For endocrine therapy, an important treatment for breast cancer, some studies have shown that patients’ long-term adherence to treatment is not promising. In addition to the fact that patients are not adequately prepared for long-term post-surgical drug therapy, the more important reason for non-adherence is the discomfort caused by adverse drug reactions. The side effects of endocrine therapy vary from drug to drug, mainly in the bone, joint muscle, gynecological and cardiovascular systems.
Bone adverse reactions
Who is at risk for osteoporosis?
Lowered estrogen levels increase the risk of fracture, with normal postmenopausal women having twice the risk of natural fracture as men. There are many factors that affect bone health in breast cancer patients during treatment, including entry into menopause, aromatase inhibitor therapy, chemotherapy, oophorectomy, or application of drugs to suppress ovarian function artificially induced to a postmenopausal state. Individuals at high risk for developing osteoporosis include the following:
- More than 65 years of age;
- Women aged 60 to 64 years with a family history of osteoporosis, weight <70 kg, previous history of non-traumatic fracture or other risk factors;
- Postmenopausal, treated with an aromatase inhibitor;
- Premature menopause due to treatment (e.g. chemotherapy).
Patients with breast cancer have a 31% increased risk of fracture compared with women without tumors. The two main classes of endocrine therapy have different effects on bone health; tamoxifen has estrogen-like effects and so is protective of the bone, whereas aromatase inhibitors (anastrozole, letrozole, exemestane, etc.) can increase the incidence of osteoporosis as well as fractures.
How to deal with osteoporosis?
To reduce osteoporosis and bone loss, breast cancer patients treated with aromatase inhibitors usually take calcium and vitamin D routinely, increase physical activity, prevent falls, reduce tobacco and caffeine intake, and get regular bone density testing. For patients at high risk of developing osteoporosis as mentioned above, screening bone density is recommended. 2011 China Anti-Cancer Association guidelines and specifications for breast cancer diagnosis and treatment recommend that those using aromatase inhibitors should have bone density testing every 6 months, and if the T score is <-2.5, bisphosphonates are recommended; if the T score is -1.0 to -2.5, bisphosphonates can be considered; if T score > -1.0, bisphosphonates are not recommended; vitamin D and calcium are routinely given for T scores ≤ -1.0.
Biphosphonates are often used if a breast cancer patient has severe osteoporosis. The new drug denosumab, which has emerged in recent years, can also significantly improve bone density.
Joint muscle symptoms
Who is at risk for joint muscle symptoms?
The common bone, joint, and muscle symptoms of menopause are associated with decreased estrogen levels. The incidence of joint pain is significantly higher in those receiving aromatase inhibitor therapy than in those on tamoxifen. One study reported that the incidence of bone and muscle pain in breast cancer patients treated with aromatase inhibitors can be up to 60%, and the rate of discontinuation can be up to 20%. Some patients have also experienced a reduction in pain with longer dosing.
How do I cope?
Before and during aromatase inhibitor therapy, doctors usually evaluate bone and joint muscle symptoms to rule out pain caused by bone metastases, osteoarthritis, and rheumatoid arthritis.
For pain caused by aromatase inhibitors, vitamin D and calcium supplements and appropriate physical activity may be given for mild cases, and NSAIDs may be given for significant pain. Your doctor may also consider a 3 to 4 week “drug holiday,” a period of time off the medication. In addition, because the 3 commonly used aromatase inhibitors do not have identical mechanisms of action, physicians may consider switching to other endocrine medications.
Gynecologic adverse reactions
Because of its estrogen-like effects, long-term use of tamoxifen may lead to adverse effects such as hot flashes, vaginal bleeding, endometrial thickening, uterine fibroids, and ovarian cysts. A serious adverse effect is the possibility of endometrial cancer, but the incidence is low, about 0.3%.
People on long-term tamoxifen use may be advised to have regular ultrasound to check the thickness of the endometrium and to treat the thickened endometrium if necessary.