Current imaging examinations are capable of detecting microscopic breast lesions that may not be clinically palpable. With the advancement of imaging technology, the detection rate of nonpalpable breast lesions (NPBLs) has been increasing. Biopsy of some of the nonpalpable breast lesions can improve the early diagnosis and early treatment rate of breast cancer, which is important for improving the treatment outcome of breast cancer. 1. Surgical biopsy under localization 1.1 Evaluation of clinical application Surgical biopsy under localization of breast is most widely used clinically with metal wire stereotactic excisional biopsy under X-ray, and other surgical biopsies under localization include ultrasound and magnetic resonance-guided localization. Mammography can detect some NPBLs, such as clusters of microcalcifications, suspicious masses, and areas of dense or structurally distorted breast tissue. NPBLs are graded according to the breast imaging reporting and data system (BI-RADS) developed by the American college of Radiology (ACR) [1], where lesions with BI-RADS grades 2-5 are potentially malignant and can be considered for localized surgical biopsy. The metal positioning wire was left at a distance of less than 1 cm from the lesion under the guidance of molybdenum X-ray, and a 2-3 cm diameter specimen was excised along the tip of the positioning wire, and mammograms of the surgically excised specimen were taken immediately and compared with preoperative imaging data to ensure complete excision of the lesion for pathological examination. 1.2 Selection of indications There are different perceptions regarding the indications for surgical biopsy of NPBLs: Zhong Yuxin et al [2] found that the overall positive predictive value was 26.3% (55/209) and the positive predictive value for BI-RADS grade 2, 3, 4 and 5 lesions was 0% (0/21) by analyzing the clinical data of 209 NPBLs resected by metallic wire localization in 190 women, respectively. The BI-RADS system is also applicable to the imaging classification of NPBLs in women in China, and it is recommended that local excisional biopsies should be actively performed for BI-RADS grade 4 and 5 lesions, while BI-RADS grade 2 and 3 lesions should be followed up regularly. Raza S et al [3] studied 880 biopsies of BI-RADS grade 3 and 4 breast lesions in 725 patients: with almost equal numbers of biopsies of clinically palpable lesions and NPBLs, the malignancy rate of biopsies of clinically palpable lesions was 11%, while the malignancy rate of biopsies of NPBLs was 22%. Markopoulos C et al [4] concluded that NPBLs including clusters of microcalcifications, solid masses, and areas of distorted tissue structure should undergo localized surgical biopsy. Today, when the concept of minimally invasive has been generally accepted, surgical biopsy of NPBLs without localization is gradually decreasing. Surgical biopsy after applying metallic wire stereotaxic localization can complete a comprehensive evaluation of NPBLs with less damage than traditional blind excisional biopsy, but this technique is still an open surgery, which removes more tissue and is still more traumatic. The literature reports that the positive prediction rate of metal-wire stereotactic excisional biopsy for NPBLs is 25.9%-28.4% [4-6], indicating that nearly 75% of patients can avoid such biopsy surgery, and this part of patients should consider less invasive stereotactic aspiration biopsy or vacuum-assisted aspiration biopsy; for cases in which metal-wire stereotactic excisional biopsy is malignant, further surgical treatment is is unavoidable and surgical biopsy will not affect the final degree of tissue damage, surgical biopsy can be considered; in addition, for cases in which stereotactic aspiration biopsy or vacuum-assisted aspiration biopsy fails or provides insufficient diagnostic information, additional surgical excisional biopsy is necessary. 2. stereotactic aspiration biopsy 2.1 Clinical application evaluation According to the main sampling methods, stereotactic aspiration biopsy mainly includes fine needle aspiration (FNA) and stereotactic core needle biopsy (SCNB). SCNB is an ultrasound or X-ray stereotactic-guided, large-bore needle with a cutting function that is poked through the skin to biopsy the breast lesion. Compared to traditional surgical excisional biopsy with wire positioning, SCNB requires repeated punctures, but it is less painful and less disruptive to the breast tissue structure, avoiding complicated medical procedures in the perioperative period. According to a statistical study of 258900 women who underwent mammography screening, from 1995 to 2005, the proportion of breast lesions receiving percutaneous biopsy before surgery increased from 42.4% to 100%; the proportion of malignant lesions confirmed by percutaneous biopsy before surgery increased from 27.1% to 92.7%; the proportion of FNA to obtain a diagnosis gradually decreased from 91.3% to 14.5%, while The proportion of core needle aspiration biopsy gradually increased from 8.7% to 86.5%. The pathological results of core needle aspiration biopsy samples can better differentiate benign and malignant breast lesions and are more widely used clinically.Wolf R et al [8] compared the modality of first biopsy of NPBLs: out of 182 BI-RADS grade 5 NPBLs in 178 patients, 156 NPBLs specimens were invasive carcinoma or carcinoma in situ and core needle biopsy was used as the first biopsy modality ( 59.3%, 108/182), 95 cases of invasive carcinoma or carcinoma in situ were detected, and the margin-negative rate of initial surgery was 74% (70/95), which was significantly higher than the margin-negative rate obtained with surgery as the first biopsy modality (28%, 17/61, P<0.05); fewer surgical operations were obtained with core needle biopsy as the first biopsy modality (1.29 ± 0.05 and 1.8 ± 0.05, P<0.05). It is recommended that core needle biopsy be used as the initial biopsy modality for BI-RADS grade 5 NPBLs.Schueller G et al. showed high concordance (95.8%, kappa = 0.93) between biopsy results and surgical resection results and follow-up results by performing ultrasound-guided 14G core needle biopsy in 1352 NPBLs. It is considered that ultrasound-guided 14G core needle biopsy can be used as an alternative to surgical resection biopsy. 2.2 Problems of SCNB Although the clinical application of SCNB is becoming more and more widespread, more and more breast diseases with palpable lesions can be replaced by core-needle aspiration biopsy as an alternative to traditional surgical excisional biopsy. However, there are still some problems with SCNB for NPBLs. It has been suggested that SCNB and surgical biopsy provide information on tumor histological type, tumor grade, hormone receptor expression, and HER-2 expression that is not yet fully consistent [10]. Although both methods are equally sensitive in evaluating hormone receptor and HER-2 receptor expression, due to the heterogeneity of the lesions, SCNB should be punctured at least three times when evaluating HER-2 receptor expression and more than three times when evaluating PR expression; SCNB is less sensitive (95%) in evaluating ER expression, so even if ER negative expression is obtained by multiple punctures, surgery should still be ER testing should be repeated after excision of the specimen. A study of SCNB performed on 271 non-mass calcifications showed that the malignancy sensitivity rate for immediate surgery after SCNB was 90%, while it decreased to 82% when combined with data after long-term follow-up. Similarly, it was reported that 8% of cases diagnosed as benign by SCNB were eventually diagnosed as malignant at subsequent follow-up. Another study of 2403 patients undergoing SCNB in NPBLs from 22 centers showed that the overall sensitivity, specificity and accuracy of SCNB were 91%, 100% and 98%, respectively; the diagnosis of subclinical breast masses was more sensitive and accurate than the diagnosis of microcalcifications without masses (96%, 99% and 84%, 96%, P < 0.001). It was also found that SCNB had a 16% failure rate when applied to the diagnosis of microcalcifications in the breast due to the absence of calcifications in the punctured specimen. This suggests that the false-negative rate of SCNB is higher than that of surgical excisional biopsy; there is a significant decrease in sensitivity and accuracy when SCNB is used for calcification biopsy without masses, as well as some problems of tissue underestimation and failure rate. The reasons for these problems are mainly due to the fact that SCNB sampling is too small, the lesion is heterogeneous, and the sampling portion cannot fully represent the whole lesion; in addition, there are some special sites of NPBLs (such as lesions close to the chest wall), and the SCNB operation itself has difficulties, which affects the diagnostic results and also leads to a certain failure rate. Therefore, it is generally believed that SCNB cannot completely replace surgical biopsy yet. Vacuum-assisted biopsy 3.1 Clinical application evaluation The Mammotome vacuum-assisted biopsy system, which can be used for vacuum-assisted breast biopsy (VABB) under ultrasound or X-ray guidance, has a commonly used rotary needle of 11G, and the amount of tissue it obtains is three times that of a 14G needle. Compared to core needle aspiration biopsy, the Mammotome can obtain 35 mg of tissue in one pass, whereas the core needle aspiration gun can only obtain 12 mg of tissue in one pass; the Mammotome also does not require repeated puncture sampling and has fewer complications than core needle aspiration biopsy. Although core needle biopsy can meet clinical needs, Mammotome biopsies are more reliable for prognostic and predictive index testing. The diagnostic results obtained by Mammotome biopsy using different rotary needles also differ. According to Jackman RJ et al, when performing breast microcalcification biopsy, the percentage of biopsy specimens without calcified foci was higher with the 14G vacuum-assisted biopsy system, with a failure rate of 4% (4/96), while the failure rate of breast microcalcification biopsy with the 11G vacuum-assisted biopsy system was lower (1%, 19/14). The 11G vacuum-assisted biopsy system has a lower false-negative rate than the 14G core needle and 14G vacuum-assisted biopsy system, which is close to surgical excisional biopsy. 3.2 Problems Due to the large volume of Mammotome biopsy sampling, there is a risk of complete excision of smaller lesions, especially for lesions less than 1 cm in diameter, which will directly affect the localization of lesions for further surgical treatment and the determination of lesion margins during breast-conserving surgery [19]. In addition, there is a certain rate of underdiagnosis of VABB; Peter D et al [20] followed up 404 patients with NPBLs who underwent VABB, and of the 354 patients who obtained follow-up (mean follow-up of 22.4 months), the false-negative rate was 1.4% (5/354). The application of VABB in NPBLs with scattered microcalcifications or multiple clusters of calcifications was considered to be limited. There is a certain failure rate of VABB (10.5%) due to unidentifiable lesions, lesion location and mammary gland size resulting in inaccessible needles, and a certain underestimation rate of lesions (9%) due to limited tissue taken [21]. For these reasons, Mammotome biopsy cannot completely replace surgical biopsy either. 4. post-biopsy management Both SCNB, and Mammotome biopsy have the potential to provide incomplete and inaccurate diagnostic information; therefore, follow-up should be intensified for cases diagnosed as benign by puncture biopsy. jackman et al [22] recommended starting the 1st imaging examination 6-12 months after biopsy, and once in 12 months for at least 36 months. Supplementary surgical biopsies are also required in some cases. The recommended indications for supplemental surgical biopsy are [23]: (i) puncture biopsy suggesting high-risk lesions (e.g., atypical hyperplasia of the breast) or intraductal carcinoma in situ; (ii) insufficient specimen volume or puncture results suggesting normal tissue such as normal breast, skin, or fat; (iii) puncture results that are highly inconsistent with the X-ray imaging diagnosis; and (iv) X-ray findings of enlarged lesions or increased calcified spots during follow-up, suggesting another biopsy. With the development of imaging technology and the improvement of people's health concept, more NPBLs will be diagnosed by biopsy, and the more damaging biopsy methods will be gradually replaced by safer and more effective minimally invasive biopsy methods. At present, the indications of different minimally invasive biopsy methods are still overlapping, and further research on the indications of different minimally invasive biopsy methods will be carried out to make the application of minimally invasive biopsy technology more efficient and reasonable, and gradually realize the individualized diagnosis and treatment of breast diseases.