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Lobular Carcinoma in Situ or Atypical Lobular Hyperplasia at Core-Needle Biopsy: Is Excisional Biopsy Necessary?¹

¹ From the Department of Radiology, TC 2910N, University of Michigan Health System, 1500 E Medical Center Dr, Ann Arbor, MI 48109-0326 (M.C.F., M.A.H., A.V.N., C.P.); and Department of Radiology, William Beaumont Hospital, Royal Oak, Mich (N.E.G., M.R.). Received May 28, 2003; revision requested August 12; revision received October 3; accepted November 6. Address correspondence to M.A.H.

	ABSTRACT

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
PURPOSE: To retrospectively determine frequency of invasive cancer or ductal carcinoma in situ (DCIS) at excisional biopsy in women with atypical lobular hyperplasia (ALH) or lobular carcinoma in situ (LCIS) at percutaneous core-needle biopsy (CNB).

MATERIALS AND METHODS: Review of results in 6,081 consecutive patients who underwent CNB at two institutions revealed that in 35 (0.58%), LCIS (n = 15) or ALH (n = 20) was the pathologic finding with highest risk. Patient age range was 41–84 years (mean, 59 years). Of 35 patients, 26 (74%) underwent excisional biopsy and nine (26%) underwent mammographic follow-up for longer than 2 years. Lesions with a pathologic upgrade were noted when invasive cancer or DCIS occurred at the CNB site. CNB results in patients with a diagnosis of atypical ductal hyperplasia (ADH) (75 of 6,081 [1.2%]) were reviewed; these patients underwent subsequent excisional biopsy. Statistical comparison of frequency of upgrading of lesions in patients with a diagnosis of LCIS or ALH at CNB and in those with a diagnosis of ADH at CNB was performed (Pearson ² test).

RESULTS: In six (17%) of 35 (95% CI: 4.7%, 29.6%) patients, lesions were upgraded to DCIS (n = 4) or invasive cancer (n = 2). In 15 patients with LCIS diagnosed at CNB, lesions in four (27%) were upgraded to either DCIS or invasive cancer. In 20 patients with ALH diagnosed at CNB, lesions were upgraded to DCIS in two (10%). Lesions in nine patients who underwent mammographic follow-up were stable. No mammographic or technical findings distinguished patients with upgraded lesions from those whose lesions were not upgraded. In 12 (16%) of 75 (95% CI: 7.7%, 24.3%) patients with ADH, lesions were upgraded. Difference between the upgrade rate in patients with LCIS or ALH and that in those with ADH was not significant (P = .88).

CONCLUSION: Lesions in 17% of patients with LCIS or ALH at CNB were upgraded to invasive cancer or DCIS; this rate was similar to the upgrade rate in patients with ADH. Excisional biopsy is supported when LCIS, ALH, or ADH is diagnosed at CNB.

© RSNA, 2004

Index terms: Breast, biopsy, 00.1261 • Breast neoplasms, diagnosis, 00.31, 00.32

	INTRODUCTION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
Lobular carcinoma in situ (LCIS) and atypical lobular hyperplasia (ALH) lesions diagnosed at excisional biopsy are associated with an increased risk of malignancy in either breast (1). Both lesions are assumed to be widely disseminated throughout breast tissue whenever they are found, and they have close to 100% prevalence of multicentricity and bilaterality. LCIS is found in approximately 5% of all breast malignancies when LCIS is considered a malignancy and in 1% of all breast biopsy specimens (1). The true incidence of LCIS is unknown, as it is often not detectable at mammography (1,2). LCIS has been reported to impart as much as a 12-fold increased risk of subsequent invasive breast carcinoma (1).

Women who receive a diagnosis of ALH at excisional biopsy have a risk of developing subsequent carcinoma that is higher than that in age-matched control subjects but lower than that in women with LCIS (3,4). This risk is equally applicable to both breasts (1). Subsequent malignancies may occur longer than 15 years after initial diagnosis of LCIS and are often ductal rather than lobular histologically (1). LCIS occurs exclusively in women at a mean age of 45 years. This mean age is approximately 15 years younger than the mean age at which invasive carcinoma occurs (1). Women who receive a diagnosis of LCIS or ALH at excisional biopsy currently receive a recommendation for observation (5). They may be eligible for preventive chemotherapy with tamoxifen (Nolvadex; Zeneca Pharmaceuticals, Wilmington, Del) (6).

Some pathologists suggested the use of the term lobular neoplasia to reflect the spectrum of change that ranges from ALH to LCIS and to reflect the ambivalent potential for malignancy (7). However, others suggested that the term is too broad (3). ALH represents a proliferation of monomorphic cells in a nondistended lobule or small lobular duct, whereas LCIS is characterized by distention (4,7,8). Although histologic differentiation between ductal carcinoma in situ (DCIS) and LCIS often is not difficult, areas of overlap exist. The amount of tissue submitted for analysis may relate to a more accurate diagnosis (8–11).

The treatment of patients with ALH or LCIS diagnosed at percutaneous core-needle biopsy (CNB) is not well established, and few guidelines exist (3,8,12,13). Uncertainty in regard to the need for excisional biopsy originates from conflicting opinions with respect to the biologic behavior of lobular lesions and the infrequency of LCIS lesions diagnosed at CNB for which the patient has undergone excisional biopsy (2). Investigators in some studies (3,4,13) analyzed only small numbers of patients with isolated LCIS or ALH at CNB, and results with these small numbers have limited their ability to draw absolute conclusions. Recommendations for treatment range from follow-up to excision. No general consensus remains. In contrast, there is consensus in regard to the need to perform excisional biopsy when another high-risk lesion, namely atypical ductal hyperplasia (ADH), is diagnosed at CNB (14).

The purpose of this study was to retrospectively determine the frequency of invasive cancer or DCIS at excisional biopsy in women who receive a diagnosis of ALH or LCIS at CNB.

	MATERIALS AND METHODS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
Institutional review board approval was obtained at both institutions prior to the commencement of this retrospective study. Written informed consent of patients was not required.

Combined data were obtained from two large institutions, an academic medical center (University of Michigan, Ann Arbor) and a private hospital (William Beaumont Hospital, Royal Oak, Mich). Hereafter, the academic medical center will be identified as institution A and the private hospital, as institution B. Patients with a diagnosis of LCIS or ALH were identified from computerized breast imaging records and from manually retrieved files of consecutive cases of patients who were undergoing CNB. Our goal was to assess outcome when CNB findings indicated LCIS or ALH as the benign diagnosis with highest risk. Patients in whom the diagnosis of LCIS or ALH at CNB was associated with invasive cancer, DCIS, or ADH were excluded from the study population, as these diagnoses would mandate excision. Also excluded were patients who had LCIS or ALH with associated high-risk lesions such as papillary lesions, radial sclerosing lesions, or phyllodes tumors at CNB, because the presence of these findings also would prompt excision. Hence, the study population included only those patients who had LCIS or ALH as the pathologic finding of highest risk or the most clinically important histologic diagnosis at CNB. Patients who had LCIS or ALH that was associated with benign findings, such as fibrocystic change, at CNB were included. In those patients who did not undergo subsequent excisional biopsy, mammographic follow-up for at least 24 months after CNB was required to establish stability for study entry.

In 6,081 consecutive patients, a review of results at image-guided CNB (M.C.F., N.E.G.) performed between 1997 and 2002 (at institution A, 1997–2002; at institution B, 2000–2002) revealed that 35 (0.58%) patients fulfilled study criteria. Fifteen patients had LCIS and 20 had ALH. During the same period, 75 (1.2%) patients had ADH that was diagnosed at CNB.

CNB Methods
During the study, stereotactic biopsy was performed with dedicated prone stereotactic biopsy tables (Fischer, Denver Colo; Lorad Medical Systems, Danbury, Conn). At institution A, vacuum-assisted CNB devices (Mammotome; Ethicon Endosurgery, Cincinnati, Ohio) were exclusively used. CNB with 11-gauge vacuum-assisted needles (Ethicon Endosurgery) was performed in the majority of patients. At the discretion of the physician who performed CNB, 14-gauge vacuum-assisted needles occasionally were used, primarily in the early years of the study. According to institutional protocol, 12 specimens were routinely obtained in a radial fashion at clock positions in 2-hour increments. For example, single specimens were obtained twice at 12-, 2-, 4-, 6-, 8-, and 10-o’clock positions. Additional specimens were obtained as clinically indicated. Radiography of a specimen was routinely performed in all patients with calcifications. A postbiopsy image was obtained in patients with lesions identified as masses.

At institution B, vacuum-assisted CNB devices (Mammotome; Ethicon Endosurgery) were exclusively used. In all patients with calcifications and masses, 11-gauge vacuum-assisted needles were used. According to institutional protocol, a minimum of six specimens were routinely obtained in a radial fashion at clock positions in 2-hour increments. Additional specimens were obtained as clinically indicated. Radiographs of specimens were obtained in all patients with calcifications and masses.

In 34 (97%) of 35 patients, LCIS or ALH was diagnosed at stereotactic CNB. From six to 21 (mean, nine) core samples were obtained in these patients. In 34 patients, diagnosis was established with 11-gauge vacuum-assisted CNB in 31 (91%) and with 14-gauge vacuum-assisted CNB in three (9%). Radiologists who performed CNBs were certified according to the Mammography Quality Standards Act, with subspecialty concentration in breast imaging. Because of the length of the study, experience and radiologists varied. The radiologist’s experience as of 2001 was used to express the radiologists’ years in practice. In 2001, 15 radiologists performed CNB with experience ranging from 1 to 24 years (mean, 7.1 years).

Sonographically guided biopsy was performed with patients in the supine position and with high-resolution sonographic equipment (model 700, GE Medical Systems, Milwaukee Wis; HDL, ATL, Bothell, Wash). Generally, 12–13-MHz transducers were used. At institution A, disposable 14-gauge core biopsy needles from various manufacturers were used. According to institutional protocol, five specimens were obtained in each patient. At institution B, 14-gauge automated core biopsy needles were used. According to institutional protocol, a minimum of three specimens were obtained in each patient. In one (3%) of 35 patients with LCIS diagnosed at CNB with sonographic guidance, five specimens were obtained with a 14-gauge needle. Sonographic guidance was used for biopsy of masses and not of calcifications.

The decision regarding the choice of sonographically guided versus stereotactic biopsy was left to the discretion of the radiologist who performed the procedure. Biopsy of calcifications was exclusively performed with stereotactic methods. Biopsy of masses was performed with either sonographic guidance or stereotaxis. Overall, biopsy in 4,298 (71%) of 6,081 patients was performed with stereotactic methods. Marker clips were placed at the site of biopsy when the entire lesion was excised.

Pathologic Results
The prospective pathologic report rendered by the institutional pathologist at the time of CNB was considered the definitive CNB pathologic result unless a preliminary opinion was rendered with a recommendation for a second pathologic consultation. If that was the case, the pathologic result following the second consultation was considered the definitive pathologic result. No such formal consultation was documented for any of the patients with LCIS or ALH. Pathologic specimens that were obtained at the time of CNB were immediately placed in formalin and stained with hematoxylin-eosin according to institutional protocols. All sections were processed in total, and material from the paraffin-embedded material was reviewed by the pathologist. If calcifications were noted on the radiograph of the specimen and were not present at histologic review, paraffin-block radiography with repeat histologic sectioning was routinely performed.

Because there was no definitive protocol for treatment of the patients with LCIS and ALH, treatment varied. However, most patients (26 [74%] of 35) underwent excisional biopsy following CNB when pathologic results indicated a diagnosis of ALH or LCIS, especially in the later years of the study. Excisional biopsy was performed with guidance with mammographic or sonographic wire localization technique. Radiography of the specimen was performed to confirm excision of the appropriate area, which frequently had been marked with a radiopaque marker at the time of CNB. The specimen was then processed routinely by pathologists. The tissue was reviewed by the pathologist after hematoxylin-eosin staining and sectioning.

For the purpose of this study, patients were classified in two categories: upgrade and nonupgrade. In 26 patients who underwent excisional biopsy, a pathologic upgrade of a lesion was noted when a pathologic diagnosis of invasive cancer or DCIS was determined at excisional biopsy in those whose LCIS or ALH lesions were diagnosed at prior CNB. A nonupgrade of a lesion was noted in patients with histologic results at excisional biopsy that indicated a diagnosis other than invasive cancer or DCIS; that diagnosis included LCIS, ALH, components of fibrocystic change, and other benign pathologic findings. Patients with ADH diagnosed at excisional biopsy were classified in the nonupgrade category. In nine (26%) of 35 patients who underwent mammographic follow-up without excisional biopsy, a nonupgrade classification was rendered when mammographic findings were stable at follow-up of 2 years or longer.

Data Collection
Mammographic interpretation was rendered by radiologists certified according to the Mammography Quality Standards Act at Food and Drug Administration–approved facilities. In 2001, the experience of mammographers ranged from 1 to 29 years (mean, 10.5 years). Initial prospective mammographic findings that led to the recommendation for CNB were recorded. This included breast mammographic findings (masses, calcifications, or developing densities) and prospective final assessment categories of the Breast Imaging Reporting and Data System (15). CNB procedures and reports were reviewed (M.C.F.) for technical problems, insufficient sampling, and discordant sampling (eg, calcifications present in the breast that were not retrieved at CNB). Residual calcifications that were present after CNB and were apparent at mammography after CNB were recorded in patients whose initial mammographic finding at presentation was microcalcifications at the retrospective review of images (M.C.F.). Mammographic maximal diameter was measured on the images with a ruler without magnification correction at retrospective review (M.C.F.).

Clinical parameters (patient age, menstrual status, family history of breast cancer, and personal prior history of breast cancer) were also recorded. A comparison was made between patients classified in the upgrade and nonupgrade categories.

To compare the risk of a pathologic upgrade from LCIS or ALH with the risk of that from ADH, we reviewed institutional results for the same 6,081 patients who underwent image-guided CNB. Seventy-five patients who received a diagnosis of ADH at CNB underwent subsequent excisional biopsy during the same period. As we did for patients with LCIS and ALH, we also excluded those patients who had an associated invasive cancer or DCIS associated with ADH at CNB.

Statistical Analysis
Statistical comparison of the frequency of upgrading of lesions between patients with LCIS or ALH at CNB and those with ADH at CNB was performed with the Pearson ² test by using mathematic software (S-Plus, version 5.1; MathSoft, Seattle, Wash). A difference with a P value less than .05 was considered significant. CIs were determined with normal approximation of the binomial distribution at the 95% level.

	RESULTS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
The age range of the patients was 41–84 years (mean, 59 years). The age range of those with upgraded lesions was 41–84 years (mean, 55 years) (Table 1). There was a trend of more frequent upgrades in women with a family history of disease (three [50%] of six for upgrade category vs seven [24%] of 29 for nonupgrade category), but the difference was not significant (P = .20).

The mammographic appearance of LCIS diagnosed at CNB is presented in Tables 2 and 3. In 15 patients, findings included calcifications (12 [80%] patients), mass with calcifications (one [7%] patient), and mass alone (two [13%] patients). Of the four patients with lesions that were histologically upgraded, the mammographic findings at presentation were calcifications (two [50%] patients), mass with calcifications (one [25%] patient), and mass alone (one [25%] patient). Of the patients who had calcifications, nine had residual calcifications following CNB, and three had no residual calcifications. Of three patients with upgraded lesions, two had residual calcifications and one had no residual calcifications. The mammographic appearance of upgraded invasive cancers was calcifications alone (one patient) and a mass with faint calcifications (one patient).

The mean diameter of the mammographic abnormality in patients with LCIS was 9.5 mm (range, 3–30 mm). The mean size of upgraded lesions was 9 mm (range, 5–20 mm).

Review of CNB results in four patients with lesions that were upgraded histologically demonstrated no technical failure, premature termination, or inadequate sampling of the primary finding. One upgraded lesion was a mass with faint calcifications. The mass was adequately sampled although the calcifications were not. In four patients, two underwent 11-gauge vacuum-assisted CNB, one underwent 14-gauge vacuum-assisted CNB, and one underwent 14-gauge sonographically guided CNB.

ALH Data
ALH was diagnosed at CNB in 20 (0.3%) of 6,081 patients. Overall, lesions in two (10%) of these 20 patients were upgraded (Table 2). Subsequent excisional biopsies were performed in 14 (67%) of 21 patients. Lesions in two (14%) of these 14 patients were upgraded to DCIS (Table 3). For the remaining patients, lesions in five patients revealed the same ALH pathologic findings and those in seven patients revealed benign pathologic findings. In the remaining six patients who did not undergo biopsy, follow-up was performed for a mean of 36 months (range, 24–48 months). No patient developed a subsequent carcinoma. The mammographic appearance of ALH was similar to that of LCIS in 20 patients: 17 (85%) had calcifications, two (10%) had a mass, and one (5%) had a developing density (Table 2). In two patients with lesions that were upgraded histologically, both had calcifications.

The mean diameter of the mammographic abnormality for patients with ALH was 11.6 mm (range, 3–40 mm). The mean size of the two lesions that were upgraded was 23 mm (range, 5–40 mm).

Review of CNB results in two patients with upgraded lesions demonstrated no technical problems. In both patients, the index abnormality was satisfactorily sampled at the time of CNB. In both patients, 11-gauge vacuum-assisted stereotactic CNB was performed. Residual calcifications were noted in upgraded lesions in two of two patients.

ADH Data
During the same study period, in 75 (1.2%) of 6,081 patients, ADH was diagnosed at CNB. The frequency of upgrading of lesions diagnosed as ADH at CNB to ductal carcinoma or invasive cancer at subsequent excisional biopsy was 16% (12 of 75 patients) (95% CI: 7.7%, 24.3%). The difference between the upgrade rate of LCIS or ALH and that of ADH was not significant (P = .88).

	DISCUSSION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
At CNB, a diagnosis of LCIS or ALH was upgraded to invasive cancer or DCIS in 17% (six of 35) of patients. This number increased to 23% (six of 26 patients) when only those patients in whom excisional biopsy was performed were considered completely evaluated. This frequency of upgrading of lesions to DCIS and invasive cancer is essentially identical to the rate of upgrading in our study of 16% (12 of 75 patients) for ADH lesions discovered at CNB and subsequently upgraded to DCIS or invasive cancer at excisional biopsy.

LCIS or ALH, which was the benign entity with the highest risk as defined in our study, was an unusual and infrequent finding at CNB, with a frequency of only 0.58%. This frequency is slightly lower than that in previously published articles by Liberman et al (3) and Berg et al (4), who reported a frequency of 1.2% and 1.8%, respectively. Hence, it would be unusual for practicing radiologists to gain much experience with these histologic entities and outcome on the basis of personal experience alone.

Treatment of patients with LCIS or ALH at CNB has been controversial, which is likely caused by the small number of cases. Liberman et al (3) examined 13 patients with LCIS who subsequently underwent excisional biopsy. However, nine patients had not only LCIS but also mixed histologic findings that included other high-risk lesions. Lesions in five patients with LCIS alone were not upgraded to DCIS or invasive cancer. Berg et al (4) examined 15 patients with ALH or LCIS who subsequently underwent excisional biopsy. They found that lesions in 7% of the patients were upgraded to DCIS. They viewed residual calcifications as markers for higher risk. Although the number of cases was small, neither Liberman et al (3) nor Berg et al (4) advocated uniform excision for patients with LCIS or ALH at CNB.

Excisional biopsy for patients with ADH diagnosed at CNB has been widely accepted in the United States (16). This acceptance followed reports of underestimation of DCIS or invasive cancer. The recommendation for excision following the diagnosis of ADH at CNB was established after Jackman et al (17) and Liberman et al (18) reported the upgrade rates of 56% and 52%, respectively, of lesions to malignancy at excision.

Findings in subsequent studies (16,19) demonstrated underestimation of rates of malignancy ranging from 11% to 25% of lesions diagnosed as ADH in patients who underwent percutaneous biopsy. Darling et al (20) demonstrated that 27% (38 of 139) of lesions diagnosed as ADH at CNB performed with large (11- or 14-gauge) needles were upgraded to DCIS or invasive ductal carcinoma at excision. Our study findings demonstrated an upgrade rate of 16% (12 of 75) (95% CI: 7.7%, 24.3%).

More recently, Jackman et al (21) evaluated clinical and mammographic features in 104 lesions diagnosed as ADH at 11-gauge stereotactic biopsy to characterize lesions as "probably benign" in patients for whom they would recommend follow-up instead of excision. However, they found "no clinical, mammographic, and/or biopsy features that could be used to define a substantial subset of lesions with a less than 2% chance of carcinoma at subsequent surgical excision." Therefore, the recommendation for excision of all lesions diagnosed as ADH at CNB remains the current standard of care (14).

Since findings in our study showed that the risk of upgrading lesions diagnosed as ALH or LCIS is similar to the risk of upgrading those diagnosed as ADH, it would seem prudent that all patients with ALH or LCIS undergo surgical resection to establish definitive histologic results. This argument is supported by several lines of reasoning.

First, American radiologists typically recommend biopsy for mammographic lesions for which the probability of malignancy exceeds 2%. For example, patients with mammographic findings classified as Breast Imaging Reporting and Data System category 4 and 5 undergo biopsy, whereas patients with category 3, namely probably benign findings, are followed up without biopsy. It has been established that category 3 confers a risk of malignancy generally less than 2% (22–25). Hence, radiologists in the United States recommend biopsy for lesions with Breast Imaging Reporting and Data System category 4 and 5 assessments, with probability of malignancy from 3% to 100%. The risk of finding invasive cancer or DCIS in patients with ALH and LCIS in our study exceeds the lower clinical biopsy threshold of 2%. In our study, the lower value of the confidence limit was 4.7%, with an upper value of 29.6%.

Second, ADH lesions are routinely excised after CNB. For ADH and LCIS or ALH lesions, probability of upgrading was essentially identical in our study. If one routinely performs excisional biopsy in patients with ADH, it would be consistent practice to perform excisional biopsy in those with LCIS or ALH.

Third, as in the recent study of Jackman et al (21), we were unable to identify particular mammographic findings, technical findings, or unusual features that would be used to segregate those patients whose lesions would be upgraded from those patients whose lesions would not. In our study, the lesion was upgraded in one patient who underwent complete removal of calcifications. This result suggests that histologic analysis remains necessary to find the patient with an unusual upgraded lesion.

The clinical effect of performing excisional biopsy in patients with LCIS or ALH would be minimal, since isolated LCIS or ALH is an infrequent finding. In our experience, only 0.58% of patients who underwent CNB had this diagnosis.

In our study, calcifications were the most common mammographic finding that led to a diagnosis of ALH or LCIS. Some researchers believe that LCIS has no distinguishing mammographic appearance, and many believe that its discovery is therefore an incidental finding (26,27). This forms one argument for follow-up as opposed to biopsy for patients with this lesion; that is, since the reason for biopsy (ie, calcifications) pathologically may not directly relate to the finding (ie, LCIS or ALH), any further surgical discovery would in itself be an incidental finding. Even if true, one would still recommend excisional biopsy, since cancer is found relatively frequently at or near the site of ALH or LCIS at CNB. However, Georgian-Smith and Lawton (28) found that calcifications can be directly associated with LCIS, especially the pleomorphic form of LCIS. Their findings suggest that at least some LCIS lesions are not incidental findings, and a sample removed at an area near LCIS or ALH at CNB may not be adequate.

In the majority of patients, a pathologic upgrade of lesions will not occur. These women will then undergo treatment of LCIS or ALH. Currently, most oncologists view these entities as a risk marker and not carcinoma. Most women in the United States are followed up with periodic mammography and a clinical examination. Because of the elevated risk in patients with this lesion, some individuals may be eligible for preventive chemotherapy. Findings of the National Surgical Adjuvant Breast and Bowel Project P-1 Study, in which tamoxifen was used as a preventive chemotherapeutic agent, demonstrated that women with LCIS had a significantly decreased risk of developing subsequent breast cancer after 4 years of treatment. This risk was reduced by 56% (6) in the group receiving tamoxifen. Risk of the preventive chemotherapeutic medications must be balanced with their benefit.

There were several limitations of our study. We reviewed CNB findings in more than 6,000 patients, but only a small number of patients actually fulfilled the study criteria. Thus, the power of the study was limited and CIs regarding the percentage of upgrades were large (95% CI: 4.7%, 29.6%). Variability between pathologists regarding the diagnosis of ALH and LCIS exists. For this reason, we structured our study to simulate routine clinical care. We combined data from an academic center and a large private hospital. We used the original pathologic report as the true report, as this is the information presented to the radiologist, the patient, and the physician following CNB. Prospective decisions are rendered on the basis of this report. In studies in which retrospective pathologic interpretation is employed, significant differences may or may not be found. It is possible that pathologic criteria that will help the radiologist to distinguish between abnormalities may be developed in the future to determine which patients with LCIS, ALH, or ADH can be observed and which will receive a recommendation to undergo biopsy.

We chose to examine combined data from a large academic medical center and a large private hospital, with multiple radiologists and pathologists, to provide data that would reflect U.S. practice. Technical differences among practices may contribute to potential differences in results. Most (89% [31 of 35]) of our results at CNB that showed LCIS or ALH were obtained with 11-gauge vacuum-assisted needles and with large numbers of samples. It might be expected that the upgrade rate may actually be higher if smaller needles and smaller numbers of samples were obtained, a trend reported in patients with ADH (21). Although at least a 2-year mammographic follow-up was required for patients in whom excisional biopsy was not performed, slow tumor growth may occur and would not be detected in this period. In our study, overall upgrade rate of 17% (95% CI: 4.7%, 29.6%) could therefore reflect a lower boundary of upgrading of lesions, since not all women underwent excisional biopsy.

In summary, we found that the upgrade rate for LCIS and ALH was at least 17%. This number is similar to our upgrade rate for ADH. Excisional biopsy is supported when LCIS, ALH, or ADH is found at percutaneous CNB.

	ACKNOWLEDGMENTS

 
We thank Bin Nan, PhD, Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, for providing statistical support for this manuscript.

	FOOTNOTES

 
See also the editorial by Cohen in this issue.

Abbreviations: ADH = atypical ductal hyperplasia, ALH = atypical lobular hyperplasia, CNB = core-needle biopsy, DCIS = ductal carcinoma in situ, LCIS = lobular carcinoma in situ

Author contributions: Guarantors of integrity of entire study, M.C.F., M.A.H., N.E.G., M.R.; study concepts, M.C.F., M.A.H., N.E.G., M.R.; study design, all authors; literature research, all authors; clinical studies, M.C.F., M.A.H., N.E.G., M.R.; data acquisition, M.C.F., M.A.H., N.E.G., M.R.; data analysis/interpretation, all authors; manuscript preparation, definition of intellectual content, editing, revision/review, and final version approval, all authors

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