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Context: Long-term, postmenopausal use of hormone replacement therapy (HRT) appears to increase breast cancer risk. Whether the effect of HRT use on risk of breast cancer varies among histological types of invasive carcinoma is unknown.Objective: To determine associations between HRT use and risk of ductal carcinoma in situ (DCIS), invasive carcinoma with favorable histology, and invasive ductal or lobular carcinoma.Design: Prospective cohort study whose participants were followed up continuously for 11 years from January 1986 to December 1996.Setting and Participants: Iowa Women's Health Study, a population-based random sample of postmenopausal women aged 55 to 69 years in 1986. A total of 1520 incident breast cancer cases occurred in the at-risk cohort of 37 105 women.Main Outcome Measures: Multivariate-adjusted relative risk (RR) of tumor-specific breast cancers associated with duration of ever, current, or past HRT use.Results: Duration of ever HRT use was associated with risk of invasive carcinoma with a favorable histology, with an RR of 1.81 (95% confidence interval [CI], 1.07-3.07) for those who used HRT 5 or fewer years vs an RR of 2.65 (95% CI, 1.34-5.23) for those who used HRT for more than 5 years (P for trend = .005) after adjustment for age and other breast cancer risk factors. There was no association between ever HRT use and the incidence of DCIS or invasive ductal or lobular carcinoma. Among current hormone users, after adjusting for age and other breast cancer risk factors, the RRs (95% CIs) of invasive carcinoma with a favorable histology were 4.42 (2.00-9.76) and 2.63 (1.18-5.89) for 5 or fewer years of use and for more than 5 years of use, respectively. Risk of invasive ductal or lobular carcinoma was associated with current use (< or =5 years) of HRT with an RR of 1.38 (95% CI, 1.03-1.85).Conclusions: Exposure to HRT was associated most strongly with an increased risk of invasive breast cancer with a favorable prognosis. These data add important clinical information for assessing the risks and benefits of HRT use. [ABSTRACT FROM AUTHOR]

Prospective, randomized clinical trials have demonstrated that the alternatives of mastectomy or conservative surgery plus radiation therapy provide equivalent survival for patients with invasive breast cancer. The identification of a subset of women who could undergo conservative surgery without radiotherapy would avoid the costs, inconvenience, and complications of radiotherapy and is an important research goal. Four randomized trials comparing conservative surgery alone with conservative surgery plus radiotherapy have demonstrated an average reduction in the risk of disease recurrence in the breast of 84% with the use of radiotherapy. No significant differences in survival have been observed, although the available studies lack sufficient numbers of patients to demonstrate a potential small, but clinically important, survival advantage for patients treated with radiotherapy. Subset analysis in the randomized trials and prospective studies of highly selected patients have failed to consistently identify a group of patients who do not benefit from radiation therapy. Any recurrence of breast cancer is psychologically devastating, and fewer than one half of the patients who have had disease recurrence after conservative surgery alone have undergone further breast-conserving treatment. At present, a group of patients who do not require radiotherapy has not been reproducibly identified, and radiotherapy should remain a part of breast-conserving therapy for invasive carcinoma. [ABSTRACT FROM AUTHOR]

Guidelines for the locoregional treatment of primary breast cancer were last published by the US National Institutes of Health in 1991. Since then, new surgical and radiotherapeutic techniques have been developed, clinical trials have provided new evidence, and intriguing long-term effects have emerged from global metadatabases. A revision of these guidelines is therefore necessary and timely. To address this concern, in October 2008, a group of opinion leaders from Austria, Denmark, France, Germany, Italy, the Netherlands, the United Kingdom, and the United States who have worked and published in the field of locoregional treatment met and collectively prepared and approved the described set of recommendations for the use of surgery and radiotherapy in primary breast cancer outside of clinical trials. [ABSTRACT FROM AUTHOR]

HIV prevalence is increasing in China. The proportion of infection attributable to heterosexual sex in China is also on the rise. The scale of internal migration for work is likely to be one of the factors contributing to these changing patterns, but little is known about HIV-related knowledge, perceptions and risk behaviours of China's migrant workers. This study aimed to investigate HIV-related knowledge, attitudes and risk behaviours of male rural-to-urban migrant workers in Chengdu and to identify factors associated with risk behaviours. In 2005, a cross-sectional questionnaire survey was completed by 163 male construction- and factory-based migrant workers aged 18-35 years. With a mean age of 26 years, just 30% had completed senior middle school and 47% were currently married. Respondents were highly mobile, worked long hours and were relatively poorly paid. As migrants, their access to urban services and benefits was restricted, making it difficult for family members to join them. Knowledge of HIV transmission was generally poor and discriminatory attitudes towards people with HIV were commonplace. Seventy-five percent were sexually experienced, among whom 88% had had sexual relations in the last 12 months. Of these, 30% had had two or more partners and 20% had paid for sex. Just 36% had used a condom during the most recent sexual encounter with a sex worker. Around 70% thought it was 'impossible' for them to become infected, yet a significant sub-group were engaging in sexual behaviours that place them at risk of infection with HIV and sexually transmitted infections (STIs). Logistic Regression found a significant association between having multiple sexual partners and both education level and marital status. Education was also found to be significantly associated with purchasing sex. Targeted HIV-prevention programs for male migrant workers in Chengdu, especially for those who are single and less educated, are urgently needed. [ABSTRACT FROM AUTHOR]

The t(12;21)(p13;q22) translocation generates the TEL-AML1 (TEL, translocation-Ets-leukemia; AML1, acute myeloid leukemia-1) (ETV6-RUNX1) fusion product and is the most common chromosomal abnormality in pediatric leukemia. Our previous studies using a murine fetal liver transplantation model demonstrated that TEL-AML1 promotes the self-renewal of B-cell precursors in vitro and enhances the expansion of hematopoietic stem cells (HSCs) in vivo. This is consistent with the hypothesis that TEL-AML1 induces expansion of a preleukemic clone. Several studies have described domains within TEL-AML1 involved in the transcriptional regulation of specific target genes. However, it is unclear which of these domains is important for the activity of TEL-AML1 in preleukemic hematopoiesis. In order to examine this, we have generated a panel of deletion mutants and expressed them in HSCs. These experiments demonstrate that TEL-AML1 requires multiple domains from both TEL and AML1 to alter hematopoiesis. Furthermore, mutation of a single amino-acid residue within the runt homology domain of AML1, required for DNA binding, was sufficient to abrogate TEL-AML1 activity. These data suggest that TEL-AML1 acts as an aberrant transcription factor to perturb multiple pathways during hematopoiesis.Oncogene (2007) 26, 4404–4414; doi:10.1038/sj.onc.1210227; published online 22 January 2007 [ABSTRACT FROM AUTHOR]

Focuses on advances in endocrine therapy for metastatic breast cancer. Characteristics of endocrine therapy; Aromatase enzymes that can be used in endocrine therapy.

Smoking in Vietnam, as elsewhere in Asia, is strongly sex-linked. A 1997 national prevalence survey found about half of males but just 3.4% of females used tobacco regularly. Little is known about smoking-related health awareness or attitudes in Vietnam. There is concern that women may take up smoking if rapid social change brings alteration in traditional gender norms that discourage this behaviour. Effective tobacco control depends upon accurate understanding of prevailing knowledge and views. This paper reports on a 1999-2000 collaborative study into smoking attitudes, practices and health awareness, with particular reference to gender norms. A survey, based partly on findings from initial focus groups, was administered to young female students (n = 1018) and factory workers (n = 1002) in Ho Chi Minh City, Vietnam's largest metropolis. Participants were recruited through random cluster sampling. Results indicated that smoking continues to be shunned by the vast majority of young urban students and factory workers, although prevalence was slightly higher than found in national surveys, and there was a moderate degree of experimentation. Perhaps of greater concern was the degree of ambivalence voiced about taking up smoking in the future. Moreover, while nearly all expressed awareness of negative health effects of tobacco, these were vaguely worded and excluded key mortality risks. Gender norms appeared to be strongly enduring, with female non-smoking attributed overwhelmingly to its 'inappropriateness'. Male smoking was seen as normative. Overall, workers (representing a low-income, less-educated population) had higher rates of tobacco use and less health knowledge than students. The paper concludes with a discussion about ramifications for public health interventions. [ABSTRACT FROM AUTHOR]

Focuses on a combined qualitative and quantitative study conducted in Chiang Mai, Thailand. Intensification of conflicts between women's productive and reproductive roles by development and social change; Investigation of experiences of those who resumed employment within six months after delivery; Obstacles faced by women to maintain lactation while working.

We previously reported that stable transfection of protein kinase C alpha (PKCalpha) into T47D human breast cancer cells results in tamoxifen (TAM)-resistant tumour growth. Relevance of PKCalpha expression in clinical specimens was determined by comparing PKCalpha expression in tumours from patients exhibiting disease recurrence with patients remaining disease-free following TAM treatment. Our results suggest that PKCalpha expression may predict TAM treatment failure. [ABSTRACT FROM AUTHOR]

A reply by B.J. Mehrara and M. Morrow to a letter to the editor about their article "Prophylactic mastectomy and the timing of breast reconstruction," in the previous issue is presented.

The article offers information on the significance of prophylactic mastectomy (PM) and the timing of breast reconstruction to women with breast cancer in the U.S. As stated, patients experiencing PM with immediate breast reconstruction proved to have high degrees of satisfaction and a lack of decisional regret. Thus, the reconstructive technique used is a major factor in the length of operation, risk of morbidity and time to retrieval.

We have adopted an analysis that produces a post hoc prediction of the time course of electromyogram (EMG) activity from the discharge of ensembles of neurons recorded sequentially from the primary motor cortex (M1) of a monkey. Over several recording sessions, we collected data from 50 M1 neurons and several distal forelimb muscles during a stereotyped precision grip task. Ensemble averages were constructed from 5 to 10 trials for each neuron and EMG signal. We used multiple linear regression on randomly chosen subsets of these neurons to find the best fit between the neuronal and EMG data. The fixed delay between neuronal and EMG signals that yielded the largest coefficient of determination (R(2)) between predicted and actual EMG was 50 ms. R(2) averaged 0.83 for ensembles composed of 15 neurons. If, instead, each neuronal signal was delayed by the time of its peak cross-correlation with the EMG signal, R(2) increased to 0.88. Using all 50 neurons, R(2) under these conditions averaged nearly 0.97. A similar analysis was conducted with signals recorded during both a power grip and a precision grip task. Quality of the fit dropped dramatically when parameters from the precision grip for a given set of neurons were used to fit data recorded during the power grip. However, when a single set of regression parameters was used to fit a combination of the two tasks, the quality of the fits decreased by <10% from that of a single task. [ABSTRACT FROM AUTHOR]

Background: Given accumulating evidence supporting postmastectomy radiotherapy (PMRT) in selected patients, it is important to evaluate patterns and correlates of PMRT utilization, including communication and attitudinal factors.Methods: The authors surveyed 2382 patients diagnosed with breast cancer in 2002 and reported to the Los Angeles and Detroit Surveillance, Epidemiology, and End Results registries (n=1844, 77.4% response rate). Analyses were restricted to patients with nonmetastatic invasive breast cancer treated by mastectomy who had decided whether or not to undergo PMRT (n=396). The authors assessed rates of explanation, recommendation, and receipt of radiation by indication grouping, defined primarily by the 2001 American Society of Clinical Oncology guidelines. They evaluated correlates of PMRT receipt, including tumor and sociodemographic characteristics. They also explored patients' self-reported reasons for nonreceipt of PMRT.Results: The adjusted proportion in each indication group reporting that a provider had explained radiation was high (77% of those in whom PMRT was indicated, 76% of those in whom medical opinion was divided, and 73% of those in whom PMRT was not indicated; P=.10). The adjusted proportions reporting recommendations for radiation (86%, 35%, and 17%, respectively) and receipt (81%, 34%, and 10%, respectively) varied significantly by indication grouping (P<.001). On multivariate analysis, tumor size (P<.001), lymph node status (P<.001), comorbidity (P=.02), and chemotherapy receipt (P=.003) were found to be independent significant correlates of PMRT receipt. The most common reasons cited for not pursuing PMRT were lack of physician recommendation and perceived lack of need.Conclusions: PMRT receipt is strongly correlated with clinical indication. The authors found no sociodemographic disparities in utilization. However, approximately one-fifth of patients with strong indications did not receive treatment. [ABSTRACT FROM AUTHOR]

Farnesyl transferase inhibitors (FTIs) target signal-transduction pathways responsible for the proliferation and survival of hematologic malignancies, including acute myelogenous leukemias (AML). Lonafarnib has been shown to be a potent inhibitor of Pgp-mediated drug efflux. On the basis of these findings, we examined the Pgp-inhibitory properties of tipifarnib and assessed its activity when combined with anthracyclines. The effects of tipifarnib on cell proliferation, induction of apoptosis and inhibition of Pgp-mediated anthracycline efflux were analyzed in two human leukemia cell lines overexpressing Pgp (CCRF-CEM and KG1a). Measurement of residual daunorubicin (DNR)-mediated fluorescence after incubation with DNR and tipifarnib demonstrated that tipifarnib significantly inhibited DNR efflux in CCRF-CEM with an IC(50) value less than 0.5 microM. Proliferation and apoptosis assays after exposure to DNR in the presence or absence of tipifarnib demonstrated synergistic inhibition of cellular proliferation, and induction of apoptosis with the combination of tipifarnib and DNR. Similar data was obtained with an enantiomer of tipifarnib that possesses no FTI activity. Incubation with tipifarnib and DNR did not interfere with inhibition of the post-translational processing of HDJ-2. These data suggest that tipifarnib possesses Pgp-inhibitory activity in addition to its FTI activity. In high risk and refractory patients these properties may be exploited as a dual targeting mechanism in the therapy of AML. [ABSTRACT FROM AUTHOR]

Summary:To establish the incidence of CMV viremia after allogeneic blood stem cell transplantation, we studied 51 consecutive allogeneic peripheral blood stem cell (PBSC) transplant recipients. A total of 12 recipients were at moderate risk for CMV disease and 39 were at high risk. Conditioning regimens varied, but GvHD prophylaxis consisted of tacrolimus and mini-methotrexate in all patients. All patients received prophylactic ganciclovir from admission until day -2 and prophylactic acyclovir from day -1 until day 180 after transplantation. CMV viremia was treated with ganciclovir. Using a PCR-based technique, the cumulative incidence of CMV viremia was 31±14% by day 100 and 35±14% by day 150. Donor type, CMV risk group, underlying disorder, conditioning regimen, GvHD, and steroid use were not associated with the risk for CMV viremia. No cases of CMV disease occurred. We hypothesize that the low rate of CMV viremia and the absence of CMV disease in this cohort of PBSCT transplant recipients, which contrasts with other reports, may be related to the prophylactic use of high-dose acyclovir and possibly to pretransplant use of ganciclovir.Bone Marrow Transplantation (2003) 31, 813-816. doi:10.1038/sj.bmt.1703916 [ABSTRACT FROM AUTHOR]

Background: Nipple‐sparing mastectomy (NSM) is being performed increasingly for risk reduction in high‐risk groups. There are limited data regarding complications and oncological outcomes in women undergoing bilateral prophylactic NSM. This study reviewed institutional experience with prophylactic NSM, and examined the indications, rates of postoperative complications, incidence of occult malignant disease and subsequent breast cancer diagnosis. Methods: Women who had bilateral prophylactic NSM between 2000 and 2016 were identified from a prospectively maintained database. Rates of postoperative complications, incidental breast cancer, recurrence and overall survival were evaluated. Results: A total of 192 women underwent 384 prophylactic NSMs. Indications included BRCA1 or BRCA2 mutations in 117 patients (60·9 per cent), family history of breast cancer in 35 (18·2 per cent), lobular carcinoma in situ in 29 (15·1 per cent) and other reasons in 11 (5·7 per cent). Immediate breast reconstruction was performed in 191 patients. Of 384 NSMs, 116 breasts (30·2 per cent) had some evidence of skin necrosis at follow‐up, which resolved spontaneously in most; only 24 breasts (6·3 per cent) required debridement. Overall, there was at least one complication in 129 breasts (33·6 per cent); 3·6 and 1·6 per cent had incidental findings of ductal carcinoma in situ and invasive breast cancer respectively. The nipple–areola complex was preserved entirely in 378 mastectomies. After a median follow‐up of 36·8 months, there had been no deaths and no new breast cancer diagnoses. Conclusion: These findings support the use of prophylactic NSM in high‐risk patients. The nipples could be preserved in the majority of patients, postoperative complication rates were low, and, with limited follow‐up, there were no new breast cancers. [ABSTRACT FROM AUTHOR]

Background: Young age at breast cancer diagnosis is associated with negative prognostic outcomes, and breast cancer in black women often manifests at a young age. This study evaluated the effect of age on breast cancer management and outcomes in black women. Methods: This was a retrospective cohort study of all black women treated for invasive breast cancer between 2005 and 2010 at a specialized tertiary‐care cancer centre. Clinical and treatment characteristics were compared by age. Kaplan–Meier methodology was used to estimate overall survival (OS) and disease‐free survival (DFS). Results: A total of 666 black women were identified. Median BMI was 30 (range 17–56) kg/m2 and median tumour size was 16 (1–155) mm. Most tumours were oestrogen receptor‐positive (66·4 per cent). Women were stratified by age: less than 40 years (74, 11·1 per cent) versus 40 years or more (592, 88·9 per cent). Younger women were significantly more likely to have a mastectomy, axillary lymph node dissection and to receive chemotherapy, and were more likely to have lymphovascular invasion and positive lymph nodes, than older women. The 5‐year OS rate was 88·0 (95 per cent c.i. 86·0 to 91·0) per cent and the 5‐year DFS rate was 82·0 (79·0 to 85·0) per cent. There was no statistically significant difference in OS by age (P = 0·236). Although DFS was inferior in younger women on univariable analysis (71 versus 88 per cent; P < 0·001), no association was found with age on multivariable analysis. Conclusion: Young black women with breast cancer had more adverse pathological factors, received more aggressive treatment, and had worse DFS on univariable analysis. Young age at diagnosis was, however, not an independent predictor of outcome. [ABSTRACT FROM AUTHOR]

Discusses the selection of the proper treatment for ductal carcinoma in situ (DCIS). Increase in DCIS incidence rates; Confusing variety of treatments for the disease; Role of tamoxifen; Mastectomy, excision and radiation therapy, and excision alone; Importance of tailoring the intensity of cancer treatment with respect to an individual's risk of recurrence.

Background Nipple-sparing mastectomy ( NSM) is associated with improved cosmesis and is being performed increasingly. Its role in BRCA mutation carriers has not been well described. This was a study of the indications for, and outcomes of, NSM in BRCA mutation carriers. Methods BRCA mutation carriers who underwent NSM were identified. Details of patient demographics, surgical procedures, complications, and relevant disease stage and follow-up were recorded. Results A total of 177 NSMs were performed in 89 BRCA mutation carriers between September 2005 and December 2013. Twenty-six patients of median age 41 years had NSM for early-stage breast cancer and a contralateral prophylactic mastectomy. Mean tumour size was 1·4 (range 0·1-3·5) cm. Sixty-three patients of median age 39 years had prophylactic NSM, eight of whom had an incidental diagnosis of ductal carcinoma in situ. There were no local or regional recurrences in the 26 patients with breast cancer at a median follow-up of 28 (i.q.r. 15-43) months. There were no newly diagnosed breast cancers in the 63 patients undergoing prophylactic NSM at a median follow-up of 26 (11-42) months. All patients had immediate breast reconstruction. Five patients (6 per cent) required subsequent excision of the nipple-areola complex for oncological or other reasons. Skin desquamation occurred in 68 (38·4 per cent) of the 177 breasts, and most resolved without intervention. Debridement was required in 13 (7·3 per cent) of the 177 breasts, and tissue-expander or implant removal was necessary in six instances (3·4 per cent). Conclusion NSM is an acceptable choice for patients with BRCA mutations, with no evidence of compromise to oncological safety at short-term follow-up. Complication rates were acceptable, and subsequent excision of the nipple-areola complex was rarely required. [ABSTRACT FROM AUTHOR]

There are well over a quarter of a billion chronic hepatitis B virus (HBV) carriers across the globe. Most carriers are at high risk for development of liver cirrhosis and subsequent progression to hepatocellular carcinoma. It is therefore imperative to develop new approaches for immunotherapy against this infection. Antibodies and cytotoxic T cells to different HBV antigens are believed to be important for reducing viral load and clearing HBV-infected cells from the liver. Some of the major challenges facing current vaccine candidates have been their inability to induce both humoral and cellular immunity to multiple antigenic targets and the induction of potent immune responses against the major genotypes of HBV. In this study, highly optimized synthetic DNA plasmids against the HBV consensus core (HBc) and surface (HBs) antigens genotypes A and C were developed and evaluated for their immune potential. These plasmids, which encode the most prevalent genotypes of the virus, were observed to individually induce binding antibodies to HBs antigens and drove robust cell-mediated immunity in animal models. Similar responses to both HBc and HBs antigens were observed when mice and non-human primates were inoculated with the HBc-HBs cocktails. In addition to the cytotoxic T lymphocyte activities exhibited by the immunized mice, the vaccine-induced responses were broadly distributed across multiple antigenic epitopes. These elements are believed to be important to develop an effective therapeutic vaccine. These data support further evaluation of multivalent synthetic plasmids as therapeutic HBV vaccines. [ABSTRACT FROM AUTHOR]

An abstract of the research paper "Potent cellular immune responses after therapeutic immunization of HIV-positive patients with the PENNVAX-B DNA vaccine in a Phase I Trial," by P. Tebas and colleagues is presented.

DNA-based vaccines, while highly immunogenic in mice, generate significantly weaker responses in primates. Therefore, current efforts are aimed at increasing their immunogenicity, which include optimizing the plasmid/gene, the vaccine formulation and method of delivery. For example, co-immunization with molecular adjuvants encoding an immunomodulatory protein has been shown to improve the antigen (Ag)-specific immune response. Thus, the incorporation of enhancing elements, such as these, may be particularly important in the influenza model in which high titered antibody (Ab) responses are critical for protection. In this regard, we compared the ability of plasmid-encoded high-mobility group box 1 protein (HMGB1), a novel cytokine in which we have previously mutated in order to increase DNA vaccine immunogenicity, with boost Ag-specific immune responses during DNA vaccination with influenza A/PR/8/34 nucleoprotein or the hemagglutinin of A novel H1N1/09. We show that the HMGB1 adjuvant is capable of enhancing adaptive effector and memory immune responses. Although Ag-specific antibodies were detected in all vaccinated animals, a greater neutralizing Ab response was associated with the HMGB1 adjuvant. Furthermore, these responses improved CD8 T+-cell effector and memory responses and provided protection against a lethal mucosal influenza A/PR/8/34 challenge. Thus, co-immunization with HMGB1 has strong in vivo adjuvant activity during the development of immunity against plasmid-encoded Ag. [ABSTRACT FROM AUTHOR]

The magnitude of the immune response to a DNA vaccine depends on three criteria-the optimized vector design, the use of a suitable adjuvant and the successful delivery and subsequent expression of the plasmid in the target tissue. In vivo electroporation (EP) has proved to be particularly effective in efficiently delivering DNA immunogens to the muscle and the skin, and indeed several devices have entered into human clinical trials. Here, we report on a novel concept of DNA delivery to the dermal tissue using a minimally invasive EP device, which is powered using low-voltage parameters. We show that this prototype device containing a novel 4 × 4-electrode array results in robust and reproducible transfection of dermal tissue and subsequent antigen expression at the injection site. Using DNA encoding for NP and M2e influenza antigens, we further show induction of potent cellular responses in a mouse model as measured by antigen-specific T-cell ELISpot assays. Importantly, 100% of the immunized animals were protected when challenged with VN/1203/04 (H5N1) strain of influenza. We have also extended our findings to a guinea-pig model and demonstrated induction of HI titers greater than 1:40 against a pandemic novel H1N1 virus showing proof of concept efficacy for DNA delivery with the prototype device in a broad spectrum of species and using multiple antigens. Finally, we were able to generate protective HI titers in macaques against the same novel H1N1 strain. Our results suggest that the minimally invasive dermal device may offer a safe, tolerable and efficient method to administer DNA vaccinations in a prophylactic setting, and thus potentially represents an important new option for improved DNA vaccine delivery in vivo. [ABSTRACT FROM AUTHOR]

Multiple randomized trials demonstrate equivalent survival between BCT and mastectomy, but clinical outcomes research must also evaluate patient satisfaction and quality of life. This review analyzes existing patient-reported outcome (PRO) measures in oncologic breast surgery to assess utility and make recommendations for future research. We performed a systematic literature review to identify PRO measures used in oncologic breast surgery patients. After applying inclusion and exclusion criteria, qualifying instruments were assessed for adherence to international guidelines for health outcomes instrument development and validation. Ten measures underwent development and psychometric evaluation in an oncologic breast surgery population. Five of ten measures (EORTC QLQ BR-23, FACT-B, HBIS, BIBCQ, and BREAST-Q) reported an adequate development and validation process. Three of these 5 measures (EORTC QLQ BR-23, FACT-B, HBIS) focused on non-surgical treatment issues. A fourth instrument (BIBCQ) did not address aesthetic concerns after breast reconstruction. The fifth instrument (BREAST-Q) was developed for use in patients undergoing mastectomy ± reconstruction, but did not address breast-conserving therapy. Overall, two key limitations were noted: 1) surgery-specific issues of breast-conserving surgery patients were not well represented and 2) measures were largely developed without the aid of newer psychometric methods that may improve their clinical utility. Reliable and valid PRO measures in breast cancer patients exist, but even the best instruments do not address all important surgery-specific and psychometric issues of oncologic breast surgery patients. Newer psychometric methods would facilitate development of scales for use in individual patient care as well as group level comparisons. [ABSTRACT FROM AUTHOR]

Background: Multiple studies have suggested that resection of the primary tumor improves survival in patients with stage IV breast cancer, yet in the era of targeted therapy, the relation between surgery and tumor molecular subtype is unknown. The objective of the current study was to identify subsets of patients who may benefit from primary tumor treatment and assess the frequency of local disease progression.Methods: Patients presenting with stage IV breast cancer and intact primary tumors (n = 186) were identified from a prospectively maintained clinical database (2000-2004) and clinical data were abstracted (grading determined according to the American Joint Committee on Cancer staging system).Results: Surgery was performed in 69 (37%) patients: 34 (49%) patients with unknown metastatic disease at the time of surgery, 15 (22%) patients for local control, 14 (20%) patients for palliation, and in 6 (9%) patients to obtain tissue. Surgical patients were more likely to be HER-2/neu negative (P = .001), and to have smaller tumors (P = .05) and solitary metastasis (P <.001). Local therapy included axillary lymph node clearance in 33 (48%) patients and postoperative radiotherapy in 9 (13%) patients. The median survival was 35 months. Cox regression analysis identified estrogen receptor (ER) positivity (hazard ratio [HR], 0.47; 95% confidence interval [95% CI], 0.29-0.76), progesterone receptor (PR) positivity (HR, 0.57; 95% CI, 0.36-0.90), and HER-2/neu amplification (HR, 0.51; 95% CI, 0.34-0.77) as being predictive of improved survival. There was a trend toward improved survival with surgery (HR, 0.71; 95% CI, 0.47-1.06). On exploratory analyses, surgery was found to be associated with improved survival in patients with ER/PR positive or HER-2/neu-amplified disease (P = .004). No survival benefit was observed in patients with triple-negative disease.Conclusions: Although a trend toward improved survival with surgery was observed, it was noted most strongly in patients with ER/PR positive and/or HER-2/neu-amplified disease. This suggests that the impact of local control is greatest in the presence of effective targeted therapy, and supports the need for further study to define patient subsets that will benefit most. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) regulate the expression of multiple proteins in a dose-dependent manner. We hypothesized that increased expression of miRNAs encoded on chromosome 21 (chr 21) contribute to the leukemogenic function of trisomy 21. The levels of chr 21 miRNAs were quantified by qRT-PCR in four types of childhood acute lymphoblastic leukemia (ALL) characterized by either numerical (trisomy or tetrasomy) or structural abnormalities of chr 21. Suprisingly, high expression of the hsa-mir-125b-2 cluster, consisting of three miRNAs, was identified in leukemias with the structural ETV6/RUNX1 abnormality and not in ALLs with trisomy 21. Manipulation of ETV6/RUNX1 expression and chromatin immunoprecipitation studies showed that the high expression of the miRNA cluster is an event independent of the ETV6/RUNX1 fusion protein. Overexpression of hsa-mir-125b-2 conferred a survival advantage to Ba/F3 cells after IL-3 withdrawal or a broad spectrum of apoptotic stimuli through inhibition of caspase 3 activation. Conversely, knockdown of the endogenous miR-125b in the ETV6/RUNX1 leukemia cell line REH increased apoptosis after Doxorubicin and Staurosporine treatments. P53 protein levels were not altered by miR-125b. Together, these results suggest that the expression of hsa-mir-125b-2 in ETV6/RUNX1 ALL provides survival advantage to growth inhibitory signals in a p53-independent manner. [ABSTRACT FROM AUTHOR]