Breast ultrasonography (BU) in the screening protocol for women at hereditary-familial risk of breast cancer: has the time come to rethink the role of BU according to different risk categories?

This article evaluates the breast cancer (BC) screening efficacy of biannual ultrasound (US) in three different risk categories. In a single-center, prospective, nonrandomized comparison study, BRCA mutation carriers and women with high risk (HR) or intermediate risk (IR) received mammography (MMG), ultrasound, (US) and Magnetic Resonance Imaging (MRI), scheduled according to the risk categories. Single and combined sensitivity were evaluated in specific groups of risk and the US performance at six-monthly interval was notably considered. Among 2,313 asymptomatic women at different risk (136 mutation carriers, 1,749 at HR and 428 at IR) 211 developed a BC, of which 193 (91.5%) were screen detected BC (SDBC) and 18 (8.5%) were interval BC (IBC). The SDBC detection rate (DR) was 11.2 per 1.000 person-years (37.9, 8.5 and 16.1 for BRCA, HR and IR, respectively); 116 BC were detected by MMG (DR = 6.6 × 1,000 persons-years), 62 by US (DR = 3.6 × 1,000 persons-years) and 15 by MRI, that was applied only in 60 BRCA women (DR = 37 × 1,000 persons-years). At the six-monthly US, 52 BC were detected (DR = 3.0 × 1,000 persons/years), of which 8 were BRCA-related. The most sensitive technique was MRI (93.7%) followed by MMG (55%) and US (29.4%). Combined sensitivity for MMG plus US was 100% in HR and 80.4% for IR women (p < 0.01). In BRCA mutated patients, MRI alone with annual US performed after six months, could be offered. In HR patients, MMG plus biannual US provide the most sensitive diagnosis and for IR group an annual MMG could be sufficient.

Magnetic resonance imaging and ultrasonography in predicting infiltrating residual disease after preoperative chemotherapy in stage II-III breast cancer.

BACKGROUND: This study was designed to evaluate the accuracy of breast magnetic resonance imaging (MRI) and ultrasonography (US) in predicting the extent of breast residual disease after preoperative chemotherapy. METHODS: Patients with stage II-III invasive breast tumors who received preoperative chemotherapy and were imaged with post-treatment MRI were included. Histopathological verification was available for all patients. The longest diameter of residual tumor measured with MRI and US has been compared with the infiltrating residual tumor size at pathologic evaluation. RESULTS: A total of 108 patients were enrolled: 59 were imaged with both MRI and US (MRI group), and 49 were imaged with US only (non-MRI group). The non-MRI group was enrolled as an external control to avoid possible bias in the selection of patients. In the MRI group, the means of the deltas between MRI residual tumor size and pathologic size and between US and pathologic size were 0.16 cm and -0.06 cm respectively (P = not significant). Overall, a discrepancy limited in the interval from -0.5 cm to +0.5 cm compared with the pathologic size was observed in 54% and 51% of the patients with MRI and US, respectively (P = not significant). The linear correlation between the radiological measurement and pathologic tumor size was r = 0.53 for MRI and r = 0.66 for breast US. In the non-MRI group, the mean of the deltas between US residual tumor size and pathologic size was 0.06 cm, and the linear correlation was r = 0.79. CONCLUSIONS: In this series of patients, MRI and US do not show significant differences in predicting the breast residual infiltrating tumor after preoperative chemotherapy.

Contrast-enhanced ultrasound in the characterisation of breast masses: utility of quantitative analysis in comparison with MRI.

OBJECTIVE: To evaluate the reliability of contrast-enhanced ultrasound quantitative analysis (CE-US) in characterizing breast lesions, in comparison with MRI. MATERIALS: Thirty-nine patients with breast lesions BI-RADS 3-5 at US or mammography underwent CE-US and MRI. All lesions underwent histological and quantitative enhancement evaluation with both imaging methods. B-mode US, colour/power Doppler US and CE-US were used; an amplitude and phase modulation technique (CPS) read the signals produced by microbubbles and dedicated software produced the following parameters on time/intensity (T/I) curves: peak %, time to peak (TTP), mean transit time (MTT), regional blood volume (RBV) and regional blood flow (RBF). Student's t test was used to calculate the diagnostic accuracy of CE-US parameters compared with histological results. MRI (1.5 T) was performed before and after bolus gadolinium enhancement. Time/intensity curves were generated for all nodules and Fischer's multimodal score was used to classify them. RESULTS: Pathology showed 43 nodules (11 benign; 32 malignant). Peak and RBF were the most significant parameters in differential diagnosis, with p values of 0.02 and 0.004, respectively. Positive predictive value (PPV) of CE-US evaluation was 91%, negative predictive value (NPV) was 73% with a high concordance index (k = 0.59) with MRI. CONCLUSIONS: CE-US quantitative analysis offers an objective and reproducible assessment of lesion vascularisation, with good correlation with the results of MRI.

Breast cancer screening in women at increased risk according to different family histories: an update of the Modena Study Group experience.

BACKGROUND: Breast cancer (BC) detection in women with a genetic susceptibility or strong family history is considered mandatory compared with BC screening in the general population. However, screening modalities depend on the level of risk. Here we present an update of our screening programs based on risk classification. METHODS: We defined different risk categories and surveillance strategies to identify early BC in 1325 healthy women recruited by the Modena Study Group for familial breast and ovarian cancer. Four BC risk categories included BRCA1/2 carriers, increased, intermediate, and slightly increased risk. Women who developed BC from January 1, 1994, through December 31, 2005 (N = 44) were compared with the number of expected cases matched for age and period. BRCA1/2 carriers were identified by mutational analysis. Other risk groups were defined by different levels of family history for breast or ovarian cancer (OC). The standardized incidence ratio (SIR) was used to evaluate the observed and expected ratio among groups. All statistical tests were two-sided. RESULTS: After a median follow-up of 55 months, there was a statistically significant difference between observed and expected incidence [SIR = 4.9; 95% confidence interval (CI) = 1.6 to 7.6; p < 0.001]. The incidence observed among BRCA carriers (SIR = 20.3; 95% CI = 3.1 to 83.9; P < 0.001), women at increased (SIR = 4.5; 95% CI = 1.5 to 8.3; P < 0.001) or intermediate risk (SIR = 7.0, 95% CI = 2.0 to 17.1; P = 0.0018) was higher than expected, while the difference between observed and expected among women at slightly increased risk was not statistically significant (SIR = 2.4, 95% CI = 0.9 to 8.3; P = .74). CONCLUSION: The rate of cancers detected in women at high risk according to BRCA status or strong family history, as defined according to our operational criteria, was significantly higher than expected in an age-matched general population. However, we failed to identify a greater incidence of BC in the slightly increased risk group. These results support the effectiveness of the proposed program to identify and monitor individuals at high risk, whereas prospective trials are needed for women belonging to families with sporadic BC or OC.