Contrast-Enhanced Mammography Versus MRI in the Evaluation of Neoadjuvant Therapy Response in Patients With Breast Cancer: A Prospective Study.

BACKGROUND. Contrast-enhanced mammography (CEM) is rapidly expanding as a credible alternative to MRI in various clinical settings. OBJECTIVE. The purpose of this study was to compare CEM and MRI for neoadjuvant therapy (NAT) response assessment in patients with breast cancer. METHODS. This prospective study included 51 patients (mean age, 46 ± 11 [SD] years) with biopsy-proven breast cancer who were candidates for NAT from May 2015 to April 2018. Patients underwent both CEM and MRI before, during, and after NAT (pre-NAT, mid-NAT, and post-NAT, respectively). Post-NAT CEM included a 6-minute delayed acquisition. One breast radiologist with experience in CEM reviewed CEM examinations; one breast radiologist with experience in MRI reviewed MRI examinations. The radiologists assessed for the presence of an enhancing lesion; if an enhancing lesion was detected, its size was measured. RECIST version 1.1 response assessment categories were derived. Pathologic complete response (pCR) was defined as absence of both invasive cancer and ductal carcinoma in situ (DCIS). RESULTS. Of 51 patients, 16 achieved pCR. CEM yielded systematically lower size measurements compared with MRI (mean difference, -0.2 mm for pre-NAT, -0.7 mm for mid-NAT, and -0.3 mm for post-NAT). All post-NAT imaging tests yielded systematically larger size measurements compared with pathology (mean difference, 0.8 mm for CEM, 1.2 mm for MRI, and 1.9 mm for delayed CEM). Of 12 patients with residual DCIS, an enhancing lesion was detected in seven on post-NAT CEM, eight on post-NAT MRI, and nine on post-NAT delayed CEM. Agreement of RECIST response categories between CEM and MRI, expressed as kappa coefficient, was 0.791 at mid-NAT and 0.871 at post-NAT. For detecting pCR by post-NAT imaging, sensitivity and specificity were 81% and 83% for CEM, 100% and 86% for MRI, and 81% and 89% for delayed CEM. Sensitivity was significantly higher for MRI than CEM (p = .001) and delayed CEM (p = .002); remaining comparisons were not significant (p > .05). CONCLUSION. After NAT for breast cancer, CEM and MRI yielded comparable assessments of lesion size (both slightly overestimated vs pathology) and RECIST categories and showed no significant difference in specificity for pCR. MRI had higher sensitivity for pCR. Delayed CEM acquisition may help detect residual DCIS. CLINICAL IMPACT. Although MRI remains the preferred test for NAT response monitoring, the findings support CEM as a useful alternative when MRI is contraindicated or not tolerated.

Structured reporting of x-ray mammography in the first diagnosis of breast cancer: a Delphi consensus proposal.

BACKGROUND: Radiology is an essential tool in the management of a patient. The aim of this manuscript was to build structured report (SR) Mammography based in Breast Cancer. METHODS: A working team of 16 experts (group A) was composed to create a SR for Mammography Breast Cancer. A further working group of 4 experts (group B), blinded to the activities of the group A, was composed to assess the quality and clinical usefulness of the SR final draft. Modified Delphi process was used to assess level of agreement for all report sections. Cronbach's alpha (Cα) correlation coefficient was used to assess internal consistency and to measure quality analysis according to the average inter-item correlation. RESULTS: The final SR version was built by including n = 2 items in Personal Data, n = 4 items in Setting, n = 2 items in Comparison with previous breast examination, n = 19 items in Anamnesis and clinical context; n = 10 items in Technique; n = 1 item in Radiation dose; n = 5 items Parenchymal pattern; n = 28 items in Description of the finding; n = 12 items in Diagnostic categories and Report and n = 1 item in Conclusions. The overall mean score of the experts and the sum of score for structured report were 4.9 and 807 in the second round. The Cronbach's alpha (Cα) correlation coefficient was 0.82 in the second round. About the quality evaluation, the overall mean score of the experts was 3.3. The Cronbach's alpha (Cα) correlation coefficient was 0.90. CONCLUSIONS: Structured reporting improves the quality, clarity and reproducibility of reports across departments, cities, countries and internationally and will assist patient management and improve breast health care and facilitate research.

Breast imaging and cancer diagnosis during the COVID-19 pandemic: recommendations from the Italian College of Breast Radiologists by SIRM.

The Italian College of Breast Radiologists by the Italian Society of Medical Radiology (SIRM) provides recommendations for breast care provision and procedural prioritization during COVID-19 pandemic, being aware that medical decisions must be currently taken balancing patient's individual and community safety: (1) patients having a scheduled or to-be-scheduled appointment for in-depth diagnostic breast imaging or needle biopsy should confirm the appointment or obtain a new one; (2) patients who have suspicious symptoms of breast cancer (in particular: new onset palpable nodule; skin or nipple retraction; orange peel skin; unilateral secretion from the nipple) should request non-deferrable tests at radiology services; (3) asymptomatic women performing annual mammographic follow-up after breast cancer treatment should preferably schedule the appointment within 1 year and 3 months from the previous check, compatibly with the local organizational conditions; (4) asymptomatic women who have not responded to the invitation for screening mammography after the onset of the pandemic or have been informed of the suspension of the screening activity should schedule the check preferably within 3 months from the date of the not performed check, compatibly with local organizational conditions. The Italian College of Breast Radiologists by SIRM recommends precautions to protect both patients and healthcare workers (radiologists, radiographers, nurses, and reception staff) from infection or disease spread on the occasion of breast imaging procedures, particularly mammography, breast ultrasound, breast magnetic resonance imaging, and breast intervention procedures.

Breast arterial calcifications on mammography: intra- and inter-observer reproducibility of a semi-automatic quantification tool.

PURPOSE: A strong association between breast arterial calcifications (BAC) and cardiovascular disease has been demonstrated. However, BAC quantification tools are lacking. We evaluated the intra- and inter-observer reproducibility of a semi-automatic tool for BAC quantification on digital mammograms. MATERIALS AND METHODS: A multivendor image dataset of 212 mammographic views, 106 cranio-caudal (CC) and 106 medio-lateral oblique (MLO), were retrospectively selected from 53 subjects if BAC were seen in at least one view. Images were segmented twice by two intensively trained residents in Radiodiagnostics with > 6-month experience in mammography using a semi-automatic software. The two observers (O1, O2) independently positioned rectangular ROIs where they recognized BAC on both CC and MLO views, separately. The adaptive thresholding algorithm automatically provided the BAC amount in mm2. Number, size, and position of the ROIs were observer-dependent. Total BAC amount was calculated for each patient. Bland-Altman analysis was used. RESULTS: Total BAC amount was 56.6 (IQR 18.1-91.1) and 41.0 (IQR 18.8-90.9) for O1 and O2, respectively. Intra-observer Bland-Altman analysis showed a bias of 11.9 mm2, a coefficient of repeatability of 32.7 mm2, an average measurement of 72.8 mm2, for a 55% reproducibility; the same data were - 7.0, 61.4, 63.4 mm2, and only 3%, respectively, for the inter-observer analysis. CONCLUSION: Our semi-automatic tool for BAC quantification showed a poor reproducibility. These results pointed out that the human identification of BAC represents the main source of variability. Further research is needed to translate BAC quantification into clinical practice.

Digital breast tomosynthesis (DBT): recommendations from the Italian College of Breast Radiologists (ICBR) by the Italian Society of Medical Radiology (SIRM) and the Italian Group for Mammography Screening (GISMa).

This position paper, issued by ICBR/SIRM and GISMa, summarizes the evidence on DBT and provides recommendations for its use. In the screening setting, DBT in adjunct to digital mammography (DM) increased detection rate by 0.5-2.7‰ and decreased false positives by 0.8-3.6% compared to DM alone in observational and double-testing experimental studies. The reduction in recall rate could be less prominent in those screening programs which already have low recall rates with DM. The increase in radiation exposure associated with DM/DBT protocols has been solved by the introduction of synthetic mammograms (sDM) reconstructed from DBT datasets. Thus, whenever possible, sDM/DBT should be preferred to DM/DBT. However, before introducing DBT as a routine screening tool for average-risk women, we should wait for the results of randomized controlled trials and for a statistically significant and clinically relevant reduction in the interval cancer rate, hopefully associated with a reduction in the advanced cancer rate. Otherwise, a potential for overdiagnosis and overtreatment cannot be excluded. Studies exploring this issue are ongoing. Screening of women at intermediate risk should follow the same recommendations, with particular protocols for women with previous BC history. In high-risk women, if mammography is performed as an adjunct to MRI or in the case of MRI contraindications, sDM/DBT protocols are suggested. Evidence exists in favor of DBT usage in women with clinical symptoms/signs and asymptomatic women with screen-detected findings recalled for work-up. The possibility to perform needle biopsy or localization under DBT guidance should be offered when DBT-only findings need characterization or surgery.

Breast cancer screening with tomosynthesis (3D mammography) with acquired or synthetic 2D mammography compared with 2D mammography alone (STORM-2): a population-based prospective study.

BACKGROUND: Breast tomosynthesis (pseudo-3D mammography) improves breast cancer detection when added to 2D mammography. In this study, we examined whether integrating 3D mammography with either standard 2D mammography acquisitions or with synthetic 2D images (reconstructed from 3D mammography) would detect more cases of breast cancer than 2D mammography alone, to potentially reduce the radiation burden from the combination of 2D plus 3D acquisitions. METHODS: The Screening with Tomosynthesis Or standard Mammography-2 (STORM-2) study was a prospective population-based screening study comparing integrated 3D mammography (dual-acquisition 2D-3D mammography or 2D synthetic-3D mammography) with 2D mammography alone. Asymptomatic women aged 49 years or older who attended population-based screening in Trento, Italy were recruited for the study. All participants underwent digital mammography with 2D and 3D mammography acquisitions, with the use of software that allowed synthetic 2D mammographic images to be reconstructed from 3D acquisitions. Mammography screen-reading was done in two parallel double-readings conducted sequentially for 2D acquisitions followed by integrated acquisitions. Recall based on a positive mammography result was defined as recall at any screen read. Primary outcome measures were a comparison between integrated (2D-3D or 2D synthetic-3D) mammography and 2D mammography alone of the number of cases of screen-detected breast cancer, the cancer detection rate per 1000 screens, the incremental cancer detection rate, and the number and percentage of false-positive recalls. FINDINGS: Between May 31, 2013, and May 29, 2015, 10 255 women were invited to participate, of whom 9672 agreed to participate and were screened. In these 9672 participants (median age 58 years [IQR 53-63]), screening detected 90 cases of breast cancer, including 74 invasive breast cancers, in 85 women (five women had bilateral breast cancer). To account for these bilateral cancers in cancer detection rate estimates, the number of screens used for analysis was 9677. Both 2D-3D mammography (cancer detection rate 8·5 per 1000 screens [82 cancers detected in 9677 screens]; 95% CI 6·7-10·5) and 2D synthetic-3D mammography (8·8 per 1000 [85 in 9677]; 7·0-10·8) had significantly higher rates of breast cancer detection than 2D mammography alone (6·3 per 1000 [61 in 9677], 4·8-8·1; p<0·0001 for both comparisons). The cancer detection rate did not differ significantly between 2D-3D mammography and 2D synthetic-3D mammography (p=0·58). Compared with 2D mammography alone, the incremental cancer detection rate from 2D-3D mammography was 2·2 per 1000 screens (95% CI 1·2-3·3) and that from 2D synthetic-3D mammography was 2·5 per 1000 (1·4-3·8). Compared with the proportion of false-positive recalls from 2D mammography alone (328 of 9587 participants not found to have cancer at assessment) [3·42%; 95% CI 3·07-3·80]), false-positive recall was significantly higher for 2D-3D mammography (381 of 9587 [3·97%; 3·59-4·38], p=0·00063) and for 2D synthetic-3D mammography (427 of 9587 [4·45%; 4·05-4·89], p<0·0001). INTERPRETATION: Integration of 3D mammography (2D-3D or 2D synthetic-3D) detected more cases of breast cancer than 2D mammography alone, but increased the percentage of false-positive recalls in sequential screen-reading. These results should be considered in the context of the trade-off between benefits and harms inherent in population breast cancer screening, including that significantly increased breast cancer detection from integrating 3D mammography into screening has the potential to augment screening benefit and also possibly contribute to overdiagnosis. FUNDING: None.

Mammographic density: Comparison of visual assessment with fully automatic calculation on a multivendor dataset.

OBJECTIVES: To compare breast density (BD) assessment provided by an automated BD evaluator (ABDE) with that provided by a panel of experienced breast radiologists, on a multivendor dataset. METHODS: Twenty-one radiologists assessed 613 screening/diagnostic digital mammograms from nine centers and six different vendors, using the BI-RADS a, b, c, and d density classification. The same mammograms were also evaluated by an ABDE providing the ratio between fibroglandular and total breast area on a continuous scale and, automatically, the BI-RADS score. A panel majority report (PMR) was used as reference standard. Agreement (κ) and accuracy (proportion of cases correctly classified) were calculated for binary (BI-RADS a-b versus c-d) and 4-class classification. RESULTS: While the agreement of individual radiologists with the PMR ranged from κ = 0.483 to κ = 0.885, the ABDE correctly classified 563/613 mammograms (92 %). A substantial agreement for binary classification was found for individual reader pairs (κ = 0.620, standard deviation [SD] = 0.140), individual versus PMR (κ = 0.736, SD = 0.117), and individual versus ABDE (κ = 0.674, SD = 0.095). Agreement between ABDE and PMR was almost perfect (κ = 0.831). CONCLUSIONS: The ABDE showed an almost perfect agreement with a 21-radiologist panel in binary BD classification on a multivendor dataset, earning a chance as a reproducible alternative to visual evaluation. KEY POINTS: Individual BD assessment differs from PMR with κ as low as 0.483. An ABDE correctly classified 92 % of mammograms with almost perfect agreement (κ = 0.831). An ABDE can be a valid alternative to subjective BD assessment.

Effective transcutaneous immunization using a combination of iontophoresis and nanoparticles.

Needle-free immunization strategies have been sought for years. Transcutaneous immunization using electroporation has been studied, but the high electrical voltage that must be applied may be painful and cause irreversible cell damage. The application of a weak electric field, such as in iontophoresis, has never been attempted. The aim of this work was to verify the potential of employing iontophoresis for transcutaneous immunization using ovalbumin (OVA) as a model antigen. To target the antigen presenting cells that are located in the viable epidermis, a vaccine formulation composed of OVA-loaded liposomes and silver nanoparticles (NPAg) was developed. In vitro cathodal iontophoresis of the OVA-liposomes associated with NPAg increased OVA penetration into the viable epidermis by 92-fold in comparison to passive delivery. In vivo, transcutaneous immunization with a suitable combination of liposome and iontophoresis induced the production of antibodies, differentiation of immune-competent cells and appeared to present an alternative strategy for needle-free vaccination.

Mammography and MRI for screening women who underwent chest radiation therapy (lymphoma survivors): recommendations for surveillance from the Italian College of Breast Radiologists by SIRM.

Women who underwent chest radiation therapy (CRT) during pediatric/young-adult age (typically, lymphoma survivors) have an increased breast cancer risk, in particular for high doses. The cumulative incidence from 40 to 45 years of age is 13-20 %, similar to that of BRCA mutation carriers for whom contrast-enhanced magnetic resonance imaging (MRI) is recommended. However, in women who underwent CRT, MRI sensitivity is lower (63-80 %) and that of mammography higher (67-70 %) than those observed in women with hereditary predisposition, due to a higher incidence of ductal carcinoma in situ with microcalcifications and low neoangiogenesis. A sensitivity close to 95 % can be obtained only using mammography as an adjunct to MRI. Considering the available evidence, women who underwent CRT before 30 receiving a cumulative dose ≥10 Gy should be invited after 25 (or, at least, 8 years after CRT) to attend the following program: 1. interview about individual risk profile and potential of breast imaging; 2. annual MRI using the same protocol recommended for women with hereditary predisposition; 3. annual bilateral two-view full-field digital mammography or digital breast tomosynthesis (DBT) with synthetic 2D reconstructions. Mammography and MRI can be performed at once or alternately every 6 months. In the case of MRI or contrast material contraindications, ultrasound will be performed instead of MRI. Reporting using BI-RADS is recommended. At the age for entering population screening, the individual risk profile will be discussed with the woman about opting for only mammography/DBT screening or for continuing the intensive protocol.

Factors associated with breast screening radiologists' annual mammogram reading volume in Italy.

PURPOSE: Screening mammogram reading volume (SMRV) and total (screening and clinical) mammogram reading volume (TMRV) per year are strongly associated with the radiologist's diagnostic performance in breast cancer screening. The current article reports the prevalence and correlates of a SMRV and a TMRV ≥5000 among Italian breast screening radiologists. MATERIALS AND METHODS: A questionnaire survey was carried out in 2013-2014 by the Italian Group for Mammography Screening (GISMa). The questionnaire included items of information for radiologist's experience-related characteristics and for facility-level factors supposedly associated with SMRV and TMRV. Multivariate analysis was performed using backward stepwise multiple logistic regression models. RESULTS: Data for 235 radiologists from 51 local screening programmes were received. Of the 222 radiologists who were eligible, 133 (59.9 %) reported a SMRV ≥5000 and 163 (73.4 %) a TMRV ≥5000. Multivariate factors positively associated with both characteristics included: the number of years of experience reading mammograms; the percentage of total working time dedicated to breast imaging and breast care; the participation in diagnostic assessment; and the availability of digital tomosynthesis at facility. Full-time dedication to breast imaging and breast care was associated with the highest odds ratio for a SMRV and a TMRV ≥5000, i.e. 11.80 and 46.74, respectively, versus a percentage of time ≤50 %. An early (<2000) year of implementation of the screening programme and the availability of vacuum-assisted biopsy at facility were associated with a SMRV and, respectively, a TMRV ≥5000. CONCLUSIONS: Increasing the proportion of radiologists with full-time dedication to breast imaging and breast care qualified as the most effective approach to improve SMRV and TMRV.

Recommendations for breast imaging follow-up of women with a previous history of breast cancer: position paper from the Italian Group for Mammography Screening (GISMa) and the Italian College of Breast Radiologists (ICBR) by SIRM.

Women who were previously treated for breast cancer (BC) are an important particular subgroup of women at intermediate BC risk. Their breast follow-up should be planned taking in consideration a 1.0-1.5 % annual rate of loco-regional recurrences and new ipsilateral or contralateral BCs during 15-20 years, and be based on a regional/district invitation system. This activity should be carried out by a Department of Radiology integrating screening and diagnostics in the context of a Breast Unit. We recommend the adoption of protocols dedicated to women previously treated for BC, with a clear definition of responsibilities, methods for invitation, site(s) of visits, methods for clinical and radiological evaluation, follow-up duration, role and function of family doctors and specialists. These women will be invited to get a mammogram in dedicated sessions starting from the year after the end of treatment. The planned follow-up duration will be at least 10 years and will be defined on the basis of patient's age and preferences, taking into consideration organizational matters. Special agreements can be defined in the case of women who have their follow-up planned at other qualified centers. Dedicated screening sessions should include: evaluation of familial/personal history (if previously not done) for identifying high-risk conditions which could indicate a different screening strategy; immediate evaluation of mammograms by one or, when possible, two breast radiologists with possible addition of supplemental mammographic views, digital breast tomosynthesis, clinical breast examination, breast ultrasound; and prompt planning of possible further workup. Results of these screening sessions should be set apart from those of general female population screening and presented in dedicated reports. The following research issues are suggested: further risk stratification and effectiveness of follow-up protocols differentiated also for BC pathologic subtype and molecular classification, and evaluation of different models of survivorship care, also in terms of cost-effectiveness.

ω-3 in meat products: benefits and effects on lipid oxidative stability.

Although ω-3 intake has been associated with numerous health benefits, its addition to certain food matrices, and in particular meat products, may involve various technological barriers influencing the final quality of the products. Lipid oxidation must be highlighted due to the modification of both the sensory characteristics and the shelf-life of meat products. In order to reduce the impact of chemical changes and promote oxidative stability, the use of natural antioxidants has gained ground owing to the health and safety advantages linked to its effectiveness at reducing lipid oxidation. Many natural compounds have also been successfully tested in animal feed, in order to protect the raw meat materials and reduce the risk of lipid oxidation in processed products. This review aims to address the challenges and advantages of the incorporation of ω-3 fatty acids in raw meat materials and processed meat products, and to describe the use of different compounds to enhance lipid oxidative stability. © 2015 Society of Chemical Industry.

Comparison of three different immunoassays in the diagnosis of heparin-induced thrombocytopenia.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is caused by platelet activating antibodies that recognize platelet factor 4/heparin (PF4/H) complexes. Laboratory testing plays a key role in the diagnosis of HIT. As functional assays are unfeasible for most clinical laboratories, antigen binding assays are commonly used in routine testing. However, their low specificity leads to overdiagnosis of HIT. Therefore, it is advisable to improve screening tests in this setting. METHODS: Blood samples from 114 patients in whom HIT was suspected were investigated using a chemiluminescence test (HemosIL® AcuStar HIT-IgG), a PF4/H IgG enzyme immunoassay (Lifecodes PF4 IgG), an IgG-specific lateral flow immunoassay heparin-induced thrombocytopenia (LFI-HIT, STic Expert® HIT) and the heparin-induced platelet aggregation (HIPA) test. RESULTS: Twenty-nine (25.4%) out of 114 subjects with suspected HIT had a positive HIPA test. None of patients with a 4Ts score <4 were positive at HIPA. HemosIL® AcuStar HIT-IgG showed the best performance in term of sensitivity and specificity when used as single test. Receiver operating characteristic (ROC) analysis showed optimization of sensitivity and specificity using a cut-off of 1.13 U/mL (0.95 and 0.98, respectively). As an alternative approach, a strategy based on screening samples by STic Expert® HIT and then retesting positive results by Lifecodes PF4 IgG (cut-off 1 OD) or HemosIL® AcuStar HIT-IgG (cut-off 1.3 U/mL) showed a performance compared to a single test approach by HemosIL® AcuStar HIT-IgG. CONCLUSIONS: The HemosIL® AcuStar HIT or a combinatorial approach with the STic Expert® HIT and the PF4/H IgG enzyme immunoassay provide an accurate diagnosis of immune HIT.

Problems, solutions, and perspectives in the evaluation of interval cancers in Italian mammography screening programmes: a position paper from the Italian group for mammography screening (GISMa).

In this position paper, a self-convened team of experts from the Italian Group for Mammography Screening (Gruppo italiano screening mammografico, GISMa) pointed out the problems that increasingly hamper the feasibility and validity of the estimate of the proportional incidence of interval breast cancer (IBC) in Italy, suggested potential solutions and an agenda for research, and proposed that the question of the sensitivity of mammography be viewed in a larger perspective, with a greater attention to radiological review activities and breast radiology quality assurance programmes. The main problems are as follows: the coverage of cancer registration is incomplete; the robustness of using the pre-screening incidence rates as underlying rates decreases with time since the start of screening; the intermediate mammograms performed for early detection purposes may cause an overrepresentation of IBCs; the classification of many borderline screening histories is prone to subjectivity; and, finally, the composition of cohorts of women with negative screening results is uncertain, because several mammography reports are neither clearly negative nor clearly positive, and because of the limitations and instability of the electronic mammography records. Several possibilities can be considered to cope with these issues: standard methods for using the hospital discharge records in the identification of IBCs should be established; for the calculation of regional estimates of the underlying incidence, a suitable mathematical model should be identified; the definition of IBC according to the 2008 GISMa guidelines needs to be updated, especially with respect to in situ cancers and to invasive cancers with borderline screening histories; a closer adherence to standard screening protocols, with a simplified patient management, would make it easier to objectively identify IBCs; alternative methods for estimating the sensitivity of mammography should be taken into consideration; and, finally, analysis could be restricted to the absolute incidence rate of IBC, which would make comparison of the risk between neighbouring populations possible. Epidemiologists must extend their attention to the prevention of the risk of IBC and the implementation of breast radiology quality assurance practices. Epidemiologists and radiologists can share common objectives: it is necessary to promote the idea that the availability of a registry-based series of IBCs is not a prerequisite for their radiological review; radiological review of breast cancers greater than 20mm in size detected at second and subsequent screens, that are potential substitutes for IBCs, needs radiological and epidemiological validation studies; the advent of digital mammography brings about the possibility to create libraries of mammograms accessible online, which enables the conduct of large studies of the diagnostic variability of radiologists; and, finally, epidemiologists and radiologists have the responsibility to monitor the effects that a loss of cumulative professional experience in screening centres, due to the imminent retirement of a substantial proportion of healthcare workforce, could cause on their performance.

Integration of 3D digital mammography with tomosynthesis for population breast-cancer screening (STORM): a prospective comparison study.

BACKGROUND: Digital breast tomosynthesis with 3D images might overcome some of the limitations of conventional 2D mammography for detection of breast cancer. We investigated the effect of integrated 2D and 3D mammography in population breast-cancer screening. METHODS: Screening with Tomosynthesis OR standard Mammography (STORM) was a prospective comparative study. We recruited asymptomatic women aged 48 years or older who attended population-based breast-cancer screening through the Trento and Verona screening services (Italy) from August, 2011, to June, 2012. We did screen-reading in two sequential phases-2D only and integrated 2D and 3D mammography-yielding paired data for each screen. Standard double-reading by breast radiologists determined whether to recall the participant based on positive mammography at either screen read. Outcomes were measured from final assessment or excision histology. Primary outcome measures were the number of detected cancers, the number of detected cancers per 1000 screens, the number and proportion of false positive recalls, and incremental cancer detection attributable to integrated 2D and 3D mammography. We compared paired binary data with McNemar's test. FINDINGS: 7292 women were screened (median age 58 years [IQR 54-63]). We detected 59 breast cancers (including 52 invasive cancers) in 57 women. Both 2D and integrated 2D and 3D screening detected 39 cancers. We detected 20 cancers with integrated 2D and 3D only versus none with 2D screening only (p<0.0001). Cancer detection rates were 5.3 cancers per 1000 screens (95% CI 3.8-7.3) for 2D only, and 8.1 cancers per 1000 screens (6.2-10.4) for integrated 2D and 3D screening. The incremental cancer detection rate attributable to integrated 2D and 3D mammography was 2.7 cancers per 1000 screens (1.7-4.2). 395 screens (5.5%; 95% CI 5.0-6.0) resulted in false positive recalls: 181 at both screen reads, and 141 with 2D only versus 73 with integrated 2D and 3D screening (p<0.0001). We estimated that conditional recall (positive integrated 2D and 3D mammography as a condition to recall) could have reduced false positive recalls by 17.2% (95% CI 13.6-21.3) without missing any of the cancers detected in the study population. INTERPRETATION: Integrated 2D and 3D mammography improves breast-cancer detection and has the potential to reduce false positive recalls. Randomised controlled trials are needed to compare integrated 2D and 3D mammography with 2D mammography for breast cancer screening. FUNDING: National Breast Cancer Foundation, Australia; National Health and Medical Research Council, Australia; Hologic, USA; Technologic, Italy.

Third national surgical consensus conference of the Italian Association of Breast Surgeons (ANISC) on management after neoadjuvant chemotherapy: The difficulty in reaching a consensus.

INTRODUCTION: Neoadjuvant chemotherapy (NAC) has a profound impact on surgical management of breast cancer. For this reason, the Italian Association of Breast Surgeons (ANISC) promoted the third national Consensus Conference on this subject, open to multidisciplinary specialists. MATERIALS AND METHODS: The Consensus Conference was held on-line in November 2022, and after an introductory session with five core-team experts, participants were asked to vote on eleven controversial issues, while results were collected in real-time with a polling system. RESULTS: A total of 164 dedicated specialists from 74 Breast Centers participated. Consensus was reached for only three of the eleven issues, including: 1) the indication to assess the response with Magnetic Resonance Imaging (79 %); 2) the need to re-assess the biological factors of the residual tumor if present (96 %); 3) the possibility of omitting a formal axillary node dissection for cN1 patients if a pathologic Complete Response (pCR) was confirmed with analysis of one or more sentinel lymph nodes (82 %). The majority voted in favor of mapping both the breast and nodal lesions pre-NAC (59 %), and against the omission of sentinel lymph node biopsy in cN0 patients in the case of pathologic or clinical Complete Response (69 %). In cases of cT3/cN1+ tumors with pCR, only 8 % of participants considered appropriate the omission of Post-Mastectomy Radiation Therapy. CONCLUSION: There is still a wide variability in surgical approaches after NAC in the "real world". As NAC is increasingly used, multidisciplinary teams should be attuned to conforming their procedures to the rapid advances in this field.

Cyclic variations of bone resorption mediators and markers in the different phases of the menstrual cycle.

Female hormones are very important in regulating bone homeostasis; the drop of estrogen levels occurring at menopause is linked to a dramatic prevalence of bone resorption on formation. Only a small number of studies investigated the relationship between changes in circulating female sex hormones and the markers and mediators of bone homeostasis and they showed conflicting results. To explore such relationships we studied 20 young fertile healthy women, aged between 19 and 32 years. None had received hormone treatment for at least 6 months. We assayed luteinizing hormone, follicle-stimulating hormone, progesterone and 17ß-estradiol, as well as the levels of osteoprotegerin (OPG), C-terminal telopeptide of collagen type I (CTx) and RANKL (receptor activator of nuclear factor-B ligand) in samples drawn from every subject at four different times during the menstrual cycle when estrogens are lowest, at the start of the cycle: T 0 (2-4th day); when estrogens are highest, in the pre-ovulatory period: T 14 (12-14th day); when progesterone activity is highest, in the advanced luteal phase: T 26 (24-26th day); and again at the start of the next cycle: T 01 (2-4th day). We observed that CTx levels are highest at the start of the cycle, decreased significantly from T 0 to T 26 (pfwe = 0.0455) and then increased from T 26 to T 01 (pfwe = 0.0415); OPG, on the other hand, which was also highest at the start of the cycle, decreased significantly from T 0 to T 14 (pfwe = 0.02) and then increased, though not significantly, from T 14 to T 01; no variation was observed in RANKL values at any time. We observed inverse correlations between estradiol and OPG levels, which became highly significant at T 01 between estradiol nadir and OPG peak levels (pfw = 0.0095). Furthermore, the increase of estradiol from T 0 to T 14 was negatively correlated with the concomitant decrease of OPG (pfwe = 0.0277), as was the fall of estradiol from T 26 to T 01 with the OPG peak levels, both at T 01 (pfw = 0.0045) and at T 0 (pfwe = 0.0381). We also observed direct correlations between the OPG levels and the variations of progesterone in the preceding intervals, but they never attained statistical significance. We conclude that OPG and CTx fluctuation during the menstrual cycle are likely due to the physiological variations of sex steroids levels.

A multicentric, single arm, prospective, stratified clinical investigation to evaluate MammoWave's ability in breast lesions detection.

Microwave imaging is a safe and promising new technology in breast radiology, avoiding discomfort of breast compression and usage of ionizing radiation. This paper presents the first prospective microwave breast imaging study during which both symptomatic and asymptomatic subjects were recruited. Specifically, a prospective multicentre international clinical trial was performed in 2020-2021, to investigate the capability of a microwave imaging device (MammoWave) in allowing distinction between breasts with no radiological finding (NF) and breasts with radiological findings (WF), i.e., with benign or malignant lesions. Each breast scan was performed with the volunteers lying on a dedicated examination table in a comfortable prone position. MammoWave output was compared to reference standard (i.e., radiologic study obtained within the last month and integrated with histological one if available and deemed necessary by responsible investigator) to classify breasts into NF/WF categories. MammoWave output consists of a selection of microwave images' features (determined prior to trials' start), which allow distinction between NF and WF breasts (using statistical significance p<0.05). 353 women were enrolled in the study (mean age 51 years ± 12 [SD], minimum age 19, maximum age 78); MammoWave data from the first 15 women of each site, all with NF breasts, were used for calibration. Following central assessor evaluation, 111 NF (48 dense) and 272 WF (136 dense) breasts were used for comparison with MammoWave output. 272 WF comprised 182 benign findings and 90 malignant histology-confirmed cancer. A sensitivity of 82.3% was achieved (95%CI: 0.78-0.87); sensitivity is maintained when limiting the investigation to histology-confirmed breasts cancer only (90 histology-confirmed breasts cancer have been included in this analysis, having sizes ranging from 3 mm to 60 mm). Specificity value of approximately 50% was achieved as expected, since thresholds were calculated (for each feature) using median value obtained after recruiting the first 15 women (of each site), all NF. This prospective trial may represent another step for introducing microwave imaging into clinical practice, for helping in breast lesion identification in asymptomatic women.

Pathologic response and residual tumor cellularity after neo-adjuvant chemotherapy predict prognosis in breast cancer patients.

INTRODUCTION: Residual tumor cellularity (RTC) and pathologic complete response (pCR) after neo-adjuvant chemotherapy (NAC) are prognostic factors associated with improved outcomes in breast cancer (BC). However, the majority of patients achieve partial pathologic response (pPR) and no clear correlation between RTC patterns and outcomes was described. Our aims were to define predictive factors for pCR and compare different outcomes of patients with pCR or pPR and with different RTC patterns. MATERIALS AND METHODS: Baseline and post-NAC demographics, clinicopathological characteristics, post-operative data, survival and recurrence status were recorded from our institutional database. A multivariable analysis was performed using a logistic regression model to identify independent predictors of pCR. Disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS) analyses were performed using the Kaplan-Meier method. RESULTS: Overall, of the 495 patients analyzed, 148 (29.9%) achieved pCR, 347 (70.1%) had pPR, and the median RTC was 40%. Multivariable analysis identified 3 independent factors predictive of pCR: tumor stage before NAC (cT1-2 84.5% versus cT3-4 15.5%), BC sub-type (HER2-positive 54.7% versus triple-negative 29.8% versus luminal-like 15.5%), and vascular invasion (absence 98.0% versus presence 2.0%). We found statistically significant longer DFS, DDFS, and OS in patients with pCR and with RTC <40%; no difference was observed in terms of OS between RTC <40% and RTC ≥40% groups. CONCLUSIONS: Tumor stage before NAC, BC sub-type, and vascular invasion are significant and independent factors associated with pCR. Patients with pCR and with RTC <40% have longer DFS, DDFS, and OS compared with patients with pPR.