Risk Of Breast Cancer-specific Mortality Research Articles

Disparities in breast cancer characteristics and outcomes by race/ethnicity

Disparities in breast cancer stage and mortality by race/ethnicity in the United States are persistent and well known. However, few studies have assessed differences across racial/ethnic subgroups of women broadly defined as Hispanic, Asian, or Pacific Islander, particularly using more recent data. Using data from 17 population-based cancer registries in the Surveillance, Epidemiology, and End Results (SEER) program, we evaluated the relationships between race/ethnicity and breast cancer stage, hormone receptor status, treatment, and mortality. The cohort consisted of 229,594 women 40-79 years of age diagnosed with invasive breast carcinoma between January 2000 and December 2006, including 176,094 non-Hispanic whites, 20,486 Blacks, 15,835 Hispanic whites, 14,951 Asians, 1,224 Pacific Islanders, and 1,004 American Indians/Alaska Natives. With respect to statistically significant findings, American Indian/Alaska Native, Asian Indian/Pakistani, Black, Filipino, Hawaiian, Mexican, Puerto Rican, and Samoan women had 1.3-7.1-fold higher odds of presenting with stage IV breast cancer compared to non-Hispanic white women. Almost all groups were more likely to be diagnosed with estrogen receptor-negative/progesterone receptor-negative (ER-/PR-) disease with Black and Puerto Rican women having the highest odds ratios (2.4 and 1.9-fold increases, respectively) compared to non-Hispanic whites. Lastly, Black, Hawaiian, Puerto Rican, and Samoan patients had 1.5-1.8-fold elevated risks of breast cancer-specific mortality. Breast cancer disparities persist by race/ethnicity, though there is substantial variation within subgroups of women broadly defined as Hispanic or Asian. Targeted, multi-pronged interventions that are culturally appropriate may be important means of reducing the magnitudes of these disparities.

Gene promoter methylation is associated with increased mortality among women with breast cancer

To better understand breast cancer etiology and progression, we explored the association between promoter methylation status of three breast cancer-related genes (BRCA1, APC, and p16) and survival in a large cohort of women with breast cancer. About 800 archived tumor tissues were collected from women diagnosed with a first primary invasive or in situ breast cancer in 1996-1997. The vital status of the participants was followed through the end of year 2005 with a mean follow-up time of 8.0 years. Promoter methylation was assessed by methylation-specific PCR (for BRCA1) and MethyLight (for APC and p16). The association of promoter methylation and breast cancer mortality was evaluated by Cox-proportional hazards models. Methylated promoters were found in 59.0, 48.4, and 3.6% of the tumor samples for BRCA1, APC, and p16, respectively. Breast cancer-specific mortality was strongly associated with promoter methylation of p16 [HR and 95% CI: 3.53 (1.83-6.78)], whereas the associations with of BRCA1 and APC were less pronounced [HR and 95% CI: 1.81 (1.18-2.78) and 1.46 (0.98-2.17), respectively]. Similar associations were observed with all-cause mortality. As the number of methylated genes increased, the risk of breast cancer-specific mortality also increased in a dose-dependent manner (P, trend = 0.01). Importantly, even with our results stratified by hormone receptor status, promoter methylation of the three genes remained predictive of mortality. Our results suggest that promoter methylation could be promising epigenetic markers to be considered for breast cancer survival.

Geriatric assessment in older patients with breast cancer.

Most cases of breast cancer are diagnosed in older adults. Older women have an increased risk for breast cancer-specific mortality and are at higher risk for treatment-associated morbidity than younger women. However, they are also less likely to be offered preventive care or adjuvant therapy for this disease. Major gaps in evidence exist regarding the optimal evaluation and treatment of older women with breast cancer because of significant underrepresentation in clinical trials. Chronologic age alone is an inadequate predictor of treatment tolerance and benefit in this heterogeneous population. Multiple issues uniquely associated with aging impact cancer care, including functional impairment, comorbidity, social support, cognitive function, psychological state, and financial stress. Applying geriatric principles and assessment to this older adult population would inform decision making by providing estimates of life expectancy and identifying individuals most vulnerable to morbidity. Ongoing research is seeking to identify which assessment tools can best predict outcomes in this population, and thus guide experts in tailoring treatments to maximize benefits in older adults with breast cancer.

BRCA1 promoter methylation is associated with increased mortality among women with breast cancer

Promoter-CpG island hypermethylation has been proposed as an alternative mechanism to inactivate BRCA1 in the breast where somatic mutations of BRCA1 are rare. To better understand breast cancer etiology and progression, we explored the association between BRCA1 promoter methylation status and prognostic factors as well as survival among women with breast cancer. Promoter methylation of BRCA1 was assessed in 851 archived tumor tissues collected from a population-based study of women diagnosed with invasive or in situ breast cancer in 1996-1997, and who were followed for vital status through the end of 2002. About 59% of the tumors were methylated at the promoter of BRCA1. The BRCA1 promoter methylation was more frequent in invasive cancers (P = 0.02) and among premenopausal cases (P = 0.05). BRCA1 promoter methylation was associated with increased risk of breast cancer-specific mortality (age-adjusted HR 1.71; 95% CI: 1.05-2.78) and all-cause mortality (age-adjusted HR 1.49; 95% CI: 1.02-2.18). Neither dietary methyl intakes in the year prior to the baseline interview nor the functional polymorphisms in one-carbon metabolism were associated with BRCA1 methylation status. Our study is the first epidemiological investigation on the prognostic value of BRCA1 promoter methylation in a large population-based cohort of breast cancer patients. Our results indicate that BRCA1 promoter methylation is an important factor to consider in predicting breast cancer survival.

Impact of Treatment and Socioeconomic Status on Racial Disparities in Survival Among Older Women With Breast Cancer

To examine racial/ethnic disparities in mortality and survival in a large nationwide and population-based cohort of women with breast cancer after simultaneously controlling for differences in comorbidity, treatment, and socioeconomic status. A cohort of 35,029 women with stage I-IIIA breast cancer at age > or = 65 from 1992 to 1999 was identified from the surveillance, epidemiology, and end results-medicare linked databases with up to 11 years of follow-up. Cox proportional hazard regression analysis was performed to determine the risk of all-cause and breast cancer-specific mortality. African-American women with breast cancer were more likely to live in the poorest quartiles of socioeconomic status at the census tract level than whites (73.7% versus 20.7%, P < 0.001). Those living in communities with the lowest socioeconomic status were 11% more likely to die than those in the highest (hazard ratio, 1.10; 95% confidence interval, 1.04-1.16). The risk of dying changed slightly after controlling for race/ethnicity (1.11; 1.05-1.18). Compared with white women with breast cancer, crude hazard ratios of all-cause and breast cancer-specific mortality were 1.35 (1.27-1.45) and 1.83 (1.56-2.16) for African-Americans. After adjusting for treatment and socioeconomic status, hazard ratio of all-cause mortality was no longer significant in African-Americans (1.02; 0.84-1.10), whereas the risk of breast cancer-specific mortality was marginally higher in African-Americans (1.21; 1.01-1.46). Racial disparities in overall survival between African-American and white women with breast cancer were not present after controlling for treatment and socioeconomic status. Efforts to eliminate these barriers have important public health implications for reducing disparities in health outcomes.

Hormone receptor status, tumor characteristics, and prognosis: a prospective cohort of breast cancer patients

BackgroundBreast cancer patients with tumors that are estrogen receptor (ER)-positive and/or progesterone receptor (PR)-positive have lower risks of mortality after their diagnosis compared to women with ER- and/or PR-negative disease. However, few studies have evaluated variations in the risks of breast cancer-specific mortality across ER/PR status by either demographic or clinical characteristics.MethodsUsing data from 11 population-based cancer registries that participate in the SEER (Surveillance, Epidemiology, and End Results) program, 155,175 women at least 30 years old with a primary diagnosis of invasive breast carcinoma from 1990 to 2001 were included in the study. Associations between joint hormone receptor status and breast cancer mortality risk within categories of diagnosis age, diagnosis year, race/ethnicity, histologic tumor type, stage, grade, size, and axillary lymph node status were evaluated using the Cox proportional hazards model.ResultsCompared to ER+/PR+ cases, elevations in risk of mortality were observed across all subcategories of age at diagnosis, ranging from 1.2- to 1.5-fold differences for ER+/PR- cases, 1.5- to 2.1-fold differences for ER-/PR+ cases, and 2.1- to 2.6-fold differences for ER-/PR- cases. Greater differences were observed in analyses stratified by grade; among women with low-grade lesions, ER-/PR- patients had a 2.6-fold (95% confidence interval [CI] 1.7 to 3.9) to 3.1-fold (95% CI 2.8 to 3.4) increased risk of mortality compared to ER+/PR+ patients, but among women with high-grade lesions, they had a 2.1-fold (95% CI 1.9 to 2.2) to 2.3-fold (95% CI 1.8 to 2.8) increased risk.ConclusionCompared to women with ER+/PR+ tumors, women with ER+/PR-, ER-/PR+, or ER-/PR- tumors experienced higher risks of mortality, which were largely independent of the various demographic and clinical tumor characteristics assessed in this study. The higher relative mortality risks identified among ER-/PR- patients with small or low-grade tumors raise the question of whether there may be a beneficial role for adjuvant chemotherapy in this population.