Estradiol’s Role in Anastrozole Efficacy for Breast Cancer Prevention

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Estradiol’s Role in Anastrozole Efficacy for Breast Cancer Prevention

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Estradiol’s Role in Anastrozole Efficacy for Breast Cancer Prevention

Influence of Estradiol Serum Concentration on the Efficacy of Anastrozole in Preventing Breast Cancer in Postmenopausal Women at High Risk.

Anastrozole is an aromatase inhibitor used in the treatment and prevention of breast cancer. Its mechanism of action involves inhibiting aromatase enzyme activity, reducing the production of estrogen. Estrogen plays a crucial role in the development of breast cancer, and by inhibiting its production, anastrozole can lower the risk of breast cancer.

After menopause, ovaries cease estrogen production, and adipose tissue becomes the primary source of estrogen. Elevated serum levels of estradiol and testosterone after menopause are recognized as increasing the risk of breast cancer. By inhibiting aromatase, anastrozole reduces estrogen levels, thus decreasing the risk of breast cancer.

Anastrozole is typically administered orally once a day. However, its usage comes with some side effects, including joint pain, osteoporosis, fatigue, and headaches. Therefore, before using anastrozole, a thorough discussion and assessment with a doctor are recommended to weigh the pros and cons and determine suitability for individual use.

A recent randomized, controlled, double-blind trial published in Lancet Oncology investigated the impact of serum estradiol, testosterone, and SHBG concentrations on the risk of breast cancer in postmenopausal women at high risk, as well as the influence on the efficacy of the aromatase inhibitor anastrozole. The aim was to assist clinicians in identifying women who would benefit the most from aromatase inhibitors.

Study Details:

The study utilized data from the IBIS-II prevention trial, conducted in 153 breast cancer treatment centers across 18 countries. Participants were postmenopausal women aged 40-70 at high risk of breast cancer. The primary analysis focused on the impact of baseline estradiol to sex hormone-binding globulin (SHBG) ratio (estradiol-SHBG ratio) on the incidence of all breast cancers, including ductal carcinoma in situ (the primary trial endpoint).

In the trial, women were randomly assigned (1:1) to receive either anastrozole (1 mg/day, orally) or placebo treatment, once daily, for 5 years.

Between February 2, 2003, and January 31, 2012, 3864 women were recruited, with 1920 receiving anastrozole and 1944 receiving placebo. The median follow-up time was 131 months (IQR 106-156). During this period, the anastrozole group had 85 cases (4.4%) of breast cancer, while the placebo group had 165 cases (8.5%). After exclusions, the anastrozole group had 212 individuals (72 cases, 140 controls), and the placebo group had 416 individuals (142 cases, 274 controls).

Study Results:

The study found that as the estradiol-SHBG ratio increased, the placebo group showed an upward trend in breast cancer risk (trend per quartile: 1.25 [95% CI 1.08 to 1.45], p=0.0033), while the anastrozole group did not exhibit this trend (1.06 [0.86 to 1.30], p=0.60). The impact of testosterone-SHBG ratio on breast cancer was weaker in the placebo group (trend: 1.21 [1.05 to 1.41], p=0.011) compared to the anastrozole group (trend: 1.18 [0.96 to 1.46], p=0.11).

In the second quartile (0.55 [95% CI 0.13 to 0.78]), third quartile (0.54 [0.22 to 0.74]), and fourth quartile (0.56 [0.23 to 0.76]) of the estradiol-SHBG ratio, anastrozole demonstrated relative benefits. However, no significant effect was observed in the first quartile (0.18 [-0.60 to 0.59]).

To our knowledge, this is the first report on the impact of serum estradiol concentration on aromatase inhibitor treatment. The study confirms that the aromatase inhibitor anastrozole has relative benefits in preventing breast cancer in postmenopausal women at high risk. However, these benefits are limited to women with moderate or high estradiol-SHBG ratios, with no apparent effect on women in the lowest quartile.

These findings suggest that measuring estradiol, testosterone, and SHBG has broader potential roles, helping identify high-risk individuals and determining potential responses to endocrine therapy.

Overall:

Aromatase inhibitors are the most effective choice for treating early estrogen receptor-positive breast cancer and preventing breast cancer in postmenopausal women at high risk. The role of serum hormones in determining the effectiveness of preventive hormone therapy for individual women is a key question revealed in this study. A more significant question is the value of these measurements in selecting adjuvant therapy.

Serum hormone assays are cost-effective, and increased routine use of hormone assays in high-risk diagnosis and early breast cancer treatment can significantly improve disease management. It can assist clinicians in identifying women who would benefit the most from using aromatase inhibitors for breast cancer prevention.

Estradiol’s Role in Anastrozole Efficacy for Breast Cancer Prevention

Reference:
“Effect of baseline oestradiol serum concentration on the efficacy of anastrozole for preventing breast cancer in postmenopausal women at high risk: a case-control study of the IBIS-II prevention trial,” Lancet Oncol 2024; 25: 108–16.

(source:internet, reference only)

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