The majority of breast cancers today are diagnosed at early stages, meaning that the cancer may or may not have spread to lymph nodes, but does not involve skin or muscle. Even in early-stage breast cancer, with small tumors and no involvement of lymph nodes, adjuvant treatments may prolong life and reduce risk of recurrence. These extra treatments include hormone medications, chemotherapy, or both. You will also need to sit down with a medical oncologist to ask about the likelihood of cancer coming back outside of the breast area and about what treatments you can consider. In addition, you should ask to what extent each of these treatments may help to lower the risk of the cancer coming back, thereby helping you live longer.
Anyone who has a tumor that is estrogen or progesterone receptor-positive should strongly consider taking a hormone treatment, regardless of whether they are old or young, or pre- or postmenopausal. If a breast cancer is hormone-receptor positive (estrogen or progesterone receptors are present), then a strategy that reduces the effect of estrogen on cancer cells is recommended.
Tamoxifen is the most common agent in current use, and because doctors have over thirty years’ experience with tamoxifen, the benefits as well as the possible side effects are well understood. Tamoxifen interferes with the binding of estrogen to its receptor; therefore, it has what is called an antiestrogenic effect on breast tissue and the tumor cells, but may have estrogen-like effects on the bone, lipids, and the uterus. Because of this, tamoxifen is sometimes referred to as a selective estrogen receptor modulator, or a designer estrogen. Tamoxifen can reduce the risk of cancer recurring in the treated breast, reduce the risk of cancer coming back outside of the breast in distant organs, and reduce the risk of a new cancer in the opposite breast by 50 percent.
Tamoxifen is taken orally in the form of a pill and is usually prescribed for five years. It is generally started after completion of chemotherapy and may be given at the same time as radiation.
For postmenopausal women, a new class of hormonal agents can be considered. These are aromatase inhibitors and include medications such as anas-trozole (Arimidex), letrozole (Femara), and exemestane (Aromasin). In premenopausal woman, estrogen is produced primarily by the ovaries. In postmenopausal women, once the ovaries have stopped producing estrogen, estrogen is produced by the conversion of androgens from fatty tissue using an enzyme called aromatase. Aromatase inhibitors work in postmenopausal women to reduce estrogen production so that the hormone does not have a chance to stimulate cancer growth.
Studies have compared anastrozole to tamoxifen and it appears that anas-trozole is as good, if not better, than tamoxifen, but long-term follow-up of women on these newer medications is not yet available. Side effects noted in early studies include hot flashes and joint and muscle pain. There is a slightly higher risk of osteoporosis and bone fracture with anastrozole, in contrast with the slight protective effect of tamoxifen. In addition, anastrozole is associated with a lower risk of blood clots than tamoxifen and does not appear to increase the risk of cancer of the uterus.
Tamoxifen is generally recommended for five years. This is because studies have shown that two years are better than one, five years are better than two, but ten years are not better than five. In fact, doctors see a tendency for slight worsening of prognosis after five years, possibly due to the cancer becoming resistant to tamoxifen. In addition, more years of tamoxifen is more time during which serious side effects like blood clots and endometrial cancer may develop. These two side effects in particular are seen more frequently in women over sixty.
The aromatase inhibitor letrozole has been studied in women who have completed five years of tamoxifen and then take letrozole. This strategy is associated with a 43 percent further reduction in the risk of cancer recurring or new cancer developing in the opposite breast. Side effects of letrozole are similar to anastrozole and include hot flashes, joint and muscle pain, and increased risk of osteoporosis.
Studies have recently been reported using aromatase inhibitors such as exemestane, following two to three years of tamoxifen use. This strategy was associated with fewer recurrences compared to five years of tamoxifen, although at this early stage no difference in overall survival has yet been reported.
Many questions remain unanswered. Is it better for a woman to take tamoxifen for five years and then take an aromatase inhibitor? Is it better to use tamoxifen for two to three years and then follow with the aromatase inhibitor? Is it better to start with an aromatase inhibitor in the first place? What is the optimal duration for using the aromatase inhibitors and what are the long-term side effects? Several large studies are underway that we hope will help answer these questions.