All breast cancers are now tested for the estrogen and progesterone receptors. These receptors are molecules in the cancer cells that can accept hormones and influence the growth of the cancer. Breast cancers that are hormone receptor positive have two important characteristics. First, they tend to be less aggressive than the same type of breast cancer that is hormone receptor negative. They also are influenced by various hormone manipulations that generally decrease the level of estrogen in the body. The percent of patients that have positive estrogen receptor increases with age. The response to various hormone manipulations is proportional to the level of estrogen receptor meaning that patients with high levels of estrogen receptor are more responsive to various hormone manipulations.
Anti-hormonal drugs that have been developed during the past 20 or 30 years include:
- Tamoxifen - An estrogen receptor blocker that stops the effect of estrogen in the tumor cell and places the tumor cell either in a resting state or causes the tumor cell to die. Tamoxifen is effective in both premenopausal and postmenopausal patients. The drug is generally well tolerated, but does have an increased incidence of uterine cancer and deep vein thrombosis, but these complications are rare and generally seen in patients over 65.
- Aromatase inhibitors including Arimidex (zoledronic acid), Femara (letrozole), and Aromasin (exemestane) are oral medications that decrease the body's production of estrogen in the ovaries, the adrenal glands, and in fat tissue. These are used in a variety of situations in breast cancer, but only in postmenopausal women. They are generally well tolerated, but do have some arthritis-like effects and in longer-term use are associated with some decrease in bone density.
- Faslodex (Fulvestrant) - blocks the estrogen receptor and is also effective in postmenopausal women and is generally very well tolerated. It is given as a monthly intramuscular injection.
- LHRH Agonists - Injections that stop the ovaries from producing estrogen and can be used in some situations in place of chemotherapy and can also be used to suppress the ovaries long term.
Patients with invasive breast cancer who are shown to be estrogen receptor positive may benefit by additional antiestrogen therapy. In premenopausal patients, the usual recommendation for therapy is five years of tamoxifen, but there are a number of research studies looking at more aggressive anti-estrogen manipulation including LHRH agonist, followed by either tamoxifen or an aromatase inhibitor. The results of these studies are pending, but should be available in the next year or two. In postmenopausal patients, it has now been shown that the initial approach that yields the most benefit is to start with an aromatase inhibitor. This clearly decreases the chance of recurrence and increases the long-term disease free survival. Various research studies are now looking into whether more than five years of an aromatase inhibitor is beneficial and early indications are that 10 years of anti-estrogen therapy in some situations may be more effective than five years.
In situations in which breast cancer has recurred in distant sites and the tumor is estrogen receptor positive, hormone manipulation may control the tumor for many years. A sequence of hormone therapies can often keep the disease under control for many years before chemotherapy is needed. Hormone therapy is much easier and often has longer response rates than chemotherapy. Various hormone manipulations include tamoxifen in both premenopausal and postmenopausal women. In postmenopausal women, the aromatase inhibitors and Faslodex also play an important role in tumor control. If patients are responsive to these hormone therapies, other hormone approaches might include Faslodex or Megace or high dose estrogen.