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Breast Imaging |
1 From the Institute of Radiology, Ambulatory Care Center Steyr, Stadtplatz 30, A-4400 Steyr, Austria (O.G., G.H., M.M., C.G.); Department of Radiology, University of Vienna, Austria (T.H.H., M.H.F., R.M.); and Department of Radiology, University of California Medical Center, San Francisco (E.A.S.). Received November 17, 2003; revision requested February 5, 2004; revision received February 27; accepted April 16. Address correspondence to O.G. (e-mail: oswald.graf@utanet.at).
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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MATERIALS AND METHODS: No institutional review board approval or patient consent was required. This retrospective analysis, based on final imaging reports, included 152 patients (age range, 28–77 years; mean age, 48.3 years) with 157 palpable noncalcified solid masses that were classified as probably benign at initial mammography and US. Of 152 patients, 108 underwent follow-up with mammography and US (6-month intervals for 2 years, then 12-month intervals). The remaining 44 patients underwent surgical or needle biopsy after initial imaging. Lesions were analyzed at initial and follow-up examinations. Statistical analysis included Student t test and corresponding exact 95% confidence intervals.
RESULTS: In 108 patients who underwent follow-up only, 112 lesions were palpable. In 102 (94.4%) of 108 patients, masses remained stable during follow-up. Lesions were followed for at least 2 years (mean, 4.1 years; range, 2–7 years). In six (5.6%) patients, palpable lesions increased in size during follow-up; these lesions were benign at subsequent open biopsy. No breast carcinoma was diagnosed in the 44 patients with 45 palpable lesions who underwent biopsy after initial imaging. Of 157 lesions, no malignant tumors were observed (exact one-sided 95% confidence interval: 0%, 1.95%).
CONCLUSION: The data strongly suggest that palpable noncalcified solid breast masses with benign morphology at mammography and US can be managed similarly to nonpalpable BI-RADS category 3 lesions, with short-term follow-up (6-month intervals for 2 years). More data, based on a larger series, are required to determine whether this conclusion is correct.
© RSNA, 2004
Index terms: Breast, biopsy, 00.1261 • Breast neoplasms, diagnosis, 00.31 • Breast neoplasms, radiography, 00.11 • Breast neoplasms, US, 00.1298
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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When a nonpalpable mass with benign morphology is detected at screening mammography, the standard practice in many institutions is to follow the lesion if, after a full diagnostic imaging evaluation, it is judged to have a 2% or lower probability of cancer (called a probably benign lesion) (11–14). Follow-up of nonpalpable probably benign lesions (Breast Imaging Reporting and Data System [BI-RADS] category 3) has been reported in several studies (15–21). Furthermore, study results have shown that women with palpable abnormalities but negative results at mammography and ultrasonography (US) (BI-RADS category 1) are at very low risk for cancer but should be followed up at short-term intervals with clinical examination and imaging if biopsy is not performed (22–26).
However, if a circumscribed noncalcified solid mass is palpable, the recommended management is usually to obtain a tissue diagnosis, even when, according to morphologic criteria, the mass is probably benign (27–29). The rationale behind this recommendation is the absence of published data on the safety and efficacy of periodic imaging surveillance for palpable circumscribed noncalcified solid breast masses. In women who refuse to undergo surgical biopsy, the consensus is that diagnosis of a benign lesion requires the combination of a clinical examination, imaging, and nonsurgical tissue biopsy (the triple test) (30,31). However, some women refuse even needle biopsy if the clinical and morphologic criteria suggest that the palpable lesion is probably benign (22). Thus, the purpose of our study was to determine whether palpable noncalcified solid breast masses with benign morphology at both mammography and US can be managed safely in a way similar to nonpalpable probably benign lesions (BI-RADS category 3)—that is, with periodic imaging surveillance—and to determine whether biopsy can be averted for most of these lesions.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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For this type of retrospective analysis, approval by the institutional review board was not required at our institution; informed consent was not required, because patient anonymity was maintained.
There were 235 patients in whom the palpable abnormality met the morphologic criteria reported for probably benign masses, as assessed by the original interpreting radiologists. On the basis of the reports, 83 of 235 patients were subsequently excluded from analysis. Fourteen of these 83 were women younger than 25 years of age and were excluded because only US was performed in these cases, since 25 years of age was our lower limit for diagnostic mammography, and breast cancer is exceedingly rare in women this young. In 42 of 83 patients, the palpable mass was obscured by dense breast tissue on the mammogram and was characterized only on US images; these women were excluded because lesion characteristics could not be defined at mammography in these patients. Twenty-seven of the 83 patients did not undergo at least 2 years of follow-up and did not undergo biopsy; they were also excluded from study. Thus, the study included 152 women (age range, 28–77 years; mean, 48.3 years ± 9.7 [standard deviation]; median, 47 years). Twenty-five (16.4%) of the 152 women were younger than 40 years.
Imaging and Image Evaluation
In each patient, full clinical examination of both breasts was performed by the referring physicians. At clinical breast examination, 157 palpable lesions were detected in 152 patients by those physicians. The women were subsequently referred to our institution to undergo diagnostic mammography and US. Patient history (eg, breast cancer, previous biopsy) was recorded. At the time of imaging, the area of interest was determined from the written imaging request, the patient was asked to identify the lump for which she was referred, and we performed a brief physical examination of the area of concern.
Mammographic examinations were performed with a dedicated mammography unit (Senographe 800T; GE Medical Systems, Milwaukee, Wis). Film processing optimized for the mammographic unit was used (Kodak, Rochester, NY). Standard-view mammograms were obtained in the craniocaudal and mediolateral oblique projections. Five radiologists, each with 5–20 years of experience in mammography and US, were involved in interpreting the images. After viewing the standard images, additional views (mediolateral view, spot compression, magnification) were ordered by a radiologist in 124 (81.6%) of 152 patients. US was performed by the same radiologist, immediately after viewing the mammograms, by using 10–14-MHz linear array transducers (Ultramark 9 HDI, Advanced Technology Laboratories, Bothell, Wash; Powervision 6000, Toshiba, Tokyo, Japan). At US, the area of the palpable abnormality was examined. Subsequently, all mammograms and US images were evaluated by at least two experienced breast radiologists (O.G., T.H.H., G.H., R.M.) in consensus at the time of the initial examination, as well as at each follow-up examination.
The following mammographic and US criteria were used to define a probably benign lesion (15–22,32–34): On the mammogram, lesions were characterized as circumscribed noncalcified masses with a round, an oval, or a slightly lobular contour. Circumscribed masses with partially obscured (<25%) margins caused by adjacent isodense normal tissue were included as probably benign findings, but none of the margins of a given mass were judged to be either indistinct or spiculated (Fig 1a, 1b). Probably benign masses may have the same density as or may have higher or lower density than benign fibroglandular breast tissue, but these masses do not contain fat.
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The number, location, side, and size (greatest diameter at mammography and US) of the lesions detected at clinical breast examination, mammography, and US were recorded. A lesion-to-lesion correlation was performed at follow-up examinations.
Management of Palpable Probably Benign Lesions
The patient and the referring physician were informed that the palpable abnormality corresponded to a solid mass with morphologic characteristics that suggested that the lesion was probably benign. Patients were told that, on the basis of morphologic criteria alone, the probability of a carcinoma is less than 2% when such lesions are nonpalpable and that, at our institution, periodic imaging surveillance is standard practice for these lesions (11–21). Patients were told that the recommended management for a palpable mass with similar morphology is still to obtain a tissue diagnosis, since there are no published data that establish the safety and efficacy of periodic imaging surveillance. The decision to undergo biopsy (surgical or needle) or periodic imaging surveillance was made by the patient and the referring physician on the basis of their preferences and the analysis of all criteria, which included patient history and findings at clinical breast examination. Periodic imaging surveillance was offered as an alternative for patients who refused to undergo immediate biopsy.
Of the 152 patients, 108 (71%; age range, 28–77 years; mean age, 48.0 years ± 9.8) chose to undergo periodic imaging surveillance. Forty-four (29%; age range, 31–69 years; mean age, 48.7 years ± 9.7) of 152 patients chose to undergo surgical or needle biopsy after initial imaging. The age difference between these groups of patients was not statistically significant (P = .75).
In the 108 patients who chose to undergo imaging surveillance, a short-term follow-up study with US was scheduled for 3 months after the initial examination, and further follow-up studies with mammography and US were scheduled at 6-month intervals for the first 2 years. After the first 2 years, we performed follow-up at our regular recommended screening interval, which is 1 year. The duration of follow-up from the initial examination to the last follow-up examination was recorded for every patient. After each follow-up study with mammography and US, the patient underwent a follow-up clinical breast examination performed by the referring physician.
Lesion progression at follow-up studies (enlargement or changes from initial border characteristics) was considered an indication for surgical or needle biopsy (2).
In 32 of the 44 patients who chose to undergo biopsy after initial imaging, surgical biopsy was performed. In the remaining 12 patients, 14-gauge core needle biopsy was performed. Given the nonzero false-negative rate for needle biopsies, periodic imaging surveillance was continued after needle biopsy in those patients.
Statistical Analysis
Statistical analysis of lesion size was performed by using the Statview program (Abacus Concepts, Berkeley, Calif). In those patients who had more than one palpable mass, the size of each lesion was measured. Results are expressed as mean ± 1 standard deviation. P values were determined by using the unpaired Student t test, and P < .05 was considered to indicate statistical significance.
To demonstrate that the number of retrospectively included cases was sufficient to prove the study assumption (<2% of the masses were malignant), frequencies were described by using percentages, and corresponding exact 95% confidence intervals were calculated (Clopper-Pearson method). The clustering dependency of data for patients with more than one palpable lesion was taken into account, and the corresponding 95% confidence intervals were calculated from the total number of patients rather than from the total number of palpable lesions.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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At clinical breast examination, 112 lumps were palpable in the 108 patients who chose periodic imaging surveillance. These lumps corresponded to the lesions for which the patients were referred. In 105 of 108 patients, a solitary lesion was palpable. Two patients each had two palpable lumps (one in each breast), and one patient had three palpable lumps (two in the left breast and one in the right breast) at clinical breast examination.
The mean size of the lesions at initial imaging was 18.0 mm ± 6.1 (range, 7–38 mm).
In 102 (94.4%) of 108 patients, the palpable lesion did not increase in size, and the margins remained stable during the follow-up period (Fig 2). In six patients (5.6%), an increase in the diameter of the palpable mass and/or a change in the initial border characteristics was observed at follow-up, and surgical biopsy was subsequently performed. At histologic work-up, fibroadenoma was diagnosed in each of these cases. An increase in size and a change in the initial shape of the lesion was observed between the 6-month and 12-month follow-up examinations in one patient (Fig 3), and, in the remaining five patients, an increase in the lesion size was observed over a 12-month period. At the 3-month follow-up examination, which included only US, no substantial changes in lesion size or border characteristics were observed in any of the 108 patients.
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By combining the six patients in whom lesion size increased at follow-up and the patient with suspicious microcalcifications that were unrelated to the palpable mass, a benign histologic diagnosis after surgical biopsy was available in seven of the 108 patients in whom follow-up was initially performed.
In 101 of 108 patients, no histologic diagnosis is available, and the palpable lesions are still under surveillance. In all of these patients, follow-up was performed for at least 2 years (range, 2–7 years; mean, 4.1 years). At the time this report is being published, of 101 patients, 23 have been under surveillance for more than 2 years, 26 have been under surveillance for more than 3 years, and 52 have been under surveillance for 4 years or longer.
Of the patients in whom the palpable mass remained stable at imaging, none underwent biopsy because of findings at clinical follow-up breast examinations performed by the referring physician.
Biopsy
Of the 44 patients who chose to undergo biopsy, five had a history of breast carcinoma in the contralateral breast. One patient had a history of surgical biopsy with a diagnosis of fibroadenoma. Of 44 patients, 43 (97.7%) had a solitary lump at clinical breast examination. In one patient (2.3%), two lesions were palpable in the left breast. Thus, 45 lesions were palpable in 44 patients. These lumps corresponded to the lesions for which the patients were referred to our institution.
The mean size of the lesions in these patients was 17.7 mm ± 6.0 (range, 7–30 mm). The difference between the size of palpable lesions in this group and the size of palpable lesions in patients in whom follow-up was performed was not statistically significant (P = .16).
No malignancy was diagnosed at excisional biopsy or core needle biopsy in any of these 44 patients. Forty-three of 45 palpable lesions were fibroadenomas at histologic work-up. The other two histologic diagnoses were adenomyoepithelioma and benign fibrocystic changes.
In 12 of 44 patients in whom 14-gauge core needle biopsy was performed, fibroadenoma was diagnosed at histologic work-up. Imaging surveillance after biopsy did not show any enlargement or other suspicious changes in these lesions for at least 2 years.
When we combine the patients in whom follow-up was performed and those in whom biopsy was performed, we have observed no malignant tumors in 152 patients with 157 palpable lesions. The exact one-sided 95% confidence interval for this number of patients (0%, 1.95%) indicates that the likelihood of malignancy for these lesions is less than 2%.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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However, BI-RADS category 3 has traditionally been used only for nonpalpable lesions. This is because, to date, only nonpalpable lesions have been shown to have such a low likelihood of malignancy that periodic imaging surveillance is a safe and effective alternative to immediate tissue diagnosis. The results of this study strongly suggest that the palpable, circumscribed, noncalcified, solid breast mass also can be placed in BI-RADS category 3 when findings at mammography and US suggest that the mass is probably benign and that biopsy will be averted if the lesion remains stable at mammographic follow-up. Our results show that the probability of cancer is as low in palpable lesions as it is in nonpalpable BI-RADS category 3 lesions.
The rather small number of included patients should be considered a limitation of this study. However, the exact one-sided 95% confidence interval (0%, 1.95%) confirmed the adequacy of the number of patients to prove our study hypothesis, which is that palpable probably benign lesions have a less than 2% likelihood of malignancy. All surveillance studies, if large and of sufficiently long duration, will demonstrate a finite number of cancers from a population of circumscribed solid masses. More data from a larger series will provide the greater statistical power needed to establish the clinical acceptability of managing palpable noncalcified solid breast masses with periodic mammographic surveillance; this management would be similar to what has already been established for nonpalpable probably benign lesions.
Every benign or malignant lesion is nonpalpable at inception and for some subsequent time; it becomes palpable only when a specific size is reached. Whether a mass is palpable is determined by the size of the lesion, its location in the breast, and the size of the breast itself. We relied on morphologic characteristics at imaging when lesions were evaluated for the first time. Temporal stability at follow-up corroborated our assessment of a probably benign lesion. In our study, none of the noncalcified solid masses that were deemed probably benign proved to be malignant. In those patients in whom no tissue diagnosis was available, the chance that one of the palpable noncalcified solid masses would be malignant is extremely low, since all such lesions remained stable in size and border characteristics for a period of at least 2 years (range, 2–7 years; mean, 4.1 years). Excisional biopsy did not reveal a malignant lesion in those six patients in whom the lesion had increased in size at follow-up, in the patient in whom the lesion was excised at the time of surgery for newly developed microcalcifications that were unrelated to the palpable mass, or in those 44 patients in whom biopsy was performed instead of mammographic surveillance.
As with nonpalpable probably benign lesions, if follow-up of a palpable mass is considered as an alternative to immediate biopsy, it is essential that lesions strictly meet the reported and established criteria for benignity (35–37). We did not encounter a single palpable cancer that showed benign morphology at imaging in our patients. Our data support the hypothesis that cancers that have progressed to a palpable size and still show benign morphology at imaging are rare.
However, follow-up of a palpable mass with benign morphology may be more risky than follow-up of a nonpalpable lesion. On the chance that the lesion is malignant, the risk for metastasis is higher, since palpable masses are usually larger than nonpalpable lesions (38). We performed the first follow-up study with US 3 months after the initial examination. We believed that monitoring of palpable probably benign lesions very closely in the beginning of follow-up might help to demonstrate suspicious changes early. However, no significant changes were found at 3-month follow-up US.
While a minimum of 2 years of follow-up has been widely accepted as an indicator of benignity for nonpalpable masses, no standards have been established for palpable probably benign lesions. We chose surveillance intervals similar to those recommended for nonpalpable lesions. After following a lesion at 6-month intervals for the first 2 years, we lengthened our interval to 12 months. We believed that a lesion that has progressed to a palpable size and has remained stable for at least 2 years is very likely benign. Although, to our knowledge, there were no published data on this issue prior to our study, we assumed that if a benign-appearing palpable mass (usually larger than a nonpalpable mass) is actually malignant, it should demonstrate malignant changes at imaging no later in its course than would a nonpalpable mass.
Since a palpable benign lesion could conceivably obscure an adjacent developing cancer at clinical breast examination, we believed that, in addition to demonstrating stability at mammography, surveillance of internal features of the lesion and observation of its surroundings with US might help to reduce the risk of a false-negative assessment. After initial characterization of a mass at mammography and US, and given the established validity of mammographic surveillance, follow-up with mammography alone would be sufficient to demonstrate stability. However, additional surveillance with US bolstered our level of confidence in the management of the probably benign mass.
As in nonpalpable BI-RADS category 3 lesions, it is essential that the patient and the referring physician are aware of the fact that the lesion may be malignant despite the benign morphology. We told our patients that less than 2% of nonpalpable circumscribed masses prove to be malignant at biopsy and that standard practice is usually to follow the lesion (11–14). However, for palpable lesions with similar morphology, the effectiveness and safety of periodic imaging surveillance had not, to our knowledge, been documented prior to our study. The refusal to undergo biopsy and decision to undergo imaging surveillance should be made only if the potential shortcomings of imaging are completely understood. We recommend biopsy in those women for whom the perceived level of risk is unacceptable. On the condition that findings of a full clinical breast examination performed by the referring physician do not require immediate tissue diagnosis, we now perform imaging surveillance for those women who reject surgical or needle biopsy.
The final decision for follow-up or biopsy was made by the patient and the referring physician and was based on analysis of the imaging report, the full clinical breast examination performed by the referring physician, and the patient history (also assessed by the referring physician). Although we did not consider patient history when making our imaging assessments, it is interesting to note that a history of surgical biopsy that yielded a benign result or a history of breast cancer could influence the patient’s decision for biopsy versus follow-up. Fifteen (13.9%) of the 108 patients who chose follow-up had undergone a previous surgical biopsy with benign results, whereas only one (2.3%) of the 44 patients who chose biopsy had undergone a previous surgical biopsy with benign results. On the other hand, five (11.4%) of the 44 patients in the biopsy group had a history of breast cancer, but no patient in the follow-up group had such a history.
In conclusion, the use of periodic mammographic surveillance for nonpalpable probably benign masses is now widely accepted. Our data suggest that palpable masses that display the same probably benign features at mammography and US can be managed in a similar way and that biopsy will be averted if such lesions remain stable at follow-up. More data, based on a larger series, will help to establish the clinical acceptability of periodic surveillance for palpable probably benign masses.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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Authors stated no financial relationship to disclose.
Author contributions: Guarantor of integrity of entire study, O.G.; study concepts, O.G., T.H.H.; study design, O.G., T.H.H., E.A.S.; literature research, O.G., M.H.F., G.H., M.M.; clinical studies, O.G., T.H.H., G.H., R.M.; data acquisition, O.G., G.H., M.M., C.G., R.M.; data analysis/interpretation, O.G., T.H.H., G.H., M.M., R.M.; statistical analysis, C.G.; manuscript preparation, O.G., M.H.F., G.H.; manuscript editing, O.G., M.H.F., C.G.; manuscript definition of intellectual content, revision/review, and final version approval, O.G., T.H.H., E.A.S.
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REFERENCES |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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