Keywords
B3 lesion - breast surgery - breast surgery - malignancy - malignancy - surgical excision - VAE
Introduction
Breast cancer is the most commonly diagnosed malignancy in women, with a rising incidence trend. Despite a minor decrease in fatality rates, it remains the primary cause of death among women attributed to oncologic pathology.[1] In recent years, advancements in diagnostic technology and the implementation of screening campaigns have successfully facilitated the early detection of breast cancers in numerous cases. The combination of novel surgical procedures and targeted biological treatments has resulted in a notable improvement in disease-free survival and overall survival rates.[2] There is a substantial body of research that supports the significant influence of lifestyle and environmental factors, including cigarette smoking, physical activity, late pregnancy, and food, on the primary prevention of breast cancer.[3] Nevertheless, it should be noted that primary prevention strategies may not be able to modify all characteristics associated with the development of breast cancer. Nonmodifiable risk factors encompass several characteristics that cannot be altered or influenced by individuals. These factors include age, sex, genetic mutations, breast tissue density, hormone-related factors, a previous history of breast cancer, and noncancerous breast disorders such as breast lesions with unknown malignant potential (B3).[4]
B3 refers to a collection of benign breast lesions that exhibit varying levels of risk of developing breast cancer either concurrently or in the future.[5] B3 lesions encompass several pathological entities, such as flat epithelial atypia, atypical ductal hyperplasia, classic-type lobular carcinoma in situ, atypical lobular hyperplasia, papillary lesions, radial scars (RSs), benign phyllodes tumors, and other unclassified or not otherwise described B3 lesions. The B3 category, however, represents a relatively small proportion of all core biopsies, ranging between 5 and 10%.[6] Management of these lesions has been controversial and challenging for the multidisciplinary team. The risk of malignancy associated with these varies between 9.9 and 35.1% following open excision, with notable variations based on the specific histological subtype.[7]
Currently, there is ongoing debate surrounding the management of B3 lesions due to the high rates of underestimation associated with percutaneous core needle biopsy (CNB) in this category.[8] Therefore, it is crucial to identify clinical, imaging, and histologic characteristics that can aid in excluding malignancy and determining appropriate treatment for patients. Historically, B3 lesions have been managed with diagnostic surgical open excision due to the potential for progression to malignant lesions. Nevertheless, due to the fact that a significant number of these lesions were ultimately determined to be benign based on histological analysis, there has been a shift toward adopting more conservative strategies such as vacuum-assisted excision (VAE) and/or regular monitoring as suggested alternatives.[9] The research endeavors have primarily concentrated on identifying the predictive factors associated with synchronous malignant lesions in the cases diagnosed with B3. It is worth noting that only one study has been conducted thus far to assess the long-term follow-up risk associated with these characteristics.[10] At present, there exists a lack of consensus and established criteria among breast societies regarding the therapy and subsequent monitoring of women who have undergone surgical or percutaneous excision of B3 lesions.
The objective of VAE is to do representative sampling and extract approximately 4 g of tissue, which is equivalent to a diagnostic surgical biopsy. In the event that a B3 lesion undergoes a transformation into malignancy subsequent to a VAE procedure, it becomes necessary to pursue therapeutic surgery. When a VAE procedure results in a benign diagnosis, it is recommended to undergo annual mammographic surveillance for a period of 5 years for lesions that are associated with epithelial atypia. However, no additional surveillance is required for lesions that do not exhibit atypia. This is in accordance with the National Health Service (NHS) Breast Screening Programme, United Kingdom, 2016 on management of B3 lesions[11] ([Fig. 1]).
Fig. 1 NHS screening guidance for B3 lesions.
In such cases, routine mammographic screening is advised, following the standard screening interval of 3 years.[12]
The objective of this study was to evaluate the efficacy of utilizing VAE for the management of B3 lesions, as well as to determine the rate of malignant upgrades.
Materials and Methods
This observational study was conducted at Surrey and Sussex NHS Trust Redhill from October 2019 to October 2022. Through nonprobability consecutive sampling, 75 women between the ages of 25 and 85 years who were diagnosed with B3 lesion after initial breast screening were included in the present study. Women with concurrent in situ breast or invasive breast cancer were excluded from the present study. The female participants who obtained a B3 result were divided into two groups: those who exhibited atypia and those who did not exhibit atypia. Subsequently, the groups were further categorized into two subgroups: women who met the criteria for VAE and those who met the criteria for surgery. According to the guidelines, women who have had a B3 histology indicating the presence of spindle cell lesions, papilloma with atypia, or fibroepithelial lesions are deemed suitable candidates for surgery instead of VAE. All lesions classified as B3 were diagnosed and their subsequent care was documented. The upgrades in both the B3 group with atypia and the B3 group without atypia were examined in terms of ductal carcinoma in situ (DCIS), invasive status, and grade. The data obtained were analyzed using the SPSS version 21. Continuous variables were presented as mean ± standard deviation (SD), while categorical data were represented as frequency and percentages. Student's t-test was employed to assess the disparity in upgrading rates across the study groups. A p-value ≤0.05 was considered statistically significant.
Results
[Table 1] presents the clinical and demographic parameters of the recruited participants. The mean ± SD of the participants' ages in the present study was 52.17 ± 10.3 years. The majority of the participants (65%) in the study had a family history of breast cancer. About 65% of the participants in the present study had B3 lesions in their left breast and 43% of the participants had lesions located in the upper inner area of the breast. The majority of the participants in the study had B3 lesions without atypia (75%). VAE was performed in 70 participants, with 31 participants discharged and 22 remained under surveillance. This was in accordance with NHS Breast screening guidance ([Fig. 1]). Two patients had continued treatment post-VAE for contralateral cancer. Out of 70 participants, only 15 had lesions upgrade after VAE (21.4%). Fourteen lesions were upgraded to DCIS and microinvasive cancer was seen in only 1 patient. [Table 2] presents the clinical and demographic parameters of the study participants without atypia (n = 56) and with atypia (n = 19) B3 breast lesions. Upgrade to DCIS was higher in the group with atypia (37%). Only one patient had an upgrade to microinvasive cancer, which was also in the group with atypia.
Table 1
Clinical and demographic parameters of the recruited participants
|
Parameters
|
Mean/frequency (n = 75)
|
|
Age (y)
|
52.17 ± 10.3
|
|
Hormone replacement therapy (HRT)
|
12 (16%)
|
|
Family history
|
49 (65%)
|
|
Breast side
|
|
Left
|
46 (61%)
|
|
Right
|
28(37%)
|
|
Size of lesion
|
14.8 ± 11.57 (3–34 mm)
|
|
Breast area
|
|
Central
|
9 (12%)
|
|
Lower inner
|
11 (15%)
|
|
Lower outer
|
10 (13%)
|
|
Inner
|
2 (2%)
|
|
Upper outer
|
32 (43%)
|
|
upper inner
|
10 (13%)
|
|
Type of B3 lesion
|
|
Without atypia
|
56 (75%)
|
|
Atypia
|
19 (25%)
|
|
VAE performed
|
70 (93%)
|
|
VAE results
|
|
Surveillance
|
22 (31%)
|
|
With surgical plan for contralateral cancer
|
2 (2.8%)
|
|
Discharge
|
31 (44%)
|
|
WG diagnostic excision
|
14 (20%)
|
|
Mastectomy
|
1 (1.4%)
|
|
Upgrade
|
15 (21%)
|
|
DCIS
|
14 (93%)
|
|
Microinvasive
|
1 (7%)
|
Abbreviations: DCIS, ductal carcinoma in situ; VAE, vacuum-assisted excision; WG, wire guided.
Table 2
Comparison of clinical and demographic parameters of the participants in study groups
|
Parameters
|
Atypia (n = 19)
|
Without atypia (n = 56)
|
p-value
|
|
Age
|
52.11 ± 9.9
|
52.6 ± 10.6
|
0.391
|
|
Hormone replacement therapy (HRT)
|
2 (11%)
|
10 (18%)
|
1.000
|
|
Family history
|
9 (11%)
|
40 (71%)
|
0.495
|
|
Breast side
|
|
Left
|
12 (63%)
|
34 (61%)
|
0.749
|
|
Right
|
7 (37%)
|
19 (34%)
|
|
Size of lesion
|
17.875 ± 12.04 mm
|
14.6 ± 11.4 mm
|
0.194
|
|
Breast area
|
|
Central
|
2 (11%)
|
7 (13%)
|
|
|
Lower inner
|
5 (26%)
|
6 (9%)
|
|
Lower outer
|
1 (5%)
|
9 (16%)
|
|
Inner
|
0 (0%)
|
2 (3%)
|
|
Upper outer
|
10 (53%)
|
22 (39%)
|
|
Upper inner
|
1 (5%)
|
9 (16%)
|
|
VAE performed
|
16 (84%)
|
54 (96%)
|
0.083
|
|
VAE results
|
|
Surveillance
|
4 (21%)
|
18 (32%)
|
|
|
With surgical plan for contralateral cancer
|
2 (9%)
|
0 (0%)
|
|
Discharge
|
2 (11%)
|
29 (51%)
|
|
WG diagnostic
|
10 (53%)
|
6 (9%)
|
|
Mastectomy
|
1 (5%)
|
0 (0%)
|
|
Up gradation
|
7 (37%)
|
8 (14.2%)
|
0.96
|
|
DCIS
|
7 (37%)
|
7 (13%)
|
0.96
|
|
Invasive
|
1 (5%)
|
0 (0%)
|
0.331
|
Abbreviations: DCIS, ductal carcinoma in situ; VAE, vacuum-assisted excision.
Discussion
The use of VAE has been recently implemented as a viable alternative to diagnostic surgical excision for specific B3 lesions. The findings of our study indicate that the process known as VAE is both safe and successful. Specifically, we saw that 93% of women diagnosed with a B3 lesion were able to avoid receiving an open surgical biopsy by opting for VAE instead. In our study, the incidence of malignant upgrades following VAE was found to be notably low, specifically at 21%. This outcome indicates that a significant majority of women were able to obtain a benign diagnosis without the need for any additional treatment. Historically, the management of B3 lesions has involved surgical excision.[9] However, it is becoming recognized that this approach may result in overtreatment, as the rates of malignant upgrading are found to be low, as evidenced by the findings of this study. Despite the potential negative consequence of VAE, it has the advantage of facilitating conclusive patient management by a single therapeutic surgical intervention, as opposed to the conventional approach of two separate surgical procedures: one for diagnosis and another for therapy. The underestimation of malignancy in excised B3 lesions has been shown to range from around 10 to 35% according to multiple studies.[6]
[13]
[14]
[15] There exist empirical data indicating a decline in the proportion with time.[16] For instance, Rakha et al observed a decrease in the positive predictive value of a B3 diagnosis from 25 to 10%.[15] The observed upgrade rate of 21% in this particular series undergoing VAE falls within the lower range as stated in existing literature. There are several possible explanations for the observed decline in cases. One contributing factor could be the enhanced accuracy of mammographic techniques and ultrasound resolution, leading to an increased detection of RSs. Additionally, the growing utilization of vacuum-assisted biopsy may have had a role in this drop.[15] In the present study, the progression to malignancy was found to have an association with the presence of atypia on the original biopsy, with a rate of 37% (7 out of 19 cases), in contrast to a complete absence of progression if atypia was not detected in the prior biopsy (8 out of 56 cases). The correlation between B3 lesions exhibiting atypia and the heightened likelihood of a malignant outcome is widely acknowledged in the academic literature. The historical data from 1999 to 2006 revealed a notable disparity in the rate of upgrades for B3 lesions, with and without atypia, amounting to 36 and 7%, respectively.[17] In a recent study conducted by Mayer et al, it was shown that there was an overall upgrade rate of 10%. Furthermore, the incidence of malignancy was much lower in lesions without atypia, measuring at 4.8%, compared with lesions with atypia, which had a rate of 24%.[18] The significant disparity in upgrade rates has resulted in implementing a requirement that the presence or absence of epithelial atypia must be explicitly indicated for all B3 lesions.[19] The advantages of VAE include the avoidance of hazards commonly associated with cost-effectiveness, general anesthesia, high levels of patient satisfaction, and favorable cosmetic outcomes.[20]
[21] In the case of minor B3 lesions, the objective was to eliminate the anomaly with the use of VAE. If a lesion is localized and has a size of less than 15 mm, there is a high probability that it can be completely removed with diagnostic excision of VAE. However, it should be noted that this may not accurately represent the number of pathological alterations.[22] In the cases in which the lesions exceeded a size of 15 mm, complete sampling was not consistently achievable. However, the primary objective remained getting a sample of the abnormality that was adequate enough to rule out any associated cancer. In our analysis, it is reassuring to note that there was no observed correlation between the size of the lesion and the likelihood of it progressing to malignancy. This could be due to a smaller sample size. It is worth mentioning, however, that earlier studies have shown such a link.[8] It is not anticipated that open diagnostic surgical methods would completely eliminate big lesions. In instances of this nature, a surgical specimen with an approximate weight of 4 g is deemed suitable for diagnostic purposes. The VAE has the objective of achieving a similar outcome.[5]
The follow-up plan is based on the guidance provided by the NHS Breast Screening Programme, 2016,[11] where the indication for 5 yearly surveillance mammogram is mainly based on the presence of atypia. However, in our study, 32% of patients without atypia were followed up with a mammogram due to low- to moderate-risk family history.
Conclusion
In summary, based on the available literature, it is generally recommended to conduct additional sampling to rule out any potential malignancy when a B3 lesion is found. The conventional method of utilizing an open diagnostic surgical excision is often considered excessive treatment by a significant number of women. The utilization of VAE presents a secure and efficient approach for the treatment of B3 lesions, resulting in a decrease in the frequency of invasive surgical interventions. This study provides evidence supporting the effectiveness of this method, as the incidence of malignant transformations following a VAE is found to be minimal, especially for B3 lesions lacking epithelial atypia.
