Estrogen for Triple Negative Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Estrogen for Triple Negative Breast Cancer (NCT01083641), a na phase 2 study. The primary outcome is Determine Tumor Objective Response (OR) Rates.

2. Clinical Question

The study asked whether estradiol treatment was associated with objective tumor responses in advanced breast cancer described as hormone receptor negative and Her2/neu negative. Its official title specifies metastatic triple negative breast cancer. It also proposed laboratory research on tumor tissue, including an examination of estrogen receptor beta and whether its presence might relate to response to estrogen.

The study also listed clinical benefit, progression-free survival and median overall survival as secondary outcomes. The record describes a laboratory aim involving estrogen receptor beta in tumor tissue, but does not report laboratory results or a statistical relationship between that marker and response. The clinical question is therefore broader than a simple treatment-versus-control comparison: the study was intended to describe response following estradiol and explore a possible tissue marker, but the posted record does not provide outcome estimates with which to assess either question.

3. Trial Design

This was a phase II, single-group study sponsored by the University of Wisconsin, Madison. The registry lists estradiol as the drug intervention and estrogen therapy as the arm. Allocation is recorded as not applicable, masking as none, and the study model as single group. There is no randomized comparison or concurrent control arm. Any interpretation must therefore focus on what the registry records about the treated group, rather than a treatment effect estimated against a control group.

Enrollment is listed as 17. That is the registry enrollment figure; the number of participants who received treatment, contributed to each outcome, or were included in an analysis is not reported in the registry record. The study is marked terminated. Its start is listed as 2010-01 and its primary completion as 2013-06. The reason for termination, the date of termination and the circumstances surrounding completion are not reported in the registry record.

The primary outcome was the percentage of participants with an objective response, defined as complete response plus partial response under RECIST version 1.1. The outcome timeframe was up to 4 years. Secondary outcomes listed are clinical benefit, progression-free survival and median overall survival. The brief description also states an intention to examine tumor tissue from an original diagnosis or biopsy for estrogen receptor beta. The record does not report the tissue analysis methods or findings.

No detailed protocol, treatment schedule, outcome assessment schedule, eligibility criteria, sample-size justification, interim-analysis plan or statistical analysis plan is reported in the registry record. The registry lists four outcome measures and no analyses. Thus, although the design and intended outcomes can be described, the posted material does not establish how many participants contributed data to each outcome or how the intended analyses were carried out.

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.

Overall Study

Reasons for not completing this period:

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.

Population: Adult women with measurable advanced TNBC.

6. Primary Endpoint

The registry lists the primary outcome as Determine Tumor Objective Response (OR) Rates, measured over Up to 4 years.

The primary endpoint was the objective response rate, expressed as the percentage of participants with a complete or partial tumor response. The registry specifies RECIST version 1.1: complete response means disappearance of all target lesions, while partial response means at least a 30% decrease in the sum of target-lesion diameters relative to the baseline sum. The stated assessment timeframe was up to 4 years.

As a general statistical concept, a binary response endpoint classifies each participant according to whether the defined event occurred. Reporting a percentage can make the frequency of responses easy to interpret, while a confidence interval conveys uncertainty around the estimate. The interval is especially important when the study group is small, because the observed percentage alone does not show how precisely the underlying response frequency has been estimated.

The registry identifies the endpoint and says that a 95% confidence interval was the dispersion measure. However, neither the observed response percentage nor its confidence interval is reported in the registry record. The stated definition therefore clarifies what the study intended to count, but cannot establish how many participants responded or how precise any response estimate was. The number analyzed for this endpoint and the handling of participants without an evaluable response are also not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study’s primary outcome is a binary participant-level measure: a participant either meets the response definition or does not. The registry expresses the endpoint as a percentage and specifies complete response plus partial response under RECIST version 1.1. Complete response is defined as disappearance of all target lesions. Partial response is defined as at least a 30% decrease in the sum of target-lesion diameters, using the baseline sum as the reference. The timeframe is listed as up to 4 years.

As a general statistical concept, a proportion summarizes the frequency of an event in the group being studied. Its interpretation depends on having a clear event definition, a known denominator and sufficiently complete outcome ascertainment. Here, the planned definition and registry enrollment are available, but the analyzed denominator, outcome count and observed proportion are not reported in the registry record. Enrollment should not automatically be treated as the number included in the primary analysis.

The registry specifies a 95% confidence interval for the primary percentage. In general, a confidence interval describes uncertainty around an estimate under the statistical procedure used to construct it. It does not guarantee that the estimate is correct, and its interpretation depends on the analysis assumptions and data. The interval itself, the method used to calculate it and the response estimate are not reported in the registry record. Therefore, no assessment of the primary endpoint’s statistical precision is possible from the posted result information.

The design is single group, with no randomized comparator. As a general statistical point, a single-group percentage describes outcomes in that group; it does not provide the same comparison as a randomized treatment-versus-control analysis. The registry’s allocation entry is not applicable and its masking entry is none. The record does not report an adjusted comparison or any analysis, and lists zero analyses. No p-value or treatment contrast is available to interpret.

The secondary outcomes are clinical benefit, progression-free survival and median overall survival. These are distinct from the primary response endpoint. As a general concept, time-to-event outcomes require definitions of the event, time origin, censoring and analysis population to interpret their estimates. The registry does not report the detailed definitions, analysis methods, estimates or uncertainty for these secondary outcomes. The outcome labels alone do not establish what results were observed.

The brief description also identifies a planned laboratory examination of tumor tissue for estrogen receptor beta. As a general statistical matter, a marker analysis requires clear specification of how the marker is measured and classified, which samples are available, and how its relationship to clinical outcomes is assessed. Those methods, the number of samples, and any results are not reported in the registry record. The proposed laboratory work cannot be treated as evidence of a marker-response association.

The sample-size assumptions described for planning illustrations are not the trial’s own design justification. As a general concept, such illustrations can show how a hypothetical future study’s size might vary with assumptions about an effect and statistical criteria. They are planning aids, not observed power, and they do not recover an unreported response estimate or validate the study’s design. The registry does not report its own sample-size justification, so no claim about the intended precision or power of this trial is supported.

In general, over-dispersion matters when outcome variability is greater than a statistical model assumes, because uncertainty estimates based on an overly restrictive variance model may be too small. No model or over-dispersion assessment is reported for this study, and the primary endpoint is described as a percentage rather than through a reported model-based analysis. This concept is relevant to statistical interpretation in general, but there is no basis to say whether over-dispersion was present.

Finally, the registry’s status is terminated, and no analyses are listed. Neither fact supplies the missing outcome estimates or explains the conduct of the analysis. Details such as analysis populations, missing-data handling, sensitivity analyses, interim looks and multiplicity adjustment are not reported in the registry record. The methods that can be discussed are therefore limited to the endpoint definition, stated timeframe, design classification and the general meaning of statistical measures.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Estrogen Therapy")
n      <- c(15)
events <- c(1)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Estrogen Therapy  15  1  6.7  0.2  31.9  1.2  29.8  1.6  30.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome, objective response rate, and three secondary outcomes: clinical benefit, progression-free survival and median overall survival. It also records four outcome measures and zero analyses. The observed outcomes and their statistical results are not reported in the registry record.

As a general statistical concept, evaluating several outcomes can raise a multiplicity concern: the chance of obtaining at least one apparently notable result may increase when many questions are tested. Prespecified priority and any adjustment strategy help readers understand how multiple findings should be interpreted. The registry does not report a multiplicity strategy, a hierarchy among secondary outcomes, or an analysis plan. It is therefore not possible to determine how multiple outcomes were handled.

Missing-data methods and analysis populations are also not reported in the registry record. The enrollment figure is 17, but the numbers included in each endpoint analysis, the number with incomplete follow-up, and the reasons for missing outcome information are not stated. The record does not describe imputation, exclusion rules, sensitivity analyses or how participants without an evaluable response were classified.

These omissions matter because the denominator and completeness of follow-up affect how an outcome estimate should be read. They also prevent assessment of whether results might differ under alternative assumptions about missing observations. The registry record does not provide enough information to determine the impact of missing data or multiplicity on the study’s intended conclusions.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: dyspnea (11.8%), vomiting (11.8%), dizziness (5.9%), fatigue (5.9%), fever (5.9%).

The estrogen therapy group lists 17 participants at risk for serious adverse events, with 4 recorded as affected. For other adverse events, 17 participants are listed at risk and 17 as affected. The registry lists the following serious adverse-event terms and percentages: dyspnea, 11.8%; vomiting, 11.8%; dizziness, 5.9%; fatigue, 5.9%; fever, 5.9%; and headache, 5.9%.

These entries describe reported safety figures, not a comparison with an untreated or alternative-treatment group. The listed terms do not establish whether events occurred in the same or different participants, and the record does not provide narratives, timing, severity grades beyond the serious-event classification, or attribution to treatment. The number of deaths is not reported in the registry record.

As a general statistical concept, adverse-event percentages are most interpretable when the event definitions, observation period, participant denominator and reporting rules are clear. The registry figures should be read as descriptive entries; they do not by themselves establish the cause of an event or quantify comparative risk. Additional safety detail is not reported in the registry record.

13. What the Result Does, and Does Not, Mean

The record establishes that a phase II, single-group study of estradiol was registered for metastatic triple negative breast cancer and that its primary endpoint was objective response under RECIST version 1.1. It also records an enrollment of 17, a terminated status, and selected serious and other adverse-event figures. These registry entries describe the study and its posted entries.

The record does not report the primary response percentage or its 95% confidence interval. It therefore does not show the observed frequency of objective response or the precision of an estimate. It also does not report results for clinical benefit, progression-free survival or median overall survival. The planned laboratory investigation of estrogen receptor beta has no reported findings in the registry record.

Even a reported response percentage from a single group would not, by itself, supply a randomized comparison. The design has no comparator arm, and no adjusted comparison or analysis is listed. The registry information cannot establish how outcomes would have differed under another treatment or without estradiol. It also cannot answer whether the results apply to people outside the study’s enrolled group, whose detailed characteristics are not reported.

The safety entries are descriptive and have no control group for comparison. They do not establish that estradiol caused the listed events, and the available record does not provide enough detail to characterize their timing, severity or attribution. The reason the study was terminated is not reported in the registry record.

These limits do not negate the value of a clearly defined endpoint or the importance of reporting outcomes. They identify what can and cannot be concluded from this registry record: the design and planned questions are described, but efficacy estimates, survival results, marker findings and a comparative safety assessment are not reported.

14. Why This Trial Matters Statistically

This trial is statistically instructive because its registry record separates a clear endpoint definition from the results needed to estimate that endpoint. The primary outcome is specified as an objective-response percentage using RECIST version 1.1, with a 95% confidence interval and a timeframe up to 4 years. Yet the response estimate and interval are not reported. Naming an outcome and its intended summary does not substitute for posting the observed data and uncertainty.

The single-group design also illustrates the distinction between describing an outcome and estimating a comparative effect. A one-arm study can describe outcomes in its group, but without a concurrent comparator it cannot provide a randomized contrast. The design should therefore shape the language used to interpret any results; no treatment-versus-control effect is available in this record.

The registry’s enrollment figure of 17 highlights why denominators and precision are central to interpreting a proportion. The analyzed population and confidence interval are not reported, so the reader cannot assess how much information supports the primary estimate. In general, reporting both an estimate and uncertainty helps prevent an isolated percentage from being read as more precise than the data warrant.

The record also lists several secondary outcomes and a laboratory aim involving estrogen receptor beta. That breadth makes prespecification, analysis populations and multiplicity relevant statistical considerations in general. However, the registry does not report the analysis plan, handling of missing data, multiplicity approach or results for those questions. This case underscores how design details and outcome reporting together determine the strength of statistical interpretation.

15. 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.

Several trial-specific limitations constrain interpretation of the registry record. The study is single group, with no comparator, and masking is listed as none. Consequently, the record cannot provide a randomized comparison of outcomes. The registry reports enrollment of 17, but does not state how many participants received treatment or contributed to the primary or secondary outcome analyses.

The study is marked terminated. The reason for termination, the termination date and whether planned follow-up was completed are not reported in the registry record. Although primary completion is listed as 2013-06 and the primary endpoint timeframe as up to 4 years, actual participant follow-up and the completeness of response assessment are not described.

The objective-response definition is specified, but the response result and 95% confidence interval are absent. Results for the listed secondary outcomes are also not reported. The record does not describe missing-data handling, analysis populations, sensitivity analyses, or the statistical methods used. The planned estrogen receptor beta tissue work has no reported methods or findings.

The safety entries include counts of participants affected and selected serious-event percentages, but not event-level details, timing, severity grading beyond the serious classification, treatment attribution or a comparison group. Deaths are not reported in the registry record. Eligibility details and characteristics of the enrolled participants are also not reported, limiting assessment of who contributed to the findings and how broadly they might apply.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Estrogen for Triple Negative Breast Cancer — NCT01083641.
• Registry record last updated 2019-12-09; status last verified 2017-03.
• Results first posted 2017-03-07.
• 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.

19. Record Summary

NCT01083641 is a phase II, single-group study of estradiol for metastatic triple negative breast cancer, sponsored by the University of Wisconsin, Madison. The registry lists enrollment of 17, a start of 2010-01, primary completion of 2013-06 and status of terminated. There was no comparator arm.

The primary endpoint was the percentage of participants with an objective response under RECIST version 1.1, assessed up to 4 years, with a planned 95% confidence interval. The response estimate and interval are not reported in the registry record. Clinical benefit, progression-free survival and median overall survival are listed as secondary outcomes, with no results reported. The record also describes planned tumor-tissue research on estrogen receptor beta.

Safety entries list 4 of 17 participants affected by serious adverse events and 17 of 17 affected by other adverse events. The reason for termination, analysis methods, analyzed populations and outcome results are not reported in the registry record.