Social inequality and incidence of and survival from breast cancer in a population-based study in Denmark, 1994-2003

We investigated the effects of socioeconomic, demographic and health-related indicators on the incidence of and survival from breast cancer diagnosed in 1994-2003 with follow-up through 2006 in Denmark using information from nationwide population-based registers. The analyses were based on data on 25,855 patients with breast cancer in a cohort of 3.22 million people born between 1925 and 1973 and aged >or=30 years. In general, the incidence of breast cancer increased with increasing social advantage, with unemployment or retirement, with increasing urbanicity and with being single or divorced. A history of admission for a psychiatric disorder increased the incidence of breast cancer. The overall relative short-term survival was high (96%), but survival improved with higher educational level and income. Whilst the relative 5-year survival after breast cancer was high (79%), there was significantly poorer relative survival amongst less advantaged and single women.     

Socioeconomic gradients in clinical stage at presentation and survival among breast cancer patients in the Stockholm area 1977-1997

A program to ensure an equivalent standard of care for all patients with breast cancer was initiated in the Stockholm area in the mid 1970s. As part of an evaluation of this program, social gradients in clinical stage at presentation and survival were analyzed among patients diagnosed during 1977 through 1997. The patients (n = 15,021) were selected from a database covering about 88% of all diagnosed breast cancer cases in the region. Putative associations were analyzed between clinical stage, survival and different socioeconomic indicators (level of education, income and occupation). There were significant social differences (p < 0.01) in distribution of clinical stage as well as in total and stage-specific survival. High income, more skilled work and a high level of education were all associated with clinically less advanced tumors and hence better survival. However, stage-specific survival differences were mostly generated by differences in nonbreast cancer mortality. The results indicate social inequalities regarding awareness of the disease and/or access to early detection. Social gradients in nonbreast cancer mortality were also found to influence observed survival. In contrast, we observed no significant social differences in stage-specific breast cancer mortality.     

Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases

Two of the most important prognostic indicators for breast cancer are tumor size and extent of axillary lymph node involvement. Data on 24,740 cases recorded in the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute were used to evaluate the breast cancer survival experience in a representative sample of women from the United States. Actuarial (life table) methods were used to investigate the 5-year relative survival rates in cases with known operative/pathologic axillary lymph node status and primary tumor diameter. Survival rates varied from 45.5% for tumor diameters equal to or greater than 5 cm with positive axillary nodes to 96.3% for tumors less than 2 cm and with no involved nodes. The relation between tumor size and lymph node status was investigated in detail. Tumor diameter and lymph node status were found to act as independent but additive prognostic indicators. As tumor size increased, survival decreased regardless of lymph node status; and as lymph node involvement increased, survival status also decreased regardless of tumor size. A linear relation was found between tumor diameter and the percent of cases with positive lymph node involvement. The results of our analyses suggest that disease progression to distant sites does not occur exclusively via the axillary lymph nodes, but rather that lymph node status serves as an indicator of the tumor's ability to spread.     

Social class is an important and independent prognostic factor of breast cancer mortality

Reasons of the important impact of socioeconomic status on breast cancer prognosis are far from established. This study aims to evaluate and explain the social disparities in breast cancer survival in the Swiss canton of Geneva, where healthcare costs and life expectancy are among the highest in the world. This population-based study included all 3,920 female residents of Geneva, who were diagnosed with invasive breast cancer before the age of 70 years between 1980 and 2000. Patients were divided into 4 socioeconomic groups, according to the woman's last occupation. We used Cox multivariate regression analysis to identify reasons for the socioeconomic inequalities in breast cancer survival. Compared to patients of high social class, those of low social class had an increased risk (unadjusted hazard ratio [HR] 2.4, 95% CI: 1.6-3.5) of dying as a result of breast cancer. These women were more often foreigners, less frequently had screen-detected cancer and were at more advanced stage at diagnosis. They less frequently underwent breast-conserving surgery, hormonal therapy, and chemotherapy, in particular, in case of axillary lymph node involvement. When adjusting for all these factors, patients of low social class still had a significantly increased risk of dying of breast cancer (HR 1.8, 95% CI: 1.2-2.6). Overmortality linked to low SES is only partly explained by delayed diagnosis, unfavorable tumor characteristics and suboptimal treatments. Other factors, not measured in this study, also could play a role. While waiting for the outcome of other researches, we should consider socioeconomic status as an independent prognostic factor and provide intensified support and surveillance to women of low social class.     

Factores pronósticos del cáncer de mama. Modelo predictivo

Introduction. Breast cancer remains the most frecuent tumor among women in developed countries. The prognosis is linked to a great variety clinic and pathological factors. The objectives from this study are to identify markers related to survival of patients with primary diagnosis of breast cancer. Material and methods. We have reviewed the medical dossier from 2.227 consecutive women diagnosed for infiltrating breast cancer between January 1966 and december 2000 in a single institution. For statistic analysis we used 10.0 SPSS software. Results. In the univariate analysis, factors with the strongest predictive value for overall survival were: PEV, estrogene and progesterone receptors, TNM stage, lymphatic vessel involvement, histologic grade, Scarff differentiation and mitosis rate, elastosis, presence of histiocitosis, and the percentage of involved stage I and III lymph nodes (Berg clasification). In the multivariate analysis, 5 factors; progesterone receptors, Scarff mitotic rate, lymphatic vessel involvement, percentage of involved stage I lymph nodes, and presence of metastasis; were independent prognostic markers of survival. Conclusions. Many independent factors interact in the survival of patients with primary breast cancer. Determination of hormonal receptors, mainly progesterone’s, appear as the most powerful indicators. The analysis has generated a prognostic simplified classification, based in the 5 independent variables, that provides specific rates for survival at 2, 5 and 10 years.     

Association between prognosis and hormone receptors in women with breast cancer

Axillary node involvement, hormone receptors, tumor differentiation, and obesity have been linked to breast cancer prognosis. We have evaluated which of these factors have an independent association with disease-free survival using the Cox Proportional Hazards model. The study was carried out in 377 patients with breast cancer who underwent mastectomy and axillary node dissection between 1977 and 1984. In the univariate analysis all of the above factors were associated with differences in disease-free survival, and all entered the stepwise model. Among women with negative nodes and those with one to three positive nodes, tumor differentiation was a significant indicator of prognosis, while hormone receptors did not have prognostic significance. The opposite was noted in women with four or more involved nodes, among whom negative hormone receptors was the only significant marker of poor prognosis together with presence of obesity. Among young women node involvement and hormone receptors were significant prognostic indicators, while among older women all four variables were independent prognostic markers. These results indicate a marked heterogeneity among subgroups of women with breast cancer in relation to prognostic markers.     

Importance of the level of axillary involvement in relation to traditional variables in the prognosis of breast cancer.

Survival in breast cancer correlates with the presence of metastatic lymph nodes, so that removal and pathological examination of the axillary nodes provides the most important prognostic information and basis for planning subsequent therapy. However as the size of primary tumours at diagnosis is decreasing, the likelihood of axillary involvement is also declining, so that the indications for axillary dissection are undergoing radical revision. To definitively establish the value of removing all three axillary lymph node levels (as defined by Berg) in node positive breast cancer, retrospective analysis of a large series receiving complete dissection was carried out. consecutive breast cancer patients (n=1003) with positive axillary nodes were analyzed: all received identical axillary treatment and the three levels were tagged with metal disks to facilitate recognition and pathological examination. Follow-up (mean 97 months) was exceptionally complete. The length of disease-free and overall survival were taken as the primary endpoints. The variables considered in the statistical analysis were tumour size, number of metastatic nodes, axillary invasion by level (the three classic levels), perilymphnodal invasion and age. By univariate analysis, overall and disease-free survival decreased significantly as tumour diameter, number of involved lymph nodes, and involvement by axillary level increased. Multivariate analysis assessing the relative importance of these variables when all were considered together found that they were all important independent predictive factors for survival. This study confirms the importance of tumour size and number of metastatic axillary nodes as predictors of outcome in breast cancer. In addition, the level of axillary invasion as a third independent factor of equal importance to the established indicators was identified. When axillary dissection is performed it should be complete, and all three Berg levels tagged separately, so that involvement by level can be ascertained. This provides additional important prognostic information on which to base subsequent treatment decisions.     

Breast cancer survivorship: the role of perceived discrimination and sexual orientation

Breast cancer disproportionately affects sexual minority women (SMW) compared to heterosexual women and a small but growing literature indicates that SMW may have diminished survivorship outcomes; outcomes that are measurably and importantly different from heterosexual breast cancer survivors. However, it remains unknown how sexual orientation influences breast cancer survivorship outcomes such as quality of life. One possible route of influence is SMW’s perceived discrimination in the health care setting. This cross-sectional study examines SMW perceptions of discrimination as one of the multiple facets of the breast cancer survivorship process. This study assessed SMW breast cancer survivor’s perceptions of discrimination during their breast cancer treatment experience and secondarily, examined the role of this perceived discrimination on SMW’s quality of life. Sixty-eight purposefully sampled sexual minority breast cancer survivors completed assessments of quality of life, perceived discrimination, perceived social support and perceived stress via an online survey. Statistical analyses point to perceived discrimination and perceived social support as important indicators for predicting SMW’s quality of life. Future research on SMW’s breast cancer survivorship should include measures of perceived discrimination.     

Aurora kinase A suppresses metabolic stress-induced autophagic cell death by activating mTOR signaling in breast cancer cells

Aberrant Aur-A signaling is associated with tumor malignant behaviors. However, its involvement in tumor metabolic stress is not fully elucidated. In the present study, prolonged nutrient deprivation was conducted into breast cancer cells to mimic metabolic stress in tumors. In these cells, autophagy was induced, leading to caspase-independent cell death, which was blocked by either targeted knockdown of autophagic gene ATG5 or autophagy inhibitor 3-Methyladenine (3-MA). Aur-A overexpression mediated resistance to autophagic cell death and promoted breast cancer cells survival when exposed to metabolic stress. Moreover, we provided evidence that Aur-A suppressed autophagy in a kinase-dependent manner. Furthermore, we revealed that Aur-A overexpression enhanced the mammalian target of rapamycin (mTOR) activity under metabolic stress by inhibiting glycogen synthase kinase 3β (GSK3β). Inhibition of mTOR activity by rapamycin sensitized Aur-A-overexpressed breast cancer cells to metabolic stress-induced cell death. Consistently, we presented an inverse correlation between Aur-A expression (high) and autophagic levels (low) in clinical breast cancer samples. In conclusion, our data provided a novel insight into the cyto-protective role of Aur-A against metabolic stress by suppressing autophagic cell death, which might help to develop alternative cell death avenues for breast cancer therapy.     

No evidence that social stress is associated with breast cancer incidence

Women commonly attribute the experience of stress as a contributory cause of breast cancer. The purpose of this study is to investigate the associations between a history of social stress and breast cancer risk. A total of 11,467 women with no prior history of breast cancer, participants in the European Prospective Investigation into Cancer (EPIC)-Norfolk population-based prospective cohort study, completed a comprehensive assessment of lifetime social adversity exposure. Summary measures of social adversity were defined according to difficult circumstances in childhood, stressful life events and longer-term difficulties in adulthood, derived measures representing the subjective ‘impact’ of life events and associated ‘stress adaptive capacity’, and perceived stress over a 10-year period. Incident breast cancers were identified through linkage with cancer registry data. During 102,514 (median 9) person-years of follow-up, 313 incident breast cancers were identified. No associations were observed between any of the summary social adversity measures and subsequent breast cancer risk, with or without adjustment for age, menopausal status, parity, use of menopausal hormones, age at menarche, age at first birth, family history of breast cancer, physical activity, social class, body mass index, height, and alcohol intake. This study found no evidence that social stress exposure or individual differences in its experience are associated with the development of breast cancer. These findings may aid strategies designed to meet the psychosocial and emotional needs of breast cancer survivors and may be interpreted in a positive way in the context of commonly voiced beliefs that the experience of stress is a contributory cause of their disease.     

Clinical Significance and Management of Sentinel Node Micrometastasis in Invasive Breast Cancer

Axillary node status is one of the most important prognostic indicators in patients with invasive breast cancer. Sentinel node biopsy allows an exhaustive examination of the lymph node and has led to an increased detection rate of small tumor deposits. Patients with micrometastatic deposits can have nonsentinel node involvement, including macrometastatic deposits. Sentinel node micrometastases are associated with an adverse impact on disease recurrence and survival. Axillary dissection does not offer an advantage in reducing the incidence of disease recurrence or survival. However, the long-term outcomes can be improved with the use of adjuvant chemotherapy, and it would be reasonable to consider systemic treatment in these patients.     

C-erbB-2 oncoprotein expression versus internal mammary lymph node metastases as additional prognostic factors in patients with axillary lymph node-positive breast cancer.

The relationship was assessed between c-erbB-2 oncoprotein expression and other prognostic factors in breast cancer, such as axillary and internal mammary node metastases. The value of these indicators was analyzed in estimating prognosis, especially in patients with axillary node-positive breast cancer. These results showed that c-erbB-2 is significantly related to clinical stage and axillary node metastases. A univariate study revealed that disease-free and overall survival were correlated significantly with clinical stage, tumor size, axillary and internal mammary node metastases, and 21N status. Among the patients with axillary node involvement, however, 21N status did not appear to be a significant additional prognostic factor. Internal mammary node metastases were significant. In a multivariate study, only axillary and internal mammary node metastases were significant prognostic factors for either the entire group of patients or those with positive axillary nodes. Therefore, axillary node dissection and biopsy of the internal mammary nodes may provide important prognostic information for patients with breast cancer.     

Racial/ethnic differences and potential psychological benefits in use of the internet by women with breast cancer

Many websites on the Internet offer information to breast cancer patients and are increasingly being used. The authors investigated the potential psychological benefits of Internet use and how it varied as a function of race/ethnicity among 180 white, African American, and Hispanic American breast cancer patients who used the Internet for medical information. Using standardized psychological measures, as measured by the Interpersonal Support Evaluation List (ISEL), Internet use among minorities was associated with greater overall, appraisal, and tangible social support (p's<0.05) but not belonging and self-esteem social support than among whites. No differences were observed for stress, depressive symptoms, loneliness, and coping. Since numerous studies suggest that social support may be related to survival, Internet use for breast health issues may have special clinical relevance to racial/ethnic minority groups.     

Long-term inequalities in breast cancer survival--a ten year follow-up study of patients managed within a National Health Care System (Sweden)

Introduction. Converging epidemiological evidence based on studies of different designs in a variety of populations and settings show that cancer survival tends to be poorer in low compared to high socioeconomic groups. In an extension of an earlier register-based study, we examined the influence of socioeconomic factors on long-term survival in women with a first diagnosis of invasive breast cancer in 1993 in Sweden, a country with a policy of providing equal access to health care to all at nominal cost within a National Health Care System. Material and methods. The study was based on data set generated by record linkages between the Swedish Cancer Register, Census databases and the Cause of Death Register. Four different categorical variables were used as indicators of socioeconomic standing. Cox proportional hazard regression models were used to estimate the effects of socioeconomic status on risk of death. Results. Of 4 645 eligible women with breast cancer, 1 016 had died from breast cancer at the end of follow-up on December 31, 2003. After adjustment for tumour size and age at diagnosis, risk of death was 19% lower among women belonging to a household of high compared to low socioeconomic status (HR high versus low 0.81; 95% CI: 0.67-0.97). Discussion. These findings indicate that social inequalities in breast cancer survival persist at least up to ten years after an initial diagnosis. While social gradients detected shortly after diagnosis may mainly reflect an influence of socioeconomic differences in overall health status and frailty, differentials persisting beyond five years rather point to a long-term influence of disparities in management of both primary tumours and recurrences. Further studies are needed to explore whether the present findings reflect amendable inequalities in access to state-of- the-art treatment. For all calendar periods, observed survival in the most privileged groups sets the goal for what is achievable for all breast cancer patients.     

High-dose chemotherapy for breast cancer: is another look warranted?

PURPOSE OF REVIEW: Controversy has surrounded the use of high-dose chemotherapy for breast cancer for more than a decade. Numerous randomized trials have compared high-dose chemotherapy with standard-dose chemotherapy in metastatic breast cancer and high-risk primary breast cancer, defined by extensive axillary node involvement or inflammatory disease. The authors review the main research results of high-dose chemotherapy for breast cancer in 2002 to 2003. RECENT FINDINGS: Preliminary analyses of three randomized trials in metastatic breast cancer and seven in high-risk primary breast cancer have been reported during this period. An advantage in event-free survival has been observed in all three studies in metastatic disease and in four of the high-risk primary cancer trials, albeit with no impact on overall survival at short follow-up. These early results are consistent with the most recent Cochrane reviews, which included trials reported through mid 2002. SUMMARY: An early event-free survival advantage is apparent in favor of high-dose chemotherapy in both high-risk primary and metastatic breast cancer. Longer follow-up of those and most other trials is required to detect translation of the event-free survival differences into benefits in overall survival. High-dose chemotherapy remains a valid research strategy in event-free survival and high-risk primary breast cancer.     

应用Cox比例风险模型对188例乳腺癌患者术后长期生存质量影响的临床研究

目的探讨乳腺癌术后各种病理因素对乳腺癌患者长期生存质量的影响及在预后评估中的作用.方法选择16个可能对乳腺癌术后长期生存产生影响的临床病理因素, 应用Cox比例风险模型对188例乳腺癌术后的患者进行综合多因素分析.结果除TNM分期、病理分化程度及手术方式等临床病理因素外, 患者术后情感功能、认知功能及社会生活功能的变化也是影响乳腺癌术后患者长期生存质量的重要因素.结论乳腺癌患者术后情感功能、认知功能及社会生活功能的变化也是判断乳癌术后患者长期生存质量的重要指标.临床上应该结合这些因素以使乳癌术后患者预后判断更准确、更全面.     

Clinical progression of breast cancer malignant behavior: what to expect and when to expect it.

PURPOSE: Seemingly localized breast cancer is a heterogeneous mix of truly localized cancers and cancers with occult metastases. Our purpose is to determine the parameters of metastatic proclivity for the different clinical presentations of operable breast cancer and to present quantitative prognostic information useful to both doctors and patients. PATIENTS AND METHODS: A series of regionally treated breast cancer patients was analyzed to determine the likelihood and time of the appearance of clinical metastases for different clinical subgroups. Patients operated on at the University of Chicago from 1927 to 1987 for clinically regionally localized breast cancer, who received no systemic therapy as a part of their initial treatment, were included. Overall survival and distant disease-free survival in this mature series are analyzed. RESULTS: Metastagenicity, the metastatic proclivity of a tumor, increases with both tumor size and nodal involvement. This is also true for virulence, which is the rate at which these metastases appear. Each clinical group has a cured population, even those with extensive nodal involvement. A table provides a tool for determining the proportion of risk expended in each clinical group as a function of the distant disease-free survival. Whereas the likelihood of metastasis increases with tumor size and nodal involvement, the time to their appearance decreases. CONCLUSIONS: Breast cancer metastagenicity and virulence are heterogeneous even within clinically similar groups of operable breast cancer patients. Tumor progression is correlated with increasing tumor size and nodal involvement. Markers are needed to identify individual tumor virulence and metastagenicity.     

Breast carcinoma metastatic to the bladder and renal pelvis requiring fulguration

Breast cancer metastatic to the bladder has rarely been reported in the literature. A patient presented to our institution with pathologically confirmed breast cancer metastatic to the bladder with renal pelvis involvement as seen on retrograde pyelography. We believe cystoscopy with biopsy and fulguration to be the treatment of choice for breast cancer that has metastasized to the bladder because of the low rate of survival in patients with hematuria related to metastatic breast cancer.     

Social networks and survival after breast cancer diagnosis

Introduction  

Evidence has been inconsistent regarding the impact of social networks on survival after breast cancer diagnosis. We prospectively examined the relation between components of social integration and survival in a large cohort of breast cancer survivors.     

Socioeconomic effects on breast cancer survival: proportion attributable to stage and morphology

Breast cancer patients of lower socioeconomic status tend to have poorer survival. Among 10 865 cases of breast cancer from the East Anglian Cancer Registry diagnosed between 1982 and 1993, we estimated the extent to which the differences in survival by socioeconomic status, measured by both occupational and area-based methods, can be explained by differences between socioeconomic groups in stage and morphological type of tumour. In univariate survival analyses, lower social class (manual occupation) was associated with a relative hazard of 1.32 (95% CI 1.12-1.55) for death from breast cancer as underlying cause. Women resident in the most deprived area had a relative hazard of 1.21 (0.95-1.54) for death from breast cancer as underlying cause. Stage of disease accounted for 28% of the effect of social class on survival but for none of the effect of deprivation category. Morphological type accounted for 3% of the effect of social class and none of the effect of deprivation category. Thus, stage at presentation explains some but not all of the socioeconomic differences in breast cancer survival. Future research on histological grade and socioeconomic status is indicated.