What is the primary treatment for estrogen receptor-positive (ER+) breast cancer?

From the Guidelines

The primary treatment for estrogen receptor-positive (ER+) breast cancer is endocrine therapy, which typically involves medications such as tamoxifen or aromatase inhibitors, with treatment duration usually ranging from 5-10 years. The choice of medication depends on menopausal status, with premenopausal women typically receiving tamoxifen and postmenopausal women often starting with an aromatase inhibitor 1. According to the most recent guidelines, tamoxifen is the most firmly established adjuvant endocrine therapy, decreasing the annual odds of recurrence by 41% and the annual odds of death by 31% in patients with ER-positive breast cancer 1.

Treatment Options

• Tamoxifen (typically 20mg daily for 5-10 years) is a common medication for ER+ breast cancer, blocking estrogen receptors and reducing recurrence risk 1.
• Aromatase inhibitors, such as anastrozole (1mg daily), letrozole (2.5mg daily), or exemestane (25mg daily), prevent the conversion of androgens to estrogen in postmenopausal women and are often used in combination with tamoxifen or as an alternative 1.
• The treatment duration is usually 5-10 years, with some patients benefiting from extended therapy, especially those with a higher risk of recurrence based on factors such as nodal involvement, larger tumors, and other adverse prognostic features in the cancer 1.

Considerations for Treatment

• Patient preferences and individualized treatment decisions are critical, taking into account the magnitude of potential benefit and the associated risks of treatment 1.
• Regular monitoring for side effects and adherence to the prescribed regimen is essential for optimal outcomes.
• Endocrine therapy may be used alone or in combination with other treatments such as surgery, radiation, or chemotherapy, depending on the stage and characteristics of the cancer.

Recent Guidelines

The most recent guidelines from 2024 recommend tamoxifen as the most firmly established adjuvant endocrine therapy for ER+ breast cancer, with aromatase inhibitors also being effective options 1. The 2019 guidelines from the ASCO adjuvant endocrine therapy Expert Panel recommend extended duration therapy with any one of the following strategies: AI for up to a total of 10 years; or tamoxifen for 2 to 3 years followed by AI for 7 to 8 years; or tamoxifen for 5 years followed by AI for 5 years; or tamoxifen for 10 years 1.

From the FDA Drug Label

EXEMESTANE is indicated for adjuvant treatment of postmenopausal women with estrogen-receptor positive early breast cancer who have received two to three years of tamoxifen and are switched to EXEMESTANE for completion of a total of five consecutive years of adjuvant hormonal therapy Tamoxifen citrate tablets are effective in the treatment of metastatic breast cancer in women and men. In premenopausal women with metastatic breast cancer, tamoxifen is an alternative to oophorectomy or ovarian irradiation Available evidence indicates that patients whose tumors are estrogen receptor positive are more likely to benefit from tamoxifen therapy.

The primary treatment for estrogen receptor-positive (ER+) breast cancer includes hormonal therapy with medications such as:

• Tamoxifen: used in premenopausal and postmenopausal women
• Exemestane: used in postmenopausal women, often after 2-3 years of tamoxifen therapy Key points to consider:
• Estrogen receptor status is crucial in determining the treatment approach
• Adjuvant hormonal therapy is a common treatment strategy for ER+ breast cancer
• The choice of hormonal therapy depends on menopausal status and other individual factors 2 3

From the Research

Estrogen Receptor-Positive (ER+) Breast Cancer Treatment

The primary treatment for estrogen receptor-positive (ER+) breast cancer involves endocrine therapy, which aims to reduce the growth of cancer cells by blocking the production or action of estrogen.

• The standard treatment for premenopausal women with ER+ breast cancer is tamoxifen, which acts by competitive antagonism of estrogen at its receptor site 4.
• For postmenopausal women with ER+ breast cancer, aromatase inhibitors (AIs) have become the standard endocrine treatment, as they interfere with the conversion of androgens into estrogens, resulting in low estradiol levels 5, 6.
• Available options for endocrine therapy in perimenopausal women and those recently postmenopausal include tamoxifen for 10 years, tamoxifen for 5 years followed by aromatase inhibitors, tamoxifen with a luteinizing hormone-releasing hormone (LHRH) agonist, aromatase inhibitor with an LHRH agonist, or aromatase inhibitor with bilateral oophorectomy 7.
• Ovarian suppression (OS) is another method of endocrine therapy and has been shown to decrease the risk of recurrence and confer a survival advantage when used as the sole source of hormone therapy 4.
• The role of aromatase inhibitors in the premenopausal setting remains undefined, but studies such as SOFT and TEXT aim to shed light on the effect of OS and AI in premenopausal ER+ breast cancer 4.

Adjuvant Endocrine Therapy

Adjuvant endocrine therapy is used to reduce the risk of recurrence in patients with hormone receptor-positive breast cancer.

• Tamoxifen has been the standard adjuvant endocrine therapy for premenopausal women with hormone receptor-positive breast cancer for more than 2 decades, but emerging results suggest that either switching to an aromatase inhibitor after 5 years of tamoxifen or continuing tamoxifen for an additional 5 years can further decrease relapse risk 7.
• Aromatase inhibitors have been shown to be superior to tamoxifen in reducing the risk of recurrence in postmenopausal women with hormone-dependent breast cancer 5, 8.
• The combination of ovarian function suppression and tamoxifen or chemotherapy is not conclusively superior to ovarian function suppression alone in patients aged less than 50 years with ER+ breast cancer 8.