Cancer-specific Mortality In Women Research Articles

Hormone replacement therapy and cancer mortality in women with 17 site-specific cancers: a cohort study using linked medical records

BackgroundThere is limited evidence on the safety of Hormone Replacement Therapy (HRT) in women with cancer. Therefore, we systematically examined HRT use and cancer-specific mortality in women with 17 site-specific cancers.MethodsWomen newly diagnosed with 17 site-specific cancers from 1998 to 2019, were identified from general practitioner (GP) records, hospital diagnoses or cancer registries in Scotland, Wales and England. Breast cancer patients were excluded because HRT is contraindicated in breast cancer patients. The primary outcome was time to cancer-specific mortality. Time-dependent Cox regression models were used to calculate adjusted hazard ratios (HR) and 95% confidence intervals (95% CIs) for cancer-specific mortality by systemic HRT use.ResultsThe combined cancer cohorts contained 182,589 women across 17 cancer sites. Overall 7% of patients used systemic HRT after their cancer diagnosis. There was no evidence that HRT users, compared with non-users, had higher cancer-specific mortality at any cancer site. In particular, no increase was observed in common cancers including lung (adjusted HR = 0.98 95% CI 0.90, 1.07), colorectal (adjusted HR = 0.79 95% CI 0.70, 0.90), and melanoma (adjusted HR = 0.77 95% CI 0.58, 1.02).ConclusionsWe observed no evidence of increased cancer-specific mortality in women with a range of cancers (excluding breast) receiving HRT.

Low thyroid hormone receptor alpha-2 (THR\u03b1-2) tumor expression is associated with unfavorable tumor characteristics and high breast cancer mortality

BackgroundThe active thyroid hormone triiodothyronine (T3) has been found to have an estrogen-like effect on breast cancer cells. Thyroid hormone receptor alpha-2 (THRα-2) acts as an antagonist for triiodothyronine (T3) signaling, and a low expression has been associated with unfavorable tumor characteristics and a higher mortality in breast cancer. However, the evidence are not conclusive. The present study evaluates tumor-specific THRα-2 expression in invasive breast cancers and its association with tumor characteristics and long-term mortality in a large population.MethodThe Malmö Diet and Cancer Study (MDCS), a population-based cohort in Sweden that included 17,035 women from 1991 to 1996, was used. Women diagnosed with breast cancer during 1991–2010 were eligible for inclusion. A tissue micro array was constructed from stored tumor material and stained for THRα-2 using immunohistochemistry. Tumors from 654 patients were scored regarding the intensity and the fraction of cells stained, then dichotomized into low or high expression. Date and cause of death were collected up until 2018-12-31. Tumor- and patient characteristics were available from the MDCS. Missing data was imputed using chained equations. Logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for low vs high expression of THRα-2 related to specific tumor factors. Mortality was evaluated with Kaplan–Meier curves and Cox regression, rendering hazard ratios (HRs). Analyses were also stratified for estrogen receptor (ER) status.ResultsWe found strong evidence of an association between low THRα-2 and unfavorable tumor characteristics, including estrogen receptor negativity: OR 4.04 (95% CI 2.28–7.15) and tumor size > 20–50 mm: OR 2.20 (95% CI 1.39–3.49). We found evidence of increased breast cancer-specific mortality for women with low THRα-2, HR 1.38 (95% CI 0.96–1.99), which remained after adjusting for age at diagnosis, HR 1.48 (95% CI 1.03–2.14), but not after adjusting for relevant prognostic factors, HR 0.98 (95% CI 0.66–1.45). THRα-2 expression in ER-negative tumors had an inverse correlation with overall mortality, HR 0.27 (95% CI 0.11–0.65).ConclusionLow tumor-specific THRα-2 expression was in this study associated with prognostically unfavorable tumor characteristics and a higher mortality in breast cancer, but not independent from other prognostic factors.

Hormone replacement therapy in women with cancer and risk of cancer-specific mortality and cardiovascular disease: a protocol for a cohort study from Scotland and Wales

BackgroundHormone replacement therapy (HRT) is widely used and has proven benefits for women with menopausal symptoms. An increasing number of women with cancer experience menopausal symptoms but the safety of HRT use in women with cancer is unclear. There are particular concerns that HRT could accelerate cancer progression in women with cancer, and also that HRT could increase the risk of cardiovascular disease in such women. Therefore, our primary aim is to determine whether HRT use alters the risk of cancer-specific mortality in women with a range of common cancers. Our secondary objectives are to investigate whether HRT alters the risk of second cancers, cardiovascular disease, venous thromboembolism and all-cause mortality.MethodsThe study will utilise independent population-based data from Wales using the SAIL databank and Scotland based upon the national Prescribing Information System. The study will include women newly diagnosed with common cancers from 2000 to 2016, identified from cancer registries. Women with breast cancers will be excluded. HRT will be ascertained using electronic prescribing in Wales or dispensing records in Scotland. The primary outcome will be time to cancer-specific mortality from national mortality records. Time-dependent cox regression models will be used to calculate hazard ratios (HR) and 95% confidence intervals (95% CIs) for cancer specific death in HRT users compared with non-users after cancer diagnosis after adjusting for relevant confounders, stratified by cancer site. Analysis will be repeated investigating the impact of HRT use immediately before cancer diagnosis. Secondary analyses will be conducted on the risk of second cancers, cardiovascular disease, venous thromboembolism and all-cause mortality. Analyses will be conducted within each cohort and pooled across cohorts.DiscussionOur study will provide evidence to inform guidance given to women diagnosed with cancer on the safety of HRT use and/or guide modifications to clinical practice.

Holocaust Experience and Mortality Patterns: 4-Decade Follow-up in a Population-Based Cohort.

Research on mortality associated with exposure to the Holocaust is relevant for a better understanding of the effects of genocides on survivors. To our knowledge, previous studies have not investigated the long-term cause-specific mortality of Holocaust survivors. We compared mortality rates among Israelis born in European countries controlled by the Nazis during World War II with those among Israelis of European descent who did not have this exposure. Records of 22,671 people (45% women; 5,042 survivors) from the population-based Jerusalem Perinatal Study (1964-1976) were linked to the Israeli Population Registry, which was updated through 2016. Cox models were used for analysis, with 2-sided tests of statistical significance. Risk of all-cause mortality was higher among exposed women (hazard ratio (HR)=1.15, 95% confidence interval (CI): 1.05, 1.27) than in unexposed women. No association was found between Holocaust exposure and male all-cause mortality. In both sexes, survivors had higher cancer-specific mortality (HR=1.17 (95% CI: 1.01, 1.35) in women and HR=1.14 (95% CI: 1.01, 1.28) in men). Exposed men also had excess mortality due to coronary heart disease (HR=1.39, 95% CI: 1.09, 1.77) and lower mortality from other known causes combined (HR=0.86, 95% CI: 0.75, 0.99). In summary, experiencing the Holocaust was associated with excess all-cause and cancer-specific mortality in women and cancer- and coronary heart disease-specific mortality in men.

Lipid levels and survival after obesity-related cancer in the Women’s Health Initiative CVD biomarker cohort.

e13618 Background: Previous investigations have demonstrated an inconclusive relationship between lipid biomarkers and mortality after cancer. Methods: We used data from 2,279 postmenopausal women diagnosed with 13 obesity-related cancers, who were part of the Women’s Health Initiative (WHI) lipid biomarkers cohort, to evaluate the relationship between lipid levels measured at study entry prior to cancer diagnosis, and mortality after cancer. Baseline lipid measurements consisted of HDL-Cholesterol, LDL-Cholesterol, and non-HDL-Cholesterol with ranges of measurement listed in the table. Obesity-related cancers included: meningioma, thyroid, adenocarcinoma of esophagus, breast, multiple myeloma, liver, kidney, gallbladder, stomach, uterus, pancreas, ovaries, and colorectal. The age adjusted relationship between baseline lipids and all-cause mortality as well as mortality due to cancer were estimated using Cox proportional hazards models and Fine-Gray models, respectively. Results: The majority of women in the cohort had either desirable or acceptable lipid levels (86% HDL-C, 30% LDL-C and 61% non-HDL-C. Low vs. desirable HDL-C levels were associated with higher risk of all-cause mortality (hazard ratio (HR) 1.54, 95% confidence interval [CI] [1.48, 1.60], p <.001) and higher cancer mortality (sub-distribution hazard ratio (SHR)1.9, 95% CI [1.51, 2.3], p <.001). High non-HDL-C vs desirable, was associated with higher all-cause mortality (HR 1.13, 95% CI [1.06, 1.21], p = .001) however no significant impact on cancer mortality (SHR 1.06, 95% CI [0.87, 1.30], p = 0.563). LDL-C levels demonstrated a more complex relationship with mortality, nevertheless, very high LDL-C levels were associated with higher risk of all-cause mortality (HR 1.63, 95% CI,1.21-2.2, p = ,0.001) and cancer-specific mortality (HR 1.78, 95% CI 1.22-2.63, p = 0.003). Conclusions: Elevated LDL-C and lower HDL-C may be associated with a lower risk of all-cause and cancer specific mortality in women diagnosed with obesity related cancers in the WHI. Results of multivariable adjustment for important predictors of mortality including race/ethnicity, medication use and other socio-demographic and clinical factors will be presented. [Table: see text]

Cytoplasmic Cyclin E Is an Independent Marker of Aggressive Tumor Biology and Breast Cancer-Specific Mortality in Women over 70 Years of Age.

Multi-cohort analysis demonstrated that cytoplasmic cyclin E expression in primary breast tumors predicts aggressive disease. However, compared to their younger counterparts, older patients have favorable tumor biology and are less likely to die of breast cancer. Biomarkers therefore require interpretation in this specific context. Here, we assess data on cytoplasmic cyclin E from a UK cohort of older women alongside a panel of >20 biomarkers. Between 1973 and 2010, 813 women ≥70 years of age underwent initial surgery for early breast cancer, from which a tissue microarray was constructed (n = 517). Biomarker expression was assessed by immunohistochemistry. Multivariate analysis of breast cancer-specific survival was performed using Cox’s proportional hazards. We found that cytoplasmic cyclin E was the only biological factor independently predictive of breast cancer-specific survival in this cohort of older women (hazard ratio (HR) = 6.23, 95% confidence interval (CI) = 1.93–20.14; p = 0.002). At ten years, 42% of older patients with cytoplasmic cyclin E-positive tumors had died of breast cancer versus 8% of negative cases (p < 0.0005). We conclude that cytoplasmic cyclin E is an exquisite marker of aggressive tumor biology in older women. Patients with cytoplasmic cyclin E-negative tumors are unlikely to die of breast cancer. These data have the potential to influence treatment strategy in older patients.

Excess mortality from breast cancer in female breast cancer patients with severe mental illness

Women with a history of severe mental illness (SMI) have elevated breast cancer mortality. Few studies have compared cancer-specific mortality in women with breast cancer with or without SMI to reveal gaps in breast cancer treatment outcomes. We compared breast-cancer specific mortality in women with or without SMI and investigated effects of stage at presentation, comorbidity, and differences in cancer treatment. Women with their first breast cancer diagnosis in 1990–2013 (n = 80,671) were identified from the Finnish Cancer Registry, their preceding hospital admissions due to SMI (n = 4,837) from the Hospital Discharge Register and deaths from the Causes of Death Statistics. Competing risk models were used in statistical analysis. When controlling for age, year of cancer diagnosis, and comorbidity, breast cancer mortality was significantly elevated in patients with SMI. Relative mortality was highest in breast cancer patients with non-affective psychosis, partly explained by stage at presentation. Mortality was also significantly elevated in breast cancer patients with a substance use disorder and mood disorder. Patients with SMI received radiotherapy significantly less often than patients without SMI. Our findings emphasize the need to improve early detection of breast cancer in women with SMI and the collaboration between mental health care and oncological teams.

Adjuvant Chemotherapy for Breast Cancer in Older Women: An Analysis of Retrospective English Cancer Registration Data

AimsAdjuvant chemotherapy is recommended as a treatment for women with high recurrence risk early breast cancer. Older women are less likely to receive chemotherapy than younger women. This study investigated the impact of chemotherapy on breast cancer-specific survival in women aged 70 + years using English registry data. Materials and methodsCancer registration data were obtained from two English regions from 2002 to 2012 (n = 29 728). The impact of patient-level characteristics on the probability of receiving adjuvant chemotherapy was explored using logistic regression. Survival modelling was undertaken to show the effect of chemotherapy and age/health status on breast cancer-specific survival. Missing data were handled using multiple imputation. ResultsIn total, 11 735 surgically treated early breast cancer patients were identified. Use of adjuvant chemotherapy has increased over time. Younger age at diagnosis, increased nodal involvement, tumour size and grade, oestrogen receptor-negative or human epidermal growth factor receptor 2-positive disease were all associated with increased probability of receiving chemotherapy. Chemotherapy was associated with a significant reduction in the hazard of breast cancer-specific mortality in women with high risk cancer, after adjusting for patient-level characteristics (hazard ratio 0.74, 95% confidence interval 0.67–0.81). DiscussionChemotherapy is associated with an improved breast cancer-specific survival in older women with early breast cancer at high risk of recurrence . Lower rates of chemotherapy use in older women may, therefore, contribute to inferior cancer outcomes. Decisions on potential benefits for individual patients should be made on the basis of life expectancy, treatment tolerance and patient preference.

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

PurposeTo 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).MethodsThe 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.ResultsSeparated (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.ConclusionsThe risk of mortality associated with marital status is dependent on race/ethnicity. Only white and API women with TNBC have a marital advantage.

Abstract P6-08-21: Early breast cancer-specific mortality in women with early stage breast cancer: Epidemiological and clinical characteristics

Abstract Background and Aim: The five-year survival for women with stage I-II breast cancer is 93-100%. Despite standard of care treatment, a small subset of these women suffer early breast cancer-specific mortality and die within 12 months of diagnosis. This subset of women has not been previously described. The aim of this study is to characterize the incidence, demographics, and clinical characteristics of women with early stage breast cancer who suffer early breast cancer-specific mortality. Methods: Retrospective population study of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registry of women diagnosed with stage I, IIA, or IIB breast cancer between 2004 and 2010. Data were filtered to histology codes 8500-8543 and 8575. Patient demographics (age, race, ethnicity) and clinical characteristics (stage, T stage, N stage, grade, ER status, PR status) of women in the early mortality subset were compared with those of women who survived &amp;gt; 12 months via the Chi-square test and the student t-test. Results: 259,380 women formed the basis of our analysis. 4,572 women (0.018%) died within 12 months of diagnosis. Compared with those who survived &amp;gt; 12 months, women who suffered early breast cancer-specific mortality were on average older (mean age 65.7 years versus 60.3 years, p&amp;lt;0.00001) and more likely to be Hispanic (14.3% versus 8.9%, p&amp;lt;0.00001) or black (11.0% versus 9.1%, p&amp;lt;0.00001). Clinical characteristics associated with early mortality included higher stage (stage IIA 34.2% versus 29.4%, stage IIB 21.8% versus 12.9%, p&amp;lt;0.00001), higher T stage (T2 40.5% versus 28.1%, T3 3.1% versus 1.6%, p&amp;lt;0.00001), higher N stage (N1 29.7% versus 23.2%, N2 0.8% versus 0.4%, N3 0.4% versus 0.1%, p&amp;lt;0.00001), higher grade (moderate 39.3% versus 42.5%, high 40.0% versus 31.5%, p&amp;lt;0.00001), higher rates of ER negativity (27.2% versus 19.0%, p&amp;lt;0.00001), and higher rates of PR negativity (38.5% versus 30.2%, p&amp;lt;0.00001). Conclusions: Breast cancer-specific mortality within 12 months of diagnosis of stage I-II breast cancer is a rare phenomenon which has not been previously characterized. There are several demographic and clinical features associated with early mortality, however further research is needed to identify specific prognostic factors that will allow identification of women at risk for early mortality at the time of diagnosis. Citation Format: Johnson HM, Wong JH, Vohra NA, Muzaffar M. Early breast cancer-specific mortality in women with early stage breast cancer: Epidemiological and clinical characteristics [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-08-21.

Elevated tumor LDLR expression accelerates LDL cholesterol-mediated breast cancer growth in mouse models of hyperlipidemia

Obesity is associated with an increase in cancer-specific mortality in women with breast cancer. Elevated cholesterol, particularly low-density lipoprotein cholesterol (LDL-C) is frequently seen in obese women. Here, we aimed to determine the importance of elevated circulating LDL, and LDL receptor (LDLR) expression in tumor cells, on the growth of breast cancer using mouse models of hyperlipidemia. We describe two novel immunodeficient mouse models of hyperlipidemia (Rag1−/−/LDLR−/− and Rag1−/−/ApoE (apolipoprotein E)−/− mice), in addition to established immunocompetent LDLR−/− and ApoE−/− mice. The mice were used to study the effects of elevated LDL-C in human triple negative (MDA-MB-231) and mouse Her2/Neu overexpressing (MCNeuA) breast cancers. Tumors derived from MCNeuA and MDA-MB-231 cells had high LDLR expression and formed larger tumors in mice with high circulating LDL-C concentrations than in mice with lower LDL-C. Silencing the LDLR in the tumor cells led to decreased growth of Her2Neu overexpressing tumors in LDLR−/− and ApoE−/− mice, with increased Caspase 3 cleavage. Additionally, in vitro, silencing the LDLR led to decreased cell survival in serum-starved conditions, associated with Caspase 3 cleavage. Examining publically available human datasets, we found that high LDLR expression in human breast cancers was associated with decreased recurrence-free survival, particularly in patients treated with systemic therapies. Overall, our results highlight the importance of the LDLR in the growth of triple negative and HER2 overexpressing breast cancers in the setting of elevated circulating LDL-C, which may be important contributing factors to the increased recurrence and mortality in obese women with breast cancer.

An updated PREDICT breast cancer prognostication and treatment benefit prediction model with independent validation

BackgroundPREDICT is a breast cancer prognostic and treatment benefit model implemented online. The overall fit of the model has been good in multiple independent case series, but PREDICT has been shown to underestimate breast cancer specific mortality in women diagnosed under the age of 40. Another limitation is the use of discrete categories for tumour size and node status resulting in ‘step’ changes in risk estimates on moving between categories. We have refitted the PREDICT prognostic model using the original cohort of cases from East Anglia with updated survival time in order to take into account age at diagnosis and to smooth out the survival function for tumour size and node status.MethodsMultivariable Cox regression models were used to fit separate models for ER negative and ER positive disease. Continuous variables were fitted using fractional polynomials and a smoothed baseline hazard was obtained by regressing the baseline cumulative hazard for each patients against time using fractional polynomials. The fit of the prognostic models were then tested in three independent data sets that had also been used to validate the original version of PREDICT.ResultsIn the model fitting data, after adjusting for other prognostic variables, there is an increase in risk of breast cancer specific mortality in younger and older patients with ER positive disease, with a substantial increase in risk for women diagnosed before the age of 35. In ER negative disease the risk increases slightly with age. The association between breast cancer specific mortality and both tumour size and number of positive nodes was non-linear with a more marked increase in risk with increasing size and increasing number of nodes in ER positive disease.The overall calibration and discrimination of the new version of PREDICT (v2) was good and comparable to that of the previous version in both model development and validation data sets. However, the calibration of v2 improved over v1 in patients diagnosed under the age of 40.ConclusionsThe PREDICT v2 is an improved prognostication and treatment benefit model compared with v1. The online version should continue to aid clinical decision making in women with early breast cancer.

Time trend in mesothelioma and lung cancer risk in asbestos workers in Italy

This study aims at investigating, in asbestos exposed workers, the time trend of their risk of mesothelioma and of other neoplasm after very long latency and after the cessation of asbestos exposure. We pooled a large number of Italian cohorts of asbestos workers and updated mortality follow-up. The pool of data for statistical analyses includes 51,988 workers, of which 6,058 women: 54.2% was alive at follow-up, 42.6% was dead, and 2.8%was lost. Cause of death is known for 94.3%: 2,548 deaths from lung cancer, 748 frompleural cancer, 173 fromperitoneal cancer, and 434 from asbestosis. An exposure index is being developed to compare the different cohorts. Data analysis is in progress. This study will have the size for analysing not only time trends in mesothelioma, but also the occurrence of rarer diseases and cancer specific mortality in women.

Physical activity before and after breast cancer diagnosis and survival - the Norwegian women and cancer cohort study.

BackgroundThe main aim of this study was to investigate pre- and post-diagnostic physical activity (PA) levels, as well as changes in pre- and post-diagnostic PA levels, and their association with all-cause and breast cancer-specific mortality in women with breast cancer. Our study will add to the knowledge on whether a modifiable behavior such as PA can improve survival.MethodsWe included 1,327 women with breast cancer from the population-based Norwegian Women and Cancer study, which enrolled women from 1991 to 2003. Breast cancer cases were identified through linkage to the Cancer Registry of Norway; date and cause of death were obtained from the National Register for Causes of Death through 31 December 2012. Self-reported pre- and post-diagnostic PA levels were assessed, and Cox proportional hazard regression and spline regression were used to evaluate the associations.ResultsPre-diagnostic PA levels were not associated with all-cause or breast cancer-specific mortality. Post-diagnostic PA levels were associated with a significant trend (P < 0.001) of decreased all-cause and breast cancer-specific mortality, which was stronger among older women (aged 50–74 years) and did not differ across categories of body mass index. All-cause mortality (hazard ratio [HR] = 1.76, 95 % confidence interval [CI] 1.21–2.56) and breast cancer-specific mortality (HR = 2.05, 95 % CI 1.35–3.10) increased among women who reduced their post-diagnostic PA level. These values were similar among women whose maintained an inactive PA level pre- and post-diagnosis.ConclusionOverall, we observed a dose–response trend, with an inverse association between increased post-diagnostic PA level and all-cause and breast cancer-specific mortality, as well as a higher mortality risk among women who reduced their post-diagnostic PA levels. Our results are very promising for women with breast cancer, and indicate that health care professionals should consider adding PA as a part of primary cancer treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1971-9) contains supplementary material, which is available to authorized users.

Smoking and mortality after breast cancer diagnosis: the health and functioning in women study.

We examined the effect of smoking on long-term mortality from breast cancer and other causes among a cohort of women with breast cancer. A total of 975 women diagnosed with breast cancer and aged 40–84 years were followed for a median follow-up of 11 years in the U.S. Health and Functioning in Women (HFW) study. The impact of the individual smoking status and smoking intensity reported in the first few months following breast cancer diagnosis on the risk of mortality from breast cancer and other causes was examined using Cox proportional hazards models. In this study, former smoking was associated with increased risk of other-cause mortality (hazard ratio [HR] = 1.47, 95% confidence interval [CI]: 1.13–1.90), and the risk doubled with increased intensity (HR for <50 pack-years [py]: 1.36, 95% CI: 1.03–1.79; HR for ≥50 py: 2.45, 95% CI: 1.41–4.23). Current smoking (HR = 2.45, 95% CI: 1.81–3.32) and each additional 10 py smoked (HR = 1.16, 95% CI: 1.11–1.22) were associated with statistically significant increases in the risk of other-cause mortality. The effect of current smoking on other-cause mortality decreased with advancing stage and increasing body mass index (BMI). Breast cancer-specific mortality was associated with current smoking of ≥50 py (HR = 2.36, 95% CI: 1.26–4.44), and each additional 10 py smoked (HR = 1.07, 95% CI: 1.01–1. 14). Current smoking, but not former smoking, was associated with increased risk of breast cancer-specific mortality in women with local disease (HR = 2.32, 95% CI: 1.32–4.09), but not in those with regional and distant disease (HR = 1.10, 95% CI: 0.73–1.68). Our findings suggest that current smoking at the time of breast cancer diagnosis may be associated with increased risk of breast-cancer specific and other-cause mortality, whereas former smoking is associated with increased risk of other-cause mortality. Smoking cessation at the time of diagnosis may lead to better prognosis among women with breast cancer.

Effect of Involved Lymph Node Size on Cancer-Specific Mortality in Women With Node-Positive Breast Cancer

As adjuvant therapy options for breast cancer expand, accurate estimates of cancer-specific outcomes are increasingly important in order to appropriately tailor therapy. Among node-positive patients, the number of involved lymph nodes (LN) is used as the proxy for the burden of disease. However, there is large variability in the size of the involved LN. We hypothesized that larger involved LNs portend a worse prognosis than smaller LNs.

Non-steroidal anti-inflammatory drug use, hormone receptor status, and breast cancer-specific mortality in the Carolina Breast Cancer Study.

Epidemiologic studies report a protective association between non-steroidal anti-inflammatory drug (NSAID) use and hormone receptor-positive breast cancer risk, a finding consistent with NSAID-mediated suppression of aromatase-driven estrogen biosynthesis. However, the association between NSAID use and breast cancer-specific mortality is uncertain and it is unknown whether this relationship differs by hormone receptor status. This study comprised 935 invasive breast cancer cases, of which 490 were estrogen receptor (ER)-positive, enrolled between 1996 and 2001 in the Carolina Breast Cancer Study. Self-reported NSAID use in the decade prior to diagnosis was categorized by duration and regularity of use. Differences in tumor size, stage, node, and receptor status by NSAID use were examined using Chi-square tests. Associations between NSAID use and breast cancer-specific mortality were examined using age- and race-adjusted Cox proportional hazards analysis. Tumor characteristics did not differ by NSAID use. Increased duration and regularity of NSAID use was associated with reduced breast cancer-specific mortality in women with ER-positive tumors (long-term regular use (≥8days/month for≥3years) versus no use; hazard ratio (HR) 0.48; 95% confidence interval (CI) 0.23-0.98), with a statistically significant trend with increasing duration and regularity (p-trend=0.036). There was no association for ER-negative cases (HR 1.19; 95%CI 0.50-2.81; p-trend=0.891). Long-term, regular NSAID use in the decade prior to breast cancer diagnosis was associated with reduced breast cancer-specific mortality in ER-positive cases. If confirmed, these findings support the hypothesis that potential chemopreventive properties of NSAIDs are mediated, at least in part, through suppression of estrogen biosynthesis.

Association Between Ginseng Intake and Mortality: Kangwha Cohort Study

Panax ginseng C.A. Meyer is a well-known medicinal herb in North America and Europe. The purpose of this study was to investigate the association between ginseng intake and mortality among members of the Korean population. We followed 6282 subjects who were 55 years of age or older in March 1985 until December 31, 2003. The Cox proportional hazard regression model was used to evaluate effects of ginseng intake on mortality. Adjusting for age, education, occupation, drinking, smoking, self-reported chronic disease, body mass index, and blood pressure, all-cause mortality for male ginseng users was significantly lower than that for male nonusers (Hazard ratio [HR] = 0.90; 95% confidence interval [CI], 0.81-0.99). However, such an association was not observed in women (HR = 1.03; 95% CI, 0.94-1.13). Cancer-specific mortality was lower in female ginseng users than female nonusers after adjustment of relevant covariates (HR = 0.80; 95% CI, 0.60-1.08). Compared to nonusers, the HR for cancer-specific mortality in women was 0.84 in infrequent users (95% CI, 0.62-1.15) and 0.61 in frequent users (95% CI, 0.32-1.14) (p for trend, 0.09), which is not statistically significant. The cancer-specific mortality was not associated with ginseng intake in male subjects (HR = 0.95; 95% CI, 0.76-1.20). Mortality caused by cardiovascular diseases was not related to ginseng intake in both men and women. The 18.8-year progressive cohort study showed that ginseng intake decreased all-cause mortality in older males, but such life prolongation effect was not shown in women.