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Endocrine Treatments for Breast Cancer

For Women With Estrogen-Dependent Breast Cancer: Endocrine Therapy Can Greatly Improve Survival Rates

By John Casey

Updated August 09, 2010

(LifeWire) - Breast cancer is an extremely complicated disease. However, at its simplest, it can be divided into two types; one is known as estrogen receptor-positive breast cancer, which needs the female hormone estrogen to grow, and the other, which does not depend on estrogen, is known as estrogen-receptor negative. Endocrine therapies, sometimes called hormonal therapies, target the estrogen receptor-positive type, which accounts for about 65% of all breast cancer.

Hormones are chemical messages that regulate and control a variety of bodily functions from reproduction to metabolism to mood. The body's endocrine system consists of glands and other tissues that secrete hormones or aid in their synthesis.

Endocrine therapy is usually part of a comprehensive breast cancer treatment plan that may also vary to include surgery, chemotherapy or radiation therapy.

It is this combination of approaches that has helped transform breast cancer treatment, bringing profound improvements in survival rates. Today, according to the Susan G. Komen For the Cure breast cancer foundation, when the disease is caught early -- that is, before it spreads beyond the breast tissue -- the 5-year survival rate is better than 95%.

It's All About Blocking Estrogen

Hormonal therapies for breast cancer are all about blocking the production of estrogen or limiting its ability to reach the tumor cells that need it to grow.

Estrogen is one of the main female hormones regulating reproduction. In younger women, the ovaries produce estrogen. After menopause, they stop, and a woman will no longer have periods. But postmenopausal women still produce a limited amount of the hormone. Another part of the endocrine system, the adrenal glands, makes a hormone called androgen. And aromatase, an enzyme that is produced by fat cells, can convert androgen into estrogen.

Probably the simplest -- although also the most invasive -- method of endocrine therapy is surgical removal of the ovaries, or an oophorectomy. No ovaries means little estrogen will be available to the tumor, and that means better survival rates for women with estrogen receptor-positive cancer, whether it's confined to the breast tissue or has spread, or metastasized, to other parts of the body.

But in a younger patient, removal of the ovaries is a drastic step, transforming a premenopausal woman who could have children into a postmenopausal woman who cannot. Many premenopausal women choose other hormonal-based approaches to avoid sacrificing their ability to have children, as well as to defer the various unwelcome symptoms of the menopausal transition.

Drug Therapies

The following two types of drug therapies used in treatment are as follows:

Selective Estrogen Receptor Modulators -- The endocrine therapy of choice for premenopausal women is the class of drugs known as selective estrogen receptor modulators (SERMs), which are taken orally. Probably the best known of these is Nolvadex (tamoxifen). SERMs work by blocking estrogen in breast tissue; but in other parts of the body this effect can produce side effects similar to those who are in the menopausal transition, such as vaginal dryness, excessive sweating, sleeplessness and hot flashes.

SERMs can reduce the growth of tumors even in relatively advanced cases. If a patient is at high risk and has a family history of breast cancer, then her clinician may prescribe SERMs as a preventive measure before any sign of cancer. The success rate for these drugs is good. In studies of estrogen receptor-positive cancer, nearly 60% of women taking SERMs experience a reduction in tumor growth.

Because they react in different ways and in different parts of the body, SERMs can have good as well as bad side effects.

On one hand, they can increase a patient's risk for heart attack, stroke, uterine cancer and blood clots in veins of the legs. When they first take the drug, some women also experience what are known as flares. The flares may involve an increase in pain and in the size of tumors located near the skin's surface, but these effects usually pass in a few weeks, and the worst symptoms can often be controlled with other medications.

On the plus side, along with their potent anti-cancer properties, tamoxifen and other SERMs can help slow or even prevent osteoporosis.

Aromatase Inhibitors -- These drugs, known as AIs, block the body's means of making estrogen via the enzyme aromatase. These drugs are now considered to be first-line endocrine therapy for metastatic estrogen-receptor positive breast cancer in post-menopausal women. They are also considered to be first-line adjuvant therapy for "curable" estrogen-receptor positive breast cancer in women who are beyond menopause. In both these scenarios, AIs are more effective than SERMs.

Unlike SERMs, the AIs do not appear to increase the risk for uterine cancer or cardiovascular problems. On the other hand, they don't confer any protection against osteoporosis. AIs are not prescribed alone for pre-menopausal women because they can cause large, painful cystic growths on the ovaries. They are used in pre-menopausal women only in combination with drug-based ovarian suppression.

The most significant advantage of AIs over SERMS is a better overall effectiveness. Women with metastatic breast cancer have better survival rates when taking AIs. For these reasons, the AIs are usually the first endocrine therapy used for postmenopausal women.

Where Hormonal Therapy Is Headed

Some scientists speculate that endocrine therapies probably won't significantly boost breast cancer survival rates much further, although refinements of existing therapies will continue. Despite such views, research into hormone-based therapies is considerable and ongoing.

For example, researchers are focusing on the different ways in which breast cancer responds to estrogen. They hope that by studying the genetic underpinnings of tumor types, they can further improve response and survival rates. Much of this work looks at why some forms of breast cancer respond to endocrine therapy and some don't. A related issue is why some tumor types that initially respond well become resistant to endocrine therapy thereafter.

More About Aromatase Inhibitors

Sources:

Hayes, Daniel, MD. "Endocrine Therapy for Metastatic Breast Cancer." Uptodate.com. 3 Jul 2008.

Ellis, Matthew. "Current and Future Choices in Endocrine Therapy." Breast Cancer Research. 9:Suppl. 2 (2007). S15.

Ingle, James. "Adjuvant Endocrine Therapy in Postmenopausal Breast Cancer." Clinical Cancer Research 9(2003): 480S-485S.

Pritchard, Kathleen. "Endocrinology and Hormone Therapy in Breast Cancer: Endocrine Therapy in Premenopausal Women." Breast Cancer Research. 7:2 (2005). 70-76.

LifeWire, a part of The New York Times Company, provides original and syndicated online lifestyle content. John Casey is a health and science writer in New York City. He has written for the New York Times, Parade magazine, WebMD.com, CBS HealthWatch.com and other publications.
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