Effects of estrogen receptor expression and histopathology on annual hazard rates of death from breast cancer.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Anderson
William F
WF
DHHS/NIH/NCI/Division of Cancer Epidemiology and Genetics, Biostatistics Branch, EPS, Room 8036, 6120 Executive Blvd, Rockville, MD 20852-7244, USA. wanderso@mail.nih.gov
Chen
Bingshu E
BE
Jatoi
Ismail
I
Rosenberg
Philip S
PS