What is the reduction in breast cancer recurrence risk with aromatase inhibitors (AIs) compared to no treatment?

From the Guidelines

Aromatase inhibitors reduce breast cancer recurrence risk by approximately 30-50% compared to not taking them. These medications, which include anastrozole (Arimidex), letrozole (Femara), and exemestane (Aromasin), are typically prescribed for postmenopausal women with hormone receptor-positive breast cancer 1. The standard treatment duration is 5-10 years, with the medication taken once daily as an oral tablet. Aromatase inhibitors work by blocking the enzyme aromatase, which converts androgens into estrogens in postmenopausal women, thereby dramatically reducing estrogen levels in the body. Since many breast cancers depend on estrogen to grow, lowering estrogen levels helps prevent cancer recurrence.

Some key points to consider when prescribing aromatase inhibitors include:

• The ATAC trial showed that anastrozole is superior to tamoxifen or the combination of tamoxifen and anastrozole in the adjuvant endocrine therapy of postmenopausal patients with HR-positive breast cancer, with a hazard ratio for disease-free survival of 0.85 (95% CI, 0.76-0.94; P = 0.003) 1.
• The BIG 1-98 trial demonstrated that letrozole alone for 5 years is superior to tamoxifen alone for 5 years, with a hazard ratio for disease-free survival of 0.81 (95% CI, 0.70-0.93; log rank P = 0.003) 1.
• Side effects may include joint pain, bone loss, hot flashes, and increased risk of fractures, so calcium and vitamin D supplements are often recommended alongside these medications 1.
• Regular bone density monitoring is also important during treatment, as aromatase inhibitors can increase the risk of osteoporosis and fractures 1.
• For premenopausal women, tamoxifen is typically used instead, as aromatase inhibitors are not effective before menopause 1.

It's also important to consider the duration of adjuvant endocrine therapy, as recent studies have shown that extended therapy may provide additional benefits in reducing recurrence and death from breast cancer 1. The MA-17 trial demonstrated that extended therapy with letrozole provides benefit in postmenopausal patients with HR-positive, early-stage breast cancer, with a hazard ratio for disease-free survival of 0.52 (95% CI, 0.45-0.61) and an improved overall survival (HR, 0.61; 95% CI, 0.52-0.71) compared with placebo 1.

From the FDA Drug Label

The planned duration of treatment for patients in the study was 5 years, but the trial was terminated early because of an interim analysis showing a favorable letrozole effect on time without recurrence or contralateral breast cancer Table 9: Extended Adjuvant Study Results Letrozole N = 2582 Placebo N = 2586 Hazard Ratio (95% CI) P-Value Disease Free Survival (DFS)1Events122 (4.7%)193 (7.5%)0.62 (0.49,0.78) Table 10: Update of Extended Adjuvant Study Results Letrozole N = 2582 (%)Placebo N = 2586 (%)Hazard Ratio1 (95% CI) P-Value2 Disease Free Survival (DFS) events3344 (13.3)402 (15.5)0.89 (0.77,1.03)0.12 Breast cancer recurrence (Protocol definition of DFS events 4)2092860.75 (0.63,0. 89)0.001

Aromatase Inhibitors Reduce Breast Cancer Recurrence Risk

• The study results show that letrozole significantly reduced the risk of breast cancer recurrence or contralateral breast cancer compared with placebo, with a hazard ratio of 0.75 (95% CI 0.63,0.89; P=0.001) 2.
• This translates to a 25% reduction in the risk of breast cancer recurrence.
• However, the overall disease-free survival benefit was less pronounced, with a hazard ratio of 0.89 (95% CI 0.77,1.03) due to the high rate of switching to letrozole in the placebo arm.

From the Research

Aromatase Inhibitors and Breast Cancer Recurrence Risk

• Aromatase inhibitors (AIs) have been shown to reduce the risk of breast cancer recurrence in postmenopausal women with hormone receptor-positive breast cancer 3, 4, 5, 6, 7.
• The Arimidex, Tamoxifen Alone or in Combination (ATAC) trial, the Intergroup Exemestane Study (IES), and the MA-17 trial confirmed the superiority of AIs over tamoxifen in women with early-stage breast carcinoma, improving disease-free survival (DFS) considerably 3.
• The 4-year DFS rate was 86.9% on anastrozole and 84.5% on tamoxifen (P = 0.03) in the ATAC trial, and the 3-year DFS rate was 91.5% on exemestane and 86.8% on tamoxifen (P = 0.00005) in the IES 3.
• The MA-17 trial found a 4-year estimated DFS rate of 93% on letrozole and 87% on placebo (P < or = 0.001) 3.
• A systematic review of nine randomized controlled trials and one meta-analysis found that eight of these trials reported significantly improved disease-free survival in the arms that involved aromatase inhibitors 5.
• Aromatase inhibitors provide an alternative to tamoxifen as adjuvant therapy for post-menopausal, hormone-receptor-positive breast cancer patients, with options including anastrozole and letrozole for five years, as well as anastrozole and exemestane following two to three years of tamoxifen, for a total five years of hormonal therapy 5, 6.

Reduction in Breast Cancer Recurrence Risk

• The use of aromatase inhibitors as adjuvant therapy has been shown to reduce the risk of breast cancer recurrence by improving disease-free survival 3, 5, 6.
• The magnitude of the reduction in recurrence risk varies depending on the specific aromatase inhibitor and the treatment regimen used, but overall, aromatase inhibitors have been shown to be more effective than tamoxifen in reducing the risk of recurrence 3, 5, 6.
• The reduction in recurrence risk is thought to be due to the ability of aromatase inhibitors to more effectively suppress estrogen production in postmenopausal women, which is a key driver of hormone receptor-positive breast cancer growth 4, 7.