Androgen receptor expression and outcome of neoadjuvant chemotherapy in triple-negative breast cancer.

OBJECTIVE: Triple-negative breast cancers (TNBC) include a heterogeneous group of diseases, characterized by the lack of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) expression. TNBC that shows an overexpression of the androgen receptor (AR) defines the phenotype known as "luminal androgen receptor" (LAR), while the absence of the AR defines a "quadruple negative breast cancer" (QNBC). Several reports have associated AR positivity with a lower response to neoadjuvant chemotherapy (NAC), while divergent data have been reported about the impact of AR positivity on survival. The aim of this study was to retrospectively review our series of patients with TNBC tested for AR and submitted to NAC and compare pathologic complete response (pCR) rates in patients with a LAR phenotype or with QNBC. PATIENTS AND METHODS: The clinical records of all patients with TNBC tested for AR that underwent NAC at our Institution from January 1, 2015 to June 30, 2019 were reviewed. Histopathological features as well as ER, PgR, Ki67, HER2 values, clinical and pathological stage, and results of BRCA gene expression profiling were registered for all patients. RESULTS: Of the 145 TNBC patients treated by NAC, 20 (13.8%) had a LAR phenotype, while 125 (86.2%) had a QNBC. Overall, a pCR was achieved in 52 patients (35.8%). Patients with LAR phenotype had a lower rate of pCR as compared to patients with QNBC phenotype (25% vs. 37.6%). High Ki67 values (>50%) were observed less frequently in patients with a LAR phenotype (50% vs. 76.8% in QNBC). CONCLUSIONS: Our data seem to confirm that the LAR phenotype is associated to lower rates of pCR after neoadjuvant chemotherapy; routine assessment of AR expression in addition to classical biomarkers in patients with TNBC could help to better personalize treatment.

Is subareolar intraoperative biopsy still necessary to predict nipple involvement?

OBJECTIVE: To predict the occult tumor involvement of nipple-areola complex (NAC) using preoperative MR imaging and to investigate whether the intraoperative histopathological examination of the subareolar tissue is still necessary. PATIENTS AND METHODS: Out of 712 patients submitted to nipple-sparing mastectomy (NSM) between 2014 and 2019, we selected 188 patients who underwent preoperative breast MRI. Breast MRI and intraoperative histopathological examination of the subareolar tissue were performed to predict NAC involvement at permanent pathology. All parameters were correlated with final pathological NAC assessment by univariate and multivariate analysis. RESULTS: Forty-three patients (22.9%) had tumor involvement of the NAC. At univariate analysis, non-mass enhancement type (p = 0.009), multifocality/multicentricity (p = 0.002), median tumor size (p < 0.001), median tumor-NAC distance measured by MRI (p < 0.001), tumor-NAC distance ≤ 10 mm (p < 0.001) and tumor-NAC distance ≤ 20 mm (p < 0.001), and lymphovascular invasion (p = 0.001) were significantly correlated with NAC involvement. At multivariate analysis, only tumor-NAC distance ≤ 10 mm retained statistical significance. The sensitivity and specificity of MRI tumor-NAC distance ≤ 10 mm were 79.1% and 97.2% and those of intraoperative pathologic assessment were 74,4% and 100%, respectively. CONCLUSIONS: Tumor-NAC distance is the only reliable MRI characteristic that can predict NAC involvement in breast cancer patients. Although several cut-offs showed promising performances, intraoperative pathologic assessment is still mandatory.

Role of DWI assessing nodal involvement and response to neoadjuvant chemotherapy in advanced breast cancer.

OBJECTIVE: To explore the role of diffusion-weighted imaging (DWI) in the staging of axillary lymph nodes and the restaging after neoadjuvant chemotherapy (NAD) in advanced breast cancer. PATIENTS AND METHODS: MRI examinations of forty-two patients diagnosed with advanced breast cancer addressed to NAD and axillary lymph node dissection (ALND) were reviewed. Apparent diffusion coefficients (ADC) of each visible node in DWI in the pathologic axilla (PA) and healthy axilla (HA) were measured at the time of diagnosis (t0) and after chemotherapy (t1); mean values of the ADC were calculated. Patients were classified as responders (R), non-responders (NR), macrometastasis (MA), micrometastasis (Mi). RESULTS: Mean ADC was 0.92 ± 0.07 x 10-3 mm2/sec at t0 and 0.97 ± 0.06 x 10-3 mm2/sec at t1 (p = 0.284) in PA, 0.89 ± 0.06 x 10-3 mm2/sec at t0 and 0.92 ± 0.06 x 10-3 mm2/sec at t1 (p = 0.403) in HA, 0.95 ± 0.111 x 10-3 mm2/sec at t0 and 0.95 ± 0.14 x 10-3 mm2/sec at t1 (p = 0.954) in R group, 0.90 ± 0.09 x 10-3 mm2/sec at t0 and 0.97 ± 0.07 x 10-3 mm2/sec at t1 (p = 0.085) in NR group, 0.86 ± 0.10 x 10-3 mm2/sec at t0 and 0.99 ± 0.09 x 10-3 mm2/sec at t1 (p = 0.055) in MA, and 0.99 ± 0.23 x 10-3 mm2/sec at t0 and 0.95 ± 0.15 x 10-3 mm2/sec at t1 in Mi (p = 0.667). CONCLUSIONS: Mean ADC between PA and HA, R and NR, MA and Mi did not significantly differ at t0 and t1 (p > 0.05). Variation in mean ADC between t0 and t1 was not significant in all groups (p > 0.05), except for a trend toward significance (p = 0.055) in MA. DWI has a potential role in restaging of macrometastatic axillary nodes after NAD.

New trends in breast cancer surgery: a therapeutic approach increasingly efficacy and respectful of the patient.

The surgical management of breast cancer has undergone continuous and profound changes over the last 40 years. The evolution from aggressive and mutilating treatment to conservative approach has been long, but constant, despite the controversies that appeared every time a new procedure came to light. Today, the aesthetic satisfaction of breast cancer patients coupled with the oncological safety is the goal of the modern breast surgeon. Breast-conserving surgery with adjuvant radiotherapy is considered the gold standard approach for patients with early stage breast cancer and the recent introduction of "oncoplastic techniques" has furtherly increased the use of breast-conserving procedures. Mastectomy remains a valid surgical alternative in selected cases and is usually associated with immediate reconstructive procedures. New surgical procedures called "conservative mastectomies" are emerging as techniques that combine oncological safety and cosmesis by entirely removing the breast parenchyma sparing the breast skin and nipple-areola complex. Staging of the axilla has also gradually evolved toward less aggressive approaches with the adoption of sentinel node biopsy and new therapeutic strategies are emerging in patients with a pathological positivity in sentinel lymph node biopsy. The present work will highlight the new surgical treatment options increasingly efficacy and respectful of breast cancer patients.

Beta2-adrenergic activity modulates vascular tone regulation in lecithin:cholesterol acyltransferase knockout mice.

Lecithin:cholesterol acyltransferase (LCAT) deficiency is associated with hypoalphalipoproteinemia, generally a predisposing factor for premature coronary heart disease. The evidence of accelerated atherosclerosis in LCAT-deficient subjects is however controversial. In this study, the effect of LCAT deficiency on vascular tone and endothelial function was investigated in LCAT knockout mice, which reproduce the human lipoprotein phenotype. Aortas from wild-type (Lcat(wt)) and LCAT knockout (Lcat(KO)) mice exposed to noradrenaline showed reduced contractility in Lcat(KO) mice (P<0.005), whereas acetylcholine exposure showed a lower NO-dependent relaxation in Lcat(KO) mice (P<0.05). Quantitative PCR and Western blotting analyses suggested an adequate eNOS expression in Lcat(KO) mouse aortas. Real-time PCR analysis indicated increased expression of ß2-adrenergic receptors vs wild-type mice. Aorta stimulation with noradrenaline in the presence of propranolol, to abolish the ß-mediated relaxation, showed the same contractile response in the two mouse lines. Furthermore, propranolol pretreatment of mouse aortas exposed to L-NAME prevented the difference in responses between Lcat(wt) and Lcat(KO) mice. The results indicate that LCAT deficiency leads to increased ß2-adrenergic relaxation and to a consequently decreased NO-mediated vasodilation that can be reversed to guarantee a correct vascular tone. The present study suggests that LCAT deficiency is not associated with an impaired vascular reactivity.

Acquired lecithin:cholesterol acyltransferase deficiency as a major factor in lowering plasma HDL levels in chronic kidney disease.

OBJECTIVES: It has been suggested that a low plasma high-density lipoprotein cholesterol (HDL-C) level contributes to the high cardiovascular disease risk of patients with chronic kidney disease (CKD), especially those undergoing haemodialysis (HD). The present study was conducted to gain further understanding of the mechanism(s) responsible for the low HDL-C levels in patients with CKD and to separate the impact of HD from that of the underlying CKD. METHODS: Plasma lipids and lipoproteins, HDL subclasses and various cholesterol esterification parameters were measured in a total of 248 patients with CKD, 198 of whom were undergoing HD treatment and 40 healthy subjects. RESULTS: Chronic kidney disease was found to be associated with highly significant reductions in plasma HDL-C, unesterified cholesterol, apolipoprotein (apo)A-I, apoA-II and LpA-I:A-II levels in both CKD cohorts (with and without HD treatment). The cholesterol esterification process was markedly impaired, as indicated by reductions in plasma lecithin:cholesterol acyltransferase (LCAT) concentration and activity and cholesterol esterification rate, and by an increase in the plasma preß-HDL content. HD treatment was associated with a further lowering of HDL levels and impaired plasma cholesterol esterification. The plasma HDL-C level was highly significantly correlated with LCAT concentration (R = 0.438, P < 0.001), LCAT activity (R = 0.243, P < 0.001) and cholesterol esterification rate (R = 0.149, P = 0.031). Highly significant correlations were also found between plasma LCAT concentration and levels of apoA-I (R = 0.432, P < 0.001), apoA-II (R = 0.275, P < 0.001), LpA-I (R = 0.326, P < 0.001) and LpA-I:A-II (R = 0.346, P < 0.001). CONCLUSION: Acquired LCAT deficiency is a major cause of low plasma HDL levels in patients with CKD, thus LCAT is an attractive target for therapeutic intervention to reverse dyslipidaemia, and possibly lower the cardiovascular disease risk in these patients.

Genetic determinants of HDL metabolism.

Plasma high density lipoproteins (HDL) comprise a highly heterogeneous family of lipoprotein particles, with subclasses that can be separated and identified according to density, size, surface charge as well as shape and protein composition. There is evidence that these subclasses may differ in their functional properties. The individual plasma HDL cholesterol (HDL-C) level is generally taken as a snapshot of the steady-state concentration of all circulating HDL subclasses together, but this is insufficient to capture the structural and functional variation in HDL particles. HDL are continuously remodeled and metabolized in plasma and interstitial fluids, through the interaction with a large number of factors, including structural proteins, membrane transporters, enzymes, transfer proteins and receptors. Genetic variation in these factors can lead to essential changes in plasma HDL levels, and to remarkable changes in HDL particle density, size, surface charge, shape, and composition in lipids and apolipoproteins. This review discusses the impact of rare mutations and common variants in genes encoding factors involved in HDL remodeling and metabolism on plasma HDL-C levels and particle distribution. The study of the effects of human genetic variation in major players in HDL metabolism provides important clues on how individual factors modulate the formation, maturation, remodeling and catabolism of HDL.

Update on oncoplastic breast surgery.

Oncoplastic surgery of the breast (OPS) has generated great excitement over the past years and has become an integrated component of the surgical treatment of breast cancer. Oncoplastic surgical procedures associate the best surgical oncologic principles to achieve wide tumor-free margins with the best principles of plastic surgery to optimize cosmetic outcomes. Thanks to oncoplastic techniques, the role of breast conserving surgery (BCS) has been extended to include a group of patients who would otherwise require mastectomy to achieve adequate tumor clearance. As OPS continues to gain acceptance and diffusion, an optimal and systematic approach to these techniques is becoming increasingly necessary. This article has the aim to review the essential principles and techniques associated with oncoplastic surgery, based on the data acquired through an extensive search of the PUBMED and MEDLINE database for articles published using the key words "breast cancer oncoplastic surgery". This review analyzes possible the advantages", classifications, indications, and the criteria for a proper selection of oncoplastic techniques to facilitate one's ability to master these procedures and make OPS a safe and an effective procedure.

The role of oxidized regenerate cellulose to prevent cosmetic defects in oncoplastic breast surgery.

BACKGROUND: Breast conserving surgery (BCS) combined with postoperative radiotherapy has become the gold standard of locoregional treatment for the majority of patients with early-stage breast cancer, offering equivalent survival and improved body image and lifestyle scores as compared to mastectomy. In an attempt to optimize the oncologic safety and cosmetic results of BCS, oncoplastic procedures (OPP) have been introduced in recent years combining the best principles of surgical oncology with those of plastic surgery. However, even with the use of OPP, cosmetic outcomes may result unsatisfying when a large volume of parenchyma has to be removed, particularly in small-medium size breasts. AIM: The aim of this article is to report our preliminary results with the use of oxidized regenerate cellulose (ORC) (Tabotamp fibrillar, Johnson & Johnson; Ethicon, USA) as an agent to prevent cosmetic defects in patients undergoing OPP for breast cancer and to analyze the technical refinements that can enhance its efficacy in optimizing cosmetic defects. METHODS: Different OPP are selected based on the location and size of the tumor as well as volume and shape of the breast. After excision of the tumor, glandular flaps are created by dissection of the residual parenchyma from the pectoralis and serratus muscles and from the skin. After careful haemostasis, five layers of ORC are positioned on the pectoralis major in the residual cavity and covered by advancement of the glandular flaps. Two additional layers of ORC are positioned above the flaps and covered by cutaneous-subcutaenous flaps. RESULTS: The use of ORC after OPP has shown promising preliminary results, indicating a good tolerability and positive effects on cosmesis. CONCLUSIONS: This simple and reliable surgical technique may allow not only to reduce the rate of post-operative bleeding and infection at the surgical site but also to improve cosmetic results.

Diffusion-weighted imaging in breast cancer: relationship between apparent diffusion coefficient and tumour aggressiveness.

AIM: To assess the utility of diffusion-weighted imaging in diagnosing and characterizing breast malignancy. MATERIALS AND METHODS: From April 2006 to April 2009, all consecutive patients with breast cancer undergoing breast magnetic resonance imaging (MRI) and subsequent surgery in our hospital were enrolled in this study. MRI was performed using a 1.5 T MRI unit using a dedicated, bilateral, four-channel breast coil. The MRI protocol included a diffusion sequence acquired using b values of 0 and 1000 s/mm(2). For each malignant lesion the relationships between tumour grade and histology and the relative value of the apparent diffusion coefficient (ADC) were analysed. RESULTS: There were 136 female patients with 162 lesions. Histology revealed 149 invasive carcinomas and 13 ductal carcinomas in situ. There were 34 grade 1, 61 grade 2, and 67 grade 3 lesions. The mean ADC value of all malignant lesions was 1.03×10(-3) mm(2)/s. The mean ADC values for invasive and in situ carcinomas were 1.03×10(-3) mm(2)/s and 1.05×10(-3) mm(2)/s, respectively. The mean ADC values for grade 1, 2, and 3 tumours were 1.25×10(-3) mm(2)/s, 1.02×10(-3) mm(2)/s, and 0.92×10(-3) mm(2)/s, respectively. A statistically significant (p<0.001) inverse correlation was disclosed between the ADC value and the tumour grading. The mean ADC value of the "less aggressive" group of disease (G1 and in situ lesions) was 1.19×10(-3) mm(2)/s, whereas the mean ADC value of the "more aggressive" group (G2-G3 invasive carcinomas) was 0.96×10(-3) mm(2)/s (p<0.001). CONCLUSION: The study confirms the usefulness of diffusion imaging in assessing the aggressiveness of breast tumours. ADC appears to be a promising parameter in the evaluation of the degree of malignancy of breast cancer tissue.

High uptake of colonoscopy in first-degree relatives of patients with colorectal cancer in a healthcare region: a population-based, prospective study.

BACKGROUND AND STUDY AIMS: A screening program in first-degree relatives (FDRs) of colorectal cancer (CRC) patients (index patients) was started in Trentino, Italy, to analyze factors that influence uptake of CRC screening among invited FDRs (first objective) and to describe colorectal findings among those undergoing colonoscopy (secondary objective). PATIENTS AND METHODS: FDRs aged between 45 and 75 years were invited; exclusion criteria were: colonoscopy or barium enema in the preceding 5 years, a history of familial adenomatous polyposis, hereditary nonpolyposis colorectal cancer, inflammatory bowel diseases, and severe comorbidities. FDRs who were eligible but were not invited for screening because consent was not obtained from the index patients were considered as the control group. FDRs were invited by the education campaign targeted at the population at risk (both study and control groups); in the study group, interventions targeting individuals at risk (letters, phone calls, face-to-face counseling) were implemented. RESULTS: Starting from 626 new index cases of diagnosed CRC, 725 FDRs were invited to counseling; 77.6 % of these attended for colonoscopy in the study group vs. 8 % in the control group ( P < 0.0001). Predictors of colonoscopy uptake were FDR age above 60 years [odds ratio (OR) 2.50, 95 %CI 1.72 - 3.62], complex family history (simple family history: one CRC at age above 60 years; complex family history: one CRC at age below 60 or two or more CRC; OR 1.54; 95 %CI 1.04 - 2.33) and living in a rural area (OR 1.64, 95 %CI 1.12 - 2.44). Of the 560 FDRs in the study group, 186 (33.8 %) had adenomas, and 48 (8.8 %) had advanced adenomas or cancer. CONCLUSIONS: Interventions that target FDRs of patients with CRC, especially those younger than 60 years, with a complex family history of CRC and who live in a rural area, may improve uptake of CRC screening via colonoscopy.

Parametric analysis of the strength in the ''Toronto'' osseous-prosthesis system.

AIM: The aim of this work is to analyze how the different distributions of the chewing load could be related to dental prosthesis fractures of the Toronto restoration via the fulfilment of a virtual parametric model. Moreover investigation about implant positions and perspectives in comparison with a virtual medial plane was made to evaluate the incidence of screw and prosthesis breakage. METHODS: Finite element analysis of the lower jaw was performed to underline parameters and mechanical features of dental implants connected with the fractures of the prosthetic restoration. Jaw virtual model and 3D fixtures (Global Sweden and Martina) were created by Cosmos-Solid Works. Matlab was used to recreate the distribution of an unspecific chewing phase analyzing the overall load on the fixtures of the lower jaw. RESULTS: Four virtual 3D models were performed with Matchad 14, for data analysis. The study investigated frontal and horizontal planes and vertical direction of the occlusal forces. Data results showed how position and perspective of fixtures strongly influenced the stress distribution upon the bone of the jaw; safeguard of prostheses elements like cantilever, passing screws, and dental implants are strictly related to a correct selection of the dental implant position. CONCLUSIONS: The 3D geometry of the jaw is an important condition for the choice of position, number, diameter and length of dental implants used for Toronto prostheses. This study would suggest a virtual ''method'' to help the surgeon choosing a correct model for a prosthetic rehabilitation evaluating position, perspective, and stress distribution of the chewing strengths.

Conservative treatment of the central breast cancer with nipple-areolar resection: an alternative oncoplastic technique.

Conservative surgery with radiation therapy is the standard treatment for early-stage breast cancer. Nevertheless, the patients with subareolar breast cancer have been often excluded from breast-conserving surgery and treated with mastectomy because of the unacceptable cosmetic effect associated with the resection of the nipple-areola complex (NAC), as well as oncologic concerns about multicentricity or multifocality associated with these tumours. We show a conservative "oncoplastic technique" in which the resection of the central portion of the breast, including the NAC, can allow a wide excision of the tumour with uninvolved margins of resection and good cosmetic results.

Conservative and radical oncoplastic approches in the surgical treatment of breast cancer.

In the attempt to optimise the balance between the risk of local recurrence and the cosmetic outcomes in breast surgery, new surgical procedures, so-called oncoplastic techniques, have been introduced in recent years. The term oncoplastic surgery refers to surgery on the basis of oncological principles during which the techniques of plastic surgery are used, mostly for reconstructive and cosmetic reasons. The advantage of the oncoplastic surgery for breast cancer is the possibility of performing a wider excision of the tumour with a good cosmetic result. Oncoplastic surgery is a broad concept that can be used for several different combinations of oncological surgery and plastic surgery: excision of the tumour by reduction mammoplasty, tumour excision followed by remodelling mammoplasty, mastectomy with immediate reconstruction of the breast and partial mastectomy with reconstruction. Careful patient selection and preoperative planning are key components for the success of any oncoplastic operation for breast cancer. Accurate preoperative evaluation of the clinical and biological features of the tumour as well as of the morphological aspects of the breast allow the surgeon to make a decision if a conservative or radical approach is preferable and select the most effective oncoplastic surgical technique. In this review we summarise the indications, advantages and limitations of several oncoplastic procedures.

Update in the treatment of locally advanced breast cancer: a multidisciplinary approach.

Locally advanced breast cancer represents a wide variety of neoplasms and constitutes approximately 10%-20% of the newly diagnosed breast cancers. These cancers may have widely different clinical and biological characteristics. According to the American Joint Committee on Cancer (AJCC) staging system, all of stage III disease is considered locally advanced. The clinical treatment of locally advanced breast cancer is complex and should be tailored to the individual patient. In this paper we discuss the options of management of locally advanced breast cancer, focusing on a multidisciplinary approach through a combined-modality care involving surgery, radiotherapy and systemic therapy.