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Method to Test Whether Late Extended Letrozole, Rather Than Self- Selection, Improves the Outcome in Patients With Breast Cancer Who Have Completed 5 Years of Tamoxifen

Department of Surgery and Molecular Oncology, Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom

To the Editor:

Using an analysis of just one arm of the MA-17 trial, Goss et al¹ conclude in the title of their article that late extended letrozole improves outcome in women in early-stage breast cancer who complete 5 years of tamoxifen. However, the presented data cannot justify the title or the conclusion.

It is well recognized that women from a better socioeconomic background, those who choose to have earlier investigations and prompt treatment—the healthy women—fare better than others. This major unexplained confounding factor cannot be completely compensated by any of the means, statistical or otherwise, employed by the authors and could contribute significantly toward the difference in the outcomes of those who chose to switch from placebo to letrozole and those who chose not to switch.

A simple study that could test whether this difference is because of self-selection. Just ask all the women who were in the other arm—the letrozole arm of the study— to first imagine that they were receiving the placebo in the original random assignment. Then, ask them the exact question that was posed to the women in the placebo arm, including the exact information sheet about the benefit of letrozole, asking them whether they would want to switch or not. Then, compare the outcome of those women who would have wanted to switch with those who would not or could not decide (as the latter would have just maintained status quo and remained on the placebo). If there is no difference in the outcome of these two groups, then we could take the conclusions of the latest article more seriously. If there is a difference, then the benefit of extended letrozole could be estimated from the comparison of the differences in each arm. The principle is explained in Figure 1.

View larger version (19K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig 1. A, B, C, and D represent the survival in each of the four groups, two of which (A* and C*) will be available if the suggestions in this letter are followed. The minus notation is used to represent formal statistical comparison. The effect of letrozole can be estimated by following the steps in blue in the lower two rows. (B –D) will give an estimate of the combined effect of self-selection and letrozole. This is the only result available from the current article. (A –C) will give an estimate of the effect of self-selection only. If this is zero then the original conclusion stands stronger. If not, then (B –D) and (A –C) will give the best approximation of the effect of letrozole—the right answer to the question posed in this article.

The author(s) indicated no potential conflicts of interest.

REFERENCE

1. Goss PE, Ingle JN, Pater JL, et al: Late extended adjuvant treatment with letrozole improves outcome in women with early-stage breast cancer who complete 5 years of tamoxifen. J Clin Oncol 26:1948-1955 2008[Abstract/Free Full Text]

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  Paul E. Goss
  JCO 2008 26: 3291-3292 [Full Text]

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• Late Extended Adjuvant Treatment With Letrozole Improves Outcome in Women With Early-Stage Breast Cancer Who Complete 5 Years of Tamoxifen
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  JCO 2008 26: 1948-1955 [Abstract] [Full Text]

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