Are aromatase inhibitors (AIs) used to treat Human Epidermal growth factor Receptor 2 (HER2) negative breast cancer?

From the Guidelines

Aromatase inhibitors (AIs) are recommended for the treatment of HER2-negative breast cancer in postmenopausal women with hormone receptor-positive disease, as they have been shown to improve disease-free survival and reduce the risk of recurrence 1. The main AIs used in clinical practice include anastrozole (Arimidex) at 1 mg daily, letrozole (Femara) at 2.5 mg daily, and exemestane (Aromasin) at 25 mg daily. These medications are typically prescribed for 5-10 years, either as initial therapy or following 2-3 years of tamoxifen treatment. AIs work by blocking the enzyme aromatase, which converts androgens to estrogens in postmenopausal women, thereby reducing estrogen levels that can stimulate hormone-dependent breast cancer growth. They are particularly effective in postmenopausal women because their primary source of estrogen comes from peripheral conversion rather than ovarian production. Some key points to consider when using AIs include:

• Common side effects include joint pain, bone loss, and increased risk of fractures, so calcium and vitamin D supplementation along with bone density monitoring are recommended during treatment 1.
• In premenopausal women with HER2-negative breast cancer, ovarian suppression therapy is typically needed alongside AIs since the ovaries remain the primary source of estrogen in these patients 1.
• The choice of AI and treatment duration should be individualized based on patient factors, such as menopausal status, tumor biology, and prior treatment exposure 1. It's worth noting that the most recent and highest quality study 1 supports the use of AIs in this patient population, and this recommendation is consistent with current clinical practice guidelines.

From the FDA Drug Label

INDICATIONS AND USAGE EXEMESTANE is an aromatase inhibitor 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 (14.1). • treatment of advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy (14.2).

INDICATIONS AND USAGE Letrozole Tablets, USP are aromatase inhibitor indicated for: Adjuvant treatment of postmenopausal women with hormone receptor positive early breast cancer ( 1.1) Extended adjuvant treatment of postmenopausal women with early breast cancer who have received prior standard adjuvant tamoxifen therapy ( 1.2) First and second-line treatment of postmenopausal women with hormone receptor positive or unknown advanced breast cancer ( 1.3)

Aromatase inhibitors are used to treat hormone receptor positive breast cancer. Since HER2 negative breast cancer can be hormone receptor positive, aromatase inhibitors can be used to treat HER2 negative breast cancer if it is also hormone receptor positive 2 3.

• Key points:
  • Aromatase inhibitors are indicated for hormone receptor positive breast cancer
  • HER2 negative breast cancer may be hormone receptor positive
  • Aromatase inhibitors can be used to treat HER2 negative and hormone receptor positive breast cancer

From the Research

Treatment of HER2 Negative Breast Cancer

• Aromatase inhibitors (AIs) are used to treat hormone receptor-positive, HER2-negative breast cancer in postmenopausal women 4, 5, 6, 7.
• The use of AIs, such as anastrozole, letrozole, and exemestane, has been shown to improve disease-free survival and overall survival in patients with hormone receptor-positive, HER2-negative breast cancer 4, 6, 7.
• AIs are often used as adjuvant therapy for early-stage breast cancer and as first-line treatment for advanced or metastatic breast cancer 6, 7.
• The choice of AI may depend on individual patient factors, such as menopausal status and tumor characteristics 4, 7.

Specific AIs Used

• Letrozole and anastrozole are non-steroidal AIs that have been shown to be effective in the treatment of hormone receptor-positive, HER2-negative breast cancer 4, 5, 7.
• Exemestane is a steroidal AI that has also been shown to be effective in the treatment of hormone receptor-positive, HER2-negative breast cancer 5, 6, 7.
• The use of AIs in combination with other therapies, such as CDK4/6 inhibitors, has been shown to improve progression-free survival in patients with hormone receptor-positive, HER2-negative breast cancer 5.

Recent Developments

• Recent trials have demonstrated the efficacy of adding abemaciclib to endocrine therapy (ET) for high-risk early-stage hormone-receptor-positive, HER2-negative breast cancer 8.
• The use of olaparib in combination with ET has also been shown to improve invasive disease-free survival, distant recurrence-free survival, and overall survival in patients with germline BRCA1/BRCA2 mutations 8.
• Ovarian function suppression (OFS) in combination with adjuvant tamoxifen or aromatase inhibition (AI) has been shown to be effective in premenopausal women with high-risk tumors 8.