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Originally published as JCO Early Release 10.1200/JCO.2008.20.5294 on January 12 2009 © 2009 American Society of Clinical Oncology.
Weight Loss After Breast Cancer Diagnosis May Not Improve PrognosisDepartment of Family Practice, University of California Davis Medical School, Davis, CA To the Editor: In Journal of Clinical Oncology, Litton et al1 and Griggs and Sabel2 have suggested weight reduction as a potential antitumor intervention in obese women with newly diagnosed breast cancer. A wide variety of studies have documented the more advanced disease at diagnosis,3 and worse prognosis after diagnosis,4–6 associated with obesity in women with breast cancer. This poor prognosis seems to be independent of menopausal status, smoking habits, tumor stage, and tumor hormone binding characteristics. However, these observations should not be interpreted to suggest that an improved prognosis might be expected in those women who are able to lose weight, even if the weight loss were sufficient enough to diminish the altered hormonal levels characteristic of obesity. At inception, the developing genetic characteristics of each breast cancer are apparently influenced by the biochemical-hormonal tissue environment of the patient, resulting in different primary tumor genetic characteristics in obese and nonobese women. These include differences in the frequency and concentration of hormone receptor sites,7,8 nuclear grade,1 and cancer stage,1 and seem likely to have already influenced primary growth, metastasis, and growth of metastatic tissues before tumor diagnosis. After primary tumor removal, they also likely continue to influence additional metastasis, growth of metastatic tissues, and response of these malignant tissues to antitumor therapy.9 The similar prognosis for obese and nonobese women receiving tamoxifen therapy for relatively less aggressive estrogen receptor–positive, node-negative tumors10 supports an association between tumor prognosis and the obesity-associated genetic characteristic of primary tumors, rather than between tumor recurrence rates and the altered hormonal levels characteristic of obesity. In a study of 176 women undergoing mastectomy with positive axillary nodes, the median diameter of each primary tumor among the 72 obese women was 20% smaller than that among the otherwise similar 104 nonobese women, but the largest axillary metastasis in each obese woman averaged 20% larger than the similar node metastasis in each nonobese woman, after controlling for multiple other factors, including the number of positive nodes.11 Axillary metastasis to primary tumor ratios were 36% higher in obese women. These differences were independent of patient age, smoking habits, tumor stage, and estrogen receptor status, and seemed explainable only by the presence of more highly malignant tumors among these obese women associated with earlier tumor metastasis, or by the more rapid growth of node metastases before diagnosis. Genetic differences responsible for this pattern will likely eventually be identified, but loss of weight after primary tumor removal seems unlikely to modify their subsequent influence on tumor behavior. Any study examining the influence of postdiagnosis weight reduction on subsequent tumor prognosis would include the potential handicap of creating undeserved guilt among women with recurrent tumors who had been unsuccessful in their efforts to lose weight. The risks of any proposed antitumor intervention should be clearly understood by both patients and their therapists. Most overweight women are sensitive about their excess weight and have generally been unsuccessful in programs designed to help them lose it. Although the diagnosis of breast cancer may stimulate some women to be more successful in these programs, weight loss may be more difficult for others because of their new diagnosis as well as any new symptoms induced by antitumor therapy. If weight loss is recommended to these women, physicians should be certain that their patients clearly understand the absence of evidence suggesting weight loss as a technique for limiting tumor recurrences, in order to protect against inappropriate self-criticism. Otherwise, women who develop recurrent tumors after unsuccessful efforts to lose weight might be penalized by participation in the study. AUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. REFERENCES
1. Litton J, Gonzales-Angulo A, Warneke C, et al: Relationship between obesity and pathologic response to neoadjuvant chemotherapy among women with operable breast cancer. J Clin Oncol 26:4072–4077, 2008. 2. Griggs J, Sabel M: Obesity and cancer treatment: Weighing the evidence. J Clin Oncol 26:4060–4062, 2008. 3. Hahn KM, Bondy ML, Selvan M, et al: Factors associated with advanced disease stage at diagnosis in a population-based study of patients with newly diagnosed breast cancer. Am J Epidemiol 166:103–144, 2007. 4. Berclaz G, Li S, Price K, et al: Body mass index as a prognostic feature in operable breast cancer: The international breast cancer study group experience. Ann Oncol 15:875–884, 2004. 5. Tao MH, Shu XO, Ruan ZX, et al: Association of overweight with breast cancer survival. Am J Epidemiol 163:101–107, 2006. 6. Loi S, Milne R, Friedlander M, et al: Obesity and outcomes in premenopausal and postmenopausal breast cancer. Cancer Epidemiol Biomarkers Prev 14:1686–1691, 2005. 7. Daling JR, Malone KE, Doody DR, et al: Relation of body mass index to tumor markers and survival among young women with invasive ductal breast carcinoma. Cancer 92:720–729, 2001.[CrossRef][Medline] 8. Enger S, Ross R, Paganini-Hill A, et al: Body size, physical activity, and breast cancer hormone receptor status: Results from two case-control studies. Cancer Epidemiol Biomarkers Prev 9:681–687, 2000. 9. Bastarrachea J, Hortobagyi G, Smith T, et al: Obesity as an adverse prognostic factor for patients receiving adjuvant chemotherapy for breast cancer. Ann Intern Med 119:18–25, 1993. 10. Dignam J, Wieand K, Johnson K, et al: Obesity, tamoxifen use, and outcomes in women with estrogen receptor-positive early-stage breast cancer. J Natl Cancer Inst 95:1467–1476, 2003. 11. Daniell H, Tam E, Filice A: Larger axillary metastases in obese women and smokers with breast cancer: An influence by host factors on early tumor behavior. Breast Cancer Res Treat 25:193–201, 1993.[CrossRef][Medline]
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Copyright © 2009 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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