Aging Mammary Stem Cells and Breast Cancer Prevention: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Aging Mammary Stem Cells and Breast Cancer Prevention (NCT02642094), a na phase 2 study. The primary outcome is The Effect of Short-term Rapamycin Treatment on the Frequency of Luminal Progenitor Epithelial Cells.

2. Clinical Question

3. Trial Design

The registry lists this as a phase 2, single-group study with allocation recorded as NA and no masking. Its title is “Aging Mammary Stem Cells and Breast Cancer Prevention,” and the listed condition is Cancer of Breast. The sponsor is LuZhe Sun. The record gives a start date of 2016-07, a primary completion date of 2022-03-01, and a status of terminated. Enrollment is listed as 58.

The treatment description specifies low-dose rapamycin at 2 mg/day for 5-7 days. A surgical specimen was to be obtained 3-7 days after the last dose. The specimens were to be evaluated for lesion size, nuclear grade, and presence of necrosis in core biopsy and surgical specimens. These details describe the intended treatment and specimen collection, not the actual timing or completeness of every participant’s procedures.

The primary outcome description focuses on frequency of luminal progenitor epithelial cells and says that mean data were compared between control and treatment groups with an unpaired t test. At the same time, the design is labeled single-group, and the registry’s own caution says the comparison is not randomized and that the arms are not a like-for-like control comparison. The source, eligibility, and timing of the controls are not reported in the registry record. Consequently, the control comparison cannot be interpreted as a randomized treatment contrast.

The record says fresh surgical tissues and mammary epithelial cell profiles by flowcytometry were obtained from 27 patients in the treatment group. This is the stated population for the primary comparison, but the record does not describe why other enrolled participants are not included in that statement, nor whether the enrollment figure refers to the same analysis population. The registry lists five outcome measures and five analyses, but details of the other outcomes are not reported in 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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Tissue samples were randomly selected from 12 patients with DCIS who participated in the treatment study

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: This was a non-random, open-label, phase II, window of opportunity trial to investigate a possible inhibition of mammary stem cells (MaSCs) in non-cancerous tissue and/or malignant markers by rapamycin in patients with non-invasive breast cancer. A total of 40 patients agreed to undergo the treatment and 38 successfully completed the regiment. The control group for providing non-cancerous breast tissue included 12 patients with non-invasive breast cancer and 6 with invasive cancer.

6. Primary Endpoint

The registry lists the primary outcome as The Effect of Short-term Rapamycin Treatment on the Frequency of Luminal Progenitor Epithelial Cells, measured over 5-7 day rapamycin treatment plus 3-7 day washout for the treatment group..

The primary endpoint is the frequency of luminal progenitor epithelial cells, expressed as a percentage of total lineage neg. cells. It is a continuous measure summarized using a mean and standard deviation. The registry describes measurement of the cell population from mammary epithelial cell profiles obtained by flowcytometry.

Cell-population frequency can be used to characterize the composition of sampled tissue. In this study, the planned comparison was between control and treated patients, and the stated aim was to assess changes in the luminal progenitor population after short-term rapamycin treatment. The broader study summary also describes examining malignant markers and aberrant mammary stem/progenitor cell numbers in surgical specimens. The record does not explain how the cell frequency was selected as a surrogate for cancer prevention, or establish that a change in this measure would predict a clinical outcome.

The timeframe combines a 5-7 day treatment period with a 3-7 day washout before the specimen assessment in the treatment group. This makes the endpoint a tissue measurement around surgery, rather than a long-term measure of cancer incidence or recurrence. The primary outcome title and measurement unit are reported, but the actual group means, standard deviations, estimated difference, and uncertainty around that difference are not reported in the registry record. Without those results, the magnitude and precision of any observed difference cannot be evaluated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is this? The primary outcome is continuous: it is a measured frequency expressed as a percentage of total lineage neg. cells. The registry says the analysis parameter is the mean and the dispersion measure is the standard deviation. A mean describes the central value of the observations, while a standard deviation describes how spread out individual observations are around that mean. These summaries answer different questions: the mean is about the group’s average, and the standard deviation is about variation among observations.

What does the stated test compare? The record says the mean luminal progenitor cell data were compared between control and treatment groups using an unpaired t test. In general, an unpaired t test evaluates whether the means in two independent groups are compatible with a common underlying mean, under assumptions about the data and the comparison. “Unpaired” means that the test does not treat each observation in one group as matched to a particular observation in the other group. The registry does not report the test statistic, degrees of freedom, p-value, or an estimated mean difference for this endpoint.

Why does the comparison structure matter? A statistical test can quantify evidence for a difference under its model, but it cannot by itself make groups comparable. The registry identifies the study as single-group, records allocation as NA, and cautions that the comparison is not randomized and that the arms are not like-for-like. The primary outcome description refers to controls, yet the control group’s source and selection are not reported in the registry record. In general, group differences in a nonrandomized comparison may reflect differences in participant characteristics, tissue collection, or other factors, as well as any treatment-related difference. The posted design information does not establish how such factors were addressed.

What would a confidence interval add? In general, a confidence interval gives a range of estimates compatible with the observed data and the statistical model at a stated confidence level. Its width conveys precision: a wider interval indicates less precise estimation than a narrower interval. A p-value and a confidence interval are not interchangeable. A p-value summarizes how surprising data would be under a specified null model; an interval communicates plausible values for the effect estimate under its assumptions. The registry does not report a confidence interval or a primary outcome estimate, so neither the size nor precision of the comparison can be assessed.

How should the sample-size illustrations be understood? The record’s assumptions describe planning illustrations based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustrations are described as the total number of events for time-to-event outcomes and participants per arm for other outcomes. These are planning calculations, not observed trial results and not observed power. The registry does not report the numerical illustrations in the information available for this analysis, and the actual observed primary effect is not reported. A planning estimate derived from an observed effect would not establish that the original study was designed with that effect in mind.

Why can over-dispersion matter in general? For count outcomes, over-dispersion means that the observed variability exceeds what a simple model assumes. If it is ignored, standard errors can be too small and statistical evidence can appear stronger than warranted. This primary endpoint, however, is described as a continuous measure analyzed by means and an unpaired t test, not as a count outcome. The registry does not report a count model for this endpoint. General concerns about over-dispersion should not be mistaken for a method used in this analysis.

What can be learned from the available method description? It identifies the measurement, summary statistics, comparison named by the registry, and the stated tissue-analysis population. It does not provide enough information to reproduce or independently evaluate the primary analysis. Details such as the handling of missing measurements, distributional checks, covariate adjustment, control selection, or sensitivity analyses are not reported in the registry record. The test name alone does not resolve those uncertainties.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Control", "Treatment Group")
n   <- c(18, 27)
m   <- c(11.82, 6.178)
sp  <- c(9.221, 5.525)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Control  18  11.820  9.221  7.235  16.405
CARM  Treatment Group  27  6.178  5.525  3.992  8.364

11. Multiplicity, Missing Data and Analysis Populations

The registry lists five outcome measures and five analyses. The record does not describe a prespecified multiplicity strategy, such as a hierarchy of outcomes, an adjustment to control false-positive risk across several tests, or a designation of which analyses are confirmatory. That strategy is not reported in the registry record. When multiple outcomes or analyses are examined, general statistical practice distinguishes the chance of a finding within a single test from the chance of at least one apparently notable finding across a family of tests. Without the analysis plan and results, the implications of multiple testing cannot be quantified.

The primary outcome description says fresh surgical tissues and mammary epithelial cell profiles by flowcytometry were obtained from 27 patients in the treatment group. It does not give a participant flow, reasons for unavailable specimens, or the number of control observations. Enrollment is listed as 58, but the record does not explain how enrollment relates to the outcome-specific population. The difference between those descriptions should not be treated as a known count of missing outcomes or as evidence about why data were unavailable.

How missing outcome data were handled is not reported in the registry record. There is no reported imputation method, missingness assessment, or sensitivity analysis for the primary endpoint. The analysis population is not described as intention-to-treat, per-protocol, or another named population. These omissions limit assessment of whether the analyzed tissue samples represent the enrolled participants and how missing measurements might affect the estimate.

12. 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’s adverse-event figures list 40 at risk for serious events, 0 affected by a serious event, 40 at risk for other adverse events, 24 affected by other adverse events, and 0 deaths. These are registry counts, not a comparison between randomized treatment groups. No top serious adverse-event terms are listed.

The counts should be read within the categories and denominators recorded, rather than combined or treated as a complete account of all harms. The record does not explain how the safety population relates to the 27 patients described for fresh tissue and flowcytometry, or to the enrollment figure of 58. It also does not report event definitions, severity, timing, attribution to treatment, or the nature of the other adverse events. The absence of listed serious-event terms does not fill in those details.

These figures describe what the registry reports; they do not by themselves establish the cause of an event or characterize safety beyond the recorded categories and population. The reason for any difference between the adverse-event population and other study populations is not reported in the registry record.

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

The record establishes that the study aimed to examine short-term rapamycin treatment in relation to mammary cell populations measured in surgical specimens. It identifies a continuous primary endpoint, its measurement unit, the use of means and standard deviations, and an unpaired t test for the described comparison. It also reports that tissue and cell profiles were obtained from 27 patients in the treatment group.

What the posted information does not establish is the observed primary outcome result. No group means, standard deviations, between-group estimate, confidence interval, or p-value are reported in the registry record. As a result, no direction, magnitude, or precision of a difference can be stated from this record. The absence of these results is not evidence that there was no difference; it means the primary comparison cannot be evaluated from the reported information.

The record also does not establish a causal treatment effect. It identifies a single-group design, allocation as NA, and a nonrandomized, not-like-for-like comparison, while the primary outcome description refers to controls. Control selection and comparability are not reported. Statistical adjustment, if any, is not described. Even a documented group difference would require careful interpretation in light of those design limitations.

The endpoint is a tissue cell-frequency measure assessed around a brief treatment and washout period. It is not a reported measure of cancer prevention over time. The registry’s title and study summary describe a prevention-related motivation, but the primary endpoint alone does not establish a clinical prevention benefit, and the record does not report a link between this cell measure and later clinical outcomes.

The posted safety counts should likewise be interpreted narrowly. They report no serious events among the recorded serious-event population and 24 affected by other adverse events among the recorded other-event population, but event descriptions and the relationship of those populations to the tissue analysis are not reported. Overall, the record supports a description of the research question and some study procedures, not a quantitative conclusion about the primary outcome or a clinical effect.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of why a clearly stated research question is not the same as an interpretable result. The record specifies a cellular endpoint, a short treatment period, a specimen-based assessment, and a named test. Those elements help readers understand what investigators intended to measure. But without the outcome estimates and their uncertainty, the central comparison cannot be judged quantitatively.

The mismatch between the single-group design label and the primary outcome’s reference to controls is also important. The record itself cautions that the comparison is nonrandomized and not like-for-like. This illustrates a general point: statistical testing addresses uncertainty under a model, while study design governs how confidently a group contrast can be attributed to an intervention. A test cannot remove bias arising from an unclear or noncomparable control group.

The distinction between a laboratory endpoint and a clinical outcome matters as well. Cell frequencies can be useful measurements for biological research, but a change in a tissue marker does not automatically translate into a change in later disease outcomes. The registry record describes a prevention-related research aim yet does not report a clinical prevention endpoint or validation connecting the primary measure to one.

Finally, the differences among enrollment, tissue-analysis, and safety-population descriptions show why each analysis population needs clear documentation. Knowing who contributed data, how missing measurements were handled, and how controls were selected is necessary to understand the scope and limitations of an estimate. Those details, together with complete results and multiplicity methods, are not reported in the registry record.

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 limitations specific to this record constrain interpretation. The primary outcome description refers to control and treatment groups, while the registry classifies the study as single-group and allocation as NA. The source and selection of controls, their participant characteristics, and whether tissue was collected and processed comparably are not reported. The record explicitly cautions that the arms are not a like-for-like comparison.

The tissue-analysis description identifies 27 treatment-group patients, whereas enrollment is listed as 58. The record does not explain the relationship between these populations, give reasons for unavailable tissue profiles, or describe the primary analysis population in a formal way. This prevents assessment of selection into the tissue analysis and limits understanding of missing data.

The primary outcome results themselves are not reported: group summaries, an effect estimate, uncertainty, and test results are absent. The record also does not explain whether the analysis included adjustment for other variables, how assumptions were checked, or how any missing observations were handled. Although five outcome measures and five analyses are listed, a multiplicity approach is not reported.

The endpoint is a laboratory measure from surgical specimens collected around short-term treatment. The record does not report a clinical prevention outcome or explain whether the cell-frequency measure predicts later clinical outcomes. The reason the study was terminated is not reported in the registry record. Safety event descriptions and their relationship to the tissue-analysis population are also not reported, limiting detailed interpretation of the safety counts.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Aging Mammary Stem Cells and Breast Cancer Prevention — NCT02642094.
• Registry record last updated 2023-12-05; status last verified 2023-12.
• Results first posted 2023-12-05.
• 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.

19. Record Summary

The registry describes a phase 2 study of short-term rapamycin for examining mammary cell populations in surgical specimens. It lists a single-group design, allocation NA, no masking, enrollment of 58, and terminated status. The treatment description specifies 2 mg/day for 5-7 days, followed by a surgical specimen 3-7 days after the last dose.

The primary endpoint is luminal progenitor epithelial cell frequency as a percentage of total lineage neg. cells, summarized by means and standard deviations. The record says data from 27 treatment-group patients with fresh tissue and flowcytometry profiles were compared with controls using an unpaired t test. The control-group details are not reported, and the registry cautions that the comparison is nonrandomized and not like-for-like.

The primary outcome estimates and their uncertainty are not reported in the registry record, so the size and direction of the comparison cannot be assessed. Safety counts list 0 serious events, 24 affected by other adverse events, and 0 deaths in their recorded populations.