Barlow's Model Research Articles

Abstract 268: Absolute breast cancer risk according to three risk prediction models: Inverse associations with risk of death and poor prognostic features

Abstract Predicted absolute breast cancer risk is an important factor for women to consider in making decisions about screening and prevention. If breast cancer risk models preferentially predict risk of indolent cancers, then using these tools to guide screening may reduce mortality less than expected. In contrast, if models perform well in determining risk of fatal breast cancers, these tools may help reduce mortality by guiding targeted interventions. Accordingly, we assessed relationships of women's predicted breast cancer risk, as estimated with the Breast Cancer Risk Assessment Tool (BCRAT; http://www.cancer.gov/bcrisktool/), Breast Cancer Surveillance Consortium (BCSC) risk calculator (https://tools.bcsc-scc.org/BC5yearRisk/) and Barlow model, with risk of death and tumor features. Using information collected in the BCSC from 37,939 women prior to the diagnosis of invasive breast cancer (1996-2007), we calculated predicted 5-year breast cancer risk (stratified as <1%; 1-2.5%; >2.5%) with the BCRAT, BCSC and Barlow models. Cox models were used to estimate the association between breast cancer risk strata and 10-year survival following a breast cancer diagnosis. Separate models were analyzed for women less than age 50 years and 50 years or older at diagnosis, adjusted for covariates. To elucidate relationships between predicted breast cancer risk and risk of death, we compared features of cancers by risk strata. Mean age at breast cancer diagnosis was 60 years. There were a total of 6,021 deaths of which 2,993 (49.7%) were ascribed to breast cancer. Estimated breast cancer risk varied by model; Barlow assigned 36.5% of women to the highest risk strata (>2.5% absolute risk at 5 years) versus 21.0% for BCSC and 5.5% for BCRAT. For each model, women at lowest breast cancer risk experienced the highest risk of breast cancer death. Women above age 50 years whose predicted breast cancer risk was in the two highest strata were at lower risk of death than those in the lowest risk stratum (HRs for breast cancer death ranged from 0.69-0.84 for the 3 models, with all but one estimate statistically significant). Compared with women at highest breast cancer risk, women at lowest risk developed a significantly higher percentage of breast cancers that were larger than 2 cm, grade 3, associated with positive nodes, higher than stage IIA and classified as interval cancers (detected following a negative screening mammogram). Analyses excluding women with missing risk factor data yielded similar interpretations. Higher breast cancer risk, as predicted with BCRAT, BCSC and Barlow models, is inversely associated with risk of breast cancer death. Application of existing breast cancer risk models to guide screening and prevention may yield less than expected reductions in mortality. Citation Format: Mark E. Sherman, Laura Ichikawa, Diana Miglioretti, Pamela Vacek, Jeffrey Tice, Ruth Pfeiffer, Karla Kerlikowske, Gretchen Gierach. Absolute breast cancer risk according to three risk prediction models: Inverse associations with risk of death and poor prognostic features. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 268. doi:10.1158/1538-7445.AM2014-268

Sexual and Affective Responses to Same- and Opposite-Sex Stimuli in Heterosexual and Homosexual Men: Assessment and Manipulation of Visual Attention

Affective and cognitive factors play an important role in the activation and regulation of men's sexual arousal. Barlow (1986) argued that initial affective reactions determine the allocation of attention to sexual stimuli. We applied Barlow's model to our understanding of the role of sexual arousal in sexual orientation, where sexual arousal patterns have consistently been found to be congruent with self-reported orientation in men, but not in women. Visual attention of 28 heterosexual and 22 homosexual men to same- and opposite-sex erotic stimuli was assessed and experimentally-directed by means of a newly developed software application, while genital (penile rigidity) and affective responses (self-reported and physiological) were measured. In line with previous research, we found "category specificity" in men's sexual arousal, in that sexual responses were strongest to orientation-congruent stimuli. Also, both homosexual and heterosexual men experienced stronger sexual responses to conditions in which their attention was directed to sexual versus nonsexual content of orientation-congruent stimuli. Only homosexual men manifested higher sexual responses when their visual attention was directed towards the sexual content of orientation-incongruent stimuli. Heterosexual men experienced weaker positive and stronger negative affective responses to orientation-incongruent content, suggestive of potential avoidance or inhibitory mechanisms.

An assessment of existing models for individualized breast cancer risk estimation in a screening program in Spain

BackgroundThe aim of this study was to evaluate the calibration and discriminatory power of three predictive models of breast cancer risk.MethodsWe included 13,760 women who were first-time participants in the Sabadell-Cerdanyola Breast Cancer Screening Program, in Catalonia, Spain. Projections of risk were obtained at three and five years for invasive cancer using the Gail, Chen and Barlow models. Incidence and mortality data were obtained from the Catalan registries. The calibration and discrimination of the models were assessed using the Hosmer-Lemeshow C statistic, the area under the receiver operating characteristic curve (AUC) and the Harrell’s C statistic.ResultsThe Gail and Chen models showed good calibration while the Barlow model overestimated the number of cases: the ratio between estimated and observed values at 5 years ranged from 0.86 to 1.55 for the first two models and from 1.82 to 3.44 for the Barlow model. The 5-year projection for the Chen and Barlow models had the highest discrimination, with an AUC around 0.58. The Harrell’s C statistic showed very similar values in the 5-year projection for each of the models. Although they passed the calibration test, the Gail and Chen models overestimated the number of cases in some breast density categories.ConclusionsThese models cannot be used as a measure of individual risk in early detection programs to customize screening strategies. The inclusion of longitudinal measures of breast density or other risk factors in joint models of survival and longitudinal data may be a step towards personalized early detection of BC.

Abstract P6-09-02: Risk of Breast Cancer Associated with Hormone Replacement Therapy Use Differs by Age, Race, and Breast Density

Abstract Background: Observational studies and randomized trials have demonstrated an association between hormone replacement therapy (HRT) use and increased risk for breast cancer. However, this risk may vary by age and other factors, including breast density and race/ethnicity. Using data from the Breast Cancer Surveillance Consortium (BCSC), we investigate whether self-reported HRT use in the peri-menopausal and immediate post-menopausal age groups is associated with breast cancer, and also whether risk associated with HRT use differs by breast density and race. Subjects and Methods: The BCSC is a longitudinal registry of mammography screening in seven U.S. centers. In the breast cancer risk prediction model developed by Barlow et al (J Natl Cancer Inst 2006 98:1204-14), HRT use and ten other features were identified as risk factorsfor breast cancer. Data for our study consists of 1,642,824 screens and 9,300 breast cancers among the post-menopausal women aged > 44 in this cohort. Logistic regression models were used to estimate odds ratios for breast cancer associated with HRT use within race, age, and density strata, adjusting for other variables from the Barlow model. Multiple imputation methods were used to accommodate missing data for HRT (14%) and other predictors. Results: Breast cancer risk for HRT use varied by age, with no risk excess among women aged 45-49 and risk excess of 20% or greater for women aged 50-64 (Table 1). Women >64 had a smaller excess risk with HRT use. There was no significant excess risk at any age for Black women, while White women age 50-64 had > 20% excess risk for HRT use. White women with higher breast density had increased risk with HRT use, while Black women did not. Table 1: Odds ratios (95% confidence interval) for HRT use (yes/no) Conclusions: In this large cohort of mammography-screened women, HRT use did not increase breast cancer risk in the peri-menopausal period (age 45-49). Women with low breast density had smaller risk increments associated with HRT than those with high density. For Black women, increased breast cancer risk due to HRT was not apparent at any age or breast density category. Data collection for the BCSC was supported by a NCI-funded Breast Cancer Surveillance Consortium co-operative agreement (U01CA63740, U01CA86076, U01CA86082, U01CA63736, U01CA70013, U01CA69976, U01CA63731, U01CA70040). Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-09-02.

Non-Erotic Thoughts, Attentional Focus, and Sexual Problems in a Community Sample

According to Barlow's model of sexual dysfunction, anxiety in sexual situations leads to attentional focus on sexual performance at the expense of erotic cues, which compromises sexual arousal. This negative experience will enhance anxiety in future sexual situations, and non-erotic thoughts (NETs) relevant to performance will receive attentional priority. Previous research with student samples (Purdon & Holdaway, 2006; Purdon & Watson, 2010) has found that people experience many types of NETs in addition to performance-relevant thoughts, and that, consistent with Barlow's model, the frequency of and anxiety evoked by these thoughts is positively associated with sexual problems. Extending this previous work, the current study found that, in a community sample of women (N=81) and men (N=72) in long-term relationships, women were more likely to report body image concerns and external consequences of the sexual activity, while men were more likely to report performance-related concerns. Equally likely among men and women were thoughts about emotional consequences of the sexual activity. Regardless of thought content, experiencing more frequent NETs was associated with more sexual problems in both women and men. Moreover, as per Barlow's model, greater negative affect in anticipation of and during sexual activity predicted greater frequency of NETs and greater anxiety in response to NETs was associated with greater difficulty dismissing the thoughts. However, greater difficulty in refocusing on erotic thoughts during sexual activity uniquely predicted more sexual problems above the frequency and dismissability of NETs. Together, these data support the cognitive interference mechanism implicated by Barlow's causal model of sexual dysfunction and have implications for the treatment of sexual problems.

The conceptual relationship between panic disorder and male erectile dysfunction

Despite evidence of a relationship between sexual dysfunction and panic disorder, there havebeen few clinical reports addressing the nature of the association between these phenomena. We present three case reports of men diagnosed with panic disorder with agoraphobia, who presented for treatment of erectile problems. In each of the three cases, the similarity between sensationsexperienced during sexual arousal and those experienced during panic attacks is noted. The purpose of these case presentations is to stimulate further empirical examination of sexpanic states and to alert practitioners of the possible assessment and treatment implications for such individuals. The symptomatic overlap exhibited in these cases is conceptualized from both a psychobiological model of panic disorder and from Barlow's model of sexual dysfunction in an effort to provide a theoretical framework to guide future research and clinical assessment.

Phobic anxiety in panic disorder: Cognition, heart rate, and subjective anxiety

This study investigated the relationships among cognition, physiological arousal, and subjective anxiety in the ongoing experience of phobic anxiety in panic disorder. Twenty subjects with panic disorder and some degree of agoraphobic avoidance were monitored during exposure to fear-provoking situations. Extent of negativity in reported thoughts (percent negative thoughts) was significantly correlated to mean heart rate and peak subjective anxiety. Reporting of individual negative thoughts was associated with high levels of subjective anxiety but not heart rate. Data were also analysed in terms of thought sequences. Results indicate that heart rate increased with longer negative thought sequences and that this was in the context of elevated subjective anxiety. Longer sequences of positive thoughts were associated with increasing heart rate but also declining subjective anxiety. The findings were interpreted as providing some support for Barlow's model of anxiety; however, the data indicate that relationships among cognition, subjective anxiety, and physiological arousal in phobic anxiety are both complex and dynamic.

Disorders of Emotion: Questions About Clarity and Integration

Nevertheless, we do not find ourselves wholly persuaded by Barlow's model. Two major problems with the current formulation are a lack of clarity in the initial exposition and the doubtful or unclear validity of certain formulations that are clearly stated. In addition, despite Barlow's emphasis on the importance of complex causal models, and on the need to integrate both psychological and biological perspectives, we find his treatment of both these issues ultimately disappointing. We address each of these problematic features of Barlow's model.

Depression and Anxiety: Disorders of Emotion or Cognition?

Based on developments in emotion theory, Barlow presents a model of psychopathological disorders that is both exciting and broad in its theoretical scope. He suggests that disorders of anxiety and depression (as well as anger and mania) are fundamentally disorders and that they have their origins in the inappropriate and spontaneous firing of certain primitive, basic, negative emotions such as fear (panic in its clinical manifestation) and sadness, respectively, in individuals who are biologically overreactive to stressful life events. These spontaneously firing negative emotions or false alarms occur unpredictably; when they do, they may become the focus of perceptions of uncontrollability among individuals who are also psychologically vulnerable to the development of anxiety and depressive disorders. Thus, those persons who possess an overreactive neurobiological response to stressful life events as well as early experiences with lack of control will be likely to develop clinically significant episodes of anxiety or depression when triggered by unexpected bouts of these negative emotions. In Barlow's view, then, anxiety and depressive disorders share common biological and psychological diatheses as well as a common mediating mechanism, perceptions of uncontrollability over bouts of panic or sadness and the development of anxious apprehension about one's ability to cope with future threats. What determines whether a person becomes anxious and remains so, or also develops depression, is the degree of his or her psychological vulnerability, the severity of current stressors, and the availability of coping mechanisms. According to Barlow, whereas the anxious individual continues to try to cope, the depressed individual has given up. In this commentary, I question Barlow's assumption that anxiety and depressive disorders are fundamentally disorders. In addition, I evaluate Barlow's model of emotional disorders with specific reference to the model's ability to account for the relationship between anxiety and depression. In so doing, I compare Barlow's model to another, more fundamentally cognitive, theory of the relationship between some anxiety and depressive disorders (Alloy, Kelly, Mineka, & Clements, 1990).

Toward Further Clarification of Barlow's Model of Depression

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The Concept of Uncontrollability

The capacity to integrate different perspectives of complex phenomena and formulate researchable models is David Barlow's great strength. The current article lays out such a model of emotional disorders (for a more complete elaboration of his ideas, see his recent book, Anxiety and Its Disorders; Barlow, 1988). Barlow's model of the genesis of emotional disorders is ethologically based, with a role for learning, and acknowledgment of the contribution of neurophysiologic processes. Barlow focuses on the role of learned processes and automatic behavioral reactivity, placing particular emphasis on an ongoing sense of uncontrollability as a core psychological disturbance, underlying the development of pathological states of anxiety and depression. Barlow presents empirical evidence from clinical, human experimental, and animal work to support his theory. As usual, his points are tightly argued and well supported. My commentary focuses on an exploration of the concept of sense of control, including thoughts about its definition, its relationship to aggression, and the role interpersonal relationships play in its development and stability. Panic disorder is used to illustrate some potential implications of including the dimension of controllability in clinical and research models.