Phase 2 Study of Lovastatin as Breast Cancer Chemoprevention: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 2 Study of Lovastatin as Breast Cancer Chemoprevention (NCT00285857), a na phase 2 study. The primary outcome is Change in the Incidence of Abnormal Breast Duct Cytology After Treatment With Lovastatin 80 mg/Day.

2. Clinical Question

3. Trial Design

This is a Phase 2, single-group study of lovastatin for modification of abnormal breast duct cytology and risk-associated biomarkers in women at high inherited risk of breast cancer. Stanford University is listed as the sponsor. The registry records enrollment of 30 and describes a 6-month course of lovastatin 80 mg/day, taken as 40 mg orally twice daily.

The design does not include a like-for-like control group: allocation is listed as NA, the model is single group, and masking is none. The primary outcome is framed as a change from pre-treatment to post-treatment cytology, so participants serve as their own reference over time. This can describe within-participant changes, but it cannot by itself separate a treatment-associated change from changes related to time, measurement, or other influences.

The record gives a start date of 2005-11, a primary completion date of 2010-05, and a status of terminated. It does not state why the study was terminated or whether termination affected enrollment, follow-up, or analysis. The registry lists four outcome measures: the primary cytology outcome and secondary outcomes concerning mammographic density, total cholesterol, and low density lipoprotein (LDL). It records zero analyses. Results for those outcomes, including the number of participants assessed at follow-up, are not reported in the registry record.

The registry record does not report a sample-size justification, a planned analysis model, or a prespecified statistical testing strategy. The separate planning assumptions describe a two-arm illustration, unlike this single-group design, and should not be read as the study’s original design or as evidence of 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:

Analysis population for the primary outcome, as defined in the registry: Participants either at least one of the following: * Deleterious germline mutation in BRCA1, BRCA2, CDH1, or TP53 * Lifetime breast cancer risk of breast cancer of 20 % as estimated by the Claus model * Personal history of estrogen receptor andprogesterone receptor-negative breast cancer.

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 Change in the Incidence of Abnormal Breast Duct Cytology After Treatment With Lovastatin 80 mg/Day, measured over 6 months.

The primary endpoint concerns change in the incidence of abnormal breast duct cytology after lovastatin treatment, measured in participants at 6 months. Cytology was evaluated before and after treatment using random periareolar fine needle aspiration (RPFNA). The registry says specimens were scored qualitatively and quantitatively with the Masood semiquantitative scale; higher scores indicate greater abnormality.

The recorded score ranges classify specimens as follows: 06-10, non-proliferative breast disease (NPBD); 11-14, proliferative breast disease without atypia (PBD-A); 15-18, proliferative breast disease with atypia (PBD+A); and 19-24, carcinoma in situ and invasive cancer (CIS/IC). If repeated RPFNA attempts yielded no cells, the specimen was classified as acellular.

The record calls a change from NPBD to PBD-A unfavorable, a change from NPBD to acellular equivocal, and a change from PBD-A to NPBD favorable. These categories make the direction of certain cytology changes interpretable, but the registry does not explain how other transitions were classified in the primary analysis. Nor does it report participant counts by starting category, ending category, or change category.

A cytology endpoint can describe a change in a measured risk-associated marker; it is not itself a reported count of breast cancer diagnoses. The registry record gives no primary-outcome result, so the magnitude, direction, and precision of any observed change cannot be assessed from the posted information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group before-and-after design estimate?

In a single-group before-and-after design, each participant’s post-treatment measurement can be compared with that participant’s pre-treatment measurement. This approach can describe how measurements changed among participants assessed at both times. It differs from a randomized comparison, where outcomes in separate groups are compared under different assigned conditions. The registry records this study as single group, with allocation listed as NA and masking as none; it does not describe a control group.

A within-participant comparison can reduce the influence of stable characteristics that differ between people, because the participant is compared with their own earlier measurement. But it does not remove influences that change over time, nor does it establish what would have happened in the same period without treatment. General statistical interpretation therefore distinguishes an observed change over time from a causal treatment effect. In this record, no numerical change is reported, so even the descriptive within-participant result cannot be evaluated.

How should the cytology scale be understood?

The primary outcome uses RPFNA specimens scored on the Masood semiquantitative scale. The registry says higher numbers represent increasing degrees of abnormality and gives category ranges for NPBD, PBD-A, PBD+A, and CIS/IC. It also specifies an acellular classification when multiple aspiration attempts yield no cells. These are ordered categories: the scale conveys levels of cytologic abnormality, rather than a direct measurement on a continuous scale where equal score differences necessarily have equal meaning.

The registry designates three transitions: NPBD to PBD-A as unfavorable, NPBD to acellular as equivocal, and PBD-A to NPBD as favorable. The record does not state how all other possible transitions were grouped or how the stated categories were combined to produce the primary endpoint. It also does not report whether the analysis used the full ordered scale, a binary classification, or another summary. Those analysis details are not reported in the registry record.

Why does the endpoint’s form matter?

The primary outcome is described in terms of participants and is classified as a binary outcome with event counts. For a binary endpoint, an analysis generally depends on how an event is defined and on how participants with unavailable or unevaluable measurements are handled. A count alone describes how many participants met a definition; an estimate of uncertainty also depends on the denominator and the analysis method. The registry does not provide the primary event definition in enough detail to reconstruct all classifications, nor does it report endpoint counts or an uncertainty estimate.

When measurements are paired within participants, the pairing is relevant: each person’s two assessments are linked. An analysis that treats the pre-treatment and post-treatment observations as unrelated would not reflect that structure. This is a general methodological point, not a description of an analysis confirmed in the registry. The registry records zero analyses and does not state how the repeated measurements were modeled.

What do confidence intervals and p-values ordinarily convey?

In general, a confidence interval expresses uncertainty around an estimated effect under a specified statistical model and its assumptions. A narrower interval indicates greater precision within that framework; a wider interval indicates less precision. A p-value, in general, describes how compatible the observed data are with a stated null hypothesis under the assumptions of a test. Neither quantity alone conveys the clinical importance of an effect, and neither corrects weaknesses in the design or measurement.

No primary-outcome estimate, confidence interval, or p-value is reported in the registry record. It is therefore not possible to discuss statistical significance, precision, or the compatibility of the observed data with a null hypothesis. General explanations of these methods do not imply that any particular test was conducted in this study.

How do the planning assumptions relate to the design?

The registry’s planning-illustration description specifies a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is expressed as a stated fraction of the observed effect. For time-to-event illustrations, it describes total events using the Schoenfeld approach; other illustrations are expressed as participants per arm. These are stated assumptions for planning illustrations, not a sample-size justification documented as the trial’s own design.

Those assumptions describe two-arm planning, while the trial is recorded as single group with no like-for-like control comparison. The registry does not report calculated planning values in the study description, nor does it report that the trial was designed around those assumptions. Any planning illustration based on an observed effect is not observed power, and it should not be treated as a substitute for a prespecified design justification. The study’s original sample-size rationale is not reported in the registry record.

More generally, planning calculations depend on the target effect, outcome variability, type I error, allocation, and analysis model. If the actual design or outcome differs from the assumptions, the calculation may not describe the study’s operating characteristics. A post hoc illustration based on an observed effect is especially distinct from prospective planning because its effect assumption comes from the observed data. No such calculation establishes whether a result is real or clinically meaningful.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures: the primary cytology outcome and secondary outcomes for mammographic density, total cholesterol, and LDL. Testing or estimating several outcomes can raise multiplicity concerns. In general, when many hypotheses are examined, the chance of at least one apparently notable result can increase unless the analysis strategy accounts for the number and relationship of the comparisons. The record does not state whether any adjustment, hierarchy, or other multiplicity strategy was planned.

The registry records zero analyses. It does not report outcome estimates, test results, confidence intervals, or which outcomes were analyzed. Therefore, it is not possible to assess whether multiplicity affected interpretation or whether any primary-versus-secondary distinction was maintained in an analysis.

Missing-data handling is also not reported. The primary assessment could yield an acellular specimen after multiple RPFNA attempts, and the registry defines that specimen category as equivocal for a specified transition from NPBD. That endpoint rule does not explain how the analysis handled participants without a post-treatment assessment, incomplete follow-up, or other unavailable measurements. The number of participants with paired pre-treatment and post-treatment cytology is not reported in the registry record.

The record does not define analysis populations, such as whether analyses included everyone enrolled, only participants with evaluable specimens, or a different group. It also does not report adherence, withdrawals, or a participant disposition summary. Without these details, the denominator for an efficacy result and the potential consequences of missing assessments cannot be assessed. These omissions limit interpretation independently of the choice of statistical test.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry’s safety record lists 30 participants at risk for serious adverse events in the lovastatin group and zero serious adverse events. It lists 30 at risk for other adverse events and three other adverse events. These are reported counts, not percentages, and the record does not provide further detail about the event terms in the safety summary.

The deaths field is null, so deaths are not reported in the registry record. The absence of listed serious-event terms does not provide information about event severity beyond the reported serious-event count, and the registry does not describe how events were collected, attributed, or monitored. It also does not give a breakdown of the three other adverse events, their timing, or whether individual participants experienced more than one event.

Safety counts should be read separately from the cytology outcome. They do not establish whether the primary endpoint changed, and they do not supply a comparison with an untreated or alternative-treatment group. With a single-group safety summary, the posted counts describe what the registry records for this study group; they do not quantify comparative risk.

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

The registry record documents a study question, a six-month lovastatin regimen, a single-group design, and a plan to assess breast duct cytology before and after treatment. It also identifies secondary measures of mammographic density, total cholesterol, and LDL. These details explain what the study set out to examine, but the record does not report outcome analyses for these measures.

In particular, there is no posted primary-outcome count or estimate showing how cytology changed, and no confidence interval or p-value. The record therefore does not establish the direction, magnitude, or precision of a cytology change. It also does not establish that no change occurred; an unreported result cannot be interpreted as a null finding.

Even if a before-and-after result were available, the single-group design would limit causal interpretation. A change over time in this group would not, by itself, distinguish an effect of lovastatin from other influences on measurements or changes over time. There is no comparator group in the registry record against which to evaluate that counterfactual.

The primary endpoint is a cytology classification, not a reported clinical outcome of breast cancer incidence. The registry’s stated purpose concerns modification of abnormal duct cytology and risk-associated biomarkers; it does not report evidence that the study measured a reduction in breast cancer diagnoses. Nor does the safety summary provide a comparative safety estimate.

The most supportable interpretation is therefore limited to the study’s recorded design and endpoint definitions, alongside the posted safety counts. The status is terminated, but the reason and its implications for follow-up and analysis are not reported. The posted information does not permit conclusions about treatment efficacy, the size of any biomarker change, or the precision of an effect estimate.

13. Why This Trial Matters Statistically

Statistically, this study illustrates the distinction between a research question and an interpretable result. The registry clearly identifies a population at high inherited risk, a specified lovastatin regimen, a pre-treatment and post-treatment cytology assessment, and a classification system for specimens. Yet it records zero analyses and does not report primary or secondary outcome results. Without those results, the scientific question cannot be answered from the registry record.

The design also makes the comparison structure important. A single-group before-and-after assessment can describe change among assessed participants, but it does not offer a concurrent control group. Recognizing this distinction prevents a within-group change from being mistaken for a controlled treatment effect. It also highlights why an effect estimate needs context about its design, uncertainty, and missing observations.

The endpoint itself raises useful measurement questions. The Masood scale orders cytology categories, while the primary outcome is described as a change in incidence and the record assigns favorable, unfavorable, or equivocal labels to only specified transitions. Clear reporting of the full classification and the analysis population would be needed to understand how participant-level observations become an endpoint estimate.

Finally, the registry’s planning-illustration assumptions describe two-arm calculations, whereas the trial is single group. Keeping planning illustrations separate from the trial’s original rationale—and from observed results—is important for sound interpretation. The record does not report the study’s own sample-size justification, analysis plan, or outcome estimates, so these remain unresolved rather than inferable from the design description.

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.

Several limitations are specific to the information recorded for this trial. The study is single group, with allocation listed as NA and no masking. There is no control group for a concurrent comparison, so the design cannot isolate a treatment effect from other changes occurring between the pre-treatment and post-treatment assessments.

The status is terminated, but the registry does not state why. It does not say whether termination affected the planned enrollment, treatment exposure, follow-up period, or analyses. Although enrollment is listed as 30, the number with paired and evaluable cytology assessments is not reported. The record also does not provide a participant flow description, withdrawal information, or adherence results.

The endpoint description specifies how several cytology transitions are interpreted, but it does not explain how all possible transitions entered the primary analysis. It does not report the event count, denominator, effect estimate, confidence interval, p-value, or analysis method. Results for the listed secondary outcomes are likewise not reported, and the registry records zero analyses.

There is no reported sample-size justification, prespecified statistical plan, missing-data approach, or analysis-population definition. The separate planning assumptions describe a two-arm illustration, which does not match the recorded single-group study design; the registry does not identify those assumptions as the trial’s original design. The safety record also lacks event-term details and reports deaths as null rather than as a count. These gaps prevent assessment of outcome precision, completeness, and comparative safety from the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Phase 2 Study of Lovastatin as Breast Cancer Chemoprevention — NCT00285857.
• Registry record last updated 2017-03-09; status last verified 2017-01.
• Results first posted 2017-03-09.
• 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 2, single-group study sponsored by Stanford University, with enrollment of 30 and status recorded as terminated. The intervention was lovastatin 80 mg/day for 6 months, taken as 40 mg orally twice daily. The primary outcome was change in abnormal breast duct cytology assessed before and after treatment using RPFNA and the Masood semiquantitative scale.

There was no separate comparator group, allocation was listed as NA, and masking was none. The record lists secondary outcomes for mammographic density, total cholesterol, and LDL, but records zero analyses and does not report efficacy results. The reason for termination, outcome denominators, missing-data approach, analysis population, and original sample-size justification are not reported in the registry record.

The safety summary records zero serious adverse events among 30 at risk and three other adverse events among 30 at risk. Deaths are not reported in the registry record. The available information describes the study’s design and measurements, but does not give an estimate of the primary outcome or its precision.