With all the positive effects associated with tamoxifen, one would think all women would want to undergo the five-year regimen, since breast cancer is the second cause of cancer deaths in women.
Cynthia R. Biron, RDH
If you are at moderate to high risk for breast cancer, chances are your gynecologist will tell you about the use of tamoxifen (Novadex) as a breast cancer chemopreventive agent. Whether or not you are a candidate for the treatment is determined by a host of factors, such as genetic predisposition, age, health conditions, and personal decisions. Weighing the risks and benefits of the treatment will be the determining factor in the decision of whether or not to undergo tamoxifen treatment.
The candidates for tamoxifen are evaluated for eligibility by the "Breast Cancer Gail Model Risk Assessment Tool" (see related article), which is used to calculate a patient`s five-year risk of developing breast cancer. The Gail Model, however, does not include genetic predisposition as the main factor in determining breast cancer risk. Many individuals who get breast cancer do not have the genetic predisposition, and many individuals who do have the gene mutation do not get breast cancer even when they live a long life. It appears that many factors are involved. Those who test positive for the BRCA1 or 2 gene mutation, though, are at increased risk for breast cancer and should consider tamoxifen chemoprevention. Al-though out of the 183,000 breast cancer cases diagnosed annually, only 5,000 to 9,000 are linked to the genetic mutation.
Testing for BRCA1 and 2 mutations are of concern due to the psychological effects that result from learning that one is a carrier, as well as the false sense of security one can get when testing negative for the gene mutation. The privileged information of a history of being a carrier of the genetic mutation may not always be kept perfectly confidential. Insurance rates, job opportunities, and personal relationships all could be adversely affected. So testing for the gene mutation means risks as well as benefits. The physician must thoroughly discuss this with the patient.
Other factors are also linked to breast cancer. The older the patient, the higher the risk of breast cancer. High-fat diets, obesity, smoking during puberty, taking birth control pills longer than 10 years, hormone-replacement therapy, and drinking two to three alcoholic beverages per week have each been linked to a slight increase in risk of breast cancer. Combinations of these factors would possibly compound risks. Most breast cancers involve estrogen-positive receptors. So the longer the breast tissues are exposed to estrogen, the greater the risk of cellular changes of malignancy. Early onset of menstrual periods and late menopause result in longer exposure of breast tissue to estrogen.
In addition, the earlier a woman has children, the better. In addition, breast feeding has been shown to make changes in breast tissue that can reduce incidence of breast cancer. Breast tissue undergoes changes during young women`s pregnancies, and those changes reduce the risk of breast cancer. Having children after age 30 or not giving birth at all seems to increase the risk of contracting breast cancer. The breast tissue changes that create a resistance to breast cancer do not occur when one has a first child in her late twenties or older, or not at all. Other possible links to breast cancer will be revealed with future research.
How does tamoxifen work?
Tamoxifen is a triphenylethylene derivative that functions as a selective estrogen receptor modulator (SERM). It binds with high affinity to estrogen receptors and mimics the effects of estrogens in tissues that improve bone metabolism and reduce cholesterol and improve cardiovascular health. In contrast, it is an anti-estrogen in the breast. Its use as an antineoplastic in the successful treatment of breast cancer compelled oncologists and researchers to conduct studies in its use as a breast cancer chemoprevention.
In determining the effectiveness of tamoxifen, 13,388 women at high risk for developing breast cancer were studied in the National Surgical Adjuvant Breast and Bowel Project (NSABBP) Breast Cancer Prevention Trial (BCPT). The participants were randomized and given either 20 mg of tamoxifen per day or a placebo for five years. The results of the study were released in April 1998 and indicated that tamoxifen use demonstrated a 49 percent (P<.00001) reduction in invasive breast cancer and a 50 percent (P<.002) reduction in noninvasive breast cancer.
With all the positive effects associated with tamoxifen, one would think all women would want to undergo the five-year regimen, since breast cancer is the second cause of cancer deaths in women (lung cancer is the first). The theory that "a drug always produces more than one effect" is also true of tamoxifen, and some of the effects are adverse.
Tamoxifen has been linked with an increased incidence of endometrial cancer. So far it has been reported that over 200 patients who have received tamoxifen treatment have developed cancer of the endometrium. This represents two out of every 1,000 tamoxifen-treated women. The elevation is small, and the risk is far outweighed by the number of lives saved by tamoxifen. Another study conducted with 324 case patients and 671 matched control subjects showed that women who had been exposed to tamoxifen treatment for more than five years had a 4.06-fold greater odds of getting endometrial cancer than those who had not had this exposure.
Other risks associated with tamoxifen treatment include stroke, pulmonary embolism, and deep-vein thrombosis, all of which are greater risks as a woman ages. For this reason, researchers have indicated that tamoxifen is best for younger women who are at high risk for breast cancer. Of course, most younger women have their uterus intact, and have difficulty deciding if they want to take the risk of getting endometrial cancer by taking tamoxifen to prevent breast cancer.
Women taking tamoxifen may experience menopausal symptoms such as "hot flashes," vaginal dryness, and sexual dysfunction. In a study of 57 women taking tamoxifen for breast cancer treatment, 54 percent reported discomfort during intercourse.
The risks and adverse effects associated with tamoxifen have caused researchers to look at other agents for chemoprevention of breast cancer. A trial is currently being conducted with raloxifene - a benzothiopene derivative similar to tamoxifen, but without the risks of endometrial cancer in humans and liver cancer in rats. Whether it could be nearly as effective as tamoxifen is will possibly be discovered in the current study.
Other agents that have shown promise as breast cancer chemopreventives include: anastrozle, letrozole, exemestane, rogletimide, fadrozole, vorozole, and formestane. Retinoids such as isotretinoin (Accutane) and carotenoids, such as beta-carotene and lycopene, in addition to well-known antioxidants such as vitamin C and E, and selenium, are all part of the future research in the movement to eliminate breast cancer.
If we cannot prevent breast cancer, we must detect it early. Mammograms as prescribed by your physician, monthly self-breast exams, and annual examinations by your physician/ gynecologist are the basics for early detection. The list of lifestyle changes for prevention is lengthy and often difficult to maintain. A low-fat diet, daily exercise, and little to no alcoholic beverages or tobacco products as a list is in and of itself a tall order.
One must be very self-disciplined to do it all. Or could moderation in all areas be the key? Any way you look at it, much is being done to wipe out breast cancer in our lifetime.
References available upon request
Cynthia R. Biron, RDH, is chair of the dental hygiene program at Tallahassee Community College. She is also a certified emergency medical technician.
Breast cancer risks
According to the Gail Model, candidates deemed at significant risk are:
* Age 35 or older with history of lobular carcinoma in situ (LCIS)
* or age 35 or older with five-year predicted risk of breast cancer at 1.67 perecent or greater based on the following risk factors:
* Current age (risk increases with age)
* Number of first-degree relatives with breast cancer
* History and number of breast biopsies
* History of atypical hyperplasia
* Age at menarche (under 12)
* Age at first live birth or nulliparity
Examples of five-year risk at or greater than 1.67 percent
Age 35 or older with any of these combinations:
* One first-degree relative with history
* Two or more benign biopsies
* Biopsy showing atypical hyperplasia
or
* Two first-degree relatives with history
* One benign biopsy
or
* LCIS
Age 40 or older with any of these combinations:
* One first-degree relative with history
* Two or more benign biopsies
* First live birth at 25-plus; under age 12 at menarche
or
* Two first-degree relatives with history
* First live birth at 19 or younger
or
* One first-degree relative with history
* Biopsy showing atypical hyperplasia
Age 45 or older with any of these combinations:
* Two first-degree relatives with history
* First live birth at 24 or younger
or
* One first-degree relative with history
* One benign breast biopsy
* Under 12 at menarche
* First live birth at 20 or older
Age 50 or older with any of these combinations:
* Two first-degree relatives with history
or
* One biopsy showing atypical hyperplasia
* First live birth at 30 or older
* Under 12 at menarche
or
* Two breast biopsies
* History of atypical hyperplasia
* First live birth at 30 or older
Age 55 or older with any of these combinations:
* One first-degree relative with history
* One benign biopsy
* Under 12 at menarche
or
* Two breast biopsies
* History of atypical hyperplasia
* First live birth at 20 or older
