For early-stage breast cancer that is estrogen receptor (ER) and/or progesterone receptor (PR) positive, physicians typically give adjuvant endocrine therapy postoperatively. When choosing an endocrine therapy drug, the patient’s menstrual status (menopausal or not), breast cancer stage, risk of recurrence, tolerance to the drug, drug side effects, patient adherence to the drug (compliance), and cost of the drug are usually taken into account.
What are the commonly used endocrine drugs?
Anti-estrogen drugs
Including tamoxifen, toremifene, etc. Tamoxifen is taken 2 times a day and Toremifene is taken 1 time a day. The most common adverse reactions include hot flashes, night sweats, and may lead to vaginal dryness. Those taking tamoxifen may also experience endometrial thickening, endometrial cancer, and deep vein thrombosis.
Aromatase inhibitors
Including Letrozole (Letrozole), Anastrozole (Anastrozole), and Exemestane (Exemestane), all need to be taken 1 time per day. Common adverse reactions include bone loss (i.e., calcium loss) or osteoporosis, joint pain or numbness, and elevated blood lipids.
Ovarian function suppression drugs
These drugs, which inhibit ovarian function, include goserelin, leuprorelin, and triptorelin. It is generally administered every 28 days 1 time, and also once every 3 months. Generally need to continue the medication 5 years. These drugs can be used in combination with exemestane, anastrozole, letrozole, and also with tamoxifen. Adverse effects are mainly postmenopausal discomfort but are generally well tolerated.
How to choose medication for premenopausal women?
Initial treatment: tamoxifen for 5 years
If the risk of breast cancer recurrence is assessed to be average, doctors usually give tamoxifen first for 5 years.
Tamoxifen adjuvant endocrine therapy for 5 years in ER-positive early-stage breast cancer reduces the annual recurrence rate by 39% and the annual mortality rate by 31%, and is more effective for 5 years than tamoxifen for 1 or 2 years, reducing recurrence by 18% and mortality by 9%.
For some patients, especially those at high risk of recurrence, physicians may add ovarian suppression to tamoxifen therapy, either with drugs or with radiation to the ovaries or removal of the ovaries. Chemotherapy is also usually required for those at higher risk of recurrence, specifically patients with lymph node metastases, large tumors, high tumor grade, invasive lymphovascular invasion, and a high risk of recurrence based on genetic testing (recurrence score > 31 in the 21 Genetic Recurrence Trial). In addition, young women aged ≤ 35 years were at higher risk of relapse. Among patients receiving chemotherapy, tamoxifen + ovarian function inhibition reduced the 5-year risk of recurrence by 22% compared with those on tamoxifen only.
After 5 years of tamoxifen treatment: continue or switch to aromatase inhibitor therapy 5 years
- If you are not menopausal after 5 years of tamoxifen therapy and your breast cancer is well tolerated and has not recurred, your doctor may consider extending endocrine therapy and continuing tamoxifen therapy for 5 years. After 5 years of adjuvant endocrine therapy, there is still a risk of distant recurrence that warrants consideration of extended endocrine therapy. In patients treated initially with tamoxifen, the risk of recurrence was lower with continued extension of therapy to 10 years (from 20.8% to 18%) and mortality was lower (from 11.5% to 9.7%).
- If you are menopausal after 5 years of tamoxifen treatment and your breast cancer has not recurred, your doctor may also consider extending endocrine therapy for another 5 years, switching to an aromatase inhibitor, or continuing tamoxifen. In patients who were menopausal after 5 years of tamoxifen treatment, continuing letrozole for 5 years was associated with a 48% reduction in recurrence rates and a 39% reduction in overall mortality compared with no further endocrine therapy.
High risk of recurrence, aromatase inhibitors usually chosen for initial treatment
If the risk of breast cancer recurrence is high, doctors may consider giving an aromatase inhibitor first for 5 years when starting treatment. If menopause has occurred, an aromatase inhibitor (eg, exemestane) alone may be used, but if not yet menopausal, ovarian function suppression therapy is needed to bring the patient to menopausal status.
For patients receiving chemotherapy, the use of exemestane + ovarian function suppression in initial therapy reduced the risk of death by 36% compared with tamoxifen alone. In premenopausal patients with hormone receptor-positive early-stage breast cancer, exemestane + ovarian suppression also reduced the recurrence rate by 34% compared with tamoxifen + ovarian suppression.
Therefore, tamoxifen + ovarian function inhibition may be sufficient for those at low risk of recurrence, whereas aromatase inhibitor + ovarian function inhibition is more effective for those at high risk of recurrence.
How do postmenopausal women choose their medications?
Initial treatment: aromatase inhibitor therapy for 5 years
For postmenopausal women, doctors usually start with aromatase inhibitors for 5 years. In ER-positive postmenopausal breast cancer patients, the use of an aromatase inhibitor at 5 years of initial treatment resulted in a lower recurrence rate compared with tamoxifen, especially at years 0-1 and 2-4, with a 36% and 20% reduction in the risk of recurrence, respectively, as well as a 15% reduction in 10-year mortality.
After 5 years of aromatase inhibitor therapy: possible continuation of endocrine therapy
After 5 years of initial aromatase inhibitor therapy, if the patient tolerates the drug well and the breast cancer has not recurred, the physician may give an additional 5 years of extended aromatase inhibitor therapy. However, there are inconsistent findings on whether extended treatment after 5 years of aromatase inhibitor therapy is beneficial. Typically, physicians use the following approach.
- For those at higher risk of relapse, such as staging ≥T3 or positive lymph nodes, an extension of endocrine therapy may be favored.
- For those with smaller tumors and negative lymph nodes, because it is unclear whether the risk of late recurrence outweighs the side effects and risks associated with prolonged endocrine therapy, prolonged endocrine therapy may be considered if it is well tolerated and the patient is keen to minimize the risk of new breast cancer, but may be discontinued after 5 years of initial therapy if the patient prefers to avoid side effects.
- For those receiving extended adjuvant endocrine therapy, the standard course of treatment is an extended 5 years, as this is the length of time evaluated in most trials.
There are other options for initial therapy
- Aromatase inhibitor therapy for 2 to 3 years and sequential tamoxifen therapy for 2 to 3 years, for a total length of treatment of 5 years.
- Tamoxifen treatment for 2 to 3 years, sequential aromatase inhibitor treatment for 2 to 3 years, total length of treatment 5 years.
- Tamoxifen for 4.5 to 6 years and sequential aromatase inhibitor or tamoxifen for 5 years for a total duration of treatment of 9.5 to 11 years.
- Tamoxifen treatment for 2 to 3 years, sequential aromatase inhibitor treatment for 5 years, total length of treatment 7 to 8 years.
No aromatase inhibitors, but also traditional tamoxifen regimen
Tamoxifen may be given for 5 or 10 years if there is a contraindication to the use of an aromatase inhibitor, intolerance to an aromatase inhibitor, or refusal of aromatase inhibitor therapy. Tamoxifen for 5 or 10 years is the traditional treatment option for postmenopausal women with early-stage breast cancer and can reduce recurrence and mortality rates. This traditional treatment option is available when aromatase inhibitors are not available.
In summary, when choosing an endocrine therapy drug, doctors usually take into account the patient’s menstrual status, risk of recurrence, and other factors to make the most appropriate decision. Please follow your doctor’s advice and choose the best endocrine treatment option for you, after all, only what is right for you is the best.