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Showing content from https://pubmed.ncbi.nlm.nih.gov/29426360/ below:

Not all false positive diagnoses are equal: On the prognostic implications of false-positive diagnoses made in breast MRI versus in mammography / digital tomosynthesis screening

doi: 10.1186/s13058-018-0937-7. Not all false positive diagnoses are equal: On the prognostic implications of false-positive diagnoses made in breast MRI versus in mammography / digital tomosynthesis screening

Affiliations

¹ Department of Diagnostic and Interventional Radiology, Hospital of the University of Aachen, RWTH, Pauwelsstrasse 30, 52074, Aachen, Germany. ckuhl@ukaachen.de.
² Department of Diagnostic and Interventional Radiology, Hospital of the University of Aachen, RWTH, Pauwelsstrasse 30, 52074, Aachen, Germany.
³ Department of Pathology, Hospital of the University of Aachen, RWTH, Aachen, Germany.

PMID: 29426360
PMCID: PMC5807753
DOI: 10.1186/s13058-018-0937-7

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Not all false positive diagnoses are equal: On the prognostic implications of false-positive diagnoses made in breast MRI versus in mammography / digital tomosynthesis screening

Christiane K Kuhl et al. Breast Cancer Res. 2018.

doi: 10.1186/s13058-018-0937-7. Affiliations

¹ Department of Diagnostic and Interventional Radiology, Hospital of the University of Aachen, RWTH, Pauwelsstrasse 30, 52074, Aachen, Germany. ckuhl@ukaachen.de.
² Department of Diagnostic and Interventional Radiology, Hospital of the University of Aachen, RWTH, Pauwelsstrasse 30, 52074, Aachen, Germany.
³ Department of Pathology, Hospital of the University of Aachen, RWTH, Aachen, Germany.

PMID: 29426360
PMCID: PMC5807753
DOI: 10.1186/s13058-018-0937-7

Item in Clipboard

Abstract

Background: Breast magnetic resonance imaging (MRI) has been reported to frequently result in false-positive diagnoses, limiting its positive predictive value (PPV). However, for PPV calculation, all nonmalignant tissue changes are equally considered false-positive, although the respective prognostic importance, and thus patient management implications, of different pathologies may well differ. We investigated the pathology of false-positive diagnoses made by MRI compared with radiographic (digital mammography/tomosynthesis [DM/DBT]) screening.

Methods: We conducted an institutional review board-approved prospective analysis of 710 consecutive asymptomatic women at average risk for breast cancer who underwent vacuum biopsy with or without surgical biopsy for screen-detected DM/DBT (n = 344) or MRI (n = 366) findings. We compared the frequency of false-positive biopsies (given by PPV3), as well as the types of nonmalignant tissue changes that caused the respective false-positive biopsies. In an order of increasing relative risk of subsequent breast cancer, pathologies of false-positive biopsies were categorized as nonproliferative, simple proliferative, complex proliferative, or atypical proliferative (including lobular carcinoma in situ/lobular intraepithelial neoplasia). The Mann-Whitney U test was used to compare distributions.

Results: Histology yielded nonmalignant tissue in 202 of 366 biopsies done for positive MRI studies and 195 of 344 biopsies for positive DM/DBT studies, respectively, yielding a similar PPV3 percentages of 44.8% (164 of 202) and 43.3% (149 of 202) for both methods. However, the distribution of tissue types that caused false-positive diagnoses differed significantly (p < 0.0001). On the basis of MRI, high-risk atypical proliferative changes (40.1%; 81 of 202) were most common, followed by complex proliferative changes (23.8%; 48 of 202). In DM/DBT, low-risk, nonproliferative changes were the dominant reason for false-positive diagnoses (49.7%; 97 of 195), followed by simple proliferative changes (25.2%; 51 of 195). Low-risk nonproliferative changes resulted in false-positive diagnoses based on MRI as infrequently as did high-risk atypical proliferative changes based on DM/DBT (18.8% [38 of 202] vs. 18.0% [35 of 195]). The likelihood of a false-positive diagnosis including atypias was twice as high in women undergoing biopsy for MRI findings (81 of 202; 40%) as for those with DM/DBT findings (35 of 195; 18%).

Conclusions: The prognostic importance, and thus the clinical implications, of false-positive diagnoses made on the basis of breast MRI vs. radiographic screening differed significantly, with a reversed prevalence of high- and low-risk lesions. This should be taken into account when discussing the rate of false-positive diagnoses (i.e., PPV levels of MRI vs. radiographic screening). Current benchmarks that rate the utility of breast cancer screening programs (i.e., cancer detection rates and PPVs) do not reflect these substantial biological differences and the different prognostic implications.

Keywords: Atypia; Biopsy; Breast MRI; Digital breast tomosynthesis; Digital mammography; False-positive diagnoses; Magnetic resonance imaging; Positive predictive value (PPV).

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Conflict of interest statement Ethics approval and consent to participate

All participants signed informed consent forms. The study was approved by the ethics committee of the University of Aachen, RWTH (OHRP IRB no. 00007576) under the vote EK 20517.

Consent for publication

All authors approved the manuscript and consented to its publication. All participants signed informed consent forms for publication.

Competing interests

The authors declare that they have no competing interests.

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Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures
Fig. 1

False-positive digital mammography (DM)/digital breast…

Fig. 1

False-positive digital mammography (DM)/digital breast tomosynthesis (DBT) screening diagnosis. Screening DBT ( a…

Fig. 1

False-positive digital mammography (DM)/digital breast tomosynthesis (DBT) screening diagnosis. Screening DBT (a) with reconstructed 2D DM (C-view) (b) and higher-magnification view (c) in a 55-year-old woman at average risk revealed clustered calcifications in the left upper outer quadrant. DBT was rated as Breast Imaging Reporting and Data System 4, and DBT-guided vacuum biopsy was performed (d–g). Histology revealed fibrocystic changes with sclerosing adenosis and no atypia (h and i). Overview biopsy specimen (h) and higher-magnification view (i) of H&E stains. No immunohistochemistry was necessary. a–c Screening DBT (a) with reconstructed 2D DM (C-view) (b) and higher-magnification view (c). d–g DBT-guided vacuum biopsy was performed, including clip placement. h and i Overview biopsy specimen (h) and higher-magnification view (i) of H&E stains. No immunohistochemistry was necessary

Fig. 2

False-positive magnetic resonance imaging (MRI)…

Fig. 2

False-positive magnetic resonance imaging (MRI) screening diagnosis. Screening breast MRI ( a and…

Fig. 2

False-positive magnetic resonance imaging (MRI) screening diagnosis. Screening breast MRI (a and b) in a 51-year-old woman at average risk undergoing screening MRI. MRI showed moderate background enhancement (American College of Radiology C) and a nonmass enhancement with segmental distribution in the right breast (arrow in a). MRI-guided vacuum biopsy was performed (c–f). Histology revealed atypical ductal hyperplasia (ADH), flat epithelial atypia, and sclerosing adenosis (g). Immunohistochemical staining was needed to confirm ADH (h). The patient subsequently underwent open surgery, which confirmed the presence of ADH; no ductal carcinoma in situ or invasive cancer was found. The patient has been in follow-up, including serial MRI, for 2 years, so far without a diagnosis of invasive cancer. a and b Screening diagnostic breast MRI. First postcontrast subtracted (a) and nonsubtracted images (b). c–f MRI-guided vacuum biopsy of the segmental nonmass enhancement in the right breast (black arrows in d). First postcontrast subtracted (c) and nonsubtracted images (d), T2-weighted turbo spin echo (TSE) before (e) and after (f) biopsy with the biopsy cavity, which demonstrates successful biopsy (yellow arrow). g and h Histology after H&E staining (g) and immunohistochemical staining with cytokeratin 5/6 (CK5/6) (h). a and b Screening diagnostic breast MRI. First postcontrast subtracted (a) and nonsubtracted image (b). c–f MRI-guided vacuum biopsy of the segmental nonmass enhancement in the right breast (black arrows in d). First postcontrast subtracted (c) and nonsubtracted images (d), T2-weighted TSE before (e) and after (f) biopsy with the biopsy cavity, which demonstrates successful biopsy (yellow arrow). g and h Histology after H&E staining (g) and immunohistochemical staining with CK5/6 (h)

Fig. 3

Distribution of tissue changes causing…

Fig. 3

Distribution of tissue changes causing false-positive finding based on magnetic resonance imaging (MRI)…

Fig. 3

Distribution of tissue changes causing false-positive finding based on magnetic resonance imaging (MRI) vs. digital mammography/digital breast tomosynthesis (DM/DBT)