False-Negative Rates of Breast Cancer Screening with and without Digital Breast Tomosynthesis.

Background Screening with digital breast tomosynthesis (DBT) improves breast cancer detection and recall rates compared with those obtained with digital mammography (DM); however, the impact of DBT on patient survival has not been established. False-negative (FN) screening examinations can be a surrogate for long-term outcomes, such as breast cancer morbidity and mortality. Purpose To determine if screening with DBT is associated with lower FN rates, detection of cancers with more favorable prognoses, and improved performance outcomes versus DM. Materials and Methods This retrospective study involved 10 academic and community practices. DM screening examinations 1 year prior to DBT implementation and DBT screening examinations from the start date until June 30, 2013, were linked to cancers through June 30, 2014, with data collection in 2016 and analysis in 2018-2019. Cancers after FN examinations were characterized by presentation, either symptomatic or asymptomatic. FN rates, sensitivity, specificity, cancer detection and recall rates, positive predictive values, tumor size, histologic features, and receptor profile were compared. Results A total of 380 641 screening examinations were included. There were 183 989 DBT and 196 652 DM examinations. With DBT, rates trended lower for overall FN examinations (DBT, 0.6 per 1000 screens; DM, 0.7 per 1000 screens; P = .20) and symptomatic FN examinations (DBT, 0.4 per 1000 screens; DM, 0.5 per 1000 screens; P = .21). Asymptomatic FN rates trended higher in women with dense breasts (DBT, 0.14 per 1000 screens; DM: 0.07 per 1000 screens; P = .07). With DBT, improved sensitivity (DBT, 89.8% [966 of 1076 cancers]; DM, 85.6% [789 of 922 cancers]; P = .004) and specificity (DBT, 90.7% [165 830 of 182 913 examinations]; DM, 89.1% [174 480 of 195 730 examinations]; P < .001) were observed. Overall, cancers identified with DBT were more frequently invasive (P < .001), had fewer positive lymph nodes (P = .04) and distant metastases (P = .01), and had lower odds of an FN finding of advanced cancer (odds ratio, 0.9 [95% CI: 0.5, 1.5]). Conclusion Screening with digital breast tomosynthesis improves sensitivity and specificity and reveals more invasive cancers with fewer nodal or distant metastases. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Schattner in this issue.

Effect of age on breast cancer screening using tomosynthesis in combination with digital mammography.

PURPOSE: To determine the effect of tomosynthesis imaging as a function of age for breast cancer screening. METHODS: Screening performance metrics from 13 institutions were examined for 12 months prior to introduction of tomosynthesis (period 1) and compared to those after introduction of tomosynthesis (period 2, range 3-22 months). Screening metrics for women ages 40-49, 50-59, 60-69, and 70+ , included rates per 1000 screens for recalls, biopsies, cancers, and invasive cancers detected. RESULTS: Performance parameters were compared for women screened with digital mammography alone (n = 278,908) and digital mammography + tomosynthesis (n = 173,414). Addition of tomosynthesis to digital mammography produced significant reductions in recall rates for all age groups and significant increases in cancer detection rates for women 40-69. Largest recall rate reduction with tomosynthesis was for women 40-49, decreasing from 137 (95% CI 117-156) to 115 (95% CI 95-135); difference, -22 (95% CI -26 to -18; P < .001). Simultaneous increase in invasive cancer detection rate for women 40-49 from 1.6 (95% CI 1.2-1.9) to 2.7 (95% CI 2.2-3.1) with tomosynthesis (difference, 1.1; 95% CI 0.6-1.6; P < .001) was observed. CONCLUSIONS: Addition of tomosynthesis to digital mammography increased invasive cancer detection rates for women 40-69 and decreased recall rates for all age groups with largest performance gains seen in women 40-49. The similar performance seen with tomosynthesis screening for women in their 40s compared to digital mammography for women in their 50s argues strongly for commencement of mammography screening at age 40 using tomosynthesis.

Update on Preoperative Breast Localization.

The radiologist plays an important role in detection, diagnosis, localization, pathologic correlation, and follow-up imaging of breast cancer. A successful breast surgical treatment program relies on the image guidance tools and skills of the radiologist and surgeon. This article reviews the evolving tools available for preoperative localization. Non-wire devices provide a safe, efficient, noninferior alternative to wire localization and can be placed 0 to 30 days before scheduled surgery. This technology may evolve to other longer-term, efficient, and cost-effective applications for patients who require neoadjuvant treatment or who have findings visible only at MR imaging.

ACR Appropriateness Criteria Breast Cancer Screening.

Mammography is the recommended method for breast cancer screening of women in the general population. However, mammography alone does not perform as well as mammography plus supplemental screening in high-risk women. Therefore, supplemental screening with MRI or ultrasound is recommended in selected high-risk populations. Screening breast MRI is recommended in women at high risk for breast cancer on the basis of family history or genetic predisposition. Ultrasound is an option for those high-risk women who cannot undergo MRI. Recent literature also supports the use of breast MRI in some women of intermediate risk, and ultrasound may be an option for intermediate-risk women with dense breasts. There is insufficient evidence to support the use of other imaging modalities, such as thermography, breast-specific gamma imaging, positron emission mammography, and optical imaging, for breast cancer screening. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review includes an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

ACR Appropriateness Criteria Stage I Breast Cancer: Initial Workup and Surveillance for Local Recurrence and Distant Metastases in Asymptomatic Women.

Women newly diagnosed with stage 1 breast cancer have an early-stage disease that can be effectively treated. Evidence provides little justification for performing imaging to exclude metastasis in asymptomatic women with stage I breast cancer. No differences have been found in survival or quality of life in women regardless of whether they underwent initial workup for metastatic disease. These women generally prefer intensive follow-up to detect an early recurrence. However, survival rates do not differ between women who obtain intensive screening and surveillance, with imaging and laboratory studies, and women who undergo testing only as a result of development of symptoms or findings on clinical examinations. In addition, quality of life is similar for women who undergo intensive surveillance compared with those who do not. American Society of Clinical Oncology and National Comprehensive Cancer Network guidelines state that annual mammography is the only imaging examination that should be performed to detect a localized breast recurrence in asymptomatic patients. Additional imaging may be needed if the patient has locoregional symptoms. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review by the panel include extensive analysis of current medical literature from peer-reviewed journals and application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures. When evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

ACR Appropriateness Criteria® Stage I Breast Carcinoma.

Stage I breast carcinoma is classified when an invasive breast carcinoma is ≤2 cm in diameter (T1), with no regional (axillary) lymph node metastases (N0) and no distant metastases (M0). The most common sites for metastases from breast cancer are the skeleton, lung, liver, and brain. In general, women and health care professionals prefer intensive screening and surveillance after a diagnosis of breast cancer. Screening protocols include conventional imaging such as chest radiography, bone scan, ultrasound of the liver, and MRI of brain. It is uncertain whether PET/CT will serve as a replacement for current imaging technologies. However, there are no survival or quality-of-life differences for women who undergo intensive screening and surveillance after a diagnosis of stage I breast carcinoma compared with those who do not. The ACR Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

ACR Appropriateness Criteria Palpable Breast Masses.

A palpable breast mass is one of the most common presenting features of breast carcinoma. However, the clinical features are frequently nonspecific. Imaging performed before biopsy is helpful in characterizing the nature of the mass. For women with clinically detected breast masses, the vast majority will require evaluation with ultrasound. Diagnostic mammography is the initial imaging modality of choice for women aged ≥ 40 years; ultrasound is typically necessary unless a definitively benign mass is identified as the etiology of the clinical finding. For evaluating women aged <30 years and women who are pregnant or lactating, ultrasound is used for initial evaluation. For women aged 30 to 39 years, either ultrasound or diagnostic mammography may be used for initial evaluation. MRI is rarely indicated to evaluate a clinically detected finding. Biopsy is indicated for masses with suspicious features. Short-term follow-up is a reasonable alternative to biopsy for solid masses with probably benign features suggesting fibroadenoma. Correlation between imaging and the clinical finding is essential. The ACR Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Identification and expression of GnRH2 and GnRH3 in the black sea bass (Centropristis striata), a hermaphroditic teleost.

We cloned two cDNAs for two gonadotropin-releasing hormones, GnRH2 (chicken GnRH-II) and GnRH3 (salmon GnRH), respectively, from the black sea bass (Centropristis striata). Black sea bass are protogynous hermaphroditic teleosts that change from females to males between 2 and 5 years of age. Similar to other GnRH precursors, the precursors of black sea bass GnRH2 and GnRH23 consisted of a signal peptide, decapeptide, a downstream processing site, and a GnRH-associated peptide. Our analyses failed to identify GnRH1. GnRH3 precursor transcript was more widely distributed in a variety of tissues compared with GnRH2. Further examination of GnRH expression and gonadal histology was done in black sea bass from three different size groups: small (11.4-44.1 g), medium (179.4-352.2 g) and large (393.8-607.3 g). Interestingly, GnRH3 expression occurred only in the pituitaries of males in the small and medium groups compared with expression of GnRH2. Future functional studies of the sea bass GnRHs will be valuable in elucidating the potential underlying neuroendocrine mechanisms of black sea bass reproduction and may ultimately contribute to management advances in this commercially important fish.

ACR Appropriateness Criteria stage I breast cancer: initial workup and surveillance for local recurrence and distant metastases in asymptomatic women.

Women newly diagnosed with stage 1 breast cancer have an early-stage disease that can be effectively treated. Evidence provides little justification for performing imaging to exclude metastasis in asymptomatic women with stage I breast cancer. No differences have been found in survival or quality of life in women regardless of whether they underwent initial workup for metastatic disease. These women generally prefer intensive follow-up to detect an early recurrence. However, survival rates do not differ between women who obtain intensive screening and surveillance, with imaging and laboratory studies, and women who undergo testing only as a result of development of symptoms or findings on clinical examinations. In addition, quality of life is similar for women who undergo intensive surveillance compared with those who do not. American Society of Clinical Oncology and National Comprehensive Cancer Network guidelines state that annual mammography is the only imaging examination that should be performed to detect a localized breast recurrence in asymptomatic patients. Additional imaging may be needed if the patient has locoregional symptoms. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review by the panel include extensive analysis of current medical literature from peer-reviewed journals and application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures. When evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Diffusion of accelerated partial breast radiotherapy in the United States: physician-level and patient-level analyses.

PURPOSE: To evaluate diffusion of brachytherapy-based accelerated partial breast radiotherapy (RT) in the United States, a new breast cancer treatment requiring 5 days twice daily, rather than daily treatment for 6-7 weeks. It has limited long-term effectiveness data compared with standard whole breast RT. DATA AND METHODS: We used 2005-2008 Medicare claims for female Medicare beneficiaries receiving RT after breast-conserving surgery merged with physician and area-based data (n=74,254 patient-subjects; n=1901 physicians), applying logistic regression to estimate: (1) proportion of patients for whom the radiation oncologist used brachytherapy-based accelerated RT, and (2) probability a patient received brachytherapy-based accelerated RT, clustering on physician. RESULTS: Use of accelerated partial breast RT increased over time (8% in 2005 to 17% in 2008). Physician-level analysis indicates rural physicians were less likely to perform accelerated RT [odds ratio (OR): 0.35-0.49; P<0.002)]; as were those licensed 20+years [OR: 0.54; 95% confidence interval (CI), 0.39-0.74]. Overall, 11.7% of patients received accelerated RT. Treatment post 2005 was associated with increasing odds of receiving accelerated RT (P<0.0001). Older age was associated with lower odds of receiving accelerated RT (reference, 66-69 years old, OR: 0.90, P<0.006), as was black (OR: 0.73;95% CI, 0.63-0.85) or other race (OR: 0.80; 95% CI, 0.65-1.00), living in rural areas (OR: 0.8; P<0.0001), or seeing an older physician [20+years postgraduation (OR: 0.7; 95% CI, 0.5-0.9)]. Patients living in counties with more hospitals with advanced RT facilities were more likely to undergo accelerated RT (OR: 1.4; 95% CI, 1.1-1.8). DISCUSSION: This new technology appears to be in the early phase of diffusion across the United States and is more rapidly being taken up in younger, white patients living in urban and suburban areas with availability of advanced RT facilities. Rural and older patient populations are not tending to undergo the treatment.

Breast cancer screening using tomosynthesis in combination with digital mammography.

IMPORTANCE: Mammography plays a key role in early breast cancer detection. Single-institution studies have shown that adding tomosynthesis to mammography increases cancer detection and reduces false-positive results. OBJECTIVE: To determine if mammography combined with tomosynthesis is associated with better performance of breast screening programs in the United States. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of screening performance metrics from 13 academic and nonacademic breast centers using mixed models adjusting for site as a random effect. EXPOSURES: Period 1: digital mammography screening examinations 1 year before tomosynthesis implementation (start dates ranged from March 2010 to October 2011 through the date of tomosynthesis implementation); period 2: digital mammography plus tomosynthesis examinations from initiation of tomosynthesis screening (March 2011 to October 2012) through December 31, 2012. MAIN OUTCOMES AND MEASURES: Recall rate for additional imaging, cancer detection rate, and positive predictive values for recall and for biopsy. RESULTS: A total of 454,850 examinations (n=281,187 digital mammography; n=173,663 digital mammography + tomosynthesis) were evaluated. With digital mammography, 29,726 patients were recalled and 5056 biopsies resulted in cancer diagnosis in 1207 patients (n=815 invasive; n=392 in situ). With digital mammography + tomosynthesis, 15,541 patients were recalled and 3285 biopsies resulted in cancer diagnosis in 950 patients (n=707 invasive; n=243 in situ). Model-adjusted rates per 1000 screens were as follows: for recall rate, 107 (95% CI, 89-124) with digital mammography vs 91 (95% CI, 73-108) with digital mammography + tomosynthesis; difference, -16 (95% CI, -18 to -14; P < .001); for biopsies, 18.1 (95% CI, 15.4-20.8) with digital mammography vs 19.3 (95% CI, 16.6-22.1) with digital mammography + tomosynthesis; difference, 1.3 (95% CI, 0.4-2.1; P = .004); for cancer detection, 4.2 (95% CI, 3.8-4.7) with digital mammography vs 5.4 (95% CI, 4.9-6.0) with digital mammography + tomosynthesis; difference, 1.2 (95% CI, 0.8-1.6; P < .001); and for invasive cancer detection, 2.9 (95% CI, 2.5-3.2) with digital mammography vs 4.1 (95% CI, 3.7-4.5) with digital mammography + tomosynthesis; difference, 1.2 (95% CI, 0.8-1.6; P < .001). The in situ cancer detection rate was 1.4 (95% CI, 1.2-1.6) per 1000 screens with both methods. Adding tomosynthesis was associated with an increase in the positive predictive value for recall from 4.3% to 6.4% (difference, 2.1%; 95% CI, 1.7%-2.5%; P < .001) and for biopsy from 24.2% to 29.2% (difference, 5.0%; 95% CI, 3.0%-7.0%; P < .001). CONCLUSIONS AND RELEVANCE: Addition of tomosynthesis to digital mammography was associated with a decrease in recall rate and an increase in cancer detection rate. Further studies are needed to assess the relationship to clinical outcomes.

ACR appropriateness criteria palpable breast masses.

A palpable breast mass is one of the most common presenting features of breast carcinoma. However, the clinical features are frequently nonspecific. Imaging performed before biopsy is helpful in characterizing the nature of the mass. For women with clinically detected breast masses, the vast majority will require evaluation with ultrasound. Diagnostic mammography is the initial imaging modality of choice for women aged ≥ 40 years; ultrasound is typically necessary unless a definitively benign mass is identified as the etiology of the clinical finding. For evaluating women aged <30 years and women who are pregnant or lactating, ultrasound is used for initial evaluation. For women aged 30 to 39 years, either ultrasound or diagnostic mammography may be used for initial evaluation. MRI is rarely indicated to evaluate a clinically detected finding. Biopsy is indicated for masses with suspicious features. Short-term follow-up is a reasonable alternative to biopsy for solid masses with probably benign features suggesting fibroadenoma. Correlation between imaging and the clinical finding is essential. The ACR Appropriateness Criteria(®) are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Expression of three GnRH receptors in specific tissues in male and female sea lampreys Petromyzon marinus at three distinct life stages.

Two recently cloned gonadotropin-releasing hormone (GnRH) receptors (lamprey GnRH-R-2 and lamprey GnRH-R-3) along with lamprey (l) GnRH-R-1 were shown to share similar structural features and amino acid motifs common to other vertebrate receptors. Here we report on our findings of RNA expression of these three GnRH receptors in the three major life stages (larval, parasitic, and adult phases) of the sea lamprey, Petromyzon marinus, a basal vertebrate. For each stage, we examined the expression of messenger RNA encoding the receptors in the brain, pituitary, gonad, heart, muscle, liver, eye, intestine, kidney, skin, thyroid, gill, and endostyle by RT-PCR. In adult lampreys, the spatial expression of the three receptors in the brain and pituitary was investigated by in situ hybridization. In general, the receptors were more widely expressed in adult tissues as compared to parasitic-phase tissues and least widely expressed in the larval tissues. There were noted differences in male and female lampreys in the adult and parasitic phases for all three receptors. The data showed the presence of all three receptor transcripts in brain tissues for adult and parasitic phases and all three receptor transcripts were expressed in the adult pituitaries, but not in the parasitic pituitaries. However, in the larval phase, only lGnRH-R-1 was expressed in the larval brain and pituitary. In situ hybridization revealed that lGnRH-R-2 and -3 were expressed in the pineal tissue of adult female lampreys while lGnRH-R-1 was expressed in the pineal in adult male lampreys, all restricted to the pineal pellucida. In summary, these data provide an initial comparative analysis of expression of three lamprey GnRH receptors suggesting differential regulation within males and females at three different life/reproductive stages.

ACR Appropriateness Criteria Breast Cancer Screening.

Mammography is the recommended method for breast cancer screening of women in the general population. However, mammography alone does not perform as well as mammography plus supplemental screening in high-risk women. Therefore, supplemental screening with MRI or ultrasound is recommended in selected high-risk populations. Screening breast MRI is recommended in women at high risk for breast cancer on the basis of family history or genetic predisposition. Ultrasound is an option for those high-risk women who cannot undergo MRI. Recent literature also supports the use of breast MRI in some women of intermediate risk, and ultrasound may be an option for intermediate-risk women with dense breasts. There is insufficient evidence to support the use of other imaging modalities, such as thermography, breast-specific gamma imaging, positron emission mammography, and optical imaging, for breast cancer screening. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review includes an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

ACR Appropriateness Criteria® stage I breast carcinoma.

Stage I breast carcinoma is classified when an invasive breast carcinoma is ≤2 cm in diameter (T1), with no regional (axillary) lymph node metastases (N0) and no distant metastases (M0). The most common sites for metastases from breast cancer are the skeleton, lung, liver, and brain. In general, women and health care professionals prefer intensive screening and surveillance after a diagnosis of breast cancer. Screening protocols include conventional imaging such as chest radiography, bone scan, ultrasound of the liver, and MRI of brain. It is uncertain whether PET/CT will serve as a replacement for current imaging technologies. However, there are no survival or quality-of-life differences for women who undergo intensive screening and surveillance after a diagnosis of stage I breast carcinoma compared with those who do not. The ACR Appropriateness Criteria(®) are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

HDR brachytherapy with surface applicators: technical considerations and dosimetry.

HDR surface molds offer an alternative radiotherapy modality to electrons for the treatment of skin lesions. Treatment planning and dosimetry are discussed for two types of surface molds used in our clinic. Standard rectangular applicators are used on a variety of sites where surface curvature is minimal. In these cases an idealized planar geometry is used for treatment planning dose calculations. The calculations yield treatment dose uniformity at the prescription depth in tissue as well as skin dose, as a percentage of the treatment dose, and its dose uniformity. The availability of optimization techniques results in superior dose uniformity at depth but the dose at the skin has to be carefully evaluated. We have studied the dependence of these dosimetric parameters on the size of the surface mold and the type of optimization procedure used in the dosimetry calculations. The second type of surface applicator involves the use of a customized silicone rubber mold attached to a thermoplastic mask of the patient. We have used them to treat lesions of the face where surface curvatures are appreciable and reproducibility of setup is more critical. In these cases a CT data set is used for reconstruction of the catheters, activation of relevant dwell positions and dosimetry, including optimization. Towards establishing effective methods for quality assurance of the optimized HDR surface mold planning calculations, we have compared their dosimetry to both a classical brachytherapy system and to one based on an analytical model of the applicator. The classical system yields an independent verification of the integrated activity used in the planning calculations, whereas the analytical model is used to evaluate depth dose dependence on mold size and optimization.