What is the Tyrer-Cuzick (Tyrer-Cuzick model, a breast cancer risk assessment tool) lifetime risk for breast cancer?

From the Guidelines

The Tyrer-Cuzick model is the most appropriate tool for calculating a woman's lifetime risk of developing breast cancer, as it considers multiple risk factors, including age, family history, hormonal factors, benign breast disease history, body mass index, and breast density, and provides a more comprehensive assessment than other models, such as the BCRAT model, especially in women with a strong family history of breast cancer or other high-risk features 1.

Key Features of the Tyrer-Cuzick Model

• The model evaluates multiple risk factors to provide a personalized estimate of breast cancer risk
• It is particularly useful in women with a strong family history of breast cancer, as it considers the age at onset of cancer in family members and cancer in second-degree relatives
• The model provides 10-year and residual absolute lifetime risk estimates, and in Version 8, a 5-year risk can also be estimated
• A Tyrer-Cuzick lifetime risk score of 20% or greater is generally considered high risk, often qualifying women for enhanced screening protocols such as annual mammography plus breast MRI

Clinical Applications of the Tyrer-Cuzick Model

• Healthcare providers use the Tyrer-Cuzick score to determine appropriate screening intervals and consider chemoprevention options like tamoxifen or raloxifene
• The model helps guide personalized screening and prevention strategies, taking into account individual risk factors and medical history
• Women with a calculated 5-year risk of ≥ 3% or with a 10-year absolute risk of ≥ 5% should be offered endocrine therapy, as well as those with atypical hyperplasia or lobular carcinoma in situ, who have a four- to 10-fold increase in breast cancer risk compared to those without a precursor lesion 1

Importance of Regular Updates and Improvements

• The Tyrer-Cuzick model is regularly updated to improve accuracy, with the current version (v8) incorporating breast density as a risk factor, which significantly improves risk prediction compared to earlier versions
• These updates ensure that the model remains a valuable tool for healthcare providers to assess breast cancer risk and develop effective prevention and screening strategies, as supported by recent studies on breast cancer risk assessment and management 1

From the Research

Tyrer-Cuzick Lifetime Risk

• The Tyrer-Cuzick model is used to estimate the lifetime risk of breast cancer in women, taking into account various risk factors such as family history, genetic mutations, and reproductive factors.
• Studies have shown that chemoprevention with selective estrogen receptor modulators (SERMs) such as tamoxifen and raloxifene can reduce the risk of breast cancer in high-risk women 2, 3, 4, 5.
• A meta-analysis of nine studies found that tamoxifen and raloxifene significantly reduced the breast cancer risk in women with BRCA1/2 mutations, with a risk ratio of 0.80 (95% CI 0.72-0.88, p = 0.04) 5.
• The benefit-risk assessment of tamoxifen and raloxifene for breast cancer chemoprevention depends on age, race, breast cancer risk, and history of hysterectomy, with postmenopausal women with an intact uterus having a better benefit-risk index for raloxifene than for tamoxifen 4.
• The use of tamoxifen and raloxifene as chemopreventive agents for breast cancer risk reduction in BRCA1/2 mutation carriers has been shown to be effective, with similar efficacy for both BRCA1 and BRCA2 carriers 5.

Chemoprevention Options

• Tamoxifen has been shown to reduce the risk of breast cancer by as much as 50% in high-risk women, but its use is associated with an increased risk of thromboembolic events, endometrial cancer, and cataracts 3, 4.
• Raloxifene has been shown to be as effective as tamoxifen in reducing the risk of invasive breast cancer in postmenopausal women, with a lower risk of thromboembolic events, endometrial cancer, and cataracts 3, 4.
• The aromatase inhibitors (AIs) have been shown to decrease the incidence of contralateral breast cancer when used in the adjuvant setting, and are being evaluated in ongoing primary prevention studies 3.

Imaging Modalities

• Mammographic density and breast magnetic resonance imaging (MRI) volume can be used as surrogate endpoint biomarkers for breast cancer chemoprevention trials, with raloxifene having been shown to significantly decrease MRI volume in premenopausal women at increased risk for breast cancer 6.