Extending hormonal therapy to treat breast cancer.
Approximately two-thirds of all breast cancer is positive for estrogen
receptors (ER) and progesterone receptors (PR). These receptors are the
proteins in the cell that estrogen and progesterone bind to. This binding
has to occur before estrogen and progesterone can act on the cell. In
breast cancers that are ER and/or PR positive, the presence of these receptors
allows hormones to stimulate the cancer cell, thus essentially fueling
the growth and survival of the cancer. Medications that block either the
body’s production of estrogen and progesterone, or the action of
these hormones on the cell, are a crucial part of the treatment for breast
cancer patients whose tumors are ER and/or PR positive.
The optimal duration of hormonal therapy has been the subject of many studies
over the years. Early studies with tamoxifen (a drug which prevents estrogen
from binding to its receptor) indicated that treatment should continue
for at least five years, because shorter durations of treatment were clearly
inferior. However, more definitive studies which were reported this decade
clearly showed that extending the length of tamoxifen use from five years
to ten years reduced the risk of breast cancer recurrence.
Another approach to hormonal therapy for breast cancer, which is used only
in postmenopausal women, is the use of any of the drugs which belong to
the class known as aromatase inhibitors. Even after menopause, the body
still makes some estrogen in tissues other than the ovaries, and aromatase
is an enzyme that is required for this estrogen production. The currently
used aromatase inhibitors are anastrozole, letrozole and exemestane.
Some women take tamoxifen for two to five years and then switch to an aromatase
inhibitor (AI). Many studies have looked at this strategy, and the data
clearly show that treatment with an AI after tamoxifen decreases the risk
of breast cancer relapse. However, the optimal duration of AI therapy
remains unclear. Aromatase inhibitors can also be used as stand-alone
hormonal therapy in postmenopausal women. However, optimal duration of
treatment with an AI alone is also unclear.
The approach of many oncologists is to make a recommendation based in part
upon the patient’s risk of relapse. For a very low risk patient,
the risks and side effects of extending treatment beyond five years may
be difficult to justify, but in a patient with a very high risk of recurrence,
the risk/benefit ratio probably favors continuing therapy for up to ten
years, and perhaps even fifteen. There is a test which can be performed
on the original tumor specimen to estimate the patient’s risk of
a late relapse (i.e., after five years). All of the available information
about the characteristics of the patient’s tumor, and knowledge
of her other health issues, if any, need to be taken into consideration
by the patient and her physician so that they can make a well informed
joint decision about the best course of action in treating her cancer.