WEDNESDAY, April 9, 2003

"Quality of Life: Strategies for Living Well During Treatment"

Our special guest for the evening is Mindy Goldman, M.D. obstetrician/gynecologist at UCSF, and director of the follow-up program at the Carol Franc Buck Breast Care Center, whose particular interest is women with or at high risk for breast cancer. Many women who are dealing with cancer may not have seen a gynecologist for a while. Young women who need chemotherapy may be thrown into acute, early menopause. The symptoms can be more severe than when it occurs naturally in midlife. By far the biggest complaint is hot flashes. 25 to 50% of women on tamoxifen will experience them. Now more than ever it is important to investigate alternatives to hormones to treat menopausal symptoms. Some alternative treatments include black cohosh, and vitamin E.  Various herbal remedies such as evening primrose and dong qi still require more research to determine their safety or efficacy. It is also important to determine whether there are any drug-herb interactions. Some interactions that we do not expect can occur. Black cohosh may slow the metabolism an actually increase drug toxicity. St. John’s Wort may increase the metabolism and decrease drug efficacy, especially hormonal agents which can be used to treat breast cancer. With prescription medications, some of the antidepressants like Effexor (in low doses, 25-75mg/day) have been used for relief of hot flashes. A large randomized trial show that Effexor was significantly better than placebo. This was not the case with other antidepressants like Paxil or Prozac, so there may be a drug class effect.

Other issues dealt with in the follow-up program include sleep disturbances and sexual dysfunction. Post chemotherapy—or any therapy including radiation—many women will notice changes in their sexual functioning, decreased libido. If it associated with vaginal dryness, one can use topical estrogens or testosterone, but these have not been well studied for their safety for ER+ tumors. Some of the antidepressants may actually cause sexual dysfunction in the doses used for depression. To counter this some people use another antidepressant called Wellbutrin. Many new studies are looking at drugs like Viagra, which cause increased blood flow to the genitals and smooth muscle relaxation that are thought to improve libido.

Chemo-brain or chemo-fog, is a cognitive dysfunction associated with chemotherapy. It has been very hard to separate out the stress associated with diagnosis versus the side effects of chemotherapy. There have been no prospective studies because the testing for cognition is so complicated.

As ovarian suppression for premenopausal women becomes a larger issue, osteoporosis becomes a larger issue. We have new agents that appear to be much more potent at preserving and building bone mineral density. A new intravenous bisphosphonate called Zoledronate has been used successfully with metastatic patients. Some patients with mild bone loss actually had some recovery of bone with one or two intravenous infusions per year. It has yet to be FDA approved for prevention of bone mineral density loss, but will soon be approved for patients who fail other oral bisphosphonates. Fosamax is an oral bisphosphonate without the side ring that increases the potency of Zoledronate. It is great for preventing further bone loss, but does nothing to build bone. Fosamax can also be hard to tolerate, sometimes causing gastrointestinal upset, reflux and esophagitis.

Does Arimidex cause fewer side effects than tamoxifen? The ATAC trial compared anastrozole head to head with tamoxifen. After four years of follow-up, the findings are that anyone taking hormone drugs is at risk for hot flashes. It is very difficult to measure the intensity of these events with current scale mechanisms. Women in the U.S. are much more likely to complain of side effects than their European counterparts. So the study may be biased in that direction. Results so far indicate about 5% more hot flashes in the tamoxifen arm. These tend to diminish over time. Because tamoxifen hyper-stimulates the ovaries, premenopausal women are also developing ovarian cysts, which do not go away over time. Aromatase inhibitors can only be used in post-menopausal women.

Does diminished cognitive function have anything to do with simply getting the cancer diagnosis? When cognitive function was measured right after diagnosis, it was terrible. Initially, the patient can be totally overwhelmed. This can be especially devastating for young women.  Distractions don’t seem to help, but many women seem to perk up somewhat during treatment, because something active is being done to combat the disease.  At the end of the treatment phase there seems to be an enormous psychological drop that in many ways is greater than that seen after diagnosis, when people become panicked about their outcome.

How do you learn to live with the knowledge that there is something to worry about? Take it one day at a time. It is important in any follow-up program that women be supported psychologically through this phase. Overall quality of life seems to return to most people about a year after treatment. Many breast cancer diagnoses overlap the start of menopause, and symptoms can be similar: memory loss, hot flashes, fatigue etc.

If you have been taking herbs before your cancer diagnosis, can you go back on after treatment while still taking tamoxifen? We do not have an answer to that. The only agent that has been studied at all is St. John’s Wort and that was because of it’s anti-depressant qualities. It clearly changes metabolism and other pharmacokinetic changes that are not well understood. Herbal formulas can include hundreds of herbs that have not been studied. There is also no standardization to herbs and no government controls on these products, so the amount of active ingredient can vary.

What about fatigue? Fatigue can be enormously disabling so there has been a lot of interest in trying to improve fatigue especially during chemotherapy. Procrit is an erythropoetin related to red cell growth factor that is used for anemia. The drug is quite expensive and the results of trials so far are unclear. More research is needed. Ritalin is a drug that is being studied for use during chemotherapy to give people more energy. There is interest in testing it for use after chemotherapy, primarily in the metastatic setting, but some concern over side effects like agitation.

What is the recommendation for gynecological exams after cancer? Annual gynecological screening for cervical cancer is not necessary if one does not have multiple sexual partners. After 3 normal Pap tests in a row, it is up to the patient and the clinician to decide on the frequency of the test, between 1 to 3 years. Annual Pap smear is still recommended for women on tamoxifen.

What about bone density tests? We still do not know if bone mineral density tests predict fracture, but we do know that it can give us information on the rapidity of bone mineral loss and how aggressive we should be with treatment. For this reason it is recommended each year for women with low bone mineral density. Maybe with the advent of aromatase inhibitors in the adjuvant setting, we will be doing more. Very recent research has shown that women with high BMD have a higher risk of breast cancer, due to higher levels of testosterone.

Is there a test for cancer spread using the lymph system? This would be a good idea except that the lymph channels are quite small and it is very hard to get the fluid out unless there is some pathologic blockage. This is why blood is used. It is not ideal because while cancer cells circulate through the blood they do so at very low levels and are only identified by the time the cancer is advanced. Having an accurate test for cancer in the blood would be very helpful in diagnosing cancer early.

Can stress cause cancer? In the obstetric literature, there is some suggestion that stress can cause pre-term labor and delivery. Cancer grows for so long, it would be hard to measure the effect of stress over a long period, especially as stress seems to occur episodically. It may be that our tolerance for stress decreases with age as the incidence of cancer increases.

Does HRT cause breast cancer? We really needed a large randomized controlled trial to answer this question. The ongoing Womens’ Health Initiative study got a lot of publicity when it was determined that hormones did not prevent heart disease as originally thought. The arm of the trial with women taking both estrogen and progesterone was stopped when it was found that there were increased blood clots and strokes and associated higher incidence of breast cancer. The message is that care needs to be individualized. One piece of good news was that women who developed breast cancer and were on hormones had a lower mortality from their disease.

How long does it take to return to the premenopausal state after taking Zolodex? Zolodex suppresses the function of the ovaries and will put you into premature menopause. In a recent trial of women taking the drug for two years, about 23% never recovered their periods. Women who were over the age of 40 had a much greater risk of permanent menopause.

Next month: “A Primer on Molecular Diagnostics: Revealing the Mystery of Proteomics and DNA Array Technology”.