Recognizing Factors Contributing to PTSD May Improve Clinical Care in Patients with Breast Cancer

July 8, 2020

Researchers highlighted the importance of recognizing the environmental and biological factors that contribute to the development of PTSD, which can help inform clinical care and potentially reduce PTSD comorbidity.

An article published in Cancer discussed the risk factors for posttraumatic stress disorder (PTSD) in patients with breast cancer, as well as the role of inflammation and endocrine function.

“Although treating a patient’s breast cancer to give them the best odds of survival is critical, reducing potentially harmful effects on mental health also should be considered when possible so as to give the patient the best QOL both during and after cancer. In addition to improving QOL, to our knowledge the impact of PTSD symptoms on appropriate follow-up for cancer recurrence surveillance is not yet known and warrants further investigation.

In a meta-analysis of 38 studies evaluating breast cancer diagnoses and treatment, it was determined that 10% of women develop PTSD after a diagnosis of breast cancer. Moreover, a cancer diagnosis increases the lifetime risk of PTSD by a factor of 1.66 compared with those who have never been diagnosed with cancer. Importantly though, several environmental and biological risk factors for PTSD have been identified among this patient population.

The stage of disease has been found to positively correlate with developing PTSD, in that women who are diagnosed with a more advanced stage of breast cancer are more likely to develop PTSD. In addition, one symptom that is unique to cancer survivors is FCR, or “the fear or worry that the cancer will return or progress in the same organ or in another part of the body.” Given that breast cancer can affect women at younger ages, researchers suggested that FCR in particular may uniquely influence women due to circumstances such as the possibility of these women either wanting to have children or needing to take care of children.

Socioeconomic factors, such as educational level and income, have also been associated with risk of PTSD in patients with breast cancer. However, many models of socioeconomic risk do not account for increased rates of childhood and lifetime trauma exposure nor stressors that uniquely influence nonwhite patients.

“These socioeconomic and environmental risk factors must be taken into account when modeling disparities in psychiatric and other long-term outcomes in women diagnosed with breast cancer,” the authors wrote. “In particular, childhood trauma and chronic stress have known physiological effects that may promote the risk of both cancer and PTSD.”

More specifically, chronic stress can exert lasting effects on physiology and behavior in patients with breast cancer due to its influence on the immune system. When the sympathetic nervous system (SNS) is activated during stress, one of its effects is to stimulate inflammatory pathways; and when a proinflammatory state is maintained over time, it can contribute to a decline in physical health.

“Inflammation is a mechanism that is characteristic of both cancer and PTSD, and therefore serves as a physiological link by which one condition may exacerbate the other,” the authors wrote. “Inflammation has been shown to promote the initiation, proliferation, and survival of cancer cells as well as angiogenesis and metastasis. Moreover, increased systemic inflammation as reflected by the neutrophil to lymphocyte ratio has been reliably associated with poor prognosis in multiple cancers, possibly related to the association of inflammation with a reduction in tumor-infiltrating lymphocytes as well as blunted tumor immune responsiveness.”

However, cancer-related inflammation can also be regulated. For instance, because a cancerous tumor is partially responsible for an inflammatory response in patients with breast cancer, removing a tumor partially reduces its effect on neuroinflammatory responses. Additionally, nonselective and targeted strategies to alleviate cancer-related inflammation have also been proposed. Though much more needs to be studied regarding the interaction between inflammation, breast cancer, and stress responses, researchers indicated that by reducing systemic inflammation there will also be an increase in the effectiveness of breast cancer treatments and a reduction in risk for developing PTSD, as well as other negative psychiatric and behavioral outcomes.

In regard to ovarian hormones, breast cancer development is regulated by hormones like estrogen and progesterone, as well as other treatments which often include antiendocrine pharmacotherapy. However, antiendocrine therapies have also been known to disrupt the typical hormonal interaction with the amygdala, potentially increasing the risk of maintaining chronic PTSD symptoms. Even further, some of these treatments also block estrogen binding throughout the body and disrupt ovarian function. Therefore, antiendocrine therapies may have important psychological impacts, potentially affecting the function of brain circuits that regulate emotion.

“Furthermore, several studies of women with PTSD have suggested that estradiol may influence the formation of fear extinction memories, which represent a key mechanism for recovery from the fear responses that individuals experience after trauma exposure,” the authors wrote. “Therefore, it is possible that antiendocrine treatment may inhibit the formation of fear extinction memories in cancer survivors. Further research is needed to test this possibility.”

Given that antiendocrine therapies may be prescribed for long periods of time, researchers noted that it may be worthwhile to also assess the effects that they have in combination with other treatments, such as radiotherapy and chemotherapy. The investigators also suggested that it may be worthwhile to investigate how the treatment of patients with triple-negative breast cancer may result in different PTSD symptomology based on the difference in therapies as well as prognosis.

“It should be mentioned that the development and use of antiendocrine therapies should not be discredited because patient survival is the top priority,” the authors wrote. “However, there may be value in developing novel antiendocrine therapies that have fewer pervasive systemic effects and, whenever possible, identifying those women at risk of PTSD and depression for psychoeducation and referral to psychiatric care services.”

Overall, the researchers indicated that though many of the risk factors discussed are not modifiable, recognition of their contribution to the development of PTSD can help inform clinical care and potentially reduce PTSD comorbidity.

“To the extent that the development of PTSD after a breast cancer diagnosis is contingent on the diagnosis itself as a sudden and catastrophic event, there is reason for considerable optimism that, with the continual advancement of breast cancer therapies and increased awareness of the psychological impact of the initial diagnostic workup and clinical conveyance of prognostic information, the psychological burden of a breast cancer diagnosis may be significantly reduced,” the authors concluded.

Reference:

Brown LC, Murphy AR, Lalonde CS, Subhedar PD, Miller AH, Stevens JS. Posttraumatic Stress Disorder and Breast Cancer: Risk Factors and the Role of Inflammation and Endocrine Function. Cancer. doi:10.1002/cncr.23934.