Atorvastatin in Treating Patients With Stage IIb-III Triple Negative Breast Cancer Who Did Not Achieve a Pathologic Complete Response After Receiving Neoadjuvant Chemotherapy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Atorvastatin in Treating Patients With Stage IIb-III Triple Negative Breast Cancer Who Did Not Achieve a Pathologic Complete Response After Receiving Neoadjuvant Chemotherapy (NCT03872388), a non-randomized phase 2 study. The primary outcome is Proportions of Patients With Undetectable Circulating Tumor Cells (CTC).

2. Clinical Question

The study focuses on a population with residual cancer after preoperative chemotherapy, rather than patients who achieved a pathologic complete response. Its primary endpoint is a blood-based measure of circulating tumor cells (CTCs). The study description also places the endpoint in the context of recurrence-free survival and lists CTCs and recurrence-free survival among secondary outcomes. Those listed aims do not substitute for collected observations: no primary endpoint results are reported in the registry record.

3. Trial Design

This is a phase II multicenter pilot study sponsored by M.D. Anderson Cancer Center. The registry lists a non-randomized allocation, no masking, and a parallel model. Enrollment is recorded as 6. The study started on 2019-09-23, had a primary completion date of 2023-10-19, and is listed as terminated. The reason for termination is not reported in the registry record.

The two described groups differ by eligibility for atorvastatin. Group I receives atorvastatin for up to 24 months. Patients not eligible for atorvastatin may enter a non-statin observation group, with or without capecitabine. Since treatment assignment was not randomized, group membership may reflect eligibility or other characteristics related to patient status. The record does not report how many participants were assigned to each group, whether everyone enrolled received treatment, or the reasons for individual treatment choices.

The primary outcome is the proportion of patients with undetectable CTCs at 6 months. The registry describes secondary outcomes involving lipid levels, biomarkers, C-reactive protein, CTCs, recurrence-free survival, and adverse events. It lists 9 outcome measures, but reports 0 analyses. The primary outcome population is explicitly described as “Data were not collected.” The record does not report participant flow, outcome results, or a detailed statistical analysis plan. Consequently, the design features and stated aims can be described, but the relative outcomes of the groups cannot be assessed from the registry record.

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: 6 participants were accrued and assessed for eligibility and 4 patients were assigned to the cohort.

Only the first 6 of 8 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Data were not collected.

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: 6 participants were accrued and assessed for eligibility and 4 patients were assigned to the cohort.

Only the first 6 of 9 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Proportions of Patients With Undetectable Circulating Tumor Cells (CTC), measured over At 6 months.

The primary endpoint is the proportion of patients with undetectable circulating tumor cells at 6 months. It is intended to describe how frequently this blood-based finding occurs in patients with stage IIB/III triple-negative breast cancer who did not achieve a pathologic complete response or Residual Cancer Burden-I after neoadjuvant chemotherapy. The study description frames the estimate as applying to patients receiving atorvastatin and those not receiving it.

A proportion expresses the share of an assessed group that meets a specified condition. For this endpoint, the condition is that CTCs are undetectable at the stated follow-up time. As a general statistical point, this kind of endpoint gives a snapshot at a defined time; it does not by itself describe when an event occurs or how outcomes change beyond that time. Recurrence-free survival is listed separately among the secondary outcomes.

The endpoint cannot be interpreted quantitatively from this registry record because its population field says data were not collected. The record therefore supplies no observed proportion, group-specific estimate, confidence interval, or result at 6 months. It also does not report the assay details or the operational threshold used to classify CTCs as undetectable. The rationale for selecting this endpoint beyond the description in the study record is not reported.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a phase II, non-randomized, unmasked, parallel study. These terms convey design features, not outcome findings. A parallel design assigns participants to groups intended to be followed alongside one another. Non-randomized allocation means the record does not describe assignment by chance. As a general statistical principle, randomization helps balance both measured and unmeasured characteristics on average; without it, differences between groups may reflect who entered each group as well as treatment. This study's group descriptions specifically distinguish patients eligible for atorvastatin from patients not eligible for it.

What would a proportion estimate mean?

The primary outcome is a proportion: the share of assessed patients whose CTCs are undetectable at 6 months. Estimating it requires a defined denominator of participants assessed at that time and a count meeting the endpoint definition. The registry reports neither those counts nor an outcome population; it says data were not collected. No proportion can therefore be interpreted from the record. The CTC assay and the rule for classifying a result as undetectable are also not reported in the registry record.

How would uncertainty ordinarily be described?

As a general explanation, a confidence interval expresses uncertainty around an estimate under stated statistical assumptions. A narrower interval indicates greater precision, while a wider interval indicates less precision. Its width depends in part on the amount of information available and the variability of the measure. There is no reported primary estimate or confidence interval for this study, so neither the endpoint's observed value nor its precision can be assessed. No p-value or other primary comparison result is reported either.

Why does the allocation method matter?

The atorvastatin group and non-statin observation group are not formed through reported random assignment. Patients in the latter group are described as not eligible for atorvastatin, and capecitabine may also be used. These differences can complicate interpretation of any between-group contrast. As a general matter, statistical adjustment can address measured differences if suitable data and a prespecified or otherwise justified model are available, but it cannot guarantee removal of unmeasured confounding. The registry record does not report an adjustment strategy, baseline comparisons, or an analysis model.

What do planning illustrations tell readers?

The registry's planning assumptions describe an illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is expressed as a fraction of the observed effect. For time-to-event planning, the stated output is a total event count using the Schoenfeld approach; other planning outputs are participants per arm. These are planning illustrations, not the study's own design justification and not observed power. No sample-size justification for the trial is reported in the registry record. Since no primary outcome result is reported, an observed effect for that endpoint is unavailable in the registry record; the assumptions should not be mistaken for evidence that the study had a particular ability to detect an effect.

What can be inferred from the analysis record?

The registry lists 9 outcome measures and 0 analyses. Listing an outcome identifies an intended or recorded measure, but does not show that the measure was collected, analyzed, or reported. The primary outcome is explicitly marked as not collected. The registry does not report analysis populations, handling of missing observations, or a statistical analysis plan. It also does not report interim analyses, model details, or a method for comparing the groups. Those omissions prevent reconstruction of an efficacy analysis and limit assessment of whether any planned methods were followed.

As a general statistical concept, over-dispersion occurs when observed variability exceeds what a chosen probability model expects. In that setting, standard errors from the simpler model can be too small, making intervals too narrow and tests too optimistic. The record does not identify a model for the primary endpoint, report variability, or indicate that over-dispersion was assessed; there is no basis to say it was relevant to the study's actual analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 9 outcome measures spanning CTCs, lipid measurements, biomarkers, C-reactive protein, recurrence-free survival, and adverse events. When multiple outcomes or comparisons are tested, the chance of at least one apparently notable result can increase. As a general statistical matter, multiplicity methods may control that risk, prioritize a primary endpoint, or define a testing sequence. The registry record does not report a multiplicity strategy, a testing hierarchy beyond identifying the primary outcome, or an analysis plan. Because it lists 0 analyses and no efficacy results, there are no reported tests whose multiplicity adjustment can be evaluated.

Missing-data handling is also not reported. The primary outcome population field states that data were not collected. The record does not clarify whether this means no CTC endpoint data were collected for any enrolled participant, whether data were unavailable for a particular analysis population, or why collection did not occur. It gives no participant flow, endpoint denominators, follow-up completion, or reasons for missing observations. No assumptions or methods for handling missing data are reported.

The analysis populations are not described. The record does not say whether analyses were intended to include all enrolled participants, only treated participants, or only those with an endpoint assessment. It does not report how participants were classified if they received capecitabine, discontinued treatment, or had incomplete follow-up. These details cannot be inferred from the group descriptions or from enrollment alone. The available record therefore does not support an assessment of selection into analysis, missing-data bias, or multiplicity control.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent non-serious adverse event terms

The registry lists serious and other adverse-event counts by cohort. In Cohorts 1a, 1b, 2a, 2b, 3a, and 3b, the listed numbers at risk and affected are 0 for both serious and other events, and the listed death counts are 0. In Cohort 4a, 2 are listed at risk for serious events and 0 are listed as affected; 2 are listed at risk for other events and 2 as affected; the death count is 1. In Cohort 4b, the corresponding serious-event figures are 2 at risk and 0 affected, and the other-event figures are 2 at risk and 2 affected; the death count is 0.

These are registry counts, not rates. The record does not explain the cohort labels, provide event descriptions for the other-event counts, or report exposure time. No serious adverse-event terms are listed. Counts of zero should be read as zero recorded in those fields, not as proof that no safety events occurred outside the recorded information. The registry also does not explain how the cohort-specific safety entries relate to the enrollment total or to the treatment groups. The reason for the listed death in Cohort 4a is not reported in the registry record.

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

The record establishes that a phase II pilot study was planned to examine atorvastatin in patients with triple-negative breast cancer and residual disease after neoadjuvant chemotherapy. It describes a primary endpoint of undetectable CTCs at 6 months and a non-statin observation group that could include capecitabine. It also records enrollment of 6 and a terminated status. These registry entries describe the study, not its efficacy findings.

The record does not establish whether atorvastatin changed the proportion of patients with undetectable CTCs, whether either group had a particular CTC response, or whether recurrence-free survival differed. The primary outcome data were not collected, and 0 analyses are listed. There are no reported effect estimates, confidence intervals, or hypothesis-test results to support a quantitative conclusion. No inference about the direction or size of a treatment effect is possible from the stated study aims.

The design would also require caution in interpreting a comparative result if one were available. Allocation was non-randomized, and patients in the non-statin group are described as not eligible for atorvastatin. The groups may therefore differ in ways that matter to outcomes. The registry does not provide information needed to characterize or adjust for such differences.

The safety entries should likewise be read as counts recorded by cohort, not as comparative risks or proof of causation. The record does not provide event descriptions for other adverse events or explain the relationship of the cohort entries to the treatment groups. Overall, the registry supports statements about the study's purpose, design, and incomplete outcome reporting; it does not support claims that a treatment worked, failed, or had a particular safety profile.

13. Why This Trial Matters Statistically

This study is statistically notable because its clinical question and endpoint are clearly stated, while the registry does not report the data needed to answer that question. That distinction is important in trial interpretation: a protocol aim is not an outcome result, and enrollment alone does not establish that the endpoint was assessed. Here the primary outcome population is marked “Data were not collected,” and the registry lists 0 analyses.

The non-randomized design also illustrates why group comparisons depend on more than a numerical contrast. The treatment group descriptions distinguish patients eligible for atorvastatin from those who are not, and capecitabine may be used in the non-statin group. As a general statistical principle, differences in eligibility and treatment can create confounding. Without outcome data, group sizes, and participant characteristics, neither the size nor the source of any potential difference can be evaluated.

The record further distinguishes planning assumptions from evidence. The planning illustrations use an observed effect as their reference, but they are not the trial's own design justification and do not constitute observed power. The registry does not report a sample-size justification, analysis plan, or interim-analysis approach. Those gaps matter because readers need to know how a study intended to estimate uncertainty and interpret multiple outcomes, especially when a pilot examines several biological and clinical measures.

For clinical researchers, the main statistical lesson is to separate intended measurement from collected evidence, and descriptive cohort counts from comparative risk estimates. This registry record allows the study's question and limitations to be identified, but not a conclusion about efficacy or a precise estimate of safety.

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 primary limitation is that the registry states that data for the primary endpoint were not collected. It consequently provides no CTC outcome estimate at 6 months, no group-specific results, and no reported analysis. Enrollment is recorded as 6, but the record does not give participant flow, group sizes, treatment exposure, or endpoint denominators. It is therefore not possible to determine how enrollment translated into treatment or follow-up.

The non-randomized allocation limits the interpretation of any potential group contrast. The record describes the non-statin group as patients not eligible for atorvastatin, with or without capecitabine, but does not give reasons for ineligibility or report baseline characteristics. The groups cannot be treated as exchangeable controls on the basis of the registry description.

Several protocol and analysis details are not reported in the registry record: the reason for termination; the sample-size justification; the statistical analysis plan; analysis populations; missing-data methods; multiplicity control; and interim analyses. The registry does not describe the CTC assay or threshold for an undetectable result. The outcome list includes several biomarker and clinical measures, but their collection and results are not reported. Safety entries are cohort-specific counts without event descriptions for other adverse events or a stated relationship to treatment groups. These limitations prevent assessment of efficacy, precision, and comparative safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Atorvastatin in Treating Patients With Stage IIb-III Triple Negative Breast Cancer Who Did Not Achieve a Pathologic Complete Response After Receiving Neoadjuvant Chemotherapy — NCT03872388.
• Registry record last updated 2024-10-02; status last verified 2024-09.
• Results first posted 2024-10-02.
• 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 record describes a phase II, multicenter pilot study sponsored by M.D. Anderson Cancer Center. It is listed as non-randomized, unmasked, and parallel, with enrollment of 6 and status terminated. The primary question concerns the proportion of patients with stage IIB/III triple-negative breast cancer and residual disease after neoadjuvant chemotherapy who have undetectable CTCs at 6 months, with and without atorvastatin.

The intervention description includes atorvastatin for up to 24 months; the non-statin observation group may receive capecitabine. The registry lists 9 outcome measures and 0 analyses. It states that primary outcome data were not collected. The reason for termination, outcome results, group sizes, analysis populations, and statistical analysis plan are not reported in the registry record. The available information describes the study's aims and design but does not permit an efficacy estimate or a comparative safety conclusion.