SerpinB2 deficiency is associated with delayed mammary tumor development and decreased pro-tumorigenic macrophage polarization.

The in vivo functions of SerpinB2 in tumor cells and tumor-associated macrophages (TAMs) during breast cancer development and metastasis remain elusive. SerpinB2-deficient MMTV-PyMT mice (PyMTSB2-/-) were previously produced to explore the biological roles of SerpinB2 in breast cancer. Compared with MMTV-PyMT wild-type (PyMTWT) mice, PyMTSB2-/- mice showed delayed tumor progression and reduced CK8 + tumor cell dissemination to lymph nodes. RNA-Seq data revealed significantly enriched genes associated with inflammatory responses, especially upregulated M1 and downregulated M2 macrophage marker genes in PyMTSB2-/- tumors. Decreased CD206+M2 and increased NOS2+M1 markers were detected in the primary tumors and metastatic lymph nodes of PyMTSB2-/- mice. In an in vitro study, SerpinB2 knockdown decreased the sphere formation and migration of MDA-MB-231 cells and suppressed protumorigenic M2 polarization of RAW264.7 cells. The combination of low SerpinB2, high NOS2, and low CD206 expression was favorable for survival in patients with breast cancer, as assessed in the BreastMark dataset. Our study demonstrates that SerpinB2 deficiency delays mammary tumor development and metastasis in PyMTWT mice, along with reduced sphere formation and migration abilities of tumor cells and decreased macrophage protumorigenic polarization.

Use of imaging prediction model for omission of axillary surgery in early-stage breast cancer patients.

PURPOSE: To develop a prediction model incorporating clinicopathological information, US, and MRI to diagnose axillary lymph node (LN) metastasis with acceptable false negative rate (FNR) in patients with early stage, clinically node-negative breast cancers. METHODS: In this single center retrospective study, the inclusion criteria comprised women with clinical T1 or T2 and N0 breast cancers who underwent preoperative US and MRI between January 2017 and July 2018. Patients were temporally divided into the development and validation cohorts. Clinicopathological information, US, and MRI findings were collected. Two prediction models (US model and combined US and MRI model) were created using logistic regression analysis from the development cohort. FNRs of the two models were compared using the McNemar test. RESULTS: A total of 964 women comprised the development (603 women, 54 ± 11 years) and validation (361 women, 53 ± 10 years) cohorts with 107 (18%) and 77 (21%) axillary LN metastases in each cohort, respectively. The US model consisted of tumor size and morphology of LN on US. The combined US and MRI model consisted of asymmetry of LN number, long diameter of LN, tumor type, and multiplicity of breast cancers on MRI, in addition to tumor size and morphology of LN on US. The combined model showed significantly lower FNR than the US model in both development (5% vs. 32%, P < .001) and validation (9% vs. 35%, P < .001) cohorts. CONCLUSION: Our prediction model combining US and MRI characteristics of index cancer and LN lowered FNR compared to using US alone, and could potentially lead to avoid unnecessary SLNB in early stage, clinically node-negative breast cancers.

Beyond Breast Density: Risk Measures for Breast Cancer in Multiple Imaging Modalities.

Breast density is an independent risk factor for breast cancer. In digital mammography and digital breast tomosynthesis, breast density is assessed visually using the four-category scale developed by the American College of Radiology Breast Imaging Reporting and Data System (5th edition as of November 2022). Epidemiologically based risk models, such as the Tyrer-Cuzick model (version 8), demonstrate superior modeling performance when mammographic density is incorporated. Beyond just density, a separate mammographic measure of breast cancer risk is parenchymal textural complexity. With advancements in radiomics and deep learning, mammographic textural patterns can be assessed quantitatively and incorporated into risk models. Other supplemental screening modalities, such as breast US and MRI, offer independent risk measures complementary to those derived from mammography. Breast US allows the two components of fibroglandular tissue (stromal and glandular) to be visualized separately in a manner that is not possible with mammography. A higher glandular component at screening breast US is associated with higher risk. With MRI, a higher background parenchymal enhancement of the fibroglandular tissue has also emerged as an imaging marker for risk assessment. Imaging markers observed at mammography, US, and MRI are powerful tools in refining breast cancer risk prediction, beyond mammographic density alone.

Semiannual Breast US or MRI Screening in Patients with a Personal History of Breast Cancer.

Background The wide variability of screening imaging use in patients with a personal history of breast cancer (PHBC) warrants investigation of its comparative clinical effectiveness. While more intensive screening with US or MRI at an interval of less than 1 year could increase early-stage breast cancer detection, its benefit has not been established. Purpose To investigate the outcomes of semiannual multimodality screening in patients with PHBC. Materials and Methods An academic medical center database was retrospectively searched for patients diagnosed with breast cancer between January 2015 and June 2018 who had undergone annual mammography with either semiannual incidence US or MRI screening from July 2019 to December 2019 and three subsequent semiannual screenings over a 2-year period. The primary outcome was second breast cancers diagnosed during follow-up. Examination-level cancer detection and interval cancer rates were calculated. Screening performances were compared with χ2 or Fisher exact tests or a logistic model with generalized estimating equations. Results Our final cohort included 2758 asymptomatic women (median age, 53 years; range, 20-84 years). Among 5615 US and 1807 MRI examinations, 18 breast cancers were detected after negative findings on a prior semiannual incidence US screening examination; 44% (eight of 18) were stage 0 (three detected with MRI; five, with US), and 39% (seven of 18) were stage I (three detected with MRI; four, with US). MRI had a cancer detection rate up to 17.1 per 1000 examinations (eight of 467; 95% CI: 8.7, 33.4), and the overall cancer detection rates of US and MRI were 1.8 (10 of 5615; 95% CI: 1.0, 3.3) and 4.4 (eight of 1807; 95% CI: 2.2, 8.8) per 1000 examinations, respectively (P = .11). Conclusion Supplemental semiannual US or MRI screening depicted second breast cancers after negative findings at prior semiannual incidence US examination in patients with PHBC. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Berg in this issue.

Background Parenchymal Enhancement at Postoperative Surveillance Breast MRI: Association with Future Second Breast Cancer Risk.

Background Background parenchymal enhancement (BPE) is a known risk factor for breast cancer. However, studies on the association between BPE and second breast cancer risk are still lacking. Purpose To investigate whether BPE at surveillance breast MRI is associated with subsequent second breast cancer risk in women with a personal history of breast cancer. Materials and Methods A retrospective search of the imaging database of an academic medical center identified consecutive surveillance breast MRI examinations performed between January 2008 and December 2017 in women who underwent surgery for primary breast cancer and had no prior diagnosis of second breast cancer. BPE at surveillance breast MRI was qualitatively assessed using a four-category classification of minimal, mild, moderate, or marked. Future second breast cancer was defined as ipsilateral breast tumor recurrence or contralateral breast cancer diagnosed at least 1 year after each surveillance breast MRI examination. Factors associated with future second breast cancer risk were evaluated using the multivariable Fine-Gray subdistribution hazard model. Results Among the 2668 women (mean age at baseline surveillance breast MRI, 49 years ± 8 [SD]), 109 developed a second breast cancer (49 ipsilateral, 58 contralateral, and two ipsilateral and contralateral) at a median follow-up of 5.8 years. Mild, moderate, or marked BPE at surveillance breast MRI (hazard ratio [HR], 2.1 [95% CI: 1.4, 3.1]; P < .001), young age (<45 years) at initial breast cancer diagnosis (HR, 3.4 [95% CI: 1.7, 6.4]; P < .001), positive results from a BRCA1/2 genetic test (HR, 6.5 [95% CI: 3.5, 12.0]; P < .001), and negative hormone receptor expression in the initial breast cancer (HR, 1.6 [95% CI: 1.1, 2.6]; P = .02) were independently associated with an increased risk of future second breast cancer. Conclusion Background parenchymal enhancement at surveillance breast MRI was associated with future second breast cancer risk in women with a personal history of breast cancer. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Niell in this issue.

Transcriptome analysis of SerpinB2-deficient breast tumors provides insight into deciphering SerpinB2-mediated roles in breast cancer progression.

BACKGROUND: SerpinB2 is highly expressed in immune and tumor cells and is involved in multiple biological functions, including cell survival and remodeling for disease progression. This study prepared SerpinB2-deficient mice and analyzed the differentially expressed genes (DEGs) to determine if loss of this protein delays mammary tumor progression. RESULTS: A total of 305 DEGs (75 upregulated and 230 downregulated; > 1.5-fold difference, P < 0.05) were identified in SB2-/-;PyMT tumors compared with PyMT tumors. The DEGs were mainly involved in immune and inflammatory responses related to T cell differentiation, IFN-γ production, and lymphocyte chemotaxis based on 61 enriched GO terms, hierarchical clustering, KEGG pathways, and a functionally grouped annotation network. The significantly changed DEGs (Anxa3, Ccl17, Cxcl13, Cxcr3, IFN-γ, Nr4a1, and Sema3a) annotated with at least two GO categories in SB2-/-;PyMT tumors was validated by qRT-PCR. CONCLUSIONS: SerpinB2 deficiency alters the expression of multiple genes in mammary tumors, which might cause a delay in PyMT-induced mammary tumor progression.

Diffusion-weighted Breast MRI in Prediction of Upstaging in Women with Biopsy-proven Ductal Carcinoma in Situ.

Background Accurate preoperative prediction of upstaging in women with biopsy-proven ductal carcinoma in situ (DCIS) is important for surgical planning, but published models using predictive MRI features remain lacking. Purpose To develop and validate a predictive model based on preoperative breast MRI to predict upstaging in women with biopsy-proven DCIS and to select high-risk women who may benefit from sentinel lymph node biopsy at initial surgery. Materials and methods Consecutive women with biopsy-proven DCIS who underwent preoperative 3.0-T breast MRI including dynamic contrast-enhanced (DCE) MRI and diffusion-weighted imaging (DWI) and who underwent surgery between June 2019 and March 2020 were retrospectively identified (development set) from an academic medical center. The apparent diffusion coefficients of lesions from DWI, lesion size and morphologic features on DCE MRI scans, mammographic findings, age, symptoms, biopsy method, and DCIS grade at biopsy were collected. The presence of invasive cancer and axillary metastases was determined with surgical pathology. A predictive model for upstaging was developed by using multivariable logistic regression and validated in a subsequent prospective internal validation set recruited between July 2020 and April 2021. Results Fifty-seven (41%) of 140 women (mean age, 53 years ± 11 [SD]) in the development set and 43 (41%) of 105 women (mean age, 53 years ± 10) in the validation set were upstaged after surgery. The predictive model combining DWI and clinical-pathologic factors showed the areas under the receiver operating characteristic curve at 0.87 (95% CI: 0.80, 0.92) in the development set and 0.76 (95% CI: 0.67, 0.84) in the validation set. The predicted probability of invasive cancer showed good interobserver agreement (intraclass correlation coefficient, 0.79); the positive predictive value was 85% (28 of 33), and the negative predictive value was 92% (22 of 24). Conclusion A predictive model based on diffusion-weighted breast MRI identified women at high risk of upstaging. © RSNA, 2022 Online supplemental material is available for this article See also the editorial by Baltzer in this issue. An earlier incorrect version appeared online. This article was corrected on July 7, 2022.

US Evaluation of Axillary Lymphadenopathy Following COVID-19 Vaccination: A Prospective Longitudinal Study.

Background Both temporal changes in imaging characteristics of lymphadenopathy on US scans after COVID-19 vaccination and expected duration of radiologically evident lymphadenopathy remain uncertain. Purpose To longitudinally evaluate COVID-19 vaccine-associated lymphadenopathy on axillary US scans at various time intervals in both messenger (mRNA) and vector vaccine recipients. Materials and Methods This prospective cohort study was conducted between March 2021 and January 2022. The participants were asymptomatic women without breast cancer who had received COVID-19 vaccination. Serial follow-up US was performed in women with lymphadenopathy. The following variables were assessed: cortical thickness, number of lymph nodes, morphologic characteristics, and Doppler signal. Temporal changes in cortical thickness and number of lymph nodes during follow-up were assessed using a linear mixed model. Results Ninety-one women with lymphadenopathy in the vaccinated arm had undergone a total of 215 serial US examinations (mean age, 44 years ± 13 [SD]). Fifty-one participants had received a vector vaccine (ChAdOx1 nCoV-19 vaccine) and 40 had received an mRNA vaccine (BNT162b2 vaccine [n = 37] and mRNA-1273 vaccine [n = 3]). Three of the 91 women were lost to follow-up; thus, 88 women underwent serial US. Complete resolution of axillary lymphadenopathy was observed at a median of 6 weeks after vaccination (range, 4-7 weeks) in 26% of women (23 of 88). Among 49 women with follow-up US at a median of 12 weeks after vaccination (range, 8-14 weeks), persistent lymphadenopathy was observed in 25 (51%). During the follow-up period, the cortical thickness gradually decreased (P < .001) over time regardless of vaccine type; however, values were higher in recipients of the mRNA vaccine than in recipients of the vector vaccine (P = .02). Conclusion COVID-19 vaccine-associated axillary lymphadenopathy frequently persisted for more than 6 weeks on US scans. Lymphadenopathy should be interpreted considering vaccine type and time elapsed since vaccination. Follow-up US examination at least 12 weeks after vaccination may be reasonable, particularly for recipients of the messenger RNA vaccine. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Moy and Kim in this issue.

Abbreviated Screening MRI for Women with a History of Breast Cancer: Comparison with Full-Protocol Breast MRI.

Background Few studies have compared abbreviated breast MRI with full-protocol MRI in women with a personal history of breast cancer (PHBC), and they have not adjusted for confounding variables. Purpose To compare abbreviated breast MRI with full-protocol MRI in women with PHBC by using propensity score matching to adjust for confounding variables. Materials and Methods In this single-center retrospective study, women with PHBC who underwent full-protocol MRI (January 2008-August 2017) or abbreviated MRI (September 2017-April 2019) were identified. With use of a propensity score-matched cohort, screening performances were compared between the two MRI groups with the McNemar test or a propensity score-adjusted generalized estimating equation. The coprimary analyses were sensitivity and specificity. The secondary analyses were the cancer detection rate, interval cancer rate, positive predictive value for biopsies performed (PPV3), and Breast Imaging Reporting and Data System (BI-RADS) category 3 short-term follow-up rate. Results There were 726 women allocated to each MRI group (mean age ± SD, 50 years ± 8 for both groups). Abbreviated MRI and full-protocol MRI showed comparable sensitivity (15 of 15 cancers [100%; 95% CI: 78, 100] vs nine of 13 cancers [69%; 95% CI: 39, 91], respectively; P = .17). Abbreviated MRI showed higher specificity than full-protocol MRI (660 of 711 examinations [93%; 95% CI: 91, 95] vs 612 of 713 examinations [86%; 95% CI: 83, 88], respectively; P < .001). The cancer detection rate (21 vs 12 per 1000 examinations), interval cancer rate (0 vs five per 1000 examinations), and PPV3 (61% [14 of 23 examinations] vs 41% [nine of 22 examinations]) were comparable (all P < .05). The BI-RADS category 3 short-term follow-up rate of abbreviated MRI was less than half that of full-protocol MRI (5% [36 of 726 examinations] vs 12% [84 of 726 examinations], respectively; P < .001). Ninety-three percent (14 of 15) of cancers detected at abbreviated MRI were node-negative T1-invasive cancers (n = 6) or ductal carcinoma in situ (n = 8). Conclusion Abbreviated breast MRI showed comparable sensitivity and superior specificity to full-protocol MRI in breast cancer detection in women with a personal history of breast cancer. © RSNA, 2022 Online supplemental material is available for this article.

Microcalcifications and Peritumoral Edema Predict Survival Outcome in Luminal Breast Cancer Treated with Neoadjuvant Chemotherapy.

Background Little is known regarding findings at imaging associated with survival in patients with luminal breast cancer treated with neoadjuvant chemotherapy (NAC). Purpose To determine the relationship between imaging (MRI, US, and mammography) and clinical-pathologic variables in predicting distant metastasis-free survival (DMFS) and overall survival (OS) in patients with luminal breast cancer treated with NAC. Materials and Methods In this retrospective study, consecutive women with luminal breast cancer who underwent NAC followed by surgery were identified from the breast cancer registries of two hospitals. Women from one hospital between January 2003 and July 2015 were classified into the development cohort, and women from the other hospital between January 2007 and July 2015 were classified into the validation cohort. MRI scans, US scans, and mammograms before and after NAC (hereafter, referred to as pre- and post-NAC, respectively) and clinical-pathologic data were reviewed. Peritumoral edema was defined as the water-like high signal intensity surrounding the tumor on T2-weighted MRI scans. The prediction model was developed in the development cohort by using Cox regression and then tested in the validation cohort. Results The development cohort consisted of 318 women (68 distant metastases, 54 deaths) and the validation cohort consisted of 165 women (37 distant metastases, 14 deaths) (median age, 46 years in both cohorts). Post-NAC MRI peritumoral edema, age younger than 40 years, clinical N2 or N3, and lymphovascular invasion were associated with worse DMFS (all, P < .05). Pre-NAC mammographic microcalcifications, post-NAC MRI peritumoral edema, age older than 60 years, and clinical T3 or T4 were associated with worse OS (all, P < .05). The prediction model showed good discrimination ability (C index, 0.67-0.75 for DMFS and 0.70-0.77 for OS) and stratified prognosis into low-risk and high-risk groups (10-year DMFS rates, 79% vs 21%, respectively; and 10-year OS rates, 95%-96% vs 63%-67%, respectively) in the validation cohort. Conclusion MRI features and clinical-pathologic variables were identified that were associated with prolonged survival of patients with luminal breast cancer treated with neoadjuvant chemotherapy. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Kataoka in this issue.

No axillary surgical treatment for lymph node-negative patients after ultra-sonography [NAUTILUS]: protocol of a prospective randomized clinical trial.

BACKGROUND: Following sentinel lymph node biopsy (SLNB), the axillary recurrence rate is very low although SLNB has a false-negative rate of 5-10%. In the ACOSOG Z0011 trial, non-sentinel positive-lymph nodes were found in more than 20% of the axillary dissection group; the SLNB only group did not have a higher axillary recurrence rate. These findings raised questions about the direct therapeutic effect of the SLNB. SLNB has post-surgical complications including lymphedema. Considering advances in imaging modalities and adjuvant therapies, the role of SLNB in early breast cancer needs to be re-evaluated. METHODS: The NAUTILUS trial is a prospective multicenter randomized controlled trial involving clinical stage T1-2 and N0 breast cancer patients receiving breast-conserving surgery. Axillary ultrasound is mandatory before surgery with predefined imaging criteria for inclusion. Ultrasound-guided core needle biopsy or needle aspiration of a suspicious node is allowed. Patients will be randomized (1:1) into the no-SLNB (test) and SLNB (control) groups. A total of 1734 patients are needed, considering a 5% non-inferiority margin, 5% significance level, 80% statistical power, and 10% dropout rate. All patients in the two groups will receive ipsilateral whole-breast radiation according to a predefined protocol. The primary endpoint of this trial is the 5-year invasive disease-free survival. The secondary endpoints are overall survival, distant metastasis-free survival, axillary recurrence rate, and quality of life of the patients. DISCUSSION: This trial will provide important evidence on the oncological safety of the omission of SLNB for early breast cancer patients undergoing breast-conserving surgery and receiving whole-breast radiation, especially when the axillary lymph node is not suspicious during preoperative axillary ultrasound. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04303715 . Registered on March 11, 2020.

Cancer-associated fibroblasts induce an aggressive phenotypic shift in non-malignant breast epithelial cells via interleukin-8 and S100A8.

Cancer-associated fibroblasts (CAFs) in the tumor microenvironment have been associated with tumor progression in breast cancer. Although crosstalk between breast cancer cells and CAFs has been studied, the effect of CAFs on non-neoplastic breast epithelial cells is not fully understood to date. Here, we investigated the effect of CAFs on aggressive phenotypes in non-neoplastic MCF10A breast epithelial cells. CAFs induced epithelial-to-mesenchymal transition (EMT) and invasive phenotype in MCF10A cells. S100A8, a potential prognostic marker in several cancers, was markedly increased in MCF10A cells by CAFs. S100A8 was crucial for CAFs-induced invasive phenotype of MCF10A cells. Among cytokines increased by CAFs, interleukin (IL)-8 induced S100A8 through transcription factors p65 NF-κB and C/EBPß. In a xenograft mouse model with MCF10A cells and CAFs, tumor was not developed, suggesting that coinjection with CAFs may not be sufficient for in vivo tumorigenicity of MCF10A cells. Xenograft mouse tumor models with MDA-MB-231 breast carcinoma cells provided an in vivo evidence for the effect of CAFs on breast cancer progression as well as a crucial role of IL-8 in tumor growth and S100A8 expression in vivo. Using a tissue microarray of human breast cancer, we showed that S100A8 expression was correlated with poor outcomes. S100A8 expression was more frequently detected in cancer-adjacent normal human breast tissues than in normal breast tissues. Together, this study elucidated a novel mechanism for the acquisition of invasive phenotype of non-neoplastic breast cells induced by CAFs, suggesting that targeting IL-8 and S100A8 may be an effective strategy against breast cancer.

Prediction of axillary nodal burden in patients with invasive lobular carcinoma using MRI.

PURPOSE: To investigate clinical and imaging features associated with a high nodal burden (≥ 3 metastatic lymph nodes [LNs]) and compare diagnostic performance of US and MRI in patients with invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). METHODS: Retrospective search revealed 239 patients with ILC and 999 with IDC who underwent preoperative US and MRI between January 2016 and June 2019. Patients with ILC were propensity-score-matched with patients with IDC. Univariate and multivariate logistic regression analyses were performed to determine factors associated with ≥ 3 metastatic LNs. RESULTS: 412 patients (206 ILC and 206 IDC) were evaluated. Of all patients with ILC, 27.2% (56/206) were node-positive and 7.8% (16/206) showed a high nodal burden. In multivariate analysis, the clinical N stage was the only independent factor associated with a high nodal burden in patients with IDC (odds ratio [OR] 6.24; 95% confidence interval [CI] 1.57-24.73; P = 0.009), but not in patients with ILC. Increased cortical thickness with loss of fatty hilum on US was associated with a high nodal burden in patients with ILC (OR 58.40; 95% CI 5.09-669.71; P = 0.001) and IDC (OR 24.14; 95% CI 3.52-165.37; P = 0.001), while suspicious LN findings at MRI were independently associated with a high nodal burden in ILC only (OR 13.94; 95% CI 2.61-74.39; P = 0.002). CONCLUSION: In patients with ILC, MRI findings of suspicious LNs were helpful to predict a high nodal disease burden.

Interval Cancers after Negative Supplemental Screening Breast MRI Results in Women with a Personal History of Breast Cancer.

Background There are few interval cancer studies of incident screening MRI for women with a personal history of breast cancer (PHBC). Purpose To evaluate the performance measures of screening breast MRI in women with a PHBC across multiple rounds and to identify subgroups who might be more at risk for interval cancer. Materials and Methods Between January 2008 and March 2019, consecutive screening breast MRI studies for women who had undergone breast-conserving surgery because of breast cancer were retrospectively identified. Inclusion criteria were negative or benign findings at mammography with US, availability of at least 1 year of follow-up data, and examinations having been performed within 12 months after the initial cancer surgery. Performance measures were calculated for each round. Multivariable logistic regression analysis was performed to determine factors associated with the risk of interval cancer. Results Among the 6603 MRI examinations for 2809 women (median age, 47 years; interquartile range, 42-53 years), the cancer detection rate was 8.3 per 1000 screening examinations (55 of 6603 examinations) and the interval cancer rate was 1.5 per 1000 screening examinations (10 of 6603 examinations). The sensitivity and specificity were 85% (55 of 65 examinations; 95% CI: 76, 93) and 88.3% (5775 of 6538 examinations; 95% CI: 87.6, 89.1), respectively. At multivariable analysis, interval cancers were associated with a first-degree family history of breast cancer (odds ratio [OR], 5.4; 95% CI: 1.3, 22.5; P = .02), estrogen receptor- and progesterone receptor-negative primary cancers (OR, 3.6; 95% CI: 1.1, 12.2; P = .04), and moderate or marked background parenchymal enhancement (OR, 10.8; 95% CI: 3.3, 35.7; P < .001). Conclusion Performance of screening breast MRI in women with a personal history of breast cancer was sustained across multiple rounds, and a first-degree family history of breast cancer, estrogen receptor- and progesterone receptor-negative primary cancers, and moderate or marked background parenchymal enhancement at MRI were independently associated with the risk of developing interval cancers. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Slanetz in this issue.

Factors Affecting Pathologic Complete Response Following Neoadjuvant Chemotherapy in Breast Cancer: Development and Validation of a Predictive Nomogram.

Background There is an increasing need to develop a more accurate prediction model for pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer. Purpose To develop a nomogram based on MRI and clinical-pathologic variables to predict pCR. Materials and Methods In this single-center retrospective study, consecutive women with stage II-III breast cancer who underwent NAC followed by surgery between January 2011 and December 2017 were considered for inclusion. The women were divided into a development cohort between January 2011 and September 2015 and a validation cohort between October 2015 and December 2017. Clinical-pathologic data were collected, and mammograms and MRI scans obtained before and after NAC were analyzed. Logistic regression analyses were performed to identify independent variables associated with pCR in the development cohort from which the nomogram was created. Nomogram performance was assessed with the area under the receiver operating characteristic curve (AUC) and calibration slope. Results A total of 359 women (mean age, 49 years ± 10 [standard deviation]) were in the development cohort and 351 (49 years ± 10) in the validation cohort. Hormone receptor negativity (odds ratio [OR], 3.1; 95% CI: 1.4, 7.1; P = .006), high Ki-67 index (OR, 1.05; 95% CI: 1.03, 1.07; P < .001), and post-NAC MRI variables, including small tumor size (OR, 0.6; 95% CI: 0.4, 0.9; P = .03), low lesion-to-background parenchymal signal enhancement ratio (OR, 0.2; 95% CI: 0.1, 0.6; P = .004), and absence of enhancement in the tumor bed (OR, 3.8; 95% CI: 1.4, 10.5; P = .009) were independently associated with pCR. The nomogram incorporating these variables showed good discrimination (AUC, 0.90; 95% CI: 0.86, 0.94) and calibration abilities (calibration slope, 0.91; 95% CI: 0.69, 1.13) in the independent validation cohort. Conclusion A nomogram incorporating hormone receptor status, Ki-67 index, and MRI variables showed good discrimination and calibration abilities in predicting pathologic complete response. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Imbriaco and Ponsiglione in this issue.

Glandular Tissue Component and Breast Cancer Risk in Mammographically Dense Breasts at Screening Breast US.

Background Breast density at mammography is an established risk factor for breast cancer, but it cannot be used to distinguish between glandular and fibrous tissue. Purpose To evaluate the association between the glandular tissue component (GTC) at screening breast US and the risk of future breast cancer in women with dense breasts and the association between the GTC and lobular involution. Materials and Methods Screening breast US examinations performed in women with no prior history of breast cancer and with dense breasts with negative findings from mammography from January 2012 to December 2015 were retrospectively identified. The GTC was reported as being minimal, mild, moderate, or marked at the time of the US examination. In women who had benign breast biopsy results, the degree of lobular involution in normal background tissue was categorized as not present, mild, moderate, or complete. The GTC-related breast cancer risk in women with a cancer diagnosis or follow-up after 6 months was estimated by using Cox proportional hazards regression. Cumulative logistic regression was used to evaluate the association between the GTC and lobular involution. Results Among 8483 women (mean age, 49 years ± 8 [standard deviation]), 137 developed breast cancer over a median follow-up time of 5.3 years. Compared with a minimal or mild GTC, a moderate or marked GTC was associated with an increased cancer risk (hazard ratio, 1.5; 95% CI: 1.05, 2.1; P = .03) after adjusting for age and breast density. The GTC had an inverse association with lobular involution; women with no, mild, or moderate involution had greater odds (odds ratios of 4.9 [95% CI: 1.5, 16.6], 2.6 [95% CI: 0.95, 7.2], and 1.8 [95% CI: 0.7, 4.6], respectively) of a moderate or marked GTC than those with complete involution (P = .004). Conclusion The glandular tissue component was independently associated with the future breast cancer risk in women with dense breasts and reflects the lobular involution. It should be considered for risk stratification during screening breast US. © RSNA, 2021 Online supplemental material is available for this article.

Simultaneous Multislice Readout-Segmented Echo Planar Imaging for Diffusion-Weighted MRI in Patients With Invasive Breast Cancers.

BACKGROUND: In diffusion-weighted imaging (DWI) of breast MRI, simultaneous multislice acceleration techniques can be used for readout-segmented echo planar imaging (rs-EPI) to shorten the scan time. PURPOSE: To compare the image quality, apparent diffusion coefficient (ADC) value, and scan time of rs-EPI and simultaneous multislice rs-EPI (SMS rs-EPI) sequences. STUDY TYPE: Retrospective. SUBJECTS: In all, 134 consecutive women (mean age: 55.3 years) with invasive breast cancer who underwent preoperative MRI. FIELD STRENGTH/ SEQUENCES: 3.0T; rs-EPI sequence, prototypic SMS rs-EPI sequence and dynamic contrast-enhanced MRI (DCE-MRI) sequence ASSESSMENT: For quantitative comparison, two radiologists independently measured the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), lesion contrast, and apparent diffusion coefficient (ADC). For qualitative comparison, image quality, lesion conspicuity, and reader preference were assessed with a reference of DCE-MRI. STATISTICAL TESTS: Paired t-tests and Mann-Whitney tests were used. RESULTS: For SNR and CNR, there were no differences between the sequences (P = 0.342 and 0.665 for reader 1; P = 0.606 and P = 0.116 for reader 2). Lesion contrast of SMS rs-EPI was higher than that of rs-EPI (P < 0.05 for both reader 1 and reader 2). Mean tumor ADC was similar in rs-EPI and SMS rs-EPI sequences (0.98 ± 0.22 vs. 1.00 ± 0.22; P = 0.291 for reader 1, 0.98 ± 0.21 vs. 1.00 ± 0.22; P = 0.418 for reader 2). Regarding qualitative comparison, image quality and lesion conspicuity were higher in SMS rs-EPI than in rs-EPI (both P < 0.05 for both readers). The two readers regarded SMS rs-EPI as superior or equal to rs-EPI in over 90% of cases. The acquisition time was 4:30 minutes for rs-EPI and 2:31 minutes for SMS rs-EPI. DATA CONCLUSION: The SMS rs-EPI sequence resulted in a similar ADC value and better image quality than the rs-EPI sequence in a 44.1% reduced scan time. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: 3.

Noncontrast-Enhanced MR-Based Conductivity Imaging for Breast Cancer Detection and Lesion Differentiation.

BACKGROUND: There is increasing interest in noncontrast-enhanced MRI due to safety concerns for gadolinium contrast agents. PURPOSE: To investigate the clinical feasibility of MR-based conductivity imaging for breast cancer detection and lesion differentiation. STUDY TYPE: Prospective. SUBJECTS: One hundred and ten women, with 112 known cancers and 17 benign lesions (biopsy-proven), scheduled for preoperative MRI. FIELD STRENGTH/SEQUENCE: Non-fat-suppressed T2-weighted turbo spin-echo sequence (T2WI), dynamic contrast-enhanced MRI and diffusion-weighted imaging (DWI) at 3T. ASSESSMENT: Cancer detectability on each imaging modality was qualitatively evaluated on a per-breast basis: the conductivity maps derived from T2WI were independently reviewed by three radiologists (R1-R3). T2WI, DWI, and pre-operative digital mammography were independently reviewed by three other radiologists (R4-R6). Conductivity and apparent diffusion coefficient (ADC) measurements (mean, minimum, and maximum) were performed for 112 cancers and 17 benign lesions independently by two radiologists (R1 and R2). Tumor size was measured from surgical specimens. STATISTICAL TESTS: Cancer detection rates were compared using generalized estimating equations. Multivariable logistic regression analysis was performed to identify factors associated with cancer detectability. Discriminating ability of conductivity and ADC was evaluated by using the areas under the receiver operating characteristic curve (AUC). RESULTS: Conductivity imaging showed lower cancer detection rates (20%-32%) compared to T2WI (62%-71%), DWI (85%-90%), and mammography (79%-88%) (all P < 0.05). Fatty breast on MRI (odds ratio = 11.8, P < 0.05) and invasive tumor size (odds ratio = 1.7, P < 0.05) were associated with cancer detectability of conductivity imaging. The maximum conductivity showed comparable ability to the mean ADC in discriminating between cancers and benign lesions (AUC = 0.67 [95% CI: 0.59, 0.75] vs. 0.84 [0.76, 0.90], P = 0.06 (R1); 0.65 [0.56, 0.73] vs. 0.82 [0.74, 0.88], P = 0.07 (R2)). DATA CONCLUSION: Although conductivity imaging showed suboptimal performance in breast cancer detection, the quantitative measurement of conductivity showed the potential for lesion differentiation. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Automated breast US as the primary screening test for breast cancer among East Asian women aged 40-49 years: a multicenter prospective study.

OBJECTIVES: To prospectively evaluate the diagnostic performance of screening ABUS as the primary screening test for breast cancer among Korean women aged 40-49 years. METHODS: This prospective, multicenter study included asymptomatic Korean women aged 40-49 years from three academic centers between February 2017 and October 2019. Each participant underwent ABUS without mammography, and the ABUS images were interpreted at each hospital with double-reading by two breast radiologists. Biopsy and at least 1 year of follow-up was considered the reference standard. Diagnostic performance of ABUS screening and subgroup analyses according to patient and tumor characteristics were evaluated. RESULTS: Reference standard data were available for 959 women. The recall rate was 9.8% (95% confidence interval [CI]: 7.9%, 11.7%; 94 of 959 women) and the cancer detection yield was 5.2 per 1000 women (95% CI: -0.6, 11.1; 5 of 959 women). There was only one interval cancer. The sensitivity was 83.3% (95% CI: 53.5%, 100%; 5 of 6 cancers) and the specificity was 90.7% (95% CI: 88.8%, 92.5%; 864 of 95. women). The positive predictive values of biopsies performed (PPV3) was 20.0% (95% CI: 4.3%, 35.7%; 5 of 25 women). Women with heterogeneous background echotexture had a higher recall rate (p = .009) and lower specificity (p = .036). Women with body mass index values < 25 kg/m2 had a higher mean recall rate (p = .046). CONCLUSION: In East Asia, screening automated breast US may be an alternative to screening mammography for detecting breast cancers in women aged 40-49 years. KEY POINTS: • Automated breast US screening for breast cancer in asymptomatic women aged 40-49 is effective with 5.2 per 1000 cancer detection yield. • Women with heterogeneous background echotexture had a higher recall rate and lower specificity. • Women with body mass index < 25 kg/m2 had a higher recall rate.

Theranostics for Breast Cancer Stem Cells.

Effectively targeting and treating breast cancer stem cells (BCSCs), which have been linked to tumor development and metastasis, and recurrence still remains a challenging issue in preclinic and clinic. Screening and identifying characteristic BCSC biomarkers is important for distinguishing BCSCs from differentiated tumor cells within the tumor mass. Molecular imaging and nanotechnology are evolving as new fields that have a potentially high research and clinical impact. Developing the biocompatible contrast agents conjugated with high-affinity biomarker to selectively target BCSCs and is one of the key prerequisites for image-guided diagnosis and monitoring therapy of BCSCs. Very recently, we documented the extra domain-B fibronectin (EDB-FN), which is considered as a new putative biomarker for BCSCs (NDY-1 cell) derived from human breast carcinosarcoma. We here review BCSC-targeted theranostics in vitro and in vivo by delivering siRNA or drug using the nanoparticles conjugated with a small peptide specific to EDB-FN.