Outcome Disparities by Prognostic Indicators in HR+ Breast Cancer

Due to changing population demographics, and particularly increases in life expectancy, breast cancer diagnoses are rising in older patients. “Women older than 70 are the fastest growing segment of the female population in many countries, driving an unprecedented increase in breast cancer diagnosis in the elderly,” said Dr Steven Shak of Redwood City, CA, who was an author on the study. Despite the general underrepresentation of older women in randomized clinical trials, a recent large (N = 9766), multinational study reported worse outcomes for older patients with hormone receptor–positive (HR+) breast cancer (JAMA. 2012;307:590). To confirm this finding, and to further explore the role of tumor biology, the Surveillance, Epidemiology, and End Results (SEER) Program and Genomic Health, Inc, collaborated to electronically supplement SEER registries with 21-gene Recurrence Score® (RS) results and to further evaluate breast cancer–specific mortality.

RS results were voluntarily provided by Genomic Health to National Cancer Institute–sponsored SEER registries, and linked to SEER breast cancer cases. Eligible patients were diagnosed between January 2004 and December 2011 with stage N0 HR+ HER2– breast cancer, and had no prior malignancy or other known tumors. Breast cancer–specific mortality was determined as published in the Journal of the National Cancer Institute (2010;102:1584-1598), using the variables: (1) cause of death, (2) having only one tumor or the first of multiple tumors, (3) site of the original cancer diagnosis, and (4) comorbidities. Breast cancer–specific mortality was analyzed separately for patients younger and older than 70 years of age, and estimates of mortality were compared using a log-rank test.

Of the 184,190 eligible patients, 70% were aged <70 years and 30% were aged ≥70 years. In the <70-year-old group (median age, 55 years), 28% had RS results (35,487 of 128,712), whereas in the ≥70-year-old group (median age, 73 years), only 8% had RS results (4647 of 55,478). Notably, testing occurred 3.2 times less frequently in patients aged ≥70 years. When stratified by tumor differentiation and size, for patients aged <70 years, testing was performed more frequently in those with moderately differentiated tumors and tumors ranging in size from 10 mm to 20 mm, whereas for patients aged ≥70 years, most commonly tested tumors were well-differentiated and <10 mm. Furthermore, the reported chemotherapy use was significantly lower for patients aged ≥70 years (P <0.001).

Increasing RS results were associated with increased breast cancer–specific mortality for patients both <70 years and ≥70 years (P <0.001). As anticipated, the 5-year other-cause mortality was higher in patients ≥70 years (11%) than in patients <70 years (4%), but was not associated with RS results (P = 0.92). The 5-year breast cancer–specific mortality was worse for patients ≥70 years, and particularly for those with RS ≥18 (P <0.001). For patients aged <70 years, RS results of <18, 18-30, or ≥31 were associated with a 5-year breast cancer–specific mortality of 0.3 (95% confidence interval [CI], 0.2-0.4), 1.2 (95% CI, 0.9-1.5), and 4.5 (95% CI, 3.5-5.8), respectively. For patients ≥70 years old, RS results of <18, 18-30, or ≥31 were associated with a 5-year breast cancer–specific mortality of 1.2 (95% CI, 0.6-2.2), 2.8 (95% CI, 1.9-4.2), and 11.7 (95% CI, 7.1-18.9), respectively. For patients aged ≥70 years with no RS assay (n = 50,422; 4% chemotherapy use), the 5-year breast cancer–specific mortality was 5.4% (95% CI, 5.2%-5.6%).

Although this study was limited by its short follow-up time, and Dr Shak noted that the use of chemotherapy is “commonly underreported in the SEER database,” the results of this study reveal unsettling trends. This large population-based observational study of N0 HR+ breast cancer shows that patients in the United States who are older than 70 years with either no 21-gene assay done or an RS ≥18 (but not RS <18) have high rates of breast cancer–specific mortality when compared with their younger counterparts. “Global action needs to be taken to understand and address higher breast cancer mortality in older patients and the disparities in treatment,” said Dr Shak.

Shak S, et al. ESMO 2016. Abstract 146O.