Disparities in Breast Cancer Screening Rates Among Adults With and Without Intellectual and Developmental Disabilities.

BACKGROUND: Individuals with intellectual and developmental disabilities may face barriers in accessing healthcare, including cancer screening and detection services. We sought to assess the association of intellectual and developmental disabilities (IDD) with breast cancer screening rates. METHODS: Data from 2018 to 2020 was used to identify screening-eligible individuals from Medicare Standard Analytic Files. Adults aged 65-79 years who did not have a previous diagnosis of breast cancer were included. Multivariable regression was used to analyze the differences in breast cancer screening rates among individuals with and without IDD. RESULTS: Among 9,383,349 Medicare beneficiaries, 11,265 (0.1%) individuals met the criteria for IDD. Of note, individuals with IDD were more likely to be non-Hispanic White (90.5% vs. 87.3%), have a Charlson Comorbidity Index score ≤ 2 (66.2% vs. 85.5%), and reside in a low social vulnerability index neighborhood (35.7% vs. 34.4%). IDD was associated with reduced odds of undergoing breast cancer screening (odds ratio (OR) 0.77, 95% confidence interval (CI) 0.74-0.80; p < 0.001). Breast cancer screening rates in individuals with IDD were further influenced by social vulnerability and belonging to a racial/ethnic minority. CONCLUSIONS: Individuals with IDD may face additional barriers to breast cancer screening. The combination of IDD and social vulnerability placed patients at particularly high risk of not being screened for breast cancer.

Patient-driven decisions and perceptions of the 'safest possible choice': insights from patient-provider conversations about how some breast cancer patients choose contralateral prophylactic mastectomy.

OBJECTIVE: Observe patient-clinician communication to gain insight about the reasons underlying the choice of patients with unilateral breast cancer to undergo contralateral prophylactic mastectomy (CPM), despite lack of survival benefit, risk of harms, and cautions expressed by surgical guidelines and clinicians. METHODS & MEASURES: WORDS is a prospective study that explored patient-clinician communication and patient decision making. Participants recorded clinical visits through a downloadable mobile application. We analyzed 44 recordings from 22 patients: 9 who chose CPM, 8 who considered CPM but decided against it, and 5 who never considered CPM. We used abductive analysis combined with constructivist grounded theory methods. RESULTS: Decisions to undergo CPM are patient-driven and motivated by perceptions that CPM is the most aggressive, and therefore safest, treatment option available. These decisions are shaped not primarily by the content of conversations with clinicians, but by the history of cancer in patients' families, their own first-hand experiences with cancers among loved ones, fear for their children, and anxiety about cancer recurrence. CONCLUSION: The perception that CPM is the safest, most aggressive option strongly influences patients, despite scientific evidence to the contrary. Future efforts to address high CPM rates should focus on patient-driven decision making and cancer-related fears.

Genetic counseling and testing for females at elevated risk for breast cancer: Protocol for the randomized controlled trial of the Know Your Risk intervention.

BACKGROUND: Genetic counseling and testing have an important role in the care of patients at elevated risk for breast cancer. However, conventional pre- and post-test genetic counseling is labor and time intensive, less accessible for patients living outside major urban centers, and impractical on a large scale. A patient-driven approach to genetic counseling and testing may increase access, improve patients' experiences, affect efficiency of clinical practice, and help meet workforce demand. The objective of this 2-arm randomized controlled trial is to determine the efficacy of Know Your Risk (KYR), a genetic counseling patient preference intervention. METHODS: Females (n = 1000) at elevated risk (>20% lifetime) for breast cancer will be randomized to the KYR intervention or conventional genetic counseling. The study will provide comprehensive assessment of breast cancer risk by multigene panel testing and validated polygenic risk score. Primary outcome is adherence to National Comprehensive Cancer Network guidelines for a clinical encounter every 6-12 months and an annual mammogram (breast MRI if recommended) determined by medical record review. Secondary outcomes include adherence to other recommended cancer screening tests determined by medical record review and changes in breast cancer knowledge, perception of risk, post-test/counseling distress, and satisfaction with counseling by completion of three surveys during the study. Study aims will be evaluated for non-inferiority of the KYR intervention compared to conventional genetic counseling. CONCLUSION: If efficacious, the KYR intervention has the potential to improve patients' experience and may change how genetic counseling is delivered, inform best practices, and reduce workforce burden. TRIAL REGISTRATION: ClinicalTrials.govNCT05325151.

Depression, Inflammation, and Intestinal Permeability: Associations with Subjective and Objective Cognitive Functioning throughout Breast Cancer Survivorship.

About one-in-three breast cancer survivors have lingering cognitive complaints and objective cognitive impairment. Chronic inflammation and intestinal permeability (i.e., leaky gut), two risk factors for cognitive decline, can also fuel depression-another vulnerability for cognitive decline. The current study tested whether depression accompanied by high levels of inflammation or intestinal permeability predicted lower subjective and objective cognitive function in breast cancer survivors. We combined data from four breast cancer survivor studies (n = 613); some had repeated measurements for a total of 1015 study visits. All participants had a blood draw to obtain baseline measures of lipopolysaccharide binding protein-a measure of intestinal permeability, as well as three inflammatory markers that were incorporated into an inflammatory index: C-reactive protein, interleukin-6, and tumor necrosis factor-α. They reported depressive symptoms on the Center for Epidemiological Studies depression scale (CES-D), and a binary variable indicated clinically significant depressive symptoms (CES-D ≥ 16). The Kohli (749 observations) and the Breast Cancer Prevention Trial (591 observations) scales assessed subjective cognitive function. Objective cognitive function tests included the trail-making test, Hopkins verbal learning test, Conners continuous performance test, n-back test, FAS test, and animal-naming test (239-246 observations). Adjusting for education, age, BMI, cancer treatment type, time since treatment, study visit, and fatigue, women who had clinically elevated depressive symptoms accompanied by heightened inflammation or intestinal permeability reported poorer focus and marginally poorer memory. However, poorer performance across objective cognitive measures was not specific to inflammation-associated depression. Rather, there was some evidence of lower verbal fluency; poorer attention, verbal learning and memory, and working memory; and difficulties with visuospatial search among depressed survivors, regardless of inflammation. By themselves, inflammation and intestinal permeability less consistently predicted subjective or objective cognitive function. Breast cancer survivors with clinically significant depressive symptoms accompanied by either elevated inflammation or intestinal permeability may perceive greater cognitive difficulty, even though depression-related objective cognitive deficits may not be specific to inflammation- or leaky-gut-associated depression.

A troubled heart: Mood disorder history longitudinally predicts faster cardiopulmonary aging in breast cancer survivorship.

OBJECTIVE: Breast cancer survivors live longer due to more advanced cancer treatments; however, cardiovascular disease (CVD) is the leading non-cancer cause of death in breast cancer survivors. Previous studies have shown that depression is associated with an increased risk of CVD development. This study investigated whether depressive symptoms or mood disorder history, either independently or in combination with cardiotoxic treatments, predicted older cardiopulmonary age using a novel index-the Age Based on Exercise Stress Test (ABEST)-among breast cancer survivors. METHODS: Breast cancer survivors (N = 80, ages 26-72, stage I-IIIA) were assessed an average of 53 days (SD = 26) post-surgery, but before adjuvant treatment, and again an average of 32 (SD = 6) months thereafter. At both visits, they reported depressive symptoms on the Center for Epidemiologic Studies Depression Scale (CES-D), completed the Structured Clinical Interview for DSM-V, and engaged in an exercise stress test to obtain ABEST scores. RESULTS: Controlling for treatment type, age, education, trunk fat, antidepressant use, and time between visits, longitudinal analyses showed that breast cancer survivors with a mood disorder history had worsening ABEST scores over time, compared to their peers without this history (p = .046). Change in physical activity between Visits 1 and 2 did not mediate this relationship (95% CI: -0.16-0.51). Ancillary analyses provided some additional support for the primary finding, such that those with a mood disorder history trended toward greater decreases in Vo2max, although results were marginally non-significant (p = .095). There were no cross-sectional relationships between depressive symptoms or mood disorder history and ABEST scores (ps>.20). Treatment type did not modulate observed relationships (ps>.22). CONCLUSIONS: Breast cancer survivors with a mood disorder history may experience faster cardiopulmonary aging compared to their peers without such a history, raising risk for CVD.

Adjuvant Radiation Does Not Affect Locoregional Control Following Resection of Melanoma Satellitosis or In-Transit Disease.

BACKGROUND: This study evaluates the association of adjuvant radiation therapy (RT) with improved locoregional (LR) recurrence for resected melanoma satellitosis and in-transit disease (ITD). MATERIALS AND METHODS: Data were collected retrospectively for resected melanoma satellitosis/ITD from 1996 to 2017. RESULTS: 99 patients were identified. 20 patients (20.2%) received adjuvant RT while 79 (79.8%) did not. Mean follow-up in the RT group was 4.3 years and 4.7 years in the non-RT group. 80% of patients who underwent RT suffered a complication, most commonly dermatitis. Locoregional recurrence occurred in 9 patients (45%) treated with adjuvant RT and 30 patients (38%) in the non-RT group (P = 0.805). Median LR-DFS was 5.8 years in the RT group and 9.5 years in the non-RT group (P = 0.604). On multivariable analysis, having a close or positive margin was the only independent predictor of LR-DFS (HR 3.8 95% CI 1.7-8.7). In-transit disease was associated with improved overall survival when compared to satellitosis (HR 0.260, 95% CI 0.08-0.82). DISCUSSION: The use of adjuvant RT is not associated with improved locoregional control in resected melanoma satellitosis or ITD. Close or positive margin was the only treatment-related factor associated with decreased LR-DFS after surgical resection of satellitosis/ITD.

Distress Disorder Histories Relate to Greater Physical Symptoms Among Breast Cancer Patients and Survivors: Findings Across the Cancer Trajectory.

BACKGROUND: Psychological disorders can substantially worsen physical symptoms associated with breast cancer diagnosis and treatment, reducing survivors' quality of life and increasing recurrence risk. Distress disorders may be particularly detrimental given their physical correlates. Across two studies, we examined the relationship between a distress disorder history and physical symptoms pre- and post-adjuvant treatment - two important periods of the cancer trajectory. METHODS: Breast cancer patients awaiting adjuvant treatment (n = 147; mean age = 52.54) in study 1 and survivors 1-10 years post-treatment (n = 183; mean age = 56.11) in study 2 completed a diagnostic interview assessing lifetime presence of psychological disorders. They also rated their pain, fatigue, physical functioning, and self-rated health. Covariates included body mass index, age, cancer stage, menopause status, and physical comorbidities. RESULTS: Results from both studies indicated that a distress disorder history was associated with higher pain, fatigue, and sleep difficulties as well as lower self-rated health compared to those without such a history. CONCLUSIONS: These findings suggest that breast cancer survivors with a distress disorder may be particularly at risk for more physical symptoms, poorer sleep, and worse self-rated health both prior to and following adjuvant treatment.

Development of a web-based, theory-guided narrative intervention for women at elevated risk for breast cancer.

OBJECTIVE: To describe the development of a web-based, theory-guided narrative intervention that replaces conventional pre-test genetic counseling for women at elevated breast cancer risk. METHODS: We used an iterative process that was guided by health behavior theory and feedback from multiple stakeholder groups including: 1) content input from genetic experts; 2) study team input; 3) review of video storyboards, video example, study logo, recruitment materials, post-test patient preference counseling survey, and additional study surveys; 4) video series development; and 5) intervention review and finalization of study-related materials. RESULTS: The intervention is patient-centered providing convenience and an opportunity for an individual's preferences for post-test counseling delivery. The intervention's efficacy is being determined in a randomized controlled trial compared to conventional genetic counseling for adherence to recommended guidelines and changes in knowledge, perception of breast cancer risk, breast cancer-specific worry, and satisfaction with counseling. CONCLUSION: If efficacious, the intervention may improve the delivery of the genetic testing and counseling process, inform best practices, and reduce the genetic counseling workforce burden. PRACTICE IMPLICATIONS: The developed intervention has the potential to improve the genetic testing and counseling experience for women at elevated risk for breast cancer, inform best practices, and reduce genetic counseling workforce burden.

Emotion and contralateral prophylactic mastectomy: A prospective study into surgical decision-making.

OBJECTIVE: Patients with non-familial, unilateral breast cancer have a low risk of contralateral breast cancer. Thus, clinical studies have shown no survival benefit for patients who undergo contralateral prophylactic mastectomy (CPM) compared to those undergoing unilateral surgeries for non-familial unilateral breast cancers. Despite this evidence, there has been a steady increase in rates of CPM in the U.S. Patient factors influencing this choice have been identified in previous studies, but seldom in a prospective manner. This prospective study was designed to assess emotion and any association with a patient's decision to ultimately undergo CPM. METHODS: We recruited patients with newly diagnosed, unilateral, non-metastatic breast cancer, who had not yet had surgery, to participate in a prospective, longitudinal study to examine the impact of emotions on CPM decision-making. RESULTS: Among the 86 final participants, all completed the pre-visit survey (100%) and 52 patients completed the post-visit survey (60%). Patients undergoing CPM were significantly younger than those who did not. There was no statistically significant association between emotion and receipt of CPM. There was a trend towards undergoing CPM in patients with a less open personality type and those with more negative emotion, though not statistically significant. CONCLUSIONS: This study found a trend toward increased CPM receipt in those with less open personality types and more negative emotion, especially post-consultation, but none of these findings was significant. Future work should include development of cancer-specific emotion scales and larger studies of possible connections between emotion, personality type and surgical decision-making for breast cancer patients.

Affect regulation as a moderator of intentions for breast cancer chemoprevention.

Women at high risk for breast cancer (BC) may consider chemoprevention for risk reduction, but uptake is low. This study examined the role of affect regulation (the attempt to alter or control one's emotions) in decision-making about BC chemoprevention. A cross-sectional, single group design was used. High-risk women (N = 81) were surveyed. Moderation analyses specified cancer-specific distress as the independent variable, affect regulation (cognitive reappraisal or expressive suppression) as the moderator, and chemoprevention intentions (yes = 1, unsure = 0, no = -1) as the dependent variable. Cognitive reappraisal significantly moderated the relationship between cancer-specific distress and chemoprevention intentions (p = 0.03), but expressive suppression did not (p = 0.31). For the 44% of participants who were highest on reappraisal, higher cancer-specific distress was associated with greater intentions for chemoprevention. For the remaining 56%, there was no relationship between cancer-specific distress and chemoprevention intentions. Cognitive reappraisal may play an important role in decisions regarding uptake of chemoprevention.

The gut connection: Intestinal permeability as a pathway from breast cancer survivors' relationship satisfaction to inflammation across treatment.

BACKGROUND: Breast cancer survivors are prone to weakened gut barriers, allowing bacteria to migrate into the blood stream. Gut permeability fuels inflammation, which, among survivors, can elevate risk for comorbid disease development, cancer recurrence, and a poor quality of life; however, survivors' satisfying relationships can provide health benefits. This longitudinal study used a conceptual model addressing how intimate relationships is associated with health through changes in gut permeability and inflammation. METHOD: Breast cancer survivors (n = 139, stages 0-IIIC) completed a baseline visit before treatment and two follow-up visits 6 and 18 months after treatment ended. Women who had an abnormal breast cancer test followed by a benign diagnosis completed visits within a comparable timeframe (noncancer patient controls; n = 69). All women completed questionnaires assessing their relationship satisfaction and provided blood samples to assess two bacterial endotoxin biomarkers, lipopolysaccharide-binding protein (LBP) and soluble CD14 (sCD14), as well as C-reactive protein (CRP) and interleukin 6 (IL-6). RESULTS: Within-person multilevel mediation analyses showed that when a survivor's relationship satisfaction was higher than usual, her own LBP and LBP/sCD14 were lower, which was associated with lower than her own average CRP and IL-6 (95% CIs [-0.0104, -0.0002]). IL-6 was also higher when older survivors, but not younger survivors, experienced higher than usual intestinal permeability (p = .001). These effects of satisfying relationships held after accounting for cancer-related and behavioral factors. Post-hoc analyses showed LBP, sCD14, and LBP/sCD14 were associated with CRP for the cancer survivors, but only LBP and LBP/sCD14 were linked to CRP among the noncancer control patients. CONCLUSION: The gut environment is a new promising candidate for understanding a relationship's long-term health impact, particularly among those with elevated health risks. Survivors may reap multiple physiological benefits from satisfying relationships.

Distress Trajectories in Black and White Breast Cancer Survivors: From Diagnosis to Survivorship.

BACKGROUND: Black breast cancer survivors have greater morbidity and mortality than White survivors. However, evidence comparing Black survivors' psychological symptoms with their White counterparts has been mixed. Prior studies have not compared Black and White survivor's distress-related symptom trajectories from pre- to post-treatment - the goal of the current study. METHODS: At three annual visits from shortly after diagnosis to 6 and 18 months post-treatment, 195 women (n = 163 White; n = 32 Black) reported their cancer-related distress (intrusive thoughts and avoidance), perceived stress, anxiety and depressive symptoms, fatigue, and pain. RESULTS: Adjusting for age, educational attainment, income, treatment type, stage at diagnosis, and physical comorbidities, Black and White breast cancer survivors had different trajectories of cancer-related distress (p = .004), intrusive thoughts about cancer diagnosis and treatment (p = .002), perceived stress (p = .04), emotional fatigue (p = .01), and vigor (p = .02). Specifically, among White women, these distress-related symptoms improved from diagnosis to 6 months post-treatment (ps < 0.0001) and then remained stable between 6 and 18 months post-treatment, whereas Black women had persistently elevated distress - even 18 months after finishing treatment. Additionally, Black women reported more avoidance of cancer-related thoughts and emotions across visits (p = .047). Race was unrelated to the trajectories of anxiety and depressive symptoms, other fatigue subscales, or pain levels (ps > 0.08). CONCLUSION: Longitudinal assessment of the same breast cancer survivors from diagnosis to early survivorship revealed that Black and White survivors had divergent trajectories of psychological distress symptoms that were not reliably evident at a single timepoint. Overall, White women reported less psychological distress from pre- to post-treatment, but Black women's distress remained high from diagnosis to 18 months post-treatment. If left untreated, Black women's high distress levels may contribute to their poorer health throughout survivorship.

Fluctuations in depression and anxiety predict dysregulated leptin among obese breast cancer survivors.

PURPOSE: Leptin influences inflammation and tumor growth and leptin signaling is often dysregulated among obese breast cancer survivors. This leads to a lack of satiety and, ultimately, risk for further weight gain. Breast cancer survivors also experience high rates of depression and anxiety, which are linked to leptin production. This study examined how a woman's anxiety and depressive symptoms, in combination with their obesity status, were associated with leptin. METHODS: Breast cancer survivors (n = 200, stages 0-IIIa) completed a baseline visit before treatment and two follow-up visits, 6 and 18 months after treatment ended. Women completed anxiety and depression measures, and blood samples provided leptin data at each visit. This study related fluctuations in a survivor's own depression and anxiety (i.e., within-person effects), as well as average effects of depression and anxiety (i.e., between-person effects) to changes in leptin depending on BMI. RESULTS: Obese survivors' leptin was significantly higher at visits when they had higher anxiety and depression symptoms than their own average level of symptoms. In contrast, within-person fluctuations in depression and anxiety were not related to leptin levels among non-obese survivors. No significant between-person effects of depression or anxiety on leptin emerged. CONCLUSIONS: Leptin is a critical risk factor for recurrence and further health consequences. Our findings highlight how psychological health influences leptin production among breast cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: These results highlight a biological pathway that may facilitate further weight gain and health risks among distressed, obese breast cancer survivors.

Breast cancer survivors' satisfying marriages predict better psychological and physical health: A longitudinal comparison of satisfied, dissatisfied, and unmarried women.

OBJECTIVE: Breast cancer survivors who experience psychological and physical symptoms after treatment have an increased risk for comorbid disease development, reduced quality of life, and premature mortality. Identifying factors that reduce or exacerbate their symptoms may enhance their long-term health and physical functioning. This study examined how survivors' marital status and marital satisfaction-key health determinants-impacted their psychological and physical health trajectories to understand when, and for whom, marriage offers health benefits. METHODS: Breast cancer survivors (n = 209, stages 0-IIIC) completed a baseline visit before treatment and two follow-up visits 6 and 18 months after treatment ended. Women completed questionnaires assessing their marital status and satisfaction when applicable, as well as their psychological (depressive symptoms, stress) and physical (fatigue, pain) health at each visit. RESULTS: Married women-both those in satisfying and dissatisfying marriages-experienced improvements in their depressive symptoms, stress, and fatigue from pretreatment to 6- and 18-month posttreatment. Unmarried (i.e., single, divorced/separated, or widowed) women's depressive symptoms, stress, fatigue, and pain did not change over time, instead remaining elevated 6 and 18 months after treatment ended. Women in satisfying marriages also had fewer psychological and physical symptoms after treatment than those who were unmarried or in dissatisfying marriages. CONCLUSIONS: Although marriage was associated with improved psychological and physical health, the gains were most notable when survivors' marriages were satisfying. Thus, the quality of survivors' marriages, rather than the marriage itself, provided the most benefits to their psychological and physical health.

Preoperative Ultrasound Assessment of Regional Lymph Nodes in Melanoma Patients Does not Provide Reliable Nodal Staging: Results From a Large Multicenter Trial.

OBJECTIVE: To assess whether preoperative ultrasound (US) assessment of regional lymph nodes in patients who present with primary cutaneous melanoma provides accurate staging. BACKGROUND: It has been suggested that preoperative US could avoid the need for sentinel node (SN) biopsy, but in most single-institution reports, the sensitivity of preoperative US has been low. METHODS: Preoperative US data and SNB results were analyzed for patients enrolled at 20 centers participating in the screening phase of the second Multicenter Selective Lymphadenectomy Trial. Excised SNs were histopathologically assessed and considered positive if any melanoma was seen. RESULTS: SNs were identified and removed from 2859 patients who had preoperative US evaluation. Among those patients, 548 had SN metastases. US was positive (abnormal) in 87 patients (3.0%). Among SN-positive patients, 39 (7.1%) had an abnormal US. When analyzed by lymph node basin, 3302 basins were evaluated, and 38 were true positive (1.2%). By basin, the sensitivity of US was 6.6% (95% confidence interval: 4.6-8.7) and the specificity 98.0% (95% CI: 97.5-98.5). Median cross-sectional area of all SN metastases was 0.13 mm2; in US true-positive nodes, it was 6.8 mm2. US sensitivity increased with increasing Breslow thickness of the primary melanoma (0% for ≤1 mm thickness, 11.9% for >4 mm thickness). US sensitivity was not significantly greater with higher trial center volume or with pre-US lymphoscintigraphy. CONCLUSION: In the MSLT-II screening phase population, SN tumor volume was usually too small to be reliably detected by US. For accurate nodal staging to guide the management of melanoma patients, US is not an effective substitute for SN biopsy.

Worry and rumination in breast cancer patients: perseveration worsens self-rated health.

A number of studies have shown that self-rated health reliably predicts mortality. This study assessed the impact of perseveration on self-rated health, physical functioning, and physical symptoms (pain, fatigue, breast cancer symptoms) among breast cancer patients. We hypothesized that cancer-related distress would serve as an intervening variable between both worry and rumination and self-rated health, physical functioning, and physical symptoms. Women (N = 124) who were approximately 7 weeks post-surgery but pre adjuvant treatment completed the Impact of Events Scale, the Penn State Worry Questionnaire, and the Rumination Scale. They also rated their pain, fatigue, physical functioning, and self-rated health using the RAND-36 and breast cancer symptoms with the Breast Cancer Prevention Trial Symptom Checklist (BCPT). Covariates included body mass index, age, cancer stage, menopause status, and physical comorbidities. Worry was associated with higher cancer-related distress, which in turn predicted greater pain and breast cancer symptoms, poorer physical functioning, and lower self-rated health. Rumination also predicted greater cancer-related distress, which ultimately contributed to greater pain along with poorer physical functioning and self-rated health. Models with fatigue as an outcome were not significant. These findings suggest that perseveration can heighten cancer-related distress and subsequent perceptions of physical symptoms and health among breast cancer patients prior to adjuvant treatment. Perseveration early in the cancer trajectory can adversely increase the impact of a cancer diagnosis and treatment on functioning and quality of life.

Endotoxemia coupled with heightened inflammation predicts future depressive symptoms.

OBJECTIVE: Cross-sectional data have linked gut barrier abnormalities and endotoxemia with depression, even among those without gastrointestinal symptoms. This study examined longitudinal associations between endotoxemia markers and depressive symptoms, as well as the role of inflammation in this relationship. DESIGN: At three annual visits, 315 women (n=209 breast cancer survivors, n = 106 non-cancer patient controls, M=55 years old) completed the Center for Epidemiological Studies Depression questionnaire (CES-D) and provided blood samples to assess inflammatory markers - interleukin-6, tumor necrosis factor-alpha, and C-reactive protein - and endotoxemia markers - lipopolysaccharide-binding protein (LBP), soluble CD14 (sCD14), and their ratio. RESULTS: Adjusting for key demographic variables, health behaviors, visit 1 depressive symptoms, and cancer status and treatment, women with higher visit 1 LBP and LBP/sCD14 had more depressive symptoms at the two subsequent annual visits. Illustrating the notable impact, a woman at the 75th percentile for LBP or LBP/sCD14 at visit 1 was 18 % more likely to report clinically significant depressive symptoms (CES-D ≥16) at follow-up than a woman in the lowest quartile. Cancer status and treatment type did not modulate this relationship. In contrast, visit 1 depressive symptoms did not predict endotoxemia at follow-up. A significant interaction between LBP/sCD14 and inflammatory burden suggested that visit 1 endotoxemia fueled depressive symptoms only in the context of elevated inflammation. CONCLUSION: These results suggest that endotoxemia, combined with systemic inflammation, can drive depressive symptoms. These findings may implicate bacterial endotoxin translocation from the gut to the bloodstream in depression etiology. Interventions that reduce endotoxemia and inflammation may lessen the risk of depression.

Within-person changes in cancer-related distress predict breast cancer survivors' inflammation across treatment.

BACKGROUND: Among breast cancer survivors, elevated inflammation has been linked to greater recurrence risk. Psychological processes, such as cancer-related distress, can pose threats to a survivor's longevity and wellbeing. Although distress can heighten inflammation, little is known about how fluctuations in distress during and after treatment impact a woman's own inflammation - the primary question of this study. METHODS: Breast cancer survivors (n = 165, stages 0-III) completed a baseline visit before treatment and two follow-up visits 6 and 18 months after. At each visit, women completed the Impact of Events Scale to assess cancer-related distress, and a blood sample was collected to measure proinflammatory cytokines IL-6, TNF-α, IL-1ß, and IL-8. This longitudinal study related fluctuations in survivor's own cancer-related distress (i.e., within-person effects), as well as average effects of cancer-related distress between survivors (i.e., between-person effects) to inflammatory changes across visits. RESULTS: Women had elevated inflammation at visits where they expressed more cancer-related distress than what was typical. In contrast, the average cancer-related distress was not associated with inflammation. CONCLUSION: Larger increases in a women's cancer-related distress was linked with higher inflammation across visits. Comparing a survivor's own cancer-related distress to her average levels may prove useful in identifying links between distress and inflammation.

Relationship satisfaction predicts lower stress and inflammation in breast cancer survivors: A longitudinal study of within-person and between-person effects.

BACKGROUND: Breast cancer survivors with elevated inflammation have a greater risk for cancer recurrence, premature mortality, and comorbid disease development. The psychological stress survivors experience when confronted with a breast cancer diagnosis and cancer treatment can heighten inflammation. Identifying factors that reduce stress and inflammation could lead to improvements in survivors' long-term health. Accordingly, this study examined the health-enhancing effects of romantic relationships-a key health determinant-on breast cancer survivors' stress and inflammation. METHODS: Breast cancer survivors (n = 139, stages 0-IIIC) completed a baseline visit before treatment and two follow-up visits 6 and 18 months after treatment ended. Women completed self-report questionnaires assessing their romantic relationship satisfaction and perceived stress, and they provided a blood sample for serum markers of inflammation at each visit. The longitudinal design allowed for examination within and between survivors. We conducted multilevel mediation analyses to assess how changes in survivors' relationship satisfaction were related to changes in stress and inflammation from visit to visit (i.e., within-person effects), as well as how the average effects of relationship satisfaction were associated with average stress and inflammation levels throughout the study (i.e., between-person effects). RESULTS: At the within-person level, at visits in which survivors were more satisfied with their relationships, they also perceived less stress, which in turn was related to lower than their own average levels of serum C-reactive protein and proinflammatory cytokines (tumor necrosis factor-α, interleukin-6, and interleukin-1ß). At the between-person level, survivors who had greater relationship satisfaction throughout the study had lower perceived stress, which was linked to lower levels of inflammation. CONCLUSION: Breast cancer survivors in satisfying romantic relationships felt less stressed and in turn had lower inflammation throughout cancer treatment. This study illustrates the utility of a within-person approach to not only consider the average effects of relationship satisfaction, but also how changes in their own relationship satisfaction impact stress and inflammation over time. Our findings demonstrate important psychological and immunological pathways through which satisfying relationships may promote breast cancer survivors' long-term health.

Does use of axillary ultrasound in clinically node-negative patients receiving neo-adjuvant systemic therapy for breast cancer lead to surgical overtreatment?

Increased use of neo-adjuvant chemotherapy (NAC) for breast cancer has raised uncertainty regarding staging of the axilla, particularly for patients with a clinically negative axillary physical examination (PE). We sought to determine whether axillary ultrasound (AUS) prior to NAC to identify occult nodal disease is beneficial in patients with a clinically negative examination by evaluating the difference in nodal burden on final pathology in those with abnormal vs normal AUS. A retrospective review of an institutional cancer registry identified patients who underwent NAC for breast cancer and had a pretreatment AUS. Differences in the number of positive lymph nodes (PLN) in patients with a normal axillary PE and abnormal vs normal AUS prior to NAC were determined. A total of 120 patients who received NAC had a negative axillary PE prior to treatment. Fifty-three had an abnormal AUS and biopsy-proven lymph node (LN) involvement. In patients with an abnormal AUS, median number of PLNs at surgery was 1 vs 0 for those with a normal AUS (mean difference of 2.12, P < .0001). Of those patients with an abnormal AUS and biopsy-proven LN involvement, 87% underwent axillary lymph node dissection (ALND) and nearly half had no PLN on final pathology (N = 23, 43%). Patients with a clinically negative axilla and an abnormal AUS were more likely to have PLN at the time of surgery. However, almost half of those patients had no residual LN involvement. Routine AUS prior to NAC may lead to more extensive surgical management of the axilla.