Aromatase Inhibitors Show Greater Benefit in Preventing Contralateral Breast Cancer

Endocrine therapy regimens are associated with a reduction in contralateral breast cancer (CBC) cases, according to authors of a study published in npj Breast Cancer. Their findings are intended to inform clinical guidelines and support decision-making around the use of endocrine therapy to prevent CBC.¹

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Endocrine therapy is a cornerstone of breast cancer treatment, demonstrating meaningful benefits in overall survival and reducing the risk of CBC, particularly amongst patients with estrogen receptor–positive (ER+), HER2-negative (ER+/HER2-) breast cancer. ER+/HER2- breast cancer accounts for nearly 70% to 80% of all breast cancer diagnoses, representing the critical need for therapeutic options for these patients. These subtypes are aggressive and challenging to treat despite numerous advancements in existing agents and the development of new ones.²

Research suggests that aromatase inhibitors may be more effective than tamoxifen (Soltamox; Mayne Pharma Group Limited) in lowering cancer-related deaths and the risk of cancer in the opposite breast. However, many women stop hormonal therapy due to side effects. Shorter treatment durations may reduce the benefits of endocrine therapy, including protection against CBC. Previous studies have had limitations such as short follow-up periods, small sample sizes, and limited real-world applicability. As a result, there is a lack of data on how breast cancer outcomes vary over a patient’s lifetime based on age at diagnosis, treatment type, and duration, making shared decision-making more challenging.¹

The investigators aimed to establish estimates quantifying the lifetime outcomes by age at primary diagnosis, regimen, or duration associated with endocrine therapy and CBC risk. They evaluated female patients with stage 0 to 3 ER+/HER2- breast cancer who received different durations (none, 2.5, 5, 10 years) of either an aromatase inhibitor or tamoxifen. To simulate lifetime risks of CBC, primary breast cancer, and other-cause survival in patients, the investigators adapted an established Cancer Intervention and Surveillance Network (CISNET) breast cancer simulation model.¹

The data indicated that longer durations of endocrine therapy and the use of aromatase inhibitors instead of tamoxifen lead to a greater reduction in CBC cases, although the impact varies by age at diagnosis. The most significant benefit was seen with a 10-year aromatase inhibitor regimen, which prevented 11.2 CBC cases per 100 women with ER+/HER2- breast cancer compared with 6.0 cases per 100 women who received no adjuvant therapy.¹

For those on a 5-year aromatase inhibitor regimen, younger women experienced the greatest reduction in CBC cases, with 5.0 fewer cases per 100 women under 45 years old. However, this benefit declined with age, with women aged 75 and older seeing a reduction of only 2.7 cases per 100. These findings highlight the importance of both treatment duration and patient age in determining the effectiveness of endocrine therapy in reducing CBC risk.¹

These findings reinforce the importance of individualized treatment planning for patients with ER+/HER2- breast cancer. Younger women see the greatest reduction in risk, whereas older patients experience diminishing returns. By incorporating these insights into clinical guidelines, health care providers can better tailor endocrine therapy regimens to maximize benefits while considering factors like age, side effects, and treatment adherence.

REFERENCES

1. Sarkar S, Schechter C, Kurian A, et al. Impact of endocrine therapy regimens for early-stage ER+/HER2-breast cancer on contralateral breast cancer risk. npj Breast Cancer. March 26, 2025. doi:10.1038/s41523-025-00746-7

2. Tanshinlactone may inhibit the growth of ER+, HER2+, or EGFR-mutated cells in breast cancer. Pharmacy Times^®. February 24, 2025. Accessed March 27, 2025. https://www.pharmacytimes.com/view/tanshinlactone-may-inhibit-the-growth-of-er-her2-or-egfr-mutated-cells-in-breast-cancer