The Oncologist has tagged three review papers that share a first author with an expression of concern. The three papers, which have together been cited more than 1,000 times, focus on HER2, a gene that can contribute to breast cancer.
Though the papers contain errors, the conclusions — about how the HER2 gene serves as a predictive factor for breast cancer, and a target for therapies — remain unchanged, according to the EOC. The editor of the journal notes that the conclusions of the papers have been confirmed by other publications. Two of the papers are more than 10 years old, and today many patients continue to be treated with medications that target HER2, such as Herceptin.
Here’s the expression of concern:
The Editors have received information that three articles [1–3] on the subject of HER2 amplified breast cancer, previously published by this Journal, contained errors in the citation of methods and interpretation of primary data cited by the authors. Although the general conclusion of the papers remains unchanged, the Editors of The Oncologist bring these inaccuracies to the attention of readers and suggest that this information should be taken into account in making reference to these three articles [1–3] and in judging their content. This statement has been reviewed by the senior authors, who endorse this Expression of Concern.
Jeffrey S. Ross, who works at Albany Medical Center, is the first author on all three papers that the EOC applies to:
- “The HER-2/neu Oncogene in Breast Cancer: Prognostic Factor, Predictive Factor, and Target for Therapy,” published in 1998 and cited 449 times, according to Thomson Reuters Web of Science. Jonathan A. Fletcher, who works at Brigham And Women’s Hospital, is the last author.
- “The HER-2/neu Gene and Protein in Breast Cancer 2003: Biomarker and Target of Therapy,” published in 2003 and cited 361 times. Kenneth Bloom, who is the Head of Oncology & Immunotherapy at Human Longevity, Inc., is the last author. Fletcher is also a co-author on this paper.
- “The HER-2 Receptor and Breast Cancer: Ten Years of Targeted Anti–HER-2 Therapy and Personalized Medicine,” published in 2009 and cited 378 times (making it a “highly cited” paper). Gabriel N. Hortobagyi, affiliated with the MD Anderson Cancer Center, is the last author.
We asked Bruce A. Chabner, the editor in chief of The Oncologist, for more information on the specifics of the errors. He told us:
The reader who brought the concerns to the Editors’ attention has raised issues with the meta-analysis of published data linking the amplification of HER2 detected by FISH and/or overexpression of the HER2 protein detected by IHC and prognosis in breast cancer for patients not treated with anti-HER2 targeted therapies, which only became available in 1998. The reader identified a number of errors in classification of the results of the studies such as whether the data was evaluated by univariate or multivariate statistical analysis. In addition, in the review, prognosis for breast cancer was not clearly defined in terms of separating time to progression from overall survival.
The journal editor and the authors recognize the deficiencies in the analysis of prior literature in the three review articles called into question, and have published our concern. However, these deficiencies do not invalidate the papers’ primary conclusion, which has been confirmed by a number of concurrent and subsequent publications. It is generally accepted that amplification and/or overexpression of HER2 in newly diagnosed breast cancer in the pre-targeted therapy era is significantly associated with an adverse clinical outcome independent of both clinical (patient’s age for example) or pathologic (tumor grade, size, estrogen receptor status for example) parameters classically used to evaluate newly diagnosed patients. Therefore, we feel that our notice of concern is sufficient to alert our readers.
The reader who alerted the journal to the issues with the paper is Robert Fortner, a writer who is researching breast cancer for a book he’s working on. He has described his concerns with the papers on his blog.
Fletcher, who is a co-author on author on the 1998 paper, told us that:
To my understanding, the concern was with the way some of the data from various series were summarized in these reviews. My role was to provide information and examples on molecular cytogenetic detection of Her2 (which was then a less routine assay), and I wasn’t involved in summarizing the previously published data, which was the main focus of the reviews.
Hortobagyi, a senior editor at The Oncologist, told us more about the concerns regarding the 2009 paper, on which he is a co-author:
The errors mentioned referred to statements regarding “independent” prognostic value for HER2 overexpression and/or amplification. The information in question included some papers in which multivariable analyses were not performed and therefore, the word “independent’ was inappropriately used, since in the absence of such analyses, one cannot state with [certainty] that the variable indeed contributes independently to the prediction of prognosis. In some other papers referenced in the publication, HER2 expression/amplification was correlated to other prognostic biomarkers and not directly to overall survival. Therefore, the claim of HER2 being prognostic would not be directly supported by those papers. In addition, the conflict of interest of the first author was not accurate.
Here’s how the conflict of interest disclosure for Ross reads on the 2009 paper:
Jeffrey S. Ross: None
We asked Hortobagyi if the errors have affected papers that cite the 2009 review. He said:
Yes, although the weight of the evidence that exists today clearly supports the claim that HER2 overexpression/amplification is a adverse prognostic factor. Therefore, whether you include this review or not, currently accepted knowledge about HER2 would remain unchanged.
We have reached out to Ross (who has a building named after him at Albany Medical College), and Bloom. We’ll update this post with anything else we learn.
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