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Mind over Matter? Don't Kid Yourself (on Stress and BC)

I learned of a new study impli­cating stress in reduced breast cancer sur­vival by Twitter. Three days ago, a line in my feed alerted me that CNN’s health blog, “Paging Dr. Gupta,” broke embargo on the soon-​​to-​​be-​​published paper in the journal Clinical Cancer Research. It seems the story – that women who undergo a stress relief program live longer after breast cancer recur­rence – couldn’t wait.

“Less stress helps breast cancer patients” is the title of the rushed post. What the researchers, based at Ohio State’s Com­pre­hensive Cancer Center, report is that psy­cho­logical inter­vention helps to increase the quality of life and sur­vival among women with recurrent breast cancer.

The inter­vention at issue is this: weekly, small-​​group meetings of BC patients for 4 months after their initial surgery and diag­nosis. Led by clinical psy­chol­o­gists, the women met 18 times and dis­cussed strategies to reduce stress, improve mood, strengthen social net­works, eat better, exercise and adhere to medical treatments.

The current report is an extension of pre­vious findings among an ini­tially larger group of women at the time of BC diag­nosis. Then, the researchers ran­domized 227 patients after surgery, all with stage II or III disease, either to receive the inter­vention, or not, after an initial psy­cho­logical assessment and blood tests to check their immune function. The women were over­whelm­ingly Cau­casian, mostly with stage II tumors, well-​​educated and, for the most part, had ER/​PR+ tumors. What the researchers noted was that:

…As pre­dicted, patients receiving the inter­vention showed sig­nif­i­cant­low­ering of anxiety, improve­ments in per­ceived social support,improved dietary habits, and reduction in smoking…

In 2008, the same Stress and Immunity Cancer Project inves­ti­gators reported in the journal Cancer that the psy­cho­logical inter­vention reduces BC recur­rence and pro­longs sur­vival. Here’s where the results become both exciting and sus­pi­cious. In 2007, with a median follow-​​up of 11 years, 62 women (29%) in the initial study had recurrent disease. The pro­portion among those who’d received the inter­vention was indeed lower, con­firming the authors’ hypothesis that the inter­vention would help prevent BC from coming back. But the p-​​value for this dif­ference was 0.034, barely meeting the threshold for sta­tis­tical sig­nif­i­cance. Similar results were observed for overall sur­vival among the women who’d attended the group ses­sions: they had a reduced risk from death with a minimally-​​significant p-​​value (0.028) for the difference.

Now, the Ohio group reports on the 62 patients who relapsed. Before going further, I should say that it’s a bummer of a result from a medical per­spective and from mine as a BC sur­vivor out at seven years. Group support aside, 44 (71%, yikes!) of the patients with recurrent disease have died with a median time until death (after recur­rence) of 2.8 years (range: 0.9 – 11.8 years).

What the authors con­clude is that the psy­cho­logical inter­vention improved sur­vival after BC recur­rence. How the data flowed is this: among the recur­rences, there were 33 women who’d been ran­domized to the assessment only, “A” arm of the original trial and 29 who’d been ran­domized to the inter­vention, “I” arm. These numbers were whittled down to 18 patients who could be fol­lowed for con­tinued study on the “A” arm and 23 women on the “I” arm. So the total number of women eval­uated in this new report is small: just 41 women.

Among those, the women who received the psy­cho­logical inter­vention were more likely to survive, with what’s called a hazards ratio of 0.41. Here again the p-​​value is valid but mar­ginal (p= 0.014). The authors show a very limited amount of data regarding test-​​tube based studies of natural killer (NK) and T lym­pho­cytes in the dif­ferent patient groups, and suggest in the paper’s abstract that “immune indices were sig­nif­i­cantly higher for the inter­vention arm.”

What would have killed this paper (pardon the verb) had I been a reviewer is this: among the 41 women with recurrent disease, there was a major dif­ference in the treat­ments they received. According to the “Patients and Methods” section of the paper, in the section on “adherence, chemotherapy dose intensity,” the authors indicate that just 6 of the “A” patients received chemo in the 12 months fol­lowing the recur­rence, while 13 of the “I” patients got chemo in the same period.

My math: only 6 of the 18, or 33 percent of the “A” group (assessment-​​only) patients received chemo, while 13 of the 23 (56 percent) of the “I” (inter­vention) patients got chemo in the year after recur­rence. That’s a huge dif­ference in medical treatment among a very small number of patients.

My point: the small dif­ference in sur­vival after recur­rence among those women who received struc­tured psy­cho­logical support, years earlier, may be attrib­utable to the prompt chemotherapy they received upon relapse of the cancer. This seems a more plau­sible expla­nation than that group therapy-​​type ses­sions make a dif­ference in tumor biology or treatment resis­tance. (Neither outcome is proved by this study.) The dif­ference may also derive from better overall health in the women who ini­tially received the inter­vention that included advice and support regarding diet, exercise, smoking ces­sation and med­ication compliance.

My opinion:

I think there can be tremendous value in psy­cho­logical support for people with illness of any kind, whether that’s pro­vided casually by sup­portive fam­ilies and friends, one-​​on-​​one psy­chotherapy, med­ication and/​or group meetings. And it’s easy to envision that meetings in which women with similar disease sit­u­a­tions and con­cerns get together and discuss coping mech­a­nisms, how to stay healthy, eat better and exercise could have pos­itive effects on overall survival.

But the immune ben­efits of stress relief, like those pre­sented in David Servan-Schreiber’s like-​​minded Anti-​​Cancer, are bogus. There’s no sci­en­tific evi­dence that the sort of NK or T cell changes tested in this study help or hurt breast cancer growth. It’s pos­sible that a revved-​​up, stress and steroid-​​driven immune system might help kill cancer cells, or might favor their expansion. It could go either way. The effects of stress steroids on tumors vary and are complex. Pred­nisone and similar steroids, for example, which resemble the body’s natural stress steroid cor­tisol, are well-​​established and effective com­po­nents of most lym­phoma treatment reg­imens and once were a mainstay of breast cancer treatment. My point is not that the immune system doesn’t affect tumor growth. (I think it can and does.) But the effects are com­pli­cated and differ among indi­viduals and according to the spe­cific tumor type.

On linking stress and breast cancer: this argument, which is all that it is in the absence of better data, is patron­izing and demeaning to women. It’s the kind of advice we offer children, that if they think and do the right things the outcome will be favorable. Oncology doesn’t work that way. If a woman’s breast cancer comes back, it’s not because she didn’t go to support groups or relax suf­fi­ciently. Tumors grow due to inherent, malignant prop­erties of the can­cerous cells and other bio­logical factors in the body, such as other ill­nesses that may, indeed, weaken the immune system or limit a person’s capacity to receive effective treatment.

I’m all for stress reduction, as an aim in itself. But it’s not a cure for cancer.

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