Strategies to Improve Racial and Ethnic Diversity in Breast Imaging Training and Beyond.

Diversity and inclusion in breast imaging can improve creativity and innovation, enrich the workplace environment, and enhance culturally appropriate care for an increasingly diverse patient population. Current estimates predict the racial and ethnic demographics of the United States population will change markedly by the year 2060, with increases in representation of the Black demographic projected to comprise 15% of the population (currently 13.3%) and the Hispanic/Latinx demographic projected to comprise 27.5% of the population (currently 17.8%). However, matriculation rates for those who are underrepresented in medicine (URM), defined as "racial and ethnic populations that are underrepresented in the medical profession relative to their numbers in the general population," have remained largely stagnant. Black students comprise only 7.1% of medical student matriculants, and Hispanic/Latinx students comprise only 6.2% of medical school matriculants compared to the general population. The matriculation rate of URM students into diagnostic radiology is even lower, with Black trainees comprising 3.1% of radiology residents and Hispanic/Latinx trainees comprising 4.8% of radiology residents. This lack of URM radiology resident representation leads to a lack of URM potential applicants to breast imaging fellowships due to the pipeline effect. Strategies to improve diversity and inclusion in breast imaging include recruiting a diverse breast imaging workforce, establishing robust mentorship and sponsorship programs, fostering an inclusive training and workplace environment, and retaining and promoting a diverse workforce.

Clinicopathological and radiological characterization of myofibroblastoma of breast: A single institutional case review.

Myofibroblastoma is a rare type of benign myofibroblastic neoplasm in the breast. It is clinically presented as a well-circumscribed mass, usually small in size (usually less than 4.0 cm), and can mostly be cured by local excision. Rare cases of giant myofibroblastoma greater than 10 cm have been reported, but also follow a benign clinical course. Histologically, breast myofibroblastoma is featured by bland fascicles of spindle cells intermixed with thick hyalinized collagen bundles. Mast cells are frequently found within the stroma. However, a wide spectrum of morphological variants can occur in myofibroblatoma, making its diagnosis challenging sometimes. Differential diagnosis of myofibroblastoma with other spindle cell lesions in the breast, either benign or malignant, is also important in practice. In this study, we collected 15 cases of breast myofibroblastoma diagnosed in our institution during a 20 year period. The sizes of these cases range from 0.4 cm to 35.2 cm (mean is 3.7 cm). To our knowledge, the case of giant breast myofibroblastoma we presented here is the largest one reported to date. The histological examination of the cases show great morphological variations. Besides the classical type, features of cellular, collagenized, palisading, epithelioid, myxoid, myoid, solitary fibrous tumor-like are also identified in the case series. Immunohistochemical staining patterns as well as clinical features of the cases are also summarized and compared. All cases in this study show no recurrence on follow-up. In addition, cases that are important differential diagnosis for breast myofibroblastoma are also studied. Their key histological characteristics are compared with myofibroblastoma, and their immunohistochemical and molecular features are discussed.

Fast MRI breast cancer screening - Ready for prime time.

OBJECTIVE: The manuscript discusses landmark studies using abbreviated MRI for breast cancer screening. This includes abbreviated dynamic contrast enhanced MRI and diffusion weighted imaging. Our institutional experience with abbreviated MR protocol for breast cancer screening is also described. CONCLUSION: Abbreviated MRI protocols were found to demonstrate value for screening of breast cancer. It has been shown that abbreviated protocol MRI provides similar diagnostic sensitivities to full protocol MRI for breast cancer in women with increased lifetime risk. Our institutional abbreviated MRI protocol for breast cancer offers improved time and workflow efficiencies and has the potential to increase the number of breast cancers detected and the detection of pathologically relevant invasive breast cancer at earlier stages.

Implementing Abbreviated MRI Screening Into a Breast Imaging Practice.

OBJECTIVE. The purpose of this article is to describe steps for implementing abbreviated breast MRI into a breast imaging practice. CONCLUSION. Mammographic screening for breast cancer has been the standard of care. However, breast cancer remains a leading cause of death of women. Studies have shown that MRI performed with an abbreviated protocol for women at average and slightly increased risk depicts mammographically occult biologically significant cancers at early stages.

Lobular neoplasia diagnosed on breast Core biopsy: frequency of carcinoma on excision and implications for management.

The appropriate follow-up and treatment for patients with a core biopsy diagnosis of lobular neoplasia (atypical lobular hyperplasia or lobular carcinoma in situ) remains controversial. Several studies have attempted to address this issue, with recommendations ranging from close clinical follow-up or surveillance to mandatory surgical excision in all cases. We report the findings at our institution, where virtually every core needle biopsy diagnosis of lobular neoplasia results in follow-up excision. The goal of the study was to identify potential predictors of upgrade to a more significant lesion. We identified 76 patients over a 15-year period with a core biopsy diagnosis of pure lobular neoplasia and no other high-risk lesions. Subsequent surgical excision identified 10 cases (13%) that were upgraded to carcinoma. Upgrade diagnoses included invasive ductal carcinoma (n=1), invasive lobular carcinoma (n=4), ductal carcinoma in situ (n=3), and pleomorphic lobular carcinoma in situ (n=2). All 10 upgraded cases had imaging findings suspicious for malignancy including irregular masses, asymmetric densities, or pleomorphic calcifications. Of the 10 upgraded cases, 7 were diagnosed as lobular carcinoma in situ on core biopsy. The data support a role for radiologic-pathologic correlation in the evaluation of suspicious breast lesions and suggest that the extent of lobular neoplasia in core biopsy specimens may be an indicator of the likelihood of upgrade to carcinoma.

Radial scars diagnosed on breast core biopsy: Frequency of atypia and carcinoma on excision and implications for management.

AIMS: The risk of finding carcinoma in excisions following a core needle biopsy diagnosis of radial scar is not well defined and clinical management is variable. The aim of this study is to determine the frequency of high-risk lesions, ductal carcinoma in situ, and invasive carcinoma in excisions following a core biopsy diagnosis of radial scar. METHODS AND RESULTS: Dedicated breast pathologists and radiologists correlated the histologic and radiologic findings and categorized radial scars as the target lesion or an incidental finding. High-risk lesions were defined as atypical hyperplasia or classical lobular carcinoma in situ. Of the 79 radial scars identified over a 14-year period, 22 were associated with atypia or carcinoma in the core biopsy. Thirty-seven (37) of the 57 benign radial scars underwent excision with benign findings in 30 (81%), high-risk lesions in six (16%), and flat epithelial atypia in one (3%). There were no upgrades to carcinoma. One patient with a benign radial scar developed a 3-mm focus of intermediate-grade estrogen receptor-positive ductal carcinoma in situ in the same quadrant of the ipsilateral breast 72 months after excision. One patient with an incidental un-excised benign radial scar was diagnosed with ductal carcinoma in situ at a separate site of suspicious calcifications. CONCLUSIONS: In this series, none of the benign radial scars was upgraded to carcinoma. Radial scar was the targeted lesion in all cases with high-risk lesions on excision. Surgical excision may not be mandatory for patients with benign incidental radial scars on core biopsy.

Epithelial barrier function in vivo is sustained despite gaps in epithelial layers.

BACKGROUND & AIMS: Epithelial cells of the small intestine migrate to the tip of the villus at which they are shed. It is not understood how the intestinal barrier is maintained during this high cell turnover. The aim of this study was to use high-resolution in vivo light microscopy to investigate the mechanism of epithelial shedding and the site of the permeability barrier during cell shedding. METHODS: A laparotomy was performed on anesthetized mice, and a segment of small intestine was opened. The exposed epithelial surface of the intestine was imaged by multiphoton microscopy. Nuclei, cytosol, and cell membranes were imaged using the dyes Hoescht 33258, BCECF, a transgenically expressed fluorescent protein, and the membrane dye DiI. The fluorescent caspase substrate PhiPhiLux was used to detect apoptosis. RESULTS: In the epithelial monolayer, gaps were observed that lacked nuclei or cytosol but appeared to be filled with an impermeable substance. Studies with membrane impermeant fluorophores (Lucifer Yellow and Alexa-dextran) showed that the impermeable substance completely fills the void left by the absent cell. Only a fraction of gaps have either ZO-1 staining or cytoplasmic extensions from neighboring cells at the basal pole. Time-lapse studies reveal that cell shedding results in genesis of a gap and that shedding usually occurs prior to detectable cellular activation of caspase 3 or nuclear condensation. CONCLUSIONS: Results suggest that epithelial barrier function is sustained at the apical pole of the epithelial layer, despite discontinuities in the cellular layer.

Thioredoxin reductase as a potential molecular target for anticancer agents that induce oxidative stress.

Redox-sensitive signaling factors regulate multiple cellular processes, including proliferation, cell cycle, and prosurvival signaling cascades, suggesting their potential as molecular targets for anticancer agents. It is logical to set constraints that a molecular target should meet at least one of the following criteria: (1) inhibition of prosurvival signaling pathways; (2) inhibition of cell cycle progression; or (3) enhancement of the cytotoxic effects of anticancer agents. Therefore, we hypothesized that thioredoxin reductase 1 (TR), a component of several redox-regulated pathways, might represent a potential molecular target candidate in response to agents that induce oxidative stress. To address this issue, permanent cell lines overexpressing either the wild-type (pCXN2-myc-TR-wt) or a Cys-Ser mutant (pCXN2-myc-mTR) TR gene were used, as were parental HeLa cells treated with 1-methyl-1-propyl-2-imidazolyl disulfide (IV-2), a pharmacologic inhibitor of TR. Cells were exposed to the oxidative stressors, H2O2 and ionizing radiation (IR), and analyzed for changes in signal transduction, cell cycle, and cytotoxicity. Analysis of HeLa cells overexpressing the pCXN2-myc-TR-wt gene showed increased basal activity of nuclear factor kappaB (NFkappaB) and activator protein (AP-1), whereas HeLa cells expressing a pCXN2-myc-mTR gene and HeLa cells treated with IV-2 were unable to induce NFkappaB or AP-1 activity following H2O2 or IR exposure. Fluorescence-activated cell sorting analysis showed a marked accumulation of pCXN2-myc-mTR cells in the late G1 phase, whereas pCXN2-myc-TR-wt cells showed a decreased G1 subpopulation. Chemical inhibition of TR with IV-2 also completely inhibited cellular proliferation at concentrations between 10 and 25 micromol/L, resulting in a G1 phase cell cycle arrest consistent with the results from cells expressing the pCXN2-myc-mTR gene. Following exposure to H2O2 and IR, pCXN2-myc-mTR- and IV-2-treated cells were significantly more sensitive to oxidative stress-induced cytotoxicity as measured by clonogenic survival assays. Finally, IV-2-treated cells showed increased tumor cell death when treated with H2O2 and IR. These results identify TR as a potential target to enhance the cytotoxic effects of agents that induce oxidative stress, including IR.

Geldanamycin and 17-allylamino-17-demethoxygeldanamycin potentiate the in vitro and in vivo radiation response of cervical tumor cells via the heat shock protein 90-mediated intracellular signaling and cytotoxicity.

Ansamycin antibiotics inhibit function of the heat shock protein (HSP) 90, causing selective degradation of several intracellular proteins regulating such processes as proliferation, cell cycle regulation, and prosurvival signaling cascades. HSP90 has been identified previously as a molecular target for anticancer agents, including ionizing radiation (IR). Therefore, we hypothesized that the ansamycin geldanamycin and its 17-allylamino-17-demethoxy analog (17-AAG), which inhibit HSP90, would enhance tumor cell susceptibility to the cytotoxicity of IR. Treatment of two human cervical carcinoma cell lines (HeLa and SiHa) with geldanamycin and 17-AAG resulted in cytotoxicity and, when combined with IR, enhanced the radiation response, each effect with a temporal range from 6 to 48 h after drug exposure. In addition, mouse in vivo models using 17-AAG at clinically achievable concentrations yielded results that paralleled the in vitro radiosensitization studies of both single and fractioned courses of irradiation. The increase in IR-induced cell death appears to be attributable to a combination of both programmed and nonprogrammed cell death. We also measured total levels of several prosurvival and apoptotic signaling proteins. Akt1, extracellular signal-regulated kinase-1, Glut-1, HER-2/neu, Lyn, cAMP-dependent protein kinase, Raf-1, and vascular endothelial growth factor expression were down-regulated in 17-AAG-treated cells, identifying these factors as molecular markers and potential therapeutic targets. Finally, a series of immortalized and human papillomavirus-transformed cell lines were used to demonstrate that the radiosensitizing effects of 17-AAG were limited to transformed cells, suggesting a possible differential cytotoxic effect. This work shows that altered HSP90 function induces significant tumor cytotoxicity and radiosensitization, suggesting a potential therapeutic utility.