New Palpable Breast Lump With Recent Negative Mammogram: Is Repeat Mammography Necessary?

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1 Women s Imaging Original Research Leung et al. Repeat Mammogram for Breast Lump Found After Negative Mammogram Women s Imaging Original Research Stephanie E. Leung 1 Ilanit Ben-Nachum Anat Kornecki Leung SE, Ben-Nachum I, Kornecki A Keywords: mammography, palpable breast lump, ultrasound DOI: /AJR Received April 7, 2015; accepted after revision February 6, Based on a presentation at the Radiological Society of North America 2012 annual meeting, Chicago, IL. 1 All authors: Department of Diagnostic Imaging, St. Joseph s Health Care, Western University, 268 Grosvenor St, London, ON N6A 4V2, Canada. Address correspondence to A. Kornecki (Anat.Kornecki@sjhc.london.on.ca). This article is available for credit. AJR 2016; 207: X/16/ American Roentgen Ray Society New Palpable Breast Lump With Recent Negative Mammogram: Is Repeat Mammography Necessary? OBJECTIVE. The purpose of this article is to determine the utility of repeat mammography, compared with targeted ultrasound and previous mammogram, in the assessment of an interval palpable breast lump found within 1 year after a negative mammogram study. MATERIALS AND METHODS. Women who were examined for a new palpable lump with mammography and targeted ultrasound between January 2005 and December 2012, who also had a negative mammogram within the previous 6 12 months, were included. The following data were collected: age, mammographic findings, change from previous mammogram, ultrasound findings, BI-RADS category, and biopsy results. RESULTS. A total of 618 palpable lumps in 612 women (mean [± SD] age, 55.9 ± 11.2 years) were included in this study. In 314 of 618 cases (50.8%), a sonographic finding or mammographic change, or both was detected in the region of the palpable lump. Ultrasound detected a finding in 311 cases (50.3%), whereas repeat mammography detected a change in only 80 (12.9%) cases (p < 0.001). Of the 314 cases with imaging findings, 234 findings (74.5%) were detected by ultrasound alone. Repeat mammography identified a more prominent focal asymmetry in the palpable region in three cases with no sonographic correlate; none had malignancy. Eighty lesions were biopsied, and 48 (60.0%) of them were positive for malignancy. The repeat mammogram findings were unchanged for 10 of these lesions. CONCLUSION. Interval palpable breast lumps should be evaluated with targeted ultrasound. Mammography does not appear to add value beyond sonography performed by trained ultrasound technologists and should not be routinely performed. S everal guidelines exist for the diagnostic workup of a palpable breast lump. The American College of Radiology s Appropriateness Criteria recommend primary investigation with diagnostic mammography in women over the age of 40 years and either ultrasound or diagnostic mammography in patients aged years [1]. The high accuracy of combined mammographic and sonographic workup of a palpable lump has been shown in previous studies, with the negative predictive value for malignancy ranging between 99.8% and 100% [2 5]. Another study suggested that the likelihood of breast cancer in the setting of a negative mammographic and sonographic workup was approximately % [6]. A woman may present with a new palpable lump after having had a recent negative mammogram (i.e., negative for malignancy, defined as BI-RADS category 1, 2, or 3). In reviewing the literature, we did not find any guidelines regarding the assessment of the interval palpable lump. We defined an interval lump as a lump discovered within 1 year from the patient s last negative mammogram. At our center, like most centers in Canada, interval symptoms within 6 months from the patient s last negative mammogram are initially assessed with an ultrasound of the affected breast. Interval symptoms from 6 to 12 months from the last mammogram are assessed with ipsilateral mammography and ultrasound of the affected breast. Symptoms more than 12 months from the last mammogram are assessed with bilateral mammography and ipsilateral ultrasound. Our observation was that the findings of the repeat mammogram are often stable when compared with those from a recent previous mammogram. Our purpose was to determine the additive role of repeat mammography, compared with targeted ultrasound and previous mammogram, in the assessment of a new palpable breast lump found within 1 year after a negative mammogram 200 AJR:207, July 2016

2 Repeat Mammogram for Breast Lump Found After Negative Mammogram TABLE 1: Mammographic Findings of Interval Palpable Breast Lumps Indicating Change From Previous Mammogram and Biopsy Results Mammographic Finding Change From Previous Mammogram a No Change study (interval palpable breast lump). Our hypothesis is that repeat mammography does not add useful information to the ultrasound findings or the prior mammographic findings or improve patient management. Materials and Methods This study was approved by our institution s Health Sciences Research Ethics Board and the Clinical Research Impact Committee. Informed consent from patients was not required for this retrospective review. Study Population All diagnostic mammograms and breast ultrasound examinations performed at our institution between January 1, 2005, and December 31, 2012, were retrospectively identified by a search of our electronic database. Women referred for a new palpable breast lump (self-palpated or physician palpated) and examined with both mammography and targeted ultrasound, who also had a previous negative mammogram (BI-RADS category 1, 2, or 3) within the previous 6 12 months, were included. Patients who did not have an ultrasound and mammogram investigation within 90 days of each other were excluded. In total, 694 women referred for an interval palpable lump with a negative mammogram within the previous 6 12 months were identified. Eighty patients who did not have a mammogram and ultrasound evaluation within 90 days of one another and two patients with analog mammogram were excluded from the study. Six of the women presented with new bilateral palpable breast lumps. This yielded 618 palpable lumps in 612 women (mean [± SD] age, 55.9 ± 11.2 years) and constitutes our study population. Biopsy Result b More Prominent New Finding Malignant Benign Negative Mass Asymmetry Focal asymmetry Architectural distortion Other Total Note Data are number of lesions. There were 618 palpable lumps in 612 women. a Change in the region of the palpable lump compared with most recent previous mammogram obtained within the previous 6 12 months. b All lesions biopsied were visible under ultrasound, except for one focal asymmetry, which was biopsied under stereotactic guidance. Eighty lesions were biopsied. Imaging Mammograms at our institution were performed on dedicated mammography units (Senographe 2000D, DS, and Essential, all from GE Healthcare). The views obtained consisted of the standard mediolateral oblique and craniocaudad views of the side of concern with additional views obtained if required because of the patient s body habitus or location of the palpable abnormality or if requested by the reading radiologist. A skin marker was applied at the palpable site in patients with a self-detected lump. Forty-one women had bilateral mammography because they presented very close to 1 year from their last screening mammogram, to avoid the need for returning for a mammogram of the contralateral side. Targeted breast ultrasound of the region of palpable concern was performed by trained breast ultrasound technologists with over 1 year of experience using various systems (Logiq 7 or Logiq 9, both from GE Healthcare Systems; ATL HDI 5000, Philips Healthcare; Aplio XG, Toshiba). All imaging was reviewed by a breast radiologist at the time of the study. The median time between the mammogram and ultrasound was 0 days (interquartile range, 0 8 days). In 425 of 618 (68.7%) cases, both studies were performed on the same day and were supervised by the same radiologist; only patients with normal mammogram findings and fatty replaced breasts were deferred. Core biopsies were performed with a 14- or 18-gauge automated biopsy device, with at least three tissue samples routinely obtained. Data Collection Imaging reports were reviewed by the authors, and the following data were collected from the report: mammogram and targeted ultrasound findings using descriptors from the American College of Radiology BI-RADS lexicon [7], change from previous mammogram in the region of palpable abnormality, BI-RADS category, and biopsy results if applicable. The BI-RADS category assigned prospectively at the time of imaging was used. The prospective interpretations were initially made by one of three staff radiologists who had experience in reading breast imaging of at least 2 years. A positive (abnormal) assessment was defined as BI-RADS category 4 or 5 with biopsy recommended and performed. Additional data were collected from the electronic medical record for breast cancer cases, including tumor size at imaging (for invasive cancers) and tumor receptor status. The medical records of 86.5% (488/564) of the patients who were included and were not diagnosed with cancer were available and reviewed for a minimum follow-up of 24 months. Statistical Analysis Statistical analysis was completed using Sigma- Stat (version 2.03, Systat Software). Normally distributed continuous variables were reported using means and SDs, and group differences were compared with the independent samples t test. Nonnormally distributed continuous variables were reported using medians and interquartile ranges, and group differences were compared with the Mann- Whitney U test. The chi-square test and Fisher exact test were used to compare differences in proportions for categoric variables where appropriate. A p < 0.05 was considered statistically significant. Results The mammographic findings in 612 women presenting with 618 interval palpable breast lumps are summarized in Table 1. The repeat mammogram showed no change in the region of the palpable lump in 538 of 618 cases (87.0%). Of the 80 cases with a mammographic change, 38 findings were described as being previously present but now more prominent, and 42 were new findings. Most of the mammographic changes were due to the presence of a new or more conspicuous mass (45/80; 56.3%). The targeted ultrasound findings are summarized in Table 2. Ultrasound revealed normal breast parenchyma in 307 cases and identified a finding to account for the palpable lump in 311 of the 618 cases (50.3%). Among the ultrasound examinations with findings, 232 of 311 (74.6%) of the findings were benign or likely benign in nature (< 2% chance of malignancy), being assigned a BI-RADS category 2 or 3. These included solid lesions, such as benign lymph nodes, fibroadenomata, lipomas, sebaceous cysts, AJR:207, July

3 Leung et al. TABLE 2: Targeted Ultrasound Findings and BI-RADS Categorization With Biopsy Results Ultrasound Finding BI-RADS Category 1, 2, or 3 simple and minimally complicated cysts, or benign other lesions, such as fat necrosis, hematoma, abscess, and postsurgical changes. A comparison of targeted ultrasound findings and mammographic change is summarized in Figure 1. In total, 314 of 618 cases showed a change in the mammogram in the region of the palpable lump or a targeted ultrasound finding, or both: 77 had a change in their mammogram plus an ultrasound finding, 234 had an ultrasound finding without a mammographic change, and three had a mammographic change without an ultrasound correlate. Ultrasound identified statistically significantly more findings in the region of the palpable lump compared with change identified on repeat mammogram (311/618 vs 80/618; p < 0.001). Repeat mammography identified a more prominent focal asymmetry in the palpable region in three cases with no correlated sonographic abnormality. Two of these cases remained mammographically stable for over 5 years, and, in one case, benign breast parenchyma was found on stereotactic biopsy. The rate of abnormal findings, as defined in the Materials and Methods section, was 12.9% (80/618). In total, 80 lesions categorized as BI-RADS category 4 or 5 were biopsied (Tables 1 and 2). All were visible under ultrasound and were biopsied under ultrasound guidance, with the exception of one focal asymmetry, which was sonographically occult and was biopsied using stereotactic guidance. Forty-eight of the biopsied lesions were pathology-proven malignancy (Table 3). In 32 biopsies, the pathology results were benign, including the one focal asymmetry that was sonographically occult. All 48 malignancies were detected with ultrasound. In 38 of the malignancies, repeat mammography showed a change, with ultrasound showing a BI-RADS category 4 or 5 solid mass in BI-RADS Category 4 or 5 Malignant Biopsy Benign Biopsy Negative a 307 Solid mass Simple or complicated cyst Complex cyst Other Total Note Data are number of lesions. There were 618 palpable lumps in 612 women. a All lesions were biopsied under ultrasound guidance except for one sonographically occult focal asymmetry that was biopsied under stereotactic guidance. Eighty lesions were biopsied. Total 37 cases and an ill-defined hypoechoic region in one case. In 10 of the malignancies where ultrasound detected a solid lesion [8] or echo distortion [1] categorized as BI-RADS category 4 or 5, the repeat mammogram was unchanged. In four of the 10 cases, the mass was mammographically occult on both the previous and current mammogram; thus, four of 48 (8.3%) palpable malignancies were mammographically occult. There were 45 invasive breast malignancies, of which 36 showed mammographic change and nine remained stable. The median size of the invasive breast lesions that Ultrasound finding showed a mammographic change was 2.8 cm (range, cm) compared with 1.6 cm (range, cm) for those with a stable mammogram (p = 0.005). Thirteen of 36 (36.1%) of the lesions that presented with mammographic change were triple negative (tumor cells do not express the genes for estrogen receptor, progesterone receptor, and ErbB-2, also known as HER2/neu) compared with none among the nine lesions with stable mammography (p = 0.04). A minimum of 24 months of follow-up was available for 488 of 564 (86.5%) patients without cancer. Among these patients, one patient received a diagnosis of lobular invasive malignancy in the palpable region 3 months after the examinations on the basis of a biopsy that was performed by the surgeon. One patient developed a 1.3-cm invasive malignancy within the same region 29 months after presenting as new palpable lump and new imaging finding. Four hundred eighty-eight patients remained free of breast cancer within the palpable region for at least 24 months. Discussion Patients who have had a recent mammogram may present with a new breast symptom, commonly a palpable lump. In this study we found that, for women presenting 311/618 80/618 Mammographic change Fig. 1 Ultrasound findings versus mammographic changes. Data are number of lesions. There were 618 palpable lumps in 612 women. Ultrasound finding or mammographic change or both was noted in 314 of 618 cases (p < 0.001, chi-square test). (Illustration by Kornecki A) TABLE 3: Pathologic Profiles of the Biopsied Malignancies With Specifics About Mammographic Change Pathologic Profile Total Changed Mammogram Stable Mammogram Invasive ductal carcinoma Grade Grade Grade Invasive lobular carcinoma Ductal carcinoma in situ Malignant fibrous histiocytoma Melanoma Total Note Data are number of lesions. 202 AJR:207, July 2016

4 Repeat Mammogram for Breast Lump Found After Negative Mammogram with an interval palpable lump, the repeat mammogram is most often reported stable (87.1%) in comparison with a negative mammogram obtained within the previous 12 months. This is supported by the results of a previous study [9] showing that the positive predictive value, sensitivity, and odds ratio of calling a diagnostic mammogram abnormal show a statistically significant decrease when there has been a previous mammogram, although specificity does increase. Targeted ultrasound is an effective tool in the investigation of a palpable lump, identifying findings in 50.3% of cases in our study. The most common finding in the region of the palpable lump was categorized as benign or likely benign (74.6%), mostly cysts (129/618; 20.8%). Previous studies have shown the high sensitivity of ultrasound at detecting palpable lumps [8, 10]. In our study, targeted ultrasound yielded statistically significantly more diagnostic information than did repeat mammography (p < 0.001). This agrees with other studies, which found that a significant number of palpable abnormalities that were detected by ultrasound were mammographically occult [4, 11]. One recent study showed that both the sensitivity and negative predictive value of ultrasound are higher than those for mammography in patients aged years (95.7% vs 60.9% and 99.9% vs 99.2%, respectively) [12]. Although a negative ultrasound alone may be sufficient reassurance for the absence of malignancy, a larger prospective study should be done to confirm this. Eighty BI-RADS category 4 or 5 lesions were identified by ultrasound or mammography. Our abnormal interpretation rate for the combined imaging modalities of 12.9% is slightly higher than the benchmarks reported by Sickles et al. [13] of 10.5% for diagnostic mammography alone in the investigation of palpable lumps. All the lesions in our series that were pathology-proven malignancies were detected by ultrasound. In 10 of the malignancies for which ultrasound detected a suspicious finding categorized as BI-RADS category 4 or 5, the repeat mammogram was unchanged, and 8.3% of the palpable malignancies were mammographically occult. This is similar to previous studies showing that % of palpable malignant lesions are mammographically occult [4, 14, 15]. A study by Zonderland et al. [16] has shown that, in 19 of the 545 patients who underwent ultrasound for palpable masses, ultrasound showed findings that increased suspicion of malignancy where the mammogram was described as probably benign. In our study, in only three cases did repeat mammography show a change in the palpable region with no correlated sonographic abnormality. None of these patients had a malignancy. These findings are important because decreasing the use of a standard mammogram in the setting of interval breast symptoms will result in a decrease in radiation exposure to patients and a reduction in costs. We do not dispute the utility of mammography and acknowledge that noting a change in the mammogram compared with a previous mammogram may lead to a higher cancer detection rate in the diagnostic setting [17], but less so compared with ultrasound in the setting of interval lumps. Furthermore, performing a unilateral mammogram in such patients could lead to confusion and compromise the contralateral breast screening interval. In our small series of malignancies, those that showed a mammographic change tended to be larger and were more likely to have triple-negative receptor status. Previous studies have shown that palpable interval malignancies tend to be more aggressive [18, 19]. Although they are likely to show a change on mammography, they are also unlikely to be missed on ultrasound. In contrast, interval malignancies that are less aggressive will not grow as rapidly and it will be more difficult to appreciate an interval change on mammography. This suggests that it would be reasonable to use the previous recent mammogram in the initial diagnostic workup. Subtle findings may be better appreciated when reviewing the mammogram with specific attention paid to the area of palpable concern. It should be noted that any suspicious mass detected by palpation should be biopsied irrespective of imaging findings, and surgical consultation is recommended if symptoms persist. Our study suffered several limitations. First, this is a retrospective study. Second, tomosynthesis, which was not performed at the time of the study, might have affected the results and conclusion. 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