The Clinical, Biological, Psychological and Psychiatric Impact of the Diagnosis of Breast Cancer in Women.

OBJECTIVE: Psychosocial factors are correlated with the risk of breast cancer, by the lack of externalization of feelings and aggressive tendencies, or with a negative prognosis, by the presence of a high level of stress and reduced coping abilities. Impairment of psychological status should be assessed early to identify quantifiable psychooncological changes, such as depression, anxiety, and self-esteem. These indicators, measured in this study, may become psychometric markers for predicting the existence of the neoplastic process, prior to histopathological evaluations.
METHODS: 58 patients diagnosed with breast cancer and in different stages of evolution and 61 breast lumps patients were evaluated for depression, anxiety and self-esteem.
RESULTS: The correlation of depression and anxiety levels according to the evolutionary stage of the disease was as follows: in stage I cases of severe depression with significant anxiety predominate, in stage II mild depression predominates with insignificant anxiety, in stage III depression predominates moderate with significant anxiety, while in stage IV moderate depression with significant anxiety predominates.
CONCLUSIONS: The presence of significant anxiety in the uncertainty phase and the anxious-depressive clinical picture can be an alarm signal for the initiation of specific psychotherapeutic strategies, to increase the adaptive potential and resilience to the disease to ensure a therapeutic collaboration of the patient by increasing adherence and compliance. the proposed therapeutic plan. Relatively sudden anxiety in a young woman, risk factors for breast cancer, and deficient cognitive impairment require intensified clinical and paraclinical investigations to confirm early oncological diagnosis.

Introduction

Breast cancer in women is a real public health problem globally due to the high incidence (11.7% of all cancer cases), the death rate (6.9% of all cancer deaths), but also the psychological and social impact [1].

In contrast to the imperative requirements for early detection of this condition and the assessment of risk factors for the disease, the possible predictors of the evolutionary pathways of breast cancer, from the prodromal stages, are little evaluated.

In addition to physical problems, in patients with a definite diagnosis of breast cancer, following histopathological examination, emotional or mental changes were highlighted, the most common being depression, anxiety, decreased resilience to stress, cognitive dysfunction and impaired maladaptive schemas [2,3,4,5].

The presence of psychoemotional and psychosocial disorders in the context of a cancer diagnosis and the perspective of specific oncological treatment requires an early assessment of emotional status and coping capacity, especially in the case of identifying vulnerabilities specific to each patient (history of mental trauma, distress, psychological or psychological changes, and quality of life).

This screening, based on specific psychooncological tools, helps to improve the perception of the disease and the patients’ mechanisms of adaptation to the cancer diagnosis [6].

Among the risk factors associated with depression, such as socio-demographic, somatic, psychological or social, psychosocial factors have the most important role in triggering or worsening depressive symptoms in cancer patients.

Assessing the risk of depression and providing early psychooncological support can bring benefits to patients' adherence to and compliance with treatment, as well as to the prognosis of cancer [7].

Psychosocial factors are correlated with the risk of breast cancer, by the lack of externalization of feelings and aggressive tendencies, or with a negative prognosis, by the presence of a high level of stress and reduced coping abilities [8,9].

Depressive disorder is also a major public health problem, and, through its multisystemic pathogenic mechanisms, it is a real "gateway" to neoplastic pathology, especially for breast cancer.

Depression is an important risk factor for both the onset of an oncological condition and its recurrence and unfavorable evolution [10,11].

Hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis and excess endogenous cortisol cause a severe decrease in immune mechanisms in contrast to excessive increase in proinflammatory factors and endothelial dysfunction [12].

Thus, since the preclinical phases of oncological disease, psychooncological assessments that highlight depressive or anxious personality traits associated with changes in cognitive patterns, especially in the context of the presence of biological markers such as interferon-γ, interleukins (IL) IL-2, IL-6, IL-10 [13,14,15], may anticipate a major risk for breast cancer.

This risk may be increased in patients with a personal history of depressive episodes who have required specialist pharmacological treatment and who have elevated serum prolactin levels [16].

Based on these premises, we consider useful the psychooncological interpretation in two different clinical circumstances.

The first situation refers to the presence of minimal clinical indicators that may suggest a suspicion of breast cancer in women, and the second is the certainty of the cancer diagnosis by histopathological confirmation.

Thus, the psychooncological evaluation acquires a particular and important dimension in the management of any psychotraumatic moment and, through personalized early interventions, can determine the correct decisions by patients, increase self-esteem, increase active contribution and involve patients in cancer and rehabilitation therapeutic programs.

In this context, based on our clinical experience, we believe that impairment of psychological status should be assessed early to identify quantifiable psychooncological changes, such as depression, anxiety, and self-esteem.

These indicators, measured in this study, may become psychometric markers for predicting the existence of the neoplastic process, prior to histopathological evaluations.

The validity of these indicators followed during our study seems to be significant for the different stages of the disease evolution, the most important change of this type appearing in the uncertainty phase of the disease.

Identifying psychooncological factors and recognizing their predictive validity could significantly shorten the diagnosis period, as well as prepare patients for increased resilience to psychotrauma of the disease.

Material and Method

The aim of this study was to identify particular psychooncological aspects depending on the emotional behavior of patients when diagnosed with breast cancer, following histopathological confirmation.

In this regard, 58 patients diagnosed with breast cancer in different stages of evolution (group A) were enrolled in the study, in which depression, anxiety and self-esteem were assessed.

From a clinical, histopathological and neuroimaging point of view, the patients included in the study group were diagnosed in different evolutionary stages (stage I, II, III and IV), according to the oncological classifications.

All patients in this group were to have surgery, adapted to each stage of evolution.

In order to make a comparative analysis of the psychological status, 61 breast lumps patients were introduced in the study and evaluated with the same questionnaires, who were in the period of diagnostic uncertainty, after the biopsy was collected and before receiving the histopathological result (group B).

For patients diagnosed with breast cancer, the data obtained after the evaluation of each psychosociological indicator were correlated with the evolutionary stages of breast cancer, according to the oncological classifications.

Being in the waiting period for the histopathological result, the patients from group B were placed in a psychooncological stage of uncertainty.

This study received approval of the Committee for ethics and academic and scientific deontology of the University of Medicine and Pharmacy of Craiova, Romania (70/02.04.2019).

At the time of enrollment in the study, all patients signed informed consent.

The evaluation scales used were: The Hamilton Anxiety Rating Scale (HARS or HAM-A) [17], Hamilton Depression Rating Scale (HDRS or HAM-D) [18], The Rosenberg self-esteem scale (RSES) [19].

The questionnaires were completed by all patients, with no time limit, and answers were provided in situations where there were ambiguities related to the questions.

The results of the questionnaires were statistically analyzed to assess the psychological status according to the staging of the oncological disease.

Results

Depending on the scores obtained, the depression was classified as mild (scores 7-17), moderate (scores 18-24), severe (scores above 25).

Anxiety was considered insignificant at scores less than or equal to 20 and had a significant level at scores above 20.

Self-esteem levels were very low (score <26), low (27-30), moderate (31-34), high (35-39) and very high (score >39).

Depending on the oncological staging, the patients from group A were classified in stage I (12.07%), stage II (29.31%), stage III (43.10%), stage IV (15.52%).

It is observed that over half of the cases (58.62%) were diagnosed in the advanced stages of the disease (III and IV).

For patients in group A, the correlation of depression and anxiety levels according to the evolutionary stage of the disease was as follows: in stage I cases of severe depression with significant anxiety predominate, in stage II mild depression predominates with insignificant anxiety, while in stage III and IV moderate depression with significant anxiety predominates (Figure 1).

Figure 1

Levels of depression and anxiety, depending on the oncological stages, in group A

Assessment of depression levels and self-esteem according to the evolutionary stage of the disease showed that in stage I severe depression predominates with moderate self-esteem, in stage II moderate depression with low and very low self-esteem predominates, in stage III moderate depression predominates with low self-esteem, and in stage IV moderate depression with high self-esteem predominates (Figure 2).

Figure 2

Depression levels and self-esteem according to the oncological stages, in group A. Self-esteem levels: VL: very low, L: low, M; moderate, H: high VH: very high

The analysis of the results obtained in patients in group B showed that the highest number of patients had significant anxiety associated with mild or moderate depression and moderate self-esteem (30 cases, 49.18%).

Insignificant anxiety was predominantly accompanied by mild to moderate depression and low self-esteem (16 cases, 26.23%) (Figure 3).

Figure 3

Levels of depression and self-esteem according to anxiety in group B. Self-esteem levels: VL: very low, L: low, M; moderate, H: high VH: very high

For the stage of uncertainty, the most common was significant anxiety, and quantifiable depression was classified as severe, moderate, and mild, without meeting the full statistical diagnostic criteria according to the diagnostic and statistical manual of mental disorders, fifth edition (DSM-5) for depressive or anxiety disorder.

For these reasons, we have called them isolated depressive and anxiety disorders.

The association between the symptomatic models was constant in the whole group of patients undergoing histopathological evaluation, called the stage of psychooncological uncertainty.

Significant anxiety was identified in 62.3% of patients, and moderate-to-severe depression in 45.9%, outlining the appearance of anxiety-depressive personality disorder.

Self-esteem was identified in 57.38% of patients with moderate intensity.

Psychometric assessment revealed in patients at an oncological early-stage significant levels of anxiety and mild to moderate depression.

Cognitive preservation was of relatively good quality, as was the resilience, which was associated with the increased addressability of patients to oncology services and the possibility of early diagnosis and an appropriate therapeutic approach.

In patients in oncological stages II and III, the level of depression was moderate or severe, but with insignificant anxiety and moderate cognitive dysfunction, with decreased decision-making capacity and resilience to stress.

For stage IV patients, the main clinical symptom was pain, accompanied by severe depression and significant anxiety, cognitive dysfunction and significant decisional impairment.

Discussion

The analysis of the results for the whole group captures the large number of cases in advanced stages of cancer, III and IV.

Early-stage patients had significant anxiety with severe depression, but preservation of decision-making and resilience led to early addressability, and in advanced patients decision-making capacity was greatly diminished, which may explain late addressability.

Self-esteem decreases significantly with the progression of breast cancer.

We believe that depression and anxiety present from the stage of uncertainty can be an important alarm signal, which is why the psychooncological approach, based on increasing the efficiency of cognitive patterns and improving decision-making capacity, can bring early patients to oncological evaluation, staging.

Preservation of self-esteem may be associated with the major potential for improving resilience to stress and psychotraumatic events in cancer, anticipating a possible favorable outcome.

The decision-making capacity of patients can be influenced by the staging of the disease and the clinical condition, but also by the cognitive and mental status [20].

From the uncertainty phase, patients endure a real stressful existential aggression that can be amplified by the multitude of clinical and paraclinical investigations performed by different medical teams.

This condition further weakens the resilience and the predominantly clinical approach, without psychooncological support, can precipitate mixed depressive-anxiety symptoms.

The decisive moment for the psychological status is represented in the first stage by performing the biopsy and later by communicating the result of the histopathological examination.

It is the main partnership moment between the patient and the therapeutic team, when the communication must be adapted and personalized according to the psychological profile of each patient. In the absence of adequate communication strategies, depression and anxiety are amplified, and cognitive dysfunctions cancel out the ability to resist stressors.

Against this psychological background, erroneous decisions occur, which can significantly delay early therapies, but also decrease the patient's confidence in the therapeutic team.

Resilience capacities, dependent on biological factors, social support and mental and emotional status, can be improved through psychooncological therapeutic strategies, in order to develop effective coping strategies in the fight against oncological suffering [21].

It is a real "game" that includes on the one hand the patient's ability to accept the pathological condition and enrollment in an appropriate therapeutic program, and on the other hand to deny the clinical evidence and delay the therapeutic approach.

This contrasting phenomenon justifies, from our point of view, the high rate of clinical cases that present in advanced stages of disease evolution.

This development may be precipitated by the multisystemic mechanisms of depressive-anxiety disorder [22,23].

We suggest that depression and anxiety may accelerate the development of the neoplastic process and endothelial dysfunction and pharmacological therapies with psychotropic proserotonergic antidepressants (SSRIs), that increase vascular endothelial growth factor (VEGF) [24], may cause the development of tumor mass and increase the risk of metastatic [25], and the transition of the disease from the local to the regional stage or at a distance.

This precipitation can also modify the oncological therapeutic approach plan, posing the problem of a radical mutilating surgery, to the detriment of a sectorectomy-type conservative operation.

Conservative intervention helps maintain self-image, decreases depression and anxiety, enhances resilience to stress and adherence to specific cancer therapies.

In contrast, radical interventions change self-image, amplify anxiety and depression, and promote therapeutic abandonment and adverse outcome.

From a psychological point of view, this moment can be a second major psychotraumatic impact, as patients can trigger body dysmorphic disorder (BDD) [26,27,28,29].

What we consider important is that in all patients with a confirmed oncological diagnosis we found the depression-anxiety picture compared to the patients in a state of uncertainty who had an anxious-depressive clinical picture.

In addition, the intensity of anxiety depression was in stage I with the highest severity, followed by advanced stages III and IV, so that in stage II both items analyzed had a lower intensity.

When correlating depression with self-esteem, an inversely proportional ratio was observed depending on the evolutionary stages.

Severe depression was encountered in stage I, and in the other stages it was moderate. Impaired self-esteem was moderate for stage I, because in stage II and III there was low self-esteem, and in stage IV self-esteem is paradoxically high, confirming some studies that show that psychological adaptation to the disease causes a paradoxical cognitive resilience that denies clinical evidence.

Patients refuses to realize that the disease has a negative evolution [30,31].

The intensity of psychooncological symptoms, regardless of the evolutionary stage in which the disease was diagnosed, is dependent on the level of physical and mental disability at the time of oncological diagnosis and finding therapeutic options, cognitive preservation and implicitly the level of cognitive resilience to the disease, as well as the psycho-emotional support provided by both the family environment and the medical team.

The multitude of psychological, socio-economic and family stressors in the conditions of a presumption of neoplastic disease or diagnosed cancer determines a polymorphism of psychological symptoms.

The evolution of the psychological status can be linear, in the sense of gradually going through all the stages of evolution, or non-linear (chaotic), depending on the distance between the psychological symptoms in the stage of uncertainty and the diagnosis of breast cancer already in an advanced stage, III or IV.

The data provided by our study highlight the importance of interdisciplinary collaboration, the stage of diagnostic uncertainty with anxious-depressive manifestations and increased prolactin levels, having to alarm the medical team, for a quick diagnosis and immediate initiation of treatment.

The patient must be taken over by the psycho-oncologist, and if the profile of the aforementioned disorders is confirmed, the cognitive psychotherapy sessions must be started as soon as possible, allowing the patient to adapt as well as possible to the communication of the oncological diagnosis.

Behavioral cognitive psychotherapy should aim to change cognitive patterns and anxiety-depressive disorders in which the patient's hope is minimized, to a cognitive pattern of resilience based exclusively on motivation for survival.

At any evolutionary stage of oncological disease, psychooncological disorders can reach the threshold of integration into a psychiatric disorder secondary to oncological disease, which meets all the diagnostic criteria according to DSM 5.

At this point, the intervention of a psychiatrist is necessary, and the combination of psychotropic therapy can be an opportunity to improve the patient's quality of life.

Psychiatric care is required in patients undergoing surgery that causes impaired self-esteem, self-esteem and BDD, but also in patients who experience cognitive impairment following chemotherapy or radiation therapy.

The discrepancy between oncological staging and psychooncological staging is mainly determined by the lack of significant studies to demonstrate staging based on objective criteria of psychooncological disorders.

Subsequent studies can alleviate this gap by obtaining results with high clinical significance and validity for the psychooncological symptoms associated with each stage of development.

Imaging data obtained by elastography, mammography, magnetic resonance imaging (MRI) and histopathological data of the analyzed cases can guide both the oncologist for staged oncological diagnosis and the psycho-oncologist or psychiatrist to adapt and customize psychotherapeutic and pharmacological treatments according to the evolutionary stage.

The diagnosis of suspicion initially appears on imaging evaluation, which helps the clinician to determine the malignancy of the tumor by using the breast imaging reporting and data system (BI-RADS) score, which has values from 0 to 6.

BI-RADS, assesses the risk of malignancy based on an algorithm developed by the American College of Radiology, by mammography, ultrasound and MRI.

According to the classification, BI-RADS 0 represents an incomplete evaluation, BI-RADS 1-negative, BI-RADS 2-benign with 0% probability of malignancy, BI-RADS 3-probably benign with <2% risk of malignancy, BI-RADS 4-oncological suspicion, with 2-94% risk of malignancy, included in BI-RADS 4A low risk (2-9%), BI-RADS 4B moderate risk (10-49%) and BI-RADS 4C high risk (50-94%). BI-RADS 5 has a>95% risk of malignancy, and BI-RADS 6 is a malignancy diagnosed by biopsy [32].

BI-RADS 0 category requires further evaluation due to insufficient data that do not allow the assessment of the degree of malignancy, or comparison with previous examinations if any.

The re-evaluation will be able to frame the score between 1-6.

In stage 1 the examination is considered normal, in the absence of obvious changes in malignancy and routine screening is recommended.

BI-RADS 2 category identifies a benign tumor, without the appearance of a malignancy, such as a breast lump or calcifications.

In stage 3, the risk of malignancy is below 2% and re-evaluation at 6 months is recommended, even if the lesions are most likely benign (Figure 4).

Figure 4

Breast MRI which highlights multiple bilateral breast nodules, with benign features (probably breast fibroadenomas), BIRADS 3; Recommendation: breast MRI follow-up at 6 months

If the lesions increase in size, a biopsy is recommended.

The oncological lesions diagnosed at this stage have a favorable evolution.

In stage BI-RADS 4, with oncological suspicions, a biopsy is recommended to establish the precise diagnosis (Figure 5).

Figure 5

Mammography which highlights architectural distortion left upper outer quadrant (UOQ), with multiple polymorphous microcalcification, with regional distribution (15/6/13 mm extension), BIRADS 4; Recommendation: breast MRI and biopsy

In the case of BI-RADS 5, highly suggestive of a malignant tumor, spiculated mass is identified and percutaneous or surgical biopsy is recommended (Figure 6).

Figure 6

Breast MRI showing mass enhancement, irregular margins, with restricted diffusion and heterogeneous gadolinophilia, with type II and III enhancement curve, and slightly architectural distortion, measuring 26/20/18 mm, with malignant features, BIRADS 5. Recommendation: Breast biopsy.

In stage 6, with a cancer diagnosis confirmed by biopsy, specific oncological treatment is recommended [33,34].

Imaging staging should be correlated with clinical staging.

In stage I, the tumor is smaller than 2cm, without locoregional lymphadenopathy and without affecting the breast skin.

Characteristic for stage II is the tumor under 2cm with mobile locoregional adenopathy or the tumor with 2-5cm without axillary adenopathy and without skin damage. In stage III the tumor is smaller than 5cm with axillary lymph node block, or over 5cm with mobile axillary adenopathy. Skin damage, specific to stage III, may occur in the form of erythema, inflammation, ulceration, “peau d'orange” skin (skin of an orange).

For stage IV, imaging evaluation of metastases is mandatory [35,36].

If the patients go to the general physician, he can make an assessment according to the clinical and imaging data on the probability of the evolutionary stage, being able to immediately direct the patient to the oncologist.

The presence of psychooncological manifestations could cause the patient to go to a psychotherapy office, thus being able to show the psychotherapist the results of some imaging examinations.

The psychotherapist must be informed about these basic data of the potential staging of the neoplastic condition, in order not to initiate psychotherapy programs, independent of the oncological condition.

The correct attitude is determined by the possibility of orientation on paraclinical data, and in case of identification of pathological elements presented by our staging, the patient should be referred as soon as possible to an oncology service, for evaluation by a specialized team of oncologist and psycho-oncologist.

The timing of the case at the level of primary psychotherapy interventions, made by the clinical psychologist, without psychooncological specialization, can significantly delay the correct oncological diagnosis and the precocity of the specific treatment, with major negative consequences on the prognosis of the disease.

Conclusions

The presence of significant anxiety in the uncertainty phase and the anxious-depressive clinical picture can be an alarm signal for the initiation of specific psychotherapeutic strategies, to increase the adaptive potential and resilience to the disease, to ensure a therapeutic collaboration of the patient by increasing adherence and compliance to the proposed therapeutic plan.

Relatively sudden anxiety in a young woman, risk factors for breast cancer, and deficient cognitive impairment require intensified clinical and paraclinical investigations to confirm early oncological diagnosis.

The psychooncological profile can be an indicator that strengthens the suspicion of possible neoplastic disease, especially in correlation with clinical-biological, imaging and histopathological factors.

Psycho-oncological evaluation of patients, regardless of the evolutionary stage, helps patients to improve their ability to adapt to the major stress caused by the diagnosis of breast cancer and oncological treatment, to improve the prognosis and quality of life.

Conflict of interests

None to declare.