The most common forms of breast cancer are hormone-receptor positive (estrogen and/or progesterone). The goal of endocrine (hormonal) therapy is to reduce the amount of estrogen available to those cancer cells.
Hormones function as chemical messengers throughout the body. Examples are estrogen, progesterone and testosterone.
About 2-out-of-3 breast cancers test positive for hormone receptors, which means cancer cells can receive messages from circulating hormones. When a cancer cell has receptors for estrogen, it’s called estrogen-receptor positive (ER+). Likewise, if it has progesterone receptors, it’s called progesterone-receptor positive (PR+).
Having receptors means that estrogen or progesterone could stimulate the growth of these cancer cells.
How do we stop the “grow more” signal? We can
- block the effects of estrogen on the cell with selective estrogen-receptor modulators (SERMs) that block the cell receptors
- block estrogen production in the ovaries of pre-menopausal women
- block estrogen production in post-menopausal women with aromatase inhibitors
Endocrine therapy for pre-menopausal women
Pre-menopausal women with ER+ and/or PR+ breast cancer are often encouraged to take tamoxifen daily for five years. It helps reduce risk of breast cancer recurrence by almost 50%.
Tamoxifen works by blocking estrogen from reaching the cancer cell’s estrogen receptors.
The side effects of tamoxifen are … peri-menopausal and may include
- Hot flashes
- Memory loss
- Menstrual irregularity
- Mood swings
- Night sweats
In some cases, doctors encourage women who are younger than 35-40 to temporarily stop ovarian function because the ovaries are the body’s main source of estrogen production. Research has shown this to be effective in reducing the risk of breast cancer recurrence.
Women who have mutated BRCA1 or BRCA2 genes may elect to have their ovaries surgically removed (a bilateral oophorectomy).
Endocrine therapy for post-menopausal women
Our bodies continue to produce small amounts of estrogen in the adrenal glands, fat tissue and breast tissue during menopause, after the ovaries have stopped their estrogen production.
That’s why post-menopausal women with ER+ and/or PR+ breast cancer are encouraged to take either tamoxifen or an aromatase inhibitor daily for five years. New research is suggesting that a 10-year treatment may be more effective at preventing recurrence.
Although both tamoxifen and aromatase inhibitors may be part of a post-menopausal woman’s treatment, if she has lobular cancer the aromatase inhibitor is the recommended choice.
Most of a woman’s estrogen is produced in the ovaries, but the ovaries have no monopoly on estrogen production. Aromatase inhibitors work by blocking the enzyme (aromatase) that the body uses to make estrogen in the ovaries and in other tissues.
Aromatase inhibitors were introduced in the mid-1990s and include anastrozole (Arimidex®), exemestane (Aromasin®) and letrozole (Femara®).
The side effects of aromatase inhibitors are … menopausal and may include
- Elevated cholesterol
- Hot flashes
- Joint stiffness/pain
- Memory loss
- Mood swings
- Night sweats
- Vaginal dryness
One complication associated with aromatase inhibitor treatment is bone loss. Prior to beginning treatment, patients should undergo a bone density study (DEXA scan) to record baseline data. Women taking aromatase inhibitors should be sure that their diets contain sufficient calcium and vitamin D.
Finally, post-menopausal women with ER+ and/or PR+ breast cancer should avoid menopausal hormonal treatment (MHT). We’re trying to reduce the amount of estrogen in the body.
Endocrine therapy for recurrence
Hormone therapy may also be part of a treatment plan for locally recurrent hormone-sensitive breast cancer (lymph nodes, chest wall, breast) as well as metastatic breast cancer.
How do we know hormone therapy works?
A large NCI-sponsored randomized clinical trial called the Breast Cancer Prevention Trial, which kicked off in 1999, compared tamoxifen and raloxifene. The post-menopausal women in the study were at increase risk of developing breast cancer and took one of the drugs for five years. The tamoxifen treatment cut risk in half. Women taking raloxifene exhibited a 38% reduction in risk.
A long-term follow-up of another randomized trial showed that that five years of tamoxifen treatment reduced the incidence of breast cancer for at least 20 years. This research included women in eight countries.
A study of 22,850 survivors who had been diagnosed with initial breast cancer (stages 0-IV) from 1996 to 2006 found that women with ER+ or PR+ cancer who took aromatase inhibitors exclusively had the greatest risk reduction. Some women switched from tamoxifen; some took only tamoxifen. All benefited: the reduction in subsequent breast cancer risk ranged from 58% to 66% (and was affected by degree of adherence).
Combined data from nine major trials involving more than 83,000 women with ER+ breast cancer showed that SERMs reduced breast cancer incidence by 38%. Aromatase inhibitors reduced breast cancer incidence by 53%.
A meta-analysis of 31,920 post-menopausal women with ER+ breast cancer showed that taking an aromatase inhibitor for five years reduced 10-year breast cancer mortality rates by about 40% (proportionately) compared with women who had no endocrine treatment. When compared with women who took tamoxifen, the aromatase inhibitor reduced 10-year mortality rates by about 15%.
The research data support women with ER+ breast cancer taking endocrine treatment to reduce the risk of recurrence and to improve mortality rates.