Cardiovascular impact of near complete estrogen deprivation in premenopausal women with breast cancer: The CROWN study.

Survival with operable breast cancer has improved markedly in recent decades, however, treatment-related cardiovascular toxicities threaten to offset these gains. Ovarian function suppression paired with aromatase inhibition, for premenopausal women with hormone receptor (HR)-positive breast cancer, is a newer widely adopted therapy with the potential for significant long-term cardiovascular toxicity. Abrupt estrogen deprivation for non-cancer reasons is associated with accelerated coronary artery disease. Women with breast cancer treated with aromatase inhibition in addition to ovarian function suppression experience a dual hit with regards to estrogen exposure. The CaRdiac Outcomes With Near-complete estrogen deprivation (CROWN) study seeks to understand the early, subclinical natural history of cardiovascular compromise in young women undergoing near-complete estrogen deprivation (NCED) therapy. It is critical to understand the early subclinical development of cardiovascular disease to identify a window for therapeutic intervention before overt cardiovascular events occur. This three-site regional study (Atrium Health Wake Forest, Duke, and Virginia Commonwealth University) uses serial stress cardiac magnetic resonance (CMR) imaging and cardiac computed tomography angiography (CCTA) obtained during the initial two years of NCED therapy to study myocardial prefusion reserve (MPR), large cardiovascular vessel changes, left ventricular function, and other cardiovascular parameters. The CROWN cohort will consist of 90 premenopausal women with breast cancer, 67 with HR-positive disease receiving NCED and 23 comparators with HR-negative disease. Participants will undergo three annual CMR scans and 2 CCTA scans during the 2-year study period. After initial activation hurdles, accrual has been brisk, and the study is expected to complete accrual in December 2024. Efforts are in place to encourage participant retention with the study primary outcome, change in MPR between the two groups, to be reported in 2026 to 2027. The results of this study will enable premenopausal women with breast cancer to balance the health burdens of cancer at a young age and treatment-related cardiovascular morbidity. Finally, the tools developed here can be utilized to study cardiovascular risk across a range of cancer types and cancer therapies with the ultimate goals of both developing generalizable risk stratification tools as well as validating interventions which prevent overt cardiovascular compromise.

Real-World Perspectives and Practices for Pneumonitis/Interstitial Lung Disease Associated With Trastuzumab Deruxtecan Use in Human Epidermal Growth Factor Receptor 2-Expressing Metastatic Breast Cancer.

Trastuzumab deruxtecan (T-DXd) is an antibody drug conjugate with a topoisomerase I payload that targets the human epidermal growth factor receptor 2 (HER2). T-DXd is approved for patients with previously treated HER2-positive or HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/ISH-) metastatic/unresectable breast cancer (BC). In a second-line HER2-positive metastatic BC (mBC) population (DESTINY-Breast03 [ClinicalTrials.gov identifier: NCT03529110]), T-DXd demonstrated significantly improved progression-free survival (PFS) over ado-trastuzumab emtansine (12-month rate: 75.8% v 34.1%; hazard ratio, 0.28; P < .001), and in patients with HER2-low mBC treated with one prior line of chemotherapy (DESTINY-Breast04 [ClinicalTrials.gov identifier: NCT03734029]), T-DXd demonstrated significantly longer PFS and overall survival than physician's choice chemotherapy (10.1 v 5.4 months; hazard ratio, 0.51; P < .001, and 23.4 v 16.8 months; hazard ratio, 0.64; P < .001, respectively).Interstitial lung disease (ILD) is an umbrella term used for a group of diseases characterized by lung injury including pneumonitis, which can lead to irreversible lung fibrosis. ILD is a well-described adverse event associated with certain anticancer therapies, including T-DXd. An important part of T-DXd therapy for mBC consists of monitoring for and managing ILD. Although information on ILD management strategies is included in the prescribing information, additional information on patient selection, monitoring, and treatment can be beneficial in routine clinical practice. The objective of this review is to describe real-world, multidisciplinary clinical practices and institutional protocols used for patient selection/screening, monitoring, and management related to T-DXd-associated ILD.

Evaluation of alpelisib-induced hyperglycemia prophylaxis and associated risk factors in PIK3CA-mutated hormone-receptor positive, human epidermal growth factor-2 negative advanced breast cancer.

PURPOSE: SOLAR-1 investigated alpelisib-fulvestrant (ALP + FLV) in patients with HR + /HER2-, PIK3CA-mutated advanced breast cancer and demonstrated a clinically significant increase in all-grade and grade (G) 3-4 hyperglycemia (HG) compared to placebo-fulvestrant. Given high rates of HG, a preventative protocol and identification of associated risk factors was implemented. METHODS: This single-center, retrospective study included patients receiving ALP + FLV. One week before ALP initiation, patients started an insulin-sensitizer. Patients had fasting plasma glucose (FPG) levels drawn day 8, 15, 28, then monthly. Primary outcome was incidence of G2-4 HG by day 28. Risk factors assessed included age, BMI, FPG, and HbA1c. Number of risk factors were compared between patients with and without HG. RESULTS: Sixteen women were included with median age of 59 years. The cohort was 69% White, 25% Black, 75% with BMI ≥ 25 kg/m2, and 50% with history of diabetes. By day 28, 9 patients (56%) had G2-4 HG, with only 3 (19%) G3 and zero G4. Patients with G2-4 HG had a median of 2 risk factors compared to only 1 if no HG (p = 0.03). 5 patients (31%) required a temporary hold of ALP and 3 (19%) required dose reduction due to HG. 13 patients permanently discontinued ALP-9 due to disease progression and 4 from an adverse event (only 1 HG). CONCLUSION: Implementation of a HG prophylaxis protocol with ALP in a single-center study demonstrated fewer G3-4 HG events compared to that seen in SOLAR-1 (19% vs 36.6%). An increase in HG-associated risk factors correlated with a higher incidence of G2-4 HG.

NCCN Guidelines® Insights: Hematopoietic Growth Factors, Version 1.2022.

The NCCN Guidelines for Hematopoietic Growth Factors provide recommendations for the appropriate use of growth factors in the clinical management of febrile neutropenia (FN), chemotherapy-induced thrombocytopenia (CIT), and chemotherapy-induced anemia (CIA). Management and prevention of these sequelae are an integral part of supportive care for many patients undergoing cancer treatment. The purpose of these guidelines is to operationalize the evaluation, prevention, and treatment of FN, CIT, and CIA in adult patients with nonmyeloid malignancies and to enable the patient and clinician to assess management options for FN, CIT, and CIA in the context of an individual patient's condition. These NCCN Guidelines Insights provide a summary of the important recent updates to the NCCN Guidelines for Hematopoietic Growth Factors, with particular emphasis on the incorporation of a newly developed section on CIT.

Association of treatment-emergent symptoms identified by patient-reported outcomes with adjuvant endocrine therapy discontinuation.

Many patients discontinue endocrine therapy for breast cancer due to intolerance. Identification of patients at risk for discontinuation is challenging. The minimal important difference (MID) is the smallest change in a score on a patient-reported outcome (PRO) that is clinically significant. We evaluated the association between treatment-emergent symptoms detected by worsening PRO scores in units equal to the MID with discontinuation. We enrolled females with stage 0-III breast cancer initiating endocrine therapy in a prospective cohort. Participants completed PROs at baseline, 3, 6, 12, 24, 36, 48, and 60 months. Measures included PROMIS pain interference, fatigue, depression, anxiety, physical function, and sleep disturbance; Endocrine Subscale of the FACT-ES; and MOS-Sexual Problems (MOS-SP). We evaluated associations between continuous PRO scores in units corresponding to MIDs (PROMIS: 4-points; FACT-ES: 5-points; MOS-SP: 8-points) with time to endocrine therapy discontinuation using Cox proportional hazards models. Among 321 participants, 140 (43.6%) initiated tamoxifen and 181 (56.4%) initiated aromatase inhibitor (AI). The cumulative probability of discontinuation was 23% (95% CI 18-27%) at 48 months. For every 5- and 4-point worsening in endocrine symptoms and sleep disturbance respectively, participants were 13 and 14% more likely to discontinue endocrine therapy respectively (endocrine symptoms HR 1.13, 95% CI 1.02-1.25, p = 0.02; sleep disturbance HR 1.14, 95% CI 1.01-1.29, p = 0.03). AI treatment was associated with greater likelihood of discontinuation than tamoxifen. Treatment-emergent endocrine symptoms and sleep disturbance are associated with endocrine therapy discontinuation. Monitoring for worsening scores meeting or exceeding the MID on PROs may identify patients at risk for discontinuation.

Couple Communication in Cancer: Protocol for a Multi-Method Examination.

Cancer and its treatment pose challenges that affect not only patients but also their significant others, including intimate partners. Accumulating evidence suggests that couples' ability to communicate effectively plays a major role in the psychological adjustment of both individuals and the quality of their relationship. Two key conceptual models have been proposed to account for how couple communication impacts psychological and relationship adjustment: the social-cognitive processing (SCP) model and the relationship intimacy (RI) model. These models posit different mechanisms and outcomes, and thus have different implications for intervention. The purpose of this project is to test and compare the utility of these models using comprehensive and methodologically rigorous methods. Aims are: (1) to examine the overall fit of the SCP and RI models in explaining patient and partner psychological and relationship adjustment as they occur on a day-to-day basis and over the course of 1 year; (2) to examine the fit of the models for different subgroups (males vs. females, and patients vs. partners); and (3) to examine the utility of various methods of assessing communication by examining the degree to which baseline indices from different measurement strategies predict self-reported adjustment at 1-year follow up. The study employs a longitudinal, multi-method approach to examining communication processes including: standard self-report questionnaires assessing process and outcome variables collected quarterly over the course of 1 year; smartphone-based ecological momentary assessments to sample participant reports in real time; and laboratory-based couple conversations from which we derive observational measures of communicative behavior and affective expression, as well as vocal indices of emotional arousal. Participants are patients with stage II-IV breast, colon, rectal, or lung cancer and their spouses/partners, recruited from two NCI-designated comprehensive cancer centers. Results will be published in scientific journals, presented at scientific conferences, and conveyed to a larger audience through infographics and social media outlets. Findings will inform theory, measurement, and the design and implementation of efficacious interventions aimed at optimizing both patient and partner well-being.

Yoga Practice Predicts Improvements in Day-to-Day Pain in Women With Metastatic Breast Cancer.

CONTEXT: Women with metastatic breast cancer (MBC) experience a significant symptom burden, including cancer pain. Yoga is a mind-body discipline that has shown promise for alleviating cancer pain, but few studies have included patients with metastatic disease or examined the acute effects of yoga practice. OBJECTIVES: To determine whether daily pain changed significantly during a randomized controlled trial of the Mindful Yoga program among women with MBC and whether time spent in yoga practice was related to daily pain. METHODS: On alternate weeks during the intervention period, we collected daily measures of pain from a subset of 48 women randomized to either yoga (n = 30) or a support group condition (n = 18). We also assessed daily duration of yoga practice among patients randomized to yoga. RESULTS: Pain levels were low for women in both conditions, and no differential treatment effects were found on daily pain. However, among women randomized to yoga, a dose/response relationship was found between yoga practice duration and daily pain. When patients had spent relatively more time practicing yoga across two consecutive days, they were more likely to experience lower pain on the next day. This finding is consistent with an earlier MBC study. Meditation practice showed the strongest association with lower daily pain. CONCLUSION: Findings suggest that yoga practice (meditation practice in particular) is associated with acute improvements in cancer pain, and that yoga interventions may be more impactful if tested in a sample of patients with advanced cancer in which pain is relatively elevated.

Evaluating a couple-based intervention addressing sexual concerns for breast cancer survivors: study protocol for a randomized controlled trial.

BACKGROUND: Sexual concerns are distressing for breast cancer survivors and interfere with their intimate relationships. This study evaluates the efficacy of a four-session couple-based intervention delivered via telephone, called Intimacy Enhancement (IE). The IE intervention is grounded in social cognitive theory and integrates evidence-based techniques from cognitive behavioral couple therapy and sex therapy to address survivors' sexual concerns and enhance their and their partners' sexual, relationship, and psychological outcomes. METHODS: This trial is designed to evaluate the efficacy of the IE intervention in improving survivors' sexual function, the primary study outcome. Secondary outcomes include survivors' sexual distress, partners' sexual function, and survivors' and partners' relationship intimacy and quality as well as psychological distress (depressive symptoms and anxiety symptoms). Additional aims are to examine whether treatment effects on patient sexual function are mediated by sexual communication and self-efficacy for coping with sexual concerns and to explore whether survivor age and race/ethnicity moderate intervention effects on survivors' sexual function. Eligible adult female breast cancer survivors reporting sexual concerns and their intimate partners are recruited from two academic sites in the USA and are randomized to either the IE intervention or to a control condition of equal length offering education and support around breast cancer-related health topics (Living Healthy Together). The target sample size is 120 couples. Self-report outcome measures are administered to participants in both conditions at baseline (T1), post-treatment (T2), 3 months post-treatment (T3), and 6 months post-treatment (T4). DISCUSSION: Evidence-based interventions are needed to address sexual concerns for breast cancer survivors and to enhance their and their intimate partners' sexual, relationship, and psychological well-being. This randomized controlled trial will allow us to examine the efficacy of a novel couple-based intervention delivered via telephone for breast cancer survivors experiencing sexual concerns and their intimate partners, in comparison with an attention control. Findings of this study could influence clinical care for women with breast cancer and inform theory guiding cancer-related sexual rehabilitation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03930797. Registered on 24 April 2019.

NCCN Guidelines Insights: Hematopoietic Growth Factors, Version 1.2020.

Management of febrile neutropenia (FN) is an integral part of supportive care for patients undergoing cancer treatment. The NCCN Guidelines for Hematopoietic Growth Factors provide suggestions for appropriate evaluation, risk determination, prophylaxis, and management of FN. These NCCN Guidelines are intended to guide clinicians in the appropriate use of growth factors for select patients undergoing treatment of nonmyeloid malignancies. These NCCN Guidelines Insights highlight important updates to the NCCN Guidelines regarding the incorporation of newly FDA-approved granulocyte-colony stimulating factor biosimilars for the prevention and treatment of FN.

Four Conversations: A Randomized Controlled Trial of an Online, Personalized Coping and Decision Aid for Metastatic Breast Cancer Patients.

Background: Anticipating and making health care decisions about appropriate or preferred treatment around end-of-life care are intellectually challenging and emotionally distressing for metastatic breast cancer (MBC) patients, new interventions are needed. Objective: This study examined the effect of Four Conversations, an online and personalized coping and decision aid curriculum, on the completion of advance care directives and shared decision making among patients and their loved ones, clinicians, and spirit. Design: Participants were randomized 1:1 to Four Conversations or wait-listed usual care conditions. Setting: Adult breast cancer survivors with metastatic disease were recruited nationally. Measurements: Electronic surveys collected self-reported demographic, clinical, and outcome data at baseline and four weeks postintervention. Results: Participants (N = 252) were mean age 53.6 ± 11.0 years; 100% female; 88% Caucasian; 67% married; and 33% employed. Over half (54%) of treatment arm participants without an advance directive completed one by study end, most (62%) felt that Four Conversations helped them quite a bit or a great deal in making a better decision, and 90% would recommend to others. Difference in the change in decisional conflict scores for treatment and control conditions was not significant (p = 0.07). Conclusions: These results suggest that Four Conversations facilitated the completion of advance care directives. Given that reductions in decisional conflict scores between the treatment and control arms were not significant, we cannot conclude that program use was associated with improved decisional conflict among MBC survivors. Online programs can be a feasible and effective alternative to in-person support.

Perspectives on Inflammatory Breast Cancer (IBC) Research, Clinical Management and Community Engagement from the Duke IBC Consortium.

Inflammatory breast cancer (IBC) is an understudied and aggressive form of breast cancer with a poor prognosis, accounting for 2-6% of new breast cancer diagnoses but 10% of all breast cancer-related deaths in the United States. Currently there are no therapeutic regimens developed specifically for IBC, and it is critical to recognize that all aspects of treating IBC - including staging, diagnosis, and therapy - are vastly different than other breast cancers. In December 2014, under the umbrella of an interdisciplinary initiative supported by the Duke School of Medicine, researchers, clinicians, research administrators, and patient advocates formed the Duke Consortium for IBC to address the needs of patients in North Carolina (an ethnically and economically diverse state with 100 counties) and across the Southeastern United States. The primary goal of this group is to translate research into action and improve both awareness and patient care through collaborations with local, national and international IBC programs. The consortium held its inaugural meeting on Feb 28, 2018, which also marked Rare Disease Day and convened national research experts, clinicians, patients, advocates, government representatives, foundation leaders, staff, and trainees. The meeting focused on new developments and challenges in the clinical management of IBC, research challenges and opportunities, and an interactive session to garner input from patients, advocates, and community partners that would inform a strategic plan toward continuing improvements in IBC patient care, research, and education.

The impact of chemotherapy sequence on survival in node-positive invasive lobular carcinoma.

BACKGROUND AND OBJECTIVES: We sought to evaluate the impact of chemotherapy sequence on survival by comparing node-positive invasive lobular carcinoma (ILC) patients who received neoadjuvant (NACT) and adjuvant (ACT) chemotherapy. METHODS: cT1-4c, cN1-3 ILC patients in the National Cancer Data Base (2004-2013) who underwent surgery and chemotherapy were divided into NACT and ACT cohorts. Kaplan-Meier curves and Cox proportional hazards modeling were used to estimate unadjusted and adjusted overall survival (OS), respectively. RESULTS: Five thousand five hundred fifty-one (35.6%) of 15 573 ILC patients treated with chemotherapy received NACT. NACT patients had similar rates of pT3/4 disease (26.6% vs 26.2%), nodal involvement (median 3 vs 4), and number of lymph nodes examined (median 13 vs 14) but higher rates of mastectomy (81.8% vs 74.5%, P < 0.001) vs ACT patients. 3.4% of NACT patients experienced pathologic complete response (pCR). Unadjusted 10-year OS was worse for NACT vs ACT patients (65.1% vs 54.4%, log-rank P < 0.001). After adjustment for known covariates, NACT continued to be associated with worse OS (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.25-1.52). CONCLUSIONS: In node-positive ILC, NACT yielded low rates of pCR, was not associated with lower rates of mastectomy or less extensive axillary surgery, and was associated with worse survival vs ACT, suggesting limited benefit for these patients.

Partner status moderates the relationships between sexual problems and self-efficacy for managing sexual problems and psychosocial quality-of-life for postmenopausal breast cancer survivors taking adjuvant endocrine therapy.

OBJECTIVE: Past studies indicate that >90% of breast cancer survivors taking adjuvant endocrine therapy (AET) experience menopausal symptoms including sexual problems (eg, vaginal dryness, dyspareunia); however, research examining the impact of these problems on quality-of-life is limited. This cross-sectional study examined (1) the impact of sexual problems and self-efficacy for coping with sexual problems (sexual self-efficacy) on quality-of-life (ie, psychosocial quality-of-life and sexual satisfaction), and (2) partner status as a moderator of these relationships. METHODS: Postmenopausal breast cancer survivors taking AET completed measures of sexual problems (Menopause-Specific Quality-of-Life [MENQOL] sexual subscale], sexual self-efficacy, psychosocial quality-of-life (MENQOL psychosocial subscale), and sexual satisfaction (Functional Assessment of Cancer Therapy-General item). RESULTS: Bivariate analyses showed that women reporting greater sexual problems and lower sexual self-efficacy had poorer quality-of-life and less sexual satisfaction (all P-values < 0.05). Partner status moderated the relationship between sexual problems and psychosocial quality-of-life (P = 0.02); at high levels of sexual problems, unpartnered women experienced poorer psychosocial quality-of-life than partnered women. Partner status also moderated the relationship between self-efficacy and psychosocial quality-of-life (P = 0.01). Self-efficacy was unrelated to psychosocial quality-of-life for partnered women; for unpartnered women, low self-efficacy was associated with poorer quality-of-life. Partner status did not moderate the relationships between sexual problems or self-efficacy with sexual satisfaction. CONCLUSIONS: Greater sexual problems and lower sexual self-efficacy were associated with poorer psychosocial quality-of-life and sexual satisfaction among postmenopausal breast cancer survivors taking AET. Interventions to address sexual problems and sexual self-efficacy, particularly among unpartnered women, may be beneficial for improving the well-being of postmenopausal breast cancer survivors on AET.

Feasibility of a mindful yoga program for women with metastatic breast cancer: results of a randomized pilot study.

PURPOSE: Patients with metastatic breast cancer (MBC) experience high levels of symptoms. Yoga interventions have shown promise for improving cancer symptoms but have rarely been tested in patients with advanced disease. This study examined the acceptability of a comprehensive yoga program for MBC and the feasibility of conducting a randomized trial testing the intervention. METHODS: Sixty-three women with MBC were randomized with a 2:1 allocation to yoga or a support group comparison condition. Both interventions involved eight weekly group sessions. Feasibility was quantified using rates of accrual, attrition, and session attendance. Acceptability was assessed with a standardized self-report measure. Pain, fatigue, sleep quality, psychological distress, mindfulness, and functional capacity were assessed at baseline, post-intervention, and 3 and 6 months post-intervention. RESULTS: We met goals for accrual and retention, with 50% of eligible patients enrolled and 87% of randomized participants completing post-intervention surveys. Sixty-five percent of women in the yoga condition and 90% in the support group attended ≥ 4 sessions. Eighty percent of participants in the yoga condition and 65% in the support group indicated that they were highly satisfied with the intervention. Following treatment, women in the yoga intervention had modest improvements in some outcomes; however, overall symptom levels were low for women in both conditions. CONCLUSIONS: Findings suggest that the yoga intervention content was highly acceptable to patients with MBC, but that there are challenges to implementing an intervention involving eight group-based in-person sessions. Alternative modes of delivery may be necessary to reach patients most in need of intervention.

Links Between Communication and Relationship Satisfaction Among Patients With Cancer and Their Spouses: Results of a Fourteen-Day Smartphone-Based Ecological Momentary Assessment Study.

Cancer treatment poses significant challenges not just for those diagnosed with the disease but also for their intimate partners. Evidence suggests that couples' communication plays a major role in the adjustment of both individuals and in the quality of their relationship. Most descriptive studies linking communication to adjustment have relied on traditional questionnaire methodologies and cross-sectional designs, limiting external validity and discernment of temporal patterns. Using the systemic-transactional model of dyadic coping as a framework, we examined intra- and inter-personal associations between communication (both enacted and perceived) and relationship satisfaction (RS) among patients with stage II-IV breast or colorectal cancer and their spouses (N = 107 couples). Participants (mean age = 51, 64.5% female patients, and 37.4% female spouses) independently completed twice-daily ecological momentary assessments (EMA) via smartphone for 14 consecutive days. Items assessed RS and communication (expression of feelings, holding back from expression, support and criticism of partner, and parallel ratings of partner behavior). Linear mixed models employing an Actor Partner Interdependence Model were used to examine concurrent, time-lagged, and cross-lagged associations between communication and RS. Expressing one's feelings was unassociated with RS. Holding back from doing so, in contrast, was associated with lower RS for both patients and spouses in concurrent models. These effects were both intrapersonal and interpersonal, meaning that when individuals held back from expressing their feelings, they reported lower RS and so too did their partner. Giving and receiving support were associated with one's own higher RS for both patients and spouses in concurrent models, and for patients in lagged models. Conversely, criticizing one's partner and feeling criticized were maladaptive, associated with lower RS (own and in some cases, partner's). Cross-lagged analyses (evening RS to next-day afternoon communication) yielded virtually no effects, suggesting that communication may have a stronger influence on short-term RS than the reverse. Findings underscore the importance of responsive communication, more so than expression per se, in explaining both concurrent and later relationship adjustment. In addition, a focus on holding back from expressing feelings may enhance the understanding of RS for couples coping with cancer.

Early Stage HER2-Positive Breast Cancers Not Achieving a pCR From Neoadjuvant Trastuzumab- or Pertuzumab-Based Regimens Have an Immunosuppressive Phenotype.

BACKGROUND: Stromal tumor-infiltrating lymphocytes (TILs) might predict pathologic complete response (pCR) in patients with HER2-positive (HER2+) breast cancer treated with trastuzumab (H). Docetaxel (T), carboplatin (C), H, and pertuzumab (P) have immune-modulating effects. Pre- and post-treatment immune biomarkers in cancers treated with neoadjuvant TCH with or without P are lacking. In this study we quantified baseline and changes in TILs, cluster of differentiation (CD) 4+, CD8+, FoxP3+, and PD-L1+ cells using immunohistochemistry (IHC) and quantified productive T-cell receptor ß (TCRß) rearrangements and TCRß clonality using next-generation sequencing (NGS) in 30 HER2+ breast cancer tissues treated with neoadjuvant H with or without P regimens. MATERIALS AND METHODS: Thirty pre- and post-neoadjuvant TCH (n = 4) or TCHP (n = 26) breast cancer tissues were identified. TILs were quantified manually using hematoxylin and eosin. CD4, CD8, FoxP3, and PD-L1 were stained using IHC. TCRß was evaluated using NGS. Immune infiltrates were compared between pCR and non-pCR groups using the Wilcoxon rank sum test. RESULTS: A pCR occurred in 15 (n = 15; 50%) cancers (TCH n = 2; TCHP, n = 13). Pretreatment TILs, CD4+, CD8+, FoxP3+, and PD-L1+ cells were not associated with response (P = .42, P = .55, P = .19, P = .66, P = .87, respectively. Pretreatment productive TCRß and TCRß clonality did not predict response, P = .84 and P = .40, respectively). However, post-treatment CD4+ and FoxP3+ cells (T-regulatory cells) were elevated in the non-pCR cohort (P = .042 and P = .082, respectively). CONCLUSION: An increase in regulatory T cells in non-pCR tissues suggests the development of an immunosuppressive phenotype. Further investigation in a larger cohort of samples is warranted to validate these findings.

Optimizing delivery of a behavioral pain intervention in cancer patients using a sequential multiple assignment randomized trial SMART.

BACKGROUND/AIMS: Pain is common in cancer patients and results in lower quality of life, depression, poor physical functioning, financial difficulty, and decreased survival time. Behavioral pain interventions are effective and nonpharmacologic. Traditional randomized controlled trials (RCT) test interventions of fixed time and dose, which poorly represent successive treatment decisions in clinical practice. We utilize a novel approach to conduct a RCT, the sequential multiple assignment randomized trial (SMART) design, to provide comparative evidence of: 1) response to differing initial doses of a pain coping skills training (PCST) intervention and 2) intervention dose sequences adjusted based on patient response. We also examine: 3) participant characteristics moderating intervention responses and 4) cost-effectiveness and practicality. METHODS/DESIGN: Breast cancer patients (N=327) having pain (ratings≥5) are recruited and randomly assigned to: 1) PCST-Full or 2) PCST-Brief. PCST-Full consists of 5 PCST sessions. PCST-Brief consists of one 60-min PCST session. Five weeks post-randomization, participants re-rate their pain and are re-randomized, based on intervention response, to receive additional PCST sessions, maintenance calls, or no further intervention. Participants complete measures of pain intensity, interference and catastrophizing. CONCLUSIONS: Novel RCT designs may provide information that can be used to optimize behavioral pain interventions to be adaptive, better meet patients' needs, reduce barriers, and match with clinical practice. This is one of the first trials to use a novel design to evaluate symptom management in cancer patients and in chronic illness; if successful, it could serve as a model for future work with a wide range of chronic illnesses.

A Small Randomized Controlled Pilot Trial Comparing Mobile and Traditional Pain Coping Skills Training Protocols for Cancer Patients with Pain.

Psychosocial pain management interventions are efficacious for cancer pain but are underutilized. Recent advances in mobile health (mHealth) technologies provide new opportunities to decrease barriers to access psychosocial pain management interventions. The objective of this study was to gain information about the accessibility and efficacy of mobile pain coping skills training (mPCST) intervention delivered to cancer patients with pain compared to traditional in-person pain coping skills training intervention. This study randomly assigned participants (N = 30) to receive either mobile health pain coping skills training intervention delivered via Skype or traditional pain coping skills training delivered face-to-face (PCST-trad). This pilot trial suggests that mPCST is feasible, presents low burden to patients, may lead to high patient engagement, and appears to be acceptable to patients. Cancer patients with pain in the mPCST group reported decreases in pain severity and physical symptoms as well as increases in self-efficacy for pain management that were comparable to changes in the PCST-trad group (p's < 0.05). These findings suggest that mPCST, which is a highly accessible intervention, may provide benefits similar to an in-person intervention and shows promise for being feasible, acceptable, and engaging to cancer patients with pain.

Pharmacogenomics of breast cancer therapy: an update.

Clinical and histopathologic characteristics of breast cancer have long played an important role in treatment decision-making. Well-recognized prognostic factors include tumor size, node status, presence or absence of metastases, tumor grade, and hormone receptor expression. High tumor grade, presence of hormone receptors, and HER2-positivity are a few predictive markers of response to chemotherapy, endocrine manipulations, and anti-HER2 agents, respectively. However, there is much heterogeneity of outcomes in patients with similar clinical and pathologic features despite equivalent treatment regimens. Some of the differences in response to specific therapies can be attributed to somatic tumor characteristics, such as degree of estrogen receptor expression and HER2 status. In recent years, there has been great interest in evaluating the role that pharmacogenetics/pharmacogenomics, or variations in germline DNA, play in alteration of drug metabolism and activity, thus leading to disparate outcomes among patients with similar tumor characteristics. The utility of these variations in treatment decision-making remains debated. Here we review the data available to date on genomic variants that may influence response to drugs commonly used to treat breast cancer. While none of the variants reported to date have demonstrated clinical utility, ongoing prospective studies and increasing understanding of pharmacogenetics will allow us to better predict risk of toxicity or likelihood of response to specific treatments and to provide a more personalized therapy.