Carol Parise

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

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.

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.

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.

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

Abstract:  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 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

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).

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.

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.

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

BackgroundThe 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.MethodsUsing 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 DiscussionThere 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.ConclusionThe 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.

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

BackgroundRacial 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.MethodsWe 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.ResultsStage 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.ConclusionsWhen 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

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.

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.