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Introduction: One in ten women over the age of 65 will develop breast cancer. Despite this high incidence of breast cancer among older women, social support for them is often inadequate. This paper describes a qualitative study of the impact of a breast cancer diagnosis on older women from racially/ethnically diverse populations and their subsequent need for social support.Methods: Forty-seven older African American, Asian American, Caucasian and Latina women between the ages of 65 to 83 participated in a larger study examining the impact of breast cancer on women from racially/ethnically diverse populations and the meaning and nature of social support. The women completed an in-depth qualitative interview on the psychosocial impact of breast cancer and the meaning and nature of social support.Results and Conclusion: The results indicate that there are variations in reactions to a breast cancer diagnosis among older women, and that these reactions impact their experiences with seeking social support at diagnosis and during treatment. Respondents were concerned about their aging bodies, potential dependency on others, and loss of autonomy. At the same time, the severity of cancer treatment and existing co-morbidities often meant they needed to learn to receive support, and to reach out if they had no support. The implications of these findings underscore the older cancer patient's need to strengthen her supportive networks at the time of diagnosis, during treatment, and post-treatment. [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer remains one of the leading causes of morbidity and mortality for all women in the US. Current research has focused on the psychological relationship and not the sociological relationship between emotions and the experience of breast cancer survivors. This paper focuses on the emotion work involved in self-disclosing a breast cancer diagnosis in a racially or ethnically diverse population.Methods: The participants (n = 176) selected for this study were African American, Asian American, Latina, and Caucasian women who had been diagnosed with stages 0, I, or II breast cancer within the past 4 years. They completed an in-depth qualitative interview on self-disclosure and social support.Findings: The results indicate self-disclosing was done at a time when important decisions about treatment needed to be made. Different strategies for disclosure were used, all of which entailed emotion work. Respondents talked about the various elements of emotion work in the disclosure process including: managing others' worry, protecting and soothing others, and educating and instructing others. For many respondents, disclosure without calculating emotional management meant opening up to others which meant support and an increase in emotional resources.Conclusions: The findings in this paper have implications for women with breast cancer and demonstrate the need for women to be involved in honest disclosure and less emotional management of others' feelings. There is also a need for education about the nature of the cancer experience among people who are not well educated about the treatment and consequences of cancer. This need may be even stronger among racial and ethnic minorities. [ABSTRACT FROM AUTHOR]

Objectives: Prayer is becoming more widely acknowledged as a way to cope with cancer. The goal of this study was to compare differences in use of prayer between breast cancer survivors from different ethnic groups and examine how use of prayer is related to mood and quality of life.Methods: This study used a mixed methods design. One hundred and seventy-five breast cancer survivors participated in a longitudinal study of survivorship. Women completed in-depth qualitative interviews and a battery of measures including quality of life, spirituality, social support, and mood.Results: Eighty-one percent of the women prayed. There were no significant differences between the groups for any of the psychological, social support, or quality of life variables with the exception of higher benefit finding and spiritual well-being among those who prayed. The data did show that women who prayed were able to find more positive contributions from their cancer experience than women who did not pray. The interviews showed that those who prayed tended to be African American or Asian, Catholic or Protestant. The prayers were for petitioning, comfort, or praise. Some of the women stated that they had difficulty praying for themselves.Conclusions: While there seems to be few differences in terms of standardized measures of quality of life, social support, and mood between those who prayed and those who did not, the interviews showed that certain ethnic minority groups seem to find more comfort in prayer, felt closer to God, and felt more compassion and forgiveness than Caucasian women. [ABSTRACT FROM AUTHOR]

Ovarian cancer is the fourth highest cause of cancer deaths in the US. Psychosocial issues may be prevalent among these women. This study examined the efficacy of a gynecological cancer resource program. Fifty-three women completed questionnaires over a year's time. The women felt positively about the program, and used several of the services. The most used services were that of the center coordinator/nurse practitioner, the GYN support group, the hair consultant, and the imagery sessions. The social worker, massage therapist, and the nutritionist seemed to be important at the beginning of the cancer experience but not so much at later stages. Having a nurse practitioner who could talk about treatment side effects, menopause, body image, sexuality, etc., was helpful to at least half of the women. Psychological distress decreased over time, as did quality of life. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common cancer in women in the United States and constitutes a major source of medical and psychological morbidity. The psychosocial sequelae, while not always severe, can last up to a year after diagnosis. This may be a time when spiritual and social resources become important. It is known that practical and emotional support during treatment for breast cancer benefits the patient's mood and quality of life, but it is unclear as to how spirituality and spiritual well-being may benefit the patient. This study examined this question by exploring the relationships between spirituality, spiritual well-being, physical well-being, functional well-being, mood, and adjustment style in a sample of 191 women recently diagnosed with breast cancer or who had metastatic cancer. The women were asked to complete questionnaires pertaining to the above topics at enrollment to a group intervention study. Measures of spirituality, spiritual well-being, physical well-being, functional well-being, mood, and adjustment style taken at the same point in time were then correlated with each other. There were more significant correlations of spirituality and spiritual well-being with functional well-being than physical well-being, but items pertaining to meaning and peace tended to correlate significantly with physical well-being. Spirituality also correlated significantly with several coping styles, but not avoidance as has been previously suggested. Regression analyses were also performed to find the best combination of variables to predict physical and functional well-being. A combination of social well-being and several questions pertaining to peacefulness accounted for 18% of the variance in physical well-being. However, a combination of social well-being and the spiritual scales accounted for 46% of the variance in functional well-being. When the spiritual scales were examined alone, they accounted for 40% of the variance in functional well-being. The results of this study confirm the importance of spirituality and spiritual well-being in both physical and functional well-being. Asking patients about the role of spirituality in their lives may be a useful marker to predict patient's ability to cope with stress in their lives and of their quality of life. [ABSTRACT FROM AUTHOR]

This study examined the relationships among spiritual well-being, quality of life, and psychological adjustment in 142 women diagnosed with breast cancer who were participating in a larger study designed to compare the efficacy of two psychosocial support programs. Participants were given a set of questionnaires that measured spiritual well-being, quality of life, and adjustment to cancer. Results revealed a positive correlation between spiritual well-being and quality of life, as well as significant correlations between spiritual well-being and specific adjustment styles (e.g. fighting spirit). There was also a negative correlation between quality of life and use of a helpless/hopeless adjustment style, and a positive correlation between quality of life and fatalism. In regression analyses, after controlling for demographic variables and adjustment styles, spiritual well-being contributed very little additional variance in quality of life. These findings suggest that while spiritual well-being is correlated with both quality of life and psychological adjustment, the relationships among these variables are more complex and perhaps indirect than previously considered. [ABSTRACT FROM AUTHOR]

Background: Presence of cytotoxic T lymphocytes (CTL) in the tumor microenvironment (TME) predicts the effectiveness of cancer immunotherapies. The ability of toll-like receptor 3 (TLR3) ligands, interferons (IFNs) and COX2 inhibitors to synergistically induce CTL-attracting chemokines (but not regulatory T cell (Treg)-attractants) in the TME, but not in healthy tissues, observed in our preclinical studies, suggested that their systemic application can reprogram local TMEs., Methods: Six evaluable patients (33-69 years) with metastatic triple-negative breast cancer received six doses of systemic chemokine-modulating (CKM) regimen composed of TLR3 ligand (rintatolimod; 200 mg; intravenous), IFN-α2b (20 MU/m 2 ; intravenous) and COX2 inhibitor (celecoxib; 2×200 mg; oral) over 2 weeks. The predetermined primary endpoint was the intratumoral change in the expression of CTL marker, CD8α, in the post-CKM versus pre-CKM tumor biopsies. Patients received follow-up pembrolizumab (200 mg, intravenously, every 3 weeks), starting 3-8 days after completion of CKM., Results: Post-CKM biopsies showed selectively increased CTL markers CD8α (average 10.2-fold, median 5.5-fold, p=0.034) and granzyme B (GZMB; 6.1-fold, median 5.8-fold, p=0.02), but not FOXP3 (Treg marker) relative to HPRT1 expression, resulting in the increases in average CD8α/FOXP3 ratio and GZMB/FOXP3 ratio. CKM increased intratumoral CTL-attractants CCL5 and CXCL10, but not Treg-attractants CCL22 or CXCL12. In contrast, CD8 + T cells and their CXCR3 + subset showed transient decreases in blood. One clinical response (breast tumor autoamputation) and three stable diseases were observed. The patient with clinical response remains disease free, with a follow-up of 46 months as of data cut-off., Conclusions: Short-term systemic CKM selectively increases CTL numbers and CTL/Treg ratios in the TME, while transiently decreasing CTL numbers in the blood. Transient effects of CKM suggest that its simultaneous application with checkpoint blockade and other forms of immunotherapy may be needed for optimal outcomes., Competing Interests: Competing interests: No, there are no competing interests., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Most metastatic recurrences of triple negative breast cancer (TNBC) occur within five years of diagnosis, yet late relapses of TNBC (lrTNBC) do occur. Our objective was to develop a risk prediction model of lrTNBC using readily available clinicopathologic and sociodemographic features., Methods: We included patients diagnosed with stage I-III TNBC between 1998 and 2012 at ten academic cancer centers. lrTNBC was defined as relapse or mortality greater than 5 years from diagnosis. Features associated with lrTNBC were included in a multivariable logistic model using backward elimination with a p < 0.10 criterion, with a final multivariable model applied to training (70%) and independent validation (30%) cohorts., Results: A total 2210 TNBC patients with at least five years follow-up and no relapse before 5 years were included. In final multivariable model, lrTNBC was significantly associated with higher stage at diagnosis (adjusted Odds Ratio [aOR] for stage III vs I, 10.9; 95% Confidence Interval [CI], 7.5-15.9; p < 0.0001) and BMI (aOR for obese vs normal weight, 1.4; 95% CI, 1.0-1.8; p = 0.03). Final model performance was consistent between training (70%) and validation (30%) cohorts., Conclusions: A risk prediction model incorporating stage, BMI, and age at diagnosis offers potential utility for identification of patients at risk of development of lrTNBC and warrants further investigation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: It is critically important to study the real-world data of FDA-approved medications to understand the response rates and toxicities observed in the real-world population not represented in the clinical trials., Methods: We reviewed charts of patients diagnosed with metastatic, hormone receptor-positive, human epidermal growth factor receptor 2 negative, PIK3CA-mutated breast cancer treated with alpelisib from May 2019 to January 2022. Clinical characteristics and treatment outcomes were collected. The association of clinical characteristics with responses and adverse events (AEs) was evaluated using the logistic regression model., Results: 27 patients were included. Median age at alpelisib initiation 67 years (range: 44, 77 years). Majority of patients had excellent performance status at time of alpelisib initiation. Most patients had chronic comorbidities, notably; 2 patients had controlled type 2 diabetes mellitus at time of alpelisib initiation. Majority had a median of three lines of therapy (range: 1, 7) before alpelisib. Clinical responses were determined using RECIST v1.1. 3/27 (11.11%) patients discontinued therapy before response assessment due to grade 3 AEs. Overall response rate was 12.5% (3/24), with all partial responses (PR). The median duration of response was 5.77 months (range: 5.54, 8.98). 14/27 (51.9%) of patients required dose interruption/reduction. Overall, 23/27 (85.19%) patients discontinued alpelisib of which 11 (47.83%) discontinued alpelisib due to AEs. Median duration of treatment was 2 months in patients who had grade 3 AEs (range: <1.00, 8.30) and 6.28 (1.15, 10.43) in those who did not. Any grade AEs were reported in 24/27 (88.9%) patients, namely, hyperglycemia 16/27 (59.3%), nausea 11/27 (40.7%), diarrhea 10/27 (37.0%), fatigue 7/27 (25.9%) and rash 6/27 (22.2%). Grade 3 AEs were reported in 13/27 patients (50%), namely, hyperglycemia in 7/27 (53.8%) patients followed by skin rash 4/27 (30.8%), GI side effects 3/27 (23.1%). Those with progressive disease as best response to alpelisib, had more non-metabolic comorbidities, higher number of liver metastases, PIK3CA E545K mutations, and shorter duration on therapy compared to those with PR and stable disease., Conclusion: Patients should be counseled about the toxicity and modest benefit observed with alpelisib in real-world clinical practice when used in later lines of therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Alaklabi, Roy, Attwood, George, O’Connor, Early, Levine and Gandhi.)

Purpose: To examine the association between race and clinical outcomes (pathological complete response [pCR]; recurrence-free survival [RFS], and overall survival [OS]) in patients diagnosed with triple-negative (TNBC) or HER2-positive breast cancer treated with neoadjuvant chemotherapy (NAC)., Methods: Patients who self-identified as non-Hispanic white (NHW) or non-Hispanic Black (NHB) and were diagnosed with Stage I-III TNBC (n = 171 including 124 NHW and 47 NHB) and HER2-positive (n = 161 including 136 NHW and 25 NHB) breast cancer who received NAC from 2000 to 2018 at Roswell Park Comprehensive Cancer Center were included. Associations of race with pCR and survival outcomes were evaluated using logistic and Cox regression models, respectively., Results: There was no statistically significant difference in pCR between NHB and NHW patients with TNBC (31.9 vs 29.8%; OR: 1.11, 95% CI 0.54-2.29) or HER2-positive breast cancer (36.0 vs 39.7%; OR: 0.87, 95% CI 0.36-3.11). After controlling for potential confounders, including age, stage, treatment regimens, insurance status, and comorbidities, no statistically significant difference in OS or RFS was observed between NHB and NHW patients within either subtype., Conclusion: TNBC or HER2-positive breast cancer patients treated at a single academic center in Buffalo, NY, showed similar outcomes independent of patients' race. Given the known genetic diversity of African American ancestry in the US, further studies investigating the interplay between race, geography, and clinical outcomes are warranted., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Endocrine therapy resistance in advanced breast cancer remains a significant clinical problem that may be overcome with the use of histone deacetylase inhibitors such as entinostat. The ENCORE301 phase II study reported improvement in progression-free survival (PFS) and overall survival (OS) with the addition of entinostat to the steroidal aromatase inhibitor (AI) exemestane in advanced hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer., Patients and Methods: E2112 is a multicenter, randomized, double-blind, placebo-controlled phase III study that enrolled men or women with advanced HR-positive, HER2-negative breast cancer whose disease progressed after nonsteroidal AI. Participants were randomly assigned to exemestane 25 mg by mouth once daily and entinostat (EE) or placebo (EP) 5 mg by mouth once weekly. Primary end points were PFS by central review and OS. Secondary end points included safety, objective response rate, and lysine acetylation change in peripheral blood mononuclear cells between baseline and cycle 1 day 15., Results: Six hundred eight patients were randomly assigned during March 2014-October 2018. Median age was 63 years (range 29-91), 60% had visceral disease, and 84% had progressed after nonsteroidal AI in metastatic setting. Previous treatments included chemotherapy (60%), fulvestrant (30%), and cyclin-dependent kinase inhibitor (35%). Most common grade 3 and 4 adverse events in the EE arm included neutropenia (20%), hypophosphatemia (14%), anemia (8%), leukopenia (6%), fatigue (4%), diarrhea (4%), and thrombocytopenia (3%). Median PFS was 3.3 months (EE) versus 3.1 months (EP; hazard ratio = 0.87; 95% CI, 0.67 to 1.13; P = .30). Median OS was 23.4 months (EE) versus 21.7 months (EP; hazard ratio = 0.99; 95% CI, 0.82 to 1.21; P = .94). Objective response rate was 5.8% (EE) and 5.6% (EP). Pharmacodynamic analysis confirmed target inhibition in entinostat-treated patients., Conclusion: The combination of exemestane and entinostat did not improve survival in AI-resistant advanced HR-positive, HER2-negative breast cancer., Competing Interests: Roisin M. ConnollyOther Relationship: Pfizer Kathy D. MillerConsulting or Advisory Role: Merck, Genentech/Roche, Athenex, AstraZeneca, Bristol Myers Squibb/CelgeneResearch Funding: Taiho Pharmaceutical, Novartis, Seattle Genetics, Pfizer, Astex Pharmaceuticals, British Biotech, CytomX Therapeutics, Alphamab Karen L. SmithStock and Other Ownership Interests: AbbVie, Abbott LaboratoriesHonoraria: ASiM CMEResearch Funding: Pfizer Ursa A. Brown-GlabermanConsulting or Advisory Role: Novartis, Biotheranostics, Eisai, Seattle Genetics, Taiho OncologyResearch Funding: Seattle Genetics Bryan A. FallerConsulting or Advisory Role: L.E.K. ConsultingTravel, Accommodations, Expenses: Genentech, Novartis, EB SQUIBB, Celgene, Boehringer Ingelheim, Eisai, AstraZeneca, Lilly, Amgen, Merck, TakedaOpen Payments Link: https://openpaymentsdata.cms.gov/physician/127090 Adedayo A. OnitiloConsulting or Advisory Role: Kite, a Gilead Company, Envision CommunicationsSpeakers' Bureau: GlaxoSmithKline, Puma Biotechnology, Kite/Gilead, AbbVie Mark E. BurkardConsulting or Advisory Role: Pointcare Genomics, Strata Oncology, NovartisResearch Funding: AbbVie, Strata Oncology, Puma Biotechnology, Loxo, Merck, Arcus, Apollomics, Elevation Oncology, GenentechPatents, Royalties, Other Intellectual Property: I have a patent for implantable or localized drug delivery device that can sample the tumor microenvironment and deliver drug. I have a patent for a method to detect recombination events with CRISPR-mediated editing. I have a patent for conducting expansion microscopy without specialized equipment George T. BuddHonoraria: DecipheraConsulting or Advisory Role: Deciphera, Epic SciencesSpeakers' Bureau: DecipheraResearch Funding: Genentech/Roche, TRACON Pharma, Daiichi Sankyo/Lilly, AmbrxOpen Payments Link: https://openpaymentsdata.cms.gov/physician/774695/summary Ellis G. LevineResearch Funding: Oncolytic BiotechPatents, Royalties, Other Intellectual Property: UpToDate Peter A. KaufmanStock and Other Ownership Interests: AmgenHonoraria: LillyConsulting or Advisory Role: Polyphor, Roche/Genentech, Lilly, Eisai, Macrogenics, Pfizer, Merck, AstraZenecaSpeakers' Bureau: LillyResearch Funding: Eisai, Polyphor, Roche/Genentech, Lilly, Novartis, Macrogenics, Pfizer, SanofiTravel, Accommodations, Expenses: Lilly, Polyphor, Macrogenics Alexandra ThomasStock and Other Ownership Interests: Johnson & Johnson, Gilead Sciences, Bristol Myers Squibb, PfizerConsulting or Advisory Role: BeyondSpring Pharmaceuticals, LillyResearch Funding: SanofiPatents, Royalties, Other Intellectual Property: UpToDate RoyaltiesTravel, Accommodations, Expenses: Genentech Jane B. TrepelResearch Funding: Syndax, EpicentRX, AstraZeneca Antonio C. WolffConsulting or Advisory Role: Ionis PharmaceuticalsPatents, Royalties, Other Intellectual Property: Antonio Wolff has been named as inventor on one or more issued patents or pending patent applications relating to methylation in breast cancer and has assigned his rights to JHU and participates in a royalty-sharing agreement with JHUOpen Payments Link: https://openpaymentsdata.cms.gov/physician/357301/summary Joseph A. SparanoStock and Other Ownership Interests: MetastatConsulting or Advisory Role: Genentech/Roche, Novartis, AstraZeneca, Celgene, Lilly, Celldex, Pfizer, Prescient Therapeutics, Juno Therapeutics, Merrimack, Adgero Biopharmaceuticals, Cardinal Health, GlaxoSmithKline, CStone Pharmaceuticals, Epic Sciences, Daiichi Sankyo, BMSiSpeakers' Bureau: Eisai, CertaraResearch Funding: Prescient Therapeutics, Deciphera, Genentech/Roche, Merck, Novartis, Merrimack, Radius Health, Olema PharmaceuticalsTravel, Accommodations, Expenses: Menarini Silicon Biosystems, Roche/Genentech, Adgero Biopharmaceuticals, Myriad Genetics, Pfizer, AstraZeneca, Rhenium MedicalNo other potential conflicts of interest were reported.

Background: The CBR3 V244M single nucleotide polymorphism has been linked to the risk of anthracycline-related cardiomyopathy in survivors of childhood cancer. There have been limited prospective studies examining the impact of CBR3 V244M on the risk for anthracycline-related cardiotoxicity in adult cohorts., Objectives: This study evaluated the presence of associations between CBR3 V244M genotype status and changes in echocardiographic parameters in breast cancer patients undergoing doxorubicin treatment., Methods: We recruited 155 patients with breast cancer receiving treatment with doxorubicin (DOX) at Roswell Park Comprehensive Care Center (Buffalo, NY) to a prospective single arm observational pharmacogenetic study. Patients were genotyped for the CBR3 V244M variant. 92 patients received an echocardiogram at baseline (t 0 month ) and at 6 months (t 6 months ) of follow up after DOX treatment. Apical two-chamber and four-chamber echocardiographic images were used to calculate volumes and left ventricular ejection fraction (LVEF) using Simpson's biplane rule by investigators blinded to all patient data. Volumetric indices were evaluated by normalizing the cardiac volumes to the body surface area (BSA)., Results: Breast cancer patients with CBR3 GG and AG genotypes both experienced a statistically significant reduction in LVEF at 6 months following initiation of DOX treatment for breast cancer compared with their pre-DOX baseline study. Patients homozygous for the CBR3 V244M G allele (CBR3 V244) exhibited a further statistically significant decrease in LVEF at 6 months following DOX therapy in comparison with patients with heterozygous AG genotype. We found no differences in age, pre-existing cardiac diseases associated with myocardial injury, cumulative DOX dose, or concurrent use of cardioprotective medication between CBR3 genotype groups., Conclusions: CBR3 V244M genotype status is associated with changes in echocardiographic parameters suggestive of early anthracycline-related cardiomyopathy in subjects undergoing chemotherapy for breast cancer.

Background: Triple-negative breast cancer (TNBC) accounts for disproportionately poor outcomes in breast cancer, driven by a subset of rapid-relapse TNBC (rrTNBC) with marked chemoresistance, rapid metastatic spread, and poor survival. Our objective was to evaluate clinicopathologic and sociodemographic features associated with rrTNBC., Methods: We included patients diagnosed with stage I-III TNBC in 1996 through 2012 who received chemotherapy at 1 of 10 academic cancer centers. rrTNBC was defined as a distant metastatic recurrence event or death ≤24 months after diagnosis. Features associated with rrTNBC were included in a multivariable logistic model upon which backward elimination was performed with a P<.10 criterion, with a final multivariable model applied to training (70%) and independent validation (30%) cohorts., Results: Among all patients with breast cancer treated at these centers, 3,016 fit the inclusion criteria. Training cohort (n=2,112) bivariable analyses identified disease stage, insurance type, age, body mass index, race, and income as being associated with rrTNBC (P<.10). In the final multivariable model, rrTNBC was significantly associated with higher disease stage (adjusted odds ratio for stage III vs I, 16.0; 95% CI, 9.8-26.2; P<.0001), Medicaid/indigent insurance, lower income (by 2000 US Census tract), and younger age at diagnosis. Model performance was consistent between the training and validation cohorts. In sensitivity analyses, insurance type, low income, and young age were associated with rrTNBC among patients with stage I/II but not stage III disease. When comparing rrTNBC versus late relapse (>24 months), we found that insurance type and young age remained significant., Conclusions: Timing of relapse in TNBC is associated with stage of disease and distinct sociodemographic features, including insurance type, income, and age at diagnosis.

Background: Despite the approval of mTOR inhibitor everolimus and CDK4/6 inhibitors in the management of hormone-receptor-positive HER2 non-amplified metastatic breast cancer (HR+ HER2-MBC), the optimal sequence of therapy is unclear. There are no clinical data on efficacy of everolimus in HR+ HER2-MBC after cancer progresses on CDK4/6 inhibitors., Objective: The objective of this study is to find the efficacy of everolimus in HR+ HER2-MBC after they progress on a CDK4/6 inhibitor palbociclib., Methods: This is a retrospective, 2-institute review of HR+ HER2-MBC from Jan 2015 to March 2018 treated with everolimus after progression on palbociclib. Primary end point was median progression-free survival (PFS), secondary end points objective response rate (ORR), clinical benefit ratio (CBR), and overall survival (OS)., Results: Out of 41 women with median age 61 years (33, 87) enrolled, 66% had received adjuvant systemic therapy, 61% had visceral disease, and 95% had prior nonsteroidal aromatase inhibitors. About 83% women had 3 or more chemotherapy or hormonal therapies prior to everolimus. Kaplan-Meier estimates showed a median PFS of 4.2 months (95% confidence interval [CI]: 3.2-6.2). The median OS was 18.7 months (95% CI 9.5 to not reached). Objective response rate and CBR were both 17.1%., Conclusion: Everolimus was associated with modest PFS and ORR in HR+ HER2-MBCs postprogression on palbociclib., Competing Interests: Declaration of conflicting interests:The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: E.G.L. has received royalty from UpToDate. A.B. has/had consulting or advisory role for Agendia, Bayer, bioTheranostics, Celgene, Genentech/Roche, Genomic Health, Lilly, NanoString Technologies, Novartis, Pfizer, and Puma Biotechnology. A.P.E. has received honorarium from Pfizer. M.O. has received research fund from Pfizer/NCCN and has/had consulting or advisory role for Novartis and AstraZeneca. A.D. has received honorarium from Daiichi Sankyo. All other authors declare that they have no conflict of interest., (© The Author(s) 2020.)

Testicular cancer is relatively uncommon and accounts for <1% of all male tumors. However, it is the most common solid tumor in men between the ages of 20 and 34 years, and the global incidence has been steadily rising over the past several decades. Several risk factors for testicular cancer have been identified, including personal or family history of testicular cancer and cryptorchidism. Testicular germ cell tumors (GCTs) comprise 95% of malignant tumors arising in the testes and are categorized into 2 main histologic subtypes: seminoma and nonseminoma. Although nonseminoma is the more clinically aggressive tumor subtype, 5-year survival rates exceed 70% with current treatment options, even in patients with advanced or metastatic disease. Radical inguinal orchiectomy is the primary treatment for most patients with testicular GCTs. Postorchiectomy management is dictated by stage, histology, and risk classification; treatment options for nonseminoma include surveillance, systemic therapy, and nerve-sparing retroperitoneal lymph node dissection. Although rarely occurring, prognosis for patients with brain metastases remains poor, with >50% of patients dying within 1 year of diagnosis. This selection from the NCCN Guidelines for Testicular Cancer focuses on recommendations for the management of adult patients with nonseminomatous GCTs.

While all cancer patients face a bewildering array of treatments, side effects, and emotions, several researchers have shown that African American women with breast cancer experience greater stress and burdens because of unmet supportive needs associated with psychological distress, financial distress, and lower physical/functional well-being. Social support has been shown to improve health outcomes for African American breast cancer patients. The purpose of this paper is to understand the meaning of social support among African American women diagnosed with breast cancer. A total of 47 African American women with breast cancer participated in the in-depth qualitative interviews. Key findings indicate that social support was received in the context of the stability of the extended family network. Moreover, social support was received in the context of distributing the social support received among many members in their personal networks and that social support was only received on patient's own terms. The findings of this paper provide an understanding to the inter-relational and cultural meanings of receiving support by diverse cancer patients. In addition, the findings of this paper have implications for health care professionals working with African American breast cancer patients in understanding how social support can be received.

Background: View-sharing (VS) increases spatiotemporal resolution in dynamic contrast-enhanced (DCE) MRI by sharing high-frequency k-space data across temporal phases. This temporal sharing results in respiratory motion within any phase to propagate artifacts across all shared phases. Compressed sensing (CS) eliminates the need for VS by recovering missing k-space data from pseudorandom undersampling, reducing temporal blurring while maintaining spatial resolution., Purpose: To evaluate a CS reconstruction algorithm on undersampled DCE-MRI data for image quality and hepatocellular carcinoma (HCC) detection., Study Type: Retrospective., Subjects: Fifty consecutive patients undergoing MRI for HCC screening (29 males, 21 females, 52-72 years)., Field Strength/sequence: 3.0T MRI. Multiphase 3D-SPGR T 1 -weighted sequence undersampled in arterial phases with a complementary Poisson disc sampling pattern reconstructed with VS and CS algorithms., Assessment: VS and CS reconstructions evaluated by blinded assessments of image quality and anatomic delineation on Likert scales (1-4 and 1-5, respectively), and HCC detection by OPTN/UNOS criteria including a diagnostic confidence score (1-5). Blinded side-by-side reconstruction comparisons for lesion depiction and overall series preference (-3-3)., Statistical Analysis: Two-tailed Wilcoxon signed rank tests for paired nonparametric analyses with Bonferroni-Holm multiple-comparison corrections. McNemar's test for differences in lesion detection frequency and transplantation eligibility., Results: CS compared with VS demonstrated significantly improved contrast (mean 3.6 vs. 2.9, P < 0.0001) and less motion artifact (mean 3.6 vs. 3.2, P = 0.006). CS compared with VS demonstrated significantly improved delineations of liver margin (mean 4.5 vs. 3.8, P = 0.0002), portal veins (mean 4.5 vs. 3.7, P < 0.0001), and hepatic veins (mean 4.6 vs. 3.5, P < 0.0001), but significantly decreased delineation of hepatic arteries (mean 3.2 vs. 3.7, P = 0.004). No significant differences were seen in the other assessments., Data Conclusion: Applying a CS reconstruction to data acquired for a VS reconstruction significantly reduces motion artifacts in a clinical DCE protocol for HCC screening., Level of Evidence: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:984-993., (© 2018 International Society for Magnetic Resonance in Medicine.)

Purpose: The goal of this work is to propose a motion robust reconstruction method for diffusion-weighted MRI that resolves shot-to-shot phase mismatches without using phase estimation., Methods: Assuming that shot-to-shot phase variations are slowly varying, spatial-shot matrices can be formed using a local group of pixels to form columns, in which each column is from a different shot (excitation). A convex model with a locally low-rank constraint on the spatial-shot matrices is proposed. In vivo brain and breast experiments were performed to evaluate the performance of the proposed method., Results: The proposed method shows significant benefits when the motion is severe, such as for breast imaging. Furthermore, the resulting images can be used for reliable phase estimation in the context of phase-estimation-based methods to achieve even higher image quality., Conclusion: We introduced the shot-locally low-rank method, a reconstruction technique for multishot diffusion-weighted MRI without explicit phase estimation. In addition, its motion robustness can be beneficial to neuroimaging and body imaging., (© 2018 International Society for Magnetic Resonance in Medicine.)

Purpose: Outcome data on hormone receptor positive (HR + ), human epidermal growth factor receptor 2 (HER2) nonamplified (HER2 - ) metastatic breast cancer (MBC) treated with palbociclib after treatment with everolimus are lacking. The PALOMA-3 trial, showing benefit of palbociclib plus fulvestrant compared to fulvestrant alone in HR + HER2 - MBC after progression while receiving endocrine therapy excluded women previously treated with everolimus. The objective of this study was to examine outcomes of HR + HER2 - MBC with prior exposure to everolimus while receiving palbociclib-based therapy., Patients and Methods: A retrospective, single-institute review was conducted of HR + HER2 - MBC from January 2014 to November 2016 in patients treated with palbociclib after prior treatment with everolimus. Progression-free survival (PFS) was defined as the time from initiation of palbociclib to the date of progression as determined by the treating physician based on radiologic, biochemical, and/or clinical criteria. Response rates were determined on the basis of available radiologic data. Objective response rate (ORR) was defined as the rate of any complete or partial responses; clinical benefit rate (CBR) was the rate of complete response, partial response, or stable disease for at least 24 weeks., Results: Twenty-three patients with a mean (range) age of 68 (42-81) years were identified. Kaplan-Meier estimate showed median PFS of 2.9 months (95% confidence interval, 2.1-4.2); ORR was 0 of 23 and CBR was 4 (17.4%) of 23. In the PALOMA-3 trial, median PFS, ORR, and CBR of palbociclib cohort were 9.5 months (95% confidence interval, 9.2-11.0), 19%, and 67%, respectively., Conclusion: There is a limited clinical activity of palbociclib combinations after progression with everolimus combination therapy. Further studies are necessary to confirm these findings., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Although the physical and emotional impact of surgical removal of partial or complete removal of the breast as well as effects of breast cancer treatment on the individual have been well documented, little research is available on sexuality and sexual health of breast cancer survivors in a relationship context. Sexual health concerns of breast cancer survivors remain an unmet need for many. The present study consisted of qualitative interviews with 135 racially diverse, female breast cancer survivors who completed treatment to better understand their perspectives on sexual health and management of sexual problems in their potential and existing relationships after breast cancer. Key thematic findings include that breast cancer survivors have to (1) adapt to the physical and emotional traumas of breast cancer surgery and treatment, (2) navigate complicated sexual communications with potential and existing partners, and (3) negotiate intimacy and closeness without sexual intercourse with existing partners. This study demonstrates the need for healthcare providers to discuss sexual health after breast cancer with all of their patients as it is a concern that faces single and partnered breast cancer survivors months and years after treatment.

Objectives: To evaluate the effect of suboptimal dosing on the outcomes of patients who received neoadjuvant chemotherapy (NAC) and robot-assisted radical cystectomy (RARC)., Patients and Methods: We retrospectively reviewed 336 consecutive patients with urothelial carcinoma of the bladder who were treated with NAC and RARC at three academic institutions. Outcomes were compared among three groups: patients who received optimal NAC; patients who received suboptimal NAC; and those who did not receive NAC. To adjust for potential baseline differences between the three groups, propensity-score-based matching was performed. The suboptimal dose group was defined as those who received <3 cycles of cisplatin-based chemotherapy, received a decreased dosage, or those not treated with cisplatin. Primary outcomes analysed were recurrence-free survival (RFS) and overall survival (OS). Secondary outcomes were peri-operative complications and readmissions after RARC., Results: After propensity-score matching, 69 patients in the cohort received optimal-dose NAC, 41 received suboptimal NAC and 69 did not receive NAC. Complication rates and readmission rates did not differ significantly among the three groups. On multivariable analysis, suboptimal NAC and no NAC were independent predictors of worse RFS (hazard ratio [HR] 2.5, 95% confidence interval [CI] 1.2-5.7, P = 0.01 and HR 2.4, 95% CI 1.28-5.16, P = 0.01) and worse OS (HR 4.5, 95% CI 1.6-15.0, P < 0.01 and HR 4.9, 95% CI 1.9-15.6, P < 0.01) in patients who received NAC and RARC. Failure to achieve pathological complete response (ypT0N0) was also an independent predictor of worse RFS (HR 6.6, 95% CI 1.3-20.9; P = 0.02) and OS (HR 4.9, 95% CI 1.8-15.3; P = 0.02)., Conclusion: Optimal NAC resulted in a better RFS and OS when compared with suboptimal or no NAC. Suboptimal and no NAC were associated with worse OS and RFS. These findings will facilitate improved patient counseling and treatment selection., (© 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.)

Purpose: Few studies have examined predictors of quality of life (QOL) of breast cancer survivors over time., Methods: Breast cancer survivors (n=116) were asked to complete measures of QOL, mood, spirituality, and social support every 6 months from 2-4 years post treatment., Results: Overall QOL at 4 years was predicted by previous physical and functional well-being, the breast cancer-specific items, and vigor and current levels of social support (Adj R 2 =.72, F=30.53, p<.001). Physical QOL was predicted by previous levels of physical and functional well- being and current levels of functional and social/family well-being (Adj R 2 =.84, F=44.30, p<.001). Functional well- being was predicted by prior levels of physical, functional, and social/family well-being and current levels of physical well-being and vigor (Adj R 2 =.72, F=3-.53, p<.001). Emotional well-being was predicted by previous levels of emotional well-being and current physical well-being, the breast cancer-specific items, and anxiety (Adj R 2 =.60, F=26.30, p<.001). Social/family well-being was predicted by previous levels of social/family well-being, social support, and confusion (Adj R 2 =.71, F=34.18, p<<000). The breast cancer-specific items were predicted by age, previous levels of the breast cancer-specific items, confusion and current levels of emotional and functional well-being and spirituality (Adj R 2 =.58, F=17.57, p<.001)., Conclusions: Over all and specific dimensions of QOL at 4 years were predicted by different combinations of QOL, mood, and spirituality. Interventions should be tailored to which dimensions of QOL are affected and other types of QOL as well as social support, mood, and spirituality as coping mechanisms that influence the specific dimension of QOL affected.

In recent years, breast cancer rates among young Asian American women have been increasing. Despite increases in breast cancer among young Asian American women, little is known about how this population copes throughout diagnosis, treatment, and survivorship. This study was a qualitative exploration of how young Asian American women cope with breast cancer diagnosis, treatment, and survivorship. In-depth interviews with 22 young (under the age of 50) Asian American women diagnosed with early stage breast cancer were conducted. Through qualitative data analysis, three major themes emerged including moving from managing the emotions of others to expressing emotional vulnerability, moving from work and productivity to work-life balance, and moving beyond the family and reaching out to breast cancer survivors. At diagnosis, participants worked to maintain normalcy including caring for others and working during treatment. Once treatment was over, women worked to find ways to use their experience as a transformative one and also to develop more positive coping skills including expressing emotional vulnerability and reaching out to others. Further studies are needed to create and test culturally tailored supportive interventions that enhance positive coping tools among young Asian American women diagnosed by breast cancer.

Unlabelled: No predictors of a complete pathologic response (pT0) to neoadjuvant chemotherapy (NAC) in muscle-invasive bladder carcinoma have been established. We performed a retrospective analysis of 50 patients to identify potential predictors. Our results showed that the presence of additional transitional cell variants on pathologic examination (mixed tumors) predicted against pT0, suggesting the avoidance of NAC and its morbidity in these patients with mixed tumors., Background: Randomized trials have supported the use of cisplatin-based neoadjuvant chemotherapy (NAC) in muscle-invasive bladder carcinoma (MIBC) owing to the survival advantage, which has correlated with downstaging of the cancer to pT0. Only 30% to 40% of patients receiving NAC have attained a pT0 response at cystectomy; the remaining have either residual disease or progression. We aimed to identify the factors that could predict a pT0 response to NAC., Patients and Methods: Of 336 patients who had undergone robotic cystectomy at our institute from May 2007 to March 2014, we identified 50 patients who had undergone NAC for MIBC. We conducted a retrospective study, dividing these 50 patients into 2 groups, those with and without a pT0. Factors, including age, histologic features, hydronephrosis at initial presentation, and chemotherapy type, were examined by both univariate and multivariate logistic regression analysis., Results: Of the 50 patients, 14 (28%) had pT0 at cystectomy, 20 (40%) had progressive disease, and 16 (32%) had residual disease. The median age was 67.5 years, the median glomerular filtration rate at presentation was 87.5 mL/min, the patients had undergone a median of 3 NAC cycles, and the median time from the end of chemotherapy to surgery was 4 weeks. The odds of a pT0 response for pure urothelial carcinoma (UC) were approximately 11 times greater relative to cancers with transitional cell variant histologic features or mixed tumors (odds ratio 0.09, 95% confidence interval 0.021-0.380; P = .0011), including squamous, glandular differentiation, small cell, micropapillary, sarcomatoid, nested component, lymphoepithelioma-like, and plasmacytoid variants., Conclusion: The presence of pure UC favored a pT0 response to NAC compared with those with variant histologic features or mixed tumors. These potential predictors warrant prospective validation to allow the ideal selection of patients for NAC., (Copyright © 2016 Elsevier Inc. All rights reserved.)

While spirituality and religious practices are important in coping with illness or other crises, there are few ways of assessing support that people receive from members of their spiritual communities. The goal of this study was to validate a new spiritual support subscale for the Medical Outcomes Study Social Support Scale (MOS-SSS). Questions for the subscale were formed based on responses of 135 breast cancer survivors who were interviewed about their cancer experience. Exploratory factor analysis resulted in four specific factors for the MOS-SSS: emotional/informational, tangible, affectionate, and spiritual support. The new spiritual support subscale has adequate reliability and validity and may be useful in assessing an area of support that is not always addressed.

Germ cell tumors (GCTs) account for 95% of testicular cancers. Testicular GCTs constitute the most common solid tumor in men between the ages of 20 and 34 years, and the incidence of testicular GCTs has been increasing in the past 2 decades. Testicular GCTs are classified into 2 broad groups--pure seminoma and nonseminoma--which are treated differently. Pure seminomas, unlike nonseminomas, are more likely to be localized to the testis at presentation. Nonseminoma is the more clinically aggressive tumor associated with elevated serum concentrations of alphafetoprotein (AFP). The diagnosis of a seminoma is restricted to pure seminoma histology and a normal serum concentration of AFP. When both seminoma and elements of a nonseminoma are present, management follows that for a nonseminoma. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Testicular Cancer outline the diagnosis, workup, risk assessment, treatment, and follow-up schedules for patients with both pure seminoma and nonseminoma., (Copyright © 2015 by the National Comprehensive Cancer Network.)

The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for the clinical management of patients with clear cell and non-clear cell renal carcinoma. These NCCN Guidelines Insights highlight the recent updates/changes in these guidelines, and updates include axitinib as first-line treatment option for patients with clear cell renal carcinoma, new data to support pazopanib as subsequent therapy for patients with clear cell carcinoma after first-line treatment with another tyrosine kinase inhibitor, and guidelines for follow-up of patients with renal cell carcinoma., (Copyright © 2015 by the National Comprehensive Cancer Network.)

Few studies have examined the role of religion and spirituality among African American breast cancer patients. This study explored how African American women cope with breast cancer through religious and spiritual practices. Forty-seven African American women who had completed treatment for breast cancer participated in in-depth interviews about their experiences. The majority of the women mentioned using both individual and communal religious and spiritual practices to cope with their breast cancer diagnosis and treatment. The main themes that emerged in terms of the types of religious and spiritual practices included: (1) attendance at religious services, (2) comfort through prayers of others, and (3) encouragement through reading Biblical scriptures. These practices helped women "trust in the Lord" throughout the many challenges of cancer from diagnosis through survivorship. Although this study is exploratory, the findings illustrate how African American women with breast cancer use religious and spiritual practices to cope with their diagnosis and treatment. For clinicians, the findings provides an understanding of spiritual and religious needs in diverse populations and the importance of referring patients onto spiritual and religious resources and support.

Purpose: We evaluated the tolerability and cardiac safety of docetaxel, cyclophosphamide, and trastuzumab (TCyH) for the treatment of early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer and compared to the standard trastuzumab-based chemotherapy regimens doxorubicin with cyclophosphamide followed by paclitaxel and trastuzumab (AC-TH) and docetaxel, carboplatin, and trastuzumab (TCaH)., Methods: We retrospectively reviewed early-stage, resectable, HER2-positive breast cancer patients treated with trastuzumab-based chemotherapy at a single comprehensive cancer center between 2004 and 2011. Patient characteristics, comorbidities, relative dose intensity (RDI) of each regimen, tolerability, and cardiac toxicity were evaluated., Results: One hundred seventy-seven patients were included in the study (AC-TH, n=114; TCaH, n=39; TCyH, n=24). TCyH was solely administered in the adjuvant setting, whereas two-thirds of the AC-TH and TCaH groups were administered postoperatively. Patients treated with TCyH tended to have a more significant underlying cardiac history, higher Charlson comorbidity index, and were of an earlier stage. All patients treated with TCyH received granulocyte colony stimulating factor primary prophylaxis. No febrile neutropenia or grade ≥3 hematologic toxicity was observed in the TCyH group as compared to the AC-TH and TCaH groups. There were no significant differences in the rates of early termination, hospitalization, dose reduction, or RDI between the regimens. The symptomatic congestive heart failure rate between AC-TH, TCaH, and TCyH groups was not significantly different (4.4% vs. 2.6% vs. 8.3%, respectively, p=0.57). There was also no significant difference in the rate of early trastuzumab termination between patients treated with each regimen., Conclusion: TCyH is well tolerated and should be investigated as an alternative adjuvant chemotherapy option for patients who are not candidates for standard trastuzumab-containing regimens. Larger clinical trials are necessary to support the wider use of TCyH as an adjuvant regimen.

Background: Epidermal growth factor receptor overexpression is associated with poor outcomes in urothelial carcinoma (UC). Cetuximab (CTX) exhibited an antitumor effect in in vivo UC models. The efficacy of gemcitabine/cisplatin (GC) with or without CTX in patients with advanced UC was evaluated., Methods: Patients with advanced UC, measurable disease, and adequate organ function were randomized 1:2 to cisplatin (70 mg/m(2) ) on day 1 plus gemcitabine (1000 mg/m(2) ) on days 1, 8, and 15 (arm A) or GC plus CTX (500 mg/m(2) ) on days 1 and 15 (arm B). The primary endpoint was the overall response rate. The secondary endpoints were the response duration, safety, progression-free survival, overall survival, determination of whether or not CTX sensitized nonresponders to GC, and exploratory biomarker analysis. The accrual targets were 27 and 54 patients for the 2 arms, respectively. The overall response rate was reported by arm with binomial confidence intervals (CIs). Kaplan-Meier methods were used for time-to-event endpoints., Results: Eighty-eight eligible patients were randomized; 87 were toxicity-evaluable, and 85 were response-evaluable. The overall response rates were 57.1% for arm A (95% CI = 37%-76%) and 61.4% for arm B (95% CI = 48%-74%). The median progression-free survival times were 8.5 months for arm A (95% CI = 5.7-10.4 months) and 7.6 months for arm B (95% CI = 6.1-8.7 months). The median overall survival times were 17.4 months for arm A (95% CI = 12.8 months to unreached) and 14.3 months for arm B (95% CI = 11.6-22.2 months). The most common grade 3/grade 4 adverse events in both arms were myelosuppression and nausea. Thromboembolism, acneiform rash, fatigue, pain, hypersensitivity reactions, elevated transaminases, hyponatremia, and hypomagnesemia were more common in arm B; 3 grade 5 adverse events occurred in arm B. The presence of primary disease significantly correlated with thromboembolism. An increased soluble E-cadherin level after cycle 2 correlated with a higher risk of death., Conclusions: GC plus CTX was feasible but was associated with more adverse events and no improvements in outcomes., (© 2014 American Cancer Society.)

Many Filipinos have a powerful adherence to Catholicism. However, little is known about spirituality and religious involvement of Filipina Americans who have been diagnosed with breast cancer. Ten (n = 10) in-depth qualitative interviews with Filipina immigrant breast cancer survivors identified prayer to be the most common religious practice, followed by prayers by others and spiritual support from the Catholic Church. These findings can help clinicians and researchers understand the role of spirituality and religion in providing comfort and support for Filipina immigrant breast cancer patient as they face the stress of diagnosis and treatment.

Breast cancer is the most commonly diagnosed form of cancer for women regardless of race/ethnicity. Women of color are diagnosed at later stages and experience greater mortality than their White counterparts. However, there has been comparatively little research on coping with breast among racial/ethnic minorities at time of diagnosis, during treatment, or in the course of survivorship. This is despite the fact that research has repeatedly shown that distress can impact disease progression and survival. The questions asked of this systematic literature review include: (1) What is known about coping with breast cancer among major racial/ethnic groups? (2) What are the strengths and gaps in research to date? Over 120 peer-reviewed published studies (1980-2012) were reviewed. A total of 33 met criteria for inclusion including 15 quantitative, 17 qualitative, and 1 mixed methods study. The majority of studies were small sample cross-sectional studies. Only five studies were longitudinal, and two randomized-controlled intervention trials sought to improve coping among survivors. The most common topic in both quantitative and qualitative studies was spirituality and coping among African American breast cancer patients. Thirteen studies included Latinas only or in combination with other groups. Only one quantitative and one qualitative study solely addressed the Asian American population exploring coping and adjustment. In the course of this systematic literature review, we elucidate what is known about coping with breast cancer among racial/ethnic minority women and identify priorities for future research.

These NCCN Guidelines Insights highlight treatment recommendations and updates specific to the management of patients with advanced non-clear cell carcinoma included in the 2014 version of the NCCN Clinical Practice Guidelines in Oncology for Kidney Cancer.

Objective: To analyze trends in perioperative chemotherapy and optimize use of neoadjuvant chemotherapy for bladder cancer., Methods: From 2005-2012, 284 consecutive patients underwent robot-assisted radical cystectomy at our facility. Patients with disease ≥ T2 and nodal involvement and positive surgical margins were reviewed and considered candidates for referral to medical oncology for chemotherapy. The study was conducted in two phases: phase 1 included 242 consecutive patients between 2005 and 2011, and phase 2 analyzed the effect of changes in 42 patients during a 1-year period (2011-2012)., Results: In phase 1, 148 patients (61%) were candidates for neoadjuvant chemotherapy (NAC). Consultation for NAC was sought for 44 patients (29%), and 104 (71%) did not receive consultation. Of the 44 patients, 36% received NAC, 7% refused, 32% were recommended for immediate cystectomy, and 25% did not receive NAC for other reasons. Phase 2 was more stringent, with a multidisciplinary approach. Significant improvement in referral and NAC use was seen. About 78% vs 30% of patients were seen by medical oncology for consideration of NAC before robot-assisted radical cystectomy and 71% vs 36% received NAC compared with phase 1. The NAC utilization rate improved from 10.8% to 55% over 1 year with a diligent multidisciplinary approach. Medical comorbidities were the main reason for patients not receiving adjuvant chemotherapy (AC; 30% and 33%)., Conclusion: A multidisciplinary approach and coordination of services can help optimize the use of neoadjuvant chemotherapy for bladder cancer., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Pediatric palliative care has recently become a priority in the health care field and is implemented at the time of diagnosis rather than days or weeks before the child's death. Social constructivism theory in which humans generate meaning from their experiences was utilized as a general framework to determine the impact of pediatric palliative care on close relatives. The purpose of this grounded theory study was to generate a substantive theory that explains how close relatives such as grandparents, aunts, and uncles of a child with cancer experience palliative care. The participants of the study included close relatives of children in palliative care. Semistructured interviews and journaling were used to collect data. Initial, focused, and axial coding procedures were used to manage the data and a content analysis of the textual data was performed. Findings from the data suggested a process of finding meaning which helps close relatives to let go of what they cannot control while holding on to what they can control. Social change implications of this study may include improving health care programming for close relatives utilizing supportive-expressive measures. This programming may promote mental health of the close relatives who will learn to deal with their adjustment difficulties and improve their coping skills.

US Oncology Research Trial 9735 reported that TC improved overall survival when compared to doxorubicin and cyclophosphamide in early-stage breast cancer. Despite 61% grades 3-4 neutropenia in the TC arm, only 5% of patients developed febrile neutropenia (FN) without primary prophylactic GCSF (ppGCSF). TC has risen in popularity, particularly in older patients or in those where an anthracycline is contraindicated. Other studies examining the toxicity of TC without ppGCSF reported a higher incidence of FN between 23 and 46%. We reviewed our institutional experience with ppGCSF and the TC regimen. Women treated with adjuvant TC and pegfilgrastim at Roswell Park Cancer Institute were identified from the pharmacy database between 8/2006 and 11/2010. Patient characteristics and comorbidities were abstracted. Endpoints included incidence of FN, hematologic toxicities, relative dose intensity (RDI), and other acute complications. Docetaxel 75 mg/m(2) and cyclophosphamide 600 mg/m(2) were given every 21 day/cycle for a planned four cycles. All patients received pegfilgrastim 6 mg on day 3. One hundred and eleven women with median age of 56 years (27-79) were identified. Twenty-two percent of patients were ≥ 65 at diagnosis. Eight patients developed FN (7%). Ninety-five patients (86%) were able to complete four cycles. Completion rate was significantly lower in patients with age ≥ 65 (71% vs. 90%; P = 0.02). Incidence of hospitalization, delay, RDI <85%, and dose reduction were not significantly different between the age groups. The overall incidence of FN was 7%. Older patients were significantly less likely to complete four cycles of TC as planned. ppGCSF should be strongly considered in breast cancer patients receiving adjuvant TC chemotherapy.

Purpose: NY-ESO-1 cancer testis (CT) antigen is an attractive candidate for immunotherapy as a result of its high immunogenicity. The aim of this study was to explore the potential for NY-ESO-1 antigen directed immunotherapy in triple negative breast cancer (TNBC) by determining the frequency of expression by immunohistochemistry (IHC) and the degree of inherent immunogenicity to NY-ESO-1., Experimental Design: 168 TNBC and 47 ER+/HER2- primary breast cancer specimens were used to determine NY-ESO-1 frequency by IHC. As previous studies have shown that patients with a robust innate humoral immune response to CT antigens are more likely to develop CD8 T-cell responses to NY-ESO-1 peptides, we evaluated the degree to which patients with NY-ESO-1 expression had inherent immunogenicity by measuring antibodies. The relationship between NY-ESO-1 expression and CD8+ T lymphocytes was also examined., Results: The frequency of NY-ESO-1 expression in the TNBC cohort was 16% versus 2% in ER+/HER2- patients. A higher NY-ESO-1 score was associated with a younger age at diagnosis in the TNBC patients with NY-ESO-1 expression (p = 0.026). No differences in OS (p = 0.278) or PFS (p = 0.238) by NY-ESO-1 expression status were detected. Antibody responses to NY-ESO-1 were found in 73% of TNBC patients whose tumors were NY-ESO-1 positive. NY-ESO-1 positive patients had higher CD8 counts than negative patients (p = 0.018)., Conclusion: NY-ESO-1 is expressed in a substantial subset of TNBC patients and leads to a high humoral immune response in a large proportion of these individuals. Given these observations, patients with TNBC may benefit from targeted therapies directed against NY-ESO-1.

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)., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Background: Treatment of arterial bifurcation lesions using drug-eluting stents (DES) is now common clinical practice and yet the mechanisms governing drug distribution in these complex morphologies are incompletely understood. It is still not evident how to efficiently determine the efficacy of local drug delivery and quantify zones of excessive drug that are harbingers of vascular toxicity and thrombosis, and areas of depletion that are associated with tissue overgrowth and luminal re-narrowing., Methods and Results: We constructed two-phase computational models of stent-deployed arterial bifurcations simulating blood flow and drug transport to investigate the factors modulating drug distribution when the main-branch (MB) was treated using a DES. Simulations predicted extensive flow-mediated drug delivery in bifurcated vascular beds where the drug distribution patterns are heterogeneous and sensitive to relative stent position and luminal flow. A single DES in the MB coupled with large retrograde luminal flow on the lateral wall of the side-branch (SB) can provide drug deposition on the SB lumen-wall interface, except when the MB stent is downstream of the SB flow divider. In an even more dramatic fashion, the presence of the SB affects drug distribution in the stented MB. Here fluid mechanic effects play an even greater role than in the SB especially when the DES is across and downstream to the flow divider and in a manner dependent upon the Reynolds number., Conclusions: The flow effects on drug deposition and subsequent uptake from endovascular DES are amplified in bifurcation lesions. When only one branch is stented, a complex interplay occurs - drug deposition in the stented MB is altered by the flow divider imposed by the SB and in the SB by the presence of a DES in the MB. The use of DES in arterial bifurcations requires a complex calculus that balances vascular and stent geometry as well as luminal flow.