B-cell non-Hodgkin lymphoma of the breast in Waldenström's macroglobulinemia: a case report.

Background: Non-Hodgkin lymphoma (NHL) of the breast is a rare disease and can occur amongst patients affected by Waldenström's Macroglobulinemia (WM). WM is an indolent B-cell lymphoproliferative disorder with an overall incidence of about 1/100,000 in Europe. Breast imaging is not specific to breast lymphoma that often mimics benign lesions. The diagnosis is based on breast biopsy, the presence of MYD88L265P somatic mutation and immunoglobulin M (IgM) paraprotein detectable in the setting of lymphoplasmacytic infiltration by bone marrow (BM) biopsy. Case Description: A 60-year-old woman with personal and familial history of monoclonal gammopathy of undetermined significance (MGUS) and a lump in her right breast was referred to our hospital. Standard imaging showed round mass with smooth edges. The lump was biopsied and the pathology examination showed lymphoplasmacytic lymphoma (LPL) of the breast which led to final the diagnosis of WM. Conclusions: Lymphoma of the breast is a rare disease, often misdiagnosed because of the lack of specific features at mammogram and ultrasound. Core biopsy is crucial to make diagnosis of breast lymphoma and early diagnosis of WM has been shown to improve overall survival (OS). A comprehensive approach is required in order to assess patients affected by blood disorders presenting with a new breast mass that can lead to diagnosis of breast lymphoma.

Randomized Placebo Controlled Trial of Low-Dose Tamoxifen to Prevent Recurrence in Breast Noninvasive Neoplasia: A 10-Year Follow-Up of TAM-01 Study.

PURPOSE: Five-year data of the phase III trial TAM-01 showed that low-dose tamoxifen at 5 mg once daily administered for 3 years in women with intraepithelial neoplasia (IEN) reduced by 52% the recurrence of invasive breast cancer or ductal carcinoma in situ (DCIS), without additional adverse events over placebo. Here, we present the 10-year results. METHODS: We randomly assigned 500 women with breast IEN (atypical ductal hyperplasia, lobular carcinoma in situ [LCIS], or hormone-sensitive or unknown DCIS) to low-dose tamoxifen or placebo after surgery with or without irradiation. The primary end point was the incidence of invasive breast cancer or DCIS. RESULTS: The TAM-01 population included 500 women (20% atypical ductal hyperplasia, 11% LCIS, and 69% DCIS). The mean (±SD) age at the start of treatment was 54 ± 9 years, and 58% of participants were postmenopausal. After a median follow-up of 9.7 years (IQR, 8.3-10.9 years), 66 breast cancers (15 in situ; 51 invasive) were diagnosed: 25 in the tamoxifen group and 41 in the placebo group (annual rate per 1,000 person-years, 11.3 with tamoxifen v 19.5 with placebo; hazard ratio [HR], 0.58; 95% CI, 0.35 to 0.95; log-rank P = .03). Most recurrences were invasive (77%) and ipsilateral (59%). Regarding contralateral breast cancer incidence, there were six events in the tamoxifen arm and 16 in the placebo arm (HR, 0.36; 95% CI, 0.14 to 0.92; P = .025). The number needed to be treated to prevent one case of breast event with tamoxifen therapy was 22 in 5 years and 14 in 10 years. The benefit was seen across all patient subgroups. There was a significant 50% reduction of recurrence with tamoxifen in the DCIS cohort, which represents 70% of the overall population (HR, 0.50; 95% CI, 0.28 to 0.91; P = .02). No between-group difference in the incidence of serious adverse events was reported during the prolonged follow-up period. CONCLUSION: Tamoxifen 5 mg once daily for 3 years significantly prevents recurrence from noninvasive breast cancer after 7 years from treatment cessation without long-term adverse events.

Preoperative localisation of nonpalpable breast lesions using magnetic markers in a tertiary cancer centre.

BACKGROUND: We retrospectively evaluated safety and performance of magnetic seed localisation of nonpalpable breast lesions. METHODS: We reviewed records of patients with nonpalpable breast lesions preoperative localised by placing magnetic Magseed® marker between February 2019 and December 2020. During surgery, Sentimag® magnetic probe was used to localise the marker and guide surgery. Safety, lesion identification and excision with tumour with free margins and re-excision rate were assessed. RESULTS: A total of 77 Magseed® devices were placed into the breasts of 73 patients, 44 under ultrasound and 33 under stereotactic guidance (4 bilateral). All devices were retrieved as were the target lesions. Magnetic marker placement was successful in all cases without any adverse event. Intraoperative identification and excision of the localised lesion were successful in 77 of 77 of cases (100%). In three cases (all of them calcifications with the seed placed under stereotactic guidance), the seed did not reach the exact target position of the biopsy clip; thus, larger excision was needed, with localisation failure attributed to incorrect clip insertion (n = 1) or to clip dislocation (n = 2). Migration of the marker was negligible in all patients. Complete excision after the initial procedure with at least 1-mm disease-free margins was obtained in 74 out of 77 (96.1%) lesions. The re-excision rate was 3 out of 77 (4%). CONCLUSIONS: Magnetic marker localisation for nonpalpable breast lesions was safe, reliable, and effective in terms of lesion identification, excision with tumour-free margins and re-excision rate.

Radiomic and Artificial Intelligence Analysis with Textural Metrics Extracted by Contrast-Enhanced Mammography and Dynamic Contrast Magnetic Resonance Imaging to Detect Breast Malignant Lesions.

Purpose:The purpose of this study was to discriminate between benign and malignant breast lesions through several classifiers using, as predictors, radiomic metrics extracted from CEM and DCE-MRI images. In order to optimize the analysis, balancing and feature selection procedures were performed. Methods: Fifty-four patients with 79 histo-pathologically proven breast lesions (48 malignant lesions and 31 benign lesions) underwent both CEM and DCE-MRI. The lesions were retrospectively analyzed with radiomic and artificial intelligence approaches. Forty-eight textural metrics were extracted, and univariate and multivariate analyses were performed: non-parametric statistical test, receiver operating characteristic (ROC) and machine learning classifiers. Results: Considering the single metrics extracted from CEM, the best predictors were KURTOSIS (area under ROC curve (AUC) = 0.71) and SKEWNESS (AUC = 0.71) calculated on late MLO view. Considering the features calculated from DCE-MRI, the best predictors were RANGE (AUC = 0.72), ENERGY (AUC = 0.72), ENTROPY (AUC = 0.70) and GLN (gray-level nonuniformity) of the gray-level run-length matrix (AUC = 0.72). Considering the analysis with classifiers and an unbalanced dataset, no significant results were obtained. After the balancing and feature selection procedures, higher values of accuracy, specificity and AUC were reached. The best performance was obtained considering 18 robust features among all metrics derived from CEM and DCE-MRI, using a linear discriminant analysis (accuracy of 0.84 and AUC = 0.88). Conclusions: Classifiers, adjusted with adaptive synthetic sampling and feature selection, allowed for increased diagnostic performance of CEM and DCE-MRI in the differentiation between benign and malignant lesions.

Changes of narrative meaning-making markers during the different phases of breast cancer treatment for women below 50 years old.

BACKGROUND: The onset of breast cancer is considered a potential traumatic event associated with physical and psychological effects, in particular when it occurs at the age below 50. The literature lacks a longitudinal narrative exploration of breast cancer experience of young women. PARTICIPANTS AND PROCEDURE: Using the narrative device as a diachronic tool aimed at promoting semiotic connection processes during the different phases of the therapeutic path, the authors constructed an ad hoc narrative interview to explore the meaning-making processes of 10 breast cancer patients below 50 years old during three turning-point phases: pre-hospitalization (T1); postoperative counseling (T2); and adjuvant therapy (T3). The research took place at National Cancer Institute Pascale of Naples. Through an ad hoc qualitative methodology, this study identifies the prevailing modes with which the five narrative meaning-making functions are articulated in the repeated narrative during the three phases. RESULTS: The findings capture the patterns of change of narrative meaning-making markers during the illness experience, highlighting both integrated modes of connections between aspects of experience over time and moments of block in specific critical phases for women under 50. CONCLUSIONS: From a clinical health psychology point of view the results suggest the promotion of integration between the synchrony of the medical path and the diachrony of the subjective experience of women to support resources for adapting to experience.

Effect Modifiers of Low-Dose Tamoxifen in a Randomized Trial in Breast Noninvasive Disease.

PURPOSE: Low-dose tamoxifen halved recurrence after surgery in a phase III trial in breast noninvasive disease without increasing adverse events. We explored the effect of low-dose tamoxifen in clinically relevant subgroups, including menopausal status, estradiol levels, smoking, body mass index, and proliferation of baseline lesion. PATIENTS AND METHODS: Incidence of invasive breast cancer or ductal carcinoma in situ was the primary endpoint. HRs and interaction terms were estimated using Cox models. RESULTS: A favorable HR and 95% confidence interval (CI) could be demonstrated for postmenopausal status (HR = 0.30; 95% CI, 0.11-0.82 vs. HR = 0.73; 95% CI, 0.30-1.76 in premenopausal women; P interaction = 0.13), women with estradiol less than 15.8 pg/mL, presence of menopausal symptoms at baseline, and never smoking (P interaction = 0.07), although the interaction P value was >0.05 for all characteristics. Efficacy was similar in all body mass index categories. Tumors with Ki-67 above the median level of 10% had a greater benefit (HR = 0.27; 95% CI, 0.09-0.81) than those with Ki-67 ≤10% (HR = 1.58; 95% CI, 0.45-5.60; P interaction = 0.04). CONCLUSIONS: The efficacy of low-dose tamoxifen seems to be greater in postmenopausal women and in women with lower estradiol levels. Benefits appear to be larger also in women with menopausal symptoms, never smokers, and tumors with Ki-67 >10%. Our results by menopausal status provide important insight into low-dose tamoxifen personalized treatment, although caution is necessary given their exploratory nature. Observation of an improved response in tumors with Ki-67 >10% is consistent but the use of the marker in this setting is investigational.See related commentary by Fabian, p. 3510.

Longitudinal effect of emotional processing on psychological symptoms in women under 50 with breast cancer.

Breast cancer is a potential traumatic event associated with psychological symptoms, but few studies have analysed its impact in under-50 women. Emotional processing is a successful function in integrating traumatic experiences. This work analysed the relationship between emotional processing and psychological symptoms during three phases of treatment (before hospitalization, counselling after surgery and adjuvant therapy) in 50 women under the age of 50 with breast cancer. Mixed-effects models tested statistical differences among phases. There were significant differences in symptoms during the treatments: the levels of anxiety decrease from T1 to T3 (0.046), while those of hostility increase (<0.001). Emotional processing is a strong predictor of all symptoms. Clinical implications are discussed.

Randomized Placebo Controlled Trial of Low-Dose Tamoxifen to Prevent Local and Contralateral Recurrence in Breast Intraepithelial Neoplasia.

PURPOSE: Tamoxifen administered for 5 years at 20 mg/d is effective in breast cancer treatment and prevention, but toxicity has limited its broad use. Biomarker trials showed that 5 mg/d is not inferior to 20 mg/d in decreasing breast cancer proliferation. We hypothesized that a lower dose given for a shorter period could be as effective in preventing recurrence from breast intraepithelial neoplasia but have a lower toxicity than the standard dose. PATIENTS AND METHODS: We conducted a multicenter randomized trial of tamoxifen, 5 mg/d or placebo administered for 3 years after surgery in women with hormone-sensitive or unknown breast intraepithelial neoplasia, including atypical ductal hyperplasia and lobular or ductal carcinoma in situ. The primary end point was the incidence of invasive breast cancer or ductal carcinoma in situ. RESULTS: Five hundred women 75 years of age or younger were included. After a median follow-up of 5.1 years (interquartile range, 3.9-6.3 years), there were 14 neoplastic events with tamoxifen and 28 with placebo (11.6 v 23.9 per 1,000 person-years; hazard ratio, 0.48; 95% CI, 0.26 to 0.92; P = .02), which resulted in a 5-year number needed to treat of 22 (95% CI, 20 to 27). Tamoxifen decreased contralateral breast events by 75% (three v 12 events; hazard ratio, 0.25; 95% CI, 0.07 to 0.88; P = .02). Patient-reported outcomes were not different between arms except for a slight increase in frequency of daily hot flashes with tamoxifen (P = .02). There were 12 serious adverse events with tamoxifen and 16 with placebo, including one deep vein thrombosis and one stage I endometrial cancer with tamoxifen and one pulmonary embolism with placebo. CONCLUSION: Tamoxifen at 5 mg/d for 3 years can halve the recurrence of breast intraepithelial neoplasia with a limited toxicity, which provides a new treatment option in these disorders.

Underfifty Women and Breast Cancer: Narrative Markers of Meaning-Making in Traumatic Experience.

A diagnosis of breast cancer is considered a potential traumatic event associated with physical and psychological effects. In literature, an exploration of breast cancer experience in young women is lacking, able to shed light on the narrative processes of meaning-making of the experience in specific phases of treatment, as may be the initial impact with the onset of the cancer. Meaning-making processes are determinant aspects when dealing with traumatic events. The research took place at National Cancer Institute Pascale of Naples. We collected 50 ad hoc narrative interviews to explore the different domains of the experience with under-fifty women at the first phase of the hospitalization. The Narrative Interviews were analyzed through a qualitative methodology constructed ad hoc. Starting from the functions of meaning-making that the narrative mediate we have highlight the different modes to articulate the narrative functions: The Organization of Temporality: chronicled (38%), actualized (26%), suspended (18%), interrupted (16%), and confused (2%). The Search for Meaning: internalized (42%); generalized (24%); externalized (18%); suspended (16%). The Emotional Regulation: disconnected (44%), splitted (28%), pervasive (26%), and connected (2%). The Organization of self-other Relationship: supportive (46%), avoidant (22%), overturned (16%), and sacrificial (16%). The Finding Benefit: revaluating (38%), flattened (34%), and postponed (28%). The Orientation to Action: combative (38%), blocked (36%), and suspended (26%). Findings capture the impact with the onset of the cancer, identifying both risk and resource aspects. The study allows to identify a specific use of narrative device by under-fifty women who impacted with the experience of breast cancer. The ways in which meaning-making functions are articulated highlight the specificity of the first phase of the treatment of the cancer. From a clinical psychology point of view, our findings can be used as clinical narrative markers to grasp, in a diachronic way, the process of meaning-making, integration, and coping during the first phase of breast cancer experience in young women. We consider it valuable to increase longitudinal studies with young women to highlight trajectories of meaning-making during the different phases of the treatment to think about personalized intervention practices diachronically to the experience.

Intracystic papillary breast carcinoma with DCIS in a man: a case report.

Here we report a case of 50-mm lump within the left breast in a 56-year-old man. The patient underwent left total mastectomy and sentinel node biopsy. The pathology report showed low-grade intracystic papillary breast carcinoma surrounded by ductal carcinoma in situ. Sentinel node biopsy was negative. The patient was prescribed five years tamoxifen.

Angiosarcoma of the breast, the unknown-a review of the current literature.

Angiosarcoma of the breast is one of the rarest malignancies. Breast angiosarcoma can be classified into primary when arising de novo and secondary to chronic lymphoedema or breast irradiation. Molecular pathways involved in angiosarcoma development have not been described clearly, yet some gene point mutations and protein altered expression levels have been detected. So far, their management is based above all on surgery. Hence, further studies starting from the few known key points may help to develop more effective strategies based both on target therapies, together with surgery.

Use of Quantitative Morphological and Functional Features for Assessment of Axillary Lymph Node in Breast Dynamic Contrast-Enhanced Magnetic Resonance Imaging.

BACKGROUND: Axillary lymph-node assessment is considered one of the most important prognostic factors concerning breast cancer survival. OBJECTIVE: We investigated the discriminative power of morphological and functional features in assessing the axillary lymph node. METHODS: We retrospectively analysed data from 52 consecutive patients who undergone DCE-MRI and were diagnosed with primary breast carcinoma: 94 lymph nodes were identified. Per each lymph node, we extracted morphological features: circularity, compactness, convexity, curvature, elongation, diameter, eccentricity, irregularity, radial length, entropy, rectangularity, roughness, smoothness, sphericity, spiculation, surface, and volume. Moreover, we extracted functional features: time to peak (TTP), maximum signal difference (MSD), wash-in intercept (WII), wash-out intercept (WOI), wash-in slope (WIS), wash-out slope (WOS), area under gadolinium curve (AUGC), area under wash-in (AUWI), and area under wash-out (AUWO). Selection of important features in predicting metastasis has been done by means of receiver operating characteristic (ROC) analysis. Performance of linear discriminant analysis was analysed. RESULTS: All morphological features but circularity showed a significant difference between median values of metastatic lymph nodes group and nonmetastatic lymph nodes group. All dynamic parameters except for MSD and WOS showed a statistically significant difference between median values of metastatic lymph nodes group and nonmetastatic lymph nodes group. Best results for discrimination of metastatic and nonmetastatic lymph nodes were obtained by AUGC (accuracy 75.8%), WIS (accuracy 71.0%), WOS (accuracy 71.0%), and AUCWO (accuracy 72.6%) for dynamic features and by compactness (accuracy 82.3%), curvature (accuracy 71.0%), radial length (accuracy 71.0%), roughness (accuracy 74.2%), smoothness (accuracy 77.2%), and speculation (accuracy 72.6%) for morphological features. Linear combination of all morphological and/or of all dynamic features did not increase accuracy in metastatic lymph nodes discrimination. CONCLUSIONS: Compactness as morphological feature and area under time-intensity curve as dynamic feature were the best parameters in identifying metastatic lymph nodes on breast MRI.

Optical imaging of the breast: evaluation of deoxyhemoglobin concentration alteration in 166 patients with suspicious breast lesions.

BACKGROUND: We investigated the performance of optical imaging evaluating deoxyhemoglobin concentration alteration (DeHCA) in breast tissues. METHODS: We enrolled all consecutive patients from January 2015 to October 2016 with clinically suspicious and/or BI-RADS grade 3-5 lesions at mammography or ultrasound (US). Patients underwent optical imaging (ComfortScan) to evaluate for DeHCA. The reference standard was pathology from a surgical specimen for malignant lesions, pathology from a surgical specimen or core needle biopsy for benign lesions, and negative follow-up for contralateral negative breasts. Non-parametric statistics, receiver operating characteristic, and linear discrimination analyses were performed. RESULTS: Of 334 enrolled patients, 168 (50%) were excluded for technical problems and 166 (50%) (median age 52 years) were analyzed totaling 331 breasts and 176 lesions. Of these, 75 were benign (median size 19 mm) and 101 malignant (median size 20 mm). The median DeHCA score in malignant lesions (0.95, interquartile range [IQR] 1.00-0.87) was higher (p < 0.001) than in benign lesions (0.80, IQR 0.95-0.70). Using the optimal cutoff (0.85), DeHCA score was less accurate than mammography, US, and their combination, with 78% sensitivity, 52% specificity, 40% positive predictive value (PPV), and 85% negative predictive value (NPV); using a 0.8 cutoff, sensitivity reached 93% and NPV 91%, but specificity fell to 32% and PPV to 37%. The accuracy of DeHCA score linearly combined with mammography or US was higher than that of DeHCA score alone (p < 0.001) and not significantly higher than that of mammography or US alone. CONCLUSIONS: DeHCA score was significantly higher in malignant than in benign lesions, but its accuracy was significantly lower than that of mammography or US. Future refinements are needed.

Abbreviated breast dynamic contrast-enhanced MR imaging for lesion detection and characterization: the experience of an Italian oncologic center.

BACKGROUND: To evaluate the performance of an abbreviated dynamic contrast-enhanced MR imaging (MRI) protocol for breast cancer detection; a comparison with the complete diagnostic protocol has been conducted. METHODS: A retrospective analysis on 508 patients was performed. Abbreviated protocol (AP) included one pre-contrast and the first post-contrast T1-weighted series. Complete protocol (CP) consisted of four post-contrast and one pre-contrast T1-weighted series. Diagnostic performance was assessed for AP and CP. Performance comparison was made using McNemar's test for sensitivity and specificity and Moskowitz and Pepe's method as regards negative predictive value (NPV) and positive predictive value (PPV). AP has been realized in two different ways (AP1 and AP2) and they were compared by means of Cohen's κ. RESULTS: Both CP and AP revealed 206 of 207 cancers. There were no statistically significant differences between AP and CP diagnostic performance (P > 0.05). NPVs of CP and both versions of AP (99.57 vs. 99.56%, P = 0.39), as well as the specificity (77.08 vs. 75.42%, P = 0.18), were substantially equivalent. Relative predictive value method did not reveal the presence of a statistically significant difference between the PPV of CP and both versions of AP (74.91 vs. 73.57%, P = 0.099). Analysis for single lesion confirmed that both CP and AP had equivalent results: CP and AP revealed 280 of 281 malignancies. NPVs of CP and both AP versions, as well as the specificity (P > 0.05), were substantially equivalent. Relative predictive value method did not reveal the presence of a significant difference between the PPV of CP and both AP versions (70.89 vs. 70.18%, P = 0.25; 70.89 vs. 70.00%, P = 0.13). CONCLUSIONS: Abbreviated approach to breast MRI examination reduces the image acquisition and the reading time associated with MR substantially without influencing the diagnostic accuracy (high sensitivity and NPV >99.5%). AP could translate into cost-savings and could enable a higher number of examinations within the same MR session.

Animal models in studies of cardiotoxicity side effects from antiblastic drugs in patients and occupational exposed workers.

Cardiotoxicity is an important side effect of cytotoxic drugs and may be a risk factor of long-term morbidity for both patients during therapy and also for staff exposed during the phases of manipulation of antiblastic drugs. The mechanism of cardiotoxicity studied in vitro and in vivo essentially concerns the formation of free radicals leading to oxidative stress, with apoptosis of cardiac cells or immunologic reactions, but other mechanisms may play a role in antiblastic-induced cardiotoxicity. Actually, some new cytotoxic drugs like trastuzumab and cyclopentenyl cytosine show cardiotoxic effects. In this report we discuss the different mechanisms of cardiotoxicity induced by antiblastic drugs assessed using animal models.

Bovine herpesvirus type 4 infection modulates autophagy in a permissive cell line.

Bovine herpesvirus type 4 (BoHV-4), like other herpesviruses, induces a series of alterations in the host cell that modify the intracellular environment in favor of viral replication, survival and spread. This research examined the impact of BoHV-4 infection on autophagy in BoHV-4 infected Madin Darby bovine kidney (MDBK) cells. Protein extracts of BoHV-4 infected and control MDBK cells were subjected to Western blot. The concentrations of the autophagy and apoptosis-related proteins Beclin 1, p21, PI3 kinase, Akt1/2, mTOR, phospho mTOR, p62 and the light chain three (LC3) were normalized to the actin level and expressed as the densitometric ratio. Western blot analysis of virus-infected cells revealed that autophagic degradation pathway was induced in the late phase of BoHV-4 infection. After 48 h post-infection the protein LC3II, which is essential for autophagy was found to be markedly increased, while infection of MDBK cells with BoHV-4 resulted in a depletion of p62 levels. Becline 1, PI3 kinase, Akt1/2 and p21 expression increased between 24 and 48 h post-infection. Surprisingly, mTOR and its phosphorylated form, which are negative regulators of autophagy, also increased after 24 h post-infection. In conclusion, our findings suggest that BoHV-4 has developed mechanisms for modulation of autophagy that are probably part of a strategy designed to enhance viral replication and to evade the immune system. Additional studies on the relationship between autophagy and BoHV-4 replication and survival, in both lytic and latent replication phases, are needed to understand the role of autophagy in BoHV-4 pathogenesis.