Abstract
Breast cancer imaging phenotype is diverse and may relate to molecular alterations driving cancer behavior. We systematically reviewed and meta-analyzed relations between breast cancer imaging features and human epidermal growth factor receptor type 2 (HER2) overexpression as a marker of breast cancer aggressiveness. MEDLINE and EMBASE were searched for mammography, breast ultrasound, magnetic resonance imaging (MRI), and/or [18F]fluorodeoxyglucose positron emission tomography studies through February 2013. Of 68 imaging features that could be pooled (85 articles, 23,255 cancers; random-effects meta-analysis), 11 significantly related to HER2 overexpression. Results based on five or more studies and robustness in subgroup analyses were as follows: the presence of microcalcifications on mammography [pooled odds ratio (pOR), 3.14; 95% confidence interval (CI), 2.46–4.00] or ultrasound (mass-associated pOR, 2.95; 95% CI, 2.34–3.71), branching or fine linear microcalcifications (pOR, 2.11; 95% CI, 1.07–4.14) or extremely dense breasts on mammography (pOR, 1.37; 95% CI, 1.07–1.76), and washout (pOR, 1.57; 95% CI, 1.11–2.21) or fast initial kinetics (pOR, 2.60; 95% CI, 1.43–4.73) on MRI all increased the chance of HER2 overexpression. Maximum [18F]fluorodeoxyglucose standardized uptake value (SUVmax) was higher upon HER2 overexpression (pooled mean difference, +0.76; 95% CI, 0.10–1.42). These results show that several imaging features relate to HER2 overexpression, lending credibility to the hypothesis that imaging phenotype reflects cancer behavior. This implies prognostic relevance, which is especially relevant as imaging is readily available during diagnostic work-up. Cancer Epidemiol Biomarkers Prev; 23(8); 1464–83. ©2014 AACR.
Introduction
Breast cancer is the most common type of cancer and the leading cause of cancer-related death in women worldwide (1). It is a heterogeneous disease, which can be appreciated by its diverse imaging appearance (2), its histologic and molecular classifications (3–5), and its correspondingly diverse disease course. One of the most clinically relevant molecular aberrations in breast cancer is overexpression of the human epidermal growth factor receptor type 2 (HER2). HER2 overexpression occurs in 15% to 25% of invasive breast cancers, and is associated with an intrinsic worse prognosis but good response to HER2-targeted therapies (6).
Some of the many effects on the cellular level of HER2 overexpression are increased cell proliferation, cell survival, mobility, and invasiveness, as well as neo-angiogenesis by increasing vascular endothelial growth factor production (7). These cellular processes and their clinical course provide evidence that HER2-overexpressing breast cancers behave distinctly from other breast cancers, which might drive macroscopic appearance and physiologic parameters. These phenomena may be potentially visible by clinical imaging modalities. As of now, the literature relating imaging features to HER2 overexpression in breast cancer is diverse, scattered over different scientific and clinical fields, and often based on small studies. The purpose of this study was to comprehensively review that literature and use meta-analysis techniques to formally quantify the relation between imaging features and HER2-positive breast cancer. We specifically focused on established clinical imaging modalities [mammography, breast ultrasound, magnetic resonance imaging (MRI), and [18F]fluorodeoxyglucose positron emission tomography (18F-FDG PET)].
Identification of imaging features related to HER2 overexpression in breast cancer could not only increase our biologic understanding, but may also have potential future clinical relevance. Existence of imaging features related to HER2 overexpression would for instance suggest prognostic value of breast cancer imaging phenotype. Furthermore, such features may have relevance in identifying potential sampling error in cases in which HER2 status is based on tumor biopsies, as practiced for neoadjuvant treatment indication.
Materials and Methods
Literature search and study selection
We performed a comprehensive systematic literature search of MEDLINE and EMBASE on February 8, 2013 using synonyms for HER2 and the imaging modalities of interest in combination with breast cancer (Fig. 1). The search was without restrictions. After combining the searches and duplicate removal, two researchers (S.G. Elias and A. Adams) independently performed all selection and data-extraction steps. First, we assessed titles and abstracts, excluding only articles deemed ineligible for full-text evaluation by both researchers. Then, we reviewed the full text of those remaining and subsequently excluded articles only upon consensus. We documented exclusion criteria as follows: (i) non-original data (e.g., reviews, editorials, and guidelines), (ii) preclinical studies (e.g., animal or in vitro studies), (iii) case reports (i.e., studies including less than 10 patients), (iv) non-primary breast cancer (e.g., imaging of breast cancer metastasis or lymph nodes), (v) experimental breast imaging modalities (e.g., optical mammography or breast elastography), (vi) treatment evaluation studies, and (vii) no imaging features described or evaluated. We then reviewed each selected article's references to identify any articles missed by the original search. Finally, articles with insufficient data for review (e.g., presenting only P values), or studies that presented identical data on the same patients were excluded (keeping the largest series). If unsure about duplicate data, we contacted the authors. As magnetic resonance spectroscopy (MRS) and diffusion-weighted imaging (DWI) are not established clinical imaging modalities but could be implemented rather easily given the clinical availability of MRI scanners, we did not exclude these modalities but show the results in the Supplementary Results.
Overview of the MEDLINE and EMBASE literature search and study selection process. aBoth searches performed on February 8, 2013; MEDLINE query: (her-2* OR her2* OR *erbb*) AND (mri OR mammograph* OR ultrasound OR (positron emission tomography) OR imaging) AND breast; EMBASE query: “epidermal growth factor receptor 2”/exp AND (“nuclear magnetic resonance imaging”/exp OR “mammography”/exp OR “echography”/exp OR “positron emission tomography”/exp) AND “breast cancer”/exp. Explanation of exclusion reasons, be.g., reviews, editorials, guidelines, and perspectives; ce.g., optical imaging and scintimammography; dfive studies reported both on mammography and ultrasonography, and three both on DCE-MRI and 18F-FDG PET.
Overview of the MEDLINE and EMBASE literature search and study selection process. aBoth searches performed on February 8, 2013; MEDLINE query: (her-2* OR her2* OR *erbb*) AND (mri OR mammograph* OR ultrasound OR (positron emission tomography) OR imaging) AND breast; EMBASE query: “epidermal growth factor receptor 2”/exp AND (“nuclear magnetic resonance imaging”/exp OR “mammography”/exp OR “echography”/exp OR “positron emission tomography”/exp) AND “breast cancer”/exp. Explanation of exclusion reasons, be.g., reviews, editorials, guidelines, and perspectives; ce.g., optical imaging and scintimammography; dfive studies reported both on mammography and ultrasonography, and three both on DCE-MRI and 18F-FDG PET.
Data extraction
First, we extracted study characteristics [e.g., study size, overall patient and tumor characteristics, HER2 assessment methodology, imaging acquisition details, use of the Breast Imaging-Reporting and Data System (BI-RADS), which improves comparability (2), and, more specifically related to the risk of bias, whether or not image assessment was blinded for HER2 status and whether the selection of patients may have introduced selection bias]. Then, we documented the numerical results of each imaging feature in relation to HER2 status [for categorical data by cross-tabulating absolute numbers, for continuous data using means and standard deviations (SD)]. If necessary, we matched different descriptors (e.g., for mammography, we combined studies describing “well-defined mass margins” and “smooth mass margins” to the overall descriptor “circumscribed margins”; Supplementary Tables S1–S3), combined groups [e.g., if features were compared between HER2-positive, triple-negative, and estrogen receptor (ER)–positive breast cancer, we combined the latter two groups], or approximated study data (e.g., using percentages and totals to derive absolute numbers). For group combination of categorical data, we used summation following cross-tabulation. For group combination of continuous data, we used inverse variance weighted pooling. Approximation of means and SD was necessary for several DWI and 18F-FDG PET studies that did not report these parameters using methods as outlined elsewhere (8, 9). All data-extraction steps were double-checked by two researchers (S.G. Elias and A. Adams).
Meta-analysis
For pooling of study results, we used DerSimonian–Laird random effects models to allow for between-study heterogeneity. For imaging features reported as categorical data, we estimated pooled odds ratios (pOR) to describe the relation between that feature and the chance of HER2 overexpression. All breast cancers not belonging to the imaging feature category of interest served as reference category in these analyses. For imaging features reported as continuous data, we estimated pooled mean differences between HER2-positive and -negative breast cancer. We assessed between-study heterogeneity by I2 statistics in combination with Cochran Q test for heterogeneity [denoted as P(Q)], and evaluated the impact of publication bias by inspecting funnel plot asymmetry in combination with Egger tests. We used forest plots to inspect individual study data and meta-analysis results.
Besides pooling of data using all available studies, we additionally performed meta-analyses in several predefined study subgroups to evaluate possible sources of between-study heterogeneity in the results: (i) excluding studies with data on pure ductal carcinoma in situ (DCIS), to focus on invasive cancer results only; (ii) excluding studies selecting participants based on receptor expression (e.g., studies that excluded ER-positive breast cancer, thereby contrasting triple-negative to HER2 positive breast cancer) as this may threaten generalizability of the results and/or might induce selection bias; (iii) focusing on studies with a specific imaging acquisition technique [analog vs. digital for mammography; studies including 3T vs. only 1.5T field strength for MRI, as well as higher spatial resolution MRI studies (i.e., sub-mm in plane resolution and smaller than 2-mm slice thickness)]; (iv) focusing on studies based on BI-RADS; and (v) excluding studies for which we had to approximate means and SDs.
We used R version 2.15.3 (R Foundation for Statistical Computing, Vienna, Austria) for all analyses including the packages rmeta and meta (10–12). We report pooled estimates in combination with 95% confidence intervals (CI) and used two-sided P values of <0.05 for statistical significance. The report and conduct of this meta-analysis satisfies the PRISMA Statement (13).
Results
Literature search and study selection
Figure 1 shows an overview of the literature search and study selection process. The search yielded 1,673 unique articles, of which we excluded 1,469 based on title and abstract (83% because of non-original data, preclinical, or case reports), and 117 following full-text screening, of which 47 (40%) were (neo)adjuvant treatment studies, without correlation between imaging features and HER2 status. Reference cross-checking of the 87 eligible articles yielded seven additional articles not initially identified (2 nonindexed breast ultrasound articles, refs. 14, 15; 1 MRS, ref. 16; and 4 18F-FDG PET articles, refs. 17–20). We subsequently excluded five articles because of insufficient data (20–24), and four because of patient overlap (19, 25–27). Thus, we selected 85 articles for our review (14–18, 28–107), representing 81 unique patient populations, totaling 23,159 patients with 23,255 breast cancers including 4,213 HER2-positives. Four populations gave rise to two separate publications on different imaging features and/or modalities (16, 54, 61, 66, 70, 75, 81, 104). A total of 33 articles reported on mammography (28–60), 12 on breast ultrasound (14, 15, 28, 33, 41, 52, 56, 61–65), 28 on MRI (16, 66–92), and 20 on 18F-FDG PET (17, 18, 70, 87, 91, 93–107). Of these, eight articles reported on two imaging modalities: five on both breast ultrasound and mammography (28, 33, 41, 52, 56), and three on both 18F-FDG PET and DWI (70, 87), or MRS (91). Table 1 shows the characteristics of the selected studies. Most articles exclusively studied invasive breast cancer (67%), followed by both invasive breast cancer and DCIS (25%). A few studies exclusively studied DCIS (7%) or were not clear whether they studied only invasive cancer, DCIS, or both (1%). The threshold for HER2 overexpression was variable between studies, with 32% using the established clinical standard [i.e., immunohistochemistry (IHC) result of 3+, or IHC result of 2+ with gene-amplification], 27% using only IHC 3+, 29% using another threshold/method, and 12% not reporting this item. Studies reporting on MRI or 18F-FDG PET more often used the clinical standard (39% and 40%, respectively) than mammography (21%) or breast ultrasound articles (25%). Whether image assessment was blinded for HER2 status was not reported in 60% of articles. In 8% of the articles, a specific breast cancer molecular subtype (predominantly ER-positive breast cancer) was excluded in their analysis (2 MRI, 2 ultrasound, and 5 mammography studies). Study results were based on BI-RADS in 64% of mammography, 36% of ultrasound, and 65% of MRI studies (excluding studies focused on non-BI-RADS imaging features such as apparent diffusion coefficient).
Characteristics of studies reporting on mammography, breast ultrasound, MRI, and 18F-FDG PET imaging features in relation to HER2 overexpression in breast cancer
. | Patients . | Breast cancers . | HER2 assessment . | Imaging acquisition and results . | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
. | . | . | . | . | . | Histologyc . | . | Positive . | . | . | Readers . | . | ||||
Ref., country, recruitment period . | Recruitment . | N . | Age in years (range/SD) . | N . | Size in cm (range/SD) . | IDC . | Else . | DCIS . | Assayd . | Cutoff . | N (%) . | Imaging system (manufacturer) . | Imaging parameters . | N . | Blinded . | Imaging features described in reviewe,f,g,h . |
Mammography | Analog/Digital | |||||||||||||||
Agrawal et al. (28), Poland, 1992–2001 | University hospital | 184 | 57a (32–75) | 184 | NS (NS) | ![]() | ![]() | ![]() | IHC Dakopatts (K-353) | NS | 100 (54) | NS | Analog | NS | NS | Level of suspicion |
Aiello et al. (29), USA, 1988–1995 | Breast cancer screening program | 461 | NS (NS) | 461 | NS (0.1–10) | NOS | ![]() | IHC NOS | Other | 79 (17) | NS | Analog | 1 | NS | BrDe | |
Arora et al. (30), USA, 2005–2007 | Cancer center; no prior breast cancer | 1,323 | 56b (27–91) | 1,323 | 1.5b (0.1–11) | ![]() | ![]() | ![]() | IHC NOS | NS | 170 (13) | NS | Analog, digital | NS | NS | BrDe |
Badra et al. (31), Greece, 1994–2004 | University hospital; nonpalpable screen-detected | 75 | 56b (35–74) | 75 | NS (NS) | ![]() | ![]() | ![]() | IHC BioGenex (CB11) | ![]() ![]() ![]() | 34 (45) | NS | NS | 2 | NS | Cal |
Cui et al. (32), China, 2009–2011 | University hospital; triple-negative and triple-positive only | 161 | 51a (27–87) | 161 | 2.4a (NS) | ![]() | ![]() | ![]() | IHC NOS | ![]() ![]() ![]() | 44 (27) | Senographe 800T (GE) | Analog | 2 | Yes | BrDe; Mas (Mar; Sha; Cal); Cal |
Di Nubila et al. (33), Italy, 2000–2002 | Cancer center; ≤ 35 y, no prior breast cancer | 232 | 32a (22–35) | 232 | 2.3a (NS) | ![]() | ![]() | ![]() | IHC Triton (TAB250) | ![]() ![]() ![]() | 64 (28) | Senographe 2000D; Senographe DMR (GE) | Analog, digital | NS | NS | Level of suspicion; BrDe; Cal |
Enache et al. (34), Romania, 2010–2011 | General hospital; only ER− | 40 | 51a (25–88) | 40 | 4.1a (0.6–10.7) | ![]() | ![]() | ![]() | IHC Dako (polyclonal); CISH Invitrogen | ![]() ![]() ![]() | 11 (28) | NS | NS | NS | NS | BrDe; Mas (Mar; Sha; Cal); Cal (Mor); ArDi; FoAs |
Evans et al. (35), UK, 1978–1992 | University hospital | 126 | NS (NS) | 126 | NS (NS) | ![]() | ![]() | ![]() | IHC NOS (AP21N) | ![]() ![]() ![]() | 39 (31) | NS | Analog | 1 | Yes | Cal (Mor; Dis) |
Fasching et al. (36), Germany, 2001–2003 | University hospital | 423 | 60a (±13) | 423 | 1.9a (1.4) | ![]() | ![]() | ![]() | IHC NOS | ![]() ![]() ![]() | 37 (9) | Mammomat 3000 Nova (Siemens) | Analog | 1 | Yes | BrDe |
Gajdos et al. (37), USA, 1993–1999 | Tertiary care hospital | 118 | 59a (30–92) | 118 | 1.0a (0.1–3.0) | ![]() | ![]() | ![]() | IHC NOS | NS | 36 (31) | NS | Analog | 5 | Yes | Mas (Cal); Cal; ArDi |
Gu et al. (38), China, 2003–2005 | University hospital | 62 | 51a (31–79) | 62 | NS (NS) | ![]() | ![]() | ![]() | IHC NOS | ![]() ![]() ![]() | 18 (29) | Senographe DMR (GE) | Analog | NS | NS | Cal |
Jiang et al. (39), China, 2008–2010 | University hospital | 63 | 49a (27–79) | 63 | NS (0.5–9.0) | ![]() | ![]() | ![]() | IHC Golden Bridge International (CB11) | ![]() ![]() ![]() | 19 (30) | Mammomat Novation DR (Siemens) | Digital | 2 | Yes | Mas (Mar) |
Kim et al. (40), South Korea, 2005–2008 | Cancer center | 151 | 48a (26–75) | 151 | NS (NS) | ![]() | ![]() | ![]() | IHC Zymed (NS) | ![]() ![]() ![]() | 54 (36) | Selenia (Hologic) | Digital | 2 | NS | Cal |
Ko et al. (41), South Korea, 2007–2008 | Cancer center; only TN, ER+/PR−/HER2−, ER−/PR−/HER2+ | 239 | 52a (26–86) | 239 | 2.3a (NS) | ![]() | ![]() | ![]() | IHC Zymed (NS) | ![]() ![]() ![]() | 63 (26) | Selenia (Hologic) | Digital | 2 | NS | Mas (Cal); Cal; ArDi; FoAs |
Kuo et al. (42), Taiwan, 1999–2005 | University hospital; <stage IV disease, follow-up ≥ 1 y | 998 | 51a (±11) | 998 | NS (NS) | NOS | ![]() | IHC BioGenex (CB11); FISH NOS | ![]() ![]() ![]() | 156 (16) | NS | NS | 1 | NS | Level of suspicion | |
Li and Chen (43), China, 2005–2009 | University hospital | 110 | 52a (29–77) | 110 | NS (NS) | ![]() | ![]() | ![]() | IHC NOS | ![]() ![]() ![]() | 49 (45) | Giotto NOS (IMS) | Digital | 3 | Yes | Mas (Mar); Cal (Mor) |
Ma et al. (44), USA, 1994–1998 | Women's Contraceptive and Reproductive Experiences Study | 352 | 49a (35–64) | 352 | NS (NS) | NOS | ![]() | IHC Dako (10H8) | ![]() ![]() ![]() | 62 (18) | NS | Analog | 1 | NS | BrDe | |
Månsson et al. (45), Sweden, 1986–1995 | Population-based; unifocal, ≤1.5 cm | 361 | 63b (±12) | 361 | NS (0.1–1.5) | NOS | ![]() | IHC Dako (polyclonal) | Other | 142 (39) | NS | Analog | 1 | Yes | Cal | |
Mun et al. (46), South Korea, 2007–2010 | University hospital; screen-detected | 213 | 50a (30–76) | 213 | 2.4a (0.5–8.5) | ![]() | ![]() | ![]() | IHC NOS; FISH NOS | ![]() ![]() ![]() | 77 (36) | Senographe DS; Senographe Essential (GE) | Analog; digital | 2 | NS | Cal |
Palka et al. (47), Hungary, 2000–2003 | University hospital; high-risk breast cancer adjuvant study | 55 | 52a (33–70) | 55 | 3.5a (NS) | NOS | ![]() | IHC NOS | ![]() ![]() ![]() | 14 (25) | NS | NS | 1 | Yes | Cal | |
Palka et al. (48), Hungary, 2004–2006 | University hospital | 560 | 58a (28–85) | 560 | NS (NS) | ![]() | ![]() | ![]() | IHC NOS | ![]() ![]() ![]() | 85 (15) | NS | NS | ≥2 | NS | Cal |
Phipps et al. (49), USA, 1999–2008 | BCSC; no history of breast cancer | 7,281 | NS (NS) | 7,281 | NS (NS) | ![]() | ![]() | ![]() | IHC NOS; FISH NOS | ![]() ![]() ![]() | 172 (2) | NS | NS | NS | Yes | BrDe |
Pollan et al. (50), Spain, 1996–2005 | Navarre Breast Cancer Screening Program | 834 | NS (NS) | 834 | NS (NS) | ![]() | ![]() | ![]() | NS | NS | 111 (13) | NS | NS | 1 | Yes | BrDe |
Seo et al. (51), USA, 2001–2003 | University hospital | 498 | 57a (24–95) | 543 | NS (NS) | ![]() | ![]() | ![]() | IHC Dako (HercepTest); FISH PathVysion | ![]() ![]() ![]() | 159 (29) | Mammomat 3000 Nova (Siemens), Seno-graphe 2000D (GE) | Analog, digital | 1 | NS | BrDe; Mas (Mar; Sha; Cal); Cal (Mor; Dis); ArDi; FoAs; SkTh; Oth |
Shin et al. (52), South Korea, 2005–2006 | University hospital; node negative | 710 | 49a (21–81) | 715 | NS (NS) | ![]() | ![]() | ![]() | IHC NOS | ![]() ![]() ![]() | 165 (23) | Senographe DMR (GE) | Analog | 1 | Yes | Mas (Mar; Cal); Cal |
Sun et al. (53), China, 2004–2007 | General hospital | 144 | 49a (23–83) | 144 | NS (NS) | NS | IHC Beijing Zhongshan Biotechnology (NS) | NS | 58 (40) | NS | Digital | 2 | NS | Cal | ||
Taneja et al. (54), UK, 1996–1997 | University hospital | 415 | 55a (27–70) | 415 | NS (NS) | ![]() | ![]() | ![]() | IHC Dako (NS) | Other | 132 (32) | NS | Analog | 1 | Yes | BrDe; Mas (Mar); Cal; ArDi; FoAs |
Wang et al. (55), China, 2003–2006 | University hospital | 152 | 51b (27–82) | 152 | NS (NS) | ![]() | ![]() | ![]() | IHC Dako (K5204) | ![]() ![]() ![]() | 73 (48) | Gold Standard (Pan-pacific Enterprises Inc.) | Digital | 2 | Yes | Mas (Mar; Cal); Cal (Mor; Dis); ArDi; FoAs |
Wang et al. (56), USA, 1997–2003 | University hospital; only ER− | 56 | 53a (31–84) | 56 | 2.4a (0.2–8.0) | ![]() | ![]() | ![]() | IHC Dako (HercepTest); FISH PathVysion | ![]() ![]() ![]() | 23 (41) | NS | Analog | 3 | Yes | BrDe; Mas (Mar; Sha; Cal); Cal (Mor); ArDi; FoAs |
Wang et al. (57), China, 2006–2007 | General hospital | 60 | 50b (28–75) | 60 | NS (NS) | ![]() | ![]() | ![]() | IHC Fuzhou Maixin (NS) | ![]() ![]() ![]() | 30 (50) | Giotto NOS (IMS) | NS | NS | Yes | Mas (Cal); Cal; ArDi |
Wen et al. (58), China, 2010 | University hospital; no [ER+ or PR+ and HER2+] group | 477 | 55b (25–86) | 477 | 2.2b (0.5–7.0) | ![]() | ![]() | ![]() | IHC NOS | ![]() ![]() ![]() | 76 (16) | NS | Digital | ≥2 | NS | Mas (Mar; Sha; Cal); Cal (Mor; Dis); SkTh; Oth |
Yaghjyan et al. (59), USA, 1989–2004 | Nurses' Health Study; postmenopausal | 563 | NS (NS) | 563 | NS (NS) | ![]() | ![]() | ![]() | IHC NOS | ![]() ![]() ![]() | 140 (25) | NS | Analog | NS | Yes | BrDe |
Yang et al. (60), USA, 1999–2005 | Cancer center; ≤45 y premenopausal | 198 | 34a (25–46) | 198 | 2.8a (0.7–9.0) | ![]() | ![]() | ![]() | IHC NOS; FISH NOS | ![]() ![]() ![]() | 67 (34) | M3 (Hologic), Senographe DMR (GE) | Analog | 2 | Yes | BrDe; Mas (Mar; Sha; Cal); Cal; ArDi |
Breast ultrasound | Transducer bandwidth | |||||||||||||||
Agrawal et al. (28), Poland, 1992–2001 | University hospital | 184 | 57a (32–75) | 184 | NS (NS) | ![]() | ![]() | ![]() | IHC Dakopatts (K-353) | NS | 100 (54) | NS | NS | NS | NS | Level of suspicion |
Au-Yong et al. (61), UK, 1996–1997 | University hospital | 227 | 63a (27–70) | 227 | NS (NS) | ![]() | ![]() | ![]() | IHC Dako (NS) | Other | 71 (31) | NOS (Esaote) | 7.5 MHz | 2 | Yes | Mas (Sha; Ori; Mar; Hal; EcPa; PAF; Cal; Mul); Cal; Oth |
Chen et al. (14), China, 2006–2007 | Military hospital | 73 | 54a (33–85) | 73 | NS (0.5–6.6) | ![]() | ![]() | ![]() | IHC Beijing Zhongshan Biotechnology (NS) | NS | 39 (53) | Logiq7 (GE) | 8.0–10.0 MHz | NS | NS | Mas (Ori; Mar; Hal; PAF; Cal) |
Chen et al. (62), Taiwan, 2008–2009 | Cancer center | 168 | 51a (24–87) | 168 | 2.6a (0.7–5.3) | ![]() | ![]() | ![]() | IHC Dako (NS); FISH NOS | ![]() ![]() ![]() | 44 (26) | Voluson 730 (GE) | 6.0–12.0 MHz | Computer-automated | Vascularization | |
Di Nublia et al. (33), Italy, 2000–2002 | Cancer center; ≤ 35 y, no prior breast cancer | 238 | 32a (22–35) | 238 | 2.3a (NS) | ![]() | ![]() | ![]() | IHC Triton (TAB250) | ![]() ![]() ![]() | 66 (28) | Technos MPX, AU5 Harmonic (Esaote) | 7.5–13.0 MHz | NS | NS | Level of suspicion |
Kim et al. (63), South Korea, 2002–2006 | University hospital | 458 | 56a (25–87) | 458 | 2.1a (0.4–12.5) | ![]() | ![]() | ![]() | IHC Zymed (TAB250) | ![]() ![]() ![]() | 191 (42) | Logiq9 (GE); HDI-5000 (Philips) | 5.0–14.0 MHz | 1∣2 | Yes | Mas (Sha; Ori; Mar; Hal; EcPa; PAF; Cal) |
Ko et al. (41), South Korea, 2007–2008 | Cancer center; only TN, ER+/PR−/HER2−, ER−/PR−/HER2+ | 245 | 52a (26–86) | 245 | 2.3a (NS) | ![]() | ![]() | ![]() | IHC Zymed (NS) | ![]() ![]() ![]() | 65 (27) | HDI-5000, IU-22 (Philips) | 5.0–12.0 MHz | 2 | NS | Mas (Sha; Ori; Mar; Hal; EcPa; PAF) |
Li et al. (15), China, 2007–2008 | University hospital | 120 | 47a (25–80) | 120 | NS (NS) | ![]() | ![]() | ![]() | IHC MaxVision (NS) | ![]() ![]() ![]() | 99 (82) | Logiq9 (GE); Acuson Sequoia 512 (Siemens) | 7.0–14.0 MHz | NS | NS | Mas (Mar; Hal; PAF; Cal); Vascularization |
Pang et al. (64), China, (2007–2008) | University hospital | 207 | 49b (25–79) | 207 | NS (NS) | ![]() | ![]() | ![]() | IHC NOS; FISH NOS | ![]() ![]() ![]() | 62 (30) | DU8 (Esaote); HDI-5000 (Philips) | 4.0–13.0 MHz | NS | NS | Mas (Mar; PAF; Cal); Vascularization |
Shin et al. (52), South Korea, 2005–2006 | University hospital; node negative | 710 | 49a (21–81) | 715 | NS (NS) | ![]() | ![]() | ![]() | IHC NOS | ![]() ![]() ![]() | 165 (23) | HDI-5000; IU-22 (Philips) | 5.0–12.0 MHz | 1 | Yes | Mas (Sha; Cal); Cal |
Wan et al. (65), China, 2009–2011 | University hospital | 74 | 55a (32–78) | 74 | 2.5a (1.1–5.3) | ![]() | ![]() | ![]() | IHC Dako (A0485) | ![]() ![]() ![]() | 25 (34) | DU8 (Esaote) | 4.5–7.5 MHz | 3 | Yes | Enhancement patterns |
Wang et al. (56), USA, 1997–2003 | University hospital; only ER− | 32 | 53a (31–84) | 32 | 2.4a (0.2–8.0) | ![]() | ![]() | ![]() | IHC Dako (HercepTest); FISH (PathVysion) | ![]() ![]() ![]() | 17 (53) | NS | NS | 3 | Yes | Mas (Sha; Ori; Mar; EcPa; Cal); Vascularization |
MRI | Acquisition and protocol | |||||||||||||||
Agrawal et al. (66), USA, 2003–2005 | University hospital | 78 | NS (NS) | 80 | 1.7a (±1.1) | ![]() | ![]() | ![]() | NS | NS | 30 (38) | 1.5T NOS (Philips) | Bilateral; breast coil; DCE | 2 | Yes | Mas (MuFo; Sha; Mar; InEn); KiCu; TtP |
Baek et al. (16), USA, 2005–2006 | University hospital; ≥1.5 cm only | 66 | 51a (32–76) | 66 | 3.4a (1.5–8.6) | ![]() | ![]() | ![]() | IHC NOS; FISH NOS | ![]() ![]() ![]() | 21 (32) | 1.5T Eclipse (Philips) | Bilateral; breast coil; MRS | NS | NS | Cho |
Baltzer et al. (67), Germany, 2005–2006 | University hospital | 128 | 60a (30–82) | 145 | NS (NS) | ![]() | ![]() | ![]() | IHC Dako (HercepTest) | ![]() ![]() ![]() | 43 (30) | 1.5T MAGNETOM Symphony (Siemens) | Bilateral; breast coil; DCE | NA | NA | Computer aided DCE pattern |
Chang et al. (68), South Korea, 2004–2006 | University hospital | 136 | 48a (26–75) | 151 | 1.9a (0.5–5.8) | ![]() | ![]() | ![]() | IHC NOS | ![]() ![]() ![]() | 39 (26) | 1.5T MAGNETOM Sonata (Siemens) | NS; breast coil; DCE | 2 | NS | Mas (Sha; Mar; InEn); KiCu; TtP |
Chen et al. (69), USA, 2006–2010 | University hospital; neoadjuvant therapy | 50 | 49a (28–82) | 50 | 4.5a (1.7–11.8) | ![]() | ![]() | ![]() | FISH NOS | Other | 17 (34) | 3T Achieva (Philips) | Bilateral; breast coil; DCE | 1 | Yes | Mas |
Choi et al. (70), South Korea, 2008–2010 | University hospital | 117 | 52a (29–81) | 117 | 2.8a (±2.2) | ![]() | ![]() | ![]() | IHC NOS | ![]() ![]() ![]() | 50 (43) | 1.5T Achieva (Philips); 3T MAGNETOM Verio (Siemens) | NS; breast coil; DWI | 1 | NS | ADC |
Costantini et al. (71), Italy, 2007–2011 | University hospital | 225 | 53a (±12) | 225 | 3.4a (±2.0) | ![]() | ![]() | ![]() | IHC Dako (polyclonal); FISH Dako (pharmDx) | ![]() ![]() ![]() | 38 (17) | 1.5T Signa Excite (GE) | Bilateral; breast coil; DCE, DWI | 2 | NS | Mas (MuFo; Sha; Mar; InEn); KiCu; T2Si; ADC; Oth |
Fernández-Guinea et al. (72), Spain, 1999–2006 | General hospital | 68 | 56a (30–83) | 68 | 2.3a (0.6–12.0) | ![]() | ![]() | ![]() | IHC Dako (polyclonal); FISH NOS | ![]() ![]() ![]() | 27 (40) | 1.5T Signa EchoSpeed (GE) | Bilateral; breast coil; DCE | 2 | NS | Mas (Mar; InEn); KiCu; TtP; EnRa |
Girardi et al. (73), Italy, 2006–2008 | University hospital | 72 | 54a (33–87) | 72 | 2.2a (0.6–7.0) | ![]() | ![]() | ![]() | IHC NOS | ![]() ![]() ![]() | 12 (17) | 1.5T MAGNETOM Symphony (Siemens) | Bilateral; breast coil; DCE | 2 | NS | Mas (Sha; Mar; InEn; KiCu; EnRa; Fis) |
Gómez-Raposo et al. (74), Spain, 2008–2011 | University hospital; neoadjuvant therapy | 24 | NS (NS) | 24 | 4.4 (2.4–6.4)f | ![]() | ![]() | ![]() | IHC NOS | NS | 6 (25) | 3T Achieva (Philips) | NS; NS; DCE | NS | NS | Mas; KiCu |
Jeh et al. (75), South Korea, 2008–2009 | University hospital | 107 | 52a (31–81) | 107 | 3.2a (0.6–16.0) | ![]() | ![]() | ![]() | IHC NOS | ![]() ![]() ![]() | 48 (45) | 1.5T Achieva (Philips); 3T MAGNETOM Verio (Siemens) | NS; breast coil; DCE | 2 | NS | Mas (Sha; Mar; InEn) |
Kim et al. (76), South Korea, 2005–2008 | University hospital | 62 | 47a (26–70) | 62 | NS (NS) | ![]() | ![]() | ![]() | NS | NS | 30 (48) | 1.5T MAGNETOM Avanto (Siemens) | Bilateral; breast coil; DCE | 2 | Yes | TtP; Oth |
Kim et al. (77), South Korea, 2007 | University hospital | 62 | 54a (36–86) | 62 | 2.2b (NS) | ![]() | ![]() | ![]() | IHC Novocastra (NS) | ![]() ![]() ![]() | 15 (24) | 1.5T Signa TwinSpeed (GE) | NS; breast coil; DWI | 2 | NS | ADC |
Koo et al. (78), South Korea, 2009–2010 | University hospital | 68 | 54a (33–77) | 68 | 1.9a (0.1–5.5) | ![]() | ![]() | ![]() | IHC NOS; FISH NOS | ![]() ![]() ![]() | 10 (15) | 1.5T Signa HDx (GE) | Bilateral; breast coil; DCE | 2 | NS | Perfusion parameters |
Lee et al. (79), South Korea, 2004 | University hospital | 194 | 47a (26–76) | 194 | 2.2a (0.1–6.0) | ![]() | ![]() | ![]() | IHC Novocastra (NS) | ![]() ![]() ![]() | 24 (12) | 1.5T MAGNETOM Sonata (Siemens) | Unilateral; breast coil; DCE | 2 | Yes | Mas (Sha; Mar; InEn); KiCu; TtP; EnRa; Oth |
Liu and Peng (80), China, 2007–2009 | University hospital | 41 | 51a (36–70) | 41 | 2.6a (NS) | ![]() | ![]() | ![]() | IHC NOS | ![]() ![]() ![]() | 29 (71) | 1.5T Signa TwinSpeed (GE); 3T Signa HDxt (GE) | Bilateral; breast coil; DCE | 2 | Yes | Mas |
Loo et al. (81), the Netherlands, 2000–2008 | Cancer center; neoadjuvant therapy | 188 | 46a (23–76) | 188 | 5.0a (1.4–11.2) | ![]() | ![]() | ![]() | IHC NOS; CISH NOS | ![]() ![]() ![]() | 38 (20) | 1.5T MAGNETOM Vision (Siemens); 3T Achieva (Philips) | Bilateral; breast coil; DCE | 1 | Yes | Mas (MuFo) |
Lu et al. (82), China, 2005–2010 | University hospital; mammography occult–axillary metastasis | 17 | 53a (30–72) | 17 | 1.5a (0.2–3.5) | ![]() | ![]() | ![]() | IHC NOS | Other | 7 (41) | 1.5T Signa Infinity Excite II (GE) | NS; breast coil; DCE | 2 | NS | Mas (Mar; InEn); KiCu; Oth |
Makkat et al. (83), Belgium, 2004–2005 | University hospital | 57 | 50b (31–80) | 57 | 2.2b (NS) | ![]() | ![]() | ![]() | IHC Dako (HercepTest); FISH (PathVysion) | ![]() ![]() ![]() | 13 (23) | 1.5T Intera (Philips) | Bilateral; breast coil; DCE | 2 | NA | Tumor blood flow |
Marcos de Paz et al. (84), Spain, 2003–2009 | University hospital | 69 | 53a (31–74) | 75 | NS (NS) | ![]() | ![]() | ![]() | IHC NOS; FISH NOS | ![]() ![]() ![]() | 29 (39) | NS Signa (GE); NS Excite (GE) | NS; NS; DCE | NS | NS | Mas; KiCu; EnRa; Oth |
Martincich et al. (85), Italy, 2007–2009 | Cancer center | 190 | 47b (27–74) | 192 | 2.2a (0.6–6.5) | ![]() | ![]() | ![]() | IHC Dako (HercepTest); FISH NOS | ![]() ![]() ![]() | 40 (21) | 1.5T NOS (GE) | NS; breast coil; DWI | 1 | NS | ADC |
Montemurro et al. (86), Italy, 2003–2005 | Cancer center | 75 | 51b (27–74) | 75 | 3.6b (0.7–12.0) | ![]() | ![]() | ![]() | IHC Dako (HercepTest) | ![]() ![]() ![]() | 16 (21) | 1.5T NOS (GE) | NS; breast coil; DCE | 2 | NS | Sha; Mar; InEn; KiCu; EnRa; Fis |
Nakajo et al. (87), Japan, 2007–2008 | General hospital | 35 | 58a (35–77) | 35 | 1.6a (0.5–3.0) | ![]() | ![]() | ![]() | IHC Dako (HercepTest) | ![]() ![]() ![]() | 7 (20) | 1.5T Intera Achieva (Philips) | Unilateral; breast coil; DWI | 2 | NS | ADC |
Sah et al. (88), India, 2007–2011 | University hospital | 47 | 46a (25–75) | 47 | NS (NS) | ![]() | ![]() | ![]() | IHC NOS | ![]() ![]() ![]() | 13 (28) | 1.5T MAGNETOM Avanto (Siemens) | NS; breast coil; MRS | 1 | NS | Cho |
Shin et al. (89), South Korea, 2008–2010 | University hospital; ≥1.0 cm only | 184 | 48a (28–72) | 184 | 3.5a (1.0–10.0) | ![]() | ![]() | ![]() | IHC NOS; FISH NOS | ![]() ![]() ![]() | 50 (27) | 1.5T MAGNETOM Avanto (Siemens) | NS; breast coil; MRS | 1 | NS | Cho |
Szabó et al. (90), Sweden, NS | University hospital | 61 | 47a (34–78) | 60 | 2.4a (0.3–7.0) | ![]() | ![]() | ![]() | IHC Dako (A0485) | ![]() ![]() ![]() | 14 (23) | 1.5T MAGNETOM SP 63 (Siemens) | Bilateral; breast coil; DCE | 3 | Yes | InEn; KiCu; TtP |
Tozaki and Hoshi (91), Japan, 2008–2009 | General hospital; ≥1.5–3.0 cm only | 50 | 52a (30–86) | 50 | 2.2a (1.5–3.0) | ![]() | ![]() | ![]() | IHC Dako (NS); FISH (PathVysion) | ![]() ![]() ![]() | 6 (12) | 1.5T MAGNETOM Avanto (Siemens) | Bilateral; breast coil; MRS | NS | NS | Cho |
Youk et al. (92), South Korea, 2009–2011 | University hospital | 269 | 50a (26–83) | 271 | 2.4a (0.5–10.0) | ![]() | ![]() | ![]() | IHC Ventana (NOS); FISH (PathVysion) | ![]() ![]() ![]() | 94 (35) | 1.5T MAGNETOM Avanto (Siemens); 3T Intera Achieva (Philips) | Bilateral; breast coil; DCE, DWI | 2 | Yes | Mas (Sha; Mar; InEn); KiCu; T2Si; ADC; Oth |
FDG-PET | Acquisition and protocol | |||||||||||||||
Choi et al. (70), South Korea, 2008–2010 | University hospital | 117 | 52a (29–81) | 117 | 2.8a (±2.2) | ![]() | ![]() | ![]() | IHC NOS | ![]() ![]() ![]() | 50 (43) | Biograph Duo or Truepoint (Siemens) | FOV, NS; slice, 4.5–6.5 mm; res, NOS; fasting, NS; time, NS; dose, NS | 1 | NS | SUVmax |
Garcia Vicente et al. (93), Spain, NS | Seven hospitals; neoadjuvant therapy | 60 | 53a (±11.7) | 60 | 4.3a (±2.1) | ![]() | ![]() | ![]() | IHC NOS; FISH NOS | ![]() ![]() ![]() | 22 (37) | Discovery DST-E, 16s (GE) | FOV, NS; slice, 3.8 mm; res, NS; fasting, 4 h; time, 60′; dose, 370 MBq | 2 | Yes | SUVmax |
Gil-Rendo et al. (17), Spain, 2000–2004 | University hospital | 251 | 51a (24–87) | 251 | 2.3b (0.3–4.9) | ![]() | ![]() | ![]() | IHC Dako (A0485) | ![]() ![]() ![]() | 116 (46) | ECAT EXACT HR+ (Siemens) | FOV, 15.5-cm axial; slice, 3.9 mm; res, 4.5 mm; fasting, 6 h; time, 40–60′; dose, 370 MBq | 2 | NS | SUVmax |
Groheux et al. (94), France, 2006–2009 | General hospital; only T2, T3 or T4 | 130 | 50b (26–81) | 130 | 5.1b (2.1–14.0) | ![]() | ![]() | ![]() | IHC Novocastra (CB11) | ![]() ![]() ![]() | 24 (18) | Gemini XL (Philips) | FOV, NS; slice, NS; res, NS; fasting, 6 h; time, 60′; dose, 5 MBq/kg | 2 | Yes | SUVmax |
Heudel et al. (18), France, 2008–2009 | Cancer center | 45 | 55b (26–85) | 45 | 2.5b (0.8–9.0) | ![]() | ![]() | ![]() | IHC Dako (A0485) | ![]() ![]() ![]() | 9 (20) | Gemini (Philips) | FOV, NS; slice, NS; res, NS; fasting, 6 h; time, 60′; dose, 5 MBq/kg | NS | NS | SUVmax |
Humbert et al. (95), France, NS | Cancer center; large or locally advanced | 115 | 51a (NS) | 115 | NS (NS) | ![]() | ![]() | ![]() | IHC Ventana (4B5); FISH (ZytoLight) | ![]() ![]() ![]() | 37 (32) | C-PET Plus or Gemini GXL (Philips) | FOV, NS; slice, NS; res, NS; fasting, 6 h; time, 60–90′; dose, 2–5 MBq/kg | NS | NS | SUVmax |
Ikenaga et al. (96), Japan, 2004–2005 | General hospital | 47 | 63a (43–87) | 47 | 2.1a (0–11.9) | ![]() | ![]() | ![]() | IHC Dako (HercepTest) | ![]() ![]() ![]() | 14 (30) | Discovery LS (GE) | FOV, NS; slice, 4.25 mm; res, 5.4 mm; fasting, 6 h; time, 55–65′ after 3.7 MBq/kg | 1 | Yes | SUVmax |
Jin et al. (97), South Korea, 2006–2010 | University hospital; neoadjuvant therapy no trastuzumab | 273 | 44a (23–78) | 273 | 4.9a (0.9–15.1) | ![]() | ![]() | ![]() | IHC NOS | ![]() ![]() ![]() | 72 (26) | Discovery STE (GE), Biograph 16 or Biograph Truepoint 40 (Siemens) | FOV, NS; slice, NS; res, NS; fasting, NS; time, 60′; dose, 370–555 MBq | 2 | No | SUVmax |
Keam et al. (98), South Korea, 2006–2008 | University hospital; neaoadjuvant phase II trial | 78 | 45b (26–69) | 78 | 4.5b (2.0–11.0) | ![]() | ![]() | ![]() | IHC NOS; FISH NOS | ![]() ![]() ![]() | 17 (22) | Gemini (Philips) | FOV, NS; slice, NS; res, NS; fasting, 6 h; time, 50–75′; dose, 5.18 MBq/kg | NS | NS | SUVmax |
Kim et al. (99), South Korea, 2009–2010 | University hospital; ≥1.0 cm | 91 | 49a (26–81) | 91 | 2.2b (1.0–6.5) | ![]() | ![]() | ![]() | IHC Dako (NS); FISH NOS | ![]() ![]() ![]() | 17 (19) | Allegro (Philips) | FOV, NS; slice, NS; res, NS; fasting, 6 h; time, 60′; dose, 5.18 MBq/kg | NS | NS | SUVmax |
Koolen et al. (100), the Netherlands, 2008–2011 | Cancer center; neoadjuvant, >3.0 cm and/or positive node | 214 | 50b (41–57)i | 214 | NS (NS) | ![]() | ![]() | ![]() | IHC NOS; CISH NOS | ![]() ![]() ![]() | 53 (25) | Gemini TF (Philips) | FOV, NS; slice, 2 mm; res, 2 mm × 2 mm; fasting, 6 h; time, 60′; dose, 180–240 MBq | 4 | NS | SUVmax |
Mavi et al. (101), USA, NS | University hospital, >0.5 cm | 116 | 51b (24–80) | 116 | NS (0.5-NS) | ![]() | ![]() | ![]() | IHC Dako (HercepTest) | ![]() ![]() ![]() | 20 (17) | Allegro (Philips) | FOV, NS; slice, 4 mm; res, NS; fasting, 4 h; time, 60′; dose, 2.5–5.2 MBq/kg | 1 | NS | SUVmax |
Nakajo et al. (87), Japan, 2007–2008 | General hospital; >5 mm | 35 | 58a (35–77) | 35 | 1.6a (0.5–3.0) | ![]() | ![]() | ![]() | IHC Dako (HercepTest) | ![]() ![]() ![]() | 7 (20) | Discovery STE (GE) | FOV, NS; slice, NS; res, 5.1 mm; fasting, 5 h; time, 60′; dose, 3.7 MBq/kg | 2 | NS | SUVmax |
Osborne et al. (102), USA, 2001–2004 | Cancer center; >5.0 cm and/or positive node | 32 | 50a (28–72) | 32 | 3.0a (0.2–8.4) | ![]() | ![]() | ![]() | IHC NOS; FISH NOS | ![]() ![]() ![]() | 13 (41) | Advance or Discovery LS (GE), Biograph (Siemens) | FOV, NS; slice, NS; res, NS; fasting, 6 h; time, 50–60′; dose, 370–555 MBq | NS | NS | SUVmax |
Sanli et al. (103), Turkey, 2009–2011 | University hospital | 79 | 53a (21–81) | 79 | 3.0b (0.7–10.0) | ![]() | ![]() | ![]() | IHC Thermo scientific (SP3) | ![]() ![]() ![]() | 28 (35) | NS | FOV, NS; slice, NS; res, NS; fasting, 6 h; time, 60′; dose, 370–550 MBq | NS | NS | SUVmax |
Straver et al. (104), the Netherlands, 2007, NS | Cancer center; >3.0 cm and/or positive node | 37 | 49a (30–68) | 37 | NS (NS) | ![]() | ![]() | ![]() | NS | NS | 11 (30) | Gemini TF (Philips) | FOV, NS; slice, NS; res, 2 mm; fasting, 6 h; time, 60′; dose, 180–240 MBq | 3 | NS | SUVmax |
Tozaki and Hoshi (91), Japan, 2008–2009 | General hospital; ≥1.5–3.0 cm only | 50 | 52a (30–86) | 50 | 2.2a (1.5–3.0) | ![]() | ![]() | ![]() | IHC Dako (NS); FISH (PathVysion) | ![]() ![]() ![]() | 6 (12) | Discovery ST (GE) | FOV, 15.7-cm axial; slice, 3.3 mm; res, NS; fasting, NS; time, NS; dose, 4.3 MBq/kg | NS | NS | SUVmax |
Ueda et al. (105), Japan, 2005–2007 | University hospital | 145 | 54a (34–81) | 145 | NS (NS) | ![]() | ![]() | ![]() | IHC Dako (NS) | ![]() ![]() ![]() | 31 (21) | Biograph LSO Emotion (Siemens) | FOV, NS; slice and res, NS; fasting, 4 h; time, 60′; dose, 3.7 MBq/kg | NS | NS | SUVmax |
Ueda et al. (106), Japan, 2007–2008 | University hospital; only ER+ neoadjuvant therapy | 11 | 74a (±9.3) | 12 | 2.6a (±1.0) | ![]() | ![]() | ![]() | IHC NOS | ![]() ![]() ![]() | 2 (17) | Biograph Duo (Siemens) | FOV, 15.8 cm; slice, 2.5 mm; res, 6.3 mm; fasting, 6 h; time, 60′; dose, 3.7 MBq/kg | 2 | NS | SUVmax |
Wang et al. (107), USA, 2007–2009 | University hospital | 98 | 53a (±13) | 100 | 3.5a (0.5–13.0) | ![]() | ![]() | ![]() | IHC NOS; FISH NOS | ![]() ![]() ![]() | 18 (18) | (Dedicated) PEM Flex Solo (Naviscan) | FOV, 24 cm ×16.4 cm; slice, NS; res, NS; fasting, 6 h; time, 121′; dose, 596 MBq | 2 | Yes | SUVmax |
. | Patients . | Breast cancers . | HER2 assessment . | Imaging acquisition and results . | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
. | . | . | . | . | . | Histologyc . | . | Positive . | . | . | Readers . | . | ||||
Ref., country, recruitment period . | Recruitment . | N . | Age in years (range/SD) . | N . | Size in cm (range/SD) . | IDC . | Else . | DCIS . | Assayd . | Cutoff . | N (%) . | Imaging system (manufacturer) . | Imaging parameters . | N . | Blinded . | Imaging features described in reviewe,f,g,h . |
Mammography | Analog/Digital | |||||||||||||||
Agrawal et al. (28), Poland, 1992–2001 | University hospital | 184 | 57a (32–75) | 184 | NS (NS) | ![]() | ![]() | ![]() | IHC Dakopatts (K-353) | NS | 100 (54) | NS | Analog | NS | NS | Level of suspicion |
Aiello et al. (29), USA, 1988–1995 | Breast cancer screening program | 461 | NS (NS) | 461 | NS (0.1–10) | NOS | ![]() | IHC NOS | Other | 79 (17) | NS | Analog | 1 | NS | BrDe | |
Arora et al. (30), USA, 2005–2007 | Cancer center; no prior breast cancer | 1,323 | 56b (27–91) | 1,323 | 1.5b (0.1–11) | ![]() | ![]() | ![]() | IHC NOS | NS | 170 (13) | NS | Analog, digital | NS | NS | BrDe |
Badra et al. (31), Greece, 1994–2004 | University hospital; nonpalpable screen-detected | 75 | 56b (35–74) | 75 | NS (NS) | ![]() | ![]() | ![]() | IHC BioGenex (CB11) | ![]() ![]() ![]() | 34 (45) | NS | NS | 2 | NS | Cal |
Cui et al. (32), China, 2009–2011 | University hospital; triple-negative and triple-positive only | 161 | 51a (27–87) | 161 | 2.4a (NS) | ![]() | ![]() | ![]() | IHC NOS | ![]() ![]() ![]() | 44 (27) | Senographe 800T (GE) | Analog | 2 | Yes | BrDe; Mas (Mar; Sha; Cal); Cal |
Di Nubila et al. (33), Italy, 2000–2002 | Cancer center; ≤ 35 y, no prior breast cancer | 232 | 32a (22–35) | 232 | 2.3a (NS) | ![]() | ![]() | ![]() | IHC Triton (TAB250) | ![]() ![]() ![]() | 64 (28) | Senographe 2000D; Senographe DMR (GE) | Analog, digital | NS | NS | Level of suspicion; BrDe; Cal |
Enache et al. (34), Romania, 2010–2011 | General hospital; only ER− | 40 | 51a (25–88) | 40 | 4.1a (0.6–10.7) | ![]() | ![]() | ![]() | IHC Dako (polyclonal); CISH Invitrogen | ![]() ![]() ![]() | 11 (28) | NS | NS | NS | NS | BrDe; Mas (Mar; Sha; Cal); Cal (Mor); ArDi; FoAs |
Evans et al. (35), UK, 1978–1992 | University hospital | 126 | NS (NS) | 126 | NS (NS) | ![]() | ![]() | ![]() | IHC NOS (AP21N) | ![]() ![]() ![]() | 39 (31) | NS | Analog | 1 | Yes | Cal (Mor; Dis) |
Fasching et al. (36), Germany, 2001–2003 | University hospital | 423 | 60a (±13) | 423 | 1.9a (1.4) | ![]() | ![]() | ![]() | IHC NOS | ![]() ![]() ![]() | 37 (9) | Mammomat 3000 Nova (Siemens) | Analog | 1 | Yes | BrDe |
Gajdos et al. (37), USA, 1993–1999 | Tertiary care hospital | 118 | 59a (30–92) | 118 | 1.0a (0.1–3.0) | ![]() | ![]() | ![]() | IHC NOS | NS | 36 (31) | NS | Analog | 5 | Yes | Mas (Cal); Cal; ArDi |
Gu et al. (38), China, 2003–2005 | University hospital | 62 | 51a (31–79) | 62 | NS (NS) | ![]() | ![]() | ![]() | IHC NOS | ![]() ![]() ![]() | 18 (29) | Senographe DMR (GE) | Analog | NS | NS | Cal |
Jiang et al. (39), China, 2008–2010 | University hospital | 63 | 49a (27–79) | 63 | NS (0.5–9.0) | ![]() | ![]() | ![]() | IHC Golden Bridge International (CB11) | ![]() ![]() ![]() | 19 (30) | Mammomat Novation DR (Siemens) | Digital | 2 | Yes | Mas (Mar) |
Kim et al. (40), South Korea, 2005–2008 | Cancer center | 151 | 48a (26–75) | 151 | NS (NS) | ![]() | ![]() | ![]() | IHC Zymed (NS) | ![]() ![]() ![]() | 54 (36) | Selenia (Hologic) | Digital | 2 | NS | Cal |
Ko et al. (41), South Korea, 2007–2008 | Cancer center; only TN, ER+/PR−/HER2−, ER−/PR−/HER2+ | 239 | 52a (26–86) | 239 | 2.3a (NS) | ![]() | ![]() | ![]() | IHC Zymed (NS) | ![]() ![]() ![]() | 63 (26) | Selenia (Hologic) | Digital | 2 | NS | Mas (Cal); Cal; ArDi; FoAs |
Kuo et al. (42), Taiwan, 1999–2005 | University hospital; <stage IV disease, follow-up ≥ 1 y | 998 | 51a (±11) | 998 | NS (NS) | NOS | ![]() | IHC BioGenex (CB11); FISH NOS | ![]() ![]() ![]() | 156 (16) | NS | NS | 1 | NS | Level of suspicion | |
Li and Chen (43), China, 2005–2009 | University hospital | 110 | 52a (29–77) | 110 | NS (NS) | ![]() | ![]() | ![]() | IHC NOS | ![]() ![]() ![]() | 49 (45) | Giotto NOS (IMS) | Digital | 3 | Yes | Mas (Mar); Cal (Mor) |
Ma et al. (44), USA, 1994–1998 | Women's Contraceptive and Reproductive Experiences Study | 352 | 49a (35–64) | 352 | NS (NS) | NOS | ![]() | IHC Dako (10H8) | ![]() ![]() ![]() | 62 (18) | NS | Analog | 1 | NS | BrDe | |
Månsson et al. (45), Sweden, 1986–1995 | Population-based; unifocal, ≤1.5 cm | 361 | 63b (±12) | 361 | NS (0.1–1.5) | NOS | ![]() | IHC Dako (polyclonal) | Other | 142 (39) | NS | Analog | 1 | Yes | Cal | |
Mun et al. (46), South Korea, 2007–2010 | University hospital; screen-detected | 213 | 50a (30–76) | 213 | 2.4a (0.5–8.5) | ![]() | ![]() | ![]() | IHC NOS; FISH NOS | ![]() ![]() ![]() | 77 (36) | Senographe DS; Senographe Essential (GE) | Analog; digital | 2 | NS | Cal |
Palka et al. (47), Hungary, 2000–2003 | University hospital; high-risk breast cancer adjuvant study | 55 | 52a (33–70) | 55 | 3.5a (NS) | NOS | ![]() | IHC NOS | ![]() ![]() ![]() | 14 (25) | NS | NS | 1 | Yes | Cal | |
Palka et al. (48), Hungary, 2004–2006 | University hospital | 560 | 58a (28–85) | 560 | NS (NS) | ![]() | ![]() | ![]() | IHC NOS | ![]() ![]() ![]() | 85 (15) | NS | NS | ≥2 | NS | Cal |
Phipps et al. (49), USA, 1999–2008 | BCSC; no history of breast cancer | 7,281 | NS (NS) | 7,281 | NS (NS) | ![]() | ![]() | ![]() | IHC NOS; FISH NOS | ![]() ![]() ![]() | 172 (2) | NS | NS | NS | Yes | BrDe |
Pollan et al. (50), Spain, 1996–2005 | Navarre Breast Cancer Screening Program | 834 | NS (NS) | 834 | NS (NS) | ![]() | ![]() | ![]() | NS | NS | 111 (13) | NS | NS | 1 | Yes | BrDe |
Seo et al. (51), USA, 2001–2003 | University hospital | 498 | 57a (24–95) | 543 | NS (NS) | ![]() | ![]() | ![]() | IHC Dako (HercepTest); FISH PathVysion | ![]() ![]() ![]() | 159 (29) | Mammomat 3000 Nova (Siemens), Seno-graphe 2000D (GE) | Analog, digital | 1 | NS | BrDe; Mas (Mar; Sha; Cal); Cal (Mor; Dis); ArDi; FoAs; SkTh; Oth |
Shin et al. (52), South Korea, 2005–2006 | University hospital; node negative | 710 | 49a (21–81) | 715 | NS (NS) | ![]() | ![]() | ![]() | IHC NOS | ![]() ![]() ![]() | 165 (23) | Senographe DMR (GE) | Analog | 1 | Yes | Mas (Mar; Cal); Cal |
Sun et al. (53), China, 2004–2007 | General hospital | 144 | 49a (23–83) | 144 | NS (NS) | NS | IHC Beijing Zhongshan Biotechnology (NS) | NS | 58 (40) | NS | Digital | 2 | NS | Cal | ||
Taneja et al. (54), UK, 1996–1997 | University hospital | 415 | 55a (27–70) | 415 | NS (NS) | ![]() | ![]() | ![]() | IHC Dako (NS) | Other | 132 (32) | NS | Analog | 1 | Yes | BrDe; Mas (Mar); Cal; ArDi; FoAs |
Wang et al. (55), China, 2003–2006 | University hospital | 152 | 51b (27–82) | 152 | NS (NS) | ![]() | ![]() | ![]() | IHC Dako (K5204) | ![]() ![]() ![]() | 73 (48) | Gold Standard (Pan-pacific Enterprises Inc.) | Digital | 2 | Yes | Mas (Mar; Cal); Cal (Mor; Dis); ArDi; FoAs |
Wang et al. (56), USA, 1997–2003 | University hospital; only ER− | 56 | 53a (31–84) | 56 | 2.4a (0.2–8.0) | ![]() | ![]() | ![]() | IHC Dako (HercepTest); FISH PathVysion | ![]() ![]() ![]() | 23 (41) | NS | Analog | 3 | Yes | BrDe; Mas (Mar; Sha; Cal); Cal (Mor); ArDi; FoAs |
Wang et al. (57), China, 2006–2007 | General hospital | 60 | 50b (28–75) | 60 | NS (NS) | ![]() | ![]() | ![]() | IHC Fuzhou Maixin (NS) | ![]() ![]() ![]() | 30 (50) | Giotto NOS (IMS) | NS | NS | Yes | Mas (Cal); Cal; ArDi |
Wen et al. (58), China, 2010 | University hospital; no [ER+ or PR+ and HER2+] group | 477 | 55b (25–86) | 477 | 2.2b (0.5–7.0) | ![]() | ![]() | ![]() | IHC NOS | ![]() ![]() ![]() | 76 (16) | NS | Digital | ≥2 | NS | Mas (Mar; Sha; Cal); Cal (Mor; Dis); SkTh; Oth |
Yaghjyan et al. (59), USA, 1989–2004 | Nurses' Health Study; postmenopausal | 563 | NS (NS) | 563 | NS (NS) | ![]() | ![]() | ![]() | IHC NOS | ![]() ![]() ![]() | 140 (25) | NS | Analog | NS | Yes | BrDe |
Yang et al. (60), USA, 1999–2005 | Cancer center; ≤45 y premenopausal | 198 | 34a (25–46) | 198 | 2.8a (0.7–9.0) | ![]() | ![]() | ![]() | IHC NOS; FISH NOS | ![]() ![]() ![]() | 67 (34) | M3 (Hologic), Senographe DMR (GE) | Analog | 2 | Yes | BrDe; Mas (Mar; Sha; Cal); Cal; ArDi |
Breast ultrasound | Transducer bandwidth | |||||||||||||||
Agrawal et al. (28), Poland, 1992–2001 | University hospital | 184 | 57a (32–75) | 184 | NS (NS) | ![]() | ![]() | ![]() | IHC Dakopatts (K-353) | NS | 100 (54) | NS | NS | NS | NS | Level of suspicion |
Au-Yong et al. (61), UK, 1996–1997 | University hospital | 227 | 63 |