Assessing Adjuvant Breast Cancer Therapy Benefit
Authors: Arthur M. Sleeper, Steven M. Sorscher, Leah L. Dietrich, Charles L. Loprinzi, Stephan D. Thomé
Journal: Journal of Clinical Oncology (2001)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2001.19.12.3157 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11408515 Assessing Adjuvant Breast Cancer Therapy Benefit Arthur M. SleeperxArthur M. SleeperSearch for articles by this author Steven M. SorscherxSteven M. SorscherSearch for articles by this author , Leah L. DietrichxLeah L. DietrichSearch for articles by this author Charles L. LoprinzixCharles L. LoprinziSearch for articles by this author , Stephan D. ThoméxStephan D. ThoméSearch for articles by this author Show More Ravenel Oncology Center, Martinsville, VAGundersen Clinic, Ltd, La Crosse, WIMayo Clinic, Rochester, MN https://doi.org/10.1200/JCO.2001.19.12.3157 First Page Full Text PDF Figures and Tables © 2001 by American Society of Clinical OncologyjcoJ Clin OncolJournal of Clinical OncologyJCO0732-183X1527-7755American Society of Clinical OncologyjcoJ Clin OncolJournal of Clinical OncologyJCO0732-183X1527-7755American Society of Clinical OncologyResponse15062001Response15062001To the Editor:In the article by Loprinzi and Thomé,1 the authors describe, as an example, a 55-year-old, node-negative, estrogen receptor–positive breast cancer patient who will improve her 10-year disease-free survival from 70% to 79% with combined adjuvant therapy while her chance of being free of disease recurrence will actually improve to 87%. In other words, she apparently benefits an additional 8% because she will die of another cause. Although at first glance these distinctions are confusing, such calculations underscore the obvious importance of considering age and comorbidity in advising patients and also in realizing that although the Numeracy program, according to the authors, “can factor in the mortality that would be associated with a woman who was otherwise healthy, based on causes of mortality other than breast cancer,” the online program currently available (http://mhs.mayo.edu/adjuvant) does not.In Reply:We appreciate the opportunity to respond to the letters authored by Dr Arthur M. Sleeper and Drs Steven M. Sorscher and Leah L. Dietrich. First, Sorscher and Dietrich insightfully raise a seemingly confounding issue dealing with why the overview analysis reports an improved outcome (in terms of annual proportional reductions in risk recurrence) for disease-free survivals versus overall survivals.1 This reported differential effect suggests, in the patient example cited, that combined adjuvant therapy provides an 8% additional benefit for survival (as opposed to disease-free survival). There are at least three reasons for this discrepancy, one of which, as Sorscher and Dietrich surmise, is that some patients, despite developing recurrent breast cancer, will die of causes other than breast cancer. Two other reasons, however, are that (1) the overview analysis counts a contralateral breast cancer as a recurrence and (2) the delay between recurrence and death makes the benefits sound more robust regarding recurrence, as opposed to death. As might be predicted, the latter reason should become less prominent as the overview data further mature. This effect is evident in the most recent overview analyses, which were recently presented at a recent National Institutes of Health Consensus Development Conference but which have yet to be published.It is noteworthy, as we discussed in our publication, that we use the terms 10-year survival and 10-year disease-free survival interchangeably when talking about eventual prognosis, given that these two percentages are relatively close to each other. It is true that the online version of Numeracy, at http://mhs.mayo.edu/adjuvant, does not allow for factoring in comorbid conditions. For this online version of Numeracy, we felt that a simple pull-down menu with automated data entry would be best for most expected users. Nonetheless, there is an available Numeracy spreadsheet program that does have the ability to change 10-year baseline risk estimates and efficacy estimates at will. We are happy to provide interested physicians with a copy of this spreadsheet program (please request at email: [email protected]).Moving on to respond to comments from Dr Sleeper, let us address the five problems that he lists. Sleeper first takes issue with the baseline risk that we used. We admit that this risk is opinion generated. However, it is not individual physician opinion-generated information, which, as illustrated in Table 2 of our article2 and in a previous publication,3 is very diverse. Rather, it is an average opinion from a number of clinicians who regularly see patients with breast cancer. We are impressed with the remarkable correlation between prognosis seen in our program with that seen with the method from Ravdin et al.4 With regard to the relatively modest differences in opinions between our baseline estimates and those of Ravdin et al,4 it is not clear which one is more or less correct. Although we are hopeful that more precise baseline prognoses will be generated in the future, we are unaware of more helpful baseline prognosis information to use for individual patients.Sleeper’s next concern deals with whether annual proportional risk reduction is an accurate way of understanding chemotherapy effects across patients with different tumor sizes and different nodal situations. We note that we did not define this relative or proportional mechanism of describing the benefits of adjuvant therapy, a mechanism that has been routinely used to describe adjuvant treatment benefits in recent reports of clinical trials and in adjuvant meta-analyses and overviews. Rather, our article sought to better translate individual patient proportional benefits into absolute benefits.Sleeper’s next concern deals with Table 8. In contrast to Sleeper’s assertion, this table contains information regarding both patients with and without involved axillary lymph nodes. We agree with Sleeper that the information regarding small, node-negative cancers might be most helpful for allowing a patient and her physician to better understand the potential benefits from systemic therapy. In addition, however, we believe that understanding the relative benefits of adjuvant therapy in node-positive patients would be helpful for many patients so that they can better know the magnitude of benefit for which they are receiving toxic therapy.The fourth problem that Sleeper notes is that other prognostic variables, such as histology, were not included in our baseline prognostic model. We will admit that there are many different prognostic tools that have been studied in groups of patients. Nonetheless, given the vast diversity of opinions regarding the best two established features (that being the number of involved axillary lymph nodes and tumor size), the use of less robust prognostic factors, in individual patient cases, is not established. Sleeper is referred to Fig 4 in a previously published article,2 which illustrates the limited value from adding weaker prognostic factor information to prognostic opinions based on axillary lymph node status and tumor size.Sleeper’s last concern deals with the fact that paclitaxel is not fully established, effective therapy for patients in the adjuvant setting. We agree, as indicated by reminding him that this was noted in our article on four separate occasions.Sleeper ends his letter looking to the future when, hopefully, better prognostic information will be available, as opposed to trying to better understand how to use the data that are accessible to us today. We, too, look forward to the future when better prognostic information should be available. In contrast to Sleeper, however, we do believe that there is room for a better understanding of the prognostic information that is currently available so as to better be able to inform and treat those patients we see in our practice today. The multiple, positive, unsolicited comments that we have received from colleagues since the publication of this article indicates to us that compiling available information in an accessible manner is worthwhile. Sometimes old hash does taste better after rewarming.REFERENCE1. Loprinzi CL, Thomé SD: Understanding the utility of adjuvant systemic therapy of primary breast cancer. J Clin Oncol 19:: 972,2001-979, Link, Google Scholar1. Early Breast Cancer Trialists’ Collaborative Group: Polychemotherapy for early breast cancer: An overview of the randomised trials. Lancet 352:930-942, 1998 Google Scholar2. Loprinzi CL, Thomé SD: Understanding the utility of adjuvant systemic therapy for primary breast cancer. J Clin Oncol 19:: 972,2001-979, Link, Google Scholar3. Loprinzi CL, Ravdin PM, De Laurentiis M, et al: Do American oncologists know how to use prognostic variables for patients with newly diagnosed primary breast cancer? J Clin Oncol 12:: 1422,1994-1426, Link, Google Scholar4. Ravdin PM, Siminoff LA, Davis GJ, et al: Computer program to assist in making decisions about adjuvant therapy for women with early breast cancer. J Clin Oncol 19:: 980,2001-991, Link, Google Scholar