Irradiation as an Alternative to Mastectomy for Early Breast Cancer—An Important Consideration Because of Changes in Laws

Between May 1973 and December 1980 there were 76 patients (78 breasts) with clinical stage I or II breast carcinoma treated by biopsy and definitive radiotherapy at Stanford University Medical Center. Local-regional control has been achieved thus far in 76 of 78 cases (97 percent) with a median follow-up time of 26 months. Transient lymphedema of the breast, arm edema and breast fibrosis were the most commonly noted complications. The cosmetic result was analyzed and scored as excellent in 78 percent, satisfactory in 18 percent and unsatisfactory in 4 percent. The three unsatisfactory results occurred in patients in whom severe fibrosis developed as a result of suboptimal radiation techniques. Interdisciplinary cooperation among surgical, medical and radiation oncologists is important. The 97 percent local-regional control and the 96 percent excellent-to-satisfactory results support the use of primary radiotherapy in early stage breast carcinoma.     

Socioeconomic Disparity in Breast Cancer Detection in Hong Kong – A High Income City: Retrospective Epidemiological Study Using the Breast Cancer Registry

Background

It is not known whether socioeconomic disparities affect the detection of breast cancer in Asian countries where the incidence of breast cancer is a rising trend. In this study, we explore the socioeconomic profiles of women and the stage of the disease at the time of diagnosis in breast cancer patients aged 40 or over in Hong Kong.

Method

During the period 2008 to 2011, 5393 breast cancer patients registered with the Hong Kong Breast Cancer Registry. Participants and their clinicians were asked to complete standardised questionnaires including patient socio-demographics, health history and risk factors, the course of the disease, post-treatment physical discomfort and psychosocial impact, follow-up recurrence and survival status.

Results

Monthly household incomes, educational levels and the practice of regular screening are independently associated with the stage of the disease at diagnosis. Higher socioeconomic status and a higher educational level were associated with an earlier stage of the disease at the time of diagnosis. Yearly clinical examinations, ultrasound and mammographic screening every 2 to 3 years were significantly associated with the earlier detection of breast cancer.

Conclusion

There were socioeconomic disparities among Hong Kong women who were found to have breast cancer. Population-based screening policies, including raising awareness among women at risk, should be implemented.     

Detection of Cervical Cancer—A Study of Motivation for Cytological Screening

Annual cytological examination of cervical scrapings should virtually eliminate deaths from cervical cancer, but many deaths still occur because not all women are sufficiently motivated to have the examination.As part of a San Diego County Medical Society cancer control project, 2000 women were interviewed to evaluate motivating influences. It was found that most of the 70 per cent who had had the examination were motivated by the advice of physicians, rather than directly by lay publicity. Women who had not had the examination, more commonly the old and the poor, were not antagonistic but mostly unmotivated. Lay education to induce women to seek medical advice, and education of physicians to get them to urge and to carry out their part in routine annual cytologic examination of cervical exudate probably could bring about virtual elimination of death from cervical cancer.     

Estimating key parameters in periodic breast cancer screening—Application to the Canadian National Breast Screening Study data

Problem statement: Breast cancer screening in women of younger age has been controversial. The screening sensitivities, transition probabilities and sojourn time distributions are estimated for females aged 40–49 years and 50–59 years separately, using the Canadian National Breast Screening Study (CNBSS) data. The purpose is to estimate the lead time distribution and the probability of not detecting the cancer early. Approach: Within the 40–49-year-old and 50–59-year-old cohorts separately, the age-independent statistical model was applied. Bayesian estimators along with 95% highest probability density (HPD) credible intervals (CI) were calculated. Bayesian hypothesis testing was used to compare the parameter estimates of the two cohorts. The lead time density was also estimated for both the 40–49 and 50–59-year-old cohorts. Results: The screening sensitivity, transition probability of the disease, and mean sojourn time were all found to increase with age. For the 40–49-year-old and 50–59-year-old cohorts, the posterior mean sensitivities were 0.70 (95% HPD-CI: 0.46, 0.93) and 0.77 (0.61, 0.93), respectively. The posterior mean transition probabilities were 0.0023 (0.0018, 0.0027) and 0.0031 (0.0024, 0.0038), while the posterior mean sojourn times were 2.55 (1.56, 4.26) years and 3.15 (2.12, 4.96) years. Bayes factors for the ratio of posterior probabilities that the respective parameter was larger vs. smaller in the 50–59-year-old cohort were estimated to be 2.09, 40.8 and 3.0 for the sensitivity, transition probability, and mean sojourn time, respectively. All three Bayes factors were larger than two, indicating greater than 2:1 odds in favor of the hypothesis that each of these parameters was greater in the 50–59-year-old cohort. The estimated mean lead times were 0.83 years and 0.96 years if the two cohorts were screened annually. Conclusions: The increase in sensitivity corresponds to an increase in the mean sojourn time. Breast cancer in younger women is more difficult to detect by screening tests and is more aggressive than breast cancer in older women. Women aged 50–59 tend to benefit more from screening compared with women aged 40–49.     

Plant Responses to Brief Touching: A Mechanism for Early Neighbour Detection?

In natural habitats plants can be exposed to brief and light contact with neighbouring plants. This mechanical stimulus may represent a cue that induces responses to nearby plants. However, little is known about the effect of touching on plant growth and interaction with insect herbivores. To simulate contact between plants, a soft brush was used to apply light and brief mechanical stimuli to terminal leaves of potato Solanum tuberosum L. The number of non-glandular trichomes on the leaf surface was counted on images made by light microscope while glandular trichomes and pavement cells were counted on images made under scanning electronic microscope. Volatile compounds were identified and quantified using coupled gas chromatography–mass spectrometry (GC-MS). Treated plants changed their pattern of biomass distribution; they had lower stem mass fraction and higher branch and leaf mass fraction than untouched plants. Size, weight and number of tubers were not significantly affected. Touching did not cause trichome damage nor change their total number on touched terminal leaves. However, on primary leaves the number of glandular trichomes and pavement cells was significantly increased. Touching altered the volatile emission of treated plants; they released higher quantities of the sesquiterpenes (E)-β-caryophyllene, germacrene D-4-ol and (E)-nerolidol, and lower quantities of the terpenes (E)-ocimene and linalool, indicating a systemic effect of the treatment. The odour of touched plants was significantly less preferred by the aphids Macrosiphum euphorbiae and Myzus persicae compared to odour of untouched plants. The results suggest that light contact may have a potential role in the detection of neighbouring plants and may affect plant-insect interactions.     

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.     

Genetic Features of Metachronous Esophageal Cancer Developed in Hodgkin’s Lymphoma or Breast Cancer Long-Term Survivors: An Exploratory Study

BackgroundDevelopment of novel therapeutic drugs and regimens for cancer treatment has led to improvements in patient long-term survival. This success has, however, been accompanied by the increased occurrence of second primary cancers. Indeed, patients who received regional radiotherapy for Hodgkin’s Lymphoma (HL) or breast cancer may develop, many years later, a solid metachronous tumor in the irradiated field. Despite extensive epidemiological studies, little information is available on the genetic changes involved in the pathogenesis of these solid therapy-related neoplasms.MethodsUsing microsatellite markers located in 7 chromosomal regions frequently deleted in sporadic esophageal cancer, we investigated loss of heterozygosity (LOH) and microsatellite instability (MSI) in 46 paired (normal and tumor) samples. Twenty samples were of esophageal carcinoma developed in HL or breast cancer long-term survivors: 14 squamous cell carcinomas (ESCC) and 6 adenocarcinomas (EADC), while 26 samples, used as control, were of sporadic esophageal cancer (15 ESCC and 11 EADC).ResultsWe found that, though the overall LOH frequency at the studied chromosomal regions was similar among metachronous and sporadic tumors, the latter exhibited a statistically different higher LOH frequency at 17q21.31 (p = 0.018). By stratifying for tumor histotype we observed that LOH at 3p24.1, 5q11.2 and 9p21.3 were more frequent in ESCC than in EADC suggesting a different role of the genetic determinants located nearby these regions in the development of the two esophageal cancer histotypes.ConclusionsAltogether, our results strengthen the genetic diversity among ESCC and EADC whether they occurred spontaneously or after therapeutic treatments. The presence of histotype-specific alterations in esophageal carcinoma arisen in HL or breast cancer long-term survivors suggests that their transformation process, though the putative different etiological origin, may retrace sporadic ESCC and EADC carcinogenesis.     

Maximal Sensitive Dependence and the Optimal Path to Epidemic Extinction

Extinction of an epidemic or a species is a rare event that occurs due to a large, rare stochastic fluctuation. Although the extinction process is dynamically unstable, it follows an optimal path that maximizes the probability of extinction. We show that the optimal path is also directly related to the finite-time Lyapunov exponents of the underlying dynamical system in that the optimal path displays maximum sensitivity to initial conditions. We consider several stochastic epidemic models, and examine the extinction process in a dynamical systems framework. Using the dynamics of the finite-time Lyapunov exponents as a constructive tool, we demonstrate that the dynamical systems viewpoint of extinction evolves naturally toward the optimal path.     

Detection of RASSF1A and RAR? Hypermethylation in Serum DNA from Breast Cancer Patients

Breast cancer is fast emerging as the leading cancer amongst females, especially in young females in metropolitan cities in India. The epigenetic alterations involved in the onset and progression of breast cancer may serve as biomarkers for early detection and prognosis of the disease. Furthermore, using body fluids such as serum offers a non-invasive method to procure multiple samples for such analyses. In this study, we examined methylation status of two normally unmethylated but biologically significant cancer genes, RAS association domain family protein 1A (RASSF1A) and Retionic acid receptor ? (RAR?) by Methylation Specific PCR (MSP) in invasive ductal carcinomas of the breast and paired serum DNA. RASSF1A was found to be methylated in 17 of 20 (85%) breast tumors; while sera from 15 of 20 (75%) of the patients showed concordant methylated RASSF1A, with a sensitivity of 88%. RAR? was methylated in 2/20 (10%) breast tumors. A gene unmethylated in the tumor DNA was always found to be unmethylated in the matched serum DNA for both RASSF1A and RAR? genes; hence specificity was 100%. Immunohistochemical analysis of RAR? protein in 15 breast carcinoma patients harboring unmethylated RAR? in tumors and serum DNA showed the expression of RAR? protein in tumors and paired normal breast tissues, confirming the MSP findings, suggesting that RAR? promoter is functional in these cases. This study underscores the potential utility of DNA methylation based screening of serum, a readily accessible body fluid, as a surrogate marker for early detection of breast cancer.      

Breast Cancer Res Treat:利用微卫星变异诊断乳腺癌

<正>近日,弗吉尼亚理工大学的研究人员发现一种新的诊断标志物,可能有助于临床医生更好地预测和预防这种疾病。抗击乳腺癌的战斗是没有止境的,1/8的妇女在有生之年可能患乳腺癌,因此找到更好的预测指标非常重要。通过将乳腺癌血液样品基因组与无癌症个人的样本进行比较,研究人员精确定位了一些新的标记,不仅可以揭示乳腺癌风险,同时可能为乳腺癌的治疗产生益处。这项研究结果发表在Breast Cancer Research and Treatment杂志上。