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Originally published as JCO Early Release 10.1200/JCO.2008.17.9853 on December 15 2008 © 2009 American Society of Clinical Oncology.
In Reply
The University of Texas M. D. Anderson Cancer Center, Houston, TX Screening mammography in the elderly population is a real-life clinical situation faced by thousands of physicians and elderly women in the United States on a daily basis. Although in some cases the extent of comorbid conditions clearly precludes aggressive screening interventions, for many women older than 80 years, ordering a screening mammogram is a real dilemma for clinician and patient. There is no class I evidence based on randomized trials addressing this issue in the elderly, and it is unlikely such a study will be done (although we hope the current controversy of our study may encourage such a trial). In the absence of such information, decisions still need to be made, and our article seeks to provide data to help the discussion between physicians and their elderly patients. Substantial criticism has focused on the survival data mentioned in our study, and we acknowledge the other biases reported by Berry et al and Schonberg and McCarthy. However, we would like to emphasize that our report also illustrates the other overwhelming selection bias inherent in our study, which would prevent any meaningful conclusion on survival benefit for mammography. In fact, our study concluded that "the true efficacy of screening with respect to survival is still unknown and will remain so until a clinical trial of screening mammography is performed in this age group."1 Furthermore, it seems that a clinically important end point appears to have been missed in the ongoing controversy. Although elderly patients may die of diseases unrelated to breast cancer, coexistent breast cancer may cause significant management issues with regard to optimal local control. In fact, in our clinical practice, it is not uncommon to see elderly women with multiple comorbidities who also present with breast cancer. Since it is impossible to predict the balance between tumor growth and life expectancy for such patients, we are faced with the dilemma of how much intervention is adequate to provide local control and prevent the sequelae of uncontrolled local tumor growth, such as debilitating pain, skin breakdown, and infection. Clearly, early presentation in such cases that would allow for minimal surgical intervention, radiotherapy, or hormonal manipulation—alone or in combination—is preferable to advanced presentation that would require much more aggressive therapies and thus negatively impact quality of life. This, we believe, is our most important conclusion: more frequent screening in the elderly population does translate into earlier diagnosis and hence affords the clinician and patient an opportunity to discuss more minimal ways to treat the disease. In addition, our study has been criticized for not weighing the harms of routine screening, such as overdiagnosis, false positives, and false negatives. We agree that minimizing overdiagnosis is important; thus, we excluded patients with a diagnosis of ductal carcinoma in situ from our study. However, whether detecting ductal carcinoma in situ is considered overdiagnosis and the subsequent treatment is overtreatment remains controversial. Although we acknowledge that false negatives and false positives are possible, the frequency of such errors in the elderly population is not well studied. Last, the harms of intervention for treatment of breast cancer need to be considered. Within the general population, the morbidity and mortality related to breast surgery is relatively low,2 and even in the limited data for elderly populations, this trend still holds.3,4 Furthermore, radiation therapy and hormonal therapy for breast cancer are typically well tolerated.3,5–7 However, if chemotherapy is needed, particularly for more advanced stages of breast cancer, toxicity and treatment-related deaths are increased when compared with younger patients receiving the same regimens.8,9 The way to minimize risks from treatment is to treat at the earliest stages of disease. We agree that it is difficult to summarize adequately the findings of a study from a media press release or news article. This is not a novel concept in reporting the findings of a study, and we hope no clinician gathers evidence for practice from reading only the headline of a layman's press article. We believe that it is the responsibility of clinicians to advise patients on all clinical studies, because even randomized studies do not often match individual patient needs and scenarios. The investigators hope that this study encourages such discussions between the patient and physicians. In summary, as more American women live longer and as the means of treating their comorbid conditions continue to improve, how to screen and manage elderly women for breast cancer will become an even more pressing problem. It is clear that more data are needed in these areas. Ideally, such data would be obtained through randomized controlled trials and would address not only mortality but local control and quality of life. Until such questions are answered, controversy will abound, and clinicians and patients will need to consider all facets of the debate in making appropriate individualized decisions. We want to thank the editors of Journal of Clinical Oncology for recognizing our research and understanding the complexities involved in providing optimal patient care. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. REFERENCES
1. Badgwell BD, Giordano SH, Duan ZZ, et al: Mammography before diagnosis among women age 80 years and older with breast cancer. J Clin Oncol 26:2482–2488, 2008. 2. El-Tamer MB, Ward BM, Schifftner T, et al: Morbidity and mortality following breast cancer surgery in women: National benchmarks for standards of care. Ann Surg 245:665–671, 2007.[CrossRef][Medline] 3. Rosenkranz KM, Bedrosian I, Feng L, et al: Breast cancer in the very elderly: Treatment patterns and complications in a tertiary cancer center. Am J Surg 192:541–544, 2006.[CrossRef][Medline] 4. Warren JL, Riley GF, Potosky AL, et al: Trends and outcomes of outpatient mastectomy in elderly women. J Natl Cancer Inst 90:833–840, 1998. 5. Huguenin P, Sauer M, Glanzmann C, et al: Radiotherapy for carcinomas of the head and neck in elderly patients. Strahlenther Onkol 172:485–488, 1996.[Medline] 6. Wyckoff J, Greenberg H, Sanderson R, et al: Breast irradiation in the older woman: A toxicity study. J Am Geriatr Soc 42:150–152, 1994.[Medline] 7. Semiglazov VF, Semiglazov VV, Dashyan GA, et al: Phase 2 randomized trial of primary endocrine therapy versus chemotherapy in postmenopausal patients with estrogen receptor-positive breast cancer. Cancer 110:244–254, 2007.[CrossRef][Medline] 8. Muss HB, Woolf S, Berry D, et al: Adjuvant chemotherapy in older and younger women with lymph node-positive breast cancer. JAMA 293:1073–1081, 2005. 9. Pinder MC, Duan Z, Goodwin JS, et al: Congestive heart failure in older women treated with adjuvant anthracycline chemotherapy for breast cancer. J Clin Oncol 25:3808–3815, 2007.
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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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