Breast Screening (Above Average Risk Women)

high_risk

Breast Screening in Asymptomatic Above Average Risk Women

• Women with an increased risk of developing breast cancer can develop a malignancy at a relatively young age compared to women at ‘average risk’. It is therefore necessary to begin screening these ‘above average risk’ women at an earlier age than one would for women at ‘average risk’
• This increased risk of breast cancer can usually be ascertained from a positive family history. In a small proportion of these women a gene mutation (most commonly BRCA 1 and BRCA 2) is responsible
• They also have a higher interval cancer rate and therefore screening intervals need to be adjusted to reduce the rate of interval cancers
• Mammography may be less sensitive in younger women where the breast tissue may be mammographically dense
• Contrast enhanced MRI has developed as a potential screening modality in women at ‘high risk’ of developing breast cancer and several large prospective trials have proved its efficacy in this regard

risk_assessment

Risk Assessment

• The selection of the most appropriate screening regimen, begins by establishing the risk of breast cancer in any individual woman
• The following table is a composite of recommendations for risk assessment and is a guide 1

cbe_us_mammo

Clinical Breast Examination + Mammography ± Ultrasound

• Clinical breast examination (CBE) has been shown to solely detect between 4.6-10.7% of breast cancers. 2 However, this systematic review of the literature included patients who were both asymptomatic and those presenting to their physician with a breast symptom. Thus this may over-estimate the usefulness of CBE in a truly asymptomatic population 3
• There have been no randomised control trials to demonstrate whether CBE improves mortality 3
• Evidence generally suggests there is a reduction in breast cancer-specific mortality with mammography screening 4,5,6
• However there has been mixed evidence thus far regarding mortality in younger women specifically screened with mammography. A trial that enrolled women between the ages of 39-41 to screening mammography or control group, showed a significant reduction in breast cancer mortality in the intervention group in the first 10 years after diagnosis (RR 0.75, 95% CI 0.58-0.97) but no significant reduction from 10 to 17 years of follow-up (RR 1.02, 95% CI 0.80-1.30) 7
• Radiation dose is a concern when using mammography to screen young women. The risk of annual screening with mammography (for radiation induced breast cancer) versus the benefit (detecting de novo breast cancer) is greatest when screening is begun below the age of 30 8
• Mammography is less sensitive in younger women due to an increased likelihood of the breast tissue being dense. This has led to a call for ultrasound to be used in addition to mammography in screening for breast cancer. Several series have demonstrated a higher diagnostic yield with sonography in clinically and mammographically occult breast lesions, in women with dense breast tissue 9,10
• In one trial looking at combined screening of high risk women with ultrasound and mammography to mammography alone, ultrasonography + mammography had a higher diagnostic accuracy (0.91 vs 0.78) compared to mammography alone and greater diagnostic yield (11.8 per 1000 vs 7.6 per 1000). 11 However, there are currently no trials which have proven a mortality benefit
• Women at a lifetime risk of breast cancer of between 1 in 8 and 1 in 4, annual mammography should commence screening at age 40. The addition of bilateral whole breast ultrasound examination should be considered in women with mammographically dense breast tissue. 8 Though CBE is of questionable value, it may reinforce the need for ongoing screening and thus should be encouraged 3

cbe_mammo_mri

Clinical Breast Examination + Mammography + Magnetic Resonance Imaging (MRI)

• Clinical breast examination (CBE) has been shown to solely detect between 4.6-10.7% of breast cancers. 2 However, this systematic review of the literature included patients who were both asymptomatic and those presenting to their physician with a breast symptom. Thus this may over-estimate the usefulness of CBE in a truly asymptomatic population. 3 A more recent trial that screened a cohort of ‘high risk’ women with CBE, mammography and MRI reported sensitivities of 17.9%, 33.3% and 79.5% respectively for the detection of invasive breast cancer 12
• There has been no randomised control trials to demonstrate whether CBE improves mortality 3
• Evidence generally suggests there is a reduction in breast cancer-specific mortality with mammography screening, 4,5,6 however the benefits are less clear at younger ages
• A recent meta-analysis showed that in women aged 39 to 49 years there was a statistically non-signification reduction in breast cancer mortality with screening (combined RR of 0.92 (95% CI 0.75-1.02)) 13
• In a diagnostic setting, MRI is a very sensitive tool for the detection of breast cancer. Especially for invasive breast cancer, the sensitivity of this imaging technique is reported to be above 95% 14
• MRI has gained recognition as a potential tool in the screening of ‘high risk’ women for breast cancer, as mammography alone has been shown to have limited efficacy in this cohort of patients 15
• There have been several large trials in high risk women that utilised MRI in a screening program. Sensitivities of 71-100% have been reported 12,16,17,18,19
• This compares favourably to screening mammography and ultrasound in the same trials; mammography 33-36% and ultrasound 33-40% respectively 16,17
• The increased diagnostic yield with MRI comes at the price of a higher number of false positive cases. Specificities of 90-97% have been reported with MRI. 12,16,17 This results in the need for further diagnostic tests, more biopsies of suspect lesions, increased costs and anxiety to the patient
• Whole breast ultrasound has not been shown to increase the cancer detection rate where contrast enhanced breast MRI and mammography are also being performed as part of surveillance. 17 Targeted ultrasound may have a role however, in the further evaluation of concerning lesions identified on MRI
• As distinct from mammography, no trials have yet been conducted to demonstrate a mortality benefit from the increased detection of breast cancer in these ‘high risk’ women with MRI. 20 Indirect measures of early tumour detection, such as lesion size and affected node disease may provide an indirect measure of the benefits of MRI compared to other diagnostic modalities 8
• Women at a lifetime risk of breast cancer of between 1 in 4 and 1 in 2, should have annual mammography commencing at the age of 40 (or 5 years before the youngest family member affected by the disease, with the earliest commencing age being 30 years). 8 Women being considered for MRI should be referred to a high risk genetic clinic. Whether the investigations should be done concurrently, or spaced at 6month intervals have yet to be determined and no evidence currently exists to support either regime. 21 Though CBE is of questionable value, it may reinforce the need for ongoing screening and thus should be encouraged 3
• Given the ongoing research into MRI as a screening tool in ‘high risk’ women, consideration should be given to referring eligible patients to multidisciplinary teams / high risk genetic clinics with developing expertise in the field. This will lead to the collation of audit data, expertise in radiological interpretation / MRI based biopsy techniques and adequate follow-up of such women

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