Aromatase inhibitors (AIs):

Aromatase inhibitors (AIs): Three drugs that stop estrogen production in postmenopausal
women have been approved to treat both early and advanced breast cancer:
letrozole (Femara®), anastrozole (Arimidex®), and exemestane (Aromasin®). They work
by blocking an enzyme (aromatase) in fat tissue that is responsible for making small
amounts of estrogen in post-menopausal women. They cannot stop the ovaries of premenopausal
women from making estrogen, so they are only effective in women whose
ovaries aren’t working (like after menopause). These drugs are taken daily as pills. So
far, each of these drugs seems to work as well as the others in treating breast cancer.
Several studies have compared these drugs with tamoxifen as adjuvant hormone therapy
in post-menopausal women. Using these drugs, either alone or after tamoxifen, has been
shown to better reduce the risk of the cancer coming back later than using tamoxifen
alone for 5 years. Schedules that are known to be helpful include:
· Tamoxifen for 2 to 3 years, followed by an aromatase inhibitor (AI) to complete 5
years of treatment
· Tamoxifen for 5 years, followed by an AI for 5 years
· An AI for 5 years
For post-menopausal women whose cancers are hormone receptor–positive, most doctors
now recommend using an AI at some point during adjuvant therapy. But it's not yet clear
if starting adjuvant therapy with one of these drugs is better than giving tamoxifen and
then switching to an AI. We still don't know if giving these drugs for more than 5 years is
more helpful than stopping at 5 years. Studies now being done should help answer these
questions.
The AIs tend to have fewer serious side effects than tamoxifen—they don't cause uterine
cancers and very rarely cause blood clots. They can, however, cause muscle pain and
joint stiffness and/or pain. The joint pain may be similar to a new feeling of having
arthritis in many different joints at one time. This side effect may improve by switching
to a different AI, but it has led some women to stop drug treatment. If this occurs, most
doctors recommend using tamoxifen to complete 5 years of hormone treatment.

Because aromatase inhibitors remove all estrogens from women after menopause, they
also cause bone thinning, sometimes leading to osteoporosis and even fractures. Many
women treated with an aromatase inhibitor are also treated with medicine to strengthen
their bones, such as bisphosphonates or denosumab (this is discussed further on).
Ovarian ablation: In pre-menopausal women, removing or shutting down the ovaries,
which are the main source of estrogens, effectively makes the woman post-menopausal.
This may allow some other hormone therapies to work better. This is most often used to
treat metastatic breast cancer.
Permanent ovarian ablation can be done by surgically removing the ovaries. This
operation is called an oophorectomy. More often, ovarian ablation is done with drugs
called luteinizing hormone-releasing hormone (LHRH) analogs, such as goserelin
(Zoladex®) or leuprolide (Lupron®). These drugs stop the signal that the body sends to
ovaries to make estrogens. They can be used alone or with tamoxifen as hormone therapy
in pre-menopausal women. They are also being used along with aromatase inhibitors in
studies of pre-menopausal women.
Chemotherapy drugs may also damage the ovaries of pre-menopausal women so they no
longer produce estrogen. In some women, ovarian function returns months or years later,
but in others, the damage to the ovaries is permanent and leads to menopause. This can
sometimes be a helpful (if unintended) consequence of chemotherapy with regard to
breast cancer treatment, although it leaves the woman infertile.
All of these methods can cause a woman to have symptoms of menopause, including hot
flashes, night sweats, vaginal dryness, and mood swings.
Fulvestrant (Faslodex®): Fulvestrant is a drug that also acts on the estrogen receptor, but
instead of just blocking it, this drug also eliminates it temporarily. It is often effective
even if the breast cancer is no longer responding to tamoxifen. It is given by injection
once a month. Hot flashes, mild nausea, and fatigue are the major side effects. It is
currently only approved by the FDA for use in post-menopausal women with advanced
breast cancer that no longer responds to tamoxifen or toremifene.
Megestrol acetate: Megestrol acetate (Megace®) is a progesterone-like drug used as a
hormone treatment of advanced breast cancer, usually for women whose cancers do not
respond to the other hormone treatments. Its major side effect is weight gain, and it is

sometimes used in higher doses to reverse weight loss in patients with advanced cancer.
This is an older drug that is no longer used very often.
Other ways to control hormones: Androgens (male hormones) may rarely be
considered after other hormone treatments for advanced breast cancer have been tried.
They are sometimes effective, but they can cause masculine characteristics to develop
such as an increase in body hair and a deeper voice.
Another option that may be tried when the cancer is no longer responding to other
hormone drugs is giving high doses of estrogen. The main risk is of serious blood clots
(like DVTs and PEs). Patients also have trouble with nausea.
Targeted therapy for breast cancer
As researchers have learned more about the gene changes in cells that cause cancer, they
have been able to develop newer drugs that specifically target these changes. These
targeted drugs work differently from standard chemotherapy (chemo) drugs. They often
have different (and less severe) side effects. They are most often used along with chemo
at this time.