Why not try to prevent breast cancer?

Can we do that? The answer is yes! I’ve talked about risk factors for breast cancer that can be lowered. We know that staying slim, exercising, not taking post-menopausal hormones containing progesterone can reduce a woman’s risk of breast cancer. But we can’t change a woman’s genes. If a woman has the wrong genes, then all these things can help, but not enough. There are drugs that can reduce breast cancer risk. These are called SERMs – an abbreviation that says that these drugs attach to sites on cells where estrogen attaches. It is thought that estrogen fuels breast cancer growth. The first of these SERMs was tamoxifen, discovered at least 30 years ago. Early studies of tamoxifen in women treated for breast cancer with this drug found that there was a reduced rate of cancer in the other breast – the one that didn’t have cancer originally. More studies found it reduces breast cancer rates in high high-risk women without the disease. But tamoxifen has side effects. The most disturbing one is that it stimulates the lining of the uterus and so that women taking it have a higher rate of cancer of the uterus. Since the development of tamoxifen, other SERM drugs have been created – raloxifene, lanoxifene, and arzofoxifene. None of these newer drugs cause uterine cancer. All the drugs have the benefit of strengthening bones – so they also prevent osteoporosis, which is actually why raloxifene was first developed. In the early trials, not only did it prevent osteoporosis, it also lowered the rate of breast cancer in the women taking it. There have been a lot of studies looking at preventing breast cancer with these drugs and recently a paper was published (Lancet, April 2013) that summarized the results of all these clinical trials. A little over 83,000 women were entered into these trials; they were given either a placebo or one of the SERMs and they were followed for around 10-15 years. The results were clear-cut but to my mind didn’t really provide direction for the average woman. The rate of breast cancer was lowered from four in one hundred women in the placebo group to two in one hundred in the women taking the SERM. But, there was no drop in the number of women who died from breast cancer. As expected, women taking the SERM had a lower rate of osteoporosis and a higher rate of uterine cancer if they were taking tamoxifen. Women taking the SERMs also had about double the rate of blood clots – a known side effect of these drugs. The authors of the study suggested that women should be taking these drugs, but to me this seems overly aggressive. They did prevent a small number of breast cancers, but as is well know these were generally the kind that are easily treated and aren’t terribly dangerous as shown by the fact that no lives were saved. And who wants to take a pill with small, non-life-saving benefits, for 5 years? This is why, according to the authors of the study, few women take these drugs to prevent breast cancer. Not to say there aren’t some women who wouldn’t possible benefit – namely those at very high risk, but, unfortunately these women haven’t been well studied to know for sure if there would be a major benefit. Indeed, many women who have a genetically determined high risk of breast cancer prefer the certainty of double mastectomies. That is almost 100 percent certain.

Another cancer we can prevent

Although no one talks about it much, one of the results of the AIDS epidemic has been that there has been an increase in the number of men diagnosed with anal cancer. This cancer arises in the anus, about a half-inch inside and above the opening. The first symptom is itching that doesn’t go away and then soreness and bleeding and finally, pain. In my practice, the only patients I saw with this were women. I wasn’t sure why until the discovery of HPV (Human Papilloma Virus). Not only is this the virus that causes cervical cancer and is sexually transmitted but now we know it also causes anal cancer. It isn’t clear whether a woman needs to have anal intercourse to increase their risk for anal cancer or whether it arises because the anus is in the same neighborhood as the vagina. With the AIDS epidemic, we began to see young men developing this cancer. This occurred mainly in the 1990’s and has continued until now. It isn’t certain why. We know that those suffering from AIDS have a lowered immune status.. Perhaps earlier, when people with AIDS were dying so quickly, the cancer never got a chance to develop. Now, as people, particularly men in the U.S. are living with the disease, it is beginning to show itself. Early in my practice, anal cancer was treated with surgery. That meant an extensive removal of the anus and a bag attached to the abdomen to drain the colon in place of the eliminated anus. Not pleasant. Later, we began using chemotherapy and radiation, which seemed to cure just as many people. Still, the tissue is never the same after this insult. How common is HPV infection and can we prevent it? According the Centers for Disease Control, about 14 million people are infected every year. So nearly all sexually active adults will be exposed to HPV at some time in their lives. Most fight off the infection but some don’t. How to prevent it? Simple. There is a vaccine that will prevent infection with HPV and will prevent most anal cancers as well as cervical cancers. It is highly effective and recommended for all children at ages 11 or 12. Of course at that age, vaccines are harder to administer because the child has something to say about getting a shot. Also, people in some parts of the country are concerned that vaccination will encourage promiscuity, because the main disease it is intended to prevent is cervical cancer. About one-third of girls have been vaccinated in the U.S. Far fewer boys have received the vaccine because it has only recently been recommended for boys. But the future looks bright if doctors and parents continue to push for vaccinations. Another cancer we can beat.

It always hurts – is there a drug to relieve the pain of neuropathy?

This comment is typical of patients with what we call peripheral neuropathy, another side effect of some chemotherapy drugs. The major drugs that cause this are platinum compounds, taxanes and vincristine. For some mysterious reason, these drugs damage nerves and cause them to produce pain or numbness or tingling. – sometimes all three. Another side effect can be that the nerves that innervate muscles fail. I remember one patient who just couldn’t flex his foot upwards and walked with a flopping motion, something we call foot drop. This nerve damage occurs at least half the time in patients exposed to the chemotherapy drugs I mentioned above. And, the longer the treatment, the greater chance that neuropathy will develop. And it is hard to treat. I remember having a peripheral neuropathy in my right arm for months after I broke my collarbone. The break must have damaged the brachial plexus, the nerves that run under the armpit and down the arm. The only thing that helped my pain was liberal quantities of gin – my drug of choice. After a few months the pain went away and I could reduce my gin intake. But for many thousands of patients who suffer from chemotherapy induced neuropathy, gin or other alcoholic drinks aren’t an option. Doctors have looked hard for useful treatments but have generally come up empty handed. Now a new study has appeared that suggests a drug called duloxetine may help. Duloxetine is a drug used for major depression and is better known as Cymbalta. The study, published in the April 3, 2013 issue of the Journal of the American Medical Association looked at over 200 patients who had developed painful neuropathy after receiving one of the neuropathy-causing drugs. Half were given Cymbalta and the other half a placebo. After 5 weeks of treatment the patients given the drug had less pain. And also important, the benefit began within the first week or two of treatment. What about side effects? In this study, they did not seem to be a problem and in general Cymbalta does not seem to have many severe side effects – especially compared to the discomfort of the neuropathy. So this drug gives hope to patients with this all too common problem and is probably better than gin.

Our most important medical test device for cancer patients – the scale.

Sometimes in my practice, the nursing assistants would forget to take a patient’s temperature or even their pulse or blood pressure. But one test they never failed to do was to weigh the patient. Nothing better indicated a patient’s clinical status than his/her weight. If their weight was stable, then they were successfully holding off the cancer. If the weight went up, perhaps they were winning the battle. But if their weight went down, it was time to worry. Of course many will say that it is the chemotherapy that is making the patients shed pounds. Not true, except for some really harsh protocols. In fact, when we started giving chemotherapy to otherwise healthy women recently operated on for breast cancer, their biggest problem was weight gain. Almost always, when a cancer patient is constantly losing weight and doesn’t have anything interfering with eating, it is because the cancer is advancing. The problem is called cancer cachexia. Although as you would expect, some of the lost weight is due to fat loss, even more important is the loss of muscle mass. Needless to say, this weight loss distresses both the patient and their family. Much of my time in talking to patients and their families was in discussing eating – what to eat – my answer – anything. There are a huge number of studies trying to figure out why this weight loss happens, but there have been no clear answers. Some of it is caused by poor appetite, but even patients who seem to be eating enough lose weight. But we do know it is bad and the patient is likely to die in the next few months. I was reminded of this problem when I saw a study on the use of melatonin to prevent weight loss in advanced cancer patients. Why melatonin I asked? Well, there is some complicated biologic reason it might work and there have been some small studies that made the drug seem promising. But, in the article I saw, melatonin was no better than a placebo. Patients taking the melatonin lost as much weight on those on the placebo. And at the end of a year, nearly 80 percent of patients in either group had died. Many drugs have been tried but none have been terribly effective. The most promising has been a drug called megestrol, a progesterone-like drug. In large doses this seemed to help some patients but the benefit has been short-lived. Steroid hormones have also been tried with the same results. Likewise marijuana, intravenous nutrition, dietary counseling, high fat meals, etc. have not proved useful. So we are left with little help. Not to say the patient shouldn’t try something, but as the editorial accompanying the melatonin article pointed out, these treatments can be expensive so don’t sell the farm to take them.

More tamoxifen may be better.

So you have been taking tamoxifen to prevent your breast cancer from coming back and are now approaching the 5-year mark. Time to stop? After all that was the deal your oncologist promised. And, enough hot flashes and worry about uterine cancer and blood clots developing. But things have changed. Your doc may recommend you keep taking the drug another 5 years. The good news is that your chance of having your cancer come back is reduced by around 25 percent. That is according to a new study just published in the journal Lancet (Mar 9 2013). There are lots of studies that show that 5 years treatment with tamoxifen is better than 2 years in lowering the chances of recurrence and death from early breast cancer, but it has been hard to get a study together of 10 years. Finally it has been done. A large team of investigators from around the world, led by the Oxford Trialists Group (believe me, the best) entered nearly 7000 women into this trial. Half were given tamoxifen for 5 years and the other half took the drug for 10 years. Then came the waiting to see what would happen. Ten years after the women started taking their tamoxifen, there was very little difference in recurrence rate between women who stopped at 5 years and those continuing to take their meds for the full ten years. But by 15 years, there were more recurrences in the 5-yer group and more deaths. At the 15-year mark, 15 percent of the women in the 5-year group had died; but only 12 percent of the women in the 10-year group had died. This means that for every hundred women taking the drug for ten years, three lives were saved. The investigators calculated that the 10-year women lowered their risk of dying by about one-fourth. What about side effects? Well there were a lot more cases of uterine cancer in the 10-year women (116 vs. 63) and a few more deaths from this cancer (17 vs. 11). The 10-year women had more blood clots but this was balanced by fewer heart attacks. So what to do? The investigators end their paper by saying that 10 years appears to be better, but that they want to see what happens to these women in another 5 years. Your choice.

Is proton therapy the best kind of radiation for prostate cancer?

My radio alarm goes off early in the morning. Often one of the first ads I hear while I am getting ready to move out of bed is from Loma Linda University Medical Center. They are pushing their proton beam radiation therapy early in the morning for old guys like me who might have prostate cancer and can’t sleep much past 5 in the morning. They hail it as causing fewer side effects than standard treatment. What they don’t say is that it is nearly twice as expensive as the standard therapy. So is it better? No one really knows. There have been no head to head comparisons with standard treatment. But, this week, The Journal of The National Cancer Institute (Jan 2, 2013) published a possible answer to this question. The researchers were radiation therapists from Yale Medical School. They looked at data from the huge Medicare database to see if they could at least get at least a sense of whether proton therapy was better. The Medicare database consists of codes. Every time a doctor treats a patient, he or she puts in one of a huge number of 5-digit codes for the diagnosis. Sore throat has one code, broken leg, another, etc. Treatments also have codes. Standard radiation had one code and proton beam another. Likewise the complications of the treatment each have their separate code. Rectal problems, bladder problems, sexual problems, all of which can occur with radiation for prostate cancer, each have their own code. The investigators identified men who had received radiation treatment for prostate cancer and using the codes separated out the ones that received proton beam from those who received conventional radiation therapy. Then they examined the men’s records after the treatment to see how many had seen their doctors for side effects of the treatment. The side effects were likely fairly severe or the treating doctors may not have listed them among their diagnoses during the follow-up visits. The researchers then counted the number of patients with side effects who received either form of therapy and compared the numbers. Bottom line: Although there were slightly fewer side effects in the proton beam men six months after treatment, the side effects numbers evened out by the end of one year. So no big differences that would justify the much higher price ($32, 000 versus $18,000) of the proton beam therapy. American medicine is captivated by newer and fancier technology. According to the report many new proton beam centers are being built. Up goes the cost of Medicare.

More tamoxifen is better!

More tamoxifen is better! When tamoxifen first appeared as a major drug to prevent recurrence in women treated for breast cancer, the major question was how long it should be given. Although it is effective in preventing the recurrence of the cancer, it can cause cancer of the uterus and many women taking it suffer from hot flashes. At first the debate was about whether to take the drug for one to two years or five years. Five years, it turns out, beat the one and two year programs. But because breast cancers that respond to tamoxifen – so called estrogen dependent cancers – tend to be slow growing, the effect of the tamoxifen shows up well after the drug is stopped. So even several years out, women who took the drug longer were living longer. That is why it took so long for this final (?) study to be published – whether ten years of tamoxifen is better than five years. After all, it took several years to recruit the nearly 13,000 women and another ten years thereafter to show that ten years of tamoxifen is better than five years. The study was very simple. Women who had taken tamoxifen for five years after surgery (perhaps radiation also) for early breast cancer were then given either another 5 years of the drug or told to stop. There were about 6500 women in each arm of the study. Fifteen years after starting tamoxifen there were 397 breast cancer deaths in the women in the five-year arm compared to 331 deaths in the group of women who took tamoxifen for 10 years. Furthermore another 25 women in the five-year group died of other causes compared to only 8 in the ten year group (tamoxifen seems to prevent coronary heart disease). What about cancer of the uterus – the feared side effect of tamoxifen? Not much to fear. There were only 17 deaths from uterine cancer in the women who took tamoxifen for ten years versus 11 deaths in the women who took it for five years. We don’t know how these women on ten years of tamoxifen felt – whether the hot flashes were a problem. But, it looks like a quarter of the women on the ten year program stopped their drug before they reached the ten year mark so side effects may have been a problem. But, bottom line, if you want the best possible chance of surviving as long as possible, go for the 10 years. Maybe, even longer. Stay tuned.