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author:("parish, Carol")
1.  Breast Cancer Survival Defined by the ER/PR/HER2 Subtypes and a Surrogate Classification according to Tumor Grade and Immunohistochemical Biomarkers 
Journal of Cancer Epidemiology  2014;2014:469251.
Introduction. ER, PR, and HER2 are routinely available in breast cancer specimens. The purpose of this study is to contrast breast cancer-specific survival for the eight ER/PR/HER2 subtypes with survival of an immunohistochemical surrogate for the molecular subtype based on the ER/PR/HER2 subtypes and tumor grade. Methods. We identified 123,780 cases of stages 1–3 primary female invasive breast cancer from California Cancer Registry. The surrogate classification was derived using ER/PR/HER2 and tumor grade. Kaplan-Meier survival analysis and Cox proportional hazards modeling were used to assess differences in survival and risk of mortality for the ER/PR/HER2 subtypes and surrogate classification within each stage. Results. The luminal B/HER2− surrogate classification had a higher risk of mortality than the luminal B/HER2+ for all stages of disease. There was no difference in risk of mortality between the ER+/PR+/HER2− and ER+/PR+/HER2+ in stage 3. With one exception in stage 3, the ER-negative subtypes all had an increased risk of mortality when compared with the ER-positive subtypes. Conclusions. Assessment of survival using ER/PR/HER2 illustrates the heterogeneity of HER2+ subtypes. The surrogate classification provides clear separation in survival and adjusted mortality but underestimates the wide variability within the subtypes that make up the classification.
PMCID: PMC4058253  PMID: 24955090
2.  Disparities in race/ethnicity and socioeconomic status: risk of mortality of breast cancer patients in the California Cancer Registry, 2000–2010 
BMC Cancer  2013;13:449.
Racial disparities in breast cancer survival have been well documented. This study examines the association of race/ethnicity and socioeconomic status (SES) on breast cancer-specific mortality in a large population of women with invasive breast cancer.
We identified 179,143 cases of stages 1–3 first primary female invasive breast cancer from the California Cancer Registry from January, 2000 through December, 2010. Cox regression, adjusted for age, year of diagnosis, grade, and ER/PR/HER2 subtype, was used to assess the association of race/ethnicity on breast cancer-specific mortality within strata of stage and SES. Hazard ratios (HR) and 95% confidence intervals were reported.
Stage 1: There was no increased risk of mortality for any race/ethnicity when compared with whites within all SES strata. Stage 2: Hispanics (HR = 0.85; 0.75, 0.97) in the lowest SES category had a reduced risk of mortality.. Blacks had the same risk of mortality as whites in the lowest SES category but an increased risk of mortality in the intermediate (HR = 1.66; 1.34, 2.06) and highest (HR = 1.41; 1.15, 1.73) SES categories. Stage 3: Hispanics (HR = 0.74; 0.64, 0.85) and APIs (HR = 0.64; 0.50, 0.82) in the lowest SES category had a reduced risk while blacks had similar mortality as whites. Blacks had an increased risk of mortality in the intermediate (HR = 1.52; 1.20, 1.92) and highest (HR = 1.53; 1.22, 1.92) SES categories.
When analysis of breast cancer-specific mortality is adjusted for age and year of diagnosis, ER/PR/HER2 subtype, and tumor grade and cases compared within stage and SES strata, much of the black/white disparity disappears. SES plays a prominent role in breast cancer-specific mortality but it does not fully explain the racial/ethnic disparities and continued research in genetic, societal, and lifestyle factors is warranted.
PMCID: PMC3850736  PMID: 24083624
Disparities; Breast cancer-specific mortality; Race/ethnicity; Socioeconomic status
3.  Safety and Observations in a Pilot Study of Lenalidomide for Treatment in Autism 
Autism Research and Treatment  2012;2012:291601.
Autism affects 1 : 88 children in the United States. Familial history of autoimmune disease, autoantibodies in the serum of mothers when there is more than one autistic offspring, and neuroglial response in CSF and brain tissue in autistic patients suggest an immunological variable may be associated with this condition. Lenalidomide has the potential to invoke changes in TNF-α with less toxicity than thalidomide. This pilot study evaluated lenalidomide at reduction of TNF-α and improvement of behavior and language in children with autism with elevated TNF-α. Subjects with elevated TNF-α were given 2.5 mgs lenalidomide daily for 12-weeks. Pharmacodynamics and safety was evaluated. Changes in language and autistic behaviors after six and twelve weeks were measured. Although statistical significance was not achieved for most measures, there were trends toward improvement. After 6-weeks, mean receptive language increased: 60.67 ± 12.06 to 65.00 ± 15.10 (P = 0.11) and symptoms of autism decreased (40.75 ± 5.96 versus 38.67 ± 7.90, P = 0.068). After 12-weeks, CSF-TNF-α declined 57% ± 25% from 80.5 ± 41.03 to 38.0 ± 31.27 (P = 0.068). Serum TNF-α declined 57% (92.50 ± 68.92 to 40.25 ± 44.53 (P = 0.048). This study suggests that lenalidomide is tolerated as a treatment by children with autism and should be further studied as a potential agent for cytockine inflammation.
PMCID: PMC3446644  PMID: 22997574
4.  Use of ER/PR/HER2 subtypes in conjunction with the 2007 St Gallen Consensus Statement for early breast cancer 
BMC Cancer  2010;10:228.
The 2007 St Gallen international expert consensus statement describes three risk categories and provides recommendations for treatment of early breast cancer. The set of recommendations on how to best treat primary breast cancer is recognized and used by clinicians worldwide. We now examine the variability of five-year survival of the 2007 St Gallen Risk Classifications utilizing the ER/PR/HER2 subtypes.
Using the population-based California Cancer Registry, 114,786 incident cases of Stages 1-3 invasive breast cancer diagnosed between 2000 and 2006 were identified. Cases were assigned to Low, Intermediate, or High Risk categories. Five-year-relative survival was computed for the three St Gallen risk categories and for the ER/PR/HER2 subtypes for further differentiation.
Results and Discussion
There were 9,124 (13%) cases classified as Low Risk, 44,234 (65%) cases as Intermediate Risk, and 14,340 (21%) as High Risk. Within the Intermediate Risk group, 33,735 (76%) were node-negative (Intermediate Risk 2) and 10,499 (24%) were node-positive (Intermediate Risk 3). For the High Risk group, 6,149 (43%) had 1 to 3 positive axillary lymph nodes (High Risk 4) and 8,191 (57%) had four or more positive lymph nodes (High Risk 5).
Using five-year relative survival as the principal criterion, we found the following: a) There was very little difference between the Low Risk and Intermediate Risk categories; b) Use of the ER/PR/HER2 subtypes within the Intermediate and High Risk categories separated each into a group with better five-year survival (ER-positive) and a group with worse survival (ER-negative), irrespective of HER2-status; c) The heterogeneity of the High Risk category was most evident when one examined the ER/PR/HER2 subtypes with four or more positive axillary lymph nodes; (d) HER2-positivity did not always translate to worse survival, as noted when one compared the triple positive subtype (ER+/PR+/HER2+) to the triple negative subtype (ER-/PR-/HER2-); and (e) ER-negativity appeared to be a stronger predictor of poor survival than HER2-positivity.
The use of ER/PR/HER2 subtype highlights the marked heterogeneity of the Intermediate and High Risk categories of the 2007 St Gallen statements. The use of ER/PR/HER2 subtypes and correlation with molecular classification of breast cancer is recommended.
PMCID: PMC2886044  PMID: 20492696

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