Increased Breast Cancer Mortality Research Articles

Estrogen Plus Progestin and Breast Cancer Incidence and Mortality in the Women’s Health Initiative Observational Study

In the Women's Health Initiative (WHI) randomized trial, estrogen plus progestin increased both breast cancer incidence and mortality. In contrast, most observational studies associate estrogen plus progestin with favorable prognosis breast cancers. To address differences, a cohort of WHI observational study participants with characteristics similar to the WHI clinical trial was studied. We identified 41 449 postmenopausal women with no prior hysterectomy and mammogram negative within 2 years who were either not hormone users (n = 25 328) or estrogen and progestin users (n = 16 121). Multivariable-adjusted Cox proportional hazard regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CI). All statistical tests were two-sided. After a mean of 11.3 (SD = 3.1) years, with 2236 breast cancers, incidence was higher in estrogen plus progestin users than in nonusers (0.60% vs 0.42%, annualized rate, respectively; HR = 1.55, 95% CI = 1.41 to 1.70, P < .001). Women initiating hormone therapy closer to menopause had higher breast cancer risk with linear diminishing influence as time from menopause increased (P < .001). Survival after breast cancer, measured from diagnosis, was similar in combined hormone therapy users and nonusers (HR = 1.03, 95% CI = 0.79 to 1.35). On a population basis, there were somewhat more deaths from breast cancer, measured from cohort entry (HR = 1.32, 95% CI = 0.90 to 1.93, P = .15), and more all-cause deaths after breast cancer (HR = 1.65, 95% CI = 1.29 to 2.12, P < .001) in estrogen plus progestin users than in nonusers. Consistent with WHI randomized trial findings, estrogen plus progestin use is associated with increased breast cancer incidence. Because prognosis after diagnosis on combined hormone therapy is similar to that of nonusers, increased breast cancer mortality can be expected.

Insufficient sleep associated with increased breast cancer mortality

To the Editor: Restless legs syndrome (RLS) is a neurological condition that ocTo the Editor Sleep disturbance increases the risk for breast cancer. For example, Kazizaki et al. [1] reported that women with short sleep duration had a higher risk of breast cancer, compared to women who slept 7 hours per day. However , little is known about sleep disturbance and breast cancer mortality. In our analysis, we assessed the risk of breast cancer death associated with insufficient sleep. Age adjusted data on sleep disturbance in the 50 states in the United States as well as the District of Columbia are from perceived insufficient rest or sleep among adults – United States, 2008 [2]. Age adjusted breast cancer mortality is from American Cancer Society Cancer Facts and Figures [3]. Data on race by state are from the 2010 US census. There was a significant correlation between percentage of persons who reported insufficient sleep everyday in the preceding 30 days versus breast cancer mortality in the 50 states in the United States as well as the District of Columbia (p = 0.013). Because breast cancer survival is higher in white women than black women [4], multiple linear regression was performed . The association of insufficient sleep everyday in the preceding 30 days with breast cancer mortality was significant (p = 0.01) and unrelated to the percentage in the white population (p = 0.114). Studies suggest that melatonin is involved in the relationship of sleep and breast cancer, and melatonin exerts an antiproliferativ e effect on breast cancer cells [5]. Moreover, breast cancer has become more prevalent for reasons that are poorly understood. Likewise, prevalen ce of sleeping difficulties and sleepiness has increased; whereas, sleep duration per night has decrease d. These sleep aberrations may be putting more women at risk for death from breast cancer.

TENDÊNCIA DA MORTALIDADE POR CÂNCER DE MAMA FEMININA NO ESTADO DA BAHIA, BRASIL, DE 1980 A 2007

O câncer de mama, doença crônica com repercussões orgânicas, econômicas e psicossociais, é a principal doença neoplásica do sexo feminino, tanto em países desenvolvidos quanto naqueles em desenvolvimento, e constitui-se em problema de saúde pública de dimensões mundiais. O objetivo deste estudo é descrever a tendência da taxa de mortalidade por câncer de mama feminina no estado da Bahia de 1980 a 2007. Os dados sobre os óbitos e sobre a população foram obtidos no SIM/Datasus e no IBGE/Datasus, respectivamente. Calcularam-se as taxas de mortalidade por faixa etária, taxas brutas e taxas padronizadas por idade, ajustadas pelo número de óbitos por causa mal definida. Para a análise da tendência temporal, utilizou-se a regressão de Poisson, com avaliação de superdispersão. Os resultados apontam que, em Salvador, a taxa bruta teve um aumento médio anual de 1,13% e a taxa padronizada, uma redução de 0,34%. A inspeção da curva revela um incremento de 0,46% até 1997 e uma redução de 2,33% desse ano em diante. Observou-se uma tendência crescente de 1,39% na faixa etária de 20 a 49. Entre as mulheres com idade maior ou igual a 50 anos ocorreu uma redução de 2,73% a partir de 1997. No estado da Bahia, as taxas de mortalidade padronizadas variaram de 4,71/100.000 em 1980 a 7,92/100.000 em 2007. Observou-se um aumento de 2,70% na taxa não padronizada por idade, ajustada pelo número de óbitos por causa mal definida. A taxa padronizada experimentou um aumento médio anual de 1,52%. As taxas ajustadas pelo número de óbitos por causa mal definida entre as mulheres abaixo e acima de 50 anos tiveram um incremento de 3,02% e de 2,45%, respectivamente. Concluiu-se que se verifica um aumento gradativo da mortalidade por câncer de mama feminina na Bahia e uma discreta tendência à redução na cidade de Salvador. Um período maior de observação será necessário para a verificação da manutenção dessas tendências.

Abstract P2-11-17: Pilot Study to Evaluate a Home-based Exercise and Weight Loss Intervention on Cardiopulmonary Fitness and Markers of Breast Cancer Risk in Postmenopausal Breast Cancer Survivors

Abstract Background: BrCa survivors have an estimated 4-fold increase in risk for developing cardiovascular disease compared to women never treated for breast cancer and a nearly 3-fold increase in breast cancer mortality in women with an exercise capacity (VO2max) less than 28mL kg−1 min−1. Cardiac events are the second most common cause of death in long-term breast cancer (BrCa) survivors. Purpose: We conducted a study to investigate the effects of standard exercise or structured exercise on targeted cardiovascular outcomes during a home-based diet and exercise intervention for breast cancer survivors. Method: Cross-sectional within- and between-group design. A total of 19 breast cancer survivors, average age of 52.6+/−9.3, were enrolled in the study. A convenient sample was enrolled into two exercise groups receiving either: standard (150 minutes per week of usual care (exercise without instruction) cardiovascular exercise + resistance training) or structured (150 minutes per week of gradual increased intensity cardiovascular exercise + resistance training) exercise instruction along with a group based behavioral weight loss intervention. All participants underwent baseline and 17 week assessments including maximal exercise testing (VO2max and minutes on the treadmill), measurements of body composition (weight, BMI, % body fat), and assessment of quality of life. Results: We report on the 16 participants who completed the baseline and 17 week assessments (9 = Standard Exercise Group; 7 = Structured Exercise Group). The structured exercise group exhibited significantly greater improvements in measures of cardiorespiratory fitness: VO2max (p = 0.05) and duration on treadmill (p = 0.02). No significant differences were noted for all other cardiorespiratory fitness testing outcomes. Significant improvements from baseline to 17 weeks were seen across both groups for all measures of body composition. Lean body mass did not significantly change from baseline to 17 weeks in both groups. There were no significant between group differences for change in body composition. Conclusion: In this study, both standard exercise and structured exercise improved CR fitness measured by VO2max, but the structured exercise group experienced significantly greater improvements. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-11-17.

Decreasing 25‐hydroxy‐vitamin D levels account for portion of the effect of increasing body mass index on breast cancer mortality

Increased body mass index (BMI) and decreased serum vitamin D are both known to be associated with increased mortality from breast cancer. However, vitamin D levels are lower in obese individuals in general. Recent studies have sought to determine whether serum vitamin D levels can account for some of the association between higher BMI and increased risk for breast cancer and found that low vitamin D levels in the overweight and obese account for up to 40% of the BMI-attributable risk of developing breast cancer. Here we reviewed the literature to determine if a similar relationship exists between vitamin D, BMI, and breast cancer mortality. Utilizing previously reported independent associations of low vitamin D and high BMI to increases in breast cancer mortality, as well as the known decrement in vitamin D per unit increase in BMI, we estimated that low vitamin D levels may be responsible for roughly 16% of the increased mortality from breast cancer in overweight and obese patients. Although this is a relatively small proportion of the effect of obesity, supplements to increase serum vitamin D levels may represent a way to reduce obesity-associated disparities in breast cancer mortality.

Abstract B49: Demographic differences in African American compared to Caucasian women with luminal A breast cancer.

Abstract Background: In a recent study, the Carolina Breast Cancer Study found that mortality rates were significantly higher in African American women (AAW) compared to Caucasian women (CW) with luminal A breast cancer. This disparity may be attributable to social and/or molecular differences. Here, we evaluated demographic data from AAW and CW with luminal A breast cancer to determine whether any factors differ between populations. Methods: The database of the Clinical Breast Care Project was queried to identify all AAW (n=115) and CW patients (n=596) with ER+/HER2- breast cancer. Demographic data recorded at the time of diagnosis were compared between populations using chi-square or Student's t-test. A cutoff of P&amp;lt;0.05 was used to define significance. Results: Age at diagnosis or menarche, parity, breastfeeding, education levels, exercise, fat intake, smoking and presence of heart disease and diabetes did not differ significantly between populations. Significantly more AAW began using oral contraceptives and were parous before age 18 (28% and 16%) compared to CW (7% and 4%). AAW were more likely to be obese (51% compared to 29%) and to perform at least monthly breast self-exams (97% compared to 80%) and to have hypertension (50% compared to 40%). AAW consumed significantly lower levels of caffeine (439mg/day compared to 983 mg/day) and alcohol (43% compared to 21% non-drinkers) than CW and were less likely to be married (52% compared to 74%). Pathologically, tumors from AAW and CW did not differ for stage or lymph node status, however, luminal A tumors from AAW were significantly more likely to be poorly-differentiated (25% compared to 14%) and were larger (33% compared to 21%) than those from CW. Discussion: Although luminal A tumors are considered the most favorable breast tumor subtype, ER+/HER2- tumors from AAW were larger and of higher grade than those from CW. It is not clear how differences in caffeine and alcohol consumption may impact outcome in women with luminal A breast tumors, however, use of oral contraceptives during adolescence, pregnancy at an early age (&amp;lt;20 years) and increased inflammation in the breasts of obese women have been associated with higher grade and poorer prognosis. In addition, women who are married have a more favorable prognosis than those who are single, divorced or widowed and patients with hypertension has been associated with increased breast cancer mortality. Together, these demographic factors may contribute to the outcome disparity detected in AAW compared to CW with luminal A breast cancer. Citation Format: Rachel E. Ellsworth, Craig D. Shriver. Demographic differences in African American compared to Caucasian women with luminal A breast cancer. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr B49.

Trends in mortality from cancers of the breast, colon, prostate, esophagus, and stomach in East Asia

Although substantial nutrition transition, characterized by an increased intake of energy, animal fat, and red meats, has occurred during the last several decades in East Asia, few studies have systematically evaluated temporal trends in cancer incidence or mortality among populations in this area. Therefore, we sought to investigate this question with tremendous public health implications. Data on mortality rates of cancers of the breast, colon, prostate, esophagus, and stomach for China (1988-2000), Hong Kong (1960-2006), Japan (1950-2006), Korea (1985-2006), and Singapore (1963-2006) were obtained from WHO. Joinpoint regression was used to investigate trends in mortality of these cancers. A remarkable increase in mortality rates of breast, colon, and prostate cancers and a precipitous decrease in those of esophageal and stomach cancers have been observed in selected countries (except breast cancer in Hong Kong) during the study periods. For example, the annual percentage increase in breast cancer mortality was 5.5% (95% confidence interval: 3.8, 7.3%) for the period 1985-1993 in Korea, and mortality rates for prostate cancer significantly increased by 3.2% (95% confidence interval: 3.0, 3.3%) per year from 1958 to 1993 in Japan. These changes in cancer mortality lagged ∼ 10 years behind the inception of the nutrition transition toward a westernized diet in selected countries or regions. There have been striking changes in mortality rates of breast, colon, prostate, esophageal, and stomach cancers in East Asia during the last several decades, which may be at least in part attributable to the concurrent nutrition transition.

PS1-05: Disparities in Breast Cancer Survival by Molecular Subtype and Race/Ethnicity

Background/AimsLittle information exists on breast cancer survival rates according to molecular profiles among different race/ethnic groups. We investigated the impact of molecular subtypes on breast cancer-specific survival by race/ethnicity in a large group of medically-insured women diagnosed with breast cancer.MethodsThe cohort included 20,749 diverse Kaiser Permanente Southern California (KPSC) women diagnosed with breast cancer (AJCC Stage 0?IV) between 1996 and 2007, and followed through 2009. The women?s cancers were classified into four main molecular subtypes: luminal A (ER+ and/or PR+/HER2?); luminal B (ER+ and/or PR+/HER2+); basal-like (?triple negative?, ER?/PR?/HER2?); and HER2+/ER?. The outcome was breast cancer mortality. Follow-up began on the date of surgery and ended on date of death, health plan disenrollment, or study?s end. Hazard rate ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models. We adjusted for age, tumor characteristics, cancer treatments, income, and comorbidity.ResultsOf the 20,749 women, 65% were white non-Hispanic (n=13,487); 13% Black (n=2,697); 12% Hispanic (n=2,490); and 10% Asian (n=2,075). We observed 2,019 deaths (10%) deaths due to breast cancer over 14 years of follow-up. In all race/ethnic groups combined, breast cancer mortality was higher in women with basal-like (HR 2.90, 2.38?3.53) and HER2+/ER? (HR 1.98, 1.55?2.54) tumors compared to women with luminal A subtype (referent group). In addition, we examined breast cancer mortality in each molecular subtype, stratified by race/ethnic group. Among women with luminal A tumors, Black women were more likely to die of breast cancer (HR 1.53, 1.02?2.29) than white women (referent group). In women with luminal B tumors, South Asians had a 10-fold increase in breast cancer mortality (HR=10.57, 1.42?78.64) compared to whites; however, numbers were small and the confidence interval was wide. Among women with basal-like tumors, Black women had a greater mortality risk (HR 1.36, 1.02?1.82) compared to white women. In women with HER2+/ER? tumors, breast cancer mortality was similar across the race/ethnic groups. No other comparisons were significant.DiscussionDespite similar access to healthcare, we found survival disparities by race/ethnic groups within the luminal A, luminal B, and basal-like molecular subtypes of breast cancer.

Mortality study of chemical workers exposed to dioxins: follow-up 23 years after chemical plant closure

ObjectivesTo examine the long-term effects of dioxin-exposure, particularly with regard to cancer mortality, in a follow-up 23 years after closure of the chemical plant (Hamburg, Germany).MethodsThe study comprised all persons...

Estrogen plus progestin (E+P) and breast cancer incidence and mortality.

1501 Background: In the WHI clinical trial, E+P increased both breast cancer incidence and breast cancer mortality (JAMA 2010;304:1684). In contrast, breast cancers associated with E+P use in most observational studies have a more favorable prognosis. To address differences, a cohort of WHI Observational Study participants with characteristics similar to the WHI clinical trial was identified to examine E+P association with invasive breast cancer incidence and outcome. Methods: 41,449 postmenopausal women with no prior hysterectomy and mammogram negative for breast cancer &lt; 2 years before who either were not hormone users (25,328) or were using E+P (16,121) were identified. Breast cancers were verified by centralized medical record review. Adjusted Cox proportional hazard regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CI). Additional analyses adjusted for breast cancer screening, censoring participants for incidence analyses who had a &gt; 2 year interval without a mammogram. Results: After a mean (SD) follow-up 11.3 (3.1) years, 2,236 breast cancers were diagnosed. Breast cancer incidence was higher in E+P users (0.60% vs 0.42%, annualized rate, respectively: HR 1.55, 95% CI 1.41-1.70, P&lt;0.001). Screening adjusted analyses had stronger breast cancer association (0.63% vs 0.39%, HR 1.72, 95% CI 1.54-1.93; P&lt;0.001). Survival following breast cancer, measured from diagnosis date, was similar in E+P users and non-users (HR 0.95, 95% CI 0.74-1.23). Breast cancer mortality, analyzed from cohort entry date, are shown in the table. Conclusions: E+P use is associated with increased breast cancer incidence. As breast cancer prognosis following diagnosis on E+P is similar to that of nonusers, the higher incidence with E+P leads to increased breast cancer mortality. [Table: see text]

Abstract 3580: Pre-diagnostic alcohol consumption and breast cancer recurrence and survival in postmenopausal women

Abstract Introduction: Alcohol consumption has been consistently associated with breast cancer risk. However, studies on its association with breast cancer survival produced inconsistent results. Methods: We assessed the association of alcohol consumption (in four categories &amp;lt;0.5 g/d, 0.5 to &amp;lt;6.0 g/d, 6.0 to &amp;lt;12.0 g/d, α12.0 g/d, and continuous) with survival and recurrence in a prospective cohort study in Germany of 2,706 postmenopausal breast cancer patients aged 50-74 years after excluding those with previous cancer and/or missing information on alcohol intake. Patients were diagnosed between 2001 and 2005 and vital status, causes of death, and recurrences were verified through the end of 2009. Delayed-entry Cox proportional hazards models were stratified by age at diagnosis and study centre and adjusted for other prognostic factors. Fractional polynomials were used to assess the true dose-response relation for alcohol consumption. Results: Women were enrolled in the study a median time of 105 days after diagnosis. Median follow-up times from recruitment until death/censoring or recurrence/censoring were 5.5 years and 5.6 years, respectively. Overall, 326 deaths occurred, 239 (73.3%) due to breast cancer. Further causes of death were other cancers (n=41, 12.6%), cardiovascular disease (n=22, 6.7%), and other causes (n=24, 7.4%). Of the 2,199 patients with stage I to IIIa disease and available data on recurrence status, 250 had a breast cancer recurrence. Alcohol consumption ≤ 12 g/day compared to &amp;lt; 0.5 g/day was linearly associated with a statistically significantly higher breast cancer mortality (HR, 1.71; 95% CI, 1.12 to 2.62; P for trend = 0.03). Results were no longer statistically significant when restricted to Stage I-IIIa patients (HR, 1.28; 95% CI, 0.75 to 2.20). There was no effect modification by body mass index, hormone replacement therapy use, and estrogen receptor status. Alcohol consumption ≤ 12 g/day was not associated with overall mortality (HR, 1.27; 95% CI, 0.90 to 1.80) and mortality due to other causes (HR, 0.73; 95% CI, 0.38 to 1.42). Also, no association with breast cancer recurrence was found (HR, 1.05; 95% CI, 0.71 to 1.56). Conclusion: Consumption of more than 12 g alcohol (equivalent to one alcoholic drink) per day is associated with increased breast cancer mortality but not with breast cancer recurrence. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3580. doi:1538-7445.AM2012-3580

Envejecimiento y alta prevalencia de estadios avanzados determinan la creciente mortalidad por cáncer mamario en Chile

Aging and high prevalence of advanced stages determine the increasing breast cancer mortality in Chile Aims: To test the hypothesis that ages above 54 years not included in the national program and a greater proportion of advanced stages in the public health sector that attends 75% of the population, could explain the increasing high mortality rate for this cancer in Chile. Methods: Incidence data provided by the 29 public health services (SNSS) in the country and mortality data from the Ministry of Health were used to analyse the epidemiological situation at the biggest health service (SSMSO), 1.6 million of people, compared with the country, 16 million. Results: Breast cancer was in 2009, last year with information, the fi rst cause of on- cologic death in Chilean women with 1,338 deaths and an actual mortality rate of 15.7 per 100,000 women. Deaths for gallbladder and gastric cancers were 1,295 and 1,150 respectively. Mortality for breast cancer in 2009 was 10.4 in the SSMSO. Less advanced stages with a proportion of about 20% compared with the country (30%) and more prevalent older ages were observed in this health service. Conclusions: Hypothesis is true. Targets of extended age and decreasing of less advanced stages for the country emerge from this study. To integrate levels of medical care in the SNSS and to include examination of breasts jointly with free diagnostic mammographies in women above 54 years old ordered by the nurses responsibles at the national programs of diabetes mellitus and arterial hypertension are recommended aiming to increase compliance of secondary prevention in breast cancer.

Changing concepts: Menopausal hormone therapy and breast cancer.

Hormone therapy is still used by millions of women for menopausal symptoms. Concerns regarding hormone therapy and breast cancer were initially based on case reports and retrospective case-control studies. However, recent results from large prospective cohort studies and the Women's Health Initiative (WHI) randomized placebo-controlled hormone therapy trials have substantially changed concepts regarding how estrogen alone and estrogen plus progestin influence breast cancer. The preponderance of observational studies suggested that estrogen alone and estrogen plus progestin both increased the risk of breast cancer, with cancers commonly diagnosed at an early stage. However, substantially different results emerged from the WHI randomized hormone therapy trials. In the WHI trial evaluating estrogen plus progestin in postmenopausal women with an intact uterus, combined hormone therapy statistically significantly increased the risk of breast cancer and hindered breast cancer detection, leading to delayed diagnosis and a statistically significant increase in breast cancer mortality. By contrast, estrogen alone use by postmenopausal women with prior hysterectomy in the WHI trial did not substantially interfere with breast cancer detection and statistically significantly decreased the risk of breast cancer. Differential mammography usage patterns may explain differences between observational study and randomized trial results. In clinical practice, hormone therapy users have mammograms more frequently than nonusers, leading to more and earlier stage cancer detection. By contrast, in the WHI randomized trials, mammogram frequency was protocol mandated and balanced between comparison groups. Currently, the different effects of estrogen plus progestin vs estrogen alone on breast cancer are not completely understood.

Cigarette Smoke and Breast Cancer Stem Cells

Copyright: © 2012 Kanda Y. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Epidemiological studies have suggested that cigarette smoking is related to increased breast cancer risk. In agreement with this, clinical studies indicated that smoking increases breast cancer mortality and the incidence of metastasis from the breasts to the lungs [1,2]. Cigarette smoke contains over 4000 different chemicals, many of which are toxic and carcinogenic in a variety of cells, including breast epithelial cells [3]. Among them, nicotine is considered to be related to increased cancer risk. For example, nicotine has been shown to induce resistance to the chemotherapeutic drug doxorubicin in human MCF-7 breast cancer cells [4]. Moreover, this compound has been shown to release vascular endothelial growth factor, which plays a key role in angiogenesis [5]. However, limited experimental data support direct links between breast cancer and nicotine exposure. In addition, the mechanisms by which nicotine might promote breast cancer are not fully understood.

Residential Racial Composition, Spatial Access to Care, and Breast Cancer Mortality among Women in Georgia

We explored the association between neighborhood residential racial composition and breast cancer mortality among Black and White breast cancer patients in Georgia and whether spatial access to cancer care mediates this association. Participants included 15,256 women living in 15 metropolitan statistical areas in Georgia who were diagnosed with breast cancer between 1999 and 2003. Residential racial composition was operationalized as the percent of Black residents in the census tract. We used gravity-based modeling methods to ascertain spatial access to oncology care. Multilevel Cox proportional hazards models and mediation analyses were used to test associations. Black women were 1.5 times more likely to die from breast cancer than White women. Residential racial composition had a small but significant association with breast cancer mortality (hazard ratios [HRs] = 1.04-1.08 per 10% increase in the percent of Black tract residents). Individual race did not moderate this relationship, and spatial access to care did not mediate it. Residential racial composition may be part of the socioenvironmental milieu that produces increased breast cancer mortality among Black women. However, there is a lack of evidence that spatial access to oncology care mediates these processes.

Associations of Insulin Resistance and Adiponectin With Mortality in Women With Breast Cancer

Overweight or obese breast cancer patients have a worse prognosis compared with normal-weight patients. This may be attributed to hyperinsulinemia and dysregulation of adipokine levels associated with overweight and obesity. Here, we evaluate whether low levels of adiponectin and a greater level of insulin resistance are associated with breast cancer mortality and all-cause mortality. We measured glucose, insulin, and adiponectin levels in fasting serum samples from 527 women enrolled in the Health, Eating, Activity, and Lifestyle (HEAL) Study, a multiethnic, prospective cohort study of women diagnosed with stage I-IIIA breast cancer. We evaluated the association between adiponectin and insulin and glucose levels (expressed as the Homeostatic Model Assessment [HOMA] score) represented as continuous measures and median split categories, along with breast cancer mortality and all-cause mortality, using Cox proportional hazards models. Increasing HOMA scores were associated with reduced breast cancer survival (hazard ratio [HR], 1.12; 95% CI, 1.05 to 1.20) and reduced all-cause survival (HR, 1.09; 95% CI, 1.02 to 1.15) after adjustment for possible confounders. Higher levels of adiponectin (above the median: 15.5 μg/mL) were associated with longer breast cancer survival (HR, 0.39; 95% CI, 0.15 to 0.95) after adjustment for covariates. A continuous measure of adiponectin was not associated with either breast cancer-specific or all-cause mortality. Elevated HOMA scores and low levels of adiponectin, both associated with obesity, were associated with increased breast cancer mortality. To the best of our knowledge, this is the first demonstration of the association between low levels of adiponectin and increased breast cancer mortality in breast cancer survivors.

Socioeconomic status and survival after an invasive breast cancer diagnosis

Women who live in geographic areas with high poverty rates and low levels of education experience poorer survival after a breast cancer diagnosis than women who live in communities with indicators of high socioeconomic status (SES). However, very few studies have examined individual-level SES in relation to breast cancer survival or have assessed the contextual role of community-level SES independent of individual-level SES. The authors of this report examined both individual-level and community-level SES in relation to breast cancer survival in a population-based cohort of women ages 20 to 69 years who were diagnosed with breast cancer in Wisconsin between 1995 and 2003 (N = 5820). Compared with college graduates, women who had no education beyond high school were 1.39 times more likely (95% confidence interval [CI], 1.10-1.76) to die from breast cancer. Women who had household incomes <2.5 times the poverty level were 1.46 times more likely (95% CI, 1.10-1.92) to die from breast cancer than women who had household incomes ≥5 times the poverty level. Adjusting the analysis for use of screening mammography, disease stage at diagnosis, and lifestyle factors eliminated the disparity by income, but the disparity by education persisted (hazard ratio [HR], 1.27; 95% CI, 0.99-1.61). In multilevel analyses, low community-level education was associated with increased breast cancer mortality even after adjusting for individual-level SES (HR, 1.57; 95% CI, 1.09-2.27 for ≥20% vs <10% of adults without a high school degree). The current results indicated that screening and early detection explain some of the disparity according to SES, but further research will be needed to understand the additional ways in which individual-level and community-level education are associated with survival.

CYP2C19*2 Polymorphism is Associated with Increased Survival in Breast Cancer Patients Using Tamoxifen

Variant alleles of the CYP2C19 gene were recently associated with survival in breast cancer patients on tamoxifen therapy. CYP2C19 is one of the enzymes involved in the metabolism of tamoxifen into active metabolites. We investigated the hypothesis that CYP2C19*2 and *3 variants, known for their lack of enzyme activity, are associated with an increased breast cancer mortality rate in patients using tamoxifen. In the prospective population based Rotterdam study, the association between CYP2C19*2 carriers and breast cancer mortality was studied among 80 incident users of tamoxifen. Survival was analyzed with life tables and Cox regression analysis, with drug exposure as a time-dependent variable. Adjustments were made for calendar time, average tamoxifen dose, age, the indication for tamoxifen, CYP2D6 genotype and concomitant use of CYP2C19 inhibitors or inducers. In patients on tamoxifen, CYP2C19*2 carriers were associated with a significantly longer breast cancer survival rate than patients with the wild-type (hazard ratio 0.26, 95%CI: 0.08-0.87). This study suggests that CYP2C19 genotype may possibly be a predictive factor for survival in breast cancer patients using tamoxifen.

Variation in the management of early breast cancer in rural and metropolitan centres: Implications for the organisation of rural cancer services

The study examines the management and outcomes of women with early invasive breast cancer treated in rural and metropolitan centres over a nine-year observation period. A prospective audit of the treatment and outcomes of 2081 women with early breast cancer who underwent potentially curative surgery between 1997 and 2006 in metropolitan Canberra or in the surrounding rural region was completed. Overall, there was good agreement between published guidelines and the treatment received by the women in the study. However, women treated in rural centres were less likely to receive postoperative radiotherapy after breast-conserving surgery, or to undergo axillary lymph node surgery or sentinel lymph node biopsy compared with women treated in metropolitan centres. Surgery in a rural centre was associated with increased breast cancer recurrence (HR = 1.54, p < 0.001) and increased breast cancer mortality (HR = 1.84, p < 0.001), after adjustment for age and tumour characteristics. Non-cancer related mortality was increased in women treated in rural centres compared with women travelling to a metropolitan centre for surgery (HR = 2.08; p = 0.005). There were differences in both the care provided and treatment outcomes between women treated in rural centres and women treated in metropolitan centres. However, the increased non-cancer related mortality in women treated in rural centres suggests an increased medical comorbidity in this group. Initiatives supporting rural-based surgeons to adopt new procedures such as sentinel node biopsy may help to optimise rural breast cancer treatment.

Secular trends in breast cancer mortality in five East Asian populations: Hong Kong, Japan, Korea, Singapore and Taiwan

Breast cancer risk is increasing in most Asian female populations, but little is known about the long-term mortality trend of the disease among these populations. We extracted data for Hong Kong (1979-2005), Japan (1963-2006), Korea (1985-2006), and Singapore (1963-2006) from the World Health Organization (WHO) mortality database and for Taiwan (1964-2007) from the Taiwan cancer registry. The annual age-standardized, truncated (to > or =20 years) breast cancer death rates for 11 age groups were estimated and joinpoint regression was applied to detect significant changes in breast cancer mortality. We also compared age-specific mortality rates for three calendar periods (1975-1984, 1985-1994, and 1995-2006). After 1990, breast cancer mortality tended to decrease slightly in Hong Kong and Singapore except for women aged 70+. In Taiwan and Japan, in contrast, breast cancer death rates increased throughout the entire study period. Before the 1990s, breast cancer death rates were almost the same in Taiwan and Japan; thereafter, up to 1996, they rose more steeply in Taiwan and then they began rising more rapidly in Japan than in Taiwan after 1996. The most rapid increases in breast cancer mortality, and for all age groups, were in Korea. Breast cancer mortality trends are expected to maintain the secular trend for the next decade mainly as the prevalence of risk factors changes and population ages in Japan, Korea, and Taiwan. Early detection and treatment improvement will continue to reduce the mortality rates in Hong Kong and Singapore as observed in Western countries.