Association of guideline-concordant initial systemic treatment with clinical and economic outcomes among older women with metastatic breast cancer in the United States.

PURPOSE: We examined guideline-concordant initial systemic treatment among women with metastatic breast cancer, its predictors, and if guideline-concordant treatment was associated with mortality, healthcare utilization and Medicare expenditures. METHODS: This retrospective observational cohort study was conducted using the Surveillance, Epidemiology, End Results-Medicare linked database. Women aged 66-90 years diagnosed with metastatic breast cancer during 2010-2013 (N = 1282) were included. The National Comprehensive Cancer Network treatment guidelines were used to determine the guideline-concordant initial systemic treatment following cancer diagnosis. A logistic regression analysis was conducted to examine significant predictors of guideline-concordant treatment. Generalized linear regressions were used to examine the association between guideline-concordant treatment and healthcare utilization and average monthly Medicare expenditures. RESULTS: About 74% of the study cohort received guideline-concordant initial systemic treatment. Women who received guideline-concordant treatment were significantly more likely to be comparatively younger (p < 0.05), were married/partnered (p = 0.0038), had HER2 positive tumors, and had good performance status. Adjusted hazards ratios for all-cause (2.364, p < 0.0001) and breast-cancer specific mortality (2.179, p < 0.0001) were higher for women who did not receive guideline-concordant treatment. Rates of healthcare utilization were also higher for women not receiving guideline-concordant treatment. Average monthly Medicare expenditures were 100.4% higher (95% confidence interval: $77.3%-126.5%) for women who did not receive guideline-concordant treatment compared to those who received guideline-concordant treatment (p < 0.0001). CONCLUSION: One fourth of the study cohort did not receive guideline-concordant initial systemic treatment. Guideline-concordant initial treatment was associated with reduced mortality, and lower healthcare utilization and Medicare expenditures in women with metastatic breast cancer.

Disparities in Guideline-Concordant Initial Systemic Treatment in Women with HER2-Negative Metastatic Breast Cancer: A SEER-Medicare Analysis.

BACKGROUND: Data on guideline-concordant initial systemic treatment among women with HER2-negative metastatic breast cancer (MBC) are limited. We determined the proportion of women with HER2-negative MBC who received guideline-concordant treatment and the extent to which independent variables explained differences in guideline-concordant treatment by hormone receptor (HR) status. METHODS: We conducted a retrospective cohort study using the SEER-Medicare database. We included women age >65 years diagnosed with HER2-negative MBC during 2010-2013. We used the National Comprehensive Cancer Network treatment guidelines to determine guideline-concordant initial treatment within the first 6 months of a cancer diagnosis. We conducted a multivariable logistic regression to identify the significant predictors of guideline-concordant treatment and a non-linear decomposition method to examine disparities by HR status. RESULTS: Among 1089 eligible women, 72.3% received guideline-concordant treatment. Compared to women who did not receive guideline-concordant treatment, women who received guideline-concordant treatment were more like to be comparatively older (p<0.05), married (p=0.0171), resided in areas with higher proportion of people age ≥25 years with at least four years of college education, and had positive HR status (p<0.0001). Approximately 8% of the disparity in guideline-concordant treatment by HR status was explained by their observed characteristics. Need-related factors explained the highest proportion (66.9%) of the disparity. CONCLUSION: Our findings indicate improvement of care for older women, who are single/divorced, have negative HR status, and who live in area with lower education levels. Unexplained disparities in guideline-concordant treatment by HR status can be attributed to patient preferences for treatment, physician-level factors, and perceptions.

Treatment and Survival of Medicare Beneficiaries with Colorectal Cancer: A Comparative Analysis Between a Rural State Cancer Registry and National Data.

The aim was to examine and compare with "national" estimates, receipt of colorectal cancer (CRC) treatment in the initial phase of care and survival following a CRC diagnosis in rural Medicare beneficiaries. A retrospective study was conducted on fee-for-service Medicare beneficiaries diagnosed with CRC in 2003-2006, identified from West Virginia Cancer Registry (WVCR)-Medicare linked database (N = 2119). A comparative cohort was identified from Surveillance, Epidemiology, and End Results (SEER)-Medicare (N = 38,168). CRC treatment received was ascertained from beneficiaries' Medicare claims in the 12 months post CRC diagnosis or until death, whichever happened first. Receipt of minimally appropriate CRC treatment (MACT) was defined using recommended CRC treatment guidelines. All-cause and CRC-specific mortality in the 36-month period post CRC diagnosis were examined. Differences in usage of CRC surgery, chemotherapy, and radiation were observed between the 2 populations, with those from WVCR-Medicare being less likely to receive any type of CRC surgery (adjusted odds ratio [AOR] = 0.82; 95% confidence interval [CI] = [0.73-0.93]). Overall, those from WVCR-Medicare had a lower likelihood of receiving MACT, (AOR = 0.85; 95% CI = [0.76-0.96]) compared to their national counterparts. Higher hazard of CRC mortality was observed in the WVCR-Medicare cohort (adjusted hazard ratio = 1.26; 95% CI = [1.20-1.32]) compared to the SEER-Medicare cohort. Although more beneficiaries from WVCR-Medicare were diagnosed in early-stage CRC compared to their SEER-Medicare counterparts, they had a lower likelihood of receiving MACT and a higher hazard of CRC mortality. This study highlights the need for an increased focus on improving access to care at every phase of the CRC care continuum, especially for those from rural settings.

Radiation exposure from diagnostic procedures in patients with newly diagnosed breast cancer.

Radiation exposure is associated with an increased risk of secondary cancers. Knowing the approximate radiation exposure from diagnostic procedures in the œrst year after a breast cancer diagnosis could help educate patients and allow physicians to monitor them more closely for potential risks.

Exercise and dietary advice intervention for survivors of triple-negative breast cancer: effects on body fat, physical function, quality of life, and adipokine profile.

PURPOSE: Regular exercise and healthy eating are routinely recommended for breast cancer survivors, and past studies show benefits in quality of life and decreased inflammation. However, this has not been tested specifically in triple-negative breast cancer survivors. Increasing physical activity and losing body fat are thought to positively affect inflammatory biomarkers that have been associated with breast cancer. Therefore, the primary purpose of this study was to determine if participation in an exercise and dietary counseling program can improve body fat, physical function, and quality of life in survivors of this aggressive breast cancer. Secondarily, we sought to determine if participation in the program had beneficial effects on obesity-related markers of the adipokine profile. METHODS: Sixty-six survivors of triple-negative breast cancer with BMI >25 were invited to participate. Twenty-eight enrolled and 23 completed the randomized, controlled trial (13 intervention, 10 control). Moderate-intensity aerobic exercise (150 min per week, for 12 weeks) and diet counseling were compared to usual care, education only. The primary outcome of interest was weight loss (body mass, BMI, % fat), and secondary outcomes included physical function (exercise capacity), quality of life (Function After Cancer Therapy-Breast (FACT-B)), cytokines (C-reactive protein (CRP), TNF-α, IL-6), and adipokine profile (leptin, adiponectin, insulin). RESULTS: Participants in the program lost more body fat (2.4 % loss vs. 0.4 % gain, p < 0.05) than the control group. The intervention group also improved quality of life (FACT-B total score +14 pts) and decreased sedentary time but did not improve peak exercise capacity. The intervention had no effect on serum cytokines and adipokines after 12 weeks in the program. However, serum leptin and adiponectin and their ratio were significantly correlated with BMI in the intervention group (p < 0.05). CONCLUSIONS: Exercise and dietary counseling led to loss of body fat and improved quality of life in survivors of triple-negative breast cancer. BMI was associated with favorable changes in leptin and adiponectin which may reflect a change in adiposity with intervention. Exercise and healthy eating may be equally effective in this high-risk population as in other breast cancer survivors and should be encouraged as a part of a cancer survivorship program.

Breast cancer pathology, receptor status, and patterns of metastasis in a rural appalachian population.

Breast cancer patients in rural Appalachia have a high prevalence of obesity and poverty, together with more triple-negative phenotypes. We reviewed clinical records for tumor receptor status and time to distant metastasis. Body mass index, tumor size, grade, nodal status, and receptor status were related to metastatic patterns. For 687 patients, 13.8% developed metastases to bone (n = 42) or visceral sites (n = 53). Metastases to viscera occurred within five years, a latent period which was shorter than that for bone (P = 0.042). More women with visceral metastasis presented with grade 3 tumors compared with the bone and nonmetastatic groups (P = 0.0002). There were 135/574 women (23.5%) with triple-negative breast cancer, who presented with lymph node involvement and visceral metastases (68.2% versus 24.3%; P = 0.033). Triple-negative tumors that metastasized to visceral sites were larger (P = 0.007). Developing a visceral metastasis within 10 years was higher among women with triple-negative tumors. Across all breast cancer receptor subtypes, the probability of remaining distant metastasis-free was greater for brain and liver than for lung. The excess risk of metastatic spread to visceral organs in triple-negative breast cancers, even in the absence of positive nodes, was combined with the burden of larger and more advanced tumors.

Health behaviors among breast, prostate, and colorectal cancer survivors: a US population-based case-control study, with comparisons by cancer type and gender.

PURPOSE: The aim of this study is to compare health behaviors between breast, prostate, female, and male colorectal cancer survivors to noncancer controls, stratified by short- and long-term survivors, and between cancer types and genders. METHODS: A 3:1 population-based sample of breast (6,259), prostate (3,609), female colorectal (1,082), and male colorectal (816) cancer survivors from the 2009 Behavioral Risk Factor Surveillance System survey were matched to noncancer controls on age, gender, race/ethnicity, income, insurance, and region of the US. The likelihood of flu immunization, physical check-up, cholesterol check, body mass index (BMI), physical activity, diet (5-A-Day), smoking, and alcohol use were compared between groups using binomial logistic regression models. RESULTS: Short-term breast cancer survivors were significantly more likely to meet multiple behavioral recommendations, than controls, but the likelihood decreased in the long term. Breast and female colorectal cancer survivors were up to 2.27 (95 % CI 1.90, 2.71) and 1.89 times more likely (95 % CI 1.60, 2.24) to meet the 5-A-Day and BMI recommendations, up to 0.54 times less likely (95 % CI 0.46, 0.64) to drink any alcohol, but were 0.68 times less likely (95 % CI 0.49, 0.95) to meet the physical activity recommendation, compared to prostate and male colorectal cancer survivors. CONCLUSIONS: Some cancer survivors may engage in better health behaviors shortly after diagnosis, but the majority of cancer survivors do not have better health behaviors than individuals without a history of cancer. However, a consistent pattern of behavioral differences exist between male and female cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: Gender differences in health behaviors among cancer survivors may be influenced by perceptions of masculinity/femininity and disease risk. Ongoing health behavioral promotion and disease prevention efforts could be improved by addressing these perceptions.

Weight change associated with third-generation adjuvant chemotherapy in breast cancer patients.

BACKGROUND: Studies have shown that breast cancer treatment can cause an increase in weight. Weight gain during chemotherapy is usually significant and may be associated with poor survival. However, the role of third- generation chemotherapy regimens and weight gain is not well reviewed. METHODS: We retrospectively analyzed the mean percentage weight change during the first year after breast cancer diagnosis in 246 patients at West Virginia University during September 2007 and October 2010. Kruskal-Wallis test and post hoc pairwise comparisons were used to assess the influence of age, histology, stage, ER/PR/HER2/neu status, menopausal status, and types of therapeutic modalities received on the percentage weight change. Kaplan-Meier method with log-rank test was used to evaluate recurrence-free survival (RFS). Local or distant recurrence and disease progression were events for RFS analysis and disease-free patients were censored at last follow-up. RESULTS: Mean weight gain was 0.39% (SD, 0.40) of baseline body weight, 1 year after diagnosis of breast cancer. Premenopausal status was the only factor associated with significant weight gain (+1.67% vs -0.10% for postmenopausal patients; P = .02). Stages ≥ III was associated with significant weight loss (-1.64% for stages III, IV vs +0.85% for stages 0, I, II; P = .02) and a lower RFS at 3 years and 5 years (P < .0001). Higher baseline weight (> 90th percentile) did not have any significant impact on RFS (0.84 vs 0.91; P = .19). There was no significant change in weight relative to other factors. CONCLUSIONS: Our study in patients receiving third-generation adjuvant chemotherapy regimens did not show any significant change in percentage weight with chemotherapy. Premenopausal status was the only significant factor associated with weight gain. As expected, stage III or higher disease was associated with significant weight loss and lower RFS.

A population-based study comparing HRQoL among breast, prostate, and colorectal cancer survivors to propensity score matched controls, by cancer type, and gender.

BACKGROUND: Objectives were to compare health-related quality of life (HRQoL) between breast cancer survivors, prostate cancer survivors (PCS), and colorectal cancer survivors (CCS) to matched controls, stratified by short and long-term survivors, by cancer type, and gender. METHODS: By using the 2009 Behavioral Risk Factor Surveillance System, propensity scores matched three controls to adult survivors >1 year past diagnosis (N = 11,964) on age, gender, race/ethnicity, income, insurance status, and region of the USA Chi-square tests and logistic regression models compared HRQoL outcomes (life satisfaction, activity limitations, sleep quality, emotional support, general, physical, and mental health). RESULTS: Although all cancer survivors reported worse general health (p < 0.000) and more activity limitations (p < 0.004) than controls, these disparities decreased among long-term survivors. Short-term PCS and male CCS were more likely to report worse outcomes across additional domains of HRQoL than controls, but PCS were 0.61, 0.63, and 0.70 times less likely to report activity limitations, fair/poor general health, and 1-15 bad physical health days in the past month than male CCS. Breast cancer survivors and female CCS were 2.12 and 3.17, 1.58 and 1.86, and 1.49 and 153, respectively, times more likely to report rarely/never receiving needed emotional support, 1-15 bad mental health days in the past month, and not receiving enough sleep 1-15 days in the past month than PCS and male CCS. CONCLUSIONS: Cancer survivors experience worse HRQoL than similar individuals without a history of cancer and the severity of affected HRQoL domains differ by time since diagnosis, cancer type, and gender.

Overcoming endocrine resistance in breast cancer: role of the PI3K and the mTOR pathways.

Overcoming endocrine resistance is a 21st century hurdle in the treatment of hormone receptor-positive breast cancers. Estrogen plays a role in the growth of 70% of breast cancers. There are many strategies evolved to overcome estrogen resistance. Established strategies include using drugs such as tamoxifen, a selective estrogen receptor modulator to selectively block estrogen receptors and aromatase inhibitors to decrease the synthesis of estrogen. However, endocrine resistance is commonly encountered in treating patients with standard single-therapy regimens. Recently, the role of the PI3K and the mTOR pathways has been targeted to overcome resistance. The mTOR pathway is a complex pathway regulating cell metabolism, growth and apoptosis. Novel agents such as mTOR inhibitors, PI3K inhibitors and Akt inhibitors are transitioning from bench-top research to clinical application with promising results. This article reviews the common mechanisms of endocrine resistance, and combination therapies that utilize the mTOR/PI3K pathways to overcome resistance.

Initial clinical test of a breast-PET scanner.

INTRODUCTION: The goal of this initial clinical study was to test a new positron emission/tomography imager and biopsy system (PEM/PET) in a small group of selected subjects to assess its clinical imaging capabilities. Specifically, the main task of this study is to determine whether the new system can successfully be used to produce images of known breast cancer and compare them to those acquired by standard techniques. METHODS: The PEM/PET system consists of two pairs of rotating radiation detectors located beneath a patient table. The scanner has a spatial resolution of ∼2 mm in all three dimensions. The subjects consisted of five patients diagnosed with locally advanced breast cancer ranging in age from 40 to 55 years old scheduled for pre-treatment, conventional whole body PET imaging with F-18 Fluorodeoxyglucose (FDG). The primary lesions were at least 2 cm in diameter. RESULTS: The images from the PEM/PET system demonstrated that this system is capable of identifying some lesions not visible in standard mammograms. Furthermore, while the relatively large lesions imaged in this study where all visualised by a standard whole body PET/CT scanner, some of the morphology of the tumours (ductal infiltration, for example) was better defined with the PEM/PET system. Significantly, these images were obtained immediately following a standard whole body PET scan. CONCLUSIONS: The initial testing of the new PEM/PET system demonstrated that the new system is capable of producing good quality breast-PET images compared standard methods.

Prognostic significance of the "surprise" question in cancer patients.

BACKGROUND: Physicians consistently overestimate survival for patients with cancer. The "surprise" question--"Would I be surprised if this patient died in the next year?"--improves end-of-life care by identifying patients with a poor prognosis. It has not been previously studied in patients with cancer. OBJECTIVE: To determine the efficacy of the surprise question in patients with cancer. DESIGN: Prospective cohort study. SETTING: Academic cancer center. PATIENTS: 853 consecutive patients with breast, lung, or colon cancer. MEASUREMENTS: Surprise question classification and patient status at 12 months, alive or dead, by surprise question response. RESULTS: Oncologists classified 826 of 853 prospective patients with cancer (97%) with 131 (16%) classified into the "No" group and 695 (84%) into the "Yes" group. In multivariate analysis, a "No" response identified patients with cancer who had a seven times greater hazard of death in the next year compared to patients in the "Yes" group (HR 7.787, p < 0.001). LIMITATIONS: Single center study. CONCLUSION: The surprise question is a simple, feasible, and effective tool to identify patients with cancer who have a greatly increased risk of 1-year mortality.

CA 27-29 in patients with breast cancer with pulmonary fibrosis.

Cancer antigen (CA) 27-29, which is expressed on most carcinoma cells, is a soluble form of glycoprotein MUC1. It is overexpressed in tumors involving glandular epithelial cells, such as breast tumors. Measurement of CA 27-29 has been approved by the US Food and Drug Administration for monitoring disease activity in patients with breast cancer. Although serial determination of tumor markers after primary treatment for breast cancer can preclinically detect recurrent/metastatic disease with lead times of approximately 2-9 months, the clinical value of this lead time remains to be determined. False-positive results might be observed in certain patients with no evidence of malignant disease, such as benign breast disease, ovarian cysts, and liver disease. Herein, we report a series of 4 patients with breast cancer (2 patients with interstitial lung fibrosis and 2 patients with nonspecific fibrotic lung changes) who have persistent elevation in CA 27.29 (normal, <38 U/mL).

Complete response after high-dose chemotherapy and autologous hemopoietic stem cell transplatation in metastatic breast cancer results in survival benefit.

Metastatic breast cancer is an incurable disease even with high-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplantation (ASCT). Even though phase III studies have not shown a survival advantage for this group as a whole, it is possible that a small subset of patients may benefit from HDC/ASCT with careful patient selection. A total of 198 patients from three different institutions were treated with HDC/ASCT. After complete staging, patients with central nervous system or bone marrow involvement were excluded. The HDC regimen consisted of: Carboplatin 600 mg/m(2) IV infusion over 48 hours, Thiotepa 300 mg/m(2) IV infusion over 2 hours, and Cytoxan 60 mg/kg IV infusion given over 2 hours x3 days. The median age at the time of transplant was 46 (24-62) years and median follow-up was 20 months. Hormone receptor status was known in 148 patients, of whom 84 had estrogen receptor (ER) and/or progestrone receptor (PgR)-positive tumors. Eighty patients had no evidence of disease at the time of HDC/ASCT (CR1). At the completion of HDC and ASCT, complete responses (CR) were seen in an additional 57 patients (CR2). Using Kaplan-Meier analysis, the median relapse-free survival (RFS) for the entire group was 15 months and overall survival (OS) was 27 months. The patients in CR1 had a median RFS and OS of 20.7 and 50.6 months, respectively. This was very similar to the RFS and OS in patients achieving CR2 after HDC/ASCT (p < 0.001; median: 19 and 40 months, respectively). In contrast, the patients with persistent residual disease had an RFS and OS of 7 and 12 months (p < 0.001). These data show that patients achieving a CR after HDC/ASCT have a better relapse-free and OS, when compared to patients with persistent residual disease after HDC/ASCT. This study suggests that a subset of patients with residual metastatic breast cancer after standard chemotherapy can achieve CR with HDC and ASCT which may result in better long-term outcome.

Esthesioneuroblastoma in Maffucci's syndrome.

Maffucci's syndrome consists of multiple cutaneous hemangiomas, dyschondroplasia, and enchondromas with potential for malignant change. We report a case of a 33-year-old man with Maffucci's syndrome who presented with a several month history of nasal congestion, facial pain, and diminished vision in his left eye. Radiological studies showed a large soft tissue mass centered in the sinonasal area, extending bilaterally into maxillary sinuses and orbits with compression of left optic nerve. Biopsy of the mass showed esthesioneuroblastoma (olfactory neuroblastoma). Chemotherapy resulted in initial improvement, but the tumor recurred and did not respond to further treatment, resulting in his death. Sarcomatous tumors are reported in Maffucci's syndrome, but this is a rare case of a neuroendocrine tumor in a patient with Maffucci's syndrome.

Atypical t(15;17)(q13;q12) in a patient with all-trans retinoic acid refractory secondary acute promyelocytic leukemia: a case report and review of the literature.

A 69-year-old woman developed microgranular acute promyelocytic leukemia (APL-M3) 10 months after receiving adjuvant cyclophosphamide, doxorubicin, and paclitaxel for breast cancer. Replicate bone marrow aspirate karyotypes contained a translocation between the long arms of chromosomes 15 and 17, but not at breakpoints typical for APL. Fluorescence in situ hybridization paints and RARalpha/PML cosmid probes verified that the breakpoints on chromosomes 15 and 17 were proximal to both the PML and RARalpha genes; t(15;17)(q13;12). Although the patient received induction chemotherapy and a several month trial of all-trans retinoic acid (ATRA), there was no clinical improvement or hematological remission. We suspect that this patient developed postchemotherapy secondary APL with an atypical t(15;17), which rendered her leukemic cells unresponsive to ATRA therapy.