Study population description
Our database included 2245 women who had recent-onset US-detectable breast findings. The mean age was 37.5 years (range 12–79 years). The most frequent complaint of patients was palpable nodules (86.8%). The less frequent complaints were pain (4.1%) and nipple discharge (1.2%), respectively. And 7.9% of cases are asymptomatic, which were image findings. The average maximum diameter of the lesions was 13.2 mm (range 2–75 mm). All patients were addressed to undergo US-VAEB for the first time at our institute. The median duration of imaging follow-up post-US-VAEB was 24.7 months (range 12.0–60.0 months).
The clinicopathologic characteristics of the cases are summarized in Table 1.
Table 1
The distributions of benign, B3 or malignant breast lesions according to BI-RADS-US
BI-RADS category | Benign | Rate (%) | B3 | Rate (%) | Malignant | Rate (%) |
0 2 | 3 138 | 60 97.9 | 2 3 | 40 2.1 | 0 0 | 0 0 |
3 | 1568 | 90.4 | 134 | 7.7 | 33 | 1.9 |
4 | 31 | 72.1 | 4 | 9.3 | 8 | 18.6 |
4a | 204 | 82.2 | 28 | 11.3 | 16 | 6.5 |
4b | 28 | 63.6 | 4 | 9.1 | 12 | 27.3 |
4c | 14 | 66.7 | 0 | 0 | 7 | 33.3 |
5 | 0 | 0 | 0 | 0 | 8 | 100 |
BI-RADS the Breast Imaging Reporting and Data System, US ultrasound |
BI-RADS-US category assessment based on histopathological results of VAEB
Post-US-VAEB histopathological diagnoses confirmed that there were benign, B3, and malignant breast lesions as 1986 (88.5%), 183 (8.2%), and 76 (3.4%), respectively. Malignant lesions account for the minimum amounts of VAEB cases, and the overwhelming majority of VAEB cases are nonmalignant disorders that are unnecessary biopsy, which is consistent with previous reports [21, 22]. Afterward, we subclassified the lesions according to their BI-RADS-US category assessment. The incidences of B3 and malignant breast lesions in each grade of BI-RADS were listed in Table 1. Notably, the prevalent range for B3 was from BI-RADS 3 to BI-RADS 4b. And they were rarely diagnosed in BI-RADS 4c or BI-RADS 5. On the other hand, the malignant lesions were mainly distributed in the range from BI-RADS 4b to 5, which are compatible with the literature [23].
Malignancy underestimation rate and recurrence rate of B3
Initially, there was a total of 183 cases of B3 lesions proved by US-VAEB. The histopathological results of B3 subtypes were listed in Table 2. Meanwhile, one case of atypical ductal hyperplasia (ADH) which could not be excluded from the possibility of ductal carcinoma in situ (DCIS) was finally confirmed to be invasive breast cancer by open surgery (OS). 1 case of a complex of sclerosing lesions and radial scars (CSL/RS) which was discordant with image finding was confirmed to be invasive breast cancer through OS. 1 case of a complex of papillary lesions and atypical hyperplasia (PL/ADH) which had a high risk of malignant potential was received OS subsequently and verified to be intraductal carcinoma with lobular carcinoma[24]. Besides, 5 cases were followed up after VAEB, and found recurrences at the sites of operation, which were demonstrated as malignancies via OS, including 2 cases of ADH confirmed to be DCIS and invasive ductal carcinoma respectively, 2 cases of PL confirmed to be DCIS and invasive ductal carcinoma, 1 case of phyllodes tumors (PT) diagnosed as invasive breast cancer. In general, the risk of malignancy underestimation in the B3 group of biopsy-proven was 4.4% (8/183). The individual malignancy underestimation rates of B3 subtypes were displayed in Table 2. It is noteworthy that the more underrated B3 subtypes for malignancies were PL/ADH 50% (1/2), ADH 23.1% (3/13), and CSL/RS 16.7% (1/6). The results are in line with the reports [24, 25]. Although the malignancy underestimation rate of B3 is limited, multidisciplinary communication and imaging follow-up are necessary so as not to miss malignant potential [26].
Table 2
The underestimation of B3 lesions
B3 subtype | Number | Underestimation | Rate (%) |
ADH | 13 | 3 | 23.1 |
FEA | 4 | 0 | 0 |
LN | 3 | 0 | 0 |
PL | 84 | 2 | 2.4 |
PL/ADH | 2 | 1 | 50 |
PT | 71 | 1 | 1.4 |
CSL/RS | 6 | 1 | 16.7 |
ADH atypical ductal hyperplasia; FEA flat epithelial atypia; LN classical lobular neoplasia; PL papillary lesions; PL/ADH complex of papillary lesions and atypical hyperplasia; PT phyllodes tumors; CSL/RS complex of sclerosing lesions and radial scars |
After the period of follow-up, the recurrence rates of B3 subtypes were summarized in Table 3. We noticed that the highly frequent recurrences of B3 subtypes were ADH 10% (1/10), PT 8.6% (6/70), and PL 4.9% (4/82). The recurrence rates of the later two subtypes are concordant with the literature [29, 30]. Whether the higher recurrence rate of ADH was due to its fewer cases needs further observation.
Table 3
The recurrences of B3 lesions
B3 subtype | Number | Recurrence | Rate (%) |
ADH | 10 | 1 | 10 |
FEA | 4 | 0 | 0 |
LN | 3 | 0 | 0 |
PL | 82 | 4 | 4.9 |
PL/ADH | 1 | 0 | 0 |
PT | 70 | 6 | 8.6 |
CSL/RS | 5 | 0 | 0 |
ADH atypical ductal hyperplasia; FEA flat epithelial atypia; LN classical lobular neoplasia; PL papillary lesions; PL/ADH complex of papillary lesions and atypical hyperplasia; PT phyllodes tumors; CSL/RS complex of sclerosing lesions and radial scars |
Overall consideration of both the incidence of B3 lesion and its malignancy underestimation rate, only a minority of B3 lesions should be subjected to VAEB. Combining B3 lesion’s malignancy underestimation rate with its recurrence rate, we recommend OS for ADH, PL/ADH, and PT subtypes, which is similar to those of reports [27–29].
The specific ultrasonic features and patients’ characters of B3 comparing to those of benign or malignant cases
In clinical practice, uncertain malignant potentials are the most frequent causes which disturb both patients and physicians. To a certain extent, this could explain why most of the biopsy cases are nonmalignant breast disorders. One question is presented here that could we get any clues for B3 changes before the excision biopsy? Therefore, we analyzed the differences between the ultrasonic features of B3 lesions before VAEB and their associated patients' characteristics and those of benign or malignant cases by Chi-square test / Fisher's exact test. To our best knowledge, it’s the first time that we noticed that among B3 cases, the incidences of non-menopausal patients (P = 0.002), single (P = 0.000) or blood supply abundant nodules (P = 0.000) examined by ultrasound were significantly increased, compared to those of benign cases. Also, the incidence of the irregular shape of nodules in B3 cases tended to be higher than that of benign cases (P = 0.080) (Table 4). In the meantime, we compared B3 with malignant cases and found that the incidences of patients elder than 50 years (P = 0.000), non-reproductive age (P = 0.000) and menopause (P = 0.000), and nodules with irregular shape (P = 0.000), uncircumscribed margin (P = 0.000), abundant blood supply (P = 0.002) or microcalcification (P = 0.000) in ultrasound findings were significantly increased in malignant cases (Table 4). Furthermore, univariate and multivariate binary logistic regression analyses (B3 vs benign) showed that non-menopausal patients, single or abundant blood supply nodules were significant risk factors for B3 occurrences [Table 5]. While B3 compared to malignant, univariate binary logistic regression analyses showed that patients elder than 50 years, and unclear margin, abundant blood supply or microcalcification nodules were closely associated with malignancies. Moreover, multivariate logistic regression analyses demonstrated that patients elder than 50 years, unclear margin or microcalcification nodules were significant risk factors for malignant potential [Table 6]. On these grounds, we reviewed the 8 malignancy underestimation cases in the B3 group and found that 6 out of them were elder than 50 years, and 5 out of them presented with uncircumscribed nodules, which were well covered by the malignant risk factors.
Table 4
Comparison between characters of B3 and those of benign or malignant cases
| Benign | B3 | χ2 | P | B3 | Malignant | χ2 | P |
Age | | | | | | | | |
≤ 50 | 1809 | 165 | 2.081 | 0.149 | 165 | 56 | 34.583 | 0.000 |
> 50 | 177 | 10 | | | 10 | 28 | | |
Reproductive age | | | | | | | | |
Yes | 1148 | 97 | 0.372 | 0.542 | 97 | 25 | 15.006 | 0.000 |
No | 838 | 78 | | | 78 | 59 | | |
Menopause | | | | | | | | |
No | 1767 | 169 | 9.955 | 0.002 | 169 | 58 | 39.706 | 0.000 |
Yes | 219 | 6 | | | 6 | 26 | | |
Multifocality | | | | | | | | |
Unifocal | 454 | 65 | 17.979 | 0.000 | 65 | 35 | 0.490 | 0.555 |
Multifocal | 1532 | 110 | | | 110 | 49 | | |
Shape | | | | | | | | |
Regular | 1786 | 150 | 3.064 | 0.080 | 150 | 48 | 25.733 | 0.000 |
Irregular | 200 | 25 | | | 25 | 36 | | |
Margin | | | | | | | | |
Circumscribed | 1611 | 145 | 0.319 | 0.572 | 145 | 29 | 60.137 | 0.000 |
Not circumscribed | 375 | 30 | | | 30 | 55 | | |
Microcalcification | | | | | | | | |
Absent | 1864 | 168 | 1.316 | 0.572 | 168 | 56 | 41.785 | 0.000 |
present | 122 | 7 | | | 7 | 28 | | |
Vascularity | | | | | | | | |
Absent/scarce | 1847 | 142 | 30.870 | 0.000 | 142 | 53 | 9.937 | 0.002 |
Abundant | 139 | 33 | | | 33 | 31 | | |
Table 5
Binary logistic regression analyses between characters of benign cases and those of B3
| Univariate | | Multivariate |
OR (95% CI) | P | OR (95% CI) | P |
Menopause | | | | | |
Yes | 3.491 (1.528, 7.976) | 0.003 | | 3.745 (1.628, 8.616) | 0.002 |
No | | | | | |
Multifocality | | | | | |
Multifocal | 1.994 (1.442, 2.757) | 0.000 | | 1.905 (1.370, 2.650) | 0.000 |
Unifocal | | | | | |
Shape | | | | | |
Regular | 1.488 (0.951, 2.329) | 0.082 | | 1.259 (0.788, 2.014) | 0.336 |
Irregular | | | | | |
Vascularity | | | | | |
Absent/scarce | 3.088 (2.037, 4.682) | 0.000 | | 2.691 (1.745, 4.150) | 0.000 |
Abundant | | | | | |
95% CI 95% confidence interval, OR odds ratio |
Table 6
Binary logistic regression analyses between characters of B3 cases and those of malignancies
| Univariate | | Multivariate |
OR (95% CI) | P | OR (95% CI) | P |
Age | | | | | |
≤ 50 | 8.25 (3.770, 18.053) | 0.000 | | 7.936 (3.178, 19.816) | 0.000 |
> 50 | | | | | |
Margin | | | | | |
Circumscribed | 9.167(5.044, 16.659) | 0.000 | | 7.101 (3.571, 14.119) | 0.000 |
Not circumscribed | | | | | |
Microcalcification | | | | | |
Absent | 12.000 (4.969, 28.981) | 0.000 | | 11.101 (4.010, 30.733) | 0.000 |
present | | | | | |
Vascularity | | | | | |
Absent/scarce | 2.517(1.405, 4.509) | 0.001 | | 1.711 (0.808, 3.623) | 0.161 |
Abundant | | | | | |
95% CI 95% confidence interval, OR odds ratio |