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Chronic psychological stress and its impact on the development of aggressive breast cancer

  • Universidade Estadual do Oeste do Paraná, Francisco Beltrão

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Objective: To investigate the clinicopathological findings of women diagnosed with breast cancer and study the impact of chronic psychological stress on the pathological characteristics of these tumors. Methods: We investigated a cohort composed of women diagnosed with breast cancer and divided into two groups. One group was categorized as presenting with chronic psychological stress (by using the Self-Reporting Questionnaire - SRQ-20). Another group of women with breast cancer, but with no previous history of chronic psychological stress, comprised the Control Group. Clinical and pathological data were assessed. Results: Women presenting with a history of chronic distress were significantly overweight when compared to the Control Group. Furthermore, it was observed that these stressed women also had a significant percentage of aggressive breast cancer subtype, the HER2 amplified tumor, which could be putatively associated with the loss of immunosurveillance. Conclusion: Our findings suggested an interaction among chronic psychological stress, overweight, and the development of more aggressive breast tumors.
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einstein. 2015;13(3):352-6
Chronic psychological stress and its impact on the
development of aggressive breast cancer
Estresse psicológico crônico e seu impacto no desenvolvimento
de neoplasia mamária agressiva
Thayse Fachin Cormanique1, Lirane Elize Defante Ferreto de Almeida1, Cynthia Alba Rech2,
Daniel Rech2, Ana Cristina da Silva do Amaral Herrera3, Carolina Panis1
Objective: To investigate the clinicopathological findings of women
diagnosed with breast cancer and study the impact of chronic
psychological stress on the pathological characteristics of these
tumors. Methods: We investigated a cohort composed of women
diagnosed with breast cancer and divided into two groups. One group
was categorized as presenting with chronic psychological stress
(by using the Self-Reporting Questionnaire SRQ-20). Another
group of women with breast cancer, but with no previous history of
chronic psychological stress, comprised the Control Group. Clinical
and pathological data were assessed. Results: Women presenting
with a history of chronic distress were significantly overweight
when compared to the Control Group. Furthermore, it was observed
that these stressed women also had a significant percentage of
aggressive breast cancer subtype, the HER2 amplified tumor, which
could be putatively associated with the loss of immunosurveillance.
Conclusion: Our findings suggested an interaction among chronic
psychological stress, overweight, and the development of more
aggressive breast tumors.
Keywords: Stress, psychological; Breast neoplasms; Overweight; Obesity;
Monitoring, immunologic
Objetivo: Investigar os achados clínico-patológicos de mulheres
diagnosticadas com câncer de mama e estudar o impacto do estresse
psicológico crônico nas características patológicas desses tumores.
Métodos: Investigamos uma coorte composta por mulheres
diagnosticadas com câncer de mama divididas em dois grupos. O
primeiro foi classificado pela apresentação de estresse psicológico
crônico (por meio do Self-Reporting Questionnaire − SRQ-20). Outro
grupo de mulheres com câncer de mama, mas sem história prévia
de estresse psicológico crônico, foi denominado Grupo Controle.
Os dados clínicos e patológicos foram avaliados. Resultados:
As mulheres com histórico de estresse crônico apresentaram-se
significativamente acima do peso quando comparadas com o Grupo
Controle. Além disso, verificou-se que estas mulheres estressadas
apresentaram um porcentual significativo de um subtipo de câncer
de mama agressivo, o HER2, o que poderia estar associado à possível
perda da imunovigilância. Conclusão: Nossos resultados sugeriram
uma ligação entre o estresse psicológico crônico, o excesso de peso
e o desenvolvimento de tumores de mama com maior agressividade.
Descritores: Estresse psicológico; Neoplasias da mama; Sobrepeso;
Obesidade; Monitorização imunológica
Breast cancer is a multifactorial disease, consisting of a
public health problem worldwide. Some factors that
interact among themselves contribute to the high
incidence of breast cancer, including family history,
presence of high-susceptibility genes, excessive body
weight, and chronic stress.(1-3)
In this context, chronic psychological stress is a
common finding reported by cancer patients. Stressful
e events are considered important components that can
affect the emotional state of the individuals, and their
association with loss of social support is even related to
significantly shortened survival in breast cancer patie
There is a significant positive association between early life
distress and breast cancer development.(5) Furthermore,
1 Universidade Estadual do Oeste do Paraná, Francisco Beltrão, PR, Brazil.
2 Hospital do Câncer de Francisco Beltrão, Francisco Beltrão, PR, Brazil.
3 Pontifícia Universidade Católica do Paraná, Londrina, PR, Brazil.
Corresponding author: Carolina Panis – Rua Maringá, 1.200 – Vila Nova – Zip code: 85605-010 – Francisco Beltrão, PR, Brazil – Phone: (55 46) 3055-3026 – E-mail:
Received on: Mar 1, 2015 – Accepted on: Aug 10, 2015
Conflict of interest: none.
DOI: 10.1590/S1679-45082015AO3344
Chronic psychological stress and its impact on the development of aggressive breast cancer
einstein. 2015;13(3):352-6
a systematic analysis of some studies published in the
last 30 years, investigating the causal attributions in
breast cancer patients, demonstrated that breast cancer
patient survivors consistently associate their disease
with emotional distress, among another factors.(6)
Concerning the biological impact of chronic distress,
the sustained psychological stress alone can lead to weight
gain through several biological mechanisms,(2) which
may potentially result in loss of immunosurveillance.(7)
Competent immune responses are the major defense
against cancer; therefore, their impairment is strongly
associated with the development of several types
of cancer, including breast tumors that confer poor
Although the relation between cancer development
and chronic stress has been described, little is known
concerning the impact of chronic psychological stress
in the phenotype of breast tumors. To clarify this
question, we investigated if women presenting with
chronic emotional distress could exhibit more aggressive
phenotypes of breast cancer.
To investigate clinicopathological findings from women
diagnosed with breast cancer, and study the impact
of chronic psychological stress in the pathological
characteristics of tumors.
Study design
This study included women living in the State of Paraná,
diagnosed with infiltrative carcinoma of the breast, in
the period from August 2013 to July 2014. They had
been previously scheduled to undergo chemotherapy
on a set day of the week, the same period. The selection
of patients was conducted at the Centro de Oncologia
de Francisco Beltrão (Ceonc), in the city of Francisco
Beltrão (PR), Brazil. The inclusion criteria adopted
were women with infiltrative ductal carcinoma of breast,
uni- or bilateral, diagnosed between August 2013 and
July 2014, eligible according to the Self-Reporting
Questionnaire (SRQ-20) as stress or non-stress cohorts.
To determine the sample size, we applied the following
statistical calculation, in which: N0 = size number,
Z = confidence interval, P = probability, D = error
margin, n = sample size, and N = population size:
Considering that (1) our population was approximately
100 thousand inhabitants; (2) a p value of 0.05; (3)
according to the Instituto Nacional de Câncer estimate,
the incidence of breast cancer in this region was roughly
61 cases per 100 thousand women; (4) there were about
30 thousand women in the age range of risk for breast
cancer in this area, thus, we have that the minimal
sample size of about 18 patients was needed. Taking
into account the period of the study and the fact that
we worked with patients previously scheduled on a fixed
day of the week to undergo chemotherapy, we decided
to include 17 patients in each group. In this context, this
study enrolled 34 women diagnosed with infiltrative
ductal carcinoma of the breast. This study was previously
approved by the Institutional Review Board, and all
participants signed the Informed Consent Form. The
research project was approved by the National Council
of Scientific Research Ethics Committee, under number
497.050 and CAAE: 22027213.7.0000.0107. Clinical
records were assessed and the data collected included
age at diagnosis, weight, height, comorbidities, TNM
classification, and chemotherapy regimen.
For determining the chronic psychological stress
status of patients, we conducted an initial interview to
verify the social support of the patient (family income,
type of residence, level of education, life style, and social
relationships), since we did not know if the patients were
from different social conditions. Because all patients
reported similar socioeconomic data, we continued the
study by applying the SRQ-20 for psychiatric disorder
screening.(9) This interview was applied to patients that
were in the hospital for routine chemotherapy treatment
during the period of the study.
The women enrolled in this study were categorized
into two groups: Control Group (n=17), with women
diagnosed with breast cancer with no previous history of
chronic psychological stress; Stress Group (n=17), with
women diagnosed with breast cancer with a past history
of chronic psychological stress.
Molecular subtyping of breast tumors by immunohis-
to chemistry
Formalin-fixed, paraffin-embedded samples from tumor
biopsies were immunostained with primary antibodies
for estrogen receptor (ER; anti-human estrogen receptor
alpha, clone 1D5 at 1:600; Dako, Dinamarca), progesterone
receptor (PR; anti-human progesterone, clone PGR 636 at
1:500; Dako, Dinamarca), and human epidermal growth
receptor 2 (HER-2, anti-human HER2-pY-1248, clone
PN2A at 1:500; Dako, Dinamarca), in association with
a commercial immunohistochemistry kit. Samples were
einstein. 2015;13(3):352-6
Cormanique TF, Almeida LE, Rech CA, Rech D, Herrera AC, Panis C
considered positive for ER/PR when at least 10% of the
tumor cell nuclei were stained. HER2 was considered
overexpressed when strong membrane staining (3+)
was detected or when amplification of HER2 in samples
with moderate (2+) membrane staining was observed
in Fluorescent in Situ Hybridization (FISH) analysis.
Samples were scored and categorized. They were
considered HER2-positive when the HER2 IHC score
was 3+, and HER-negative when the score was 1+ or
zero. Samples with a 2+ score were analyzed by FISH to
detect HER2 amplification (HER2 FISH pharmDx™;
Dako, Dinamarca). Samples with a 2+ IHC score and
an amplified result in FISH were considered HER2-
positive, while samples with a 2+ IHC score and a non-
amplified in FISH were considered HER2-negative.(10)
Data analysis
For clinicopathological parameters, data were expressed
as the mean ± standard error of the mean. All data were
compared by using the non-parametric Mann-Whitney
test. A p value <0.05 was considered significant. All
statistical analyses were performed using the GraphPad
Prism software version 5.0 (GraphPad Prism Software,
San Diego, CA, USA).
The mean age at diagnosis was 60.2 years. We found that
40% of patients were diagnosed as having breast cancer
by routine mammograms, and 53% reported perception
of nodules in the breasts by self-examination. The
remaining 7% had no palpable nodules, but felt pain in
breast and went to a doctor for this reason. Regarding
the verification of chronic psychological stress (Table 1),
it was observed that 79% reported a history of chronic
psychological stress. The most common traumas
related were death of family members, abandonment
by a partner, employment loss, sexual abuse, and major
depression. Moreover, 73% of patients associated the
occurrence of chronic psychological stress with breast
cancer development. A total of 47% were classified
as potential carriers of psychic disorders by the SRQ-
20. The patients who reported a positive history of
psychological stress were categorized to form the Stress
Aiming to understand the clinicopathological impact
of chronic psychological stress on breast cancer and
clinical features, we compared the data from the Stress
Group with a control cohort, composed of women
diagnosed with breast cancer with no past history of
chronic emotional stress. In this context, figure 1 shows
that the Control Group comprised mainly women with
breast cancer presenting with a normal body mass index
(BMI) (90%). On the other hand, patients from the
Stress Group exhibited a significant predominance of
overweight women (54%; p=0.0041). The molecular
subtyping of breast tumors (Figure 2) indicated the
predominance of HER2 positive tumors in the Stress
Group when compared to controls (31±1.41% versus
12±0.05%; p=0.0136).
Table 1. Main parameters employed for chronic psychological stress characterization
Parameter Mean percentage
Family relationships
Good 85
Types of psychological distress reported
Death of relatives 36
Loss of employment 9
Abandonment by partner 18
Sexual abuse 9
Depression 9
Other emotional distress 19
Received support during the treatment
Yes 93
Presented difficulty for abandoning work
Yes 57
Believes that chronic stress is associated as a cause of
the disease
Yes 73
Risk for developing mental disorders
Yes 47
*Statistically significant difference (p<0.05), Mann-Whitney test; BMI: body mass index.
Figure 1. Analysis of body mass indexes. We used the International
Classification of Body Mass Index to categorize the patients into normal weight
(BMI up to 25kg/m2) or overweight (BMI above 25kg/m2)
Chronic psychological stress and its impact on the development of aggressive breast cancer
einstein. 2015;13(3):352-6
stress and overweight are important risk factors for
breast cancer development.(1,2) Under chronic stress
conditions, there is a systemic rise in cortisol levels,
which increases appetite and favors the storage of lipids
in adipose tissue.(2) This set of biological events that
contributes to weight gain is made up of relevant risk
factors for breast cancer in the modern society,(8) and
may partly help to understand the results found in the
present study. Overweight increases the risk for breast
cancer recurrence after the primary tumor excision, and
significantly reduces the overall survival of patients(13)
by affecting the spreading of breast cancer cells.(14) This
evidence helps to understand the important percentage
of women with locally advanced disease upon diagnosis
in the Stress Group.
It is well-established that chronic inflammation
induced by the excessive availability of lipids found during
overweight and obesity conditions can promote cancer
spreading and aggressiveness, a process mediated by
tumor-driven cytokines.(1) Together, chronic psychological
stress and overweight can impair immunosurveillance
as shown in breast cancer patients by Varker et al.(7)
Altogether, these factors are putative stimuli for developing
breast tumors with aggressive characteristics.
Based on this hypothesis, we investigated the
phenotypic profile of breast tumors in both groups. Our
data revealed that women with a history of psychological
stress displayed a significant percentage of tumors
overexpressing HER2. HER2-amplified breast tumors
promote aggressive disease, with poor prognosis(14-16)
due to its rapid proliferation and spreading.(17,18) These
tumors are reported in overweight/obese women,
which exhibit enhanced disease spreading in relation
to non-obese patients.(8) In this case, the excessive
bioavailability of lipids seems to favor the epithelial
transformation of cells into HER2-amplified neoplastic
cells.(19) Menendez(20) demonstrated that HER2 cancers
take advantage of lipids as their energy source, which
is strongly favored in environments rich in fat, such as
the breast tissue of overweight or obese women. We
further observed that most patients presented with
the HER2-amplified tumor mass located in the left
breast. The left mammary gland frequently presents
more breast tissue than the right, which may benefit fat
accumulation and cancer development.(21)
These data support the hypothesis that the women
enrolled in the present study have a complex chain formed
by historical factors of psychological stress, over
and development of phenotypically aggressive breast
tumors. Our preliminary findings suggest a “vicious circle”
involving chronic psychological stress, overweight, and
breast cancer aggressiveness.
HER2: human epithelial growth factor receptor 2; TN: triple negative tumors. *Significant statistical difference (p<0.05),
Mann-Whitney’s test.
Figure 2. Molecular subtyping of tumors. The images represent the IHC labeling
for HER2
For the last years, breast cancer has been the leading
malignant neoplasm in women worldwide. This fact
deserves attention, since the list of risk factors related
with this disease is growing. Our aim was to investigate
women diagnosed with breast cancer who reported
a past history of chronic psychological stress and its
impact on clinicopathological aspects of breast cancer.
To reach this goal we initially applied the SRQ-20 as a
psychiatric screening tool to compose the stress cohort.
The SRQ-20 is an instrument developed by the World
Health Organization (WHO) to screen psychiatric disorders
in patients. It detects symptoms, such as anxiety, depression,
and psychosomatic complaints with adequate accuracy.
The SRQ-20 was previously applied and validated in
the Brazilian population,(9) including breast cancer
patients.(12) Our data demonstrated that about 47% of
patients seen during the period of the SRQ-20 application
were categorized as presenting with psychiatric distress
and included in the Stress Group.
We further selected another cohort of patients who
had a similar clinical history (age at diagnosis, family
history, general health status, and family income), but
with no prior report of chronic psychological stress to
compose the Control Group. We employed this approach
aiming to compare the impact of chronic emotional
distress on clinical and pathological characteristics
of breast tumors, in both groups. Our data indicated
that a significant portion of the women enrolled in
the Stress Group were overweight when compared
to those of the Control Group. Both psychological
einstein. 2015;13(3):352-6
Cormanique TF, Almeida LE, Rech CA, Rech D, Herrera AC, Panis C
The main limitations of our study included the small
sample size and the need for a long-term follow-up of
patients to examine the recurrence of the disease and
responsiveness to chemotherapy.
Our data suggest that chronic psychological stress may
represent a considerable risk factor for weight gain and
development of aggressive tumors in women diagnosed
with breast cancer, such as human epidermal growth
factor receptor 2-amplified breast tumors.
The authors are grateful to the Conselho Nacional
de Desenvolvimento Científico e Tecnológico (CNPq)
for grant support, and to the Centro de Oncologia de
Francisco Beltrão (Ceonc) staff for providing excellent
technical support.
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... Women newly diagnosed with BC have elevated levels of depression and anxiety [38], and thus are particularly susceptible to experiencing the downstream effects of the stress response. Notably, OW/OB women with BC are more likely to have a history of chronic stress [39]. Therefore, OW/OB women with newly diagnosed BC are highly susceptible to experience increased inflammation due to chronic and acute stress, as well as increased adiposity. ...
... Thus, although both OW/OB and NW women receiving stress management interventions reported significantly greater confidence in their ability to manage stress, unique processes occurred within OW/OB women resulting in decreased IL-6 levels over the study period. It is likely that OW/OB women, who presented with significantly higher IL-6 at baseline, were more able to benefit physiologically from a stress management intervention due to the co-occurring, and potentially interacting, effects of acute stress [38], chronic stress [39], and adiposity [24][25][26][27][28][29] on neuroendocrine regulation and inflammation. Providing coping and relaxation techniques may have been more impactful in this particularly vulnerable population. ...
Background: Overweight and obese (OW/OB) body mass index (BMI) is associated with greater inflammation and poorer outcomes in breast cancer (BC). Stress management interventions using cognitive behavioral therapy (CBT) and relaxation training (RT) have reduced inflammation in BC patients but have not been tested specifically in OW/OB patients undergoing primary treatment. We developed brief CBT and RT-based group interventions and tested their effects (vs time-matched Health Education [HE] control) on serum inflammatory cytokines (IL-6, IL-1β and TNF-α) in OW/OB vs normal weight (NW) BC patients during primary treatment. We hypothesized OW/OB women would show higher levels of inflammatory cytokines, and that stress management would decrease these cytokines more in OW/OB women than in NW women. Methods: Stage 0 - III BC patients were enrolled post-surgery and before initiating adjuvant therapy, were randomized to either 5 weeks of CBT, RT, or HE, and provided questionnaires and blood samples at baseline and 6-months. Serum cytokine levels were measured by ELISA. Repeated measures analysis of variance tested the interaction of condition by BMI by time in predicting cytokine levels over 6 months, controlling for age, stage, ethnicity, and income. Results: The sample (N = 153) majority was OW/OB (55.6%). We found differences in baseline IL-6 and IL-1β across BMI categories, with greater IL-6 (p < 0.005) and IL-1β (p < 0.04) in OW and OB vs NW women, but no difference between OW and OB women. There were no differences in baseline TNF-α among BMI groups. BMI category moderated the effect of brief stress management interventions on IL-6 changes over 6-months (p = 0.028): CBT/RT vs HE decreased IL-6 in OW/OB (p = 0.045) but not in NW patients (p = 0.664). There were no effects on IL-1β or TNF-α. Results could not be explained by differences in receipt of adjuvant therapy, prescription medications, or changes in physical activity. Conclusions: OW/OB women with newly diagnosed BC had significantly greater serum IL-6 and IL-1β than NW women post-surgery. Brief stress management delivered with primary treatment among OW/OB patients may reduce the increases in inflammatory markers known to accompany adjuvant treatments and could thus promote better outcomes. Clinical trial registration: NCT02103387.
... Clinical and epidemiological data of breast cancer in the past 30 years have suggested that chronic psychological stress is a risk factor for the development and metastasis of breast cancer (Cormanique et al., 2015;Joshi et al., 2018). However, there is limited information on how chronic psychological stress affects the metastasis and prognosis of breast cancer. ...
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Chronic psychological stress is closely correlated with breast cancer growth and metastasis. Sini San (SNS) formula is a classical prescription for relieving depression-related symptoms in traditional Chinese medicine (TCM). Current researches have suggested that chronic psychological stress is closely correlated with cancer stem cells (CSCs) and endoplasmic reticulum (ER) stress. This study aimed to investigate the effects of chronic psychological stress on ER stress-mediated breast cancer stemness and the therapeutic implication of SNS. Chronic psychological stress promoted lung metastasis in 4T1 breast tumor-bearing mice and increased the stem cell-like populations and stemness-related gene expression. Meanwhile, GRP78, a marker of ER stress, was significantly increased in the breast tumors and lung metastases under chronic psychological stress. As a biochemical hallmark of chronic psychological stress, cortisol dramatically enhanced the stem cell-like populations and mammospheres formation by activating GRP78 transcriptionally. However, GRP78 inhibitors or shRNA attenuated the stemness enhancement mediated by cortisol. Similarly, SNS inhibited chronic psychological stress-induced lung metastasis and stemness of breast cancer cells, as well as reversed cortisol-induced stem cell-like populations and mammospheres formation by attenuating GRP78 expression. Co-localization and co-immunoprecipitation experiments showed that SNS interrupted the interaction between GRP78 and LRP5 on the cell surface, thus inhibiting the Wnt/β-catenin signaling of breast CSCs. Altogether, this study not only uncovers the biological influence and molecular mechanism of chronic psychological stress on breast CSCs but also highlights SNS as a promising strategy for relieving GRP78-induced breast cancer stemness via inhibiting GRP78 activation.
... BC is one of the most studied types of cancer from the psychosomatic point of view, mainly because it is one of the most prevalent in the female population. Cormanique et al. (2015), using the Self-Reporting Questionnaire (SRQ-20) scale, developed by the World Health Organization (WHO) to screen for psychiatric disorders, showed that women with a previous history of chronic stress has a higher prevalence of the HER2 BC subtype. Dourado et al. (2018) showed an association between stressful life events after BC diagnosis, using the Holmes and Rahe Stress Scale, and the development of metastasis. ...
Full-text available
The clinical course of breast cancer (BC) and survival depend on a wide range of risk factors. From the psychosomatic point of view, BC is one of the most studied type of cancer but there is no evidence available for this relation. Therefore, in the present study we evaluate the impact of chronic life stressors in BC patients. A total of 100 BC patients were invited to participate in an interview, when information about social parameters and emotional changes in the period prior to diagnosis were collected. The emotional changes were evaluated by the Holmes and Rahe's Stress Scale, which analyzes the difficulty required for a person to readjust to society after significant changes in their life. Clinicopathological parameters were obtained from the medical records. For all data, the level of significance adopted was p <0.05. It was observed that 55.2 % of the patients have a medium and 13.8 % were at high risk for disease development related to stressful events in the period prior to the BC diagnosis. The highest stress levels were presented by separated, divorced, or widowed patients compared to married (p <0.01) and single (p = 0.037) patients. The high-risk (HR) group had a lower proportion of positivity for estrogen receptor when compared to the low (LR) and moderate risk (MR) groups (p= 0.001). In addition, a binary logistic regression analysis was performed, and we found that the relationship between the estrogen receptor and the HR of chronic stress was independently associated with the histological type of BC and lymph nodes involvement. The relationship of stressful life experiences and BC is not well established, so our study collaborates with the literature to demonstrate the importance of stress as a factor associated with the development of BC.
... Так, P. Revidi, T. Cormanique и соавт. приходят к выводу, что рак молочной железы возникает в результате сочетания таких особенностей, как склонность к депрессивным реакциям и чувству вины, неуверенность в себе, наличие длительного стресса, высокий уровень личностной тревожности и сдержанность в проявлении эмоций [9,10]. В исследованиях J. Fasano et al. подчеркивается, что женщин, заболевших раком молочной железы, отличают подавление гнева и использование отрицания в качестве способа преодоления стресса [11]. ...
The problem of survival and effectiveness of treatment for cancer is an urgent and socially significant task of modern science. Today, medicine is focused on improving the survival rate of patients with malignant neoplasms, increasing their life expectancy, and maintaining the life quality of this category of patients. Support for cancer patients is a priority in medical and psychological research, in which it is particularly important to identify the prerequisites of the disease, survival factors and psychological resources for adaptation to the disease. Breast cancer is accompanied by strong emotional stress, has a psychotraumatic effect on the patient and affects many aspects of life. The role of coping with the diagnosis, as well as with the stress caused by a long treatment process, is currently insufficiently studied. In this regard, the purpose of this work was to study coping behavior in women with breast cancer for a period of up to six months after diagnosis. It was a longitudinal study that last for three years. This article reflects the results of the first section of our study. We have found that women with breast cancer tend to suppress emotional responses and control their own experiences. When studying the age-related features of coping behavior, we found that 30-to 40-year-old women are more likely to use avoiding, social and confrontational coping than older women. Married women prefer to look for positive aspects in the current difficult life conditions, rather than unmarried. Coping behavior of women who have a job differs from coping behavior of women who have no job. The former are more likely to use such strategies as Confrontational coping, Search for social support, Escape-avoidance, Planning a solution to the problem. In addition, we found that the level of education is associated with the choice of coping strategies. For example, women with higher education tend to plan for resolving difficulties, maintain self-control, seek conditional benefits from the current situation, and are more likely to seek social support than women with secondary vocational education. The study of coping behavior in women with breast cancer as part of a longitudinal study reveals the specifics and dynamics of overcoming difficulties at the initial and subsequent stages of treatment. The identified differences will serve as the basis for creating a program for developing coping behavior and a program for psychological support of patients with cancer, as well as for further empirical study of other psychological factors of survival and disease course in patients with malignant neoplasms.
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Introduction Due to the high incidence and aggressiveness of breast cancer, understanding specific factors associated with the profile of the disease is necessary. Thus, the study aimed to analyze data from 155 patients with breast cancer, grouping them according to their clinicopathological characteristics, attended at a reference hospital for Oncology, in 2015–2020, in the southwest region of Paraná, Brazil. Material and Methods Using multivariate statistical analysis, sample data were divided into three clusters. The heterogeneity between clusters was obtained by Ward's method. The clinicopathological variables obtained from the patients' medical records were: the presence of intratumoral emboli and lymph nodes, menopausal status, molecular subtype, histological grade, TNM staging of the disease, tumor size, age at diagnóstico, weight, height, and body mass index. Results It is observed that 70% of the patients were in menopause at diagnóstico, 31.5% had tumors containing emboli, and 41% had positive lymph nodes. The prevalence of Luminal B subtype, intermediate histological grade, and TNM staging II was verified. The prevalence of the disease was higher in women aged over 50 years, representing 66% of cases. The BMI of the patients ranged from 17.63 kg/m2 to 51.26 kg/m2, with 73.55% above 25 kg/m2. Using the spatial distribution of patients, cluster analysis identified the regions with the worst averages of clinicopathological variables and the highest number of cancer cases. Conclusion Through the statistical analysis, it was possible to determine the heterogeneity of the data, so the patients were separated into three clusters. When analyzing the obtained clusters, each one of them had specific characteristics.
Cancer research has been largely focused on the cellular and molecular levels of investigation. Recent data show that not only the cell but also the extracellular matrix plays a major role in the progression of malignancy. In this way, the cells and the extracellular matrix create a specific local microenvironment that supports malignant development. At the same time, cancer implies a systemic evolution which is closely related to developmental processes and adaptation. Consequently, there is currently a real gap between the local investigation of cancer at the microenvironmental level, and the pathophysiological approach to cancer as a systemic disease. In fact, the cells and the matrix are not only complementary structures but also interdependent components that act synergistically. Such relationships lead to cell-matrix integration, a supracellular form of biological organization that supports tissue development. The emergence of this supracellular level of organization, as a structure, leads to the emergence of the supracellular control of proliferation, as a supracellular function. In humans, proliferation is generally involved in developmental processes and adaptation. These processes suppose a specific configuration at the systemic level, which generates high-order guidance for local supracellular control of proliferation. In conclusion, the supracellular control of proliferation act as an interface between the downstream level of cell division and differentiation, and upstream level of developmental processes and adaptation. Understanding these processes and their disorders is useful not only to complete the big picture of malignancy as a systemic disease, but also to open new treatment perspectives in the form of etiopathogenic (supracellular or informational) therapies.
An iterated version of the game "Prisoner's Dilemma" is used as a model of cooperation largely due to the wide range of strategies that the subjects can use. The problem of the effec-tiveness of strategies for solving the Iterated Prisoner's Dilemma (IPD) is most often considered from the point of view of information models, where strategies do not take into account the relationship that arise when real people play. Some of these strategies are obvious, others depend upon social context. In our paper, we use one of the promising directions in the development of studying IPD strategies – the use of artificial neural networks. We use neural networks as a modeling tool and as a part of game environment. The main goal of our work is to build an information model that predicts the behavior of an individual person as well as group of people in the situation of solving of social dilemma. It takes into account social relationship, including those caused by experimental influence, gender differences, and individual differences in the strategy for solving cognitive tasks. The model demonstrates the transition of individual actions into socially determined behavior. Evaluation of the effect of socialization associated with the procedure of the game provides additional information about the effectiveness and characteristics of the experimental impact.The paper defines the minimum unit of analysis of the IPD player's strategy in a group, the identity with which can be considered as a variable. It discusses the influence of the experi-mentally formed group identity on the change of preferred strategies in social dilemmas. We use the possibilities of neural networks as means of categorizing the results of the prisoner's iterative dilemma in terms of the strategy applied by the player, as well as social factors. We define the patterns of changes in the IPD player's strategy before and after socialization are determined. The paper discusses the questions of real player's inclination to use IPD solution strategies in their pure form or to use the same strategy before and after experimental inter-ventions related to social identity formation. It is shown that experimentally induced socialization can be considered as a mechanism for increasing the degree of certainty in the choice of strategies when solving IPD task. It is found out that the models based on neural networks turn out to be more efficient after experi-mentally evoked social identity in a group of 6 people; and the models based on neural net-works are least effective in the case of predicting a subject's belonging to a gender group. When solving IPD problems by real people, it turns out to be possible to talk about generalized strategies that take into account not only the evolutionary properties of «pure» strategies, but also reflect various social factors.
Background: Chronic stress has been investigated as a risk factor for breast cancer. Maternal separation (MS) of rats has been used as a chronic stress model that alters certain systemic functions, such as the immune response. Objective: The aim of this study was to determine the possible effect of MS on the development of breast tumors induced by 7,12-dimethyl benzo anthracene (DMBA). Methodology: postnatal day (PND) 1 female Wistar rats were divided into four experimental groups that either were or were not subjected to MS and either received or did not receive DMBA. For MS, PND 1 to 21 pups were separated from their mothers for 360 min/day. On PND 30, carcinomas were induced in mammary glands using DMBA. Body weight was evaluated, and the injected region was palpated. In addition, the mammary glands were subjected to histological examination, and corticosterone levels were determined in all groups. Results: DMBA-induced groups had significantly lower body weight gain compared with the non-DMBA-induced groups. Maternal separation increased the incidence of preneoplastic changes and breast carcinogenesis in DMBA-treated animals compared with control animals. Corticosterone levels were increased in both DMBA-induced and MS groups without interaction. Conclusion: MS is a possible risk factor for DMBA-induced preneoplastic changes and breast tumors in rats.
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Over the past 30 years the World Health Organization (WHO) has produced a number of assessment instruments intended for national and cross-cultural psychiatric research. WHO instruments have been tested and used in many collaborative studies involving more than 100 centres in different parts of the world. This article reviews the main WHO instruments for the assessment of (a) psychopathology, (b) disability, quality of life and satisfaction, (c) services, and (d) environment, and risks to mental health. The principles used in the development of WHO instruments, their translation and their use across cultures and settings are discussed.
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Stress causes or contributes to a huge variety of diseases and disorders. Recent evidence suggests obesity and other eating-related disorders may be among these. Immediately after a stressful event is experienced, there is a corticotropin-releasing-hormone (CRH)-mediated suppression of food intake. This diverts the body's resources away from the less pressing need to find and consume food, prioritizing fight, flight, or withdrawal behaviors so the stressful event can be dealt with. In the hours following this, however, there is a glucocorticoid-mediated stimulation of hunger and eating behavior. In the case of an acute stress that requires a physical response, such as a predator-prey interaction, this hypothalamic-pituitary-adrenal (HPA) axis modulation of food intake allows the stressful event to be dealt with and the energy used to be replaced afterward. In the case of ongoing psychological stress, however, chronically elevated glucocorticoids can lead to chronically stimulated eating behavior and excessive weight gain. In particular, stress can enhance the propensity to eat high calorie "palatable" food via its interaction with central reward pathways. Activation of this circuitry can also interact with the HPA axis to suppress its further activation, meaning not only can stress encourage eating behavior, but eating can suppress the HPA axis and the feeling of stress. In this review we will explore the theme of eating behavior and stress and how these can modulate one another. We will address the interactions between the HPA axis and eating, introducing a potential integrative role for the orexigenic hormone, ghrelin. We will also examine early life and epigenetic modulation of the HPA axis and how this can influence eating behavior. Finally, we will investigate the clinical implications of changes to HPA axis function and how this may be contributing to obesity in our society.
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Women are more likely to develop cancer in the left breast than the right. Such laterality may influence subsequent management, especially in elderly patients with heart disease who may require radiation therapy. The purpose of this study was to explore possible factors for such cancer laterality. In this work, clinical data for consecutive patients with histologically confirmed breast cancer were reviewed, with emphasis on clinical presentation and family history. Between 2005 and 2012, 687 patients with breast cancer were seen. Two women with incomplete data and eleven men were excluded. In total, 343 (50.9%) patients presented with left breast cancer, 311 (46.1%) with right breast cancer, and 20 (3.0%) with simultaneous bilateral malignancy. There were no significant differences between the three groups, especially in regards to clinical presentation and tumor characteristics. A total of 622 (92.3%) patients had unilateral primary, 20 (3.0%) had simultaneous bilateral, and 32 (4.7%) had metachronous primary breast cancer with subsequent contralateral breast cancer after 7.5-236 months. The worst 10-year survival was for bilateral simultaneous (18%) compared with unilateral (28%) and metachronous primaries (90%). There were no differences in survival in relation to breast cancer laterality, handedness, and presence or absence of a family history of cancer. There were significant similarities between patients and first-degree relatives in regards to breast cancer laterality, namely same breast (30/66, 45.5%), opposite breast (9/66, 13.6%), and bilateral cancer (27/66, 40.9, P=0.01163). This was more evident among patients and their sisters (17/32, 53.1%) or mothers (11/27, 40.7%, P=0.0689). There were also close similarities in relation to age at initial diagnosis of cancer for patients and their first-degree relatives for age differences of ≤5 years (48/166, 28.9%), 6-10 years (34/166, 20.5%), and >11 years (84/166, 50.6%, P=0.12065). High similarities between patients and their first-degree relatives in regards to cancer laterality and possibly age at initial diagnosis of cancer may suggest an underlying inherited genetic predisposition.
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Purpose: Although many studies have shown association of obesity and tumor size, the association with the lymph node status is not clear. We examined the relationship of the lymph node status and obesity and other possible factors in early breast cancer patients. Methods: In this retrospective cohort study, 1295 breast cancer patients who had axillary dissection were included. Patients were grouped according to their body mass index (BMI) values at the time of diagnosis. We analyzed the relationship between BMI and patient and tumor characteristics, especially lymph node status. Results: The median patient age was 48 years (range 20- 84). Of the patients 69.6% had modified radical mastectomy and the remaining 30.4% had breast-conserving surgery and axillary dissection. Median BMI of the patients was 27.2 kg/m(2) and 33.1% (N-429) of them had normal BMI, 36% (N-471) were overweight and 30.5% (N=395) were obese at the time of the diagnosis. Of the patients, 44.2% had N0 disease, and 55.8% had lymph node metastasis. N1 disease had 28.3% (N=367), 13.8% (N=179) had N2 and 13.7% (N=177) had N3 disease. When patients were classified as normal (≤24.9 kg/m(2)) and obese (>24.9 kg/m(2)) group, the total number of lymph nodes removed was higher in the obese group and this difference was statistically significant (18.12±10.48 and 20.36±11.37, respectively, p= 0.001). There was strong correlation between the number of the dissected lymph nodes and BMI (r=0.11; p<0.001). However, there was no statistically significant correlation between the number of metastatic lymph nodes and BMI. The mean number of the dissected and involved lymph nodes was higher in the HER2 positive group compared to the negative ones (21 vs 19, p=0.008; 6 vs 3, p<0.001; respectively) Conclusion: The number of the dissected lymph nodes was slightly higher in obese patients but there was no correlation between metastatic lymph node number and BMI. The number of the dissected and involved lymph nodes was higher in the HER2 positive group.
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Research examining immune function during obesity suggests that excessive adiposity is linked to impaired immune responses leading to pathology. The deleterious effects of obesity on immunity have been associated with the systemic proinflammatory profile generated by the secretory molecules derived from adipose cells. These include inflammatory peptides, such as TNF- α , CRP, and IL-6. Consequently, obesity is now characterized as a state of chronic low-grade systemic inflammation, a condition considerably linked to the development of comorbidity. Given the critical role of adipose tissue in the inflammatory process, especially in obese individuals, it becomes an important clinical objective to identify lifestyle factors that may affect the obesity-immune system relationship. For instance, stress, physical activity, and nutrition have each shown to be a significant lifestyle factor influencing the inflammatory profile associated with the state of obesity. Therefore, the purpose of this review is to comprehensively evaluate the impact of lifestyle factors, in particular psychological stress, physical activity, and nutrition, on obesity-related immune function with specific focus on inflammation.
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About 20 % of breast cancer patients over-express the human epidermal growth factor receptor-2 (HER2), which is associated with enhanced tumor malignancy. The influence of HER2 overexpression on oxidant/antioxidant parameters in humans remains unknown; therefore, we investigated the oxidative profile in women according to their HER2 status. Fifty-two controls and 52 breast cancer (BC) patients were enrolled. The BC patients were subdivided into HER-, negative for HER2 overexpression, and HER+, positive for HER2 overexpression. Oxidative stress profilling was measured by malondialdehyde (MDA), free 8-isoprostane F2, protein carbonyl content, nitric oxide (NO), total radical antioxidant parameter (TRAP), superoxide dismutase (SOD), catalase activity, and glutathione (GSH) levels. Total thiol content and lipoperoxidation were evaluated in HCC1954 and MCF-7. Cells overexpressing HER2 presented enhanced oxidative stress. Increased erythrocyte lipoperoxidation was found in BC patients, while plasma lipoperoxidation was detected in both the BC and HER- groups. Decreased MDA levels were found in the HER+ group, suggesting that HER2 overexpression may protects against plasma lipoperoxidation. No alteration was found for 8-isoprostane F2, NO, and carbonyl content. TRAP was decreased in BC patients, while HER2 overexpression increased SOD and prevented decreased GSH levels. These data help to understand the HER2 overexpression in oxidative signaling and may enable the development of new strategies for anti-HER2 therapy.
Obesity and overweight are established risk factors for the development of breast cancer. They are also associated with poor prognosis for higher risk of disease recurrence and lower overall survival (OS). The aim of this study was to evaluate the influence of overweight and obesity in OS in patients with locally advanced breast cancer (LABC) treated with neoadjuvant chemotherapy. This is a retrospective analysis that included 819 patients diagnosed with LABC between January 2004 and December 2008. The patients were treated with neoadjuvant chemotherapy (NAT) based on anthracyclines, taxanes, or both, followed by surgery. For comparison, patients were divided into the normal weight (NW) group or the overweight/obesity (OW/OB) group. The prevalence of overweight/obesity was 74 %. General characteristics of the patients, including age, tumor size, clinical stage, nuclear grade, hormone receptors, and HER2 expression, were similar between both groups. At a median follow-up of 28 months, we found a statistically significant difference in OS between the two groups, achieving a 91.5 % in NW patients versus 85.9 % in the OW/OB group (P = 0.050). Cox multivariate analysis demonstrated that obesity was an independent factor for poor prognosis, with a hazard ratio of 1.79 (95 % CI (Confidence Interval) 1.09-2.96; P = 0.022). This is the first Mexican study that confirms the role of OW/OB as a risk factor for poor outcome among patients with LABC. Obesity in our country is a public health problem and requires strong preventive intervention strategies for its control, especially among patients diagnosed with breast cancer.
The aim of this paper was to review published research that analyzed causal attributions for breast cancer among women previously diagnosed with breast cancer. These attributions were compared with risk factors identified by published scientific evidence in order to determine the level of agreement between cancer survivors' attributions and expert opinion. A comprehensive search for articles, published between 1982 and 2012, reporting studies on causal attributions for breast cancer among patients and survivors was undertaken. Of 5,135 potentially relevant articles, 22 studies met the inclusion criteria. Two additional articles were sourced from reference lists of included studies. Results indicated a consistent belief among survivors that their own breast cancer could be attributed to family history, environmental factors, stress, fate, or chance. Lifestyle factors were less frequently identified, despite expert health information highlighting the importance of these factors in controlling and modifying cancer risk. This review demonstrated that misperceptions about the contribution of modifiable lifestyle factors to the risk of breast cancer have remained largely unchanged over the past 30 years. The findings of this review indicate that beliefs about the causes of breast cancer among affected women are not always consistent with the judgement of experts. Breast cancer survivors did not regularly identify causal factors supported by expert consensus such as age, physical inactivity, breast density, alcohol consumption, and reproductive history. Further research examining psychological predictors of attributions and the impact of cancer prevention messages on adjustment and well-being of cancer survivors is warranted.
While early-life exposure to stress has been associated with subsequent psychiatric and cardiovascular morbidity, little is known regarding its potential role in cancer development. We hypothesized that severe emotional stress, such as the loss of a parent through death during childhood, may increase the risk of cancer in early life. Based on the Swedish Multi-Generation Register, we identified a cohort of 4,219,691 individuals who had both parents identifiable in the same register and followed the cohort from birth to the age of 40 years between 1961 and 2006. Through information retrieved from the Swedish Causes of Death and Cancer Registers, we ascertained death among the parents and cancer diagnosis among the cohort individuals. We used Poisson regression to calculate the relative risks (RRs) and 95 % confidence intervals (CIs). Parental death was not associated with total cancer risk. However, parental death during childhood was associated with a higher risk of human papillomavirus (HPV) infection-related cancers (RR 1.4; 95 % CI 1.2-1.7), and loss during early adulthood (>18 years) entailed a higher risk of cancers of the stomach (RR 1.8; 95 % CI 1.3-2.6), lung (RR 1.7; 95 % CI 1.1-2.4), rectum (RR 1.4; 95 % CI 1.0-2.0), and breast (RR 1.1; 95 % CI 1.0-1.3). A significant association was observed for pancreatic cancer for both loss during childhood (RR 2.6; 95 % CI 1.6-4.2) and afterward (RR 2.8; 95 % CI 1.9-4.3). Our results suggest that severe psychological stress in early life may be associated with premature development of certain malignancies, particularly cancers related to smoking and HPV infection.
Obesity is a major negative determinant of breast cancer outcome. However, there are contrasting data on the differential impact of obesity on specific breast cancer subtypes. In particular, very little is known on human epidermal growth factor receptor 2-positive (HER2+) tumours. We assessed the prognostic role of increased body mass index (BMI) on a consecutive series of non-metastatic HER2+ patients treated at our institution before the introduction of adjuvant Trastuzumab. We separately analysed oestrogen receptor-positive (ER+) and -negative (ER-) HER2+ cases. In ER-/HER2+ tumours we observed a significantly worse overall survival (Hazard ratio (HR) 1.79, p-value 0.041) and cumulative incidence of distant metastases (HR 2.03, p-value 0.019) in obese (BMI>30) versus normal/underweight (BMI<25) patients. Local relapses appeared to be non-significantly reduced in obese patients, masking the overall effect on disease-free survival. Outcome in ER+ tumours, instead, was not significantly different between BMI groups. Obesity significantly correlates with worse overall survival and cumulative incidence of distant metastases in ER-/HER2 positive breast cancer. Differences in the biology of breast tumours may determine individual susceptibility to obesity. The biology of the underlying tumour should be taken into account in the design of dietary intervention trials in breast cancer.