Analyzing a New Mechanism in Response to Tamoxifen Therapy in Breast Cancer Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Analyzing a New Mechanism in Response to Tamoxifen Therapy in Breast Cancer Patients (NCT01027416), a randomized na study. The primary outcome is Mean Percent Positive Proximity Ligation Assays of All Tumor Protein p53-wild Type Breast Tumors in Participants by Treatment Arm.

2. Clinical Question

The registry describes a study of the interaction between estrogen receptor-alpha and the tumor suppressor protein p53, together with tumor gene expression in response to tamoxifen. Its primary outcome focuses on the mean percentage of positive proximity ligation assay measurements in p53-wild type tumors. The comparison is between treatment arms, rather than a comparison of each participant’s measurement before and after treatment.

The registry lists the primary outcome timeframe as 2 years. The arm description specifies a 4-week course of tamoxifen; the registry record does not report further detail about the timing of sample collection or the relationship between treatment and measurement beyond the stated outcome timeframe. The question is therefore about the recorded assay measurement in the two arms, not about clinical outcomes such as tumor response, recurrence, or survival. Those outcomes are not described as the primary question in the registry record.

3. Trial Design

This was a randomized, parallel-group study with no masking. The registry lists the study as completed and gives total enrollment as 59. The two arms were No Intervention and Tamoxifen. The tamoxifen arm description specifies 20 mg orally once daily for 4 weeks; the comparator arm is described as receiving no intervention. The study phase is listed as NA.

The condition is breast cancer, and the sponsor is Roswell Park Cancer Institute. The registry gives a study start date of 2009-12-14 and primary completion as 2015-12. The title and summary describe a pilot investigation of a proposed mechanism involving estrogen receptor-alpha and p53, with an interest in tumor gene expression in response to hormonal therapy. The registry summary says that such information may eventually help with therapy selection for future patients; this is a description of the study’s motivation, not a reported clinical finding.

The primary outcome population is patients with p53-wild type breast tumors. The posted outcome summaries report 23 participants for No Intervention and 12 for Tamoxifen. These are the arm-specific counts attached to the primary outcome results, and should not be assumed to represent every participant enrolled or every participant in the safety record. The registry does not report why the outcome counts differ from the overall enrollment or give further information about participant flow.

The registry record does not report the original sample-size justification, detailed randomization procedures, allocation concealment, or additional masking procedures. It also does not report enough detail to determine how the study’s planned protocol relates to every outcome result shown. The study’s randomized, open-label, parallel-group description characterizes the broad design, but does not resolve these additional design questions.

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:

Analysis population for the primary outcome, as defined in the registry: All patients with p53-wild type breast tumors

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: All treated and eligible patients.

6. Primary Endpoint

The registry lists the primary outcome as Mean Percent Positive Proximity Ligation Assays of All Tumor Protein p53-wild Type Breast Tumors in Participants by Treatment Arm, measured over 2 years.

The primary endpoint is the mean percent positive proximity ligation assay measurement among p53-wild type breast tumors, compared by treatment arm. The registry describes the measure as the status of the interaction between estrogen receptor-alpha and p53. It reports the unit as percentage of positive PLA, the summary statistic as a mean, and variability as a standard deviation. The outcome timeframe is listed as 2 years.

A mean gives a central summary of the recorded assay values within an arm. The percentage-positive measurement is used to represent the assay signal relevant to the stated molecular question: whether the measured estrogen receptor-alpha–p53 interaction differs between the arms. The registry’s study summary also describes an interest in tumor gene expression, but gene expression is not the primary endpoint described in the primary result.

This endpoint is a laboratory measure of a proposed biological mechanism, not a direct measure of symptoms, tumor progression, recurrence, or survival. A difference in this assay measure can describe a difference in the recorded molecular outcome between arms. By itself, it cannot establish the clinical importance of that difference or determine whether it predicts patient outcomes. The registry record does not report further assay protocol details, validation information, or the exact specimen-collection schedule.

7. Results Posted in the Registry

• Tamoxifen: mean 4.40 versus 27.00 on control; difference -22.60 (95% CI -36.88 to -8.32), standardized effect d = -0.80; z-test p = 0.002.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary result is a comparison of means for a continuous measurement. The endpoint is the percentage of positive proximity ligation assay measurements in p53-wild type breast tumors. A mean condenses the measured values within an arm into a central summary, while the standard deviation describes variation among those values. Neither summary alone describes every participant’s measurement.

What does the mean difference represent?

The posted mean difference is -22.6 percentage points, calculated as the Tamoxifen arm mean minus the No Intervention arm mean. The arm means are 4.4% and 27.0%, respectively. Because the contrast is oriented as Tamoxifen minus No Intervention, a negative estimate denotes a lower arm mean for Tamoxifen. This is a difference on the endpoint’s percentage scale. It is not a percentage reduction, and it does not describe a change from baseline because no baseline comparison is reported for this primary outcome.

For a continuous endpoint, a difference in means is a direct way to express the contrast in the original measurement units. That can make the estimate easier to interpret than a standardized effect measure. The posted comparison also gives a pooled standard deviation of 28.2. Standardized effect measures express a difference relative to variability and can be useful for comparing measurements on different scales, but they do not replace the original-unit difference. The registry record does not report a sponsor analysis using a specified statistical model.

Why report standard deviations?

Standard deviations show how dispersed measurements are around each arm mean. Here, the reported standard deviations are 34.4 for No Intervention and 4.4 for Tamoxifen. The substantially different spread is a relevant feature of these summaries. General statistical explanation: when variability differs between groups, the uncertainty in a mean comparison depends on both the variability and the number of observations in each group. A pooled summary of variability can conceal such differences, so the reported comparison should be interpreted alongside the arm-specific summaries.

General statistical explanation: over-dispersion refers to data varying more than a simple model would expect. It can make model-based uncertainty too narrow if the model does not account for the extra variability. The registry record does not report that an over-dispersion model was used or that the measurement was analyzed under a particular distributional assumption. The available summaries alone do not establish which modeling approach was used in the study’s own analysis.

How should the confidence interval and p-value be read?

The 95% confidence interval for the mean difference ranges from -36.88 to -8.323 percentage points. A confidence interval gives a range of values compatible with the data under the assumptions used to form it; it communicates uncertainty around the estimate. It does not mean that the true difference has a 95% probability of lying inside this particular interval. The registry record does not report enough analysis detail to identify every assumption behind the interval.

The unadjusted p-value is 0.002. General statistical explanation: a p-value measures how unusual the observed data, or data more extreme, would be under a specified null model. It is not the probability that the null hypothesis is true, and it is not a measure of clinical importance. Because the value is unadjusted, it does not account for a family of multiple outcome tests. The registry record does not report a prespecified multiplicity procedure.

What can be inferred from the analysis record?

The registry lists zero analysis entries. The posted arm summaries and comparison statistics therefore do not come with reported model specifications, covariate lists, or sensitivity analyses in the analysis record. The p-value and interval can be described as posted, but the record does not establish whether the study used additional methods that are not represented there. The comparison is unadjusted, and there is no basis in the registry record to describe it as adjusted for participant or tumor characteristics.

General statistical explanation: randomization is intended to make treatment groups comparable on average, but it does not guarantee equal observed group characteristics in a particular study. With outcome counts of 23 and 12, chance imbalance and limited precision are relevant considerations. The registry record does not report baseline characteristics for this endpoint population, so their balance cannot be assessed from the posted results. Also, the primary outcome is restricted to participants with p53-wild type tumors; the result does not apply automatically to tumors with other p53 status.

10. Confidence Intervals and Precision

The confidence interval around the posted mean difference is -36.88 to -8.323 percentage points. Its position entirely on the negative side corresponds to the lower mean reported for Tamoxifen under the stated comparison orientation. The interval conveys uncertainty around the estimated arm difference; it does not show the range of individual participants’ assay measurements. Individual variability is instead reflected in the arm-specific standard deviations, which are 34.4 for No Intervention and 4.4 for Tamoxifen.

The interval is informative but should not be mistaken for a guarantee about the true effect. Its interpretation depends on the statistical method and assumptions used to calculate it. Those details are not reported in the registry analysis record. The posted comparison is unadjusted, and the registry record does not report a covariate-adjusted interval or an alternative analysis that could be compared with it.

The primary-outcome counts are 23 for No Intervention and 12 for Tamoxifen. These arm counts and the differing standard deviations are relevant to precision: estimates based on fewer observations and greater variability generally tend to be less precise. That is a general statistical principle, not a claim about unreported data. The registry does not report missingness by reason, participant-level assay values, or sensitivity analyses for unavailable measurements, so the extent to which missing data may affect the interval cannot be assessed.

The estimate is reported to one decimal place and the interval endpoints to the precision shown in the registry result. Additional digits would imply a level of precision not established by the record. The interval’s width also does not resolve whether the observed assay difference is clinically meaningful; the endpoint is a molecular assay measure, and the registry does not report a threshold defining a clinically important difference.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total events. They are illustrations based on the observed mean difference, not a report of the trial’s original design justification. The registry record does not report the original sample-size assumptions. These planning calculations assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect.

For planning at 100% of the observed effect, the figures are 25 participants per arm for 80% power and 33 participants per arm for 90% power. For planning at 75% of the observed effect, they are 44 participants per arm for 80% power and 59 participants per arm for 90% power. For planning at 50% of the observed effect, they are 98 participants per arm for 80% power and 131 participants per arm for 90% power.

In plain language, the 80% power column gives the illustrative number of participants per arm under the stated assumptions for a study planned to have an 80% chance of detecting the selected effect if that effect is present. The 90% column uses a higher target chance and therefore gives larger planning figures for the same effect assumption. Smaller effects need more participants to detect under otherwise similar assumptions, which is why the figures increase as the assumed fraction of the observed effect decreases.

These are planning illustrations, not observed power and not a description of what the completed study was designed to achieve. The plotted curve represents the same planning relationship across effect assumptions; it does not add evidence about the study’s observed result. The assumptions may not match the original design, whose details are not reported in the registry record.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -22.600; pooled standard deviation σ = 28.202.
2. n = 2 × (1.96 + 0.842)² × 28.202² / -22.600² = 24.4, rounded up to 25 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -22.6                      # observed difference in means
sigma <- 28.2021275793157                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1027416)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 25 (80% power), 33 (90% power)
 75% of observed effect: n per arm = 44 (80% power), 59 (90% power)
 50% of observed effect: n per arm = 98 (80% power), 131 (90% power)
power.t.test: 25.4 
Simulated power at n = 25 per arm: 0.795 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures and one secondary outcome. The primary endpoint is the mean percent positive PLA measurement in p53-wild type tumors. The listed secondary outcome concerns the total number of over-expressed genes across participants with p53-wild type breast tumors who had RNA samples available. The record does not report a multiplicity adjustment, a hierarchy for interpreting outcomes, or a prespecified strategy for controlling the chance of false-positive findings across multiple tests.

The primary comparison has an unadjusted p-value of 0.002. That value pertains to the reported primary comparison and should not be read as adjusted for other outcome testing. A multiplicity approach may affect how evidence across several outcomes is interpreted; the registry record does not say whether such an approach was planned or used. The record lists zero analysis entries, so analytic details beyond the posted summary comparison are not available.

The primary-outcome summaries include 23 participants in No Intervention and 12 in Tamoxifen. These outcome counts differ from the registry enrollment of 59. The record does not describe participant flow, explain the difference, or identify whether the outcome counts reflect unavailable specimens, eligibility restrictions, assay completion, or another reason. It would be speculative to attribute the counts to a particular cause.

The secondary outcome explicitly refers to participants with RNA samples available, indicating that the stated secondary analysis population is limited to those with available samples. The registry does not report the number with available RNA samples, missing-data handling, reasons for unavailable samples, or an assessment of whether missingness could be related to treatment or outcome. It also does not report a detailed analysis population definition, such as whether all randomized participants were included in each analysis. The effect of missing data and the generalizability of the outcome results therefore cannot be evaluated fully from the registry record.

14. 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: abdominal pain (3.2%).

The adverse-event record reports serious adverse events affecting 1 participant at risk in No Intervention and 0 participants at risk in Tamoxifen. For other adverse events, the record reports 0 affected participants at risk in No Intervention and 19 in Tamoxifen. The serious-event risk counts are 31 for No Intervention and 28 for Tamoxifen; the other-event risk counts are also 31 and 28, respectively. These are the event-specific populations listed in the safety record, not the primary-outcome counts.

Abdominal pain is listed among the top serious adverse-event terms at 3.2%. The record does not specify an arm for that term in the listed detail, so it should not be attributed to either arm based on this information alone. The registry record does not report deaths; the missing death entries should not be interpreted as a count of zero.

These figures describe what the registry safety record reports, but it does not provide event-level narratives, severity grading details, attribution to treatment, or follow-up completeness. A difference in reported counts is not by itself evidence that treatment caused an event or prevented one. Safety counts should be read separately from the primary assay comparison.

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

The posted result describes a lower mean percent positive PLA measurement in the Tamoxifen arm than in the No Intervention arm among participants included in the p53-wild type primary-outcome summaries. The unadjusted mean difference is -22.6 percentage points, with a 95% confidence interval from -36.88 to -8.323 and an unadjusted p-value of 0.002. The arm means and standard deviations provide context for that comparison, but the result remains a group-level summary of a molecular assay.

The outcome is relevant to the study’s stated interest in the relationship between estrogen receptor-alpha and p53. It does not establish why the assay measurements differ, demonstrate that the hypothesized mechanism explains a patient’s response, or show that the measurement predicts a clinical outcome. The registry summary describes tumor gene expression as an additional interest and the potential future relevance of the work, but that proposed future application is not itself a result.

The result does not establish an effect on tumor size, symptoms, recurrence, survival, or any other clinical endpoint. It also does not establish that the assay difference is clinically meaningful, since the registry record does not report a threshold for meaningful change or a link between this measurement and patient outcomes. The study is described as a pilot investigation, and the primary-outcome counts are limited to the arm-specific numbers reported for that outcome.

The registry record does not report detailed analysis methods, missing-data handling, participant flow, or a multiplicity strategy. Those omissions limit assessment of the robustness and scope of the result. The comparison should therefore be interpreted as a reported difference in assay means, with uncertainty represented by the confidence interval, rather than as a definitive conclusion about treatment response or clinical benefit.

16. Why This Trial Matters Statistically

This trial is statistically notable because it connects a randomized treatment comparison with a biomarker-oriented endpoint. The study asks about an assay measurement tied to a proposed biological interaction, rather than a direct clinical endpoint. That distinction matters: a measurable difference in a molecular outcome may inform a mechanistic hypothesis, but its patient-level or clinical relevance requires evidence beyond a difference in group means.

The registry result also illustrates why a mean should be read alongside measures of spread and the number of observations. The arm means differ, but the standard deviations differ as well, and the primary-outcome counts are 23 and 12. Those features affect how precisely a group comparison can be estimated and how broadly it can be generalized. The confidence interval makes the uncertainty around the mean difference visible, while the posted arm summaries show that participant-level variability is not the same in both groups.

For clinical researchers, the record highlights the importance of clear outcome definitions, sample availability, analysis populations, and timing. The primary outcome is restricted to p53-wild type tumors, while the secondary outcome is restricted to participants with available RNA samples. The registry record does not explain participant flow or the reasons that outcome counts differ from enrollment. Such information would help readers evaluate the population represented by each result.

The trial’s mechanistic aim and pilot description also make restraint important. The reported statistics characterize the assay comparison; they do not settle whether the mechanism predicts clinical response. A transparent account of assay procedures, analysis methods, missingness, and links to clinical outcomes would be needed to assess those broader questions.

17. 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 registry record gives a broad study design but limited detail about how the study was conducted and analyzed. It identifies randomization, no masking, and a parallel model, but does not report allocation concealment, randomization procedures, baseline characteristics, or the original sample-size justification. These omissions prevent a detailed assessment of design implementation and the comparability of the outcome populations.

The primary result is based on 23 participants in No Intervention and 12 in Tamoxifen, while total enrollment is listed as 59. The registry record does not provide a participant-flow account or explain why those figures differ. It does not report the number of participants with missing assay measurements, the reasons for missingness, or methods used to address it. The secondary outcome further specifies RNA sample availability, but does not report how many participants met that criterion.

The endpoint is a molecular assay measure in p53-wild type tumors. The registry record does not provide detailed assay methods, validation, collection schedule, or a threshold for a meaningful difference. The outcome timeframe is listed as 2 years, while the intervention description specifies tamoxifen for 4 weeks; further timing information is not reported. These gaps limit interpretation of how the assay result relates to treatment exposure.

The analysis record lists no analysis entries. It therefore does not report covariate adjustment, sensitivity analyses, missing-data procedures, or a multiplicity strategy. The primary comparison is unadjusted. Safety reporting also lacks details about event attribution, severity grading, and the absent death entries. These limitations do not invalidate the posted summaries, but they constrain how much can be concluded from them.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Analyzing a New Mechanism in Response to Tamoxifen Therapy in Breast Cancer Patients — NCT01027416.
• Registry record last updated 2026-04-21; status last verified 2026-03.
• Results first posted 2017-12-13.
• 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.

21. Record Summary

NCT01027416 is a completed randomized, open-label, parallel-group pilot study sponsored by Roswell Park Cancer Institute. It investigated tamoxifen and the proposed interaction between estrogen receptor-alpha and p53 in breast cancer. The registry lists enrollment as 59 and the phase as NA.

The primary endpoint is mean percent positive PLA in p53-wild type breast tumors, with a listed timeframe of 2 years. The posted means are 27.0% for No Intervention and 4.4% for Tamoxifen; the unadjusted mean difference is -22.6 percentage points, with a 95% confidence interval from -36.88 to -8.323 and an unadjusted p-value of 0.002. The record lists one secondary outcome concerning over-expressed genes in participants with available RNA samples.

The registry does not report detailed analysis methods, participant flow, missing-data handling, or the original sample-size justification. The posted result describes an assay difference; it does not establish a clinical effect or the clinical significance of the molecular measurement.