Precision medicine—the concept of targeting therapy to a patient’s unique genetic or other relevant characteristics—occupies a prominent place on the national agenda.1 No condition demonstrates recent efforts toward precision medicine more clearly than cancer, and particularly breast cancer. After a decade of molecular subtyping, increasingly comprehensive genomic tests are emerging into breast cancer care. The 21-gene recurrence score (RS) assay has led the way in clinical implementation and thus offers an early opportunity to measure the impact of precision medicine on cancer treatment.
The RS assay uses a gene expression algorithm to predict a hormone-receptive breast cancer’s probability of recurrence and to estimate the benefit that adjuvant systemic chemotherapy might add to endocrine therapy. First introduced in 2004,2 the RS assay has been validated in retrospective data sets and is under prospective study in the TAILORx randomized clinical trial. Various studies have assessed the RS assay’s impact on breast cancer treatment: a notable example used the multicenter National Comprehensive Cancer Network (NCCN) database and reported an association between increasing RS use and declining chemotherapy use from 2006 through 2008.3 To date, however, no study has surveyed the wider landscape of the RS assay and downstream chemotherapy use across the US population.
Dinan et al4 took advantage of the Surveillance, Epidemiology, and End Results (SEER) registry, comprising 28% of all US cancer cases, to seek a broadly representative view of RS assay use and its association with chemotherapy from 2005 through 2009, the period immediately following its introduction. The authors leveraged an effective existing data linkage, SEER-Medicare, to interrogate Medicare claims for the RS assay by women who received a diagnosis at age 65 years or older with estrogen receptor–positive breast cancer. Consistent with previous research,3 Dinan et al4 found that RS assay use was highest among women whose breast tumor characteristics (eg, size, lymph node status) conferred an intermediate risk of distant cancer recurrence, the group for whom the RS assay is most clearly indicated. They also reported a decline in chemotherapy use over time among patients who received the RS assay. However, the authors found no significant association between use of the RS assay and chemotherapy use in multivariable analysis. Instead, the strongest predictors of chemotherapy receipt were younger age and high-risk tumor characteristics. This lack of correlation between use of the RS assay and chemotherapy use, in contrast to the findings of prior studies, likely reflects the low pretest probability of chemotherapy receipt by older women due to concerns about treatment toxicity and competing health risks. Despite uniform Medicare coverage, the authors also identified less RS assay use among patients living in regions with lower educational attainment and household income, a worrisome finding that calls attention to possible disparities in access to care.
The study by Dinan et al4 adds a valuable population-based lens to our knowledge of RS adoption and chemotherapy use because prior utilization studies have been more limited in scope. However, many crucial details are missing from this bird’s-eye view. Most critical are (1) the exclusion of women younger than 65 years, who make up the majority of breast cancer patients; (2) the lack of RS assay results, which markedly limits evaluation of its impact on chemotherapy decision making; and (3) the absence of patient and physician perspectives, without which we cannot fully understand how use of the RS assay informs treatment choices. Only 14% of patients in this study received chemotherapy, compared with 40% to 50% in studies with wider age ranges; this substantial difference in systemic therapy use suggests that the RS assay use patterns observed here may not generalize to younger women. Moreover, the availability of Medicare coverage among older women does not represent the access to care barriers that younger women may face. This study’s age restriction was imposed by a limitation of the SEER registry: the absence of data collection on evaluative testing, which compelled reliance on linkage to Medicare claims for RS testing records. Further SEER shortcomings during the 2005 through 2009 period included missing data on breast tumor biomarkers that shape decisions about systemic therapy (eg, HER2); such gaps are limitations to the study by Dinan et al.4 Fortunately, the SEER program has launched a recent initiative to link genomic information to registry records. These transformative SEER changes, including novel industry partnerships for genomic data linkage, will enable a much higher-resolution view of evaluative testing and treatment decision making in future studies of cancer care.5
Both the study by Dinan et al4 in SEER-Medicare, and prior work in the NCCN database,3 offer intriguing glimpses of the RS assay’s role in the examination room. Despite their different patient populations and care settings, these studies remarkably converge on the same key finding: patients with high-risk tumor features were less likely to receive chemotherapy after use of the RS assay, but patients with low-risk tumor characteristics were more likely to receive chemotherapy when the RS assay was used.3,4 Given the gaps in available data, it is impossible to determine whether physicians followed RS guidance despite its discordance from standard tumor prognostic characteristics, or whether they chose to dismiss an RS assay result that was concordant with tumor features in favor of a different treatment path. Getting “under the hood” of such complex medical decision making requires supplementing registry data not only with genomic test results but also with measures of the patient and physician experience. We still do not know why and under what circumstances physicians choose to order an RS assay; to what extent physicians’ treatment recommendations follow RS assay results; and what role, if any, patients play in the choice to order an RS assay and in subsequent chemotherapy decisions. Ultimately, we cannot assess the effects of RS assay use on breast cancer treatment without a deeper understanding of patients’ and physicians’ perspectives. As tumor and germline assays expand from 21 genes to the whole genome, there is growing need for a framework to evaluate the contribution of precision medicine to cancer treatment quality. Research initiatives that integrate the breadth of cancer registries with the depth of physician and patient survey data5 can offer a window into the clinical encounter, along with an outward view of impact across the population.
Corresponding Author: Allison W. Kurian, MD, MSc, Division of Oncology, Stanford University School of Medicine, HRP Redwood Bldg, Room T254A, 150 Governor’s Lane, Stanford, CA 94305-5405 (firstname.lastname@example.org).
Published Online: August 27, 2015. doi:10.1001/jamaoncol.2015.2719.
Conflict of Interest Disclosures: None reported.
Funding/Support: Drs Kurian and Friese received funding from National Cancer Institute grant P01CA16323 to the University of Michigan.
Role of the Funder/Sponsor: The National Cancer Institute had no role in the preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Kurian AW, Friese CR. Precision Medicine in Breast Cancer CareAn Early Glimpse of Impact. JAMA Oncol. 2015;1(8):1109-1110. doi:10.1001/jamaoncol.2015.2719