Jewish World Review Nov. 10, 2003 / 15 Mar-Cheshvan, 5764

Post-tamoxifen treatment for breast cancer

By Robert A. Wascher, M.D., F.A.C.S. | For women who have breast cancer, Tamoxifen is an effective adjuvant treatment option when the breast cancer cells are sensitive to the female hormone estrogen, particularly in women who have already passed through menopause.

Tamoxifen acts by blocking the receptors that estrogen latches onto, thus preventing a woman's own estrogen from stimulating the growth of additional tumor cells. Based upon previous studies, taking Tamoxifen for more than five years appears to confer no more benefit than a five-year course, although the risks associated with the drug continue to increase. These risks include an enhanced risk of blood clots in the veins and lungs, uterine cancer, and cataracts.

Although a five-year course of Tamoxifen significantly reduces the risk of recurrent or new estrogen-responsive breast tumors, many women (and their physicians) have been searching for additional therapies that might benefit breast cancer patients after they've completed Tamoxifen therapy.

A second class of drugs, know as "aromatase inhibitors," have recently been developed. After menopause (or after total hysterectomy, during which a woman's ovaries are also removed), a woman's ovaries are no longer the primary source of estrogen and other female sex hormones.

However, the adrenal glands, as well as fatty tissue throughout the body, continue to produce estrogen throughout a woman's life. The aromatase inhibitors block a key enzyme, aromatase which converts steroid molecules into estrogen in the adrenal glands and fatty tissues. Early clinical studies have suggested that this new class of anti-hormonal drugs are likely to be at least as efficacious as Tamoxifen in preventing the recurrence of estrogen-sensitive breast tumors.

However, one important caveat to the use of aromatase inhibitors must be mentioned when comparing them to Tamoxifen and related "selective estrogen receptor modulators." Tamoxifen and related drugs, such as raloxifene, will block the effects of estrogen on breast cells in women with or without functioning ovaries. However, the aromatase inhibitors only act on the adrenal gland and fatty tissue sources of estrogen, and hence can only be used in women who no longer have functioning ovaries.

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A new study has just been published, and it evaluated the use of an aromatase inhibitor, letrozole, in postmenopausal women who had completed five years of Tamoxifen after being diagnosed with breast cancer. The study enrolled 5,187 women, and was prematurely shutdown when it became evident that the women taking the letrozole were experiencing significantly fewer breast cancer recurrences than the women who were taking the placebo pills.

The results of this study are reported in the current issue of the New England Journal of Medicine. The study found that, after an average of little more than two years, the group of women taking letrozole experienced 75 recurrent or new breast cancers, while a similar sized group of women taking the placebo pills experienced 132 such cancers. Following statistical analysis, it was estimated that the disease-free survival rate at four years of follow-up was 93% for the women taking letrozole, versus 87% for the women taking the placebo.

This means that, despite the very short duration of the study, the women who were taking the letrozole were significantly more likely to be alive and free of new or recurrent breast cancers when compared to the women who took the placebo pills. Due to the short duration of the study, no significant differences in overall survival rates were identified between the two groups of women in this study. However, if the disease-free survival advantages seen in the women taking letrozole persist over time, one would expect to see significant differences in the overall survival rates within about 10 years, given the natural biology of breast cancer.

A slightly higher risk of osteoporosis was seen among the women taking letrozole, which is not surprising in view of the role of estrogen in maintaining bone density. Ironically, although Tamoxifen blocks estrogen receptors in the breast and the uterus, it actually stimulates estrogen receptors in the bone, and acts like an estrogen to improve bone density.

Based upon this and other studies, it is beginning to appear that at least certain aromatase inhibitors may have a significant role to play in the prevention of breast cancer in women with a history of estrogen-sensitive breast tumors, although these drugs can only be used in women without functioning ovaries. Other studies have also shown that these drugs, when given to women with recently diagnosed breast cancer, and in place of Tamoxifen, may be as effective, if not more effective, than Tamoxifen in preventing the recurrence of preexisting or new breast cancers.


There are literally dozens of different medications currently in use to treat high blood pressure, and these drugs fall into various classifications depending upon their mechanisms of action in the body. Many studies have confirmed that the effective control of high blood pressure can prevent, or at least reduce, damage to the body's vital organs, including the brain, the heart and the kidneys. However, the proliferation of numerous different treatment regimens has left both patients and their doctors confused about the most efficacious approach to managing this insidious disease.

A new study in the current issue of the journal Lancet looked at the results of 29 different randomized clinical studies, involving 162,341 patients with high blood pressure. These diverse studies evaluated the health-sparing effects of several classes of anti-hypertensive drugs on patients with high blood pressure, including the angiotensin-converting enzyme ("ACE") inhibitors, calcium channel blockers, angiotensin-receptor blockers ("ARBs"), diuretics, and beta-blockers. While there are some clinically valid reasons why your physician might preferentially prescribe one class of high blood pressure medications for you over others (i.e., due to one or more specific health factors in your case), many if not most physicians prescribe such drugs based upon their own personal knowledge and comfort levels with certain classes of drugs.

The study in Lancet found that as long as the regimen in question targeted patients to reach significant blood pressure reduction goals, the end results, in terms of overall health, did not vary significantly from one regimen to another. Specifically, there were no major or significant differences in the incidence of heart attacks or strokes among the various regimens, as long as similar reductions in blood pressure were obtained. Indeed, the study found that the greater the reduction in blood pressure achieved, the lower the risk of subsequent cardiovascular events, irrespective of the drug or regimen used.

Once again, there may be good medical reasons why you should avoid one or more classes of medications for your high blood pressure. However, this study should reassure both you and your doctor that, whatever regimen you are on, you will be receiving the maximum protection against the dangerous effects of chronic hypertension as long as your treatment is adjusted to provide you with the greatest possible reduction in blood pressure that can be safely obtained by your regimen.


Based upon some very interesting research on Mediterranean families with an exceptionally low risk of cardiovascular disease, it has recently been discovered that bigger really is better! The so-called "good cholesterol," high-density lipoprotein, or HDL, is known to reduce the amount of cholesterol-rich plaque that forms on your arteries. The HDL particles essentially remove cholesterol deposits from the lining of your arteries, and return the excess cholesterol to the liver for excretion. Certain families in Mediterranean Europe who were found to have a very low incidence of cardiovascular disease were subsequently found to have unusually large HDL particles in their blood, which is thought to at least partially explain their resistance to heart disease. A gene that codes for this jumbo HDL particle was later identified and sequenced. Based upon this discovery, scientists theorized that injecting this large HDL molecule into patients with normal-sized HDL particles might help to reduce the size of cholesterol plaques in their arteries.

Ten hospitals in the US participated in this study, and 47 patients with known coronary artery atherosclerosis completed a series of 5 intravenous injections of the ApoA-I Milano over a period of 5 weeks. Intravascular ultrasound was used before and after the injections to measure the size of atherosclerotic plaques in their coronary arteries. The study was performed in a randomized and double-blinded manner, so that neither the patients nor the physicians knew who was receiving the ApoA-I Milano particles and who was receiving placebo injections.

The results were, frankly, quite dramatic after such a brief duration of therapy. The patients who received the HDL particles experienced an average 3.17% reduction in the volume of coronary artery plaques versus a 0.14% reduction observed in the patients who received the placebo injections.

Although this very small pilot study will require validation by additional larger scale studies, this is the first study of its type to show that established atheromatous plaques on the coronary arteries of patients with heart disease can be significantly reduced following the injection of a substance into the blood. In the best case, this approach might someday allow patients to undergo periodic treatments in their doctors' offices to melt away disease-causing plaques from their arteries. Let's hope that the results of this pilot study hold-up upon further study!

JWR contributor Dr. Robert Wascher is an oncologic surgeon, professor of surgery, oncology research scientist, and author. He lives in Honolulu with his wife and two daughters. Comment by clicking here.



© 2003, Dr. Robert A. Wascher