Biomedical subjects
Publications and source records attributed to D David Dershaw.
Imaging has a significant role in diagnosing, treating, and monitoring breast cancer. Advances in this field are having a great impact in the clinical management of this disease. Breast cancer has now become an "outpatient cancer". This article describes the role and advances of imaging in breast cancer.
PURPOSE: To prospectively evaluate the diagnostic performance of magnetic resonance (MR) spectroscopy in patients with suspicious lesions or biopsy-proved cancers at MR imaging by using histologic findings as the reference standard. MATERIALS AND METHODS: After institutional review board approval and informed consent were obtained for this HIPAA-compliant study, breast MR spectroscopy was performed in patients with suspicious or biopsy-proved malignant lesions measuring 1 cm or larger at MR imaging. Single-voxel MR spectroscopy data were collected from a single rectangular volume of interest that encompassed the lesion. MR spectroscopy findings were defined as positive if the signal-to-noise ratio of the choline resonance peak was greater than or equal to 2 and as negative in all other cases. MR spectroscopy findings were then compared with histologic findings. RESULTS: A total of 56 patients (age range, 20-77 years) with 57 lesions were imaged. The median lesion size at MR imaging was 2.3 cm (range, 1-15 cm). Histologically, 31 (54%) of 57 lesions were malignant, and 26 (46%) were benign. A choline peak was present in 34 of 57 lesions (including all cancers) and in three of 26 benign lesions, giving MR spectroscopy a sensitivity of 100% and a specificity of 88%. In 40 lesions of unknown histologic type, the use of MR spectroscopy as an adjunct to MR imaging would have significantly (P<.01) increased the positive predictive value of biopsy from 35% to 82%. If biopsy had been performed only on those lesions with a choline peak at MR spectroscopy, biopsy may have been spared in 23 (58%) of 40 lesions, and none of the cancers would have been missed. CONCLUSION: Proton MR spectroscopy was successfully incorporated into breast MR imaging studies for lesions measuring 1 cm or larger. This technique may be useful in reducing the number of lesions detected at MR imaging that require biopsy.
OBJECTIVE: The purpose of this study was to determine the impact of lesion size on the positive predictive value (PPV) of biopsy in MRI-detected breast lesions. MATERIALS AND METHODS: A retrospective review was performed of 666 consecutive nonpalpable, mammographically occult lesions that had MRI-guided localization. MRI examinations were performed using a 1.5-T magnet. Lesions were measured by the interpreting radiologist before biopsy. Malignancy rate versus lesion size was determined. RESULTS: The median MRI lesion size was 1 cm (range, 0.3-7.0 cm). Malignancy was present in 149/666 (22%) lesions, of which 80 (54%) were ductal carcinoma in situ (DCIS), 66 (44%) were invasive cancer, and three (2%) were lymphoma. The frequency of malignancy increased significantly (p = 0.0005) with lesion size, with malignancy found in one (3%) of 37 lesions less than 5 mm, 44 (17%) of 254 lesions 5-9 mm, 37 (25%) of 151 lesions 10-14 mm, 21 (28%) of 74 lesions 15-19 mm, and 46 (31%) of 150 lesions 20 mm or larger. Lesions less than 5 mm accounted for 37 (6%) of 666 lesions that had a biopsy and one (< 1%) of 149 cancers (one DCIS). Among lesions less than 10 mm, the likelihood of malignancy was highest in postmenopausal women (22% malignant) and in the extent of disease setting (22% malignant), and lowest in premenopausal women (10% malignant) and in the high-risk screening setting (10% malignant). CONCLUSION: The PPV of biopsy for lesions identified at breast MRI using a 1.5-T magnet significantly increased with increasing lesion size. Biopsy is rarely necessary for lesions smaller than 5 mm because of their low (3%) likelihood of cancer. Further work is needed to develop an algorithm that uses size in addition to other patient and lesion factors to guide biopsy recommendations for MRI-detected breast lesions.
OBJECTIVE: The purpose of this study was to determine the MRI findings and histology of clinically and mammographically occult invasive breast cancers detected by MRI. MATERIALS AND METHODS: A retrospective review was undertaken of 1,336 breast MRI examinations performed during a 2-year period. Among these, 68 nonpalpable mammographically occult invasive cancers were identified in 57 women with a median age of 50 years (range, 30-72 years). MRI findings were classified according to the breast MRI lexicon. Medical records were reviewed to determine the histology. RESULTS: Indications for performing MRI were extent of disease assessment in 72% (41/57), high-risk screening in 25% (14/57), and problem solving in 3% (2/57). MRI lesion types in these 68 invasive cancers were nonmass in 57% (39/68) and mass in 43% (29/68). Kinetics were plateau in 59% (40/68), washout in 38% (26/68), and persistent in 3% (2/68). Histology was invasive ductal cancer in 65% (44/68), mixed invasive ductal and lobular cancer in 19% (13/68), and invasive lobular cancer in 16% (11/68). The cancer stage was I in 61% (34/56), II in 32% (18/56), and more advanced in 7% (4/56). Sixty-three percent (43/68) of lesions were minimal cancers, defined as invasive cancers measuring under 1 cm. CONCLUSION: In this study of mammographically and clinically occult cancers detected by MRI, 57% (39/68) of invasive breast cancers were evident as nonmass enhancement, and 63% were minimal breast cancers.
OBJECTIVE: The study objective was to determine the cancer frequency in lesions yielding a benign, concordant diagnosis of papilloma at percutaneous breast biopsy. MATERIALS AND METHODS: Retrospective review was performed of 3,864 lesions that had percutaneous imaging-guided biopsy. In 50 lesions (1.3%), percutaneous biopsy yielded a benign, concordant diagnosis of papilloma. Surgical pathology (n = 25) or minimum 2 years' mammographic follow-up (n = 10) was available for 35 lesions that had biopsy with 11-gauge vacuum-assisted (n = 20) or 14-gauge automated (n = 15) needles. Medical records, imaging studies, and histologic results were reviewed. RESULTS: Cancer was found in five (14%) of the 35 lesions yielding a benign, concordant diagnosis of papilloma at percutaneous biopsy. Cancer histology was ductal carcinoma in situ in four (80%) and node-negative invasive cancer in one. Four (80%) of five cancers were identified due to interval change at follow-up (median, 22 months; range, 7-25 months). In six (17%) of 35 lesions, surgery revealed high-risk lesions including atypical ductal hyperplasia (n = 3), radial scar (n = 2), and lobular carcinoma in situ (n = 1). There was a significantly (p = 0.02) higher frequency of cancer or high-risk lesion in women with multiple versus solitary papillomas and a trend (p = 0.09) toward a higher cancer rate in women with versus without a family history of breast cancer. Breast cancer history, menopausal status, mammographic pattern, biopsy method, and removal of imaging target had no significant impact on cancer rate. CONCLUSION: In our study of percutaneously diagnosed papillomas, surgery revealed cancer in 14% and high-risk lesions in 17%. Lesions yielding a benign, concordant diagnosis of papilloma at percutaneous biopsy may warrant surgical excision.
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OBJECTIVE: The objective of this study was to evaluate our initial clinical experience with MRI-guided vacuum-assisted breast biopsy as an alternative to surgical excision. MATERIALS AND METHODS: A retrospective review revealed 112 consecutive nonpalpable, mammographically occult MRI-detected breast lesions scheduled for MRI-guided vacuum-assisted biopsy. Biopsy was performed with a 9-gauge vacuum-assisted biopsy probe (Suros Surgical Systems) followed by clip placement (Artemis Medical). Medical records and histologic findings were reviewed. RESULTS: Among 112 lesions, biopsy was cancelled because of nonvisualization of the lesion in 14 (12%). Of the remaining 98 lesions, tissue was successfully acquired in 95 (97%). The median number of specimens obtained was 12 (range, 6-20). The median time to perform MRI-guided biopsy was 33 min for one lesion and 56 min for two lesions. Histology in 95 lesions was benign and concordant in 52 (55%), cancer in 24 (25%), high-risk in 10 (11%), and discordant in nine (9%). MRI-guided biopsy histologies in 24 cancers were ductal carcinoma in situ in 13 (54%) and infiltrating carcinoma in 11 (46%). Seven additional cancers were found at surgery in four discordant lesions and in three high-risk lesions. The clip successfully deployed in 86 (95%) of 91 lesions. Six complications (three hematomas, two instances in which the biopsy probe pierced the skin on the far side of the breast, and one vasovagal reaction) resolved without sequelae. CONCLUSION: MRI-guided vacuum-assisted biopsy is a fast and safe alternative to surgical biopsy for MRI-detected breast lesions. Imaging-histologic correlation is necessary to ensure lesion sampling.
BACKGROUND: The purpose of the current study was to determine the frequency of 'probably benign' interpretations at breast magnetic resonance (MR) imaging screening of high-risk women and the frequency of subsequent malignancy in these women. METHODS: The authors performed a retrospective review of the records of 367 asymptomatic women with normal mammograms who had a high risk of developing breast cancer and whose first breast MR imaging screening examinations occurred during a 2-year period. The number of "probably benign" interpretations was determined, and follow-up data were obtained. RESULTS: A "probably benign" interpretation was given to 89 (24%) of 367 women. Follow-up MR imaging was performed for 70 (79%) of 89 women, with a median follow-up time of 11 months (range, 1-24 months). Twenty women subsequently underwent biopsy at a median of 9 months (range, 1-18 months) after MR imaging, due to progression on follow-up MR imaging (n=14) or for other reasons (n=6). Malignancies were found in 9 women, constituting 45% of the 20 women who underwent biopsy and 10% of the 89 women with probably benign lesions. In 6 of the 9 women who developed malignant disease (7% of the 89 women in the study), the malignancy was detected by follow-up MR imaging of an area that previously was interpreted as probably benign. Tumor histology was ductal carcinoma in situ (DCIS) in five patients and infiltrating ductal carcinoma in four. CONCLUSIONS: A "probably benign" interpretation was given to 24% of high-risk women at their first breast MR imaging screening examination. In 7-10% of women with "probably benign" interpretations, malignant disease subsequently developed in an area initially judged to be probably benign; of these malignancies, more than half were DCIS, and more than half were detected by MR imaging only.
PURPOSE: To determine the utility and histopathologic importance of ultrasonographic (US) depiction of breast lesions detected with magnetic resonance (MR) imaging. MATERIALS AND METHODS: Retrospective review was performed of 654 consecutive breast MR examinations performed from November 1999 to February 2001. This yielded 64 patients with 93 suspicious, nonpalpable, mammographically occult lesions evident on MR images and recommended for biopsy, for which directed US assessment was performed. Images, pathologic records, and medical records of these patients were reviewed for imaging findings, patient demographics, and histopathologic findings from subsequent biopsy. Statistical analysis was performed with the Fisher exact test. RESULTS: The median size of MR abnormalities was 0.9 cm (range, 0.3-5.0 cm). The pattern of enhancement was a focal mass in 76 (82%) lesions and nonmass in 17 (18%). A US correlate was identified in 21 (23%) lesions detected with MR--19 (25%) of 76 focal mass and two (11%) of 17 nonmass lesions. Carcinoma was found in nine (43%) of these lesions, of which seven (78%) were invasive carcinoma and two (22%) were ductal carcinoma in situ (DCIS). Among the lesions without a US correlate, 10 (14%) yielded carcinoma, of which five (50%) were invasive carcinoma and five (50%) were DCIS. The frequency of cancer was significantly higher for lesions that were detected with MR imaging and had a US correlate than for those that did not have a US correlate (43% vs 14%, P =.01). Overall, 19 (20%) lesions detected with MR imaging and examined with US yielded carcinoma at biopsy, and nine (47%) malignant lesions were seen on US images. US depicted seven (58%) of 12 invasive cancers and two (29%) of seven instances of DCIS. CONCLUSION: The likelihood of carcinoma was significantly higher among lesions with a US correlate (43% carcinoma) than lesions without a US correlate (14% carcinoma).
OBJECTIVE: The purpose of this study was to determine the frequency and positive predictive value of biopsy performed on the basis of MR imaging findings in the contralateral breast in women with recently diagnosed breast cancer. MATERIALS AND METHODS: We performed a retrospective review of records of 1336 consecutive breast MR imaging examinations over a 2-year period. Of these examinations, 223 imaged the asymptomatic, mammographically normal contralateral breast in women whose breast cancer was diagnosed within 6 months preceding MR imaging. Records of these 223 examinations were reviewed to determine the frequency of recommending contralateral breast biopsy and the biopsy results. RESULTS: Contralateral breast biopsy was recommended in 72 (32%) of 223 women and performed in 61 women. Cancer occult to mammography and physical examination was detected by MR imaging in 12 women, constituting 20% (12/61) of women who underwent contralateral biopsy and 5% (12/223) of women who underwent contralateral breast MR imaging. Among these 12 cancers, six (50%) were ductal carcinoma in situ (DCIS) and six (50%) were infiltrating carcinoma. The median size of infiltrating carcinoma was 0.5 cm (range, 0.1-1.0 cm). Contralateral biopsy revealed benign (n = 31) or high-risk (n = 18) lesions in 49 women, constituting 80% (49/61) of women who underwent contralateral biopsy and 22% (49/223) of women who underwent contralateral MR imaging. CONCLUSION: In women with recently diagnosed breast cancer, MR imaging of the contralateral breast led to a biopsy recommendation in 32%. Cancer was found in 20% of women who underwent contralateral breast biopsy and in 5% of women who underwent contralateral breast MR imaging.
OBJECTIVE: The purpose of this study was to review MR imaging findings in the ipsilateral breast in women with percutaneously proven breast cancer. MATERIALS AND METHODS: Retrospective review was performed of records of 70 consecutive women with percutaneously proven unilateral breast cancer who were considered candidates for breast conservation surgery and who had preoperative MR imaging of the ipsilateral breast. MR images and medical records were reviewed. RESULTS: MR imaging identified mammographically and clinically occult cancer other than the index lesion in the ipsilateral breast in 19 women (27%), including infiltrating cancer in 11 women (16%) and ductal carcinoma in situ in eight women (11%). These additional sites of cancer were in the same quadrant as the index cancer in 14 women (20%), in a different quadrant in three women (4%), and in both the same and different quadrants in two women (3%). Additional sites of cancer were more likely in women with, rather than in those without, a family history of breast cancer (42% vs 14%, p < 0.02) and in women whose index cancer was infiltrating lobular rather than other histologies (55% vs 22%, p < 0.06). In 17 women (24%), MR imaging detected ipsilateral lesions that were benign. Changes due to prior percutaneous biopsy were infrequently observed on MR images and included a clip in 12 women (17%) and a small hematoma in two women (3%). CONCLUSION: MR imaging identified additional sites of ipsilateral cancer in 27% of women with percutaneously proven breast cancer. The yield was highest in women with a family history of breast cancer or infiltrating lobular histology in the index cancer. Change after biopsy was infrequent and did not interfere with the MR imaging interpretation.
OBJECTIVE: The purpose of this study was to determine the prevalence and positive predictive value of ductal enhancement among MR imaging-detected breast lesions that had biopsy and to assess the histologic findings associated with ductal enhancement. MATERIALS AND METHODS: Retrospective review was performed of 427 nonpalpable, mammographically occult lesions that had MR imaging-guided needle localization and surgical biopsy. Lesions were reviewed by one radiologist who was unaware of the histologic outcomes and were classified according to a standardized lexicon. MR imaging and histologic findings of ductal enhancing lesions were reviewed. RESULTS: Ductal enhancement accounted for 88 (21%) of 427 lesions and 88 (59%) of 150 nonmass lesions. Histologic finding in these 88 lesions were ductal carcinoma in situ (DCIS) in 18 (20%); infiltrating carcinoma in five (6%), including three with DCIS; lobular carcinoma in situ (LCIS) in nine (10%); atypical ductal hyperplasia in eight (9%); and benign in 48 (55%). Among the 48 benign lesions, the dominant histologic findings were fibrocystic change (n = 16); ductal hyperplasia (n = 8); fibrosis (n = 8); postbiopsy change (n = 5); benign breast tissue (n = 3); sclerosing adenosis (n = 2); and single cases of fibroadenoma, fibroadenomatoid change, lymph node, mastitis, papilloma, and radial scar. Factors associated with a trend toward a higher frequency of carcinoma included clumped enhancement (p = 0.05) and synchronous ipsilateral cancer (p = 0.07). CONCLUSION: Ductal enhancement accounted for 21% of MR imaging-detected lesions that had biopsy and had a positive predictive value of 26%. Differential diagnosis of ductal enhancement includes carcinoma (usually DCIS); atypical ductal hyperplasia; LCIS; and benign findings such as fibrocystic change, ductal hyperplasia, and fibrosis.
OBJECTIVE: The purpose of this study was to determine the frequency of cancer and the positive predictive value of biopsy in the first screening round of breast MRI in women at high risk of developing breast cancer. MATERIALS AND METHODS: Retrospective review was performed of the records of 367 consecutive women at high risk of developing breast cancer who had normal findings on mammography and their first breast MRI screening examination during a 2-year period. The frequency of recommending biopsy at the first screening MRI study and the biopsy results were reviewed. RESULTS: Biopsy was recommended in 64 women (17%). Biopsy revealed cancer that was occult on mammography and physical examination in 14 (24%) of 59 women who had biopsy and in 14 (4%) of 367 women who underwent breast MRI screening. Histologic findings in 14 women with cancer were ductal carcinoma in situ in eight (57%) and infiltrating carcinoma in six (43%). The median size of infiltrating carcinoma was 0.4 cm (range, 0.1-1.2 cm). Two patients had nodes that were positive for cancer. Biopsy revealed high-risk lesions (atypical ductal hyperplasia, atypical lobular hyperplasia, lobular carcinoma in situ, or radial scar) in 13 (4%) of 367 women and other benign findings in 32 (9%) of 367 women who had MRI screening. CONCLUSION: Among women at high risk of developing breast cancer, breast MRI led to a recommendation of biopsy in 17%. Cancer was found in 24% of women who underwent biopsy and in 4% of women who had breast MRI screening. More than half the MRI-detected cancers were ductal carcinoma in situ.
OBJECTIVE: The purpose of this study was to evaluate a new method for performing MRI-guided vacuum-assisted breast biopsy in a study of lesions that had subsequent surgical excision. SUBJECTS AND METHODS. Twenty women scheduled for MRI-guided needle localization and surgical biopsy were prospectively entered in the study. MRI-guided biopsy was performed with a vacuum-assisted probe, followed by placement of a localizing clip, and then needle localization for surgical excision. Vacuum-assisted biopsy and surgical histology were correlated. RESULTS: Vacuum-assisted biopsy was successfully performed in 19 (95%) of the 20 women. The median size of 27 MRI-detected lesions that had biopsy was 1.0 cm (range, 0.4-6.4 cm). Cancer was present in eight (30%) of 27 lesions and in six (32%) of 19 women; among these eight cancers, five were infiltrating and three were ductal carcinoma in situ (DCIS). Among these 27 lesions, histology was benign at vacuum-assisted biopsy and at surgery in 19 (70%), cancer at vacuum-assisted biopsy in six (22%), atypical ductal hyperplasia at vacuum-assisted biopsy and DCIS at surgery in one (4%), and benign at vacuum-assisted biopsy with surgery showing microscopic DCIS that was occult at MRI in one (4%). The median time to perform vacuum-assisted biopsy of a single lesion was 35 min (mean, 35 min; range, 24-48 min). Placement of a localizing clip, attempted in 26 lesions, was successful in 25 (96%) of 26, and the clip was retrieved on specimen radiography in 22 (96%) of 23. One complication occurred: a hematoma that resolved with compression. CONCLUSION: MRI-guided vacuum-assisted biopsy is a fast, safe, and accurate alternative to surgical biopsy for breast lesions detected on MRI.
BACKGROUND: Breast carcinoma is one of the leading causes of excess mortality rates in Harlem, an inner-city neighborhood with the highest mortality rates and worst life expectancy in New York City. This study reports the results of a breast carcinoma screening and diagnostic program in Harlem. METHODS: Retrospective review was performed of a database of 49,750 visits to the Breast Examination Center of Harlem from 1995 to 2000. During this period, 181 breast carcinomas were diagnosed in 178 women. The medical records of these 178 women were reviewed to determine the method of detection, stage, and treatment. RESULTS: Among these women, 89% were black or Hispanic, 45% had no medical insurance, and 38% had incomes below federal poverty guidelines. Breast carcinoma stage, known for 167 carcinomas, was Stage 0 in 38 (23%), Stage I in 38 (23%), Stage II in 63 (38%), Stage III in 24 (14%), and Stage IV in 4 (2%). Fifty-six cases (34%) were minimal breast carcinomas. Of 181 breast carcinomas, 122 (67%) were palpable and 59 (33%) were nonpalpable, detected only by mammography in asymptomatic women. Nonpalpable, as opposed to palpable, breast carcinomas were significantly more likely to be ductal carcinoma in situ (30 of 55 [54%] vs. 8 of 112 [7%], P < 0.0000001) or minimal breast carcinoma (39 of 55 [71%] vs. 17 of 112 [15%], P = 0.0000001) and were more likely to be treated with breast-conserving surgery (47 of 56 [84%] vs. 76 of 110 [69%], P < 0.04). CONCLUSIONS: A breast carcinoma screening and diagnostic program has been established in Harlem, a traditionally underserved area in New York City. Early, curable breast carcinomas were detected but outreach remains a challenge, particularly for the uninsured.
Breast conservation, where appropriate, offers effective treatment for breast cancer while preserving the breast. The increased use of mammographic screening has led to increased detection of small, curable breast cancers that are amenable to breast-conserving surgery. Mammography and other imaging modalities, such as sonography and MRI, assist in the determination of the appropriateness of breast conservation and in the differentiation of recurrence from benign sequelae of treatment.
OBJECTIVE: The purpose of this study was to determine the frequency of and factors associated with performing one therapeutic operation after percutaneous diagnosis of nonpalpable breast cancer. MATERIALS AND METHODS: Retrospective review was performed of records of 350 consecutive women who had therapeutic surgery after percutaneous imaging-guided core biopsy diagnosis of nonpalpable breast cancer. Records were reviewed to determine the frequency of performing one operation and associated factors. Statistical analysis was performed. RESULTS: One operation was performed in 283 (80.9%) of 350 women, including 106 (95.5%) of 111 women who had mastectomy and 177 (74.1%) of 239 women who had breast conserving surgery. At bivariate analysis, one operation was significantly more likely in women who had no underestimation (p < 0.001), mastectomy rather than breast conservation (p < 0.001), axillary dissection during the first operation (p < 0.001), percutaneous diagnosis of infiltrating carcinoma (p = 0.001), or mammographic mass (p = 0.006). At multivariate analysis, one operation was significantly more likely if underestimation was absent (odds ratio [OR] = 10.1, 95% confidence interval [CI] = 4.2-24.7) or if mastectomy was performed (OR = 8.7, 95% CI = 3.2-23.5); for women who had breast-conserving surgery, one operation was significantly more likely if underestimation was absent (OR = 11.4, 95% CI = 3.9-33.2) or if a mammographic mass was present (OR = 2.4, 95% CI = 1.3-4.6). CONCLUSION: One operation was performed in 80.9% of women with percutaneously proven nonpalpable breast cancer, including 74.1% of women who had breast-conserving surgery and 95.5% of women who had mastectomy. Among women who had breast conservation, one operation was significantly more likely if histologic underestimation was absent or if a mammographic mass was present.
OBJECTIVE: MR imaging of the breast can depict cancer that is occult on mammography and at physical examination. Our study was undertaken to determine the ease of performance and the outcome of MR imaging-guided needle localization and surgical excision of breast lesions. MATERIALS AND METHODS: Retrospective review revealed 101 consecutive breast lesions that had preoperative MR imaging-guided needle localization with commercially available equipment, including a 1.5-T magnet with a breast surface coil, a dedicated biopsy compression device, and MR imaging-compatible hookwires. Imaging studies and medical records were reviewed. RESULTS: Histologic findings in these 101 lesions were carcinoma in 31 (30.7%), high-risk lesions (atypical ductal hyperplasia or lobular carcinoma in situ) in nine (8.9%), and benign lesions in 61 (60.4%). Fifteen (48.4%) of 31 carcinomas were ductal carcinoma in situ, and 16 (51.6%) were infiltrating carcinoma (size range, 0.1-2.0 cm; median, 1.2 cm). Carcinoma was found in 16 (45.7%) of 35 lesions detected in women with synchronous cancer, 10 (32.3%) of 31 lesions detected on MR imaging for problem solving, and five (14.3%) of 35 lesions detected on MR screening. The time range to perform MR imaging-guided localization was 15-59 min (median time, 31 min). Complications encountered in three cases were retained wire fragments in two and breakage of the wire tip in one. CONCLUSION: MR imaging-guided needle localization can be performed quickly and safely with commercially available equipment. The positive predictive value of MR imaging-guided needle localization (30.7%) was comparable to that reported for mammographically guided needle localization and was highest in women with synchronous breast cancer.