Primary Systemic Therapy in Operable/Locally Advanced Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Primary Systemic Therapy in Operable/Locally Advanced Breast Cancer (NCT00203502), a na phase 2 study. The primary outcome is Percentage of Participants With Pathological Complete Response..

2. Clinical Question

3. Trial Design

This was a phase 2, single-group study sponsored by the University of Arkansas. The registry lists 40 participants enrolled and the study status as completed. Allocation is recorded as not applicable, and masking is listed as none. In practical terms, the registered design does not include a randomized comparator or blinding. The design can describe outcomes among participants treated in the study, but it cannot by itself distinguish treatment effects from other influences on those outcomes.

The intervention is described as primary systemic treatment before surgery for operable or locally advanced breast cancer. The official title and brief summary describe sequential docetaxel, cyclophosphamide, and bevacizumab, followed by doxorubicin. The summary states that bevacizumab was to be given with chemotherapy for twelve weeks and held while doxorubicin was administered. It further describes postoperative bevacizumab beginning twenty-eight to fifty-six days after surgery and continuing for nine three-weekly infusions. These details describe the regimen in the record, not adherence or actual exposure among participants.

The primary endpoint was the percentage of evaluable participants with pathological complete response. The listed assessment was during surgery, with an average duration of one hour. The record defines the response by examination of the resected breast tissue. Other listed outcomes include clinical complete response in the breast and axillary lymph nodes after chemotherapy and bevacizumab, grade 3 or 4 adverse events, change in left ventricular ejection fraction from baseline, and pathological complete response among participants with triple-negative breast cancer.

The registry reports no analysis entries. It does not report a statistical analysis plan, a sample-size justification for the study itself, or detailed participant flow. Those items are not reported in the registry record. The planning illustrations associated with the posted results use hypothetical equal allocation between two arms, whereas the registered clinical design is single-group; those illustrations should not be read as a description of the trial's allocation or as observed power.

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.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Pathological Complete Response., measured over Participants were assessed during surgery, an average of one hour.

The primary endpoint is the percentage of evaluable participants with pathological complete response. In this study, the registry defines pathological complete response as absence of residual invasive and in situ cancer in the resected breast on hematoxylin and eosin evaluation. The assessment was to take place during surgery, with an average duration of one hour.

A pathological response endpoint records what is found in the tissue removed at surgery after preoperative treatment. It differs from a clinical assessment, which evaluates findings before or without relying on the resected tissue. The registry separately lists clinical complete response in the breast and axillary lymph nodes as a secondary outcome, so those clinical findings should not be conflated with the primary pathological definition.

Expressing the endpoint as a percentage of evaluable participants makes the denominator important: the estimate depends on how many participants were considered evaluable and how many met the response definition. Neither count nor the resulting percentage is reported in the registry record. The record specifies a 90% confidence interval for the endpoint, but does not report its limits. Without the estimate, denominator, and interval, the primary outcome's magnitude and precision cannot be assessed from the registry entry.

This endpoint captures a pathological finding at surgery. It does not, on its own, report longer-term outcomes or establish what caused the finding. No such inference should be drawn from the endpoint definition alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods information in the registry is limited. The study is designated phase 2 and single-group, with no masking and allocation recorded as not applicable. It enrolled 40 participants. The primary endpoint is a percentage among evaluable participants, and the record specifies a 90% confidence interval. However, the registry does not report the observed percentage, the number evaluated, interval limits, or a statistical analysis plan. Statistical interpretation therefore has to distinguish the endpoint's stated definition from results that are not reported.

What does a percentage endpoint represent?

In general, a percentage for a binary outcome describes the share of participants meeting a defined condition among the participants included in its denominator. For this endpoint, the condition is pathological complete response, defined as no residual invasive and in situ cancer in the resected breast on hematoxylin and eosin evaluation. The denominator is described as evaluable patients. The exact evaluable population and its size are not reported in the registry record, so the response percentage cannot be reconstructed or checked from the entry.

In general, percentages depend on both the number meeting the condition and the denominator. A percentage without those counts can be difficult to assess, especially when the denominator is smaller than total enrollment or when evaluability rules are unclear. The record does not state how missing assessments or participants without evaluable surgical tissue were handled. It would therefore be inappropriate to assume that all enrolled participants contributed to the primary endpoint.

How should a confidence interval be read?

In general, a confidence interval expresses uncertainty around an estimated quantity under a statistical method and its assumptions. A narrower interval represents greater precision than a wider interval, while the interval's location depends on the estimate. The registry specifies a 90% confidence interval for the primary percentage, but gives neither the estimate nor the interval. No conclusion about precision can be drawn from the confidence level alone.

The method used to construct the interval is not reported in the registry record. Different interval procedures can behave differently for proportions, especially when data are sparse or the estimate is near a boundary. Without the analysis specification and the response counts, it is not possible to determine which procedure was used or assess its suitability. A confidence interval would quantify uncertainty in the endpoint estimate; it would not correct the limitations of a single-group design or establish a causal effect.

What does the design allow?

A single-group design records outcomes in participants receiving the study regimen. General statistical interpretation can describe the observed group, but a treatment comparison requires a suitable contrast. No concurrent control group or randomized allocation is registered. Thus, even if the primary estimate were available, it would not by itself measure a difference from an alternative treatment. It also could not establish which part of the sequential regimen contributed to an observed outcome.

Masking is listed as none. In general, lack of masking can matter when outcomes involve judgment or when knowledge of treatment may influence assessment or reporting. The primary endpoint uses examination of resected tissue, but the registry does not describe pathology review procedures, central review, or assessor masking. Those procedures are not reported in the registry record; their presence or absence should not be inferred.

How should planning illustrations be interpreted?

General sample-size calculations are planning exercises based on chosen assumptions, not measurements of what happened in a trial. The registry's planning assumptions describe a hypothetical comparison with two-sided significance level 0.05, equal allocation between two arms, and a normal approximation; the targeted effect is expressed as a fraction of an observed effect. Those assumptions do not match the registered single-group design. Any resulting participants-per-arm values are hypothetical planning illustrations, not enrollment counts, observed power, or evidence about this trial's results.

The study's own sample-size justification and design assumptions are not reported in the registry record. The record also does not state whether an interim analysis was planned or conducted, what analysis population was used for each outcome, or whether the primary endpoint analysis was adjusted for other variables. Those details cannot be inferred from the phase designation, enrollment, or completion status.

What does over-dispersion mean in general?

For count outcomes, over-dispersion means that observed variability exceeds what a simple statistical model expects. If relevant, it can affect standard errors and confidence intervals, so an analysis may need a method that allows for additional variability. This is a general statistical concept, not a finding about this study. The primary endpoint is a percentage, and the registry does not identify an over-dispersion assessment or a count model. No claim about over-dispersion in these data can be made.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple outcomes in addition to the primary pathological complete response endpoint. These include clinical complete response in the breast and axillary lymph nodes, grade 3 or 4 adverse events, change in left ventricular ejection fraction from baseline, and pathological complete response among participants with triple-negative breast cancer. Assessing several outcomes can raise multiplicity concerns: in general, the more hypotheses tested, the greater the chance of at least one apparently notable result arising by chance if each is interpreted without adjustment.

The registry record does not report a multiplicity strategy, such as a hierarchy of outcomes or an adjustment to statistical testing. It also does not report a statistical analysis plan or analysis results. It is therefore not possible to determine which secondary outcomes were formally tested, how they were analyzed, or whether any adjustment was used. The presence of a listed outcome does not establish that its analysis was completed.

Missing-data handling and analysis populations are also not described. The primary endpoint is defined among evaluable patients, but the record does not give the evaluability criteria, the number assessed, or the treatment of participants without an evaluable pathology assessment. It does not state whether analyses used all enrolled participants, participants who received treatment, or another population. Those details are not reported in the registry record.

These gaps matter because the endpoint denominator and the handling of missing observations affect interpretation of a percentage. The record's 40 enrolled participants cannot automatically be treated as the primary endpoint denominator. Without the analysis population, missing-data rules, and results, the robustness of any estimate cannot be evaluated.

11. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: musculoskeletal pain (15.4%), fatigue (10.3%), nausea/vomiting (10.3%), infection (7.7%), diarrhea (7.7%).

The registry lists 39 participants at risk and 39 affected in the serious adverse-event group. In the other adverse-event category, it lists 39 at risk and 19 affected. These are registry counts for the recorded safety groups; they do not provide a comparison with an untreated or alternative-treatment group. The 40 enrolled participants and the 39 listed as at risk in these safety categories are distinct registry figures and should not be silently treated as the same denominator.

The serious-event terms listed with percentages are musculoskeletal pain at 15.4%, fatigue at 10.3%, nausea/vomiting at 10.3%, infection at 7.7%, diarrhea at 7.7%, and mucositis at 7.7%. The registry does not specify in this record whether the percentages refer to participants, event counts, or another calculation basis, so they should be read as the reported percentages rather than converted into counts or interpreted as comparative risks. No new rates can be calculated from these entries.

Serious adverse events and other adverse events are separate reporting categories. The term list does not by itself establish severity for every event, treatment causality, duration, or whether multiple terms occurred in the same participant. Deaths are not reported in the registry record. These data describe the recorded safety information but do not establish how the regimen compares with another option.

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

The record describes a phase 2 study of a sequential systemic-therapy regimen in operable or locally advanced breast cancer, with pathological complete response as its primary endpoint. It specifies how that endpoint was defined and that it was assessed during surgery. It also describes several secondary outcomes and includes adverse-event counts and term percentages. These details clarify what the study set out to assess and what safety information is recorded.

The key primary result is not reported in the registry record. There is no reported response percentage, number of evaluable participants, or 90% confidence interval. Without these, readers cannot assess the magnitude or precision of the primary endpoint from the registry entry. The listed outcome definition is not itself a result, and completion status does not fill in the missing estimate.

Even if a response estimate were available, the single-group design would constrain its interpretation. It could describe outcomes among participants in the study, but would not directly establish what would have occurred under another treatment. No randomized control group is listed, and the sequential regimen includes multiple agents and treatment periods. The design cannot separate the contribution of each component.

The safety figures should likewise be interpreted descriptively. They report affected participants in the registry's safety categories and percentages for selected serious-event terms, but do not provide a comparison group or establish whether events were caused by treatment. The record does not report deaths. Absence of a reported result is not evidence that an event did not occur; it means the result is not available in the registry record.

Overall, the registry entry supports a description of the study design, endpoint definition, treatment sequence, and selected safety reporting. It does not support a conclusion about the size of the primary response, its statistical precision, comparative benefit, or comparative harm. Those conclusions require results and analysis details not reported in the registry record.

13. Why This Trial Matters Statistically

This trial illustrates why endpoint definitions and endpoint results must be read separately. The registry defines pathological complete response in tissue from the resected breast, giving a specific pathological criterion. Yet it does not report the response percentage, the evaluable denominator, or the stated confidence interval. A precise definition improves clarity about what would count as an event, but cannot substitute for the observed estimate needed to judge its frequency or uncertainty.

The design also matters to the scope of inference. A single-group phase 2 study can provide descriptive information about outcomes in a treated group. Without a randomized comparison, the study does not directly estimate a difference against another strategy. This distinction is important when readers encounter a treatment sequence with several agents: an outcome cannot be attributed to one component solely from an outcome observed after the full sequence.

The registry's safety reporting offers another statistical lesson. Counts at risk and affected, along with percentages for selected terms, need context about their denominators, event definitions, and attribution. They are not comparative risks. A clear distinction between serious and other adverse-event categories, and between reported percentages and calculated rates, helps prevent stronger conclusions than the data support.

Finally, the record demonstrates the importance of transparent reporting beyond study completion. The status is completed, but the primary estimate, interval, analysis populations, missing-data handling, and statistical plan are not reported in the registry record. Without those details, readers cannot assess the result's precision or robustness. Statistical interpretation depends not only on a study's design and endpoint, but also on the availability of the analysis needed to connect those features to observed data.

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 of the registry entry is that it does not report the primary outcome result. The pathological complete response percentage, evaluable denominator, and 90% confidence interval are absent. This prevents assessment of the observed response and its precision. The record also lists zero analysis entries, so it does not provide numerical analyses for the primary or secondary outcomes.

The single-group design has no registered randomized comparator. As a result, outcomes cannot be interpreted as differences from another treatment, and the effects of individual components in the sequential regimen cannot be isolated. The absence of masking is recorded, but the registry does not describe pathology-review procedures or whether endpoint assessment was independently reviewed.

Enrollment is listed as 40, while the safety categories list 39 participants at risk. The record does not explain the relationship between these figures, give participant flow, or state how many participants were evaluable for the primary endpoint. Treatment exposure, adherence, withdrawals, and reasons for missing assessments are also not reported in the registry record.

The registry lists secondary endpoints but does not provide their results, analysis populations, or a multiplicity strategy. It also does not report the trial's own sample-size justification, detailed analysis methods, or missing-data approach. The hypothetical planning assumptions described for sample-size illustrations do not replace information about the actual study design or analysis.

Safety interpretation is limited by the absence of a comparison group and by missing detail about event ascertainment and treatment attribution. The registry reports selected serious-event terms and percentages, but the calculation basis is not specified in this record. Deaths are not reported in the registry record. These reporting limits do not establish that unreported outcomes or events did not occur.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Primary Systemic Therapy in Operable/Locally Advanced Breast Cancer — NCT00203502.
• Registry record last updated 2016-05-11; status last verified 2016-05.
• Results first posted 2016-01-05.
• 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

The registry describes a completed phase 2, open-label, single-group study sponsored by the University of Arkansas, with 40 participants enrolled for operable or locally advanced breast cancer. The treatment sequence involved docetaxel, cyclophosphamide, and bevacizumab followed by doxorubicin, with postoperative bevacizumab also described in the brief summary.

The primary endpoint was the percentage of evaluable participants with pathological complete response, defined by absence of residual invasive and in situ cancer in the resected breast. A 90% confidence interval was specified, but neither the endpoint estimate nor interval is reported in the registry record. Secondary outcomes included clinical response, adverse events, change in left ventricular ejection fraction, and pathological complete response among participants with triple-negative disease.

Safety reporting lists 39 participants at risk and 39 affected in the serious adverse-event group, and 39 at risk and 19 affected in the other adverse-event category. The record does not provide a randomized comparison, analysis results, or key details about analysis populations and missing data.