Endocrine Therapy for Postmenopausal Women: Positive Early Breast Cancer

Endocrine Therapy for Postmenopausal Women

Endocrine therapy is an important systemic treatment for all stages of hormone receptor-positive breast cancer and has seen significant advances since Beatson first made the link between the endocrine system and breast cancer more than 100 years ago. In the past few decades, modern endocrine therapies, such as the orally administered selective estrogen receptor modulator (SERM) tamoxifen, have revolutionized early breast cancer therapy, offering a real improvement in terms of both disease-free (DFS) and overall survival. Treatment guidelines now call for the determination of estrogen and progesterone receptor status in all primary breast tumors and endocrine therapy for postmenopausal women. Nonetheless it is important to note that these therapies are only recommended for women with known hormone receptor-positive disease.

Experts at AWAREmed Health and Wellness Resource Center under the able leadership of Doctor Akoury’s care are stating that unlike advanced disease, early detection of breast cancer is hypothetically curable. However treatment of early breast cancer may involve adjuvant therapy consisting of systemic endocrine therapy, chemotherapy or both. This can be done after initial surgery to remove the tumor to prevent or delay tumor recurrence. The ultimate goal of adjuvant endocrine therapy is to increase the chances of curing invasive early breast cancer, with as low a level of adverse side-effects as possible.

Historically, tamoxifen was the first successful hormonal treatment and became the ‘gold standard’ adjuvant endocrine therapy in postmenopausal women. It has been shown to be more effective than chemotherapy in women of over 50 years of age with hormone receptor-positive early breast cancer. These findings have prompted its investigation as a chemo-preventive agent in women at risk of breast cancer. Bearing in mind that this study had a short follow-up, tamoxifen was found to be associated with almost 50% reduction in new tumors compared with placebo. As a result, Nolvadex™ (tamoxifen citrate) was approved by the US Food and Drug Administration (FDA) for reducing the incidence of breast cancer in women at high risk of developing the disease. However, despite its proven effectiveness, tamoxifen therapy is still linked to a number of serious side-effects including an increased risk of endometrial cancer and sarcoma and thromboembolic disorders all of which are potentially life-threatening. This clearly limits its use both as adjuvant therapy (where it is usually recommended for up to 5 years) and in particular, as a preventative therapy. This shortcoming has prompted the search for, and development of, new agents with equal or improved efficacy and fewer side-effects.

Alternatively postmenopausal women with hormone receptor positive breast cancer may be offered adjuvant therapy with either tamoxifen or with an aromatase inhibitor. Aromatase inhibitors belong to a class of drugs that work by reducing the levels of estrogen in the body. Even if you have stopped menstruating, your body may still produce small amounts of estrogen in the adrenal glands, fat tissue and even breast tissue. These drugs for over two decades have been shown to reduce the risk of breast cancer recurrence in postmenopausal women with early stage breast cancer. Such drugs include anastrozole (Arimidex^®), exemestane (Aromasin^®) and letrozole (Femara^®).

Postmenopausal women with hormone-positive tumors may do just as well or perhaps a bit better with an aromatase inhibitor when compared to tamoxifen. It is not recommended for these women to undergo ovarian suppression as adjuvant treatment since their ovaries are not producing estrogen. Oophorectomy would be considered in this case in women who are BRCA 1 or 2 mutation carriers or have a strong family history of ovarian cancer as a preventive measure. Experts recommend that patients who are diagnosed with early stage non-invasive breast cancer (DCIS) may be given tamoxifen to prevent breast cancer from occurring in the unaffected breast. But in all this, it is important to understand that the use of aromatase inhibitors in postmenopausal women with DCIS is under investigation.

Many women stop menstruating after receiving chemotherapy, often for several months or even a few years. This does not necessarily mean they are postmenopausal. It is possible that these women could still have functioning ovaries and premenopausal hormonal levels despite the absence of their menstrual periods. Also, ovarian function could still return unexpectedly. That said, women who are premenopausal, regardless of whether they experience temporary menopause because of treatments, should not be prescribed aromatase inhibitors (unless they are participating in specific clinical research studies). Aromatase inhibitors are typically reserved for postmenopausal women with breast cancer.

Endocrine Therapy for Postmenopausal Women: Side effects of aromatase inhibitors

Like in all other medications aromatase inhibitors are also having their side effects which are generally mild and well-tolerated. They may include the following:

• High cholesterol – You may need routine screenings. If cholesterol becomes a problem, you may be asked to reduce your intake of fat from meats and other animal products.
• Hair thinning
• Hot flashes
• Decreased interest in sexual activity
• Mood swings
• Joint stiffness and pain, including carpal tunnel symptoms – In a small number of patients, this can be quite severe. If you develop severe symptoms your doctor may recommend that you temporarily stop taking it and then try another kind of aromatase inhibitor or tamoxifen.

Endocrine Therapy for Postmenopausal Women: Complications

The use of aromatase inhibitors may trigger complications where the patient loses the bone density. It is therefore advisable that all women who are considering using aromatase inhibitors to consult with their doctors about having a bone density study (DEXA scan). Besides that such patients should also take at least the minimum recommended daily allowances dose of calcium and vitamin D. and for those patients with some evidence of bone loss, your doctor may recommend that you increase your exercise level or take a calcium supplement. However if you are still experiencing problems with bone loss, a prescription of bone building drugs like a class of medications called bisphosphonates may be recommended. The drug Evista^® (raloxifene) is quite similar to tamoxifen and in general should be avoided by women who were previously diagnosed with breast cancer.

Endocrine Therapy for Postmenopausal Women: Positive Early Breast Cancer