Effects of Estrogen Receptor Expression and Histopathology on Annual Hazard Rates of Death from Breast Cancer
Breast cancer incidence rates vary according to estrogen receptor expression (ER) and histopathology. We hypothesized that annual mortality rates from breast cancer after initial diagnosis (hazard rates) might also vary by ER and histopathology.
We accessioned the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER, 1992–2002) program to estimate hazard rates according to ER (positive and negative) and histopathology (duct, tubular, lobular, medullary, inflammatory, papillary, and mucinous types). We used spline functions to model hazard rates free of strongly parametric assumptions for ER negative and positive cases overall and by histopathology.
Hazard rates for ER negative and ER positive cases were distinct and non-proportional. At 17 months, ER negative hazard rates peaked at 7.5% per year (95% CI, 7.3–7.8% per year) then declined, whereas ER positive hazard rates lacked a sharp early peak and were comparatively constant at 1.5–2% per year. Falling ER negative and constant ER positive hazard rates crossed at 7 years; after which, prognosis was better for ER negative cases. Among ER positive and negative cases, there were proportional and non-proportional hazards according to histopathologic type, but the two basic ER-associated patterns were maintained.
Hazard rates differed quantitatively and qualitatively according to ER and histopathology. These large-scale population-based results seem consistent with genomic studies, demonstrating two main classes of breast cancers with distinct prognoses according to ER expression.
Key wordsHazard function Hazard regression Survival analysis Non-proportional hazards Risk factors
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This research was supported in part by the Intramural Research Program of the NIH/National Cancer Institute.
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