Risk Factors, Protective Factors, and Hypothesized Mechanism
A variety of sociodemographic, disease-related, psychosocial, and psychological variables have been investigated to determine their relationship to post-traumatic stress (PTS) related to cancer. At present, no clear picture emerges about who is at increased risk of developing PTS after diagnosis or treatment of cancer.
Few patient characteristics have been shown to predict the occurrence of PTS. High levels of psychologic distress have been correlated with both stress symptoms [1-3] and full-syndrome post-traumatic stress disorder (PTSD) diagnoses in adult survivors. In addition, trait anxiety was found to predict post-traumatic symptoms in the parents of survivors of childhood cancer. Women who are survivors of cancer and who have a diagnosis of lifetime PTSD tend to have a history of exposure to trauma.[1,5] Demographic characteristics such as age, sex, and education level at time of diagnosis have not been reliable predictors of stress symptoms.[1,6,7]
Disease-related variables that have been associated with a higher incidence of PTSD in patients who underwent bone marrow transplant include more advanced disease and a longer hospital stay. Other studies, however, have found no association between time since diagnosis and treatment, severity of disease, or type of cancer treatment received.[1,9,10] The relationship between disease stage and post-traumatic symptoms has not been adequately studied. Most studies have not found an association; however, they typically include a limited range of disease stages or are studying early-stage cancer.
The time since diagnosis and treatment has been shown to correlate with and predict post-traumatic symptoms in survivors of osteogenic sarcoma  and Hodgkin lymphoma.[7,12] Specifically, persons who were farther from diagnosis and treatment tended to exhibit fewer symptoms. This effect, however, has not been found in studies of patients with recent recurrences, survivors of breast cancer, or survivors of childhood cancers. Duration of treatment, rather than time since treatment, has been shown to predict stress symptoms in survivors of childhood cancer. (Refer to the PDQ summary on Pediatric Supportive Care for more information.)
The presence of pain and other physical symptoms has been shown to correlate with levels of intrusive thoughts. Cancer recurrence has also been shown to increase the likelihood of stress symptoms in patients.
Psychosocial and Psychological Variables
The experience of past traumatic events appears to be an important psychosocial risk factor associated with PTS symptoms,[5,15,16] as was found in both early-stage  and metastatic breast cancer. Previous trauma in combination with recent stressful life events was significantly related to PTS symptoms.
Other psychosocial risk factors such as premorbid psychopathology,[20,21] high levels of general psychologic distress, and dysfunctional coping and attributional styles [15,23,24] have been linked to a risk for PTSD in war veterans, Holocaust survivors, and other disaster victims. In addition, several investigators have linked predisposing genetic factors  and other biologic factors (e.g., overly reactive hormonal systems and reduced hippocampal volume) to risk for PTSD.[26-28] Among social factors, the quality of the recovery environment, often measured in terms of social support, has been shown to affect risk for PTSD following exposure to combat  and burn injury. The effect of threat to life and body integrity has been documented in samples of adults and families [1,4,12] but not children.
Psychological variables that have been related to a higher incidence of PTSD include a history (precancer diagnosis) of PTSD,[5,30] increased use of avoidance coping, and lower levels of social support.
Greater perceived availability of social support is associated with fewer stress response symptoms in patients with early-stage breast cancer [17,19] and in patients who have undergone bone marrow transplant.
The availability and timeliness of accurate health-related information may also offer protection from stress response symptoms. Women who met the diagnostic criteria for acute stress disorder reported significantly less satisfaction with the communication of their cancer diagnosis; similarly, women who were unaware of their cancer stage reported higher stress response symptoms than those who were more knowledgeable about the stage of their disease. To the extent that adequacy of information reflects the quality of a patient's relationship with medical staff, another protective factor may be the quality of those relationships. Difficult patient-staff relationships have been reported to be predictors of stress response symptoms in women with cancer.
PTSD is precipitated by an intensely distressing event; however, this factor alone is not sufficient to explain the disorder. Not everyone exposed to a traumatic stressor develops the full-blown syndrome (or subsets of symptoms) or qualifies for the diagnosis. Attempts to explain these differences and to predict who is vulnerable have focused on psychologic (i.e., learning theory), biologic (especially hormonal), and social (i.e., social support) factors. Early studies of Vietnam War veterans suggested a two-factor learning theory to account for trauma-related pathology.[35,36] The same theory has also been applied to development of PTSD in patients with cancer.[37-39]
PTSD symptoms develop as a function of both classical conditioning and instrumental learning. Classical conditioning accounts for the fear responses elicited by various stimuli that are associated with the original traumatic event. Neutral stimuli (e.g., smells, sounds, and visual images) previously paired with the aversive stimuli (e.g., chemotherapy or painful procedures) eventually evoke anxiety, arousal, and fear when presented alone, even after the trauma has ended. Higher order conditioning and stimulus generalization account for the exacerbation and extension of symptoms to additional stimuli. Once established, PTSD symptoms are maintained through instrumental learning, that is, avoidant responses are reinforced because avoidance of the stimuli prevents unpleasant feelings and thoughts.
Estimates from epidemiologic studies suggest that on average, 25% to 33% of individuals who are exposed to traumatic events, including cancer, develop PTSD or subsyndromal PTSD.[26,40] Although the disorder appears to be a result of learning processes, many factors have been suggested to explain why one person develops PTSD and another does not.
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