Some breast cancer patients also undergo endocrine therapy after chemotherapy is completed. This is because these breast cancers are hormone receptor (both estrogen and progesterone receptors, which require immunohistochemical testing) positive, and cancer cell growth is nourished by estrogen, which can be well inhibited by drugs that block the nourishment of breast cancer cells by estrogen in the body.
It is now believed that endocrine therapy should be considered for hormone receptor-positive breast cancer, regardless of age, whether there are metastases in the lymph nodes, or whether adjuvant chemotherapy is needed. Endocrine therapy generally needs to be continued for 5 to 10 years to ensure complete killing of tumor cells. For breast cancer patients with the same stage, those who are hormone receptor positive are usually more likely to be cured than those who are negative.
The most commonly used drugs for endocrine therapy of breast cancer include two major classes: anti-estrogens and aromatase inhibitors.
Anti-estrogenic drugs
Anti-estrogenic drugs include tamoxifen, toremifene, and fulvestrant.
Tamoxifen
Also known as triamcinolone acetonide, it is the most commonly used endocrine therapy drug, is convenient and inexpensive to take orally, and can be used by patients of all ages, whether menopausal or not.
The clinical efficacy of tamoxifen is relatively significant. 5 years of oral tamoxifen significantly improves 10-year disease-free survival and overall survival, meaning that there is a higher likelihood of no recurrence of breast cancer and survival to 10 years within 10 years, and that tamoxifen also reduces recurrence and mortality rates and may reduce the risk of contralateral breast cancer.
Of course, long-term oral tamoxifen can cause some mild adverse effects, but only a minority of people will experience them. The most common adverse reactions include hot flashes, night sweats, and vaginal dryness. Tamoxifen may also cause endometrial thickening, endometrial cancer, and deep vein thrombosis, which are low in incidence but important to be aware of, so doctors may recommend periodic ultrasounds to review endometrial thickness and detect deep vein thrombosis in people taking oral tamoxifen to decide whether to continue or change medications.
Toremifene
Toremifene is a new generation of anti-estrogenic antineoplastic agents with efficacy equivalent to tamoxifen and less adverse effects, often used as an alternative for premenopausal patients who cannot tolerate tamoxifen.
Fulvestrant
Fulvestrant is a new class of estrogen receptor antagonist that preempts estrogen binding to estrogen receptors, leaving estrogen without a receptor to bind to in order to exert its tumor-promoting effects. This drug is mainly used for the endocrine treatment of advanced breast cancer in postmenopausal women who have failed tamoxifen and toremifene treatment. However, fulvestrant cannot be taken orally at this time and requires intramuscular injections.
Common adverse reactions include elevated serum transaminases and bradycardia, and injection site pain, nausea, bone pain, arthritis, headache, back pain, fatigue, pain in the ends of the limbs, hot flashes, vomiting, loss of appetite, malaise, musculoskeletal pain, cough, dyspnea, and constipation have also occurred.
Aromatase inhibitors (AI)
What patients are available?
The advent of aromatase inhibitors was a milestone in the history of endocrine therapy for breast cancer, but only for postmenopausal patients. They are also available for patients who have achieved irreversible artificial menopause through bilateral oophorectomy or irradiation, or who have applied drugs to achieve reversible menopausal status. It should be reminded that the determination of whether one is in a menopausal state needs to be made by a medical professional.
Why should aromatase inhibitors be used only in postmenopausal patients? This has to do with the source of estrogen in postmenopausal women. The postmenopausal woman’s ovaries are significantly degraded in their ability to produce estrogen, so the source of estrogen in the body is primarily from the conversion of androgens. Aromatase is the exclusive catalyst for the conversion of androgens to estrogen. That is, aromatase inhibitors can prevent the conversion of androgens to estrogens in postmenopausal women.
What drugs are included?
Aromatase inhibitors are also oral medications, but they are much more expensive than tamoxifen and have better efficacy than tamoxifen for postmenopausal patients.
Currently, commonly used clinical representatives belong to the third generation of aromatase inhibitors, including anastrozole, letrozole, and exemestane. The third generation aromatase inhibitors have a more specific and efficient inhibition of aromatase activity, which can reduce estrogen levels in postmenopausal women, even to levels that are not currently measurable. Depending on the mechanism of action, the three generations of aromatase inhibitors can also be divided into two categories: steroidal aromatase irreversible inactivators (exemestane) and non-steroidal aromatase reversible inhibitors (letrozole, anastrozole). Of course irreversible inactivators are more potent and have no “rebound” effect on aromatase inactivation.
What are the adverse effects?
What are the adverse effects?
Adverse effects of aromatase inhibitors include osteoporosis and an increased risk of fracture, in addition to the common hot flashes, night sweats, and possible vaginal dryness, and your doctor will remind you to review your bone density and take measures to prevent and treat osteoporosis.
In conclusion, endocrine therapy is an important treatment for hormone receptor positive breast cancer and can greatly reduce the risk of recurrence. How to choose these two major classes of endocrine therapy drugs? The doctor will choose the most suitable drug based on the scientific evaluation and comprehensive consideration of the patient’s condition, which is the “individualized and comprehensive treatment” emphasized by the oncology community, aiming to achieve the most ideal treatment effect. (Dr. Zhou Liudan, deputy director of the Department of Oncology at the First Hospital in Jianyang, Fujian Province, China, contributed to this article)
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