The association of race/ethnicity in male breast cancer survival within similar comorbidity cohorts.

BACKGROUND: Concomitant disease is associated with poor breast cancer survival in women and is more prevalent in racial/ethnic minority groups than individuals who are non-Hispanic White. The purpose of this study was to determine if race/ethnicity is associated with survival among men with breast cancer when stratifying analyses by level of comorbidity. METHODS: We used the California Cancer Registry to identify 1730 cases of men and 259,828 cases of women with breast cancer and documented Charlson Comorbidity Index (CCI). Kaplan-Meier survival and Cox regression analyses were used to compare breast cancer-specific survival and risk of mortality for African American/Black, Hispanic, and Asian/Pacific Islander men with White women and White men. RESULTS: When compared with White women, Black men with a CCI of 0 (hazard ratio [HR], 3.09; 95% CI, 1.10-1.16) and a CCI of 2+, (HR, 2.51; 95% CI, 1.42-4.42) had an increased risk of mortality when compared with White women. When compared with White men, African American men with a CCI of 0 (HR, 2.36; 95% CI, 1.45-3.85) and 2+ (HR, 2.44; 95% CI, 1.26-4.74) had an increased unadjusted risk of mortality, but these disparities were neutralized when controlling for sociodemographic and clinical factors. CONCLUSIONS: Black men with both low and high levels of concomitant disease have an increased risk of mortality when compared with both White men and women, but demographic and clinical factors are contributors to this disparity.

The influence of comorbidity on treatment and survival of triple-negative breast cancer.

Concomitant comorbidity is a key factor in treatment decision-making for breast cancer. The aim of this study was to determine how the Charlson Comorbidity Index (CCI) affected treatment and risk of mortality of women with TNBC, the subtype with the poorest prognosis. We accessed 20 177 cases of TNBC from the California Cancer Registry 2000-2015 with documented Charlson Comorbidity Index (CCI). Cox Regression was used to compute the adjusted risk of breast cancer-specific mortality for a CCI of 1 (low comorbidity) and 2+ (high comorbidity) vs a CCI of 0 (no comorbidity). Logistic regression was used to compute the association of CCI with treatment of mastectomy, lumpectomy + radiation, and chemotherapy. Analyses were conducted separately for each stage. Patients with high comorbidity CCI (2+) were less likely to receive systemic chemotherapy irrespective of Stage. High comorbidity was associated with higher breast-specific mortality in all stages of disease. High comorbidity did not have an effect on the use of lumpectomy and radiation of stage 1 breast cancer but was associated with reduced use in stages 2-4. Comorbidity was not associated with decreased risk of mastectomy except for patients with high comorbidity in stage 3. Concomitant comorbidity influences treatment decisions and breast cancer-specific mortality in patients with TNBC.

Differences in clinicopatholgic characteristics and risk of mortality between the triple positive and ER+/PR+/HER2- breast cancer subtypes.

PURPOSE: This study compared the demographic and clinicopathologic characteristics and risk of mortality between the triple positive (TP) and ER+/PR+/HER2- breast cancer subtypes. METHODS: Cases of first primary female invasive TP and ER+/PR+/HER2- breast cancer were obtained from the California Cancer Registry. Logistic regression analysis was used to compare differences in factors associated with the TP versus the ER+/PR+/HER2- subtype. Cox regression was used to compute the adjusted risk of breast cancer-specific mortality of the TP versus ER+/PR+/HER2-. RESULTS: The odds of TP versus ER+/PR+/HER2- were higher with advanced stage, high grade, low SES, ≤ 45 years of age (OR 1.48; CI 1.40-1.55), black (OR 1.11; CI 1.02-1.21), Asian/Pacific Islander (OR 1.15; CI 1.09-1.22), and uninsured (OR 1.42; CI 1.15-1.73). Unadjusted survival analysis indicated worse survival for the TP when compared with the ER+/PR+/HER2- subtype. However, adjusted risk of mortality for the TP subtype was not statistically significantly worse than the ER+/PR+/HER2- subtype. CONCLUSIONS: Young age, advanced stage and grade, low SES, black and API race, and lack of health insurance are more common in the TP subtype than in the ER+/PR+/HER2- subtype. However the risk of mortality between these two subtypes is similar.

Risk factors associated with the triple-negative breast cancer subtype within four race/ethnicities.

PURPOSE: The ER-/PR-/HER2- or triple-negative (TNBC) subtype is more prevalent among women who are young, black, Hispanic, and of lower SES. The purpose of this study is to determine if young age and low SES are associated with TNBC within four mutually exclusive race/ethnicities. METHODS: The study identified 19,283 cases of TNBC and 89,089 of ER+/PR+/HER2- from the California Cancer Registry. Logistic regression analyses were conducted separately for whites, blacks, Hispanics, and Asian/Pacific Islanders (API) to compute the adjusted odds ratios (OR) for age and SES for the TNBC versus the ER+/PR+/HER2- subtype. RESULTS: White (OR=1.37;1.23-1.53) and Hispanic and women (OR=1.35;1.17-1.56) 30-39 had increased odds of the TNBC when compared with women 50-59 of the same race/ethnicity. Black women under 40 had the same odds, and black women 40-49 had lower odds of the TNBC as black women 50-59. White, black, and Hispanic women 70 and older had decreased or the same odds of the TNBC as 50 to 59-year-old women. API women had a similar risk of TNBC at all ages. Lower SES was associated with increased risk of TNBC only for white and Hispanic women. The odds of TNBC were no worse for API women with lower SES than API women with higher SES. SES was not statistically significant for black women. CONCLUSIONS: When assessing the odds of TNBC within a single race/ethnicity, young age and low SES are risk factors only for white and Hispanic women, but not for black and API women.

Risk of mortality of node-negative, ER/PR/HER2 breast cancer subtypes in T1, T2, and T3 tumors.

PURPOSE: The purpose of this study was to assess differences in breast cancer-specific mortality within tumors of the same size when breast cancer was defined using the three tumor markers estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). METHODS: We identified 104,499 cases of node-negative primary female invasive breast cancer from the California Cancer Registry. Tumor size was categorized as T1a, T1b, T1c, T2, and T3. Breast cancer was defined using ER, PR, and HER2. Kaplan-Meier Survival analysis was conducted and Cox Regression was used to compute the adjusted risk of mortality for the ER+/PR+/HER2+, ER-/PR-/HER2- (TNBC), and ER-/PR-/HER2+ (HER2-overexpressing) subtypes when compared with the ER+/PR+/HER2-. Separate models were computed for each tumor size. RESULTS: Unadjusted survival analysis showed that for all tumor sizes, the ER+/PR+ subtypes regardless of HER status have better breast cancer-specific survival than ER-/PR- subtypes. Subtype was not an important factor for risk of mortality for T1a tumors. The ER+/PR+/HER2+ subtype was only a risk for mortality in T1b tumors that were unadjusted for treatment. For all other tumor sizes, the ER+/PR+/HER2+ had the same mortality as the ER+/PR+/HER2- subtype regardless of adjustment for treatment. The HER2-overexpressing subtype had a higher risk of mortality than the ER+/PR+/HER2- subtype except for T1b tumors that were adjusted for treatment. For all tumor sizes, the TNBC had higher hazard ratios than all other subtypes. CONCLUSIONS: T1a tumors have the same risk of mortality regardless of ER/PR/HER2 subtype, and ER and PR negativity plays a stronger role in survival than HER2 positivity for tumors of all size.

Disparities in race/ethnicity and socioeconomic status: risk of mortality of breast cancer patients in the California Cancer Registry, 2000-2010.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Disparities in receipt of adjuvant radiation therapy after breast-conserving surgery among the cancer-reporting regions of California.

BACKGROUND: Incidence and mortality of breast cancer vary according to demographic factors such as age, race/ethnicity, socioeconomic status (SES), and geographic region. This study assesses the variation of these factors in the use of adjuvant radiation therapy (RT) after breast-conserving surgery (BCS) among 8 regions of California. METHODS: The authors identified 85,574 cases of first primary female invasive breast cancer with complete data diagnosed between January 1, 2000 and December 31, 2007. Logistic regression was used to determine the association between race/ethnicity, age, SES, and receipt of RT after BCS within each of the regions of California. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed. RESULTS: Age was a significant predictor of receipt of RT after BCS in all regions. In Los Angeles (LA), lower SES was associated with decreasing odds of RT. Racial disparities were evident only in LA, where black (OR, 0.85; 95% CI, 0.74-0.97) and Hispanic (OR, 0.86; 95% CI, 0.78-0.96) women were about 15% less likely to receive RT than white women. CONCLUSIONS: Racial disparities in the receipt of RT after BCS exist only in LA, where African American and Hispanic women are less likely to receive this form of adjuvant treatment. Lower SES was also associated with a reduced likelihood of receipt of RT in LA. Women age 70 years and older are less likely to receive RT after BCS in all regions of California.

Use of ER/PR/HER2 subtypes in conjunction with the 2007 St Gallen Consensus Statement for early breast cancer.

BACKGROUND: 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. METHODS: 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. CONCLUSION: 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.

Breast cancer subtypes as defined by the estrogen receptor (ER), progesterone receptor (PR), and the human epidermal growth factor receptor 2 (HER2) among women with invasive breast cancer in California, 1999-2004.

Breast cancer research examining either molecular profiles or biomarker subtypes has focused on the estrogen receptor negative/progesterone receptor negative/human epidermal growth factor receptor 2 negative (ER-/PR-/HER2-) and ER-/PR-/HER2+ subtypes. Less is known about the epidemiology or clinical outcome of the other subtypes. This study examines the eight combinations of ER/PR/HER2 in patients with invasive breast cancer. The 5-year relative survival and the distribution among demographic, socioeconomic, and tumor characteristics of each of the subtypes are examined. Using the California Cancer Registry, 61,309 women with primary invasive breast cancer were classified according to ER/PR/HER2 status. Five-year relative survival was computed for the eight subtypes. Bivariate analyses were used to assess the distribution of cases across all subtypes. Multivariate logistic regression was used to compute the adjusted odds of having one of the five subtypes with the best and worst survival. Survival varied from 96% (ER+/PR+/HER2-) to 76% (ER-/PR-/HER2+ and ER-/PR-/HER2-). The four subtypes with the poorest survival were all ER negative. Women who were younger than age 50, non-Hispanic black or Hispanic, of the lowest SES groups, and had stage IV tumors that were undifferentiated were overrepresented in ER-/PR-/HER2+ and triple negative (ER-/PR-/HER2-) subtypes. Asian Pacific Islanders had increased odds (OR = 1.41; 95% confidence interval [CI] = 1.26-1.57) of having the ER-/PR-/HER2+ subtype. Stage III tumors (OR = 1.25; 95% CI = 1.08-1.44) and stage IV tumors (OR = 1.58; 95% CI = 1.27-1.98) had higher odds than stage I tumors of being ER-/PR-/HER2+. Stage IV tumors (OR = 0.54; 95% CI = 0.44-0.67) strongly decreased the odds of the ER-/PR-/HER2- subtype. Poorly differentiated and undifferentiated tumors were over 20 times as likely as well-differentiated tumors of being ER-/PR-/HER2- or ER-/PR-/HER2+. There are considerable differences in survival, demographics, and tumor characteristics among the eight subtypes. We recommend reporting breast cancer as an ER/PR/HER2 subtype and precisely documenting demographic and tumor characteristics.

The influence of marital status and race/ethnicity on risk of mortality for triple negative breast cancer.

PURPOSE: To assess the effect of marital status and the role of race/ethnicity on breast cancer specific mortality in women with triple negative breast cancer (TNBC). METHODS: The study utilized the California Cancer Registry to identify 22,812 cases of first primary female TNBC. Unadjusted Kaplan-Meier breast cancer specific survival was computed. Cox Proportional Hazards modeling was used to compute the adjusted risk of breast cancer specific mortality for women who were single, separated, divorced, and widowed when compared with women who were married. Models were adjusted for age, stage, tumor grade, SES, and treatment with surgery, chemotherapy, hormone therapy, and radiation therapy. Hazard ratios (HR) and 95% confidence intervals (CI) were reported. RESULTS: Separated (HR: 1.45; 95% CI: 1.14-2.01) and widowed (HR: 1.39; 95%CI: 1.23-1.57) white women had a higher risk of mortality than white married women whereas single and divorced white women had the same risk of mortality. For Asian/Pacific Islanders (API), only single (HR: 1.55; 95% CI: 1.17-2.06) and divorced (HR:1.81; 95% CI:1.26-2.60) women had a higher risk of mortality than married women. Marital status had no influence on risk of mortality for either black or Hispanic women. CONCLUSIONS: The risk of mortality associated with marital status is dependent on race/ethnicity. Only white and API women with TNBC have a marital advantage.

Regional Variation in Disparities in Breast Cancer Specific Mortality Due to Race/Ethnicity, Socioeconomic Status, and Urbanization.

PURPOSE: Disparities in breast cancer mortality due to race/ethnicity, area socioeconomic status (SES), and urbanization have been documented. This study examined if disparities in the risk of breast cancer specific mortality due to race/ethnicity, SES, and urbanization varied within diverse regions of California. METHODS: We identified 163,569 cases of first primary female invasive breast cancer from the California Cancer Registry diagnosed between January, 2000 and December, 2013. Cox regression was used to compute hazard ratios (HR) and 95 % confidence intervals for race/ethnicity, SES, and urbanization within eight regions of California. RESULTS: Blacks had an increased risk of mortality in the San Francisco Bay Area (SFBA) (HR = 1.37; 1.22-1.55), Desert Sierra (HR = 1.27; 1.08-1.49), San Diego/Orange (HR = 1.43; 1.19-1.71), and Los Angeles (LA) (HR = 1.31; 1.20-1.44). Japanese (HR = 0.62; 0.47-0.81), Chinese (HR = 0.71; 0.58-0.87), and Filipino (HR = 0.81; 0.69-0.95) women had a decreased risk of mortality in LA. Southeast Asians had a decreased risk in San Diego/Orange (HR = 0.72; 0.57-0.90) and in the SFBA (HR = 0.81; 0.67-0.98). Hispanics had a decreased risk (HR = 0.73; 0.57-0.93) and American Indians had an increased risk (HR = 2.32; 1.08-4.98) in the Tri-County region. SES was a significant risk factor for mortality in all regions except the North and Tri-County. Urbanization was a statistically significant factor for mortality only in LA (HR = 1.32; 1.08-1.60). CONCLUSIONS: Disparities in breast cancer mortality, due to race/ethnicity, SES, and urbanization vary by region which suggests that further research is warranted concerning the role of geographic regions and neighborhoods in cancer outcomes.

Breast Cancer Mortality among Asian-American Women in California: Variation according to Ethnicity and Tumor Subtype.

PURPOSE: Asian-American women have equal or better breast cancer survival rates than non-Hispanic white women, but many studies use the aggregate term "Asian/Pacific Islander" (API) or consider breast cancer as a single disease. The purpose of this study was to assess the risk of mortality in seven subgroups of Asian-Americans expressing the estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (HER2) tumor marker subtypes and determine whether the risk of mortality for the aggregate API category is reflective of the risk in all Asian ethnicities. METHODS: The study included data for 110,120 Asian and white women with stage 1 to 4 first primary invasive breast cancer from the California Cancer Registry. The Asian ethnicities identified were Pacific Islander, Southeast Asian (SEA), Indian Subcontinent, Chinese, Japanese, Filipino, and Korean. A Cox regression analysis was used to compute the risk of breast cancer-specific mortality in seven Asian ethnicities and the combined API category versus white women within each of the ER/PR/HER2 subtypes. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed. RESULTS: For the ER+/PR+/HER2- subtype, the combined API category showed a 17% (HR, 0.83; 95% CI, 0.76-0.91) lower mortality risk. This was true only for SEA (HR, 0.75; 95% CI, 0.61-0.91) and Japanese women (HR, 0.60; 95% CI, 0.45-0.81). In the ER+/PR-/HER2- subtype, SEA (HR, 0.57; 95% CI, 0.38-0.84) and Filipino women (HR, 0.71; 95% CI, 0.51-0.97) had a lower risk of mortality. Japanese (HR, 0.49; 95% CI, 0.25-0.99) and Filipino women (HR, 0.74; 95% CI, 0.58-0.94) had a lower HR for the ER-/PR-/HER2+ subtype. For triple-positive, ER+/PR+/HER2+ (HR, 0.84; 95% CI, 0.71-0.98) and triple-negative, ER-/PR-/HER2- (HR, 0.84; 95% CI, 0.74-0.94) subtypes, only the API category showed a lower risk of mortality. CONCLUSION: Breast cancer-specific mortality among Asian-American women varies according to their specific Asian ethnicity and breast cancer subtype.

The Influence of Socioeconomic Status on Racial/Ethnic Disparities among the ER/PR/HER2 Breast Cancer Subtypes.

Background. The eight ER/PR/HER2 breast cancer subtypes vary widely in demographic and clinicopathologic characteristics and survival. This study assesses the contribution of SES to the risk of mortality for blacks, Hispanics, Asian/Pacific Islanders, and American Indians when compared with white women for each ER/PR/HER2 subtype. Methods. We identified 143,184 cases of first primary female invasive breast cancer from the California Cancer Registry between 2000 and 2012. The risk of mortality was computed for each race/ethnicity within each ER/PR/HER2 subtype. Models were adjusted for tumor grade, year of diagnosis, and age. SES was added to a second set of models. Analyses were conducted separately for each stage. Results. Race/ethnicity did not contribute to the risk of mortality for any subtype in stage 1 when adjusted for SES. In stages 2, 3, and 4, race/ethnicity was associated with risk of mortality and adjustment for SES changed the risk only in some subtypes. SES reduced the risk of mortality by over 45% for American Indians with stage 2 ER+/PR+/HER2- cancer, but it decreased the risk of mortality for blacks with stage 2 triple negative cancer by less than 4%. Conclusions. Racial/ethnic disparities do not exist in all ER/PR/HER2 subtypes and, in general, SES modestly alters these disparities.

Disparities in the risk of the ER/PR/HER2 breast cancer subtypes among Asian Americans in California.

BACKGROUND: Population-based studies of breast cancer often aggregate all Asians into a single category termed Asian/Pacific Islander (API). PURPOSE: (1) Describe the demographic and clinicopathologic features of early breast cancer utilizing all eight ER/PR/HER2 subtypes among white, black, Hispanic, American Indian, seven Asian ethnicities, and the aggregate API category; (2) ascertain the risk of the ER+/PR+/HER2+, ER-/PR-/HER2-, and ER-/PR-/HER2+ subtypes when compared with the ER+/PR+/HER2- subtype, among seven Asian ethnicities versus non-Hispanic white women and (3) contrast the results with the risk of these same subtypes when using the aggregate API category. METHODS: Using the California Cancer Registry, we identified 225,441 cases of stages 1-4 first primary female invasive breast cancer. Logistic regression was used to assess the association of race with the ER+/PR+/HER2+, ER-/PR-/HER2- (triple-negative), and the ER-/PR-/HER2+ subtypes versus the ER+/PR+/HER2- when adjusted for stage, age, tumor grade, and socioeconomic status. Models were fit separately for each subtype. Odds ratios for the seven Asian ethnicities and the aggregate API category using non-Hispanic white women as the reference category were computed. RESULTS: There was an increased risk of the ER+/PR+/HER2+ subtype for the combined API category (OR=1.16; 95% CI=1.09-1.23). But only Southeast Asians (OR=1.17; 95% CI=1.04-1.31), Filipino (OR=1.23; 95% CI=1.12-1.36), and Korean (OR=1.63; 95% CI=1.38-1.99) women had an increased risk of this subtype. The reduced risk of the triple-negative subtype seen in APIs (OR=0.84; 95% CI=0.79-0.90) was only noted in Chinese (OR=0.80; 95% CI=0.70-0.91) and Filipino (OR=0.65; 95% CI=0.58-0.73) women whereas Indian Continent (OR=1.25; 95% CI=1.01-1.53) women had an increased risk of the triple-negative subtype. The race×stage interaction was statistically significant for the ER-/PR-/HER2+ subtype (p<0.05). When stratified by stage, there was no statistically significant association of race with subtype in stages 3 and 4. APIs had an increased risk of the ER-/PR-/HER2+ subtype in stage 1 (OR=1.59; 95% CI=1.37-1.75) and stage 2 (OR=1.42; 95% CI=1.28-1.58) but this risk was not seen in Pacific Islander, Indian Continent, and Japanese women for either stage. CONCLUSIONS: Among the Asian ethnicities, there is marked variability in the demographic and clinicopathologic features of breast cancer. Use of the ER/PR/HER2 subtypes reveals that the risk of the ER-/PR-/HER2-, ER+/PR+/HER2+, and ER-/PR-/HER2+ subtypes varies among the Asian population. The API category, is sometimes, but not always reflective of all Asian women.

Breast Cancer Survival Defined by the ER/PR/HER2 Subtypes and a Surrogate Classification according to Tumor Grade and Immunohistochemical Biomarkers.

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.

Factors associated with adherence to an end-of-study biopsy: lessons from the prostate cancer prevention trial (SWOG-Coordinated Intergroup Study S9217).

BACKGROUND: The Prostate Cancer Prevention Trial (PCPT) was a 7-year randomized, double-blind, placebo-controlled trial of the efficacy of finasteride for the prevention of prostate cancer with a primary outcome of histologically determined prevalence of prostate cancer at the end of 7 years. METHODS: A systematic modeling process using logistic regression identified factors available at year 6 that are associated with end-of-study (EOS) biopsy adherence at year 7, stratified by whether participants were ever prompted for a prostate biopsy by year 6. Final models were evaluated for discrimination. At year 6, 13,590 men were available for analysis. RESULTS: Participants were more likely to have the EOS biopsy if they were adherent to study visit schedules and procedures and/or were in good health (P < 0.01). Participants at larger sites and/or sites that received retention and adherence grants were also more likely to have the EOS biopsy (P < 0.05). CONCLUSIONS: Our results show good adherence to study requirements 1 year before the EOS biopsy was associated with greater odds that a participant would comply with the invasive EOS requirement. IMPACT: Monitoring adherence behaviors may identify participants at risk of nonadherence to more demanding study end points. Such information could help frame adherence intervention strategies in future trials.

Variation in breast cancer subtypes with age and race/ethnicity.

BACKGROUND: Both age and race have been identified as independent predictors of breast cancer subtype but the association of age with subtype within each race is not well understood. This study assesses the association of age with the eight breast cancer subtypes as defined by ER/PR/HER2 among white, African-American, Hispanic, and Asian/Pacific Islander women. METHODS: This study included 69,358 women with primary invasive breast cancer. Logistic regression was used to assess the association of age with each of the ER/PR/HER2 subtypes for each race adjusted for socioeconomic status, stage, grade, and tumor size. RESULTS: The odds of African-American women having a triple-negative tumor were not statistically significantly increased for women under 46 when compared to the African-American women aged 46-69 (OR=0.96; 95% CI=0.80-1.16). A similar pattern was observed for the ER-/PR-/HER2+ subtype. Hispanic women under age 46 (OR=0.83; 95% CI=0.71-0.97) and over age 70 (OR=0.71; 95% CI=0.57-0.89) were less likely to have the ER-/PR-/HER2+ subtype. Asian/Pacific Islander women under age 46 also had reduced odds (OR=0.67; 95% CI=0.55-0.82) of the ER-/PR-/HER2+ subtype. CONCLUSIONS: The ER/PR/HER2 subtypes vary with age and differences in this variation depend on race. It is important to define breast cancer using the ER/PR/HER2 subtype and the significance of age and race should not be overlooked.

The role of human epidermal growth factor receptor 2 in the survival of women with estrogen and progesterone receptor-negative, invasive breast cancer: the California Cancer Registry, 1999-2004.

BACKGROUND: Breast cancers that are negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) (triple negative [TN]) have been associated with high-grade histology, aggressive clinical behavior, and poor survival. It has been determined that breast cancers that are negative for ER and PR but positive for HER2 (double negative [DN]) share features with TN breast cancers. In this report, the authors quantified the contribution of HER2 as well as demographic and tumor characteristics to the survival of women with TN tumors, DN tumors, and other breast cancers (OBC). METHODS: In total, 61,309 women who were diagnosed with invasive breast cancer between 1999-2004 were identified in the California Cancer Registry. Demographic and tumor characteristics of women with TN tumors were compared with those from women with DN tumors and women with OBC. A compound proportional hazards regression analysis (PHPH) (a generalization of the Cox proportional hazards model) was used to model these characteristics. RESULTS: Women with TN tumors were younger, African American, Hispanic, and of lower socioeconomic status (SES), whereas women with DN tumors were slightly older; African American, and Asian/Pacific Islander. Women with TN and DN tumors presented with larger, higher grade, and higher stage than women with OBC. Survival among women with TN tumors was poorer compared with that among women with OBC but was nearly the same as that of women with DN tumors. Results of the regression analysis indicated that disease stage, tumor grade, SES, and race/ethnicity were significant risk factors for survival. Negative ER and PR status was associated with an increased risk of death. There was a small but significant difference in both long-term and short-term survival patients who had TN tumors compared with patients who had DN tumors. CONCLUSIONS: Patients with TN tumors shared many clinical, demographic, and tumor features and had survival that was very similar survival to that of patients with DN tumors, and survival for both groups contrasted greatly with survival for patients with OBC. Disease stage, tumor grade, SES, race/ethnicity, negative ER and PR status, rather than negative HER2 status, were risk factors for survival.

Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry.

BACKGROUND: Tumor markers are becoming increasingly important in breast cancer research because of their impact on prognosis, treatment, and survival, and because of their relation to breast cancer subtypes. The triple-negative phenotype is important because of its relation to the basal-like subtype of breast cancer. METHODS: Using the population-based California Cancer Registry data, we identified women diagnosed with triple-negative breast cancer between 1999 and 2003. We examined differences between triple-negative breast cancers compared with other breast cancers in relation to age, race/ethnicity, socioeconomic status (SES), stage at diagnosis, tumor grade, and relative survival. RESULTS: A total of 6370 women were identified as having triple-negative breast cancer and were compared with the 44,704 women with other breast cancers. Women with triple-negative breast cancers were significantly more likely to be under age 40 (odds ratio [OR], 1.53), and non-Hispanic black (OR, 1.77) or Hispanic (OR, 1.23). Regardless of stage at diagnosis, women with triple-negative breast cancers had poorer survival than those with other breast cancers, and non-Hispanic black women with late-stage triple-negative cancer had the poorest survival, with a 5-year relative survival of only 14%. CONCLUSIONS: Triple-negative breast cancers affect younger, non-Hispanic black and Hispanic women in areas of low SES. The tumors were diagnosed at later stage and were more aggressive, and these women had poorer survival regardless of stage. In addition, non-Hispanic black women with late-stage triple-negative breast cancer had the poorest survival of any comparable group.

Incidence, cost, and mortality of neutropenia hospitalization associated with chemotherapy.

BACKGROUND: Neutropenia is a common side effect of chemotherapy, often requiring hospitalization for treatment of severe cases. Neutropenia hospitalization (NH) rates have been reported in individual studies, but national estimates are needed. METHODS: Chemotherapy-induced NHs were identified in the 1999 hospital discharge data bases from 7 states. Cancer and chemotherapy prevalence data from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program and the National Cancer Data Base were used to calculate national NH rates for 13 cancer types. NH cost was estimated by multiplying charges by institution-specific, cost-to-charge ratios from the 1999 Centers for Medicare and Medicaid Services Hospital Cost Report. NH incidence was projected to national levels using population data from the United States Census and the Centers for Disease Control and Prevention. RESULTS: There were 20,780 discharges with documentation of cancer, chemotherapy, and neutropenia identified. Projecting to national levels, NH incidence was estimated at 60,294 cases (7.83 cases per 1000 cancer patients). The mean NH cost was 13,372 dollars. The mortality rate among patients with NH was estimated at 6.8% or 1 death for every 14 hospitalized patients. Among 13 selected cancer types, the NH rate was 34.20 cases per 1000 patients receiving chemotherapy (1 in 29 patients). NH was particularly common in patients with hematologic tumors, with an incidence of 43.3 cases per 1000 patients with such tumors (1 in 23 patients). The average NH cost for hematologic malignancies was 20,400 dollars, more than double the cost of NH for solid tumors. CONCLUSIONS: According to the current study, NH affects > 60,000 patients with cancer each year in the United States, with an average cost of 13,372 dollars per hospitalization and an associated inpatient mortality rate of 6.8%.