Bayesian and survival model for tumor relapse status and disease-specific survival, with applications to breast cancer

Breast cancer is the most common non-skin cancer and the second leading cause of cancer-related death in women in the United States. Studies on ipsilateral breast tumor relapse (IBTR) status and disease-specific survival will help guide clinic treatment and predict patient prognosis.^ After breast conservation therapy, patients with breast cancer may experience breast tumor relapse. This relapse is classified into two distinct types: true local recurrence (TR) and new ipsilateral primary tumor (NP). However, the methods used to classify the relapse types are imperfect and are prone to misclassification. In addition, some observed survival data (e.g., time to relapse and time from relapse to death)are strongly correlated with relapse types. The first part of this dissertation presents a Bayesian approach to (1) modeling the potentially misclassified relapse status and the correlated survival information, (2) estimating the sensitivity and specificity of the diagnostic methods, and (3) quantify the covariate effects on event probabilities. A shared frailty was used to account for the within-subject correlation between survival times. The inference was conducted using a Bayesian framework via Markov Chain Monte Carlo simulation implemented in softwareWinBUGS. Simulation was used to validate the Bayesian method and assess its frequentist properties. The new model has two important innovations: (1) it utilizes the additional survival times correlated with the relapse status to improve the parameter estimation, and (2) it provides tools to address the correlation between the two diagnostic methods conditional to the true relapse types.^ Prediction of patients at highest risk for IBTR after local excision of ductal carcinoma in situ (DCIS) remains a clinical concern. The goals of the second part of this dissertation were to evaluate a published nomogram from Memorial Sloan-Kettering Cancer Center, to determine the risk of IBTR in patients with DCIS treated with local excision, and to determine whether there is a subset of patients at low risk of IBTR. Patients who had undergone local excision from 1990 through 2007 at MD Anderson Cancer Center with a final diagnosis of DCIS (n=794) were included in this part. Clinicopathologic factors and the performance of the Memorial Sloan-Kettering Cancer Center nomogram for prediction of IBTR were assessed for 734 patients with complete data. Nomogram for prediction of 5- and 10-year IBTR probabilities were found to demonstrate imperfect calibration and discrimination, with an area under the receiver operating characteristic curve of .63 and a concordance index of .63. In conclusion, predictive models for IBTR in DCIS patients treated with local excision are imperfect. Our current ability to accurately predict recurrence based on clinical parameters is limited.^ The American Joint Committee on Cancer (AJCC) staging of breast cancer is widely used to determine prognosis, yet survival within each AJCC stage shows wide variation and remains unpredictable. For the third part of this dissertation, biologic markers were hypothesized to be responsible for some of this variation, and the addition of biologic markers to current AJCC staging were examined for possibly provide improved prognostication. The initial cohort included patients treated with surgery as first intervention at MDACC from 1997 to 2006. Cox proportional hazards models were used to create prognostic scoring systems. AJCC pathologic staging parameters and biologic tumor markers were investigated to devise the scoring systems. Surveillance Epidemiology and End Results (SEER) data was used as the external cohort to validate the scoring systems. Binary indicators for pathologic stage (PS), estrogen receptor status (E), and tumor grade (G) were summed to create PS+EG scoring systems devised to predict 5-year patient outcomes. These scoring systems facilitated separation of the study population into more refined subgroups than the current AJCC staging system. The ability of the PS+EG score to stratify outcomes was confirmed in both internal and external validation cohorts. The current study proposes and validates a new staging system by incorporating tumor grade and ER status into current AJCC staging. We recommend that biologic markers be incorporating into revised versions of the AJCC staging system for patients receiving surgery as the first intervention.^ Chapter 1 focuses on developing a Bayesian method to solve misclassified relapse status and application to breast cancer data. Chapter 2 focuses on evaluation of a breast cancer nomogram for predicting risk of IBTR in patients with DCIS after local excision gives the statement of the problem in the clinical research. Chapter 3 focuses on validation of a novel staging system for disease-specific survival in patients with breast cancer treated with surgery as the first intervention. ^

Correlates of post-diagnosis weight management among female breast cancer survivors: An Internet survey

Objective. Weight gain after cancer treatment is associated with breast cancer recurrence. In order to prolong cancer-free survivorship, interventions to manage post-diagnosis weight are sometimes conducted. However, little is known about what factors are associated with weight management behaviors among cancer survivors. In this study, we examined associations of demographic, clinical, and psychosocial variables with weight management behaviors in female breast cancer survivors. We also examined whether knowledge about post-diagnosis weight gain and its risk is associated with weight management behaviors. ^ Methods. 251 female breast cancer survivors completed an internet survey. They reported current performance of three weight management behaviors (general weight management, physical activity, and healthy diet). We also measured attitude, elf-efficacy, knowledge and social support regarding these behaviors along with demographic and clinical characteristics. ^ Results. Multiple regression models for the weight management behaviors explained 17% of the variance in general weight management, 45% in physical activity and 34% in healthy dieting. The models had 9–14 predictor variables which differed in each model. The variables associated with all three behaviors were social support and self-efficacy. Self-efficacy showed the strongest contribution in all models. The knowledge about weight gain and its risks was not associated with any weight management behaviors. However, women who obtained the knowledge during cancer treatment were more likely to engage in physical activity and healthy dieting. ^ Conclusions. The findings suggest that an intervention designed to increase their self-efficacy to manage weight, to be physically active, to eat healthy will effectively promote survivors to engage in these behaviors. Knowledge may motivate women to manage post-diagnosis weight about risk if information is provided during cancer treatment.^

Effect of insurance status on stage of breast cancer diagnosis

Objective: The purpose of this study is to compare the stages of breast cancer presented between the insured and uninsured patients diagnosed at The Rose, an active non-profit breast healthcare organization to determine if uninsured patients present with more advanced stage breast cancer as compared to their insured counterparts. ^ Study Design: Retrospective cross-sectional study. ^ Methods: The study included 1,265 patients who received breast healthcare services and were diagnosed with breast cancer at The Rose between FY 2007 and FY 2012. 738 of the patients in the study were presumably uninsured since their breast healthcare services were sponsored through various funding sources and they were navigated into treatment through The Rose patient navigation program. We compared breast cancer stages for women who had insurance with those who did not have insurance. The effects of age and race/ethnicity along with the insurance status on the stage of reast cancer diagnosis were also analyzed. We calculated the odds ratio using the contingency tables; and estimated odds ratios (ORs) and 95% confidence intervals (CIs) using ordinal logistic regression by applying multiple imputation method for missing tumor stage data. ^ Results: The ordered logistic regression analysis with ordered tumor stage as dependent variable and uninsured as independent variable gave us an odds ratio of 1.73 (OR=1.73; p-value<0.05; 95% CI: 1.36 - 2.12). ^ Conclusions: Insurance status is a strong predictor of stage of breast cancer diagnosed among women seen at The Rose. Uninsured women seen at The Rose are almost twice as likely to present at a advanced stage of breast cancer as opposed to their insured counterparts.^

Breast cancer risk factors among Mexican-American women

Introduction: The average age of onset of breast cancer among Hispanic women is 50 years, more than a decade earlier than non-Hispanic white women. Age at diagnosis is an important prognostic factor for breast cancer; younger age at onset is more likely to be associated with advanced disease, poorer prognosis, hormone receptor negative breast tumors, and a greater likelihood of hereditary breast cancer. Studies of breast cancer risk factors including reproductive risk factors, family history of breast cancer, and breast cancer subtype have been conducted predominately in non-Hispanic whites. Breast cancer is a heterogeneous disease with the presence of clinically, biologically, and epidemiologically distinct subtypes that also differ with respect to their risk factors. The associations between reproductive risk factors and family history of breast cancer have been well documented in the literature. However, only a few studies have assessed these associations with breast cancer subtype in Hispanic populations. Methods: To assess the associations between reproductive risk factors and family history of breast cancer we conducted three separate studies. First, we conducted a case-control study of 172 Mexican-American breast cancer cases and 344 age matched controls residing in Harris County, TX to assess reproductive and other risk factors. We conducted logistic regression analysis to assess differences in cases and controls adjusted for age at diagnosis and birthplace and then we conducted a multinomial logistic regression analysis to compare reproductive risk factors among the breast tumor subtypes. In a second study, we identified 139 breast cancer patients with a first- or second-degree family history of breast cancer and 298 without a family history from the ELLA Bi-National Breast Cancer Study. In this analysis, we also computed a multinomial logistic regression to evaluate associations between family history of breast cancer and breast cancer subtypes, and logistic regression to estimate associations between breast cancer screening practices with family history of breast cancer. In the final study, we employed a cross-sectional study design in 7279 Mexican-American women in the Mano a Mano Cohort Study. We evaluated associations with family history of breast cancer and breast cancer risk factors including body mass index (BMI), lifestyle factors, migration history, and adherence to American Cancer Society (ACS) guidelines. Results: In the results of our first analyses, reproductive risk factors differed in the magnitude and direction of associations when stratified by age and birthplace among cases and controls. In our second study, family history of breast cancer, and having at least one relative diagnosed at an early age (<50 years) was associated with triple negative breast cancer (TNBC). Mammography prior to receiving a breast cancer diagnosis was associated with family history of breast cancer. In our third study that assessed lifestyle factors, migration history and family history of breast cancer; we found that women with a first-degree family history of breast cancer were more overweight or obese compared with their counterparts without a family history. There was no indication that having a family history contributed to women practicing healthier lifestyle behaviors and/or adhering to the ACS guidelines for cancer prevention. Conclusions: We observed that among Mexican-American women, reproductive risk factors were associated with breast cancer where the woman was born (US or Mexico). Having a family history of breast cancer, especially having either a first- or second-degree relative diagnosed at a younger age, was strongly associated with TNBC subtype. These results are consistent with other published studies in this area. Further, our results indicate that women with strong family histories of breast cancer are more likely to undertake mammography but not to engage in healthier lifestyle behaviors.^

Influencia de un programa de ejercicio aeróbico en la calidad de vida de pacientes afectadas por cáncer de mama = Influence of an aerobic exercise program on breast cancer patients’ quality of life

INTRODUCCIÓN Actualmente las supervivientes de cáncer de mama viven durante más tiempo. Sin embargo, los tratamientos utilizados presentan importantes efectos secundarios que afectan y marcan su calidad de vida. Numerosos estudios han mostrado que el ejercicio es una herramienta apta, segura y efectiva reduciendo algunos de estos efectos secundarios y, en suma, mejorando la calidad de vida de estas pacientes, aspecto que presenta al ejercicio físico como una intervención integral para ellas. Por el contrario, se ha observado que las supervivientes de cáncer de mama reducen la cantidad de ejercicio que realizan después de dichos tratamientos. Por ello, el objetivo de este proyecto es examinar los efectos de un programa integral de ejercicio en la calidad de vida y la cantidad de ejercicio físico que realizan las pacientes con cáncer de mama en su tiempo, tras finalizar sus tratamientos. MATERIAL Y MÉTODOS Se diseñó un Ensayo Clínico Aleatorizado. Noventa pacientes diagnosticadas de cáncer de mama en estadios tempranos que habían terminado sus tratamientos de radioterapia y quimioterapia recientemente, fueron reclutadas por la Universidad Politécnica de Madrid, desde enero de 2013 hasta junio de 2014. Las pacientes fueron aleatorizadas tras las mediciones iniciales al grupo control (tratamientos habituales) o grupo intervención, durante tres meses. La intervención consistió en 24 clases de ejercicio combinando práctica aeróbica y de fuerza con el fin de reducir los efectos secundarios de dichos tratamientos. La calidad de vida, la cantidad de ejercicio físico realizado en tiempo de ocio, VO2max, la fuerza, la movilidad articular del hombro, la fatiga, la depresión y la ansiedad fueron medidos al inicio y después de los tres meses en todos los pacientes. RESULTADOS Un total de 89 pacientes con una media de 49.06±8.75 de edad fueron finalmente analizadas. El grupo intervención (n=44) mostraron significativamente mejores resultados en calidad de vida (p=0.0001; d=0.85), cantidad de ejercicio en tiempo de ocio (p=0.0001; d=2.77), en variables de la composición corporal, en variables físicas y en variables psicológicas comparado con el grupo control (n=45). Además, se observó una correlación significativa entre la calidad de vida y el ejercicio realizado en tiempo de ocio en el grupo intervención (r= 0.58; p=0.001), que no fue patente en el grupo control. Se observaron cambios significativos en el grupo de intervención relativos a la composición corporal, con aumento de la masa muscular (p=0.001) y reducción de la masa grasa (p=0.0001). Tanto las variables físicas como psicológicas también mostraron diferencias significativas a favor al grupo de intervención en las comparaciones entre grupos. CONCLUSIONES Según estos resultados, un programa de ejercicio físico específico es una intervención integral que mejora los hábitos y la calidad de vida de las supervivientes de cáncer de mama, lo que reduce determinados efectos secundarios de los tratamientos y aumenta la salud física y psicológica general de estas mujeres. Este tipo de intervenciones pude ser una herramienta barata y efectiva para ofrecer a los pacientes, integrada en los tratamientos habituales. ABSTRACT INTRODUCTION It is well known that breast cancer survivors are living longer. However, breast cancer treatments present serious side effects, which could affect breast cancer survivors’ (BCS) health and quality of life (QoL). Exercise has been presented as a feasible, safe and effective tool in reducing some of these side effects and to improve survivors’ QoL, acting as an integrative treatment for them, although it has been observed that BCS reduce their leisure time exercise (LTE) levels. Therefore, the aim of this study was to examine the effects of an integrative exercise program in QoL and LTE in BCS after the completion of their adjuvant treatment. MATERIAL AND METHODS A randomized controlled trial (RCT) was designed. Ninety patients diagnosed with an early stage of breast cancer and who recently finished chemotherapy and radiotherapy treatments were recruited by the Technical University of Madrid from January 2013 to June 2014. Patients were randomized after baseline assessments to the intervention group (IG) or to the control group (CG) (usual care) for three months. The Intervention consisted in 24 supervised exercise classes, combining aerobic and resistance exercises in order to reduce the most common side effects of the treatments. QoL, LTE, body composition, VO2max, strength, shoulder range of motion, fatigue, depression and self-esteem were measured in all the patients at baseline and after three months. RESULTS A total of 89 patients aged 49.06±8.75 years were finally assessed. IG (n=44) showed significant better results in QoL (p=0.0001; d=0.85), LTE (p=0.0001; d=2.77), in body composition, in the physical variable and in psychological outcomes, compared with the CG (n=45). In addition, a correlation between QoL and LTE (r= 0.58; p=0.001) was found in the IG, while CG did not show this correlation. Significant changes in body composition were observed in the group comparisons, especially in lean mass (p=0.001) and body fat mass (p= 0.0001). Positive changes were also observed in the physical and psychological variables in comparisons between groups. CONCLUSIONS These results suggest that this exercise program may be an integrative intervention, which is able to improve QoL and LTE levels in breast cancer survivors, reducing breast cancer side effects of treatments and improving their physical and psychological general health. Exercise may be an effective and inexpensive strategy to be included in patients integrative care.

The cancer growth suppressor gene mda-7 selectively induces apoptosis in human breast cancer cells and inhibits tumor growth in nude mice

A differentiation induction subtraction hybridization strategy is being used to identify and clone genes involved in growth control and terminal differentiation in human cancer cells. This scheme identified melanoma differentiation associated gene-7 (mda-7), whose expression is up-regulated as a consequence of terminal differentiation in human melanoma cells. Forced expression of mda-7 is growth inhibitory toward diverse human tumor cells. The present studies elucidate the mechanism by which mda-7 selectively suppresses the growth of human breast cancer cells and the consequence of ectopic expression of mda-7 on human breast tumor formation in vivo in nude mice. Infection of wild-type, mutant, and null p53 human breast cancer cells with a recombinant type 5 adenovirus expressing mda-7, Ad.mda-7 S, inhibited growth and induced programmed cell death (apoptosis). Induction of apoptosis correlated with an increase in BAX protein, an established inducer of programmed cell death, and an increase in the ratio of BAX to BCL-2, an established inhibitor of apoptosis. Infection of breast carcinoma cells with Ad.mda-7 S before injection into nude mice inhibited tumor development. In contrast, ectopic expression of mda-7 did not significantly alter cell cycle kinetics, growth rate, or survival in normal human mammary epithelial cells. These data suggest that mda-7 induces its selective anticancer properties in human breast carcinoma cells by promoting apoptosis that occurs independent of p53 status. On the basis of its selective anticancer inhibitory activity and its direct antitumor effects, mda-7 may represent a new class of cancer suppressor genes that could prove useful for the targeted therapy of human cancer.

Increased expression of preprotachykinin-I and neurokinin receptors in human breast cancer cells: Implications for bone marrow metastasis

Neuropeptides are implicated in many tumors, breast cancer (BC) included. Preprotachykinin-I (PPT-I) encodes multiple neuropeptides with pleiotropic functions such as neurotransmission, immune/hematopoietic modulation, angiogenesis, and mitogenesis. PPT-I is constitutively expressed in some tumors. In this study, we investigated a role for PPT-I and its receptors, neurokinin-1 (NK-1) and NK-2, in BC by using quantitative reverse transcription–PCR, ELISA, and in situ hybridization. Compared with normal mammary epithelial cells (n = 2) and benign breast biopsies (n = 21), BC cell lines (n = 7) and malignant breast biopsies (n = 25) showed increased expression of PPT-I and NK-1. NK-2 levels were high in normal and malignant cells. Specific NK-1 and NK-2 antagonists inhibited BC cell proliferation, suggesting autocrine and/or intercrine stimulation of BC cells by PPT-I peptides. NK-2 showed no effect on the proliferation of normal cells but mediated the proliferation of BC cells. Cytosolic extracts from malignant BC cells enhanced PPT-I translation whereas extracts from normal mammary epithelial cells caused no change. These enhancing effects may be protein-specific because a similar increase was observed for IL-6 translation and no effect was observed for IL-1α and stem cell factor. The data suggest that PPT-I peptides and their receptors may be important in BC development. Considering that PPT-I peptides are hematopoietic modulators, these results could be extended to understand early integration of BC cells in the bone marrow, a preferred site of metastasis. Molecular signaling transduced by PPT-I peptides and the mechanism that enhances translation of PPT-I mRNA could lead to innovative strategies for BC treatments and metastasis.

Hormonal prevention of breast cancer: Mimicking the protective effect of pregnancy

Full term pregnancy early in life is the most effective natural protection against breast cancer in women. Rats treated with chemical carcinogen are similarly protected by a previous pregnancy from mammary carcinogenesis. Proliferation and differentiation of the mammary gland does not explain this phenomenon, as shown by the relative ineffectiveness of perphenazine, a potent mitogenic and differentiating agent. Here, we show that short term treatment of nulliparous rats with pregnancy levels of estradiol 17β and progesterone has high efficacy in protecting them from chemical carcinogen induced mammary cancers. Because the mammary gland is exposed to the highest physiological concentrations of estradiol and progesterone during full term pregnancy, it is these elevated levels of hormones that likely induce protection from mammary cancer. Thus, it appears possible to mimic the protective effects of pregnancy against breast cancer in nulliparous rats by short term specific hormonal intervention.

Treatment of a human breast cancer xenograft with an adenovirus vector containing an interferon gene results in rapid regression due to viral oncolysis and gene therapy.

Treatment of a human breast cancer cell line (MDA-MB-435) in nude mice with a recombinant adenovirus containing the human interferon (IFN) consensus gene, IFN-con1 (ad5/IFN), resulted in tumor regression in 100% of the animals. Tumor regression occurred when virus was injected either within 24 hr of tumor cell implantation or with established tumors. However, regression of the tumor was also observed in controls in which either the wild-type virus or a recombinant virus containing the luciferase gene was used, although tumor growth was not completely suppressed. Tumor regression was accompanied by a decrease in p53 expression. Two other tumors, the human myelogenous leukemic cell line K562 and the hamster melanoma tumor RPMI 1846, also responded to treatment but only with ad5/IFN. In the case of K562 tumors, there was complete regression of the tumor, and tumors derived from RPMI 1846 showed partial regression. We propose that the complete regression of the breast cancer with the recombinant virus ad5/IFN was the result of two events: viral oncolysis in which tumor cells are being selectively lysed by the replication-competent virus and the enhanced effect of expression of the IFN-con1 gene. K562 and RPMI 1846 tumors regressed only as a result of IFN gene therapy. This was confirmed by in vitro analysis. Our results indicate that a combination of viral oncolysis with a virus of low pathogenicity, itself resistant to the effects of IFN and IFN gene therapy, might be a fruitful approach to the treatment of a variety of different tumors, in particular breast cancers.

Confirming the Association Between Affective Disturbance and Perceived Cognitive Dysfunction Among Breast Cancer Patients: A Meta-Analysis of Available Literature

Purpose: Breast cancer is the most frequently diagnosed cancer among women worldwide. While undergoing chemotherapy treatment for breast cancer, patients often report experiencing "chemobrain." Previous literature reports correlations between psychological distress and these perceived cognitive problems. The aim of the present study was to examine the strength of the association between affective disturbance and subjective cognitive dysfunction.Methods: This study included a meta-analysis of the literature reporting a correlation between mood and subjective cognitive dysfunction. Eight studies with 1344 breast cancer patients treated with chemotherapy were selected based on stringent study inclusion criteria. Studies reporting a correlation coefficient between mood and subjective cognitive dysfunction were included.Results: In these data, there was no significant correlation between affective disturbance and subjective cognitive dysfunction. A random effects model yielded an overall weighted mean effect size of 0.12.Conclusion: Although this meta-analysis did not confirm the correlation between mood and subjective cognitive dysfunction, there was a clear association between these factors in the original disaggregated analyses, and they are clearly impactful from the time of diagnosis through long-term after care. The clinical implications of the present study and future directions for research are discussed.

Improving supportive care for women with breast cancer in Australia: The challenge of modifying health systems

Although the benefits of many psychosocial support strategies in improving well being in women with breast cancer have been demonstrated, few women receive these programs as part of routine care. This paper provides some recommendations, based on experience in Australia, about how access to evidence-based supportive care strategies might be improved through modification of health systems. It demonstrates the paucity of research about the costs and health service implications of psychosocial support strategies, which is vital to health planning and service delivery change. It outlines the systematic approach taken in Australia to improving psychosocial support nationally by: the development of research reviews; preparation of guidelines about supportive care, implementation of programs to foster the adoption of guidelines through modification of policy, health service delivery and clinician training; and monitoring programs. Coalitions of government, health care professionals and consumers are key to effective lobbying for change. If all women with breast cancer are to receive better supportive care, there is a need for approaches which: refocus the research effort in psycho-oncology; develop more strategic approaches to generating change in health systems and health policy and foster partnerships to advocate for improved resources. Copyright (C) 2003 John Wiley Sons, Ltd.

Changes in survival after breast cancer: improvements in diagnosis or treatment?

We have compared 5-year survival rates in two cohorts of women diagnosed with breast cancer in Brisbane, Australia, between 1981-1984 and 1990-1994. Tumours diagnosed in the early 1990s were significantly smaller and less likely to have nodal involvement than those diagnosed 10 years earlier (P < 0.0001). The size difference was particularly striking for women aged over 50 at diagnosis, those targeted for screening. Five-year survival was greater among women diagnosed in the 1990s (84% vs. 74%; hazard ratio (HR) 0.61, 95% confidence interval (CI) 0.46-0.81). After adjusting for the effects of tumour size and nodal status this difference was reduced, but women diagnosed more recently still showed improved survival (HR 0.75; 95% CI 0.56-1.01) and disease-free survival (HR 0.72; 0.56-0.92) at 5 years. This suggests that both earlier diagnosis and changes in breast cancer treatment have contributed to improved breast cancer survival. (C) 2003 Elsevier Ltd. All rights reserved.

Improving the physical status and quality of life of women treated for breast cancer: A pilot study of a structured exercise intervention

Background and Objectives: This pilot project assessed the acceptability of a mixed-type, moderate-intensity exercise programme following breast cancer treatment, and the impact on presence of lymphoedema, fitness, body composition, fatigue, mood and quality of life. Methods: Ten women completed the programme and measures of fitness (submaximal ergometer test), body composition (bio-electrical impedance), lympoedema (bio-electrical impedance and arm circumferences), fatigue (revised Piper Fatigue Scale), mood (Hospital Anxiety and Depression Scale), quality of life (FACT-B) and general well-being, at baseline, completion of the programme, and 6-week and 3-month follow-up. Results: Participation in the programme caused no adverse effect on the presence of lymphoedema. There was a trend towards reduction in fatigue and improved quality of life across the testing phases. Women rated the programme extremely favourably, citing benefits of the support of other women, trained guidance, and the opportunity to experience different types of exercise. Conclusions: A mixed-type, moderate-intensity exercise program in a group format is acceptable to women following breast cancer treatment, with the potential to reduce fatigue and improve quality of life, without exacerbating or precipitating lymphoedema. This pilot work needs to be confirmed in larger randomised studies. (C) 2004 Wiley-Liss, Inc.

Children's and family needs of young women with advanced breast cancer: A review

This article reviews literature about the impact of advanced breast cancer on children and families. It is clear that the adjustment of the family is influenced by disease stage and maternal adjustment, the needs of the particular child relating closely to their developmental stage. Interventions with children and families to promote adjustment when a parent has advanced cancer are also discussed, including implications for clinical practice.

Columnar cell lesions of the breast: The missing link in breast cancer progression? A morphological and molecular analysis

Columnar cell lesions (CCLs) of the breast are a spectrum of lesions that have posed difficulties to pathologists for many years, prompting discussion concerning their biologic and clinical significance. We present a study of CCL in context with hyperplasia of usual type (HUT) and the more advanced lesions ductal carcinoma in situ (DCIS) and invasive ductal carcinoma. A total of 81 lesions from 18 patients were subjected to a comprehensive morphologic review based upon a modified version of Schnitt's classification system for CCL, immunophenotypic analysis (estrogen receptor [ER], progesterone receptor [PgR], Her2/neu, cytokeratin 5/6 [CK5/6], cytokeratin 14 [CK14], E-cadherin, p53) and for the first time, a whole genome molecular analysis by comparative genomic hybridization. Multiple CCLs from 3 patients were studied in particular detail, with topographic information and/or showing a morphologic spectrum of CCL within individual terminal duct lobular units. CCLs were ER an PgR positive, CK5/6 and CK14 negative, exhibit low numbers of genetic alterations and recurrent 16q loss, features that are similar to those of low grade in situ and invasive carcinoma. The molecular genetic profiles closely reflect the degree of proliferation and atypia in CCL, indicating some of these lesions represent both a morphologic and molecular continuum. In addition, overlapping chromosomal alterations between CCL and more advanced lesions within individual terminal duct lobular units suggest a commonality in molecular evolution. These data further support the hypothesis that CCLs are a nonobligate, intermediary step in the development of some forms of low grade in situ and invasive carcinoma. Copyright: © 2005 Lippincott Williams & Wilkins, Inc.