Tumor Markers in Older Patients With Early Breast Cancer: Why Are We Still Doing Useless Tests?

In the article that accompanies this editorial, Ramsey et al report the results of their study on tumor marker use among older women with early-stage breast cancer. The study is a Seer-Medicare database analysis that examined the use of tumor markers (CA-15.3, CA-27.29 and carcinoembryonic antigen [CEA]) among 39,650 women 65 years and older who had been diagnosed with breast cancer between the years 2001 to 2007. Findings from the study showed that a significant minority (42%) of women completed at least one tumor marker test during the period 2 years after diagnosis with an average of 5.7 tests per each woman, and an increase in the number of tests per person with increasing calendar year. In addition, the cost of medical care was 29% higher among women who completed tumor marker testing, compared with women who did not. These finding are consistent with findings from other studies, and suggest that use of tumor markers to predict recurrence after primary treatment of breast cancer is a common practice among oncologists despite the fact that current guidelines do not support their use for this indication. Ramsey et al identified factors that were independently associated with tumor marker use. Younger women, women diagnosed later rather than sooner, and women with more advanced stage at diagnosis, were more likely to undergo testing for tumor markers. Given the independent association of age with tumor marker testing, with younger women more likely to have undergone tumor marker testing, it is likely that these findings represent an underestimation of the scope of tumor marker testing within the oncology community as the study population was limited to women 65 years and older. Since 1996, the American Society of Clinical Oncology (ASCO) has periodically published guidelines for use of tumor markers in the management of breast cancer. The ASCO guidelines in 1996, 1997, 2000, and most recently in 2007, uniformly, do not recommend or support the use of CA-15.3, CA-27.29, and CEA for screening, diagnosis, staging of breast cancer, or as surveillance tests for detecting recurrence after primary treatment of breast cancer. The most current National Cancer Comprehensive Network (NCCN) guidelines on the management of breast cancer also does not recommend the use of tumor markers for surveillance after primary treatment for breast cancer. Furthermore, in an effort similar to the American Board of Internal medicine “Choosing Wisely Campaign,” ASCO’s Cost of Care Task Force in 2012 identified breast cancer tumor marker testing, after treatment with curative intent, as one of five key cost-cutting opportunities in oncology care which will improve care and reduce unnecessary expense for patients, their families, and society at large. Despite these recommendations, findings from Ramsey et al continue to show routine use of breast cancer tumor markers in nonmetastatic breast cancer by a significant proportion of oncologists. Even more concerning is the rising use of tumor markers over time, despite periodic updates. However, it is important to note that because the study population was diagnosed through to 2007 and followed prospectively for 2 years after diagnosis the impact of the 2007 ASCO update and ASCO’s Cost of Care Task Force recommendations on the pattern of tumor marker use may not be captured by the reported study. Regardless of the study caveats, tumor marker use after primary treatment of early-stage breast cancer appears to frequent. Reasons for continued use of these tumor markers remain unknown and may be multifactorial. While ASCO tumor marker guidelines do not recommend tumor markers due to lack of evidence of benefit to patients, observational studies have shown a prognostic association between CA 15.3 and CA 27.29, and recurrence after primary treatment of breast cancer. In addition, it has been shown that CA27.29 can predict breast cancer recurrence, 5.3 months before clinical symptoms or test results. However, these results do not translate into a survival benefit as the diagnosis of metastatic disease is not, as yet, a curable condition, therefore finding metastases with a few month lead time is not associated with benefit to the patient. Indeed, there is significant morbidity associated with unnecessary tumor marker testing in the early-stage setting including the distress and ongoing anxiety of the patient with a positive tumor marker in the setting of negative metastatic work-up, and excess testing resulting from this finding. This cost of excess testing in not only borne by society but is directly transferred to the patient in this era of high deductible insurance plans and the Affordable Care Act. For these reasons ASCO guidelines do not recommend routine use of CEA and CA-15.3/CA-27.29 as surveillance tests after primary treatment with curative intent. Despite ASCO and NCCN recommendations, a significant minority of oncologists continue to use these tumor markers for surveillance in early-stage breast cancer. Factors that have been identified to be consistent with overuse of surveillance testing, including tumor markers, for breast cancer survivors include older age providers, lower provider self-efficacy, international medical graduates, and providers with greater perception that guideline recommendations regarding survivorship care may be conflicting or ambiguous. The 1999 JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 33 NUMBER 2 JANUARY 1