Current Breast Cancer Treatment Research Articles

Abstract A068: Targeting Akt reactivation following mTOR inhibition in breast cancer treatment

Abstract Breast cancer is the second leading cause of cancer related deaths in women and up to 60% of diagnosed cases are estrogen receptor (ER)-positive. ER-positive status is associated with a poor prognosis. While ER-positive cancers could be targeted with endocrine therapy, such as aromatase inhibitors, resistance often develops. Therefore, there is a need to better understand molecular contributions of other signaling pathways with the goal of treating patients with personalized combination therapies. The mechanistic target of rapamycin complex 1 (mTORC1) regulates cell cycle progression and proliferation and is a target of a naturally occurring inhibitor rapamycin. The 40S ribosomal S6 Kinase 1 (S6K1) is one of the best characterized downstream targets of mTORC1. The mTORC1/S6K1 pathway is often hyperactivated in breast cancer, promoting cell growth and proliferation. S6K1 is encoded by the RPS6KB1 gene, located on the 17q23 chromosomal region. While this region is amplified in several types of cancer, multi-copy amplicons are found specifically in breast cancer, underscoring the importance of S6K1 in this disease. Importantly, there is a direct link between the mTORC1/S6K1 and ER signaling pathways. S6K1 directly phosphorylates and activates ER, promoting ligand-independent ER activation and endocrine resistance. Based on this data, current FDA approved treatment of advaced ER-positive breast cancer combines mTORC1 inhibitors with endocrine therapy. Some of the concerns that arise with the use of mTORC1 inhibitors (rapamycin analogs or rapalogs) is that they promote induction of autophagy and relieve the negative feedback signaling to Akt effected by S6K1, which promotes oncogenic Akt signaling, survival, and further stimulates mTORC1/S6K1 signaling, which may contribute to acquired drug resistance and patient relapse. Our research focuses on identifying agents that could be combined with mTORC1 inhibitors to block S6K1 while maintaining negative feedback signaling to Akt. Our results show that such combination treatment does in fact prevent rapamycin-induced upregulation of Akt while maintaining inhibition of the S6K1 signaling pathway, as assayed by analysis of S6K1 targets PDCD4, eIF4B and S6. Moreover, the combination treatment inhibits autophagy and promotes apoptosis. Thus, the combined inhibition of S6K1 and Akt may prevent or reverse drug resistance in breast cancer. Citation Format: Anya Alayev, Rose B. Snyder, Marina K. Holz. Targeting Akt reactivation following mTOR inhibition in breast cancer treatment. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research: Genetics, Biology, and Clinical Applications; Oct 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2013;11(10 Suppl):Abstract nr A068.

HER2 Drives Luminal Breast Cancer Stem Cells in the Absence of HER2 Amplification: Implications for Efficacy of Adjuvant Trastuzumab

Although current breast cancer treatment guidelines limit the use of HER2-blocking agents to tumors with HER2 gene amplification, recent retrospective analyses suggest that a wider group of patients may benefit from this therapy. Using breast cancer cell lines, mouse xenograft models and matched human primary and metastatic tissues, we show that HER2 is selectively expressed in and regulates self-renewal of the cancer stem cell (CSC) population in estrogen receptor-positive (ER(+)), HER2(-) luminal breast cancers. Although trastuzumab had no effects on the growth of established luminal breast cancer mouse xenografts, administration after tumor inoculation blocked subsequent tumor growth. HER2 expression is increased in luminal tumors grown in mouse bone xenografts, as well as in bone metastases from patients with breast cancer as compared with matched primary tumors. Furthermore, this increase in HER2 protein expression was not due to gene amplification but rather was mediated by receptor activator of NF-κB (RANK)-ligand in the bone microenvironment. These studies suggest that the clinical efficacy of adjuvant trastuzumab may relate to the ability of this agent to target the CSC population in a process that does not require HER2 gene amplification. Furthermore, these studies support a CSC model in which maximal clinical benefit is achieved when CSC targeting agents are administered in the adjuvant setting. Cancer Res; 73(5); 1635-46. ©2012 AACR.

Constitutive CCND1/CDK2 activity substitutes for p53 loss, or MYC or oncogenic RAS expression in the transformation of human mammary epithelial cells.

Cancer develops following the accumulation of genetic and epigenetic alterations that inactivate tumor suppressor genes and activate proto-oncogenes. Dysregulated cyclin-dependent kinase (CDK) activity has oncogenic potential in breast cancer due to its ability to inactivate key tumor suppressor networks and drive aberrant proliferation. Accumulation or over-expression of cyclin D1 (CCND1) occurs in a majority of breast cancers and over-expression of CCND1 leads to accumulation of activated CCND1/CDK2 complexes in breast cancer cells. We describe here the role of constitutively active CCND1/CDK2 complexes in human mammary epithelial cell (HMEC) transformation. A genetically-defined, stepwise HMEC transformation model was generated by inhibiting p16 and p53 with shRNA, and expressing exogenous MYC and mutant RAS. By replacing components of this model, we demonstrate that constitutive CCND1/CDK2 activity effectively confers anchorage independent growth by inhibiting p53 or replacing MYC or oncogenic RAS expression. These findings are consistent with several clinical observations of luminal breast cancer sub-types that show elevated CCND1 typically occurs in specimens that retain wild-type p53, do not amplify MYC, and contain no RAS mutations. Taken together, these data suggest that targeted inhibition of constitutive CCND1/CDK2 activity may enhance the effectiveness of current treatments for luminal breast cancer.

A Case of Inflammatory-Edematous Breast Cancer Treated with Combination Therapy

Objectives: Current breast cancer treatment involves both standard (e.g., surgery, chemotherapy radiation therapy, and hormone therapy) and new immune therapy methods. Standard treatments are effective at early stages but their effectiveness drops with advanced stages. Recent studies suggest that bacterial and viral infection could be implicated in breast cancer pathogenesis. Therefore, pathogenic inhibition could be a feasible treatment approach. A 54-year-old woman presented with an inflammatory-edematous form of breast cancer (T4N1M1 stage). Due to the inflammatory edematous form tumor was fully metastasized and inoperable. Patients with similar condition usually have a very short life span. Methods: This patient underwent a combinatorial therapy consisting of immunocorrective and metabolism regulating therapy, as well as antimicrobial and standard chemotherapy. Results: This treatment was shown to extend patient’s life for almost two additional years. This case report demonstrates extent and possibility of using a systemic approach to treat inoperable breast cancer.

Overview of Breast Cancer Treatment and Reconstruction for Primary Care Providers

More women are diagnosed and treated for breast cancer today than at any time in the past. New technologies in the treatment of breast cancer and breast reconstruction are changing morbidity and mortality realities for women diagnosed with breast cancer. Primary care providers in women's health care can provide valuable support, education, and advocacy for their clients who are dealing with breast cancer. This article reviews current breast cancer treatment guidelines, information on breast reconstruction after cancer, and primary care recommendations for post-breast cancer care.

Carboplatin treatment of antiestrogen-resistant breast cancer cells

Antiestrogen resistance is a major clinical problem in current breast cancer treatment. Therefore, biomarkers and new treatment options for antiestrogen-resistant breast cancer are needed. In this study, we investigated whether antiestrogen‑resistant breast cancer cell lines have increased sensitivity to carboplatin, as it was previously shown with cisplatin, and whether low Bcl-2 expression levels have a potential value as marker for increased carboplatin sensitivity. Breast cancer cells resistant to the pure antiestrogen fulvestrant, and two out of four cell lines resistant to the antiestrogen tamoxifen, were more sensitive to carboplatin treatment compared to the parental MCF-7 cell line. This indicates that carboplatin may be an advantageous treatment in antiestrogen‑resistant breast cancer; however, a marker for increased sensitivity would be needed. Low Bcl-2 expression was correlated with increased carboplatin response in the tamoxifen‑resistant cell line MCF-7/TAMR-1 and overexpression of Bcl-2 in this cell line resulted in significantly reduced carboplatin sensitivity, confirming the anti-apoptotic role of Bcl-2. However, neither Bcl-2 expression alone, nor Bcl-2 in combination with Bcl-xL and Bax, could explain the observed responses to carboplatin in all tamoxifen‑resistant cell lines, indicating that more markers are needed to predict the response to carboplatin in tamoxifen‑resistant breast cancer.

The Role of Cancer Stem Cells in Breast Cancer Initiation and Progression: Potential Cancer Stem Cell-Directed Therapies

Recent studies have identified a small population of highly tumorigenic cells with stem cell properties in human breast and other solid tumors that are considered to be the source of tumor initiation and maintenance; these cells are referred to as cancer stem cells (CSCs). Preclinical data suggest that current breast cancer treatment strategies lead to CSC enrichment, contributing to chemotherapy and radiotherapy resistance, although a strong correlation with clinical parameters and prognosis is yet to be established. Importantly, overcoming treatment failure by effective targeting of CSCs may be an appealing approach, potentially leading to improved clinical outcomes for patients with breast cancer. Several preclinical studies provide promising results that support this hypothesis. The purpose of this review is to summarize the role of CSCs in breast cancer recurrence and resistance and to discuss current attempts of CSC targeting.

Surveillance after potentially curative breast cancer treatment: The impact of HMOs.

6079 Background: Over 230,000 new cases of breast cancer are diagnosed in the US annually. Most patients receive curative-intent treatment. Post-treatment surveillance is commonly done. We have previously documented dramatic variation in surveillance intensity among ASCO experts. The only surveillance modalities endorsed by ASCO for asymptomatic patients are office visit and mammogram. It is commonly believed that health maintenance organizations (HMOs) restrict test utilization. We sought to determine the effect of HMO penetration rate on the known variation in surveillance strategies. Methods: The 3245 ASCO members who indicated that breast cancer was a major clinical focus of their practice were surveyed regarding their surveillance practices. Members were asked to consider 4 idealized clinical vignettes and indicate their surveillance plan for each. A menu of 12 testing modalities was offered. Practice patterns were stratified by HMO penetration rate (0-14%, 14-22%, 22-33%, 33-61%) in each physician’s practice location. Repeated-measures ANOVA was employed for analysis. Results: Of the ASCO members surveyed, 1012 responded; 915 were evaluable. The modalities most frequently recommended were office visit, CBC, liver function tests (LFTs), and diagnostic mammogram. There was significant variation (p<0.05) in the recommended frequency of utilization of diagnostic mammogram, but in no other modalities. For example, in year 1, diagnostic mammogram was recommended 1.9 ± 1.8 (mean ±SD) times for the 0-14% penetration rate cohort and 1.5 ± 1.1 times for the 14-22% cohort. Conclusions: We found little evidence that HMOs restrict test utilization. The HMO penetration rate in the clinician’s practice location cannot account for the overall variation we have documented previously.

NFκB signaling is important for growth of antiestrogen resistant breast cancer cells

Resistance to endocrine therapy is a major clinical challenge in current treatment of estrogen receptor-positive breast cancer. The molecular mechanisms underlying resistance are yet not fully clarified. In this study, we investigated whether NFκB signaling is causally involved in antiestrogen resistant cell growth and a potential target for re-sensitizing resistant cells to endocrine therapy. We used an MCF-7-derived cell model for antiestrogen resistant breast cancer to investigate dependence on NFκB signaling for antiestrogen resistant cell growth. We found that targeting NFκB preferentially inhibited resistant cell growth. Antiestrogen resistant cells expressed increased p50 and RelB, and displayed increased phosphorylation of p65 at Ser529 and Ser536. Moreover, transcriptional activity of NFκB after stimulation with tumor necrosis factor α was enhanced in antiestrogen resistant cell lines compared to the parental cell line. Inhibition of NFκB signaling sensitized tamoxifen resistant cells to the growth inhibitory effects of tamoxifen but was not sufficient to fully restore sensitivity of fulvestrant resistant cells to fulvestrant. In support of this, depletion of p65 with siRNA in tamoxifen resistant cells increased sensitivity to tamoxifen treatment. Our data provide evidence that NFκB signaling is enhanced in antiestrogen resistant breast cancer cells and plays an important role for antiestrogen resistant cell growth and for sensitivity to tamoxifen treatment in resistant cells. Our results imply that targeting NFκB might serve as a potential novel treatment strategy for breast cancer patients with resistance toward antiestrogen.

“Diamond” mammoplasty as a part of conservative management of breast cancer: Description of a new technique

INTRODUCTIONOncoplastic surgery is an integral part of current surgical treatment of breast cancer. Superior breast quadrant is a forgiving tumor location that often allows the conservation of the breast with simple mammoplastic manoeuvres. In this report, we describe a novel modification of the classic level I mammoplasty. PRESENTATION OF CASEA 49 years patient had an ill-defined carcinoma at the 12 o’clock position that necessitated a generous tumorectomy. A diamond shaped incision was done over the tumor area and the nipple-areola complex. Peri-areolar skin was de-epithelialized and the tumorectomy was completed down to the pectoral plane. The incision was closed in a star-like shape around the areola leading to natural appearance of the breast and a limited visible suture line. DISCUSSIONWe suggest that the described technique offered an advantage over the classic omega mastopexy or the round-block technique and provided a versatile technique for oncologic management and mastopexy. CONCLUSIONThe presented technique may be considered when performing level I mammoplasty.

Bevacizumab Treatment for Advanced Breast Cancer

Significant advances in the treatment of patients with breast cancer have been made in the past 10 years. The current systemic treatment of breast cancer is characterized by the discovery of multiple cancer targets leading to treatments that are more sophisticated and specific than conventional cytotoxic chemotherapy. Two classes of compounds that have helped improve clinical outcomes are small molecules and monoclonal antibodies targeting specific tyrosine kinase receptors. Many novel targets have been discovered, and parallel multiple approaches to anticancer therapy have recently emerged from the literature. One promising strategy is targeting the proangiogenic vascular endothelial growth factors (VEGFs), either by ligand sequestration (preventing VEGF receptor binding) or inhibiting downstream receptor signaling. Bevacizumab, a monoclonal antibody directed against VEGF, has been shown to improve the efficacy of taxanes in frontline treatment of patients with metastatic breast cancer. This review outlines the most promising breast cancer studies using bevacizumab combined with traditional cytotoxic agents in advanced breast cancer. In addition, we discuss the current indications reviewed by the Oncologic Drug Advisory Committee and define our vision of how the benefit of patient clinical trials should be measured.

A study of atherosclerosis in patients after radiation for early breast cancer.

260 Background: Radiation therapy (RT) is widely used as part of curative treatment of breast cancer. However, older studies have shown increased cardiac morbidity and mortality from breast RT. A screening method is needed to detect early cardiac damage in this population. Recent data have shown that Electron beam computed tomography (EBCT) can detect early atherosclerosis in coronary arteries by identifying the amount of calcification in the coronaries. In our study we employed this tool to detect occult atherosclerosis caused by breast RT. Methods: We evaluated 20 asymptomatic patients, less than 60 years of age, treated with RT at least 5 years prior to enrollment. Nine received RT to the left and 11 to the right hemithorax. Average interval between RT and CT was 7.7 years (5-14). All patients were treated with external beam RT using tangential technique. The breast was treated to a dose of 4500-5040 cGy and the tumor bed was boosted to a total dose of 6000-6600 cGy. All patients underwent EBCT to compute the volumetric and agatston calcium scores in the coronary arteries and the aorta. Results: Of the 11 patients who had RT to right hemithorax, 8 had calcium score of 0, 2 had very minimally elevated scores and 1 had significantly elevated score (patient 19, interval -14 years). Of the 9 patients who had RT to left hemithorax, 7 had calcium score of 0. None had significantly elevated scores. In the aorta, 11 patients had score of 0 and 8 had minimally elevated scores. Conclusions: Occult atherosclerosis was not detected using EBCT calcium scores in coronaries and aorta in a significant number of patients treated with RT for breast cancer. However, the study is limited by a small sample size. [Table: see text]

Gold nano-popcorn attached SWCNT hybrid nanomaterial for targeted diagnosis and photothermal therapy of human breast cancer cells.

Breast cancer presents greatest challenge in health care in today's world. The key to ultimately successful treatment of breast cancer disease is an early and accurate diagnosis. Current breast cancer treatments are often associated with severe side effects. Driven by the need, we report the design of novel hybrid nanomaterial using gold nano popcorn-attached single wall carbon nanotube for targeted diagnosis and selective photothermal treatment. Targeted SK-BR-3 human breast cancer cell sensing have been performed in 10 cancer cells/mL level, using surface enhanced Raman scattering of single walls carbon nanotube's D and G bands. Our data show that S6 aptamer attached hybrid nanomaterial based SERS assay is highly sensitive to targeted human breast cancer SK-BR-3 cell line and it will be able to distinguish it from other non targeted MDA-MB breast cancer cell line and HaCaT normal skin cell line. Our results also show that 10 min of photothermal therapy treatment by 1.5 W/cm(2) power, 785 nm laser is enough to kill cancer cells very effectively using S6 aptamer attached hybrid nanomaterials. Possible mechanisms for targeted sensing and operating principle for highly efficient photothermal therapy have been discussed. Our experimental results reported here open up a new possibility for using aptamers modified hybrid nanomaterial for reliable diagnosis and targeted therapy of cancer cell lines quickly.

An interview with Larisa Fleysher

chronic oedema? Working as an oncology nurse specialist, I frequently encountered patients with breast cancer-related lymphoedema. Current breast cancer treatment modalities put patients at risk for developing upper extremity lymphoedema, which in turn may become chronic oedema if prompt interventions are not exercised. Lymphoedema related to breast cancer treatment is a common and overlooked complication of breast cancer treatment. Having survived breast cancer, these patients now had to learn how to ‘survive’ lymphoedema. Knowing that patient education is most important in the prevention of lymphoedema and that there were missing links in patients’ education, I decided to conduct research on risk reduction behaviours and educate breast cancer patients about lymphoedema risk-reduction behaviours.

Economic evaluation of four follow-up strategies after curative treatment for breast cancer: Results of an RCT

BackgroundAn economic evaluation was performed alongside a randomised controlled trial (ISRCTN 74071417) investigating the cost-effectiveness of nurse-led telephone follow-up instead of hospital visits, and of a short educational group programme (EGP) in the first year after breast cancer treatment. MethodThis economic evaluation (n=299) compared the one-year costs and the effects of four follow-up strategies: (1) hospital follow-up; (2) nurse-led telephone follow-up; (3) hospital follow-up plus EGP; and (4) nurse-led telephone follow-up plus EGP. Costs were measured using cost diaries and hospital registrations. Quality-adjusted life years (QALYs) were measured using the EQ-5D. Outcomes were expressed in incremental cost-effectiveness ratios (ICERs) and cost-effectiveness acceptability curves. ResultsHospital follow-up plus EGP yielded most QALYs (0.776), but also incurred the highest mean annual costs (€4914). The ICER of this strategy versus the next best alternative, nurse-led telephone follow-up plus EGP (0.772 QALYs and €3971), amounted to €235.750/QALY. Hospital and telephone follow-up without EGP both incurred higher costs and less QALYs than telephone follow-up plus EGP and were judged inferior. Hospital follow-up plus EGP was not considered cost-effective, therefore, telephone follow-up plus EGP was the preferred strategy. The probability of telephone follow-up plus EGP being cost-effective ranged from 49% to 62% for different QALY threshold values. Secondary and sensitivity analyses showed that results were robust. ConclusionNurse-led telephone follow-up plus EGP seems an appropriate and cost-effective alternative to hospital follow-up for breast cancer patients during their first year after treatment.

Abstract P6-05-05: Signaling Pathways Activated in Her 2 and ER Negative Breast Cancers

Abstract Introduction: Breast cancer is the most common cancer in women (192,370 new cases in 2009) and the second leading cause of cancer death (40,000) among women in USA. Current multimodality treatment of breast cancer is based on the level of ER expression and Her 2 gene amplification. However, no effective treatment is currently available for breast cancers with low level expression of ER and no amplification of Her 2 gene. The aim of this study is to identify protein pathways activated in the breast cancer with negative expression of ER and Her 2. Method: Protein Pathway Array was used to assess the level of protein expression and phosphorylation in 71 paired fresh frozen breast samples (tumor and adjacent benign tissue). A total 159 antibodies were evaluated which represent most important signal transduction pathways involved in proliferation, apoptosis, angiogenesis, invasion and metastasis. Several potential therapeutic kinase proteins were also assessed. Results: A total 20 proteins (PCNA, phospho-PTEN, cyclin B1 cyclin E1, CDK6, E-cadherin, NFkB, ect) were differentially expressed between normal and tumor tissues based on the statistical analysis. In Her 2 negative tumors (n=37), 3 proteins were differentially expressed and among them, 2 were up-regulated (CDK6 and HSD1) and 1 was down-regulated (IGF). In ER negative tumors (n=18), 4 proteins (HSD, SK, TDP and Slug) was up-regulated and 1 proteins were down-regulated (E-cadherin). In triple negative tumors (n=13), one protein (E-cadherin) down-regulated and 2 proteins (TDP and HSD) were up-regulated. Furthermore, based on the expression pattern of these proteins, tumors negative for both ER and Her 2 (n=15) can be clustered into 3 groups Figure 1: Subclassification of breast cancers negative for ER and Her-2 based protein pattern. Hierarchical clustering analysis of 20 differentially expressed proteins in 15 ER/Her-2 negative breast cancers. The cancers can be separated into 3 subtypes. Red indicates overexpression, green underexpression, black no change, and gray no expression. Each column represents a protein. Each row represents a sample. Conclusion: Our study showed that distinct sets of signaling pathways activated in ER and Her 2 negative breast cancers. The increased expression of cell cycle progression proteins in Her 2 negative tumors suggests activation of cell proliferation via different growth promotion pathway. Similarly, different cell proliferation pathways are also activated in ER negative tumors. This finding may be used to design future clinical trial based on the activation of different signaling pathways. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-05-05.

Keeping breast cancer survivors lymphoedema-free

With the increasing number of breast cancer survivors, post-treatment interventions to improve quality of life are gaining priority. Current breast cancer treatment modalities put patients at risk of developing upper-extremity lymphoedema. Upper-extremity lymphoedema is a common and overlooked complication of breast cancer treatment. Health professionals play an important role in identifying breast cancer and promptly referring these patients for further interventions. After successful completion of breast cancer treatment, these patients continue to have regular evaluations by their oncologists; and, provided there are no signs and symptoms of breast cancer, primary and community care health professionals will continue to play an essential role in the management of this unique patient group. As breast cancer treatment places these patients at a lifetime risk of developing upper-extremity lymphoedema, radiation oncologists, surgical and medical oncologists, and primary care practitioners must be knowledgeable and educate these patients about risk reduction behaviours. Prevention, prompt identification, and treatment of lymphoedema are the goals for achieving positive and cost-effective patient outcomes. This article aims to provide health professionals with specific educational tools with regard to the prevention, recognition, and management of upper-extremity lymphoedema; these tools should be used to change the ongoing trends in the management of breast cancer survivors' follow-up care.

Breast cancer in the personal genomics era.

Breast cancer is a heterogeneous disease with a complex etiology that develops from different cellular lineages, progresses along multiple molecular pathways, and demonstrates wide variability in response to treatment. The “standard of care” approach to breast cancer treatment in which all patients receive similar interventions is rapidly being replaced by personalized medicine, based on molecular characteristics of individual patients. Both inherited and somatic genomic variation is providing useful information for customizing treatment regimens for breast cancer to maximize efficacy and minimize adverse side effects. In this article, we review (1) hereditary breast cancer and current use of inherited susceptibility genes in patient management; (2) the potential of newly-identified breast cancer-susceptibility variants for improving risk assessment; (3) advantages and disadvantages of direct-to-consumer testing; (4) molecular characterization of sporadic breast cancer through immunohistochemistry and gene expression profiling and opportunities for personalized prognostics; and (5) pharmacogenomic influences on the effectiveness of current breast cancer treatments. Molecular genomics has the potential to revolutionize clinical practice and improve the lives of women with breast cancer.

Patient satisfaction with nurse-led telephone follow-up after curative treatment for breast cancer

BackgroundCurrent frequent follow-up after treatment for breast cancer does not meet its intended aims, but does depend on expensive and scarce specialized knowledge for routine history taking and physical examinations. The study described in this paper compared patient satisfaction with a reduced follow-up strategy, i.e. nurse-led telephone follow-up, to satisfaction with traditional hospital follow-up.MethodsPatient satisfaction was assessed among patients (n = 299) who were participants of a randomized controlled trial investigating the cost-effectiveness of several follow-up strategies in the first year after treatment for breast cancer. Data on patient satisfaction were collected at baseline, three, six and 12 months after treatment, using the Dutch version of Ware's Patient Satisfaction Questionnaire III (PSQ III). In addition to general satisfaction, the PSQ III reports on satisfaction scores for technical competence, interpersonal aspects, and access of care. Regression analysis was used to predict satisfaction scores from whether or not nurse-led telephone follow-up was received.ResultsNurse-led telephone follow-up had no statistically significant influence on general patient satisfaction (p = 0.379), satisfaction with technical competence (p = 0.249), and satisfaction with interpersonal aspects (p = 0.662). Regarding access of care, patient satisfaction scores were significantly higher for patients receiving telephone follow-up (p = 0.015). However, a mean difference at 12 months of 3.1 points was judged to be not clinically relevant.ConclusionsNo meaningful differences were found in satisfaction scores between nurse-led telephone and hospital follow-up in the first year after breast cancer treatment. With high satisfaction scores and the potential to substantially reduce clinic visits, nurse-led telephone follow-up may be an acceptable alternative to traditional hospital follow-up.Trial registration numberISRCTN 74071417.

Abstract 3280: Generation of orthotopic mouse models of breast cancer

Abstract The current systemic treatments for breast cancer include chemotherapy, and targeted approaches such as anti-hormonal and anti-Her2 treatments. These treatments are effective only in a percentage of cases and even those initially responsive tumors eventually acquire resistance. It is critical to define the mechanisms of resistance and to identify the population of resistant cells to target them efficiently. We have generated mouse models for the study of breast cancer tumors based on the orthotopic implantation of fresh primary human tumor pieces and cancer cells isolated from pleural effusions in immunodeficient mice. A total of 55 fresh tumor pieces and tumor cells isolated from 5 pleural effusions have been implanted into the cleared fat pad of nude, NOD/SCID and SCID/beige mice. Slow release estrogen pellets have been implanted in the intercapsular region at the same time as tumors. Nine out of the 60 samples implanted gave rise to palpable lesions, 5 derived from fresh tumor pieces and 4 from tumor cells isolated from pleural effusions and are being maintained by serial passages in mice. Currently we have five well-established tumors, 2 TNBC (triple negative breast cancer), 2 luminal tumors and one Her2 positive tumor. Morphologically tumors growing in mice resemble human tumors. Latency to tumor development and growth rates are being evaluated in different serial passages and host mice. Tumors at different passages are being characterized at the histological level and for the expression of ER, PR, Her2, EGFR, cytokeratins and p53, and compared with the primary human tumor. Once tumors are established and characterized we will test their sensitivity to drugs currently used in the clinic. Orthotopic tumor xenografts will allow gaining insight into the molecular mechanisms involved in the resistance. Genetic and epigenetic analysis will allow to identify the chromosomal regions related with resistance. Similarly, differential gene expression profiling will be determined by microarray analysis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3280.