Utility of routine pretreatment evaluation of left ventricular ejection fraction in breast cancer patients receiving anthracyclines.

Anthracycline-based chemotherapy is widely used in the management of breast cancer. Despite the lack of clinical evidence, obtaining prechemotherapy left ventricular ejection fraction (LVEF) by echocardiogram or multigated acquisition scan is a widely adopted practice throughout the world. We present here the results of a retrospective analysis of breast cancer patients who had LVEF measurements in anticipation of an anthracycline chemotherapy to determine whether predefined cardiac risk factors predicted for poor cardiac function. Retrospective data were analyzed from 482 female breast cancer patients in whom LVEF was measured before starting anthracycline-based chemotherapy. Baseline demographics and multiple risk factors associated with congestive heart failure were collected. Twenty-six possible risk factors for CHF were defined, and the frequency of finding an abnormal LVEF as a function of total risk factors was assessed. Statistical tests include chi-squared and logistic regression analysis. The median age of the study population was 52 years. The original chemotherapy plan was changed in 7 patients (1.45%) based on LVEF findings, all of which had asymptomatic LV dysfunction (LVEF ranging 40%-50%). In 32 patients, despite normal LVEF results, anthracyclines were omitted secondary to prior cardiac issues. In 17 patients where LVEF was reported normal, anthracyclines were skipped based on patient's preference, tumor characteristics, or upstaging of the cancer based on imaging studies. No patient with ≤2 risk factors had an abnormal LVEF (N = 350). The probability of finding an abnormal LVEF in patients without any cardiac risk factors is extremely rare. Skipping baseline LVEF assessment may be an option in some patients with no cardiac risk factors undergoing anthracycline-based chemotherapy.

Integrated Approach Reveals Role of Mitochondrial Germ-Line Mutation F18L in Respiratory Chain, Oxidative Alterations, Drug Sensitivity, and Patient Prognosis in Glioblastoma.

Glioblastoma is the most common and malignant primary brain tumour in adults, with a dismal prognosis. This is partly due to considerable inter- and intra-tumour heterogeneity. Changes in the cellular energy-producing mitochondrial respiratory chain complex (MRC) activities are a hallmark of glioblastoma relative to the normal brain, and associate with differential survival outcomes. Targeting MRC complexes with drugs can also facilitate anti-glioblastoma activity. Whether mutations in the mitochondrial DNA (mtDNA) that encode several components of the MRC contribute to these phenomena remains underexplored. We identified a germ-line mtDNA mutation (m. 14798T > C), enriched in glioblastoma relative to healthy controls, that causes an amino acid substitution F18L within the core mtDNA-encoded cytochrome b subunit of MRC complex III. F18L is predicted to alter corresponding complex III activity, and sensitivity to complex III-targeting drugs. This could in turn alter reactive oxygen species (ROS) production, cell behaviour and, consequently, patient outcomes. Here we show that, despite a heterogeneous mitochondrial background in adult glioblastoma patient biopsy-derived cell cultures, the F18L substitution associates with alterations in individual MRC complex activities, in particular a 75% increase in MRC complex II_III activity, and a 34% reduction in CoQ10, the natural substrate for MRC complex III, levels. Downstream characterisation of an F18L-carrier revealed an 87% increase in intra-cellular ROS, an altered cellular distribution of mitochondrial-specific ROS, and a 64% increased sensitivity to clomipramine, a repurposed MRC complex III-targeting drug. In patients, F18L-carriers that received the current standard of care treatment had a poorer prognosis than non-carriers (373 days vs. 415 days, respectively). Single germ-line mitochondrial mutations could predispose individuals to differential prognoses, and sensitivity to mitochondrial targeted drugs. Thus, F18L, which is present in blood could serve as a useful non-invasive biomarker for the stratification of patients into prognostically relevant groups, one of which requires a lower dose of clomipramine to achieve clinical effect, thus minimising side-effects.

Private Payer's Status Improves Male Breast Cancer Survival.

Survival from male breast cancer is influenced by many factors. This study assessed payer's status effect on survival of male breast cancer patients. This study included 8,828 male breast cancer patients diagnosed between 1998-2006 and followed to 2011 in the National Cancer Data Base. Cox regression was used to investigate the effect of payer's status and other factors on overall survival. Patients had 36.2%, 42.7%, 14.7%, and 6.5% of stage I to IV cancer, respectively. Payer status was private 47.7%, Medicare 42.6%, Medicaid 3.24%, unknown 3.59%, and uninsured 2.95%. Median overall survival (MOS) for all patients was 10.6 years. In multivariate analysis, Direct adjusted MOS was 12.46, 11.89, 9.99, 9.02, and 8.29 years for private, "unknown," Medicare, uninsured, and Medicaid payer's status, respectively. Patients with private and "unknown" payer's status showed a significant difference in survival compared to uninsured patients, while Medicaid and Medicare patients did not. Age, race, stage, grade, income, comorbidity, distance travelled, and diagnosing/treating facility were also significant predictors of survival. Treatment delay and cancer program did not have a significant influence on survival.

Effects of payer status on breast cancer survival: a retrospective study.

BACKGROUND: Breast cancer outcomes are influenced by multiple factors including access to care, and payer status is a recognized barrier to treatment access. To further define the influence of payer status on outcome, the National Cancer Data Base data from 1998-2006 was analyzed. METHOD: Data was analyzed from 976,178 female patients diagnosed with breast cancer registered in the National Cancer Data Base. Overall survival was the primary outcome variable while payer status was the primary predictor variable. Secondary predictor variables included stage, age, race, Charlson Comorbidity index, income, education, distance travelled, cancer program, diagnosing/treating facility, and treatment delay. Multivariate Cox regression was used to investigate the effect of payer status on overall survival while adjusting for secondary predictive factors. RESULTS: Uninsured (28.68%) and Medicaid (28.0%) patients had a higher percentage of patients presenting with stage III and stage IV cancer at diagnosis. In multivariate analysis, after adjusting for secondary predictor variables, payer status was a statistically significant predictor of survival. Patients with private, unknown, or Medicare status showed a decreased risk of dying compared to uninsured, with a decrease of 36%, 22%, and 15% respectively. However, Medicaid patients had an increased risk of 11% compared to uninsured. The direct adjusted median overall survival was 14.92, 14.76, 14.56, 13.64, and 12.84 years for payer status of private, unknown, Medicare, uninsured, and Medicaid respectively. CONCLUSION: We observed that patients with no insurance or Medicaid were most likely to be diagnosed at stage III and IV. Payer status showed a statistically significant relationship with overall survival. This remained true after adjusting for other predictive factors. Patients with no insurance or Medicaid had higher mortality.

Does obesity have an effect on outcomes in triple-negative breast cancer?

BACKGROUND: Among patients with breast cancer, obesity has been associated with an increased likelihood of having triple-negative breast cancer (TNBC). This association has been thought to be due to the antiapoptotic effects of obesity-related proteins. However, the effect of obesity on the outcomes in patients with TNBC remains unclear. We hypothesized that obesity would be associated with decreased overall survival and disease-free survival in these patients. MATERIALS AND METHODS: A retrospective review of a prospectively maintained database was conducted of patients treated for breast cancer at an academic medical center from March 1998 to September 2011. The body mass index (BMI) of patients with TNBC was calculated at diagnosis. The patients were categorized as normal (BMI < 25 kg/m(2)), overweight (BMI 25-30 kg/m(2)), or obese (BMI > 30 kg/m(2)). The endpoints of overall survival and disease-free survival were analyzed. RESULTS: A total of 183 patients with TNBC were included for analysis. Of the 183 patients, 24 (13.1%) were normal (BMI < 25 kg/m(2)), 42 (23.1%) were overweight (BMI 25-30 kg/m(2)), and 117 (63.7%) were obese (BMI > 30 kg/m(2)). The median follow-up period was 42.5 months. Of the 183 patients, 2 (9.1%) died in the normal group, 10 (23.1%) died in the overweight group, and 25 (21.4%) died in the obese group (P = 0.28). The patients who were overweight or obese had larger tumors (P = 0.02), a higher T stage (P = 0.001), and higher tumor grade (P = 0.01) than the normal BMI patients. By Kaplan-Meier analysis, normal patients had higher overall survival than the overweight or obese patients, but this difference was not statistically significant (P = 0.29). Disease-free survival was also not significantly different (P = 0.91). CONCLUSIONS: Despite an increased frequency of larger tumors, higher T stage, and higher tumor grade, obesity was not associated with decreased overall or disease-free survival in patients with TNBC.

Commercial insurance triples chances of breast cancer survival in a public hospital.

Breast cancer survival is affected both by endogenous factors and exogenous factors such as socioeconomic status. This study explored the relationship between insurance status and overall survival of 987 female breast cancer patients in a population served by a public hospital. All patients were offered the same level of care regardless of ability to pay. Of the 987 breast cancer patients investigated, 54.6% were African-American. 54.1% of patients were insured (commercial insurance or Medicare), 27.1% with Medicaid, and 18.8% who were uninsured. Overall median survival was 15.5 years and was not statistically significant between Caucasian and African-American women. Median survival times were 15.8, 11.3, and 8.2 years for insured, Medicaid, and uninsured groups, respectively. Uninsured patients had worse overall survival rates compared with insured patients (p < 0.05). Adjusting for other factors (e.g., stage, age, race, body mass index, and income), insurance was a significant factor affecting survival with hazard ratios of 2.24 and 3.22 for Medicaid and uninsured patients, respectively, compared with insured patients. Even in a public hospital, after adjusting for potential risk factors, insurance status still proved to be an important factor in the survival of breast cancer patients. Further research is necessary to identify causal factors related to the survival disparities associated with insurance status.

Superwarfarin intoxication: two case reports and review of pathophysiology and patient management.

Superwarfarin vitamin K antagonists are found in rat poisons and are readily available. Pediatric exposures are common but are usually asymptomatic without significant coagulopathy. Superwarfarin intoxication must be considered in any adult who presents with an unexplained coagulopathy with extreme elevation of prothrombin time and partial thromboplastin time with associated depletion of vitamin K dependent factors. If superwarfarin toxicity is confirmed, intentional ingestion should be considered, as a large quantity of ingested rat poison is necessary to induce a coagulopathy. Patients with superwarfin induced coagulopathy require several months of high dose oral and parenteral vitamin K supplementation. We describe two patients with superwarfarin toxicity treated at Louisiana State University Health in Shreveport and review pathophysiology and patient management.

Osteonecrosis of the jaw in patients with metastatic breast cancer: ethnic and socio-economic aspects.

Bisphosphonate therapy is an important adjunct to the treatment of patients with bone metastasis. Osteonecrosis of the jaw (ONJ), a complication related to bisphosphonate therapy, is reported in up to 7% of patients with metastatic breast cancer. The objective of this study was to define the prevalence and to identify risk factors associated with development of ONJ in a predominantly low socio-economic population. Medical records of patients with a diagnosis of metastatic breast cancer with bone metastasis seen between 2002 and 2007 were reviewed. All patients received a minimum of four infusions of zolendronic acid. Data on demographics, insurance status, tobacco use, concurrent therapy, body mass index, and number of zolendronic acid infusions were analyzed. Of the 110 patient analyzed, 10 developed ONJ (9%) with the mean number of zolendronic acid infusions in patients with ONJ of 22.9 ± 17. ONJ was seen more frequently in Caucasian than in African Americans patients (15% versus 2%; p = 0.019). ONJ was associated with older age at diagnosis of metastatic breast cancer (p = 0.02), tobacco use (p = 0.049), but was not associated with SES or duration of therapy. After adjusting for SES, Caucasian patients were 9.1 times more likely to have ONJ when compared with African American patients. (95% CI 1.03-81.7). Our results suggest an increase prevalence of ONJ in Caucasian breast cancer patients. However, as our study population is small, additional studies to confirm this finding are needed.

Adjuvant chemotherapy and timing of tamoxifen in postmenopausal patients with endocrine-responsive, node-positive breast cancer: a phase 3, open-label, randomised controlled trial.

BACKGROUND: Tamoxifen is standard adjuvant treatment for postmenopausal women with hormone-receptor-positive breast cancer. We assessed the benefit of adding chemotherapy to adjuvant tamoxifen and whether tamoxifen should be given concurrently or after chemotherapy. METHODS: We undertook a phase 3, parallel, randomised trial (SWOG-8814, INT-0100) in postmenopausal women with hormone-receptor-positive, node-positive breast cancer to test two major objectives: whether the primary outcome, disease-free survival, was longer with cyclophosphamide, doxorubicin, and fluorouracil (CAF) given every 4 weeks for six cycles plus 5 years of daily tamoxifen than with tamoxifen alone; and whether disease-free survival was longer with CAF followed by tamoxifen (CAF-T) than with CAF plus concurrent tamoxifen (CAFT). Overall survival and toxicity were predefined, important secondary outcomes for each objective. Patients in this open-label trial were randomly assigned by a computer algorithm in a 2:3:3 ratio (tamoxifen:CAF-T:CAFT) and analysis was by intention to treat of eligible patients. Groups were compared by stratified log-rank tests, followed by Cox regression analyses adjusted for significant prognostic factors. This trial is registered with ClinicalTrials.gov, number NCT00929591. FINDINGS: Of 1558 randomised women, 1477 (95%) were eligible for inclusion in the analysis. After a maximum of 13 years of follow-up (median 8.94 years), 637 women had a disease-free survival event (tamoxifen, 179 events in 361 patients; CAF-T, 216 events in 566 patients; CAFT, 242 events in 550 patients). For the first objective, therapy with the CAF plus tamoxifen groups combined (CAFT or CAF-T) was superior to tamoxifen alone for the primary endpoint of disease-free survival (adjusted Cox regression hazard ratio [HR] 0.76, 95% CI 0.64-0.91; p=0.002) but only marginally for the secondary endpoint of overall survival (HR 0.83, 0.68-1.01; p=0.057). For the second objective, the adjusted HRs favoured CAF-T over CAFT but did not reach significance for disease-free survival (HR 0.84, 0.70-1.01; p=0.061) or overall survival (HR 0.90, 0.73-1.10; p=0.30). Neutropenia, stomatitis, thromboembolism, congestive heart failure, and leukaemia were more frequent in the combined CAF plus tamoxifen groups than in the tamoxifen-alone group. INTERPRETATION: Chemotherapy with CAF plus tamoxifen given sequentially is more effective adjuvant therapy for postmenopausal patients with endocrine-responsive, node-positive breast cancer than is tamoxifen alone. However, it might be possible to identify some subgroups that do not benefit from anthracycline-based chemotherapy despite positive nodes. FUNDING: National Cancer Institute (US National Institutes of Health).

Trimodal therapy for inflammatory breast cancer: a surgeon's perspective.

Inflammatory breast cancer (IBC) is a rare and most aggressive form of breast cancer. The onset and progression of disease are rapid; diagnosis must be made expediently to initiate treatment quickly. In this review, the clinical presentation, trimodal therapy, surgical principles and a brief summary of the Louisiana State University at Shreveport experience with IBC are presented. With this aggressive approach, 5-year survival of better than 40-50% can be expected. This represents a substantive improvement in clinical outcome for IBC patients compared with 30 years ago.

Carcinomatous meningitis secondary to transitional cell bladder cancer.

We report a patient with carcinomatous meningitis secondary to known transitional cell carcinoma of the bladder. The patient presented with multiple focal neurological signs and symptoms. Diagnosis was suggested by magnetic resonance imaging and confirmed by analysis of the cerebrospinal fluid. He received whole brain radiotherapy despite a poor prognosis. To our knowledge, this is only the fifth reported case of neoplastic meningitis due to bladder cancer with confirmatory imaging and cytology and only the fourth reported case that presented with cranial nerve involvement.

A prospective study to validate the functional assessment of cancer therapy (FACT) for epidermal growth factor receptor inhibitor (EGFRI)-induced dermatologic toxicities FACT-EGFRI 18 questionnaire: SWOG S1013.

BACKGROUND: Papulopustular rash is a common class effect of epidermal growth factor receptor inhibitors (EGFRI) that can affect patients' health-related quality of life and cause disruptions to treatment. SWOG S1013 (NCT01416688) is a multi-center study designed to validate the Functional Assessment of Cancer Therapy EGFRI 18 (FACT-EGFRI 18) using 7-items from the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 to assess EGFRI-induced skin-related toxicities and their impact on functional status. METHODS: Patients with a diagnosis of colorectal or lung cancer to receive EGFRI therapies for at least 6 weeks were enrolled. Patient self-assessments using the FACT-EGFRI 18 were completed prior to undergoing CTCAE assessment by trained clinicians at baseline, weekly × 6, and then monthly × 3. The psychometric properties of the FACT-EGFRI 14 (skin toxicity items only) and 18 (plus 2 nail and 2 hair items) were established based on criterion validity, known groups validity, internal consistency reliability, and responsiveness to change. RESULTS: Of the 146 registered patients, 124 were evaluable. High Cronbach's alpha (> 0.70) for both FACT-EGFRI 14 and FACT-EGFRI 18 scores across assessment times were observed. Although agreement (i.e. criterion validity) between individual and summary scales of the FACT-EGFRI 18 for assessing skin toxicity was good, agreement with the clinician-reported CTCAE was only fair. The minimal important difference was determined to be 3 points. The results also demonstrated responsiveness to symptom change. DISCUSSION: Based on the results of this multi-center validation study, the FACT-EGFRI 18 patient-reported outcome instrument provided data from the patient's perspective yielding unique information as well as complementing clinician-rated CTCAE grades, especially for the symptoms of pain, pruritus, and paronychia. CONCLUSIONS: Good to excellent psychometric properties for the FACT-EGFRI 18 were demonstrated, supporting further use of this patient-reported outcomes measure. Additional validation with a more diverse group of patients should be conducted.

Paraplegia of spinal epidural compression by metastatic breast cancer and urgent radiotherapy-timeliness for naught?

Four patients who became paraplegic because of spinal epidural compression by metastatic breast cancer were treated for palliation by external beam radiation. None of the four regained ambulation after therapy. Our findings place in question the urgent need for radiotherapy in these paralytic people with the disorder, especially when they are pain-free.

Predictive value of eIF4E reduction after neoadjuvant therapy in breast cancer.

INTRODUCTION: Initiation factor 4E (eIF4E) overexpression has prognostic significance in breast cancer. Up-regulation of downstream gene products associated with high eIF4E overexpression has been linked to chemoresistance. We hypothesize patients whose tumors had eIF4E reduction after neoadjuvant chemotherapy will have lower cancer recurrence compared with those who did not. METHODS: Seventeen locally advanced breast cancer patients were accrued, and tumor specimens were obtained before and after neoadjuvant therapy. eIF4E was quantified by Western blots. Primary end-point was cancer recurrence. RESULTS: Low eIF4E was defined as < or =7.5-fold elevation and high eIF4E was >7.5-fold elevation. Of 17 patients, six tumors remained low after neoadjuvant therapy, six dropped from high to low eIF4E, and five remained high. With a median follow-up of 29 mo, four of five patients with tumors that remained high have recurred while only three of 12 patients in the low eIF4E post-therapy group have recurred (P=0.05, chi(2)). Survival analysis using the Kaplan-Meier method showed a higher rate of cancer recurrence in patients with post-treatment high eIF4E overexpression (P=0.026, log rank test). CONCLUSIONS: Breast cancer patients whose tumors had low eIF4E overexpression after neoadjuvant chemotherapy had lower cancer recurrence compared with those who did not.

Prevalence of Hepatitis B Virus, Hepatitis C Virus, and HIV Infection Among Patients With Newly Diagnosed Cancer From Academic and Community Oncology Practices.

IMPORTANCE: Universal screening of patients with newly diagnosed cancer for hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV is not routine in oncology practice, and experts disagree about whether universal screening should be performed. OBJECTIVE: To estimate the prevalence of HBV, HCV, and HIV infection among persons with newly diagnosed cancer. DESIGN, SETTING, AND PARTICIPANTS: Multicenter prospective cohort study of patients with newly diagnosed cancer (ie, identified within 120 days of cancer diagnosis) at 9 academic and 9 community oncology institutions affiliated with SWOG (formerly the Southwest Oncology Group) Cancer Research Network, a member of the National Clinical Trials Network, with enrollment from August 29, 2013, through February 15, 2017. The data analysis was conducted using data available through August 17, 2017. MAIN OUTCOMES AND MEASURES: The accrual goal was 3000 patients and the primary end point was the presence of HBV infection (previous or chronic), HCV infection, or HIV infection at enrollment. Patients with previous knowledge of infection as well as patients with unknown viral viral status were evaluated. RESULTS: Of 3092 registered patients, 3051 were eligible and evaluable. Median (range) age was 60.6 (18.2-93.7) years, 1842 (60.4%) were female, 553 (18.1%) were black, and 558 (18.3%) were Hispanic ethnicity. Screened patients had similar clinical and demographic characteristics compared with those registered. The observed infection rate for previous HBV infection was 6.5% (95% CI, 5.6%-7.4%; n = 197 of 3050 patients); chronic HBV, 0.6% (95% CI, 0.4%-1.0%; n = 19 of 3050 patients); HCV, 2.4% (95% CI, 1.9%-3.0%; n = 71 of 2990 patients); and HIV, 1.1% (95% CI, 0.8%-1.6%; n = 34 of 3045). Among those with viral infections, 8 patients with chronic HBV (42.1%; 95% CI, 20.3%-66.5%), 22 patients with HCV (31.0%; 95% CI, 20.5%-43.1%), and 2 patients with HIV (5.9%; 95% CI, 0.7%-19.7%) were newly diagnosed through the study. Among patients with infections, 4 patients with chronic HBV (21.1%; 95% CI, 6.1%-45.6%), 23 patients with HCV (32.4%; 95% CI, 21.8%-44.5%), and 7 patients with HIV (20.6%; 95% CI, 8.7%-37.9%) had no identifiable risk factors. CONCLUSIONS AND RELEVANCE: Results of this study found that a substantial proportion of patients with newly diagnosed cancer and concurrent HBV or HCV are unaware of their viral infection at the time of cancer diagnosis, and many had no identifiable risk factors for infection. Screening patients with cancer to identify HBV and HCV infection before starting treatment may be warranted to prevent viral reactivation and adverse clinical outcomes. The low rate of undiagnosed HIV infection may not support universal screening of newly diagnosed cancer patients.

Hyperglycemia-induced thioredoxin-interacting protein expression differs in breast cancer-derived cells and regulates paclitaxel IC50.

PURPOSE: We studied the hyperglycemia-induced expression of thioredoxin-interacting protein (TXNIP) expression and its relevance on the cytotoxic activity of paclitaxel in mammary epithelial-derived cell lines. EXPERIMENTAL DESIGN: Nontumorigenic cells (MCF10A); tumorigenic, nonmetastatic cells (MCF-7/T47D); and tumorigenic, metastatic cells (MDA-MB-231/MDA-MB-435s) were grown either in 5 or 20 mmol/L glucose chronically. Semiquantitative reverse transcription-PCR was used to assess TXNIP RNA expression in response to glucose. Reactive oxygen species were detected by CM-H2DCFDA (5-6-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate) and measured for mean fluorescence intensity with flow cytometry. Thioredoxin activity was assayed by the insulin disulfide-reducing assay. Proliferation was evaluated using CellTiter96 reagent with 490-nm absorption. Obtained absorbance values were used to calculate the paclitaxel IC(50) in 5 or 20 mmol/L glucose using the Chou's dose-effect equation. RESULTS: We show that hyperglycemia by itself affects the level of TXNIP RNA in breast cancer-derived cells. TXNIP RNA level differs between nontumorigenic/nonmetastatic, tumorigenic cells (low TXNIP level), and metastatic cells (high TXNIP level). The differences in TXNIP RNA level, in reactive oxygen species level, and in thioredoxin activity are all related. We further show that hyperglycemia is a favorable condition in increasing the paclitaxel cytotoxicity by causing IC(50) 3-fold decrease in metastatic breast cancer-derived MDA-MB-231 cells. The increased paclitaxel cytotoxicity is associated with an additive effect on the hyperglycemia-mediated TXNIP expression more evident in conditions of hyperglycemia than normoglycemia. CONCLUSIONS: Our study opens a new perspective on the relevance of metabolic conditions of hyperglycemia in the biology and treatment of cancer, particularly in view of the epidemic of diabetes.

Randomized, Multicenter, Placebo-Controlled Clinical Trial of Duloxetine Versus Placebo for Aromatase Inhibitor-Associated Arthralgias in Early-Stage Breast Cancer: SWOG S1202.

Purpose Adherence to aromatase inhibitor (AI) therapy for early-stage breast cancer is limited by AI-associated musculoskeletal symptoms (AIMSS). Duloxetine is US Food and Drug Administration approved for treatment of multiple chronic pain disorders. We hypothesized that treatment of AIMSS with duloxetine would improve average joint pain compared with placebo. Methods This randomized, double-blind, phase III trial included AI-treated postmenopausal women with early-stage breast cancer and who had average joint pain score of ≥ 4 out of 10 that developed or worsened since AI therapy initiation. Patients were randomly assigned 1:1 to duloxetine or placebo for 13 weeks. The primary end point was average joint pain through 12 weeks, examined using multivariable linear mixed models, adjusted for stratification factors (baseline pain score of 4 to 6 v 7 to 10 and prior taxane use). Clinically significant change in average pain was defined as a ≥ 2-point decrease from baseline. Results Of 299 enrolled patients, 127 patients treated with duloxetine and 128 who received placebo were evaluable for the primary analysis. By 12 weeks, the average joint pain score was 0.82 points lower for patients who received duloxetine compared with those who received placebo (95% CI, -1.24 to -0.40; P = .0002). Similar patterns were observed for worst joint pain, joint stiffness, pain interference, and functioning. Rates of adverse events of any grade were higher in the duloxetine-treated group (78% v 50%); rates of grade 3 adverse events were similar. Conclusion Results of treatment with duloxetine for AIMSS were superior to those of placebo among women with early-stage breast cancer, although it resulted in more frequent low-grade toxicities.

Excellent response to chemotherapy post immunotherapy.

INTRODUCTION: Immunotherapy in the form of immune checkpoint inhibitors has changed the landscape of cancer treatment. Newer monoclonal antibodies are coming up and are being tested in various cancers during different stages of treatment. With the increasing use of immune checkpoint inhibitors in the management of various types of cancers, the question is raised as to what next can be offered to a patient who has progressed on this newer treatment. Does Sequence matter? There have been reports of improved responses to chemotherapy after immunotherapy in the form of vaccines. Here we present a case series of 6 patients who progressed on immunotherapy with immune checkpoint inhibitors after initial modality of treatment (chemotherapy/radiation), subsequently received chemotherapy with excellent response. METHODS: We have a cohort of six patients who had disease progression on second line Immunotherapy for solid or hematological malignancies and had ECOG < 2. All these patients received third line salvage chemotherapy. Three patients had metastatic head and neck cancer, 2 had non-small cell lung cancer (NSCLC), and one had T -cell rich B- cell lymphoma. Prior review and approval were obtained from our institutional review board. RESULTS: All patients had an excellent response to chemotherapy in third line setting, after immune checkpoint inhibitors and most of them achieved a complete response. CONCLUSION: Targeting cancer with chemotherapy after failure of immunotherapy is a valid option and can lead to better response rates and PFS which may lead to OS. This effect may be secondary to immunotherapy removing the inhibition exerted by tumor cells or other immune cells initially followed by cytotoxic chemotherapy mediated killing of tumor cells.

Chemotherapy with taxanes in breast cancer during pregnancy: case report and review of the literature.

Two patients with breast cancer received docetaxel-containing chemotherapy as adjuvant or neoadjuvant therapy during pregnancy. The first pregnant patient began neoadjuvant therapy with doxorubicin/cyclophosphamide at 14 weeks of gestation. After 4 cycles of doxorubicin/cyclophosphamide and surgery, she received adjuvant docetaxel for 4 cycles. The second patient began neoadjuvant therapy with doxorubicin/docetaxel at 14 weeks of gestation and received 6 cycles. The fetus of the first patient had hydrocephalus on ultrasound at 17 weeks of gestation (before docetaxel therapy) that persisted on serial follow-up ultrasounds and spontaneously regressed over several months after delivery. No fetal malformations were detected in the second fetus. These 2 cases add to the existing data on the use of taxanes during pregnancy. Although the data are limited with case reports, pregnant patients with cancer can be treated with chemotherapy including taxanes during the second and third trimesters without significant risks to the fetus. Taxanes should not be excluded, if indicated, in pregnant patients with cancer.