs when the variability in count data exceeds what a model assumes. If present, standard errors and uncertainty estimates from an overly restrictive model may be too small. The registry does not report a count model, an over-dispersion assessment, or a statistical analysis plan for the primary outcome. The endpoint is described as a count of participants meeting a binary definition, but no modeling details are available. It would therefore be inappropriate to infer that any particular model or adjustment was used.
10. Multiplicity, Missing Data and Analysis Populations
The registry names objective response rate, progression-free survival, adverse event profiles and predictive tumor genetic lesions as secondary outcomes, in addition to clinical benefit as the primary endpoint. The record lists 5 outcome measures, but it does not report an analysis plan describing how outcomes were prioritized, how multiple tests were handled, or which comparisons were intended to be confirmatory. Results for the secondary outcomes are not reported in the registry record.
General statistical explanation: evaluating several outcomes can create multiple opportunities for apparently notable findings. A prespecified multiplicity approach can help control how results are interpreted across those outcomes. Without a reported approach, readers cannot determine whether any eventual statistical claims were adjusted for multiple testing or treated as exploratory. The registry lists 0 analyses; that indicates no analysis entries in the record, not that analyses were necessarily absent outside it.
For missing data, the record identifies patient #10 as having withdrawn without completing cycle 1 and as not evaluable for analysis. It does not say how the primary endpoint analysis population was defined, whether other 24-week assessments were missing, or how missing outcome information was handled. It also does not report imputation, sensitivity analyses, or other missing-data procedures. These omissions limit assessment of how participant withdrawal and incomplete follow-up might affect the endpoint estimate.
The primary endpoint is defined at 24 weeks, but the posted record gives no number meeting the endpoint and no denominator for its analysis. Without those details, neither the result nor its sensitivity to missing information can be evaluated. Protocol details and the full statistical analysis plan are not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Alternating Therapy | 0 | 20 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Alternating Therapy | 0 of 20 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Alternating Therapy | 1 of 20 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Alternating Therapy |
|---|---|---|
| Thromboembolism | Vascular disorders | 1 of 20 |
| Patient #10 discontinued treatment before completing cycle 1 due to mood changes and irritability. | Social circumstances | 1 of 20 |
The registry lists 20 participants at risk for serious adverse events, with 0 affected, and 20 at risk for other adverse events, with 1 affected. It records 0 deaths. These are counts in the posted safety summary; they are not a detailed account of event type, severity beyond the serious/other classification, timing, or relationship to treatment.
No serious adverse event terms are listed. The type of the single other adverse event is not reported in the registry record. The figures therefore permit only a limited description of the recorded counts. They should not be interpreted as evidence that no adverse events occurred beyond the categories and details presented, or as a complete safety profile.
The registry record does not provide additional information about duration of observation, exposure to each treatment, or methods for collecting and classifying adverse events. Those details would affect how safety counts are interpreted, but cannot be inferred from the event summary. The counts also do not compare alternating therapy with another regimen because the study is single group and has no listed concurrent control arm.
12. What the Result Does, and Does Not, Mean
The registry record establishes the clinical question, the alternating treatment strategy and the definition of the primary endpoint. It also reports enrollment at 3 sites and notes that patient #10 withdrew without completing cycle 1 and was not evaluable for analysis. These registry entries describe the study and its conduct, but they do not provide the primary clinical-benefit result.
Clinical benefit at 24 weeks was defined as complete response, partial response or stable disease per RECIST criteria. The count meeting that definition, its analysis denominator and an uncertainty interval are not reported in the registry record. The primary result's magnitude and precision therefore cannot be described. The registry also does not report results for objective response rate, progression-free survival, adverse event profiles or predictive tumor genetic lesions.
The biological rationale and the proposed benefit of alternating estrogen and anti-estrogen therapy are hypotheses described in the registry summary. They should not be mistaken for findings. The single-group design has no concurrent control arm, so outcomes in this study would not, on their own, establish what would have happened under continuous therapy or another treatment strategy.
The posted safety counts are limited: 0 serious adverse events among 20 at risk, 1 other adverse event among 20 at risk, and 0 deaths. Event details are sparse, and no serious event terms are listed. Those data do not replace a full safety report or permit a comparative safety assessment.
Accordingly, the registry record is useful for understanding the study question and endpoint framework, but not for determining whether the primary endpoint was met or estimating a treatment effect. The absence of posted results should be read as missing registry outcome information, not as a finding of no clinical benefit or no effect.
13. Why This Trial Matters Statistically
This trial raises a useful statistical distinction between a biological hypothesis and evidence from a design capable of testing it. The registry rationale proposes that breast cancer may shift between sensitivity to anti-estrogen therapy and sensitivity to 17B-estradiol, motivating an alternating schedule. The study design documents that schedule in a single group, while the proposed contrast with continuous therapy remains a hypothesis rather than a randomized comparison within this trial.
The primary endpoint also illustrates how a composite outcome defines the question being answered. Clinical benefit includes complete response, partial response or stable disease at 24 weeks per RECIST criteria. Combining these categories yields a measure of whether participants met the stated clinical-benefit definition, but it does not show the separate frequency of each category. Those component counts and the overall endpoint result are not reported in the registry record.
Interpretation also depends on transparent reporting of the analysis population. The record identifies an enrolled population of 20 and flags patient #10 as not evaluable after withdrawing without completing cycle 1. It does not report the endpoint denominator, missing-data approach, or primary outcome count. These details are central to understanding the estimate and how precisely it describes the enrolled group.
Finally, the registry names several secondary outcomes but posts no analysis entries. This is a reminder that listing outcomes is not the same as reporting results or a statistical plan. The record offers a concrete example of how design, endpoint definition, analysis population and result reporting jointly determine what conclusions statistics can support.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The most important limitation for interpreting the registry record is that it does not report the primary endpoint result. Although clinical benefit at 24 weeks is defined, the count meeting the definition, its analysis denominator and its uncertainty are unavailable. Secondary outcome results are also not reported in the registry record.
The single-group design has no randomized concurrent comparator. The study can be described as evaluating an alternating regimen, but the record does not support a direct comparison with continuous 17B-estradiol or continuous aromatase inhibitor therapy. The registry's stated hypothesis about preventing cancer growth is not itself evidence that the strategy achieved that objective.
Enrollment was 20 people at 3 sites. Patient #10 withdrew without completing cycle 1 and was not evaluable for analysis. The record does not specify the full endpoint analysis population, other possible missing assessments, or the handling of missing data. That prevents assessment of the extent to which endpoint evaluability could affect interpretation.
The available treatment description identifies the 8-week/16-week alternating schedule and gives instructions for 17B-estradiol, but does not provide further details on treatment exposure or adherence. The record does not report a sample-size justification, a full statistical analysis plan, or a multiplicity approach. It also does not report details of the single other adverse event. These gaps limit evaluation of statistical precision, outcome selection, treatment implementation and the completeness of safety reporting.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: ER Reactivation Therapy for Breast Cancer — NCT02188745.
- Registry record last updated 2026-09-25; status last verified 2026-09.
- Results first posted 2026-09-25.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT02188745 is a completed Phase II, single-group, unmasked trial titled ER Reactivation Therapy for Breast Cancer. The registry records 20 participants enrolled at 3 sites, with a start date of 2016-03-11 and primary completion date of 2024-01-05. The intervention was an alternating 17B-estradiol/aromatase inhibitor regimen described on an 8-week/16-week schedule.
The primary endpoint was clinical benefit at 24 weeks, defined as complete response, partial response or stable disease per RECIST criteria. Patient #10 withdrew without completing cycle 1 and was not evaluable for analysis. The primary endpoint result and secondary outcome results are not reported in the registry record.
The safety summary lists 0 serious adverse events among 20 at risk, 1 other adverse event among 20 at risk, and 0 deaths. No serious adverse event terms are listed. The registry lists 0 analyses and does not report a full statistical analysis plan or sample-size justification.