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About one week before she died, Amy Williamsen invited me to write the Afterword to this special issue of Cervantes. Amy, my wife (Valerie Hegstrom), and I shared many quixotic [...]

PurposeAlthough fear of recurrence (FCR) is common among cancer survivors, it remains unclear what factors predict initial levels (e.g., prior to surgery) or changes in FCR in the post-treatment period. Among women treated for breast cancer, this study evaluated the effects of demographic, clinical, symptom, and psychosocial adjustment characteristics on the initial (preoperative) levels of FCR and trajectories of FCR over 6 months following surgery.MethodsPrior to and for 6 months following breast cancer surgery, 396 women were assessed for demographic and clinical (disease and treatment) characteristics, symptoms, psychological adjustment characteristics, and quality of life (QOL). FCR was assessed using a four-item subscale from the QOL instrument. Hierarchical linear modeling was used to examine changes in FCR scores and to identify predictors of inter-individual differences in preoperative FCR levels and trajectories over 6 months.ResultsFrom before surgery to 6 months post-operatively, women with breast cancer showed a high degree of inter-individual variability in FCR. Preoperatively, women who lived with someone, experienced greater changes in spiritual life, had higher state anxiety, had more difficulty coping, or experienced more distress due to diagnosis or distress to family members reported higher FCR scores. Patients who reported better overall physical health and higher FCR scores at enrollment demonstrated a steeper decrease in FCR scores over time.ConclusionsThese findings highlight inter-individual heterogeneity in initial levels and changes in FCR over time among women undergoing breast cancer surgery. Further work is needed to identify and provide interventions for women experiencing FCR during and after breast cancer treatment.

ContextApproximately 30% of the women report pain in the affected breast before breast cancer surgery.ObjectivesThe purpose of this secondary analysis of our prospective study was to determine how women who experienced both preoperative and persistent postsurgical breast pain (n=107) differed from women who did not report preoperative breast pain and did (n=158) or did not (n=122) experience persistent postsurgical breast pain.MethodsDifferences in demographic and clinical characteristics were evaluated. Linear mixed effects (LME) modeling was used to evaluate for group differences in symptom severity, function, sensation, and quality of life (QOL) over time.ResultsBetween-group differences in demographic and clinical characteristics as well as trajectories of shoulder function and QOL were identified. Women with both preoperative and persistent postsurgical breast pain were younger; were more likely to report swelling, strange sensations, hardness, and numbness in the affected breast before surgery; and were more likely to have reconstruction at the time of surgery. Women with both preoperative and persistent postsurgical breast pain had more biopsies in the prior year, more lymph nodes removed, and reported more severe acute postsurgical pain than women without preoperative breast pain. The LME modeling revealed significant group effects for most outcomes evaluated. Over the six months of the study, women with both preoperative and persistent postsurgical pain had persistently poorer shoulder flexion and physical well-being than women without preoperative breast pain.ConclusionInvestigations of the etiology and molecular mechanisms of preoperative breast pain, as well as interventions for this high-risk group, are needed.

Purpose of the researchEvaluate for associations between variations in genes involved in catecholaminergic, gamma-aminobutyric acid (GABA)-ergic, and serotonergic mechanisms of neurotransmission and attentional function latent classes.Patients and methodsThis descriptive, longitudinal study was conducted at two radiation therapy departments. The sample included three latent classes of individuals with distinct trajectories of self-reported attentional function during radiation therapy, who were previously identified using growth mixture modeling among 167 oncology patients and 85 of their family caregivers. Multivariable models were used to evaluate for genotypic associations of neurotransmission genes with attentional function latent class membership, after controlling for covariates.ResultsVariations in catecholaminergic (i.e., ADRA1D rs4815675, SLC6A3 rs37022), GABAergic (i.e., SLC6A1 rs2697138), and serotonergic (i.e., HTR2A rs2296972, rs9534496) neurotransmission genes were significant predictors of latent class membership in multivariable models.ConclusionsFindings suggest that variations in genes that encode for three distinct but related neurotransmission systems are involved in alterations in attentional function. Knowledge of both phenotypic and genetic markers associated with alterations in attentional function can be used by clinicians to identify patients and family caregivers who are at higher risk for this symptom. Increased understanding of the genetic markers associated with alterations in attentional function may provide insights into the underlying mechanisms for this significant clinical problem.

PurposeAnxiety is common among cancer patients and their family caregivers (FCs) and is associated with poorer outcomes. Recently, associations between inflammation and anxiety were identified. However, the relationship between variations in cytokine genes and anxiety warrants investigation. Therefore, phenotypic and genotypic characteristics associated with trait and state anxiety were evaluated in a sample of 167 oncology patients with breast, prostate, lung, or brain cancer and 85 of their FCs.MethodsUsing multiple regression analyses, the associations between participants' demographic and clinical characteristics as well as variations in cytokine genes and trait and state anxiety were evaluated.ResultsIn the bivariate analyses, a number of phenotypic characteristics were associated with both trait and state anxiety (e.g., age, functional status). However, some associations were specific only to trait anxiety (e.g., number of comorbid conditions) or state anxiety (e.g., participation with a FC). Variations in three cytokine genes (i.e., interleukin (IL) 1 beta, IL1 receptor 2 (IL1R2), nuclear factor kappa beta 2 (NFKB2)) were associated with trait anxiety, and variations in two genes (i.e., IL1R2, tumor necrosis factor alpha (TNFA)) were associated with state anxiety.ConclusionsThese findings suggest that both trait and state anxiety need to be assessed in oncology patients and their FCs. Furthermore, variations in cytokine genes may contribute to higher levels of anxiety in oncology patients and their FCs.

The purpose of this study was to evaluate for differences in variations in pro- and anti-inflammatory cytokine genes between participants who were classified as having low and high levels of morning and evening fatigue and to evaluate for differences in phenotypic characteristics between these two groups. In a sample of 167 oncology outpatients with breast, prostate, lung, or brain cancer and 85 of their family caregivers, growth mixture modeling was used to identify latent classes of individuals based on ratings of morning and evening fatigue obtained prior to, during, and for 4 months following completion of radiation therapy. Differences in single nucleotide polymorphisms and haplotypes in 15 cytokine genes were evaluated between the latent classes. Multiple logistic regression was used to assess the effect of phenotypic and genotypic characteristics on morning and evening fatigue class membership. Associations were found between morning fatigue and number of comorbidities as well as variations in tumor necrosis factor alpha (TNFA) rs1800629 and rs3093662. Evening fatigue was associated with caring for children at home and variations in interleukin 4 (IL4) rs2243248 and TNFA rs2229094. Younger age and lower performance status were associated with both morning and evening fatigue. These findings suggest that inflammatory mediators are associated with the development of morning and evening fatigue. However, because different phenotypic characteristics and genomic markers are associated with diurnal variations in fatigue, morning and evening fatigue may be distinct but related symptoms.

Current understanding of the development of quantity representations is based primarily on performance in the number-line task. We posit that the data from number-line tasks reflect the observer's underlying representation of quantity, together with the cognitive strategies and skills required to equate line length and quantity. Here, we specify a unified theory linking the underlying psychological representation of quantity and the associated strategies in four variations of the number-line task: the production and estimation variations of the bounded and unbounded number-line tasks. Comparison of performance in the bounded and unbounded number-line tasks provides a unique and direct way to assess the role of strategy in number-line completion. Each task produces a distinct pattern of data, yet each pattern is hypothesized to arise, at least in part, from the same underlying psychological representation of quantity. Our model predicts that the estimated biases from each task should be equivalent if the different completion strategies are modeled appropriately and no other influences are at play. We test this equivalence hypothesis in two experiments. The data reveal all variations of the number-line task produce equivalent biases except for one: the estimation variation of the bounded number-line task. We discuss the important implications of these findings.

UnlabelledPersistent pain following breast cancer surgery is well documented. However, it is not well characterized in terms of the anatomic site affected (ie, breast, arm). In 2 separate growth mixture modeling analyses, we identified subgroups of women (N = 398) with distinct breast pain and arm pain trajectories. The fact that these latent classes differed by anatomic site, types of tissue affected, and neural innervation patterns suggests the need for separate evaluations of these distinct persistent pain conditions. The purposes of this companion study were to identify demographic and clinical characteristics that differed between the 2 arm pain classes and determine if differences existed over time in sensitivity in the upper inner arm and axillary lymph node dissection sites, pain qualities, pain interference, and hand and arm function, as well as to compare findings with persistent breast pain. Higher occurrence rates for depression and lymphedema were found in the moderate arm pain class. Regardless of pain group membership, sensory loss was observed in the upper inner arm and axillary lymph node dissection site. Arm pain was described similarly to neuropathic pain and interfered with daily functioning. Persistent arm pain was associated with sustained impairments in shoulder mobility.PerspectiveFor persistent breast and arm pain, changes in sensation following breast cancer surgery were notable. Persistent arm pain was associated with sustained interference with daily functioning and upper body mobility impairments. Long-term management of persistent pain following breast cancer surgery is warranted to improve the quality of survivorship for these women.

UnlabelledInterindividual variability exists in persistent breast pain following breast cancer surgery. Recently, we used growth mixture modeling to identify 3 subgroups of women (N = 398) with distinct persistent breast pain trajectories (ie, mild, moderate, severe) over 6 months following surgery. The purposes of this study were to identify demographic and clinical characteristics that differed among the breast pain classes and, using linear mixed effects modeling, to examine how changes over time and in sensitivity in the breast scar area, pain qualities, pain interference, and hand and arm function differed among these classes. Several demographic and clinical characteristics differentiated the breast pain classes. Of note, 60 to 80% of breast scar sites tested were much less sensitive than the unaffected breast. Significant group effects were observed for pain qualities and interference scores, such that, on average, women in the severe pain class reported higher scores than women in the moderate pain class. In addition, women in the moderate pain class reported higher scores than women in the mild pain class. Compared to women in the mild pain class, women in the severe pain class had significantly impaired grip strength, and women in the moderate and severe pain classes had impaired flexion and abduction.PerspectiveSubgroups of women with persistent postsurgical breast pain differed primarily with respect to the severity rather than the nature or underlying mechanisms of breast pain. Pervasive sensory loss and the association between persistent breast pain and sustained interference with function suggest the need for long-term clinical follow-up.

PurposeThis study explored the relationships between variations in cytokines genes and depressive symptoms in a sample of patients who were assessed prior to and for six months following breast cancer surgery. Phenotypic differences between Resilient (n = 155) and Subsyndromal (n = 180) depressive symptom classes, as well as variations in cytokine genes were evaluated.MethodPatients were recruited prior to surgery and followed for six months. Growth mixture modeling was used to identify distinct latent classes based on Center for Epidemiological Studies Depression (CES-D) Scale scores. Eighty-two single nucleotide polymorphisms and 35 haplotypes among 15 candidate cytokine genes were evaluated.ResultsPatients in the Subsyndromal class were significantly younger, more likely to be married or partnered, and reported a significantly lower functional status. Variation in three cytokine genes (i.e., interferon gamma receptor 1 (IFNGR1 rs9376268), interleukin 6 (IL6 rs2069840), tumor necrosis factor alpha (TNFA rs1799964)), as well as age and functional status predicted membership in the Subsyndromal versus the Resilient class.ConclusionsA variation in TNFA that was associated with Subsyndromal depressive symptoms in a sample of patients and their family caregivers was confirmed in this sample. Variations in cytokine genes may place these patients at higher risk for the development of Subsyndromal levels of depressive symptoms.

BackgroundA large amount of interindividual variability exists in the occurrence of symptoms in patients receiving chemotherapy (CTX). The purposes of the current study, which was performed in a sample of 582 oncology outpatients who were receiving CTX, were to identify subgroups of patients based on their distinct experiences with 25 commonly occurring symptoms and to identify demographic and clinical characteristics associated with subgroup membership. In addition, differences in quality of life outcomes were evaluated.MethodsOncology outpatients with breast, gastrointestinal, gynecological, or lung cancer completed the Memorial Symptom Assessment Scale before their next cycle of CTX. Latent class analysis was used to identify subgroups of patients with distinct symptom experiences.ResultsThree distinct subgroups of patients were identified (ie, 36.1% in Low class; 50.0% in Moderate class, and 13.9% in All High class). Patients in the All High class were significantly younger and more likely to be female and nonwhite, and had lower levels of social support, lower socioeconomic status, poorer functional status, and a higher level of comorbidity.ConclusionsFindings from the current study support the clinical observation that some oncology patients experience a differentially higher symptom burden during CTX. These high-risk patients experience significant decrements in quality of life.

PurposeIn this prospective, longitudinal study, we extend our findings on persistent breast pain in patients (n = 398) following breast cancer surgery and evaluate the prevalence and characteristics of persistent pain in the arm/shoulder. In addition, differences in the severity of common symptoms and quality of life outcomes measured prior to surgery, among the arm pain classes, were evaluated.Methods and samplePatients were recruited from Breast Care Centers located in a Comprehensive Cancer Center, two public hospitals, and four community practices. Patients were assessed prior to and monthly for six months following breast cancer surgery.ResultsUsing growth mixture modeling, patients were classified into no (41.6%), mild (23.6%), and moderate (34.8%) arm pain classes based on ratings of worst arm/shoulder pain. Compared to the no pain class, patients in the moderate pain class were significantly younger, had a higher body mass index, and were more likely to report preoperative breast pain and swelling in the affected breast. In addition, patients in the moderate pain class reported higher levels of depression, anxiety, and sleep disturbance than the no pain class.ConclusionsFindings suggest that approximately 35% of women experience persistent levels of moderate arm/shoulder pain in the first six months following breast cancer surgery. Moderate arm/shoulder pain is associated with clinically meaningful decrements in functional status and quality of life.

Subgroups of individuals may be at greater risk of cytokine-induced changes in attentional function. The purposes of this study were to identify subgroups of individuals with distinct trajectories of attentional function and evaluate for phenotypic and genotypic (i.e., cytokine gene polymorphisms) differences among these subgroups. Self-reported attentional function was evaluated in 252 participants (167 oncology patients and 85 family caregivers) using the Attentional Function Index before radiation therapy and at six additional assessments over 6 months. Three latent classes of attentional function were identified using growth mixture modeling: moderate (36.5%), moderate-to-high (48.0%), and high (15.5%) attentional function. Participants in the moderate class were significantly younger, with more comorbidities and lower functional status, than those in the other two classes. However, only functional status remained significant in multivariable models. Included in the genetic association analyses were 92 single nucleotide polymorphisms (SNPs) among 15 candidate genes. Additive, dominant, and recessive genetic models were assessed for each SNP. Controlling for functional status, only Interleukin 6 (IL6) rs1800795 remained a significant genotypic predictor of class membership in multivariable models. Each additional copy of the rare "G" allele was associated with a 4-fold increase in the odds of belonging to the lower attentional function class (95% confidence interval: [1.78, 8.92]; p = .001). Findings provide preliminary evidence of subgroups of individuals with distinct trajectories of attentional function and of a genetic association with an IL6 promoter polymorphism.

Preoperative breast pain in women with breast cancer may result from a number of causes. Previous work from our team found that breast pain occurred in 28.2% of women (n = 398) who were about to undergo breast cancer surgery. The occurrence of preoperative breast pain was associated with a number of demographic and clinical characteristics, as well as variation in two cytokine genes. Given that ion channels regulate excitability of sensory neurons, we hypothesized that variations in potassium channel genes would be associated with preoperative breast pain in these patients. Therefore, in this study, we evaluated for associations between single-nucleotide polymorphisms and inferred haplotypes among 10 potassium channel genes and the occurrence of preoperative breast pain in patients scheduled to undergo breast cancer surgery. Multivariable logistic regression analyses were used to identify those genetic variations that were associated with the occurrence of preoperative breast pain while controlling for age and genomic estimates of and self-reported race/ethnicity. Variations in four potassium channel genes: (1) potassium voltage-gated channel, delayed rectifier, subfamily S, member 1 (KCNS1); (2) potassium inwardly rectifying channel, subfamily J, member 3 (KCNJ3); (3) KCNJ6; and (4) potassium channel, subfamily K, member 9 (KCNK9) were associated with the occurrence of breast pain. Findings from this study warrant replication in an independent sample of women who report breast pain following one or more breast biopsies.

Subgroups of patients with breast cancer may be at greater risk for cytokine-induced changes in cognitive function after diagnosis and during treatment. The purposes of this study were to identify subgroups of patients with distinct trajectories of attentional function and evaluate for phenotypic and genotypic (i.e., cytokine gene polymorphisms) predictors of subgroup membership. Self-reported attentional function was evaluated in 397 patients with breast cancer using the Attentional Function Index before surgery and for six months after surgery (i.e., seven time points). Using growth mixture modeling, three attentional function latent classes were identified: High (41.6%), Moderate (25.4%), and Low-moderate (33.0%). Patients in the Low-moderate class were significantly younger than those in the High class, with more comorbidities and lower functional status than the other two classes. No differences were found among the classes in years of education, race/ethnicity, or other clinical characteristics. DNA was recovered from 302 patients' samples. Eighty-two single nucleotide polymorphisms among 15 candidate genes were included in the genetic association analyses. After controlling for age, comorbidities, functional status, and population stratification due to race/ethnicity, IL1R1 rs949963 remained a significant genotypic predictor of class membership in the multivariable model. Carrying the rare "A" allele (i.e., GA+AA) was associated with a twofold increase in the odds of belonging to a lower attentional function class (OR: 1.98; 95% CI: 1.18, 3.30; p=.009). Findings provide evidence of subgroups of women with breast cancer who report distinct trajectories of attentional function and of a genetic association between subgroup membership and an IL1R1 promoter polymorphism.