Hormone Therapy Or Chemotherapy Before Surgery Based on Gene Expression Analysis in Treating Patients With Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Hormone Therapy Or Chemotherapy Before Surgery Based on Gene Expression Analysis in Treating Patients With Breast Cancer (NCT01293032), a randomized na study. The primary outcome is The Proportion of Patients With RS 11-25 Who Refused the Assigned Treatment.

2. Clinical Question

3. Trial Design

This was a randomized pilot clinical trial with a parallel-group design and no masking. Virginia Commonwealth University was the sponsor. Enrollment was 59, the status is completed, the start is recorded as 2011-04, and primary completion is recorded as 2015-05. The phase is listed as NA.

The treatment strategy used the Oncotype DX gene expression Recurrence Score to guide preoperative treatment. The registry describes three score-based groups: patients with RS less than 11 were assigned hormonal therapy; those with RS 11-25 were randomized between hormonal therapy and chemotherapy; and those with RS greater than 25 were assigned chemotherapy. The primary endpoint analysis combined the intermediate-score participants assigned to both treatment arms.

The registry identifies neoadjuvant therapy, conventional surgery, laboratory biomarker analysis, gene expression analysis, systemic chemotherapy, tamoxifen, and aromatase inhibition therapy among the interventions. Detailed eligibility criteria, the randomization procedure, allocation concealment, and the intended analysis population beyond the stated combined intermediate-score group are not reported in the registry record. The available arm descriptions are truncated, so they do not provide a complete account of all treatment and follow-up procedures.

This design addresses a feasibility question rather than reporting a comparative estimate of treatment effects. The record does not report outcome analyses, and the primary endpoint result is unavailable. Consequently, the description of randomized treatment groups should not be mistaken for evidence that their outcomes were compared in a reported analysis.

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: 5/64 subjects were not assigned or randomized to an arm: delayed oncotype result, core block lost, discrepancy in a bio-marker test, and two subjects deemed not eligible. There were 5 subjects who refused assigned randomization Group 2 Arm 2. 2/5 subjects who refused Group 2 Arm 2 were treated and evaluable for response on Arm 1.

Recurrence Score(RS)Assigned/Randomized

Reasons for not completing this period:

Treatment

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Patients with an intermediate RS(11-25) assigned to Group 2, Arm 1, and Arm 2 were combined in the 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.

6. Primary Endpoint

The registry lists the primary outcome as The Proportion of Patients With RS 11-25 Who Refused the Assigned Treatment, measured over Up to 2 years.

The primary endpoint is the proportion of patients with an RS of 11-25 who refused the assigned treatment. The registry describes the analyzed population as intermediate-score patients assigned to Group 2, with participants from both Arm 1 and Arm 2 combined. The timeframe is up to 2 years. The endpoint description also frames feasibility in terms of patients refusing their assigned treatment or refusing randomization between hormonal therapy and chemotherapy.

A refusal proportion is relevant to feasibility because it describes whether participants accept the treatment assignment or randomization approach that a future trial would use. A low proportion of refusals could support the practicality of conducting a larger study, while a high proportion could signal difficulty implementing that design. This is a general interpretation of the endpoint’s role; the registry does not report the observed proportion or its confidence interval.

The stated feasibility criterion was less than 1/3 of patients with intermediate RS refusing the assigned treatment or refusing randomization. The planned summary was a proportion with a 95% confidence interval. Without the observed numerator, denominator, and interval, the registry record does not establish whether the criterion was met.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a refusal proportion represent?

As a general statistical concept, a proportion is a count of participants with a specified event divided by the number of participants in the defined analysis group. For this endpoint, the event is refusal as described in the registry, and the group is patients with RS 11-25 assigned to either of the two treatment arms. The registry says the groups were combined for this analysis. It does not report the event count or the analysis denominator, so no proportion can be reconstructed from the record.

A refusal proportion is descriptive: it summarizes how often a specified response occurred in the study population. It is not inherently a measure of treatment efficacy, and a pooled estimate does not compare the two randomized treatments. If arm-specific estimates were of interest, they would answer a different question from the combined feasibility endpoint. Such estimates are not reported in the registry record.

What does the confidence interval add?

A confidence interval is a range calculated from observed data to convey statistical uncertainty around an estimate. In general, a wider interval indicates less precision, while a narrower interval indicates greater precision under the method’s assumptions. The registry states that the refusal proportion would be accompanied by a 95% confidence interval. It does not report the interval, the method used to calculate it, or the observed proportion. The confidence level alone does not reveal whether the result met the feasibility criterion.

The criterion was expressed as less than 1/3 of intermediate-score patients refusing the assigned treatment or refusing randomization. To assess that criterion, the observed estimate and its uncertainty would be important. A point estimate near or on one side of a threshold may not give a clear account of uncertainty if the interval spans values on both sides. This is a general interpretive consideration, not a description of the unreported trial result.

What does randomization mean in this design?

In general, randomization assigns participants to study groups by chance, helping reduce systematic differences between groups at the time of assignment. Here, the registry describes randomization only for the intermediate RS group, between hormonal therapy and chemotherapy. The low-score and high-score groups are described as assigned to one treatment according to their score category, not randomized between the two treatments. This distinction matters: the primary feasibility analysis combines the randomized intermediate-score arms, but the record does not report a comparative outcome analysis for those arms.

The registry identifies the design as parallel and unmasked. In a parallel design, assigned groups receive their respective interventions during the same study period rather than crossing over between interventions. No masking means the design is not described as blinded. Specific procedures for allocation concealment, sequence generation, and handling of treatment changes are not reported in the registry record.

What can be said about analysis planning?

The record does not report a statistical analysis plan, a sample-size justification, or an interim-analysis plan. It also lists no analyses. No inferential procedure beyond the stated proportion and 95% confidence interval can be attributed to the trial from the registry record. General methods such as hypothesis tests, regression adjustment, or subgroup analysis should not be assumed to have been used.

Planning illustrations based on an observed effect are not substitutes for the trial’s original design assumptions or for observed evidence. In this record, there is no reported primary endpoint estimate from which a trial-specific observed effect could be interpreted. Illustrative sample sizes, if considered separately, would be planning scenarios rather than evidence about this pilot’s power or its results. They would not be observed power.

Why does the missing result matter statistically?

Without the number of refusals and the number assessed, readers cannot judge the magnitude or precision of the feasibility estimate. Without a reported analysis population and the handling of missing endpoint data, the effect of incomplete follow-up also cannot be assessed. A confidence interval cannot be inferred from the stated enrollment, because the enrollment count does not identify how many participants had an intermediate score, entered the combined endpoint group, or had an observed endpoint.

These limitations do not erase the value of the design description. They define what can be learned from the posted record: the intended endpoint and its rationale are documented, while its numerical result and the statistical procedures actually used are not reported.

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("Group 2 (RS 11-25)")
n      <- c(33)
events <- c(0)
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  Group 2 (RS 11-25)  33  0  0.0  0.0  10.6  0.0  10.4  0.1  10.3

11. Multiplicity, Missing Data and Analysis Populations

The primary purpose described in the registry is to assess feasibility, with a refusal proportion and 95% confidence interval as the primary endpoint summary. The registry record does not report a multiplicity strategy, a hierarchy of outcomes, or adjustments for multiple comparisons. It also lists one outcome measure and zero analyses. It is therefore not possible to determine whether any additional analyses were planned or how they would have been controlled statistically.

Missing-data methods are not reported in the registry record. The endpoint description does not state how participants with unknown refusal status, incomplete follow-up, or unavailable RS information were handled. The record also does not provide the endpoint denominator or participant flow for the combined intermediate-score group. These omissions prevent assessment of whether the reported population, if a result were available elsewhere, included all eligible participants or only those with observed endpoint data.

The analysis population is described as intermediate RS participants assigned to both arms combined. The record does not specify further population definitions, such as whether all randomized participants would be included regardless of treatment received. It also does not report an intention-to-treat analysis or a per-protocol analysis. Those approaches should not be presumed.

Because neither the endpoint result nor an analysis description is posted, the effect of missing observations, multiple testing, or analysis-population choices cannot be evaluated. These are limits on statistical interpretation, not evidence that a particular method was or was not used outside the registry record.

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

The record’s stated aim is to evaluate whether a future large multi-center trial using an RS-guided treatment strategy would be feasible. The primary endpoint focuses on refusal among patients with intermediate RS who were assigned to hormonal therapy or chemotherapy. That endpoint can inform the practicality and acceptability of the study process, but it does not itself determine which treatment produces better clinical outcomes.

The registry does not report the observed refusal proportion, its 95% confidence interval, or a conclusion relative to the stated feasibility threshold. It therefore does not establish whether the trial met its feasibility objective. The completed status and enrollment of 59 describe trial conduct, not the result of the primary endpoint.

The treatment descriptions also do not establish comparative effectiveness. Only the intermediate RS group is described as randomized between the two treatments, and no comparative outcome analyses are listed. The record does not report response, recurrence, survival, or other clinical outcome results. No claim about benefit or lack of benefit for either treatment follows from the information available in the registry record.

Likewise, the adverse-event entries should not be treated as evidence of safety. Zero counts are listed for participants at risk and affected in the event categories, but there are no evaluable denominators or reported safety analyses, and deaths are null. These fields do not establish that adverse events or deaths did not occur.

In general, a pilot feasibility study can help assess recruitment, treatment acceptance, and study procedures before a larger trial. The registry’s stated purpose is consistent with that role. However, the missing outcome result means readers cannot evaluate how well this particular study achieved the stated objective.

13. Why This Trial Matters Statistically

This trial is statistically notable for separating a feasibility question from a treatment-effect question. The primary endpoint is refusal among participants with intermediate RS, rather than a clinical outcome comparing hormonal therapy and chemotherapy. Keeping those questions distinct prevents a feasibility measure from being misread as evidence about comparative treatment benefit.

The design also illustrates how a biomarker-defined strategy can produce different assignment pathways. The registry describes hormonal therapy for the low-score group, randomization between treatments for the intermediate-score group, and chemotherapy for the high-score group. Only the intermediate group provides the randomized treatment comparison described in the record. The primary refusal analysis combines those two arms, matching its stated feasibility focus.

For statistical interpretation, a proportion accompanied by a confidence interval can communicate both the observed frequency of refusal and the uncertainty around that estimate. But the method is informative only when the event count, denominator, and interval are reported. Their absence in this record prevents assessment of whether the planned feasibility threshold was achieved.

The record also demonstrates the difference between a completed study and a fully interpretable result record. Trial status, enrollment, design, and endpoint rationale are documented, while the endpoint estimate and analyses are not. That distinction is important for readers evaluating what the registry can establish: it provides a study framework, but not the numerical evidence needed to judge the primary objective.

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 central limitation is that the registry record does not report the primary endpoint result. Although the endpoint is defined as a refusal proportion with a 95% confidence interval, neither the estimate nor its interval is posted. There is also no reported denominator or event count for the combined intermediate-score group. As a result, the feasibility criterion cannot be evaluated.

The record lists zero analyses, so there is no reported statistical comparison or inferential result to interpret. It does not report the method used to calculate the confidence interval, the handling of missing endpoint observations, or a detailed analysis population. A statistical analysis plan, multiplicity approach, interim-analysis plan, and sample-size justification are not reported in the registry record.

Several design details are also unavailable or incomplete. The arm descriptions are truncated, and the record does not report the randomization procedure, allocation concealment, full eligibility criteria, or detailed follow-up procedures. The registry’s primary purpose is feasibility, and no clinical efficacy outcome results are reported. The record therefore cannot support a comparative assessment of treatment outcomes.

The safety entries list zero at-risk and affected counts in each group, while death counts are null. Without reported denominators and an analysis, those entries cannot establish the occurrence or absence of adverse events. These limitations concern the content of the registry record; they do not determine what may have been collected or analyzed outside it.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Hormone Therapy Or Chemotherapy Before Surgery Based on Gene Expression Analysis in Treating Patients With Breast Cancer — NCT01293032.
• Registry record last updated 2016-07-12; status last verified 2016-06.
• Results first posted 2016-07-12.
• 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.

18. Record Summary

NCT01293032 is a completed randomized pilot trial sponsored by Virginia Commonwealth University. It examined an Oncotype DX Recurrence Score-guided approach to choosing preoperative hormonal therapy or chemotherapy for patients with hormone-responsive breast cancer not suitable for breast-conserving surgery. Enrollment was 59, with the start recorded as 2011-04 and primary completion as 2015-05.

The primary endpoint was the proportion of intermediate-score participants who refused assigned treatment, with a planned 95% confidence interval and a timeframe of up to 2 years. The registry describes the intermediate-score group as randomized between hormonal therapy and chemotherapy, with both arms combined for the primary analysis. The observed endpoint, confidence interval, and analyses are not reported in the registry record, so the stated feasibility objective cannot be evaluated from the posted results.