Knowledge about endocrine therapy for breast cancer
1.What is endocrine therapy?
Most breast cancers are hormone-dependent tumors. A high estrogen/androgen ratio in the body will stimulate the development and progression of breast cancer cells. Endocrine therapy refers to the treatment method of removing the hormonal stimulation of tumor cells through drugs or removal of endocrine glands to achieve anti-tumor effect.
The basic drugs of endocrine therapy for breast cancer are anti-estrogen drugs (e.g. tamoxifen, fulvestrant), aromatase inhibitors (e.g. anastrozole), luteinizing hormone-releasing hormone (LHRH) analogs (e.g. goserelin), estrogen/androgen and progestin.
2. What is the relationship between estrogen, progestin and breast cancer endocrine therapy?
Not all breast cancer patients can be treated with endocrine therapy. Only patients who are “hormone receptor positive” need to receive endocrine therapy. The term “hormone receptor positive” means that the growth of tumor is influenced by the level of hormones in the body.
Whether a patient is suitable for endocrine therapy depends on two important indicators – estrogen receptor (ER) and progesterone receptor (PR). If either of these indicators is “positive (+)”, the patient is suitable for endocrine therapy. On the contrary, if both indicators are “negative (-)”, then endocrine therapy drugs will not be effective.
3.What is an aromatase inhibitor (AI)?
Aromatase inhibitors (AI) are drugs used to inhibit the conversion of androgens to estrogen, a pre-estrogenic substance in the peripheral tissues, to reduce the level of estrogen in the body and play an anti-tumor role in postmenopausal women with breast cancer. The most commonly used drugs are third-generation aromatase inhibitors, such as anastrozole, letrozole and exemestane. The principle of action of aromatase inhibitors: In postmenopausal women, estrogen is produced through aromatase enzymes in surrounding tissues such as fat, muscle, liver and even breast cancer cells acting on androgens. Estrogen stimulates tumor growth through estrogen receptors on breast cancer cells, and AI can inhibit the activity of aromatase enzymes, thus inhibiting estrogen production and weakening the stimulating effect of estrogen on breast tumors.
4.When to start endocrine therapy?
After surgery for early stage breast cancer patients, endocrine therapy can be started 3~4 weeks after finishing the last chemotherapy. At present, it is generally advocated to take it for 5 years.
5.How to choose endocrine therapy drugs for starting treatment after breast cancer surgery?
Since the pathways of estrogen production are different between premenopausal and postmenopausal women, the starting endocrine therapy drugs for postoperative breast cancer patients will also be different.
In premenopausal women, 95% of estrogen comes from the ovaries. For this group of breast cancer patients, it is crucial to suppress the function of their ovaries and the estrogen produced by the ovaries. The starting drug of choice is tamoxifen; combined or not with ovarian depot.
In postmenopausal women, the ovaries stop producing estrogen, and estrogen in the body mainly comes from androgens secreted from fat, muscle, liver and breast tumors, which are converted into estrogen by the action of aromatase. Therefore, aromatase inhibitors, such as anastrozole, letrozole or exemestane, are preferred for postmenopausal patients for postoperative initiation therapy.
6.How to change the medication for patients using adjuvant tamoxifen therapy?
Adjuvant therapy for postmenopausal, receptor-positive breast cancer patients.
-Switch to aromatase inhibitor after 2~3 years of tamoxifen use for a total of 5 years;
-Aromatase inhibitors for 5 years after completing 5 years of tamoxifen therapy.
Postoperative adjuvant endocrine therapy in premenopausal receptor-positive patients.
-Tamoxifen for 2 to 3 years, then switch to AI until 5 years after menopause;
-Tamoxifen treatment for 2~3 years without menopause can be continued with tamoxifen up to 5 years, followed by aromatase inhibitor for 5 years after menopause.
7.What is the safety of endocrine therapy drugs?
The incidence of adverse reactions of endocrine therapy is relatively low, generally not serious, and can be tolerated by most patients. The adverse reactions of several commonly used drugs are shown in the following table.
Tamoxifen
Anastrozole
Letrozole
Exemestane
General
Weakness
(mild to moderate)
Fatigue
Weight gain
Fatigue Fever Increased body weight
Respiratory system
Difficulty breathing
Chest pain
Difficulty breathing
Cough
Gastrointestinal reactions
Lack of appetite
Nausea Vomiting Diarrhea
Nausea Diarrhea
(mild to moderate)
Nausea Constipation
Diarrhea Abdominal pain
Nausea Dry mouth Constipation Diarrhea Abdominal pain Increased appetite
Reproductive system
Menorrhagia
Vaginal bleeding or dryness induces endometrial cancer
Vaginal dryness
(mild to moderate)
Vaginal bleeding
Blood, the
vascular system
Leukocytopenia in very few people
Hot flashes
(mild to moderate)
Edema Hypertension
Cardiac arrhythmia
Hot flashes
Lymphocytopenia
Swelling
Psychoneurological symptoms
Headache Dizziness Depression
Headache
(mild to moderate)
Insomnia Dizziness
Dizziness Insomnia
Depression Anxiety
Skin
Facial flushing Rash
Hair thinning
Rash
Itching Rash
Rash
Hepatobiliary system
Abnormal liver function Elevated lipids
Alkaline phosphatase
Elevated alanine aminotransferase and aspartate aminotransferase
Liver function indicators
(alanine aminotransferase) abnormalities
Bone and joint system
Joint pain/stiffness (mild to moderate)
Arthralgia Bone pain
Pregnancy
Affects fetus
Contraindicated in pregnant or lactating women
Not yet known
Contraindicated in pregnant or lactating women