When Hot Flashes Are Good News

Oct. 30, 2008— -- No one likes the side effects of chemotherapy. But would your attitude change if you knew that the side effects might predict success with your treatment for cancer?

A study in today's issue of Lancet Oncology describes just such a finding in women with breast cancer treated with either tamoxifen or anastrozole as part of an adjuvant (preventive) treatment clinical trial.

Women who participated in the trial had been diagnosed and treated for primary breast cancer. In this study, the researchers examined the records of women who then received either anastrozole or tamoxifen to prevent the breast cancer from returning.

If a woman was treated with anastrozole or tamoxifen and developed vasomotor symptoms -- night sweats, hot flashes and sweating -- and/or joint pain after they started their medicine, then the chances that their breast cancer would return were lower than for a woman who did not develop either symptom.

The researchers can't explain why this happened. They suggested it might be related to a woman's genetic profile and how her body processed the medications, but that isn't for certain.

The end result was that, if a woman had vasomotor (usually called menopausal) symptoms, the chance that her breast cancer would return was decreased by about 16 percent. If she developed joint symptoms, the recurrence rate was reduced by about 41 percent. And, if she had both symptoms occur after treatment, the odds of recurrence were decreased by about 47 percent.

Cutting Down the Estrogen

Both anastrozole and tamoxifen decrease the effects of estrogen in post-menopausal women with breast cancer, although they work differently.

Tamoxifen is an estrogen blocker and blocks the effect of circulating estrogen on breast cancer cells in post-menopausal women whose cancers are hormone sensitive. Anastrozole works by decreasing the amount of estrogen circulating in the body substantially. (You may be surprised to learn that there is estrogen in women who are post-menopausal. For example, fat cells in post-menopausal women are a source of estrogen -- a low level source to be sure, but a source, nonetheless.)

In an interesting and thought-provoking comment, the authors note that "the occurrence of certain symptoms could be the ultimate bioassay, which might be a reflection of the degree of biologically relevant estrogen suppression produced in individual women by a specific treatment."

This isn't the first time a biologic response has been linked to positive treatment response in cancer therapy.

Shortly after the drug cetuximab (Erbitux) was investigated in the treatment of advanced colon cancer, researchers were commenting that patients in the waiting rooms quickly picked up on the fact that a rash on the face was associated with a better chance of response. The same effect was subsequently noted in patients treated with Iressa and Tarceva, which are targeted therapies used in the treatment of lung and pancreatic cancer.

In the mid-1970s, when tamoxifen was first made available for the treatment of women with metastatic breast cancer, I would not infrequently have women come to my office soon after starting this new medicine (it was revolutionary at that time because it was a pill, easy to take and generally free of side effects) complaining of bone pain. Some of these women also had significantly elevated blood calcium levels.

Findings May Encourage Adherence to Treatment

Imagine reassuring a woman with significant pain that -- based on your limited medical experience with this new pill -- this was in fact a good sign, since it had meant in many other women who had developed those same symptoms that they responded to the treatment with improvement in their breast cancer.

I went back into the medical literature and actually found an article from 1978 that described this observation, and called it a "tamoxifen flare." It also confirmed my recollection that these women actually did well with respect to their cancer.

So, with all of the fancy tests we have to measure the impact of the drugs we use, it turns out that symptoms such as joint pain and hot flashes in a woman with breast cancer treated with a hormone-blocking drug may actually be a good sign that the drug is working.

Sometimes, our bodies are better indicators of our conditions than our science.

That's actually not a new observation, but it helps remind us that with all our knowledge, we can't measure everything with a lab test or X-ray. Listening to our patients still has value.

Len Lichtenfeld is deputy chief medical officer of the American Cancer Society. You can view the full blog by clicking here.