The Breast Imaging Reporting and Data System (BI-RADS) was

710 Evaluation of Breast Imaging Reporting and Data System Category 3 Mammograms and the Use of Stereotactic Vacuum-Assisted Breast Biopsy in a Nonacademic Community Practice Angela Mendez, M.D. Fernando Cabanillas, M.D. Miguel Echenique, M.D. Keyvan Malekshamran, M.D. Iris Perez, R.T. Edwin Ramos, M.D. Auxilio Mutuo Cancer Center, Hospital Auxilio Mutuo, San Juan, Puerto Rico. BACKGROUND. Breast Imaging Reporting and Data System (BI-RADS) Category 3 represents probably benign mammographic abnormalities requiring close followup, but biopsies sometimes are performed on Category 3 abnormalities. Controversy exists as to when these biopsies are justified. The goals of the current study were to evaluate the use of stereotactic vacuum-assisted breast biopsy (SVABB) for BI-RADS 3 lesions in a nonacademic community hospital based practice, to evaluate the false- negative rate of Category 3 mammograms, and to determine whether any specific lesions misinterpreted as BI-RADS 3 abnormalities might commonly be associated with malignant disease. METHODS. From August 2000 to December 2002, the authors performed 947 SVABB procedures on 911 patients. They focused on 156 SVABBs of BI-RADS 3 abnormalities. RESULTS. Of 634 SVABB procedures requested by outside sources, 114 (18%) were performed for BI-RADS 3 abnormalities, compared with 42 (13%) of 313 SVABB procedures that were performed based on mammographic findings at the authors practice (P 0.075). After SVABB, 7 of 156 patients with BI-RADS 3 lesions were diagnosed with breast carcinoma and 1 was diagnosed with atypical ductal hyperplasia. Therefore, the false-negative rate of BI-RADS 3 mammograms was 4.5% (i.e., 7 of 156 patients). Patients with linear microcalcifications had the highest rate of cancer (4 of 14 [29%]) compared with patients without microcalcifications (1 of 64 [1.5%]) and patients with nonlinear microcalcifications (2 of 69 [2.9%]). CONCLUSIONS. The use of SVABB for BI-RADS 3 lesions reflected uncertainty regarding the potential for a diagnosis of malignant disease rather than the financial incentive of performing a SVABB was not necessary for patients with BI-RADS 3 lesions without microcalcifications or for patients with nonlinear microcalcifications. Lesions with linear (casting or branching) microcalcifications should not be considered BI-RADS 3 abnormalities. Cancer 2004;100:710 4. 2004 American Cancer Society. KEYWORDS: mammogram, Breast Imaging Reporting and Data System Category 3, stereotactic breast biopsy, percutaneous breast biopsy, breast carcinoma Address for reprints: Fernando Cabanillas, M.D., Auxilio Mutuo Cancer Center, Hospital Auxilio Mutuo, Ave. Ponce de Leon 725, San Juan, Puerto Rico 00918; Fax: (787) 771-7941; E-mail: cabanillas@auxilio.com Received September 15, 2003; revision received November 10, 2003; accepted November 13, 2003. The Breast Imaging Reporting and Data System (BI-RADS) was proposed by the American College of Radiology 1 to decrease the ambiguity regarding descriptions of mammographic lesions and to provide a common language to unambiguously describe the level of suspicion and recommended follow-up for a mammographic lesion. Annual follow-up is recommended for patients with lesions classified as BI-RADS Category 1 (negative mammogram) or 2 (benign findings). 2004 American Cancer Society DOI 10.1002/cncr.20017

BI-RADS 3 and Stereotactic Breast Biopsy/Mendez et al. 711 A 6-month follow-up has been recommended for patients with lesions assigned a BI-RADS Category 3 (probably benign) whereas a biopsy is suggested for patients with lesions classified as Category 4 (suspicious) or 5 (highly suggestive of malignancy). In spite of these guidelines, for various reasons, biopsies are performed for some BI-RADS 3 lesions, and this topic has been a matter of considerable debate and controversy. 2,3 Many do not realize that a lesion should not be categorized as a BI-RADS 3 abnormality before an imaging workup, which would include magnification views for patients with microcalcifications, is performed. After a thorough imaging workup revealing BI-RADS 3 findings, some legitimate reasons for performing a biopsy are the presence of malignant tumors in the same breast or the opposite breast, demands from extremely apprehensive patients and from patients planning a future pregnancy or augmentation or reduction surgery, and uncertainty as to whether the patient will comply with the required regular mammographic follow-up examinations; a negative stereotactic vacuum-assisted breast biopsy (SVABB) will result in less-frequent follow-up. A less legitimate reason is the fear of a malpractice suit if a diagnosis of malignancy is missed. In addition, some investigators believe that a number of biopsies for BI-RADS 3 lesions might be driven by profit motives; to our knowledge, this hypothesis has not been objectively evaluated in the existing literature. The SVABB technique is being used more frequently because, compared with excisional biopsy, it represents a minimally invasive, faster, and less expensive method for sampling nonpalpable abnormalities observed on mammography but not on sonography. If a lesion is observed on sonography, our approach is to perform a biopsy using sonographic guidance, because this option is less expensive. If the lesion is not observed on a breast sonogram, the biopsy is performed with either stereotactic guidance or by wire localization. For lesions not observed on a sonogram, we prefer the stereotactic method, because it is faster, less expensive, less painful, less invasive, and can be performed easily in the outpatient setting. SVABB is indicated most commonly for BI-RADS 4 lesions. Patients with BI-RADS 5 lesions frequently are referred directly for excisional biopsy, because of the expected high frequency of malignancy. However, in many instances, patients with BI-RADS 5 lesions undergo percutaneous biopsies to allow appropriate surgical planning and one surgical procedure. We initiated the current study with three goals in mind: 1) to evaluate the use or misuse of SVABB for BI-RADS 3 lesions in a nonacademic hospital based practice (Auxilio Mutuo Cancer Center, Hospital Auxilio Mutuo, San Juan, Puerto Rico); 2) to evaluate the false-negative rate of Category 3 mammograms; and 3) to determine whether there are any specific lesions misinterpreted as BI-RADS 3 abnormalities that might commonly be associated with malignant disease. MATERIALS AND METHODS From August 2000 to December 2002, we performed 947 SVABB procedures on 911 patients using an upright Mammomat 1000/3000 Nova Opdima digital biopsy and spot imaging system unit (Siemens-Elema AB, Solma, Sweden). The 11-gauge needle used for these biopsies was a Mammotome probe MST 11 (Ethicon Endo Surgery; Cincinnati, OH). Specimen radiography was performed routinely on all samples, and mammographic lesions were classified into four categories: 1) microcalcifications; 2) asymmetric density; 3) circumscribed mass; and 4) spiculated mass. The major indication for SVABB in the current series was a BI-RADS 4 mammogram (n 757, or 80% of all procedures). However, 156 SVABB procedures were performed for patients with BI-RADS 3 lesions. Hospital Auxilio Mutuo is a nonprofit, private institution with tertiary facilities and 510 approved beds. It is located in a metropolitan area and draws patients from the whole island. Approximately 6% of all new cancer cases on the island and 22% of those in the metropolitan area are diagnosed at our center. The Women s Imaging Center, located within our institution, houses facilities for three mammography rooms, one room for stereotactic biopsies, and three rooms for breast sonograms. It provides services to our own population of patients as well as for those referred from outside sources. Before SVABB was performed, all patients were examined by one of three radiologists assigned to the Women s Imaging Center, and all films were reviewed. The three radiologists are experienced in the field of mammography and devote 80% of their time to breast imaging. A BI-RADS category was assigned before SVABB was performed. Either a surgeon or a radiologist performed the SVABB procedure. During the current study period, four surgeons and three radiologists performed SVABB procedures. All surgeons and radiologists held credentials granted by the faculty bylaws committee; the criteria for granting credentials to surgeons are virtually identical to those proposed by the American College of Radiologists. 4 Whenever the surgeon performed SVABB, the radiologist assisted with targeting. Specimens were X-rayed before being submitted for pathologic evaluation. Subsequently, all pathology reports were reviewed by the radiologist, who assessed concordance/discordance. A BI-RADS category was assigned using the inter-

712 CANCER February 15, 2004 / Volume 100 / Number 4 pretation provided by the first radiologist who read the films, either the radiologist from another institution or the radiologist from our institution. Of the 947 mammograms administered before SVABB, 313 were performed at our center and 634 were performed at other centers before the patient was referred to our center for SVABB. False-negative findings were defined as BI-RADS 3 findings for which stereotactic biopsy yielded positive results for malignancy. A positive result on repeat biopsy of a BI-RADS 3 abnormality also was considered to indicate a false-negative mammogram. A falsenegative result also was recorded for any initial biopsy of a BI-RADS 3 lesion that was considered to be an inadequate tissue sample and that required a repeat biopsy that was positive for breast carcinoma. In addition, BI-RADS 3 lesions that upon follow-up required a repeat biopsy that was positive were considered to represent false-negative findings. The tumor registry also was evaluated in an attempt to find tumors that subsequently were diagnosed as breast carcinoma. Permission was obtained from the local institutional review board for publication of the findings summarized in the current study. RESULTS Use of SVABB in BI-RADS 3 and 4 Lesions We performed 947 SVABB procedures, of which 634 were requested by outside sources. Of these 634 SVABB procedures, 114 (18%) were for BI-RADS 3 lesions compared with 42 (13%) of the 313 that originated from our practice (P 0.075). The use of SVABB for BI-RADS 4 lesions was significantly more common in our practice than it was elsewhere (262 [84%] of 313 vs. 495 [78%] of 634; P 0.04). We also compared the rate of cancer diagnosis for patients with BI-RADS 3 lesions who were referred for SVABB from an outside source with the corresponding rate for patients in our practice. The results were almost identical in both cases, with rates of approximately 5% (Table 1). False-Negative Rate in BI-RADS 3 Lesions A BI-RADS 3 mammogram with a stereotactic biopsy positive for carcinoma was defined as a false-negative mammogram. After the SVABB procedure, 7 of the 156 patients with BI-RADS 3 lesions were diagnosed with breast carcinoma and 1 was diagnosed with atypical ductal hyperplasia (Table 1). Therefore, the false-negative rate, including only patients diagnosed with cancer, is 4.5% (i.e., 7 of 156 patients). TABLE 1 Histologic Findings in BI-RADS Category 3 Mammograms According to Source of Referral Source of SVABB referral No. Breast malignancy (%) Atypia (%) Total (%) Our practice 42 2 (4.8) 0 2 (4.8) Outside source 114 5 (4.4) 1 (0.9) 6 (5.3) TABLE 2 Histologic Findings According to Absence/Presence of Microcalcifications a Lesion No. Malignant disease (%) Any type of microcalfication 91 6 (6.5) No microcalcifications 65 1 (1.5) a P 0.13 for no microcalcifications versus microcalcifications. Correlation of Type of Lesion with Diagnosis of Malignancy We classified patients with BI-RADS 3 abnormalities according to mammographic lesion type (i.e, microcalcifications, asymmetric density, circumscribed mass, or spiculated mass). Of the 156 biopsies performed for BI-RADS 3 lesions, 92 (59%) were performed for microcalcifications, 25 (16%) for an asymmetric density, 37 (24%) for a circumscribed mass, and 2 (1.3%) for a spiculated mass. One of the two patients with a spiculated mass was known to have undergone a previous biopsy, and it was believed that the lesion probably was due to scar tissue. For that reason, the lesion was classified as a BI-RADS 3 abnormality. The second patient was believed to have a radial scar and should have been assigned a BI-RADS 4 classification rather than a BI-RADS 3 classification. The results of SVABB confirmed the presence of scar tissue in the first patient, and the second patient was diagnosed with proliferative fibrocystic disease. Of the seven cases of malignant disease, six were associated with microcalcifications. Ninety-one patients had microcalcifications. Of these 91 patients, 6 (6.5%) had malignant disease, compared with 1 of 65 patients without microcalcifications (1.5%) who had malignant disease (P 0.13; Table 2). We then focused on the pattern of microcalcifications to determine whether a correlation with malignancy or atypia existed. Information on microcalcification type was available for 83 of the 92 patients. Patients with a linear pattern of distribution had the highest rate of

BI-RADS 3 and Stereotactic Breast Biopsy/Mendez et al. 713 TABLE 3 Histologic Findings According to Microcalcification Type a Lesion No. Malignant disease (%) Atypia (%) Linear microcalcifications 14 4 (29) 0 Nonlinear microcalcifications 69 2 (2.9) 1 (1.5) a P.007 for diagnosis of malignancy for nonlinear versus linear microcalcifications. TABLE 4 Proportion of Patients with BI-RADS Category 3 Lesions Who Underwent SVABB in the Current Series Compared with Other Published Series Study Institution type No. of patients undergoing SVABB (%) Current series Community hospital 156/947 (16) Berube et al., 1998 7 Academic center 16/495 (3) Margolin et al., 2001 8 Community hospital 16/321 (5) Tate et al., 2001 9 Community hospital 87/1088 (8) Travade et al., 2002 10 Community hospital 12/206 (6) malignancy (29% [4 of 14]) compared with patients with other types of microcalcifications (4% [3 of 69]; Table 3). This observation was statistically significant (P 0.009). FIGURE 1. Left medial lateral (LML) magnification view. A cluster of microcalcifications can be seen in the left breast at the 12 o clock position (arrows). Stereotactic biopsy revealed ductal carcinoma in situ. The findings on this film originally were classified at another institution as Breast Imaging Reporting and Data System 3 abnormalities. DISCUSSION Sixteen percent (156 of 947) of patients at our practice with BI-RADS 3 lesions underwent SVABB. This is a much higher rate compared with other series, in which only 3 8% of patients with BI-RADS 3 lesions underwent SVABB (Table 4). To gain more insight into the reason for the high rate of biopsy, we evaluated the source of referral for the biopsy as a variable. We determined that the proportion of patients referred from outside sources for SVABB was higher (18%) than the proportion of patients referred from our practice (13%). Because there is no financial incentive for these outside referrals, it is logical to conclude that in our community, profit was not the major reason for the high rate of biopsy for patients with BI-RADS 3 lesions. Other possible factors include the deteriorating local malpractice climate in the island, cultural or sociologic issues, and, perhaps, an incomplete awareness in the medical community of the indications for During the past decade, the number of malpractice suits in Puerto Rico has increased substantially, and only a maximum insurance coverage of $100,000 per incident is available. Sociologic issues that might impact the performance of biopsies for BI-RADS 3 lesions include a low level of education for a fraction of patients who might not return in 6 months for a follow-up mammogram. However, it is not possible to conclusively identify from the current study the most likely explanation for the disproportionately high rate of SVABB for BI-RADS 3 lesions. BI-RADS 3 mammograms must be considered to essentially represent negative findings, because Category 3 lesions are defined as probably benign abnormalities. For this reason, if the final outcome is a diagnosis of malignant disease, the mammogram must represent false-negative findings. The literature quotes a false-negative rate ranging from 0.5% to 2% for BI-RADS 3 lesions. However, these figures are based on follow-up mammograms and not on systematic biopsies. 5,6 The false-negative rate for BI-RADS 3 mammograms at our institution was 4.5% (7 of 156; Table 1). Figure 1 shows an example of false-negative mammographic results interpreted as BI-RADS 3 findings. Table 5 compares our results with those from other series in which SVABB was performed for BI- RADS 3 lesions. To perform a fair comparison, only series that used SVABB were considered, and we excluded series in which data were derived from sonographically directed biopsies or other types of biopsies. The study performed by Margolin et al., 8 which involved sonographically guided biopsies as well as SVABB, was included; for that series, we extracted the data on patients who underwent SVABB. When we added the results of all 5 published series, there were 6 of 213 (2.8%) false-negative results, compared with 7

714 CANCER February 15, 2004 / Volume 100 / Number 4 TABLE 5 False-Negative Rate for BI-RADS Category 3 Findings in the Current Series Compared with Other Published Series Involving SVABB Study No. of false-negative results (%) Current series 7/156 (4.5) Berube et al., 1998 7 0/16 (0) Margolin et al., 2001 8 1/16 (6.3) a Tate et al., 2001 9 2/87 (2.3) Travade et al., 2002 10 0/12 (0) Obenauer et al., 2001 11 3/82 (3.7) a For the purposes of comparison, we included only stereotactic biopsy findings and excluded sonographically directed biopsy findings from this series. of 156 (4.5%) in the current series (Table 1). This difference is not statistically significant (P 0.28). Despite the lack of a significant difference in the false-negative rate between the current series and others, we set out to further investigate patients at our institution who had positive biopsies to attempt to identify a subset of patients with BI-RADS 3 lesions who had a high rate of malignant disease. We found that of the seven patients with positive SVABB findings, six had microcalcifications. Stated differently, there were 92 patients with BI-RADS 3 lesions who had mammographic microcalcifications. Six (6.5%) of these patients had positive SVABB findings, compared with only one (1.5%) patient without microcalcifications (P 0.13; Table 2). We then classified patients with microcalcifications as patients with linear distributions or patients with other microcalcification types (Table 3). Data on microcalcification type were available for 83 of 92 patients. Fourteen patients had linear distributions, and 4 (29%) of these 14 were diagnosed with malignant disease (Table 3). This result was in striking contrast with the finding that only 2 of 69 patients (2.9%) with other types of microcalcifications had positive findings on SVABB. This difference was statistically significant (P 0.007; Table 3). In conclusion, SVABB for BI-RADS 3 lesions is overused in our community. This overuse may be attributable to uncertainty regarding the diagnosis of malignant disease or to other factors, such as fear of malpractice litigation, rather than to the financial incentive to perform a Performing a biopsy for BI-RADS 3 lesions without microcalcifications or with nonlinear microcalcifications is not necessary unless other justifications exist. If, from this point onward, we were to stop performing such biopsies, we would observe a reduction of 8% in the number of SVABB procedures currently being performed. Finally, in view of the high frequency of positive findings in patients with linear microcalcifications, radiologists at our institution, as well as others, should not consider these patients to have BI-RADS 3 lesions, but rather BI- RADS 4 lesions. REFERENCES 1. American College of Radiology. Breast imaging reporting and data system, 3rd edition. Reston, VA: American College of Radiology, 1998. 2. Sickles EA, Parker SH. Appropriate role of core breast biopsy in the management of probably benign lesions. Radiology. 1993;188:315. 3. Logan-Young WW, Janus JA, Destounis SV, Hoffman NY. Appropriate role of core breast biopsy in the management of probably benign lesions. Radiology. 1994;190:313 314. 4. American College of Surgeons and American College of Radiology. Physician qualifications for stereotactic breast biopsy: a revised statement. Bull Am Coll Surg. 1998;83:30 33. 5. Varas X, Leborgne F, Leborgne J. Nonpalpable, probably benign lesions: role of follow up mammography. Radiology. 1992;184:409 414. 6. Sickles E. Periodic mammographic follow up of probably benign lesions: results of 3184 consecutive cases. Radiology. 1991;79:463 468. 7. Berube M, Curpen B, Ugolini P, Lalonde L, Ouimet-Oliva D. Level of suspicion of a mammographic lesion: use of features defined by BI-RADS lexicon and correlation with largecore breast Can Assoc Radiol J. 1998;49:223 228. 8. Margolin FR, Leung JW, Jacobs RP, Denny SR. Percutaneous imaging-guided core breast biopsy: 5 years experience in a community hospital. AJR Am J Roentgenol. 2001;177:559 564. 9. Tate PS, Rogers EL, McGee EM, et al. Stereotactic breast biopsy: a six-year surgical experience. J Ky Med Assoc. 2001; 99:98 103. 10. Travade A, Isnard A, Bagard C, et al. Stereotactic 11-gauge directional vacuum-assisted breast biopsy: experience with 249 patients. J Radiol. 2002;83:1063 1071. 11. Obenauer S, Fischer U, Baum F, Dammert S, Fuzesi L, Grabbe E. [Stereotactic vacuum core biopsy of clustered microcalcifications classified as B1-RADS 3]. Rofo Fortschr Geb Rontgenstr Neuen Bildgeb Verfahr. 2001;173:696 701.