Case 50

Published on 18/02/2015 by admin

Filed under Allergy and Immunology

Last modified 22/04/2025

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CASE 50

MG, a 50-year-old mother of two, was recently diagnosed with breast cancer. Despite favorable histology and hormone receptor typing of the tumor, indicating a projected good response to taxol and other chemotherapy, and lack of any nodal involvement, she has had trouble coming to grips with the diagnosis. She has been referred to the psychiatric service for treatment of depression. In addition, recent blood work at the hospital, along with some functional studies, suggests a subtle impairment in immune functioning, which her general practitioner is concerned might impact on longer-term prognosis. What are your concerns? What is the evidence that MG’s mental state might influence her disease? What might be done to address this issue?

QUESTIONS FOR GROUP DISCUSSION

1. There is a wealth of data indicating a link between clinical depression and immune function. What psychological factors have been identified as contributing to diminished survival in cancer patients?

2. Given the relationship identified in question 1, what adjunctive therapy would you recommend be used along with the primary treatment?

3. Assuming that you arrange for psychological counseling as adjunctive therapy for your patient, how would you monitor progression of treatment and its impact on disease progression? Is this the primary interceding variable between disease progression and mental state?

4. A recent trial has assessed evidence that adrenergic- and/or endorphin-mediated signals might be variables of importance in immunosuppression after cancer surgery. As such, what pharmacologic intervention would you recommend to improve immune functioning?

5. Which cells of the innate immune system play an important role in tumor killing? Consider your proposed intervention in question 4. What is the evidence that this drug intervention would enhance tumor killing?

RECOMMENDED APPROACH

Implications/Analysis of Family History

Although we are not provided with family history, there is evidence that susceptibility to cancer does have a genetic basis. Additionally, recent studies have identified a polymorphism in the 5-hydroxytryptamine transporter (5-HTT) gene that predisposes individuals to depression when faced with major life stresses. The 5-HTT gene encodes the transporter protein required for serotonin reuptake into neurons.

Implications/Analysis of Clinical History

MG has been diagnosed with cancer, which is high on the list of stressors for anyone. The fact that her physician has referred her to a psychiatrist rather than psychologists for counseling is an indication that he considers this depression as profound and may require drug therapy.

Implications/Analysis of Laboratory Investigation

MG’s blood work indicated that simple blood tests were normal, as were assays of innate immunity and electrophoresis of serum immunoglobulin. However, functional studies have revealed impaired NK cell cytotoxic activity, as well as diminished proliferative responses of B cells and T cells to mitogenic lectins.

These tests indicate that MG does not have a major immunologic defect but that the immune system is just not functioning optimally at this time. A number of studies have shown decreased NK cell activity in patients with a number of different cancers, so whether this decreased activity is secondary to the cancer or to depression is difficult to evaluate.

Depression has been linked to low serotonin levels, and thus antidepressants that prevent the reuptake of serotonin are prescribed for these patients. As such, one would expect that antidepressants that block the reuptake of serotonin (e.g., fluoxetine [Prozac]) would reverse immunosuppression, if a deficiency is the mechanism by which the immune system is depressed. However, studies in rodents have shown that acute administration of fluoxetine led to a decrease in mitogen-induced proliferation. This does not obviate a correlation between depression and decreases in lymphocyte proliferation but rather emphasizes that other genes may contribute to depression.

Additional Laboratory Tests

The question still remains—what is the primary interceding variable between disease progression and mental state? If one could identify this, then laboratory tests to evaluate changes after drug therapy could be initiated.

DIAGNOSIS

MG was diagnosed with depression.

THERAPY

MG’s physician has referred her to a psychiatrist.

MENTAL HEALTH AND DISEASE

There is a growing realization that mental health can affect disease, both incidence (although data here are more tenuous) and prognosis. There is a wealth of data indicating a link between clinical depression and immune function. A variety of indices used to score depression (e.g., Beck Inventory) have been used to document this relationship. In general, individuals with poor self worth and feelings of hopelessness have been found to show diminished survival compared to controls, all other factors being equal, after diagnosis in a variety of different cancers, with breast cancer being one of these. Accordingly, a major effort has been made to improve psychological factors as adjunctive therapy for cancer.

Monitoring Progression of Treatment

Less attention has been paid to how best to monitor progression of treatment. Should we be following immunologic parameters? Is this indeed the primary interceding variable between disease progression and mental state? Are there other variables we should be paying as much (or more) attention to? As one example, one might ask whether we should routinely take measurements of neurohormonal status in such patients.

Modulation of NK Cell Activity

A recent trial has assessed evidence that adrenergic and/or endorphin-mediated signals might be variables of importance in immunosuppression after cancer surgery and has suggested that we intervene (using β blockers/naltrexone) to improve immune functioning in this case, and thereby promote longer-term survival. Certainly, independent animal model data support evidence for a role for naltrexone in modulation of NK cell activity (a key player in tumor killing), whereas lymphocytes are known to possess adrenergic receptors that modulate their activity.

Conclusion

At this stage it is safest to conclude that this field is very much in its infancy and that a great deal more has to be learned before rational behavioral therapy (aimed at “improving” immune functioning in cancer patients) can be advocated.

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