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      Independent predictors of breast malignancy in screen-detected microcalcifications: biopsy results in 2545 cases

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          Abstract

          Background:

          Mammographic microcalcifications are associated with many benign lesions, ductal carcinoma in situ (DCIS) and invasive cancer. Careful assessment criteria are required to minimise benign biopsies while optimising cancer diagnosis. We wished to evaluate the assessment outcomes of microcalcifications biopsied in the setting of population-based breast cancer screening.

          Methods:

          Between January 1992 and December 2007, cases biopsied in which microcalcifications were the only imaging abnormality were included. Patient demographics, imaging features and final histology were subjected to statistical analysis to determine independent predictors of malignancy.

          Results:

          In all, 2545 lesions, with a mean diameter of 21.8 mm (s.d. 23.8 mm) and observed in patients with a mean age of 57.7 years (s.d. 8.4 years), were included. Using the grading system adopted by the RANZCR, the grade was 3 in 47.7% 4 in 28.3% and 5 in 24.0%. After assessment, 1220 lesions (47.9%) were malignant (809 DCIS only, 411 DCIS with invasive cancer) and 1325 (52.1%) were non-malignant, including 122 (4.8%) premalignant lesions (lobular carcinoma in situ, atypical lobular hyperplasia and atypical ductal hyperplasia). Only 30.9% of the DCIS was of low grade.

          Mammographic extent of microcalcifications >15 mm, imaging grade, their pattern of distribution, presence of a palpable mass and detection after the first screening episode showed significant univariate associations with malignancy. On multivariate modeling imaging grade, mammographic extent of microcalcifications >15 mm, palpable mass and screening episode were retained as independent predictors of malignancy. Radiological grade had the largest effect with lesions of grade 4 and 5 being 2.2 and 3.3 times more likely to be malignant, respectively, than grade 3 lesions.

          Conclusion:

          The radiological grading scheme used throughout Australia and parts of Europe is validated as a useful system of stratifying microcalcifications into groups with significantly different risks of malignancy. Biopsy assessment of appropriately selected microcalcifications is an effective method of detecting invasive breast cancer and DCIS, particularly of non-low-grade subtypes.

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          Molecular evolution of breast cancer.

          Peter T Simpson, Jorge S. Reis-Filho, Theodora Gale … (2005)
          Molecular analysis of invasive breast cancer and its precursors has furthered our understanding of breast cancer progression. In the past few years, new multi-step pathways of breast cancer progression have been delineated through genotypic-phenotypic correlations. Nuclear grade, more than any other pathological feature, is strongly associated with the number and pattern of molecular genetic abnormalities in breast cancer cells. Thus, there are two distinct major pathways to the evolution of low- and high-grade invasive carcinomas: whilst the former consistently show oestrogen receptor (ER) and progesterone receptor (PgR) positivity and 16q loss, the latter are usually ER/PgR-negative and show Her-2 overexpression/amplification and complex karyotypes. The boundaries between the evolutionary pathways of well-differentiated/low-grade ductal and lobular carcinomas have been blurred, with changes in E-cadherin expression being one of the few distinguishing features between the two. In addition, lesions long thought to be precursors of breast carcinomas, such as hyperplasia of usual type, are currently considered mere risk indicators, whilst columnar cell lesions are now implicated as non-obligate precursors of atypical ductal hyperplasia (ADH) and well-differentiated ductal carcinoma in situ (DCIS). However, only through the combination of comprehensive morphological analysis and cutting-edge molecular tools can this knowledge be translated into clinical practice and patient management.
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            BI-RADS lexicon for US and mammography: interobserver variability and positive predictive value.

            B Schepps, M B Mainiero, Elizabeth Lazarus … (2006)
            To retrospectively evaluate interobserver variability between breast radiologists by using terminology of the fourth edition of the Breast Imaging Reporting and Data System (BI-RADS) to categorize lesions on mammograms and sonograms and to retrospectively determine the positive predictive value (PPV) of BI-RADS categories 4a, 4b, and 4c. Institutional review board approval was obtained; informed consent was not required. This study was HIPAA compliant. Ninety-four consecutive lesions in 91 women who underwent image-guided biopsy comprised 59 masses, 32 calcifications, and three masses with calcification. Five radiologists retrospectively reviewed these lesions. Each observer described each lesion with BI-RADS terminology and assigned a final BI-RADS category. Interobserver variability was assessed with the Cohen kappa statistic. A pathologic diagnosis was available for all 94 lesions; 30 (32%) were malignant and 64 (68%) were benign. Pathologic analysis of benign lesions was performed on tissue obtained with image-guided core-needle biopsy. In cases referred for excisional biopsy after needle biopsy because of atypia or discordance, final surgical pathologic analysis was used for correlation with imaging findings. PPV for category 4 or 5 lesions was determined for all readers combined. For ultrasonographic (US) descriptors, substantial agreement was obtained for lesion orientation, shape, and boundary (kappa = 0.61, 0.66, and 0.69, respectively). Moderate agreement was obtained for lesion margin and posterior acoustic features (kappa = 0.40 for both). Fair agreement was obtained for lesion echo pattern (kappa = 0.29). For mammographic descriptors, moderate agreement was obtained for mass shape, mass margin, and calcification distribution (kappa = 0.48, 0.48, and 0.50, respectively). Fair agreement was obtained for calcification description (kappa = 0.32). Slight agreement was obtained for mass density (kappa = 0.18). Fair agreement was obtained for final assessment category (kappa = 0.28). PPVs of BI-RADS category 4 and 5 assignments were as follows: category 4a, six (6%) of 102; category 4b, 17 (15%) of 110; category 4c, 48 (53%) of 91; and category 5, 71 (91%) of 78. Interobserver agreement with the new BI-RADS terminology is good and validates the US lexicon. Subcategories 4a, 4b, and 4c are useful in predicting the likelihood of malignancy. (c) RSNA, 2006.
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              Detection of ductal carcinoma in situ in women undergoing screening mammography.

              Virginia L. Ernster, Rachel Ballard-Barbash, William Barlow … (2002)
              With the large number of women having mammography-an estimated 28.4 million U.S. women aged 40 years and older in 1998-the percentage of cancers detected as ductal carcinoma in situ (DCIS), which has an uncertain prognosis, has increased. We pooled data from seven regional mammography registries to determine the percentage of mammographically detected cancers that are DCIS and the rate of DCIS per 1000 mammograms. We analyzed data on 653 833 mammograms from 540 738 women between 40 and 84 years of age who underwent screening mammography at facilities participating in the National Cancer Institute's Breast Cancer Surveillance Consortium (BCSC) throughout 1996 and 1997. Mammography results were linked to population-based cancer and pathology registries. We calculated the percentage of screen-detected breast cancers that were DCIS, the rate of screen-detected DCIS per 1000 mammograms by age and by previous mammography status, and the sensitivity of screening mammography. Statistical tests were two-sided. A total of 3266 cases of breast cancer were identified, 591 DCIS and 2675 invasive breast cancer. The percentage of screen-detected breast cancers that were DCIS decreased with age (from 28.2% [95% confidence interval (CI) = 23.9% to 32.5%] for women aged 40-49 years to 16.0% [95% CI = 13.3% to 18.7%] for women aged 70-84 years). However, the rate of screen-detected DCIS cases per 1000 mammograms increased with age (from 0.56 [95% CI = 0.41 to 0.70] for women aged 40-49 years to 1.07 [95% CI = 0.87 to 1.27] for women aged 70-84 years). Sensitivity of screening mammography in all age groups combined was higher for detecting DCIS (86.0% [95% CI = 83.2% to 88.8%]) than it was for detecting invasive breast cancer (75.1% [95% CI = 73.5% to 76.8%]). Overall, approximately 1 in every 1300 screening mammography examinations leads to a diagnosis of DCIS. Given uncertainty about the natural history of DCIS, the clinical significance of screen-detected DCIS needs further investigation.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Br J Cancer
                Title: British Journal of Cancer
                Publisher: Nature Publishing Group
                ISSN (Print): 0007-0920
                ISSN (Electronic): 1532-1827
                Publication date (Print): 22 November 2011
                Publication date (Electronic): 03 November 2011
                Volume: 105
                Issue: 11
                Pages: 1669-1675
                Affiliations
                [1 ]BreastScreen SA and SA Pathology , 1 Goodwood Road, Wayville, South Australia 5034, Australia
                [2 ]Data Management and Analysis Centre, Discipline of Public Health, University of Adelaide , Adelaide, Australia
                Author notes
                Article
                Publisher Item ID: bjc2011466
                DOI: 10.1038/bjc.2011.466
                PMC ID: 3242612
                PubMed ID: 22052156
                SO-VID: 66a2642a-70db-4bd5-bd25-e2176307e110
                Copyright © Copyright © 2011 Cancer Research UK
                History
                Date received : 12 July 2011
                Date revision received : 18 September 2011
                Date accepted : 28 September 2011
                Categories
                Subject: Clinical Study

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: breast cancer,screening,mammography,microcalcifications
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: breast cancer, screening, mammography, microcalcifications

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