Explanation of New Report of a Connection in Breast Cancer, Stress, and the Immune System

Testing the blood of the patients, Andersen's team found measurable effects. Those who reported the highest stress had lower levels of natural killer (NK) cell lysis -- less evidence of activity by the cells that are supposed to attack tumors. 'That's the most relevant assay (test) that we did,' [Barbara] Andersen [of Ohio State University] said. 'NK cells have as their responsibility to ferret out malignant and tumor cells, attach to them, poke holes in them and kill them.' " (The abstract of the original article, in the Journal of the National Cancer Institute, may be read at the end of this document.)

The Reuters News Service reports also reported: "Andersen said her team was now doing studies to see if women given counseling survived better than women who got medical treatment alone. Sheldon Cohen of Carnegie Mellon University in Pittsburgh and Bruce Rabin of the University of Pittsburgh School of Medicine called the findings interesting. They noted that many studies had shown stress can suppress the immune system, but said the effects were short-lived. No one had yet shown stress could make cancer worse. However, they added, there was evidence that the type of changes made to the immune system by stress were the very kinds that would influence the growth and spread of tumors. 'The article by Andersen et al provides an important piece of this fascinating puzzle, but the solution is still a ways off,' they wrote in a commentary."

My work thoroughly explains the Andersen findings. In 1985 I first suggested that the major adrenal hormone, dehydroepiandrosterone (DHEA), is directly involved in the growth and development and maintenance of all tissues. Also, I proposed that the other major hormone, cortisol, originated directly as our natural "anti-DHEA" hormone. That is, in the case of the brain, DHEA motivates our behavior, and cortisol production acts in the opposite direction. This connection developed into my explanation of the "fight or slight" mechanism. When we spot an enemy, DHEA starts our fight response. If the encounter is too stressful, the stress hormone, cortisol, is produced. If too much cortisol is produced, we flee rather than fight. In my subsequent study, I discovered that cortisol, in too high a ratio to DHEA over prolonged time, is also damaging to all our tissues, especially the brain and immune system. This is what is happening in the women of the Andersen's study.

The explanation directly fits my explanation of DHEA and cortisol. DHEA is proven to stimulate an increase in natural killer cells in aged men. When DHEA is given to aged men, it was reported that: "NK cell number showed a 22-37% increase (p < .01) by 18-20 weeks of treatment with a concomitant 45% increase (p < .01) in cytotoxicity." (J. Gerontol. A. Biol. Sci. Med. Sci. 1997 Jan; 52(1): M1-M7). Cortisol has the opposite effect: "However, cortisol and ACTH significantly inhibited the NK activity of lymphocytes from AIDS (HIV disease) patients." (Immunol. Invest. 1995 Aug; 24(5): 689-699). Moreover, it is my hypothesis that reduced DHEA, and further loss of DHEA, is the cause of AIDS. That is, not only does a loss of DHEA and an increase in cortisol reduce natural killer cells, this combination of DHEA and cortisol is the cause of the reductions of CD4 immune cells, the hallmark of AIDS. It is noteworthy that Andersen found that stress reduces NKs in women with breast cancer in light of the finding that stress worsens the progression to AIDS. "This report presents the first evidence from a prospective research study that severe life event stress is associated with an increased rate of early HIV disease progression." (Am. J. Psychiatry 1997 May; 154(5): 630-634).

Reuters, above, reported that Cohen and Rabin found Andersen's report to be interesting, but "They noted that many studies had shown stress can suppress the immune system, but said the effects were short-lived." I suggest this is also explained by my idea that cortisol reduces the effects of DHEA. That is, in a fight or flight situation, we regain our composure following a threatening event. This is how nature keeps us going; we regain our normal ratio of DHEA to cortisol. Now in AIDS, DHEA first increases, then goes into severe decline. Measurable levels of DHEA are reduced in women with breast cancer, and this reduction in DHEA occurs as early as nine years prior to diagnosis (Geriatrics 1992; 37: 157). In AIDS, and women with breast cancer, DHEA is reduced and stays low. DHEA does not rebound. This is why severe stress, in the progression of HIV disease, and the severe stress of diagnosis and treatment in women with breast cancer, is so damaging. Neither are producing a rebound of DHEA to keep them going. The increases in cortisol, as a result of stress in AIDS and in women with breast cancer, makes their conditions worse.

Reuters also said that "Andersen said her team was now doing studies to see if women given counseling survived better than women who got medical treatment alone." This might help, because stress reduction is known to reduce cortisol. However, it may be that simply increasing DHEA may be enough, in women who are prone to stress. A study was done on rats that exhibit "both high anxiety and despair." It was found that "In conclusion, the results presented here show DHEA to be effective as an antidespair agent in rats with both high anxiety and despair." (Physiol. Behav. 1997 Nov; 62(5): 1053-1057). Not only would DHEA be effective in reducing the anxiety and despair of a diagnosis of breast cancer, it would increase the activity of natural killer cells.

It is known that cancer is more common in old age. DHEA naturally begins to decline around age twenty-five, and the levels in old age are very low. I think this decline in DHEA of old age reduces the natural killer cell activity during old age. Since natural killer cells attack malignant cells, malignant cells would less likely be attacked in old age for this reason. Therefore, malignant cells would be more likely to develop, increase during old age, and the spread of tumor would increase in women with breast cancer. Stress could increase the probability of spread.

This is the abstract of the original article, the one to which the Reuters article refers.

J. Natl. Cancer. Inst. 1998 Jan 7; 90(1): 30-36 "Stress and immune responses after surgical treatment for regional breast cancer"

"BACKGROUND: Adults who undergo chronic stress, such as the diagnosis and surgical treatment of breast cancer, often experience adjustment difficulties and important biologic effects. This stress can affect the immune system, possibly reducing the ability of individuals with cancer to resist disease progression and metastatic spread. We examined whether stress influences cellular immune responses in patients following breast cancer diagnosis and surgery. METHODS: We studied 116 patients recently treated surgically for invasive breast cancer. Before beginning their adjuvant therapy, all subjects completed a validated questionnaire assessing the stress of being cancer patients. A 60-mL blood sample taken from each patient was subjected to a panel of natural killer (NK) cell and T-lymphocyte assays. We then developed multiple regression models to test the contribution of psychologic stress in predicting immune function. All regression equations controlled for variables that might exert short- or long-term effects on these responses, and we also ruled out other potentially confounding variables. RESULTS: We found, reproducibly between and within assays, the following: 1) Stress level significantly predicted lower NK cell lysis, 2) stress level significantly predicted diminished response of NK cells to recombinant interferon gamma, and 3) stress level significantly predicted decreased proliferative response of peripheral blood lymphocytes to plant lectins and to a monoclonal antibody directed against the T-cell receptor. CONCLUSIONS: The data show that the physiologic effects of stress inhibit cellular immune responses that are relevant to cancer prognosis, including NK cell toxicity and T-cell responses. Additional, longitudinal studies are needed to determine the duration of these effects, their health consequences, and their biologic and/or behavioral mechanisms."