The Influence of Age on the Behaviour of Carcinoma of the Breast

A consecutive series of 1530 patients with carcinoma of the breast has been reviewed to study the influence of age and marital status on the disease.The risk of developing breast cancer increases with age, though a peak may be reached at 75 years. The risk of developing a tumour of advanced clinical stage at presentation apparently increases with age. Local recurrence rates and mortality rates are similar at all ages. It is concluded that the therapy required is similar in all age groups.The increased risk of developing breast cancer in “never married” women is in the postmenopausal period. Survival rates and the distribution of the various presenting clinical stages are similar in both single and married patients.Though ageing and marital status have an initiating effect on breast cancer, they do not have a continuing effect on the established disease.     

Prospective breast cancer risk factors prediction in Saudi women

Women's health is affected by breast cancer worldwide and Saudi Arabia (SA) is no exception. Malignancy has enormous consequences for social, psychological and public health. The aim of this study was to examine the risk factors for Saudi women from breast cancer using logistic regression models. In 135 patient cases for different stages of breast cancer was used to study case management, 270 healthy women from King Abd Alla Medical City, Mecca, SA were taken to predict the probability of women developing breast cancer, logistic regression was analyzed taking factors such as age, marital status, family history, parity, age at first full-term pregnancy, menopausal status, body mass index (BMI) and breast feeding. The logistic regression model showed that there are important risk factors (age, marital status, family history, parity, age at first full-term pregnancy, menopausal status, body mass index, and breast feeding) in development of breast cancer. Fewer cases were observed in unmarried women, age ≤30, BMI ≤20. In contrast, more cases were found with women age 41–50 married, BMI > 30, a smaller number of children, not breast feeding, age of first pregnancy ≥30, menopausal status age at 46–50. Based on our data there is role of risk factors in developing breast cancer, less BMI, the increase number of children, breast feeding, which are playing as protective factor for breast cancer.     

Association between Melanocytic Nevi and Risk of Breast Diseases: The French E3N Prospective Cohort

Background

While melanocytic nevi have been associated with genetic factors and childhood sun exposure, several observations also suggest a potential hormonal influence on nevi. To test the hypothesis that nevi are associated with breast tumor risk, we explored the relationships between number of nevi and benign and malignant breast disease risk.

Methods and Findings

We prospectively analyzed data from E3N, a cohort of French women aged 40–65 y at inclusion in 1990. Number of nevi was collected at inclusion. Hazard ratios (HRs) for breast cancer and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. Associations of number of nevi with personal history of benign breast disease (BBD) and family history of breast cancer were estimated using logistic regression. Over the period 15 June 1990–15 June 2008, 5,956 incident breast cancer cases (including 5,245 invasive tumors) were ascertained among 89,902 women. In models adjusted for age, education, and known breast cancer risk factors, women with “very many” nevi had a significantly higher breast cancer risk (HR = 1.13, 95% CI = 1.01–1.27 versus “none”; p _trend = 0.04), although significance was lost after adjustment for personal history of BBD or family history of breast cancer. The 10-y absolute risk of invasive breast cancer increased from 3,749 per 100,000 women without nevi to 4,124 (95% CI = 3,674–4,649) per 100,000 women with “very many” nevi. The association was restricted to premenopausal women (HR = 1.40, p _trend = 0.01), even after full adjustment (HR = 1.34, p _trend = 0.03; p _homogeneity = 0.04), but did not differ according to breast cancer type or hormone receptor status. In addition, we observed significantly positive dose–response relationships between number of nevi and history of biopsy-confirmed BBD (n = 5,169; p _trend<0.0001) and family history of breast cancer in first-degree relatives (n = 7,472; p _trend = 0.0003). The main limitations of our study include self-report of number of nevi using a qualitative scale, and self-reported history of biopsied BBD.

Conclusions

Our findings suggest associations between number of nevi and the risk of premenopausal breast cancer, BBD, and family history of breast cancer. More research is warranted to elucidate these relationships and to understand their underlying mechanisms. Please see later in the article for the Editors'' Summary     

Etiology of breast cancer III. Opportunities for prevention

Breast cancer, or its effects, may be preventable. Childbearing at an early age will confer some protection. Until there are other methods of primary prevention the physician must concentrate on secondary prevention, including screening. In presenting risk factors as criteria for screening we have attempted to make rational the use of screening technology. We should not easily accept screening for breast cancer as of proved value. Rather we must encourage clinical trials of various screening methods. In the meantime, while we engage in a moderate amount of screening we do so under the Scottish verdict of “not proven”.     

Marital and Reproductive Histories of Women With Cancer of the Breast and Their Sisters

In a study of 45 pairs of sisters—each pair including one sister with cancer of the breast and one without the disease—differences in marital and reproductive histories were observed. These differences included less frequent marriage, later marriage, fewer children, and a longer delay between date of marriage and the first pregnancy in the sisters with the disease. These findings appear to confirm presently known reproductive risk factors for cancer of the breast, but they also raise the possibility that unknown behavioral factors influencing the endocrine system may be delaying marriage and pregnancy.     

Etiology of breast cancer I. Genetic aspects

The subject of breast cancer is reviewed with particular emphasis on the genetic aspect of its etiology. A number of studies using various approaches gave the same results: the familial form occurs earlier and there is a higher risk in female members of the breast-cancer families. An association between breast cancer and cancer of certain other sites among women is reported. Cytogenetic studies of “cancer families” revealed increased frequency of aneuploidy in some members. However, the role of chromosome abnormalities in carcinogenesis is still not clear.     

乳腺癌患者心理韧性相关影响因素分析及心理韧性与焦虑的关系

目的:分析乳腺癌患者心理韧性的影响因素,并分析心理韧性与焦虑的关系。方法:于2017年2月～2018年4月期间,选择蚌埠医学院第二附属医院收治的乳腺癌患者287例为研究对象,分别采用心理韧性量表(RS)、焦虑自评量表(SAS)评估研究对象的心理韧性及焦虑状态,并采用多因素Logistic回归分析法分析乳腺癌患者心理韧性相关的影响因素,应用多元逐步线性回归分析法分析乳腺癌患者心理韧性与焦虑的关系。结果:乳腺癌患者RS得分为(76.72±9.82)分。单因素分析显示,不同年龄、居住地、家庭月收入及费用支出形式患者的RS得分比较差异有统计学意义(P0.05);不同文化程度、婚姻状况、手术类型及肿瘤分期患者的RS得分比较差异无统计学意义(P0.05)。多因素Logistic回归分析结果显示,年龄为20～40岁、居住地为农村、家庭月收入3000元、费用支出形式为自费是乳腺癌患者心理韧性的影响因素(P0.05)。乳腺癌患者SAS得分为(5.02±1.42)分,以心理韧性为自变量,焦虑为因变量进行多元逐步线性回归分析,结果显示,乳腺癌患者心理韧性为焦虑的预测因子,其心理韧性水平越高,焦虑程度越低(P0.05)。结论:乳腺癌患者心理韧性水平偏低,且其对患者焦虑状态具有预测作用,年龄为20～40岁、居住地为农村、家庭月收入3000元、费用支出形式为自费是乳腺癌患者心理韧性的影响因素,临床治疗中应该根据以上影响因素进行相关干预。     

Linkage to markers for the chromosome region 17q12-q21 in 13 Dutch breast cancer kindreds

We have performed linkage analysis with five markers for the chromosome region 17q12-q21 in 13 Dutch breast cancer kindreds in order to find support for the claim by Hall et al. that a gene in this region, termed “BRCA1,” is associated with predisposition to early-onset familial breast cancer. This work is part of a collaborative study, the results of which are published elsewhere in this issue. Best evidence for linkage was observed with the marker CMM86 (D17S74) in pedigrees with an average age at onset of ≤47 years (LOD score = 1.77 at 1% recombination). In one breast-ovarian cancer family with a high probability of being linked to 17q, we observed one putative recombinant between D17S250 and D17S579, which suggests that BRCA1 is proximal to D17S579.     

Risk Prediction for Breast,Endometrial, and Ovarian Cancer in White Women Aged 50 y or Older: Derivation and Validation from Population-Based Cohort Studies

Background

Breast, endometrial, and ovarian cancers share some hormonal and epidemiologic risk factors. While several models predict absolute risk of breast cancer, there are few models for ovarian cancer in the general population, and none for endometrial cancer.

Methods and Findings

Using data on white, non-Hispanic women aged 50+ y from two large population-based cohorts (the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial [PLCO] and the National Institutes of Health–AARP Diet and Health Study [NIH-AARP]), we estimated relative and attributable risks and combined them with age-specific US-population incidence and competing mortality rates. All models included parity. The breast cancer model additionally included estrogen and progestin menopausal hormone therapy (MHT) use, other MHT use, age at first live birth, menopausal status, age at menopause, family history of breast or ovarian cancer, benign breast disease/biopsies, alcohol consumption, and body mass index (BMI); the endometrial model included menopausal status, age at menopause, BMI, smoking, oral contraceptive use, MHT use, and an interaction term between BMI and MHT use; the ovarian model included oral contraceptive use, MHT use, and family history or breast or ovarian cancer. In independent validation data (Nurses'' Health Study cohort) the breast and ovarian cancer models were well calibrated; expected to observed cancer ratios were 1.00 (95% confidence interval [CI]: 0.96–1.04) for breast cancer and 1.08 (95% CI: 0.97–1.19) for ovarian cancer. The number of endometrial cancers was significantly overestimated, expected/observed = 1.20 (95% CI: 1.11–1.29). The areas under the receiver operating characteristic curves (AUCs; discriminatory power) were 0.58 (95% CI: 0.57–0.59), 0.59 (95% CI: 0.56–0.63), and 0.68 (95% CI: 0.66–0.70) for the breast, ovarian, and endometrial models, respectively.

Conclusions

These models predict absolute risks for breast, endometrial, and ovarian cancers from easily obtainable risk factors and may assist in clinical decision-making. Limitations are the modest discriminatory ability of the breast and ovarian models and that these models may not generalize to women of other races. Please see later in the article for the Editors'' Summary     

An “elite hacker”: Breast tumors exploit the normal microenvironment program to instruct their progression and biological diversity

The year 2011 marked the 40 year anniversary of Richard Nixon signing the National Cancer Act, thus declaring the beginning of the “War on Cancer” in the United States. Whereas we have made tremendous progress toward understanding the genetics of tumors in the past four decades, and in developing enabling technology to dissect the molecular underpinnings of cancer at unprecedented resolution, it is only recently that the important role of the stromal microenvironment has been studied in detail. Cancer is a tissue-specific disease, and it is becoming clear that much of what we know about breast cancer progression parallels the biology of the normal breast differentiation, of which there is still much to learn. In particular, the normal breast and breast tumors share molecular, cellular, systemic and microenvironmental influences necessary for their progression. It is therefore enticing to consider a tumor to be a “rogue hacker”—one who exploits the weaknesses of a normal program for personal benefit. Understanding normal mammary gland biology and its “security vulnerabilities” may thus leave us better equipped to target breast cancer. In this review, we will provide a brief overview of the heterotypic cellular and molecular interactions within the microenvironment of the developing mammary gland that are necessary for functional differentiation, provide evidence suggesting that similar biology—albeit imbalanced and exaggerated—is observed in breast cancer progression particularly during the transition from carcinoma in situ to invasive disease. Lastly we will present evidence suggesting that the multigene signatures currently used to model cancer heterogeneity and clinical outcome largely reflect signaling from a heterogeneous microenvironment—a recurring theme that could potentially be exploited therapeutically.     

Money Walks: Implicit Mobility Behavior and Financial Well-Being

Traditional financial decision systems (e.g. credit) had to rely on explicit individual traits like age, gender, job type, and marital status, while being oblivious to spatio-temporal mobility or the habits of the individual involved. Emerging trends in geo-aware and mobile payment systems, and the resulting “big data,” present an opportunity to study human consumption patterns across space and time. Taking inspiration from animal behavior studies that have reported significant interconnections between animal spatio-temporal “foraging” behavior and their life outcomes, we analyzed a corpus of hundreds of thousands of human economic transactions and found that financial outcomes for individuals are intricately linked with their spatio-temporal traits like exploration, engagement, and elasticity. Such features yield models that are 30% to 49% better at predicting future financial difficulties than the comparable demographic models.     

Mitochondrial metabolism in cancer metastasis: Visualizing tumor cell mitochondria and the “reverse Warburg effect” in positive lymph node tissue

We have recently proposed a new two-compartment model for understanding the Warburg effect in tumor metabolism. In this model, glycolytic stromal cells produce mitochondrial fuels (L-lactate and ketone bodies) that are then transferred to oxidative epithelial cancer cells, driving OXPHOS and mitochondrial metabolism. Thus, stromal catabolism fuels anabolic tumor growth via energy transfer. We have termed this new cancer paradigm the “reverse Warburg effect,” because stromal cells undergo aerobic glycolysis, rather than tumor cells. To assess whether this mechanism also applies during cancer cell metastasis, we analyzed the bioenergetic status of breast cancer lymph node metastases, by employing a series of metabolic protein markers. For this purpose, we used MCT4 to identify glycolytic cells. Similarly, we used TOMM20 and COX staining as markers of mitochondrial mass and OXPHOS activity, respectively. Consistent with the “reverse Warburg effect,” our results indicate that metastatic breast cancer cells amplify oxidative mitochondrial metabolism (OXPHOS) and that adjacent stromal cells are glycolytic and lack detectable mitochondria. Glycolytic stromal cells included cancer-associated fibroblasts, adipocytes and inflammatory cells. Double labeling experiments with glycolytic (MCT4) and oxidative (TOMM20 or COX) markers directly shows that at least two different metabolic compartments co-exist, side-by-side, within primary tumors and their metastases. Since cancer-associated immune cells appeared glycolytic, this observation may also explain how inflammation literally “fuels” tumor progression and metastatic dissemination, by “feeding” mitochondrial metabolism in cancer cells. Finally, MCT4(+) and TOMM20(-) “glycolytic” cancer cells were rarely observed, indicating that the conventional “Warburg effect” does not frequently occur in cancer-positive lymph node metastases.Key words: caveolin-1, oxidative stress, MCT4, metabolic coupling, tumor stroma, SLC16A3, monocarboxylic acid transporter, two-compartment tumor metabolism, metastasis, TOMM20, complex IV, OXPHOS, mitochondria, inflammation     

What Is the Optimal Threshold at Which to Recommend Breast Biopsy?

Background

A 2% threshold, traditionally used as a level above which breast biopsy recommended, has been generalized to all patients from several specific situations analyzed in the literature. We use a sequential decision analytic model considering clinical and mammography features to determine the optimal general threshold for image guided breast biopsy and the sensitivity of this threshold to variation of these features.

Methodology/Principal Findings

We built a decision analytical model called a Markov Decision Process (MDP) model, which determines the optimal threshold of breast cancer risk to perform breast biopsy in order to maximize a patient’s total quality-adjusted life years (QALYs). The optimal biopsy threshold is determined based on a patient’s probability of breast cancer estimated by a logistic regression model (LRM) which uses demographic risk factors (age, family history, and hormone use) and mammographic findings (described using the established lexicon–BI-RADS). We estimate the MDP model''s parameters using SEER data (prevalence of invasive vs. in situ disease, stage at diagnosis, and survival), US life tables (all cause mortality), and the medical literature (biopsy disutility and treatment efficacy) to determine the optimal “base case” risk threshold for breast biopsy and perform sensitivity analysis. The base case MDP model reveals that 2% is the optimal threshold for breast biopsy for patients between 42 and 75 however the thresholds below age 42 is lower (1%) and above age 75 is higher (range of 3–5%). Our sensitivity analysis reveals that the optimal biopsy threshold varies most notably with changes in age and disutility of biopsy.

Conclusions/Significance

Our MDP model validates the 2% threshold currently used for biopsy but shows this optimal threshold varies substantially with patient age and biopsy disutility.     

The Type of Breast Reconstruction May Not Influence Patient Satisfaction in the Chinese Population: A Single Institutional Experience

Background

The goal of this study was to evaluate patient satisfaction with four common types of breast reconstruction performed at our institution: latissimus dorsi myocutaneous (LDM) flap reconstruction with or without implants, pedicled transverse rectus abdominis musculocutaneous (TRAM) flap reconstruction, and free deep inferior epigastric perforator (DIEP) flap reconstruction.

Methods

A custom survey consisting of questions that assessed general and aesthetic satisfaction was sent to patients who had undergone breast reconstruction in the last 5 years. The clinical data and details of the surgery were also collected from the patients who returned the surveys. We compared satisfaction rates across the four breast reconstruction types and analyzed the effects of various factors on overall general and aesthetic satisfaction rates using a binary logistic regression model.

Result

A total of 207 (72%) patients completed the questionnaires. Overall, significant differences in general and aesthetic satisfaction among the four procedures were not observed. A multivariate analysis revealed that the factor “complications” (p = 0.001) played a significant role in general satisfaction and that the factors “> 2 years since reconstruction” (p = 0.043) and “age > 35 years” (p = 0.05) played significant roles in overall aesthetic satisfaction.

Conclusion

The present study demonstrated that the type of breast reconstruction might not influence satisfaction in Chinese patients.     

Risk factors for breast cancer in women biopsied for benign breast disease: A nested case-control study

Aim: Women with a history of benign breast disease are at increased risk of subsequent breast cancer. However, few studies have examined whether established breast cancer risk factors other than histology are associated with an altered risk of breast cancer in women with benign breast disease. We used a nested case-control design within a large, multi-center cohort of women biopsied for benign breast disease (BBD) to estimate odds ratios for breast cancer in association with exposure to a range of personal and lifestyle factors. Methods: Cases were women biopsied for BBD who subsequently developed breast cancer; controls were individually matched to cases on center and age at diagnosis and were women biopsied for BBD who did not develop breast cancer in the same follow-up interval as that for the cases. After excluding women with prevalent breast cancer, 1357 records (661 case records and 696 records) were available for analysis. We used conditional logistic regression to obtain crude and multivariable-adjusted estimates of the association between specific factors and risk of breast cancer. Results: In multivariable analyses age at first live birth, number of pregnancies, and postmenopausal status were inversely associated with risk of breast cancer. The odds ratio for women with age at first birth <25 years and ≥3 pregnancies, relative to nulliparous women, was 0.49, 95% confidence interval 0.13–0.79, and that for postmenopausal women relative to premenopausal women was 0.60, 95% CI 0.37–0.99. Conclusions: Further study of personal factors influencing the risk of breast cancer in women with BBD may help to identify subgroups of the population at increased risk of invasive disease.     

Is cancer a metabolic rebellion against host aging?: In the quest for immortality,tumor cells try to save themselves by boosting mitochondrial metabolism

Aging drives large systemic reductions in oxidative mitochondrial function, shifting the entire body metabolically toward aerobic glycolysis, a.k.a, the Warburg effect. Aging is also one of the most significant risk factors for the development of human cancers, including breast tumors. How are these two findings connected? One simplistic idea is that cancer cells rebel against the aging process by increasing their capacity for oxidative mitochondrial metabolism (OXPHOS). Then, local and systemic aerobic glycolysis in the aging host would provide energy-rich mitochondrial fuels (such as L-lactate and ketones) to directly “fuel” tumor cell growth and metastasis. This would establish a type of parasite-host relationship or “two-compartment tumor metabolism,” with glycolytic/oxidative metabolic coupling. The cancer cells (“the seeds”) would flourish in this nutrient-rich microenvironment (“the soil”), which has been fertilized by host aging. In this scenario, cancer cells are only trying to save themselves from the consequences of aging by engineering a metabolic mutiny, through the amplification of mitochondrial metabolism. We discuss the recent findings of Drs. Ron DePinho (MD Anderson) and Craig Thomspson (Sloan-Kettering) that are also consistent with this new hypothesis, linking cancer progression with metabolic aging. Using data mining and bioinformatics approaches, we also provide key evidence of a role for PGC1a/NRF1 signaling in the pathogenesis of (1) two-compartment tumor metabolism and (2) mitochondrial biogenesis in human breast cancer cells.Key words: aging, mitochondria, cancer metabolism, autophagy, mitophagy, aerobic glycolysis, oxidative phosphorylation, Metformin, drug resistance, chemoresistance, Warburg effect, metabolic compartments, parasite, PGC1a, PGC1b, NRF1, two-compartment tumor metabolism     

Association of Genetic Ancestry with Breast Cancer in Ethnically Diverse Women from Chicago

Introduction

Non-Hispanic (nH) Black and Hispanic women are disproportionately affected by early onset disease, later stage, and with more aggressive, higher grade and ER/PR negative breast cancers. The purpose of this analysis was to examine whether genetic ancestry could account for these variation in breast cancer characteristics, once data were stratified by self-reported race/ethnicity and adjusted for potential confounding by social and behavioral factors.

Methods

We used a panel of 100 ancestry informative markers (AIMs) to estimate individual genetic ancestry in 656 women from the “Breast Cancer Care in Chicago” study, a multi-ethnic cohort of breast cancer patients to examine the association between individual genetic ancestry and breast cancer characteristics. In addition we examined the association of individual AIMs and breast cancer to identify genes/regions that may potentially play a role in breast cancer disease disparities.

Results

As expected, nH Black and Hispanic patients were more likely than nH White patients to be diagnosed at later stages, with higher grade, and with ER/PR negative tumors. Higher European genetic ancestry was protective against later stage at diagnosis (OR 0.7 95%CI: 0.54–0.92) among Hispanic patients, and higher grade (OR 0.73, 95%CI: 0.56–0.95) among nH Black patients. After adjustment for multiple social and behavioral risk factors, the association with later stage remained, while the association with grade was not significant. We also found that the AIM SNP rs10954631 on chromosome 7 was associated with later stage (p = 0.02) and higher grade (p = 0.012) in nH Whites and later stage (p = 0.03) in nH Blacks.

Conclusion

Non-European genetic ancestry was associated with later stage at diagnosis in ethnic minorities. The relation between genetic ancestry and stage at diagnosis may be due to genetic factors and/or unmeasured environmental factors that are overrepresented within certain racial/ethnic groups.     

Serine 59 Phosphorylation of αB-Crystallin Down-regulates Its Anti-apoptotic Function by Binding and Sequestering Bcl-2 in Breast Cancer Cells

The small heat shock protein (sHSP) αB-crystallin is a new oncoprotein in breast carcinoma that predicts poor clinical outcome in breast cancer. However, although several reports have demonstrated that phosphorylation of sHSPs modify their structural and functional properties, the significance of αB-crystallin phosphorylation in cancer cells has not yet been investigated. In this study, we have characterized the phosphorylation status of αB-crystallin in breast epithelial carcinoma cells line MCF7 submitted to anti-cancer agents like vinblastine. We have showed that the main phosphorylation site of αB-crystallin in response to vinblastine is serine 59 and determined a correlation between this post-translational modification and higher apoptosis level. The overexpression of the serine 59 “pseudophosphorylated” mutant (S59E) induces a significant increase in the apoptosis level of vinblastine-treated MCF7 cells. In contrast, overexpression of wild-type αB-crystallin or “nonphosphorylatable” mutant (S59A) result in a resistance to this microtubule-depolymerizing agent, while inhibition of endogenous levels of αB-crystallin by expression of shRNA lowers it. Analyzing further the molecular mechanism of this phenomenon, we report for the first time that phosphorylated αB-crystallin preferentially interacts with Bcl-2, an anti-apoptotic protein, and this interaction prevents the translocation of Bcl-2 to mitochondria. Hence, this study identifies serine 59 phosphorylation as an important key in the down-regulation of αB-crystallin anti-apoptotic function in breast cancer and suggests new strategies to improve anti-cancer treatments.