Assessing the malignancy of suspicious breast microcalcifications: the role of contrast enhanced mammography.

PURPOSE: To assess the role of contrast-enhanced mammography (CEM) in predicting the malignancy of breast calcifications. MATERIAL AND METHODS: We retrospectively evaluated patients with suspicious calcifications (BIRADS 4) who underwent CEM and stereotactic vacuum-assisted biopsy (VAB) at our institution. We assessed the sensitivity (SE), specificity (SP), positive predictive value (PPV) and negative predictive value (NPV) of CEM in predicting malignancy of microcalcifications with a 95% confidence interval; we performed an overall analysis and a subgroup analysis stratified into group A-low risk (BIRADS 4a) and group B-medium/high risk (BIRADS 4b-4c). We then evaluated the correlation between enhancement and tumour proliferation index (Ki-67) for all malignant lesions. RESULTS: Data from 182 patients with 184 lesions were collected. Overall the SE of CEM in predicting the malignancy of microcalcifications was 0.70, SP was 0.85, the PPV was 0.82, the NPV was 0.76 and AUC was 0.78. SE in group A was 0.89, SP was 0.89, PPV was 0.57, NPV was 0.98 and AUC was 0.75. SE in group B was 0.68, SP was 0.80, PPV was 0.87, NPV was 0.57 and AUC was 0.75. Among malignant microcalcifications that showed enhancement (N = 52), 61.5% had Ki-67 ≥ 20% and 38.5% had low Ki-67 values. Among the lesions that did not show enhancement (N = 22), 90.9% had Ki-67 < 20% and 9.1% showed high Ki-67 values 20%. CONCLUSIONS: The absence of enhancement can be used as an indicative parameter for the absence of disease in cases of low-suspicious microcalcifications, but not in intermediate-high suspicious ones for which biopsy remains mandatory and can be used to distinguish indolent lesions from more aggressive neoplasms, with consequent reduction of overdiagnosis and overtreatment.

Exploring the Potential of Artificial Intelligence in Breast Ultrasound.

Breast ultrasound has emerged as a valuable imaging modality in the detection and characterization of breast lesions, particularly in women with dense breast tissue or contraindications for mammography. Within this framework, artificial intelligence (AI) has garnered significant attention for its potential to improve diagnostic accuracy in breast ultrasound and revolutionize the workflow. This review article aims to comprehensively explore the current state of research and development in harnessing AI's capabilities for breast ultrasound. We delve into various AI techniques, including machine learning, deep learning, as well as their applications in automating lesion detection, segmentation, and classification tasks. Furthermore, the review addresses the challenges and hurdles faced in implementing AI systems in breast ultrasound diagnostics, such as data privacy, interpretability, and regulatory approval. Ethical considerations pertaining to the integration of AI into clinical practice are also discussed, emphasizing the importance of maintaining a patient-centered approach. The integration of AI into breast ultrasound holds great promise for improving diagnostic accuracy, enhancing efficiency, and ultimately advancing patient's care. By examining the current state of research and identifying future opportunities, this review aims to contribute to the understanding and utilization of AI in breast ultrasound and encourage further interdisciplinary collaboration to maximize its potential in clinical practice.

Preoperative breast MRI positively impacts surgical outcomes of needle biopsy-diagnosed pure DCIS: a patient-matched analysis from the MIPA study.

OBJECTIVES: To investigate the influence of preoperative breast MRI on mastectomy and reoperation rates in patients with pure ductal carcinoma in situ (DCIS). METHODS: The MIPA observational study database (7245 patients) was searched for patients aged 18-80 years with pure unilateral DCIS diagnosed at core needle or vacuum-assisted biopsy (CNB/VAB) and planned for primary surgery. Patients who underwent preoperative MRI (MRI group) were matched (1:1) to those who did not receive MRI (noMRI group) according to 8 confounding covariates that drive referral to MRI (age; hormonal status; familial risk; posterior-to-nipple diameter; BI-RADS category; lesion diameter; lesion presentation; surgical planning at conventional imaging). Surgical outcomes were compared between the matched groups with nonparametric statistics after calculating odds ratios (ORs). RESULTS: Of 1005 women with pure unilateral DCIS at CNB/VAB (507 MRI group, 498 noMRI group), 309 remained in each group after matching. First-line mastectomy rate in the MRI group was 20.1% (62/309 patients, OR 2.03) compared to 11.0% in the noMRI group (34/309 patients, p = 0.003). The reoperation rate was 10.0% in the MRI group (31/309, OR for reoperation 0.40) and 22.0% in the noMRI group (68/309, p < 0.001), with a 2.53 OR of avoiding reoperation in the MRI group. The overall mastectomy rate was 23.3% in the MRI group (72/309, OR 1.40) and 17.8% in the noMRI group (55/309, p = 0.111). CONCLUSIONS: Compared to those going directly to surgery, patients with pure DCIS at CNB/VAB who underwent preoperative MRI had a higher OR for first-line mastectomy but a substantially lower OR for reoperation. CLINICAL RELEVANCE STATEMENT: When confounding factors behind MRI referral are accounted for in the comparison of patients with CNB/VAB-diagnosed pure unilateral DCIS, preoperative MRI yields a reduction of reoperations that is more than twice as high as the increase in overall mastectomies. KEY POINTS: • Confounding factors cause imbalance when investigating the influence of preoperative MRI on surgical outcomes of pure DCIS. • When patient matching is applied to women with pure unilateral DCIS, reoperation rates are significantly reduced in women who underwent preoperative MRI. • The reduction of reoperations brought about by preoperative MRI is more than double the increase in overall mastectomies.

Magnetic Localization of Breast Lesions: A Large-Scale European Evaluation in a National Cancer Institute.

INTRODUCTION: For decades the standard for preoperative breast lesions' localization has been wire localization. In recent years the options for nonwired localization have significantly expanded and include radioactive seeds, radar reflectors, radiofrequency identification tags and magnetic seeds. The aim of our study is to evaluate on a large scale the performance of preoperative magnetic seed localization of nonpalpable breast lesions. MATERIAL AND METHODS: We prospectively collected data on all patients undergoing image-guided magnetic seed localization from September 2019 to December 2022. We analyzed imaging findings, histological results, and type of surgery. The primary outcome was the successful localization rate. Secondary outcomes were the successful placement rate, the ease of percutaneous positioning, the procedural complications, and the reintervention rate. RESULTS: A total of 1123 magnetic seeds were placed in 1084 patients by 4 radiologists under ultrasound (1053) or stereotactic (70) guidance. All seeds were detectable transcutaneously in all breasts sizes and at all depths by 7 surgeons with a success rate of 100%. A total of 97.5% seeds were correctly placed into the target lesions (only 2.5% were dislocated). All radiologists have shown good compliance during the procedure, and there were no complications or safety issues. The reoperation rate was 5.1%. CONCLUSIONS: Image-guided localization with magnetic seeds is an easy, safe, reliable, and effective method for localizing nonpalpable breast lesions. Both radiologists and surgeons agreed that the technology was intuitive to use and that it can be widely applied in preoperative localization in breast units.

Efficacy and safety of vacuum-assisted excision (VAE) of fibroadenomas: experience in a tertiary centre.

PURPOSE: To evaluate the technical success and efficacy rates of US-guided percutaneous vacuum-assisted excision (VAE) of breast fibroadenomas, also assessing procedural complications and long-term patient satisfaction rates. MATERIALS AND METHODS: The institutional database of a tertiary breast cancer referral centre was retrospectively reviewed to retrieve all women with fibroadenomas who underwent US-guided VAE between May 2011 and September 2019. We subsequently included in this study all fibroadenomas with a maximum diameter of 3 cm at US and an available histological confirmation obtained by core-needle biopsy before VAE. Immediately after VAE, technical success (defined as the correct VAE execution) and the occurrence of procedural complications were evaluated. Imaging follow-up (US ± mammography) after 6, 12, 24 and 36 months was performed to evaluate technical efficacy (defined as the absence of fibroadenoma recurrence at 6-month follow-up). Long-term patient satisfaction was evaluated with telephonic interviews in October 2022. RESULTS: We retrospectively included 108 women (median age 46 years) with 110 fibroadenomas diagnosed at core-needle biopsy with a median lesion size at US of 12 mm. Technical success was obtained in 110/110 VAEs (100%). Minor procedural complications (haematomas) occurred in 7/110 VAEs (6%), whereas 8/110 patients had a fibroadenoma recurrence at 6-month follow-up, resulting in a 93% technical efficacy (102/110 VAEs). All patients available for telephonic follow-up (104/104, 100%) reported high satisfaction with VAE results. CONCLUSION: US-guided VAE is a safe and effective procedure for the excision of fibroadenomas, representing a viable alternative to surgery, with a low complication rate and high patient satisfaction.

Screening and diagnostic breast MRI: how do they impact surgical treatment? Insights from the MIPA study.

OBJECTIVES: To report mastectomy and reoperation rates in women who had breast MRI for screening (S-MRI subgroup) or diagnostic (D-MRI subgroup) purposes, using multivariable analysis for investigating the role of MRI referral/nonreferral and other covariates in driving surgical outcomes. METHODS: The MIPA observational study enrolled women aged 18-80 years with newly diagnosed breast cancer destined to have surgery as the primary treatment, in 27 centres worldwide. Mastectomy and reoperation rates were compared using non-parametric tests and multivariable analysis. RESULTS: A total of 5828 patients entered analysis, 2763 (47.4%) did not undergo MRI (noMRI subgroup) and 3065 underwent MRI (52.6%); of the latter, 2441/3065 (79.7%) underwent MRI with preoperative intent (P-MRI subgroup), 510/3065 (16.6%) D-MRI, and 114/3065 S-MRI (3.7%). The reoperation rate was 10.5% for S-MRI, 8.2% for D-MRI, and 8.5% for P-MRI, while it was 11.7% for noMRI (p ≤ 0.023 for comparisons with D-MRI and P-MRI). The overall mastectomy rate (first-line mastectomy plus conversions from conserving surgery to mastectomy) was 39.5% for S-MRI, 36.2% for P-MRI, 24.1% for D-MRI, and 18.0% for noMRI. At multivariable analysis, using noMRI as reference, the odds ratios for overall mastectomy were 2.4 (p < 0.001) for S-MRI, 1.0 (p = 0.957) for D-MRI, and 1.9 (p < 0.001) for P-MRI. CONCLUSIONS: Patients from the D-MRI subgroup had the lowest overall mastectomy rate (24.1%) among MRI subgroups and the lowest reoperation rate (8.2%) together with P-MRI (8.5%). This analysis offers an insight into how the initial indication for MRI affects the subsequent surgical treatment of breast cancer. KEY POINTS: • Of 3065 breast MRI examinations, 79.7% were performed with preoperative intent (P-MRI), 16.6% were diagnostic (D-MRI), and 3.7% were screening (S-MRI) examinations. • The D-MRI subgroup had the lowest mastectomy rate (24.1%) among MRI subgroups and the lowest reoperation rate (8.2%) together with P-MRI (8.5%). • The S-MRI subgroup had the highest mastectomy rate (39.5%) which aligns with higher-than-average risk in this subgroup, with a reoperation rate (10.5%) not significantly different to that of all other subgroups.

Utility of detection of breast calcifications with integrated real-time radiography system (IRRS) during digital breast tomosynthesis (DBT)-guided vacuum assisted biopsy (VAB): initial single-center experience.

PURPOSE: To determine whether the presence of calcifications in specimens collected during stereotactic-guided vacuum-assisted breast biopsies (VABB) is sufficient to ascertain their adequacy for final diagnosis at pathology. MATERIALS AND METHODS: Digital breast tomosynthesis (DBT)-guided VABBs were performed on 74 patients with calcifications as target. Each biopsy consisted of the collection of 12 samplings with a 9-gauge needle. This technique was integrated with a real-time radiography system (IRRS) which allowed the operator to determine whether calcifications were included in the specimens at the end of each of the 12 tissue collections through the acquisition of a radiograph of every sampling. Calcified and non-calcified specimens were separately sent to pathology and evaluated. RESULTS: A total of 888 specimens were retrieved, 471 containing calcifications and 417 without. In 105 (22.2%) samples out of 471 with calcifications cancer was detected, while the remaining 366 (77.7%) were non-cancerous. Out of 417 specimens without calcifications 56 (13.4%) were cancerous, whereas 361 (86.5%) were non-cancerous. Seven hundred and twenty-seven specimens out of all 888 were cancer-free (81.8%, 95%CI 79-84%). CONCLUSION: Although there is a statistical significative difference between calcified and non-calcified samples and the detection of cancer (p < 0.001), our study shows that the sole presence of calcifications in the specimens is not sufficient to determine their adequacy for final diagnosis at pathology because non-calcified samples can be cancerous and vice-versa. Ending biopsies when calcifications are first detected through IRRS could lead to false negative results.

Efficacy and Safety of First-line Carboplatin-paclitaxel and Carboplatin-gemcitabine in Patients With Advanced Triple-negative Breast Cancer: A Monocentric, Retrospective Comparison.

BACKGROUND: Platinum-based chemotherapy is widely used in patients with advanced triple-negative breast cancer (TNBC). However, the most effective platinum-based combination in the first-line treatment setting remains unclear. MATERIALS AND METHODS: We evaluated the efficacy of first-line carboplatin-paclitaxel (CP) or carboplatin-gemcitabine (CG) combinations in advanced TNBC patients treated between April 2007 and April 2021. CP and CG were compared in terms of progression-free survival (PFS), overall survival (OS), and incidence of adverse events (AEs). Multivariable Cox Models were used to adjust the efficacy of CP versus CG for clinically relevant covariates. RESULTS: Of 88 consecutive advanced TNBC patients receiving first-line carboplatin-based doublets, 56 (63.6%) received CP and 32 (36.4%) CG. After adjusting for clinically relevant variables, patients receiving CG had significantly better PFS when compared to CP-treated patients (HR: 0.49 (95% CI, 0.27-0.87), P value 0.014). Of note, CG was associated with better PFS only among patients previously treated with taxanes in the (neo)adjuvant setting (HR: 0.39; 95% CI, 0.21-0.75), but not in patients not exposed to taxanes (HR: 1.20; 95% CI, 0.37-3.88). CG was also independently associated with better OS when compared to CP (HR: 0.31 (95% CI: 0.15-0.64), P value 0.002). Overall, grade 3-4 AEs were more common in patients treated with CG than in patients treated with CP (68.8% vs. 21.4%, P value .009). CONCLUSION: CG and CP are effective and well tolerated first-line platinum doublets in advanced TNBC patients. CG could be more effective than CP in patients previous exposed to taxanes despite worse toxicity profile.

Moving HER2-low breast cancer predictive and prognostic data from clinical trials into the real world.

Background: Previous data, mostly from clinical trials, reported that HER2-low status is associated with low pathological complete response (pCR), and favourable prognosis. Since these findings suggest the existence of an additional breast cancer subtype, we questioned if the predictive/prognostic value of HER2-low was also relevant in the real world. Methods: Data from non-metastatic breast cancer patients treated with neoadjuvant chemotherapy and surgery (2009-2020) were retrieved from our institutional prospectively-maintained registry. Univariable and multivariable logistic models were implemented to study the association between pCR and baseline HER2 status. Univariable analysis of disease-free survival (DFS) was performed through Kaplan-Meier survival curves and log-rank tests. Results: Starting from a total of 790 consecutive cases, we identified 444 newly-diagnosed breast cancer patients featuring HER2 immunohistochemistry (IHC) 0 (HER2-0, n = 109), and 1 + or IHC 2+/in situ hybridization negative (HER2-low, n = 335) receiving anthracycline and taxane-based regimens in 88.9% of cases. Most of the patients were diagnosed with stage II (67.3%) and there was no difference of disease presentation according to HER2-status. pCR was attained by 71 (16.0%) patients and was significantly associated with increased DFS (p = 0.031). Compared to HER2-0, HER2-low cases were more likely hormone receptor-positive (81.2% vs. 43.1%, p < 0.001), well-differentiated (47.5% vs. 26.6%, p = 0.001), less proliferative (21.5% vs. 8.3%, p = 0.001) and less responsive to treatment (pCR 11.6% vs. 29.4%, p < 0.0001). There was no difference in DFS according to HER2 status, though hormone-receptor (HR) negative/HER2-low cases tended to have a worse prognosis compared to HR-negative/HER2-0. By pCR achievement, 3-years DFS was 87.5.% (75.1-100%) vs. 71.6% (65.9-77.8%) (p = 0.161) in HER2-low and 89.1% (75.8-100%) vs. 72.1% (59.7-87.0%) (p = 0.092) in HER2-0. Conclusion: Our real-world data show that HER2-low breast cancer patients represent roughly a half of the cases treated with neoadjuvant therapy, and have poor treatment response. In absence of pCR, HER2-low breast cancer patients have a dismal prognosis, especially when primary tumor hormone receptor status is negative. Studies are therefore needed to define the biology of these tumors for new therapeutic targets and to incorporate HER2-targeting agents in early-stage treatment.

Occurrence of breast-cancer-related lymphedema after reverse lymphatic mapping and selective axillary dissection versus standard surgical treatment of axilla: A two-arm randomized clinical trial.

BACKGROUND: The need for axillary dissection (AD) is declining, but it is still essential for many patients with nodal involvement who risk developing breast-cancer-related lymphedema (BCRL) with lifelong consequences. Previous nonrandomized studies found axillary reverse mapping and selective axillary dissection (ARM-SAD) a safe and feasible way to preserve the arm's lymphatic drainage. METHODS: The present two-arm prospective randomized clinical trial was held at a single comprehensive cancer center to ascertain whether ARM-SAD can reduce the risk of BCRL, compared with standard AD, in patients with node-positive breast cancer. Whatever the type of breast surgery or adjuvant treatments planned, 130 patients with nodal involvement met our inclusion criteria: 65 were randomized for AD and 65 for ARM-SAD. Twelve months after surgery, a physiatrist assessed patients for BCRL and calculated the excess volume of the operated arm. Lymphoscintigraphy was used to assess drainage impairment. Self-reports of any impairment were also recorded. RESULTS: The difference in the incidence of BCRL between the two groups was 21% (95% CI, 3-37; p = .03). A significantly lower rate of BCRL after ARM-SAD was confirmed by a multimodal analysis that included the physiatrist's findings, excess arm volume, and lymphoscintigraphic findings, but this was not matched by a significant difference in patients' self-reports. CONCLUSIONS: Our findings encourage a change of surgical approach when AD is still warranted. ARM-SAD may be an alternative to standard AD to reduce the treatment-related morbidity.

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.

Guiding vacuum-assisted biopsy in prone position: digital breast tomosynthesis vs stereotactic.

PURPOSE: To compare the performance of prone digital breast tomosynthesis (DBT)-vacuum-assisted biopsy (VAB) with prone stereotactic-guided VAB (sVAB), focusing on time of procedure, number of expositions, average glandular dose, and complications. METHODS: The institutional review board approved this retrospective study and informed consent was waived. From July 2015 to January 2017, 306 patients with 306 suspicious mammographic findings (BI-RADS ⩾4) underwent mammography-guided biopsy, prone sVAB, or prone DBT-VAB. Student t test, chi-square, and multivariate regression statistics were used. RESULTS: During the study period, 155 prone sVAB procedures in 155 patients (mean age, 56 years; age range, 39-84 years) and 151 DBT-VABs in 151 patients (mean age, 57 years; age range, 33-84 years) were performed. Mean procedure time was shorter with DBT-VAB versus sVAB (14.5 versus 17.4 minutes, respectively; p < 0.001), and fewer images were acquired with DBT-VAB versus sVAB (8 vs 11, respectively; p < 0.001); the average glandular dose was significantly lower in DBT-VAB versus sVAB (11.8 mGy versus 18 mGy, respectively; p < 0.001). There were no differences in the distribution of histologic results (p = 0.74) or breast density (p = 0.09) between the two groups. No major complications were observed in either group. CONCLUSION: Performance of prone DBT-VAB was superior to prone sVAB because it allowed a faster procedure with fewer radiologic expositions and lower radiation dose.

Contrast-enhanced digital mammography and magnetic resonance imaging: reproducibility compared to pathologic anatomy.

PURPOSE: To compare the reproducibility between contrast-enhanced digital mammography (CEDM) and magnetic resonance imaging (MRI) with the postsurgical pathologic examination. In addition, the applicability of the Breast Imaging-Reporting and Data System (BI-RADS) lexicon of MRI to CEDM was evaluated for mass lesions. METHODS: A total of 62 patients with a histologically proven diagnosis of breast cancer were included in this study, for a total of 67 lesions. Fifty-nine patients underwent both methods. The reproducibility between MRI vs CEDM and the reference standard (postoperative pathology) was assessed by considering the lesion and breast size as pivotal variables. Reproducibility was evaluated by computing the concordance correlation coefficient (CCC). Bland-Altman plots were used to depict the observed pattern of agreement as well as to estimate the associated bias. Furthermore, the pattern of agreement between the investigated methods with regard to the breast lesion characterization (i.e. mass/nonmass; shape; margins; internal enhanced characteristics) was assessed by computing the Cohen kappa and its 95% confidence interval (CI). RESULTS: The reproducibility between MRI and the reference standard and between CEDM and the reference standard showed substantial agreement, with a CCC value of 0.956 (95% CI, 0.931-0.972) and 0.950 (95% CI, 0.920-0.969), respectively. By looking at the Bland-Altman analysis, bias values of 2.344 and 1.875 mm were observed for MRI and CEDM vs reference evaluation, respectively. The agreement between MRI and CEDM is substantial with a CCC value of 0.969 (95% CI, 0.949-0.981). The Bland-Altman analysis showed bias values of -0.469 mm when comparing CEDM vs MRI. Following the Landis and Koch classification criteria, moderate agreement was observed between the two methods in describing BI-RADS descriptors of mass lesions. CONCLUSION: CEDM is able to measure and describe tumor masses comparably to MRI and can be used for surgical planning.

Sentinel Node Biopsy Alone or With Axillary Dissection in Breast Cancer Patients After Primary Chemotherapy: Long-Term Results of a Prospective Interventional Study.

OBJECTIVE: To ascertain, in cN0/1 breast cancer patients given primary chemotherapy followed by sentinel node biopsy (SNB), whether SNB alone is adequate axillary treatment if the sentinel nodes (SNs) are clear (pN0). SUMMARY BACKGROUND DATA: 2020 guidelines do not recommend SNB in most cN1 patients with clear SNs after primary chemotherapy because the high SNB false negative rate might lead to poorer outcomes. METHODS: We prospectively assigned SNB after primary chemotherapy to 353 consecutive cT2 cN0/1 patients, median age 47 years (range 22-76) treated from 2007 to 2015. If the SNs were pN0, patients generally received no further axillary treatment (SNB only); if the SNs were pN1, completion axillary dissection (AD) (SNB + AD) was usually performed. Primary outcomes were overall (OS) and disease-free (DFS) survival in SNB only versus SNB + AD patients, assessed by Kaplan-Meier and compared using log-rank test, with use of propensity scores to account for bias due to nonrandom assignment to SNB versus SNB + AD. RESULTS: Median follow-up was 108 months, interquartile range 66 to 136. OS and DFS did not differ significantly between the groups by propensity score- weighted comparison: 10-year OS 89% [95% confidence interval (CI): 81%- 99%] in SNB only patients versus 86% (95%CI: 78%-95%) in SNB + AD patients; 10-year DFS 79% (95%CI: 68%-92%) versus 69% (95%CI: 58%-81%). No SNB-only patient developed axillary failure. CONCLUSIONS: cT2 cN0/1 patients whose SNs are disease-free (pN0) after primary chemotherapy can be offered SNB (with no further axillary treatment if the SNs are negative), irrespective of axillary status beforehand, without affecting OS or DFS.

Magnetic resonance imaging before breast cancer surgery: results of an observational multicenter international prospective analysis (MIPA).

OBJECTIVES: Preoperative breast magnetic resonance imaging (MRI) can inform surgical planning but might cause overtreatment by increasing the mastectomy rate. The Multicenter International Prospective Analysis (MIPA) study investigated this controversial issue. METHODS: This observational study enrolled women aged 18-80 years with biopsy-proven breast cancer, who underwent MRI in addition to conventional imaging (mammography and/or breast ultrasonography) or conventional imaging alone before surgery as routine practice at 27 centers. Exclusion criteria included planned neoadjuvant therapy, pregnancy, personal history of any cancer, and distant metastases. RESULTS: Of 5896 analyzed patients, 2763 (46.9%) had conventional imaging only (noMRI group), and 3133 (53.1%) underwent MRI that was performed for diagnosis, screening, or unknown purposes in 692/3133 women (22.1%), with preoperative intent in 2441/3133 women (77.9%, MRI group). Patients in the MRI group were younger, had denser breasts, more cancers ≥ 20 mm, and a higher rate of invasive lobular histology than patients who underwent conventional imaging alone (p < 0.001 for all comparisons). Mastectomy was planned based on conventional imaging in 22.4% (MRI group) versus 14.4% (noMRI group) (p < 0.001). The additional planned mastectomy rate in the MRI group was 11.3%. The overall performed first- plus second-line mastectomy rate was 36.3% (MRI group) versus 18.0% (noMRI group) (p < 0.001). In women receiving conserving surgery, MRI group had a significantly lower reoperation rate (8.5% versus 11.7%, p < 0.001). CONCLUSIONS: Clinicians requested breast MRI for women with a higher a priori probability of receiving mastectomy. MRI was associated with 11.3% more mastectomies, and with 3.2% fewer reoperations in the breast conservation subgroup. KEY POINTS: • In 19% of patients of the MIPA study, breast MRI was performed for screening or diagnostic purposes. • The current patient selection to preoperative breast MRI implies an 11% increase in mastectomies, counterbalanced by a 3% reduction of the reoperation rate. • Data from the MIPA study can support discussion in tumor boards when preoperative MRI is under consideration and should be shared with patients to achieve informed decision-making.

Circulating miRNAs as Novel Non-Invasive Biomarkers to Aid the Early Diagnosis of Suspicious Breast Lesions for Which Biopsy Is Recommended.

In population-based screens, tissue biopsy remains the standard practice for women with imaging that suggests breast cancer. We examined circulating microRNAs as minimally invasive diagnostic biomarkers to discriminate malignant from benign breast lesions. miRNAs were analyzed by OpenArray in a retrospective cohort of plasma samples including 100 patients with malignant (T), 89 benign disease (B), and 99 healthy donors (HD) divided into training and testing sets and a prospective cohort (BABE) of 289 women with suspicious imaging findings who underwent tissue biopsy. miRNAs associated with disease status were identified by univariate analysis and then combined into signatures by multivariate logistic regression models. By combining 16 miRNAs differentially expressed in the T vs. HD comparison, 26 signatures were also able to significantly discriminate T from B disease. Seven of them, involving 5 specific miRNAs (miR-625, miR-423-5p, miR-370-3p, miR-181c, and miR-301b), were statistically validated in the testing set. Among the 7 signatures, the discriminatory performances of 5 were confirmed in the prospective BABE Cohort. This study identified 5 circulating miRNAs that, properly combined, distinguish malignant from benign breast disease in women with a high likelihood of malignancy.

Circulating Tumor Cell Clusters Are Frequently Detected in Women with Early-Stage Breast Cancer.

The clinical relevance of circulating tumor cell clusters (CTC-clusters) in breast cancer (BC) has been mostly studied using the CellSearch®, a marker-dependent method detecting only epithelial-enriched clusters. However, due to epithelial-to-mesenchymal transition, resorting to marker-independent approaches can improve CTC-cluster detection. Blood samples collected from healthy donors and spiked-in with tumor mammospheres, or from BC patients, were processed for CTC-cluster detection with 3 technologies: CellSearch®, CellSieve™ filters, and ScreenCell® filters. In spiked-in samples, the 3 technologies showed similar recovery capability, whereas, in 19 clinical samples processed in parallel with CellSearch® and CellSieve™ filters, filtration allowed us to detect more CTC-clusters than CellSearch® (median number = 7 versus 1, p = 0.0038). Next, samples from 37 early BC (EBC) and 23 metastatic BC (MBC) patients were processed using ScreenCell® filters for attaining both unbiased enrichment and marker-independent identification (based on cytomorphological criteria). At baseline, CTC-clusters were detected in 70% of EBC cases and in 20% of MBC patients (median number = 2, range 0-20, versus 0, range 0-15, p = 0.0015). Marker-independent approaches for CTC-cluster assessment improve detection and show that CTC-clusters are more frequent in EBC than in MBC patients, a novel finding suggesting that dissemination of CTC-clusters is an early event in BC natural history.

The P.I.N.K. Study Approach for Supporting Personalized Risk Assessment and Early Diagnosis of Breast Cancer.

Breast cancer is a clear example of excellent survival when it is detected and properly treated in the early stage. Currently, screening of this cancer relies on mammography, which may be integrated by new imaging techniques for more exhaustive evaluation. The Personalized, Integrated, Network, Knowledge (P.I.N.K.) study is a longitudinal multicentric study involving several diagnostic centres across Italy, co-ordinated by the Italian National Research Council and co-funded by the Umberto Veronesi Foundation. Aim of the study is to evaluate the increased diagnostic accuracy in detecting cancers obtained with different combinations of imaging technologies, and find the most effective diagnostic pathway matching the characteristics of an individual patient. The study foresees the enrolment of 50,000 women over the age of 40 years presenting for breast examination and providing informed consent to data handling. So far, the 15 participating centres across Italy have recruited a total of 22,848 patients. Based on the analyses of the first 175 histopathological-proven breast cancers, mammographic sensitivity was estimated to be 61.7% (n = 108 cancers), whereas diagnostic accuracy increased by 35.5% (n = 44 cancers) when mammography was integrated with other imaging modalities (ultrasound and/or digital breast tomosynthesis). Increase was mainly determined by ultrasound alone. Given the ongoing data collection and recruitment, the number of cancers detected is too low to allow any further in-depth analysis to explore links to patient characteristics. Past studies show that the uniform approach of population screening guidelines should be revised in favour of more personalised regimens, where known standards are integrated by imaging techniques most suitable for the individual's characteristics. With the ultimate goal of identifying early breast cancer detection strategies, our preliminary results suggest that integrated diagnostic approach could lead to a paradigm shift from an age-based regimen toward more specific and effective risk-based personalised screening regimens, in order to reduce mortality from breast cancer.

Uncommon site of metastatic neuroblastoma in a 15-year-old girl: case report and description of sonographic and radiographic features.

BACKGROUND: Although most breast masses in children are benign, breast cancer must be considered in the differential diagnosis. The majority are represented by sarcomas and secondary lesions. Literature reports only four cases of neuroblastoma breast metastasis, with no emphasis on radiologic features. Our work aims to furnish a description of radiologic and sonographic features of neuroblastoma metastasis in the breast. CASE DESCRIPTION: A 15-year-old girl had a round nodular mass in the outer upper quadrant of the left breast that had rapidly enlarged over the last month. An ultrasound showed two subcutaneous nodules (3.8 cm and 1.3 cm in maximum diameter), with an irregular shape, heterogeneous echogenicity (isohypoechoic), and hyperechoic foci with a posterior acoustic shadow inside. Overall, the features were highly suspicious of secondary malignant lesions. Computed tomographic scan was performed and found a large retroperitoneal mass and multiple mixed secondary lesions to the spine and hip. A 14G core needle biopsy of breast masses was performed and showed a secondary localization of neuroblastoma. CONCLUSIONS: In adolescents, metastases are the most frequent cause of malignant breast masses. Ultrasound examination should be preferred as the first imaging tool. For the differential diagnosis of breast metastasis with benign masses, a rapid enlargement, a heterogeneous echogenicity, and intralesional hyperechogenic foci could be considered features of malignancy.

Should oncoplastic breast conserving surgery be used for the treatment of early stage breast cancer? Using the GRADE approach for development of clinical recommendations.

INTRODUCTION: The potential advantages of oncoplastic breast conserving surgery (BCS) have not been validated in robust studies that constitute high levels of evidence, despite oncoplastic techniques being widely adopted around the globe. There is hence the need to define the precise role of oncoplastic BCS in the treatment of early breast cancer, with consensual recommendations for clinical practice. METHODS: A panel of world-renowned breast specialists was convened to evaluate evidence, express personal viewpoints and establish recommendations for the use of oncoplastic BCS as primary treatment of unifocal early stage breast cancers using the GRADE approach. RESULTS: According to the results of the systematic review of literature, the panelists were asked to comment on the recommendation for use of oncoplastic BCS for treatment of operable breast cancer that is suitable for breast conserving surgery, with the GRADE approach. Based on the voting outcome, the following recommendation emerged as a consensus statement: Oncoplastic breast conserving surgery should be recommended versus standard breast conserving surgery for the treatment of operable breast cancer in adult women who are suitable candidates for breast conserving surgery (with very low certainty of evidence). DISCUSSION: This review has revealed a low level of evidence for most of the important outcomes in oncoplastic surgery with lack of any randomized data and absence of standard tools for evaluation of clinical outcomes and especially patients' values. Despite areas of controversy, about one-third (36%) of panel members expressed a strong recommendation in support of oncoplastic BCS. Presumably, this reflects a synthesis of views on the relative complexity of these techniques, associated complications, impact on quality of life and costs.