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Characteristics Associated With Differences in Survival Among Black and White Women With Breast Cancer
menopause predict weight gain after breast cancer diagnosis. J Clin Oncol. 1999;17:120-129.
7. Irwin ML, Crumley D, McTiernan A, et al. Physical activity levels before and after a diagnosis of breast
carcinoma: the Health, Eating, Activity, and Lifestyle (HEAL) study. Cancer. 2003;97:1746-1757.
EPIDEMIOLOGY Characteristics Associated With Differences in Survival Among Black and White Women With Breast Cancer Silber JH, Rosenbaum PR, Clark AS, et al (The Children’s Hosp of Philadelphia, PA; Leonard and Madlyn Abramson Cancer Ctr of the Univ of Pennsylvania, Philadelphia; Univ of Pennsylvania, Philadelphia) JAMA 310:389-397, 2013
Importance.dDifference in breast cancer survival by race is a recognized problem among Medicare beneficiaries. Objective.dTo determine if racial disparity in breast cancer survival is primarily attributable to differences in presentation characteristics at diagnosis or subsequent treatment. Design, Setting, and Patients.d Comparison of 7375 black women 65 years and older diagnosed between 1991 to 2005 and 3 sets of 7375 matched white control patients selected from 99,898 white potential controls, using data for 16 US Surveillance, Epidemiology and End Results (SEER) sites in the SEER-Medicare database. All patients received follow-up through December 31, 2009, and the black case patients were matched to 3 white control populations on demographics (age, year of diagnosis, and SEER site), presentation (demographics variables plus patient comorbid conditions and tumor characteristics such as
stage, size, grade, and estrogen receptor status), and treatment (presentation variables plus details of surgery, radiation therapy, and chemotherapy). Main Outcomes and Measures.d5-Year survival. Results.dThe absolute difference in 5-year survival (blacks, 55.9%; whites, 68.8%) was 12.9% (95% CI, 11.5%-14.5%; P < .001) in the demographics match. This difference remained unchanged between 1991 and 2005. After matching on presentation characteristics, the absolute difference in 5-year survival was 4.4% (95% CI, 2.8%-5.8%; P < .001) and was 3.6% (95% CI, 2.3%-4.9%; P < .001) lower for blacks than for whites matched also on treatment. In the presentation match, fewer blacks received treatment (87.4% vs 91.8%; P < .001), time from diagnosis to treatment was longer (29.2 vs 22.8 days; P < .001), use of anthracyclines and taxols was lower (3.7% vs 5.0%; P < .001), and breast-conserving surgery without other treatment was more frequent (8.2% vs 7.3%; P ¼.04). Nevertheless, differences in survival associated with treatment differences accounted for only 0.81% of the 12.9% survival difference. Conclusions and Relevance.dIn the SEER-Medicare database, differences in breast cancer survival between black and white women did not substantially change among women diagnosed between 1991 and 2005. These differences in survival appear
primarily related to presentation characteristics at diagnosis rather than treatment differences. In an elegant and unique study, Silber and colleagues used the SEERMedicare database to dissect the various sources of survival differences between black and white breast cancer patients. Racial disparities in breast cancer survival are well documented, and therefore the basic finding in the studydan absolute difference in 5-year survival of nearly 13%, with poorer survival found in black womendis unfortunately unsurprising. Indeed, this racial difference is consistent with previously reported studies.1,2 However, by using a series of matched cohorts, the authors were able to demonstrate the relative contribution of presentation characteristics, treatment factors, and socioeconomic factors to the cumulative survival difference. Each of these factors appeared to have contributed to the survival difference to some degreedfindings consistent with prior studies that focused on these risk factors individually. The analysis from Silber and colleagues, however, directly compared the relative importance of each factor, and the results suggested that presentation characteristics were likely to be the dominant explanatory factor. Specifically, not only were racial differences correlated with differences in breast cancer presentation, with black women
Breast Diseases: A Year BookÒ Quarterly Vol 25 No 1 2014
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presenting with more advanced tumors, less favorable tumor biology (ie, estrogen receptor-negative tumors), and fewer screen-detected tumors, but the magnitude of these differences may also have been so great that the differences appeared to supersede downstream elements such as treatment differences. This study has critical implications. First, its results highlight the fact that promoting access and delivery to standard oncologic care, including preventive care and screening, remain pressing oncologic public health and health services priorities. Additionally, in an era of increasingly limited resources for healthcare spending, this study provides novel data to help guide
policy strategies. The study also suggests that improving both the process and quality of initial access to screening and breast cancer diagnosis could have a similar or greater impact on cancer survival than that expected from emerging systemic therapies, especially for the most vulnerable patients. Finally, this analysis used a novel, matched-cohort, observational study design to provide insight into the persistent problem of cancer outcome disparities, elucidating risk factors for poor outcomes that could not be easily identified using a randomized trial design. As the clinical relevance of patient-centered outcomes research continues to increase, novel but rigorous methodologies such as this matched analytical approach are
required to provide innovative and valid insights into pressing questions.
received vorinostat and those who did not. Experimental Design.dTumor specimens were collected from 25 women who received up to 6 doses of oral vorinostat 300 mg twice daily and from 25 untreated controls in a nonrandomized study. Candidate gene expression was analyzed by reverse transcription PCR (RT-PCR) using the Oncotype DX 21-gene assay, and by immunohistochemistry for Ki-67 and cleaved caspase-3. Matched samples from treated women were analyzed for gene methylation by quantitative multiplex methylation-specific PCR (QMMSP). Wilcoxon nonparametric tests were used to compare changes in quantitative gene expression levels pre- and post-vorinostat with changes in expression in untreated controls, and changes
in gene methylation between pre- and post-vorinostat samples. Results.dVorinostat was well tolerated and there were no study-related delays in treatment. Compared with untreated controls, there were statistically significant decreases in the expression of proliferation-associated genes Ki-67 (P ¼ 0.003), STK15 (P ¼ 0.005), and Cyclin B1 (P ¼ 0.03) following vorinostat, but not in other genes by the Oncotype DX assay, or in expression of Ki-67 or cleaved caspase-3 by immunohistochemistry. Changes in methylation were not observed. Conclusions.dShort-term vorinostat administration is associated with a significant decrease in expression of proliferation-associated genes in untreated breast cancers. This demonstration of biologic activity supports
G. L. Smith, MD, PhD, MPH
References 1. Komenaka IK, Martinez ME, Pennington RE Jr, et al. Race and ethnicity and breast cancer outcomes in an underinsured population. J Natl Cancer Inst. 2010;102:1178-1187. 2. Tannenbaum SL, Koru-Sengul T, Miao F, Byrne MM. Disparities in survival after female breast cancer diagnosis: a population-based study. Cancer Causes Control. 2013;24: 1705-1715.
TUMOR BIOLOGY Biomarker Modulation following Short-Term Vorinostat in Women with Newly Diagnosed Primary Breast Cancer Stearns V, Jacobs LK, Fackler MJ, et al (Johns Hopkins Univ School of Medicine, Baltimore, MD; et al) Clin Cancer Res 19:4008-4016, 2013
Purpose.dAgents that target the epigenome show activity in breast cancer models. In preclinical studies, the histone deacetylase inhibitor vorinostat induces cell-cycle arrest, apoptosis, and differentiation. We evaluated biomarker modulation in breast cancer tissues obtained from women with newly diagnosed invasive disease who
36
Breast Diseases: A Year BookÒ Quarterly Vol 25 No 1 2014
7. Irwin ML, Crumley D, McTiernan A, et al. Physical activity levels before and after a diagnosis of breast
carcinoma: the Health, Eating, Activity, and Lifestyle (HEAL) study. Cancer. 2003;97:1746-1757.
EPIDEMIOLOGY Characteristics Associated With Differences in Survival Among Black and White Women With Breast Cancer Silber JH, Rosenbaum PR, Clark AS, et al (The Children’s Hosp of Philadelphia, PA; Leonard and Madlyn Abramson Cancer Ctr of the Univ of Pennsylvania, Philadelphia; Univ of Pennsylvania, Philadelphia) JAMA 310:389-397, 2013
Importance.dDifference in breast cancer survival by race is a recognized problem among Medicare beneficiaries. Objective.dTo determine if racial disparity in breast cancer survival is primarily attributable to differences in presentation characteristics at diagnosis or subsequent treatment. Design, Setting, and Patients.d Comparison of 7375 black women 65 years and older diagnosed between 1991 to 2005 and 3 sets of 7375 matched white control patients selected from 99,898 white potential controls, using data for 16 US Surveillance, Epidemiology and End Results (SEER) sites in the SEER-Medicare database. All patients received follow-up through December 31, 2009, and the black case patients were matched to 3 white control populations on demographics (age, year of diagnosis, and SEER site), presentation (demographics variables plus patient comorbid conditions and tumor characteristics such as
stage, size, grade, and estrogen receptor status), and treatment (presentation variables plus details of surgery, radiation therapy, and chemotherapy). Main Outcomes and Measures.d5-Year survival. Results.dThe absolute difference in 5-year survival (blacks, 55.9%; whites, 68.8%) was 12.9% (95% CI, 11.5%-14.5%; P < .001) in the demographics match. This difference remained unchanged between 1991 and 2005. After matching on presentation characteristics, the absolute difference in 5-year survival was 4.4% (95% CI, 2.8%-5.8%; P < .001) and was 3.6% (95% CI, 2.3%-4.9%; P < .001) lower for blacks than for whites matched also on treatment. In the presentation match, fewer blacks received treatment (87.4% vs 91.8%; P < .001), time from diagnosis to treatment was longer (29.2 vs 22.8 days; P < .001), use of anthracyclines and taxols was lower (3.7% vs 5.0%; P < .001), and breast-conserving surgery without other treatment was more frequent (8.2% vs 7.3%; P ¼.04). Nevertheless, differences in survival associated with treatment differences accounted for only 0.81% of the 12.9% survival difference. Conclusions and Relevance.dIn the SEER-Medicare database, differences in breast cancer survival between black and white women did not substantially change among women diagnosed between 1991 and 2005. These differences in survival appear
primarily related to presentation characteristics at diagnosis rather than treatment differences. In an elegant and unique study, Silber and colleagues used the SEERMedicare database to dissect the various sources of survival differences between black and white breast cancer patients. Racial disparities in breast cancer survival are well documented, and therefore the basic finding in the studydan absolute difference in 5-year survival of nearly 13%, with poorer survival found in black womendis unfortunately unsurprising. Indeed, this racial difference is consistent with previously reported studies.1,2 However, by using a series of matched cohorts, the authors were able to demonstrate the relative contribution of presentation characteristics, treatment factors, and socioeconomic factors to the cumulative survival difference. Each of these factors appeared to have contributed to the survival difference to some degreedfindings consistent with prior studies that focused on these risk factors individually. The analysis from Silber and colleagues, however, directly compared the relative importance of each factor, and the results suggested that presentation characteristics were likely to be the dominant explanatory factor. Specifically, not only were racial differences correlated with differences in breast cancer presentation, with black women
Breast Diseases: A Year BookÒ Quarterly Vol 25 No 1 2014
35
presenting with more advanced tumors, less favorable tumor biology (ie, estrogen receptor-negative tumors), and fewer screen-detected tumors, but the magnitude of these differences may also have been so great that the differences appeared to supersede downstream elements such as treatment differences. This study has critical implications. First, its results highlight the fact that promoting access and delivery to standard oncologic care, including preventive care and screening, remain pressing oncologic public health and health services priorities. Additionally, in an era of increasingly limited resources for healthcare spending, this study provides novel data to help guide
policy strategies. The study also suggests that improving both the process and quality of initial access to screening and breast cancer diagnosis could have a similar or greater impact on cancer survival than that expected from emerging systemic therapies, especially for the most vulnerable patients. Finally, this analysis used a novel, matched-cohort, observational study design to provide insight into the persistent problem of cancer outcome disparities, elucidating risk factors for poor outcomes that could not be easily identified using a randomized trial design. As the clinical relevance of patient-centered outcomes research continues to increase, novel but rigorous methodologies such as this matched analytical approach are
required to provide innovative and valid insights into pressing questions.
received vorinostat and those who did not. Experimental Design.dTumor specimens were collected from 25 women who received up to 6 doses of oral vorinostat 300 mg twice daily and from 25 untreated controls in a nonrandomized study. Candidate gene expression was analyzed by reverse transcription PCR (RT-PCR) using the Oncotype DX 21-gene assay, and by immunohistochemistry for Ki-67 and cleaved caspase-3. Matched samples from treated women were analyzed for gene methylation by quantitative multiplex methylation-specific PCR (QMMSP). Wilcoxon nonparametric tests were used to compare changes in quantitative gene expression levels pre- and post-vorinostat with changes in expression in untreated controls, and changes
in gene methylation between pre- and post-vorinostat samples. Results.dVorinostat was well tolerated and there were no study-related delays in treatment. Compared with untreated controls, there were statistically significant decreases in the expression of proliferation-associated genes Ki-67 (P ¼ 0.003), STK15 (P ¼ 0.005), and Cyclin B1 (P ¼ 0.03) following vorinostat, but not in other genes by the Oncotype DX assay, or in expression of Ki-67 or cleaved caspase-3 by immunohistochemistry. Changes in methylation were not observed. Conclusions.dShort-term vorinostat administration is associated with a significant decrease in expression of proliferation-associated genes in untreated breast cancers. This demonstration of biologic activity supports
G. L. Smith, MD, PhD, MPH
References 1. Komenaka IK, Martinez ME, Pennington RE Jr, et al. Race and ethnicity and breast cancer outcomes in an underinsured population. J Natl Cancer Inst. 2010;102:1178-1187. 2. Tannenbaum SL, Koru-Sengul T, Miao F, Byrne MM. Disparities in survival after female breast cancer diagnosis: a population-based study. Cancer Causes Control. 2013;24: 1705-1715.
TUMOR BIOLOGY Biomarker Modulation following Short-Term Vorinostat in Women with Newly Diagnosed Primary Breast Cancer Stearns V, Jacobs LK, Fackler MJ, et al (Johns Hopkins Univ School of Medicine, Baltimore, MD; et al) Clin Cancer Res 19:4008-4016, 2013
Purpose.dAgents that target the epigenome show activity in breast cancer models. In preclinical studies, the histone deacetylase inhibitor vorinostat induces cell-cycle arrest, apoptosis, and differentiation. We evaluated biomarker modulation in breast cancer tissues obtained from women with newly diagnosed invasive disease who
36
Breast Diseases: A Year BookÒ Quarterly Vol 25 No 1 2014