Prevention Through Drugs Or Surgery - Risk Factors: Breast Cancer

Content provided by the Faculty of the Harvard Medical School

Prevention through drugs or surgery

Using medication to prevent breast cancer

If you are at high risk of developing breast cancer, your doctor might suggest lowering your risk by using chemoprevention medications that block the negative effects of estrogen specifically in your breasts. This type of drug, called aselective estrogen receptor modulator (SERM), is engineered to behave like estrogen in some tissues while interfering with the action of estrogen in other tissues. A SERM can thus mimic estrogen's useful effects on the bones while guarding the breasts from the hormone's negative effects. SERMs also help prevent recurrences of breast cancer in women whose cancers are "estrogen-receptorpositive," meaning that the cancer cells need estrogen to grow. One SERM, tamoxifen, has been approved, and others, particularly raloxifene, are being studied.

Tamoxifen citrate (Nolvadex). Tamoxifen is a SERM that stops the growth of breast cancers that are estrogen-receptor positive. It does this by occupying the same molecular receptor sites on cells that estrogen normally uses, thus preventing estrogen from connecting with the tumor to help it grow. Tamoxifen has been studied in patients since the 1980s as a treatment for breast cancer, used with or instead of chemotherapy. It was found to substantially decrease the risk of breast cancer recurrence and the development of a second breast cancer.

Tamoxifen's usefulness in cancer prevention was tested in the nationwide Breast Cancer Prevention Trial that ended in March 1998. Every day for five years, more than 13,000 women who were at high risk for breast cancer (as determined by the Gail Model) took either a 20-mg tamoxifen pill or an inactive pill (placebo). Among the women taking tamoxifen, the risk of breast cancer was cut roughly in half. These women also had fewer bone fractures in the hip, wrist, and spine.

On the other hand, postmenopausal women who take tamoxifen are at a slightly greater risk for endometrial cancer. Women who take tamoxifen should be examined regularly and be aware of possible symptoms of endometrial cancer, particularly unexplained vaginal bleeding. They should also be especially alert to swelling or pain in the legs, which can be a sign of a blood clot. In addition, cataracts (clouding of the lens of the eye) develop somewhat more frequently in women who take tamoxifen. Tamoxifen's "lesser" side effects are those often associated with menopause: hot flashes, irregular periods, headaches, nausea, and vaginal dryness or itching. Another common side effect is a feeling of weariness that often begins soon after starting the drug. In most cases it doesn't last very long.

Raloxifene hydrochloride (Evista). Like tamoxifen, raloxifene is a SERM that has been engineered to imitate estrogen in some tissues - such as the bones and liver - and block it in others, such as the breast and endometrium. Raloxifene was approved by the FDA in 1998 for osteoporosis prevention and treatment, but has not yet been approved for breast cancer prevention at the time of this writing.

One study showed raloxifene markedly reduced the incidence of breast cancer in women who were at average risk for the disease. Among postmenopausal women with osteoporosis but no history of breast cancer, there were 76% fewer cases of breast cancer among those who took raloxifene for at least three years than among those who took a placebo.

Unlike women who have used tamoxifen, the women taking raloxifene did not experience a greater incidence of endometrial hyperplasia (abnormal growth of normal cells) or endometrial cancer compared with women in the control group. However, some did develop the blood clots of deep-vein thrombosis, an infrequent but serious complication of tamoxifen, too. Less severe side effects were hot flashes, flu-like symptoms, cramps, and fluid accumulation in the legs. In another study of prevention in higher risk women, raloxifene resulted in fewer cataracts and cataract surgery than tamoxifen.

For postmenopausal women who are at high risk of developing breast cancer (a Gail model of 5 year breast cancer risk of at least 1.67%) and/or a history of lobular carcinoma in situ, raloxifene may be considered. At the current time, raloxifene should not be used in premenopausal women

Preventive surgery

Some women who are at high risk for breast cancer, especially those with a mutation of a breast cancer gene, choose to have prophylactic mastectomies, in which both breasts are removed. Because ovarian cancer is also a risk in this group, women who have completed childbearing often also elect to have an oophorectomy (removal of the ovaries).

For women who choose prophylactic mastectomies, it is important to note that a total mastectomy, in which the breast and nipple are removed, is more effective than a subcutaneous mastectomy, which preserves the nipple and areola and a small amount of ductal tissue immediately beneath them. Subcutaneous mastectomy is not used often today because the breast tissue left behind is still vulnerable to developing a cancer. However, even with a total mastectomy, it might not be possible to remove every bit of breast tissue. In a very small percentage of women who choose this therapy, this remaining tissue may and does become cancerous.

Only a few studies have looked at the long-term results of preventive breast surgery. A Mayo Clinic study published in 1999 showed that prophylactic mastectomy can be greatly protective for women who are at high or moderate risk based on their family history, providing a 90% reduction in breast cancer risk.

If you are seriously considering prophylactic surgery, it is important to have your level of risk expertly assessed at a breast health center, by a breast cancer team, or by some other source of risk-evaluating expertise. Without this analysis, you may be taking a big step with insufficient information. Seek a second opinion and the advice of a counselor who specializes in these issues.

Last updated:	April 23, 2007