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.

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.

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.

Psychosocial Outcomes of Quadrantectomy Versus Mastectomy in a Southern Italian Sample: Development and Needs of the Italian Derriford Appearance Scale 24.

BACKGROUND/AIM: Breast cancer is associated with appearance concerns and issues of appearance identity, that require an appropriate and independent assessment. The Derriford Appearance Scale (DAS) has been widely used to this end, as has been shown in UK and other international samples. The aim of this study was to determine the extent to which an Italian translation of DAS24 is valid, reliable, and culturally appropriate, while remaining user friendly. The extent to which the statistical robustness of the scale is maintained was also assessed. PATIENTS AND METHODS: Ninety-three female participants were recruited at a Breast Cancer Department in Southern Italy. According to the protocol designed by the original authors of the questionnaire, a booklet containing the DAS24ita and other scale was completed anonymously by participants. CONCLUSION: The results of the statistical analysis confirmed the validity and reliability of the DAS24ita. The DAS24ita demonstrated significant correlations with the other measures of appearance sensitivity and quality of life. The translated scale was able to differentiate among patients with differential diagnoses, and was more sensitive to these differences than generic quality-of-life scales.

Silicone lymphadenopathy: presentation of a further case containing asteroid bodies on fine-needle cytology sample.

Silicone lymphadenopathy is a recognized complication of breast augmentation. It is thought to occur when silicone droplets migrate from breast implants to lymph nodes. We report the cytologic findings in axillary and inguinal lymph node aspirate smears from a 35-year-old Italian woman, who came to our observation 10 years after bilateral cosmetic breast augmentation. A fine-needle cytology of the axillary lymph node showed extensive granulomatous inflammation, numerous histiocytes, and multinucleated giant cells containing star-shaped structures known as "asteroid bodies." The inguinal lymph node aspirate simply showed an aspecific reactive hyperplasia. No evidence of malignancy was present in any of the smears as well as in the excised axillary lymph node.

Metabolic syndrome-breast cancer link varies by intrinsic molecular subtype.

BACKGROUND: Metabolic syndrome (MS) has been shown to increase the risk of breast cancer. Existing data suggest that the strength of metabolic syndrome-breast cancer link varies by intrinsic molecular subtype, but results from worldwide literature are controversial. Primary endpoint of the study was to assess whether MS is a predictor of specific breast cancer (BC) subtype. Secondary endpoint was to determine whether components of MS can individually increase the risk of specific breast cancer subtype. METHODS: Anthropometric and metabolic variables were correlated to breast cancer specific subgroups, retrospectively. Statistical significance was considered when p ≤ 0.05 and 95% CI. RESULTS: Data analysis suggests that MS per se represents a modifiable risk factor for BC in postmenopausal [OR 6.28 (95% CI 2.79-14.11) p < 0.00001]. MS per se prevalence is higher among Luminal breast cancers in postmenopausal [OR 1.37 (95% CI 1.07-2.80) p = 0.03]. Body Mass Index (BMI) alone is associated to Luminal A subtype breast cancer risk [OR 1.12 (95% CI 0.96-2.196 p = 0.2]. Waist Circumference > 88 cm has been shown to be specifically and statistically significant associated to HER-2+ breast cancer subtypes in postmenopausal [OR 2.72 (95% CI 1.69- 10.72) p = 0.01], whilst in Luminal B it was only marginally statistical associated [OR 2.21 (95% CI 0.77-2.60) p = 0.1]. Insulin resistance showed statistical significant association to HER-2+ and Luminal B tumors [OR 2.11 (95% CI 1.66-6.69) p = 0.05] and [OR 2.33 (95% CI 1.2-4.2) p = 0.006], respectively. Hence, it has emerged that BMI is weakly associated to Luminal A breast cancers in this case series, whereas visceral obesity and insulin resistance are likely to be linked to more aggressive breast cancer subtypes. CONCLUSIONS: New molecular biomarkers unveiling metabolic syndrome related breast carcinogenesis need to be detected to further stratify breast cancer risk by subtypes.

Combination of inositol and alpha lipoic acid in metabolic syndrome-affected women: a randomized placebo-controlled trial.

BACKGROUND: Inositol has been reported to improve insulin sensitivity since it works as a second messenger achieving insulin-like effects on metabolic enzymes. The aim of this study was to evaluate the inositol and alpha lipoic acid combination effectiveness on metabolic syndrome features in postmenopausal women at risk of breast cancer. METHODS: A six-month prospective, randomized placebo-controlled trial was carried out on a total of 155 postmenopausal women affected by metabolic syndrome at risk of breast cancer, the INOSIDEX trial. All women were asked to follow a low-calorie diet and were assigned randomly to daily consumption of a combination of inositol and alpha lipoic acid (77 pts) or placebo (78 pts) for six months. Primary outcomes we wanted to achieve were both reduction of more than 20% of the HOMA-IR index and of triglycerides serum levels. Secondary outcomes expected were both the improvement of high-density lipoprotein cholesterol levels and the reduction of anthropometric features such as body mass index and waist-hip ratio. RESULTS: A significant HOMA-IR reduction of more than 20% was evidenced in 66.7% (P <0.0001) of patients, associated with a serum insulin level decrease in 89.3% (P <0.0000). A decrease in triglycerides was evidenced in 43.2% of patients consuming the supplement (P <0.0001). An increase in HDL cholesterol (48.6%) was found in the group consuming inositol with respect to the placebo group. A reduction in waist circumference and waist-hip ratio was found in the treated group with respect to the placebo group. CONCLUSIONS: Inositol combined with alpha lipoic acid can be used as a dietary supplement in insulin-resistant patients in order to increase their insulin sensitiveness. Daily consumption of inositol combined with alpha lipoic acid has a significant bearing on metabolic syndrome. As metabolic syndrome is considered a modifiable risk factor of breast tumorigenesis, further studies are required to assess whether inositol combined with alpha lipoic acid can be administered as a dietary supplement in breast cancer primary prevention. TRIAL REGISTRATION: Current Controlled Trial ISRCTN74096908.

Homeostasis model assessment to detect insulin resistance and identify patients at high risk of breast cancer development: National Cancer Institute of Naples experience.

BACKGROUND: Metabolic Syndrome (MS) has been correlated to breast carcinogenesis. MS is common in the general population (34%) and increases with age and body mass index. Although the link between obesity, MS and hormone related cancer incidence is now widely recognized, the molecular mechanisms at the basis of such increase are still poorly characterized. A crucial role is supposed to be played by the altered insulin signalling, occurring in obese patients, which fuels cancer cell growth, proliferation and survival. Therefore we focused specifically on insulin resistance to investigate clinically the potential role of insulin in breast carcinogenesis. METHODS: 975 patients were enrolled and the association between MS, insulin resistance, and breast cancer was evaluated. Women were stratified by age and menopausal status. Insulin resistance was measured through the Homeostasis Model Assessment score (HOMA-IR). The cut off value to define insulin resistance was HOMA-IR ≥ 2.50. RESULTS: Higher prevalence of MS (35%) was found among postmenopausal women with breast cancer compared to postmenopausal healthy women (19%) [OR 2.16]. A broad range of BMI spanning 19-48 Kg/m2 was calculated. Both cases and controls were characterized by BMI ≥ 25 Kg/m2 (58% of cases compared to 61% of controls). Waist circumference >88 cm was measured in 53% of cases - OR 1.58- (95% CI 0.8-2.8) and in 46% of controls. Hyperinsulinemia was detected in 7% of cases - OR 2.14 (95% CI 1.78-2.99) and only in 3% of controls. HOMA-IR score was elevated in 49% of cases compared to 34% of controls [OR 1.86], suggesting that insulin resistance can nearly double the risk of breast cancer development. Interestingly 61% of women operated for breast cancer (cases) with HOMA-IR ≥ 2.5 presented subclinical insulin resistance with fasting plasma glucose levels and fasting plasma insulin levels in the normal range. Both android fat distribution and insulin resistance correlated to MS in the subgroup of postmenopausal women affected by breast cancer. CONCLUSIONS: Our results further support the hypothesis that MS, in particular insulin resistance and abdominal fat, can be considered as risk factors for developing breast cancer after menopause. We suggest that HOMA-IR, rather than fasting plasma glucose and fasting plasma insulin levels alone, could be a valuable tool to identify patients with subclinical insulin resistance, which could be relevant for primary prevention and for high risk patient screening.

The burden of breast cancer in Italy: mastectomies and quadrantectomies performed between 2001 and 2008 based on nationwide hospital discharge records.

BACKGROUND: Where population coverage is limited, the exclusive use of Cancer Registries might limit ascertainment of incident cancer cases. We explored the potentials of Nationwide hospital discharge records (NHDRs) to capture incident breast cancer cases in Italy. METHODS: We analyzed NHDRs for mastectomies and quadrantectomies performed between 2001 and 2008. The average annual percentage change (AAPC) and related 95% Confidence Interval (CI) in the actual number of mastectomies and quadrantectomies performed during the study period were computed for the full sample and for subgroups defined by age, surgical procedure, macro-area and singular Region. Re-admissions of the same patients were separately presented. RESULTS: The overall number of mastectomies decreased, with an AAPC of -2.1% (-2.3 -1.8). This result was largely driven by the values observed for women in the 45 to 64 and 65 to 74 age subgroups (-3.0%, -3.4 -3.6 and -3.3%, -3.8 -2.8, respectively). We observed no significant reduction in mastectomies for women in the remaining age groups. Quadrantectomies showed an overall +4.7 AAPC (95%CI:4.5-4.9), with no substantial differences by age. Analyses by geographical area showed a remarkable decrease in mastectomies, with inter-regional discrepancies possibly depending upon variability in mammography screening coverage and adherence. Quadrantectomies significantly increased, with Southern Regions presenting the highest average rates. Data on repeat admissions within a year revealed a total number of 46,610 major breast surgeries between 2001 and 2008, with an overall +3.2% AAPC (95%CI:2.8-3.6). CONCLUSIONS: In Italy, NHDRs might represent a valuable supplemental data source to integrate Cancer Registries in cancer surveillance.

Metabolic syndrome affects breast cancer risk in postmenopausal women: National Cancer Institute of Naples experience.

Postmenopausal women show the highest incidence of breast cancer in the female population and are often affected by metabolic syndrome. Metabolic syndrome (MS)--characterized by central adiposity, insulin resistance, low serum high-density lipoprotein cholesterol (HDL-C), high serum triglyceride and high blood pressure--seems to be strictly correlated to breast carcinogenesis. We enrolled 777 healthy women and women with breast cancer in our nested case-control study to evaluate the association between MS and breast cancer, analyzing anthropometric parameters (weight, height, BMI, waist and hip circumference), blood pressure, serum HDL-C, triglyceride, fasting plasma glucose, insulin, testosterone and uric acid levels and administering a questionnaire about physical activity, food intake, tobacco use, alcohol abuse, personal and familial history of disease. We found an higher prevalence of metabolic syndrome (30%) in postmenopausal breast cancer patients compared to healthy women (19%). None of the individual MS features was strong enough to be considered responsible for breast carcinogenesis alone. However, of the 63 postmenopausal breast cancer cases associated to MS, 30% presented three or more MS features, suggesting that the activation of multiple molecular pathways underlying MS might contribute to tumorigenesis. Our data support the hypothesis that MS may be an indicator of breast cancer risk in postmenopausal women. The unsettlement of the hormonal arrangement in postmenopausal, along with an increase in visceral adiposity, probably favour the hormone-dependent cell proliferation, which drives tumorigenesis. Adjustments in lifestyle with physical activity intensification and healthy diet could represent modifiable factors for the primary prevention of sporadic breast cancer.

Incidence of breast cancer in Italy: mastectomies and quadrantectomies performed between 2000 and 2005.

OBJECTIVES: We aimed to determine the incidence of women's breast cancer in Italy without using statistical approximations. METHODS: We analyzed the national hospitalizations database at the Ministry of Health to calculate the number of major surgeries in Italian women (mastectomies and quadrantectomies) due to breast cancer between 2000 and 2005, overall and by age groups (<44, 45-64, 65-74 and >or= 75 years old). RESULTS: Over the six years examined, an overall number of 100,745 mastectomies and 168,147 quadrantectomies were performed. A total of 41,608 major surgeries due to breast cancer were performed in the year 2000 and this number rose to 47,200 in 2005, with a 13.4% increase over six years. CONCLUSION: by analyzing the hospitalizations database concerning major breast surgery, incidence of breast cancer in Italy was found to be 26.5% higher than the official estimations which have been computed using statistical models (namely 47,200 vs. 37,300 cases in year 2005).

Genetic and epigenetic alterations in breast cancer: what are the perspectives for clinical practice?

The worldwide incidence of breast cancer affects 1.2 million women each year. In contrast to the high occurrence of this malady, a decline in mortality is reported among industrialized countries. In this respect, both awareness campaigns and substantial progress achieved in therapy and diagnosis allowed for the enhancement of the survival rate in patients with breast cancer. Undoubtedly, oncology research programs played a relevant role in the improvement of therapeutics and diagnostics for breast cancer. Major strides were reported, especially over the last decade and a half, in better understanding molecular and cellular biology events involved in breast cancer pathogenesis and progression of the disease. However, therapeutic approaches for the treatment of patients with breast cancer need further improvement. Therapeutic interventions can chronically compromise both the state of health and quality of life of breast cancer survivors. In addition, current therapeutic approaches have not significantly improved the survival rate in patients with metastatic disease. On these grounds, it is necessary to develop more efficient therapeutics and diagnostic tools, which can improve the health and quality of life of breast cancer survivors and increase the survival rate in patients with metastatic disease. In this respect, the field of cancer research has placed a particular emphasis on the elucidation of genetic and epigenetic alterations that may lead to the pathogenesis of breast cancer and contribute to its progression.

Importance of Ezh2 polycomb protein in tumorigenesis process interfering with the pathway of growth suppressive key elements.

An understanding of the mechanisms that uncover the dynamic changes in the distribution of the chromatin modifying enzymes and regulatory proteins on their target loci could provide further insight into the phenomenon of malignant transformation. Based on the current available data, it seems more and more clear that an abnormal expression of Ezh2, a member of the Polycomb group (PcG) protein, may be involved in the tumorigenesis process, in addition, different studies identify Ezh2 as a potential marker that distinguish aggressive prostate and breast cancer from indolent one. Recent investigation show that ectopic expression of Ezh2 provides proliferative advantage to primary cells through interaction with the pathways of key elements that control cell growth arrest and differentiation, like members of the retinoblastoma (Rb) family. Here, we outline how these pathways converge and we review the recent advances on the molecular mechanisms that promote cell cycle progression through deregulation of Ezh2 protein level, providing novel links between cancer progression and chromatin remodeling machineries.

Carcinogenesis and environment: the cancer stem cell hypothesis and implications for the development of novel therapeutics and diagnostics.

Stem cell research has greatly contributed to the field of oncology with the identification and isolation of cancer stem cells from a variety of tumors. The discovery of rare subpopulations of cancer stem cells has indeed entirely changed the focus of cancer research. Normal adult stem cells and cancer stem cells can both self-renew and undergo a differentiation program that, in turn, gives rise to a high number of differentiated cells. Adult stem cells and their malignant counterparts share almost all of the same intrinsic and extrinsic factors to regulate self-renewal, differentiation and proliferation pathways. Fractions of normal and cancer stem cells are naturally more resistant to toxic injuries than any other cell type. Overall, these observations lead to the conclusion that adult stem or progenitor cells can eventually become malignant by generating cancer stem cells, which are responsible for the development and maintenance of the tumor mass. In addition, chemo-resistant cancer stem cells may cause the relapse of the disease following an apparent beneficial treatment. Indeed, the study of the biology of cancer stem cells might lead to the improvement of preventive cancer diagnosis and to the development of novel therapeutics, which must be designed to selectively target malignant stem cells without affecting normal adult stem cells.