From August 2011 to August 2014, we conducted this prospective single-center study (Department of Obstetrics and Gynecology, University Hospital Basel, Switzerland) which was approved by the local ethical committee (EKBB Nr. 123/11). To recruit women from an unselected, consecutive, mixed collective, a study information package was sent to all eligible subjects prior to the initial examination. All participating women signed the informed consent form. Study subjects were examined by meander-like and radial US on the same day by different examiners. The study population included asymptomatic women with either an increased risk for breast cancer or with dense breast tissue, symptomatic women presenting with breast pain or palpable breast lesions, and women with a history of breast cancer. We excluded men, women younger than 18 years of age, and women scheduled for minimal invasive breast biopsies.
Before the ultrasound examination, we recorded personal and family history, and performed a physical breast examination. All participants had a bilateral r-US and m-US in random order by different examiners who had access to the clinical findings, and, where available, to the mammographic results but not to the US examination of the other examiner.
All r-US were carried out by the same research fellow with limited experience in breast US who received a theoretical and practical didactic training in r-US at the onset of the study. M-US were performed by experts or beginners under the supervision of an expert, as it is common in teaching hospitals. All examiners received a yearly training in breast US.
The examiners used ultrasound equipment of the same type (EUB-7500 V 16–53 Step 3.5, Hitachi Medical Systems Europe Holding AG, Zug, Switzerland) for r-US and m-US examinations. A 50 mm wideband, high frequency (13 − 5 MHz) linear transducer (EUP-L74M; Hitachi Medical Systems Europe Holding AG, Zug, Switzerland) was employed for m-US. For r-US, a 92 mm wideband (10 − 5 MHz) linear transducer (EUP-L53L; Hitachi Medical Systems Europe Holding AG, Zug, Switzerland) was used with a water standoff (a water-filled latex cover) according to the manufacturer’s instructions (Hitachi Medical Systems Europe Holding AG, Zug, Switzerland). Both transducers had a center frequency of 7.5 MHz.
Examiners saved an image with a timestamp at the beginning and at the end of each ultrasound examination to determine the duration of the examination. The US examinations were carried out as described in Jäggi et al. (2020) [28]. In brief, both types of breast US examination were conducted with the woman lying in an oblique supine position with her ipsilateral arm raised and her hand placed behind the head to flatten the breast tissue. For r-US, the examiner moved the transducer first clockwise around the mammilla in a radial, and then in an anti-radial fashion, followed by a radial and anti-radial sweep of the upper outer quadrant to examine the axillary tail. In contrast, a meander- like scanning pattern was applied in vertical and transverse direction in m-US. Both r-US and m-US routinely included scanning of the axilla.
The examiners recorded the location of each lesion according to the clock-face. Based on the wide transducer in r-US, the mammilla is visualized as the rotation point, and thus, allowed for measuring the distance between lesion and nipple. In m-US, the nipple-lesion distance was estimated. In addition, in both US methods, the shortest distance between lesion and skin was recorded.
For m-US and m-US, we determined the dimensions of each sonographic lesion based on recordings in two orthogonal planes [28]. In addition, the morphologic features of each lesion were described. Examiners classified each lesion according to the BI-RADS Atlas [29]. Breast lesions classified as BI-RADS 4 or 5, and as BI-RADS 3 in patients with an increased breast cancer risk, were biopsied (sonographic-guided fine needle aspiration, core needle biopsy or vacuum-biopsy) for histological analysis.
Size, location, morphologic characteristics of the lesion and their final BI-RADS classification were electronically saved in the patient record (ViewPoint®, Version 5: GE Healthcare GmbH, Munich, Germany).
All data on patient and lesion characteristics extracted from the electronic patient records were entered into R (R Development Core Team 2018, Vienna, Austria) for data analysis.
Statistical methods:
Patient and lesion characteristics were summarized. Categorical data are presented as frequencies and percentages. For continuous variables, mean and standard deviation as well as range are presented.
In categorical variables, agreement between the two scanning procedures was quantified using κ-values with quadratic weights. However, for the endpoint “clock-face location” the cyclicity was taken into account by choosing weights according to the distance on the clock rather than absolute timepoints, meaning that the distance between "0" and "1" and between "11" and "0" is 1 hour in both cases.
Weighted κ-values were interpreted as suggested by Landis et al. [30]: ≤0.20 poor agreement, 0.21–0.40 fair agreement, 0.41–0.60 moderate agreement, 0.61–0.80 substantial agreement, and 0.81-1.00 excellent agreement.
In continuous variables, the agreement was quantified using intraclass-correlation (ICC) [31]. The ICC is calculated based on analysis of variance. To this end, a mixed model is fitted to the data with scanning procedure and patient as random factors, and a fixed intercept was fitted. The ICC was estimated by dividing the variation related to the patient-to-patient difference by the total variance in the data. Therefore, ICC ranged between 0 and 1 and can be interpreted as the proportion of the variation of the data, which can be attributed to patient-to-patient variability. An ICC of 1 indicates a perfect agreement between r-US and m-US and that all differences in the ratings are due to differences in the patients. For the variable “mean volume”, the data was cube-root transformed prior to fitting the model since errors in main axes were inflated by the calculation of the volume leading to outliers not acceptable in the mixed model.
ICC-values were interpreted according to Cicchetti [32] : <0.40 poor agreement, 0.40–0.59 fair agreement, 0.60–0.74 good agreement, and 0.75-1.00 excellent agreement.