Germline investigation in male breast cancer of DNA repair genes by next-generation sequencing.

PURPOSE: In order to better define the breast cancer (BC) genetic risk factors in men, a germline investigation was carried out on 81 Male BC cases by screening the 24 genes involved in BC predisposition, genome stability maintenance and DNA repair mechanisms by next-generation sequencing. METHODS: Germline DNAs were tested in a custom multi-gene panel focused on all coding exons and exon-intron boundaries of 24 selected genes using two amplicon-based assays on PGM-Ion Torrent (ThermoFisher Scientific) and MiSeq (Illumina) platforms. All variants were recorded and classified by using a custom pipeline. RESULTS: Clinical pathological data and the family history of 81 Male BC cases were gathered and analysed, revealing the average age of onset to be 61.3 years old and that in 35 cases there was a family history of BC. Our genetic screening allowed us to identify a germline mutation in 22 patients (23%) in 4 genes: BRCA2, BRIP1, MUTYH and PMS2. Moreover, 12 variants of unknown clinical significance (VUS) in 9 genes (BARD1, BRCA1, BRIP1, CHEK2, ERCC1, NBN, PALB2, PMS1, RAD50) were predicted as potentially pathogenic by in silico analysis bringing the mutation detection rate up to 40%. CONCLUSION: As expected, a positive family history is a strong predictor of germline BRCA2 mutations in male BC. Understanding the potential pathogenicity of VUS represents an extremely urgent need for the management of BC risk in Male BC cases and their own families.

Male secretory breast cancer: case in a 6-year-old boy with a peculiar gene duplication and review of the literature.

PURPOSE: Secretory breast cancer (SBC) is one of the rarest breast cancer (BC), representing the majority of BC in childhood. Nevertheless, it elicits a lot of interest both for the peculiar morphology and the characteristic genetic features. Currently, there is no consensus on optimal treatment strategy. Therefore, it is useful to report every case in order to establish treatment algorithms. METHODS: We describe the case of a 6-year-old boy diagnosed with a SBC, with peculiar genomic and immunohistochemical features. Moreover, we carried out a review of the literature in order to analyze the present state of knowledge about this rare entity. RESULTS: To the best of our knowledge, there are only 120 cases published in literature, only 32 in males and only 2 younger than 6 years. Furthermore, this one had peculiar genomic and immunohistochemical features. Indeed, even if SBC expresses basal-cell markers, our patient had a triple-negative tumor expressing both basal and luminal cell markers. Furthermore, the boy's genomic profile revealed not only positivity for the typical SBC's translocation t(12;15), but also for a 3q28 duplication, found in his father (healthy) and paternal grandfather (with a previous BC). None were positive for BRCA mutation. This locus includes only one gene encoding for a growth factor recently linked to Early Infantile Epileptic Encephalopathy-47 and Idiopathic ventricular tachycardia. Even if the literature does not provide evidence of a pathogenic role it is not possible to exclude a cancer-predisposing activity. CONCLUSIONS: SBC is a rare type of BC, characterized by triple-negative features with an unexpectedly good prognosis. More data are needed to fully understand the behavior of this cancer and genomic profiling could be helpful in improving its diagnosis and management.

The superparamagnetic iron oxide tracer: a valid alternative in sentinel node biopsy for breast cancer treatment.

The European Union has determined that from 2016 breast cancer patients should be treated in Specialist Breast Units that achieve the minimum standards for the mandatory quality indicators as defined by Eusoma. The existing standard for axillary lymph node staging in breast cancer is sentinel node biopsy (SNB), performed using Technetium-sulphur colloid (99m Tc) alone or with blue dye. The major limits of radioisotope consist in the problems linked to radioactivity, in the shortage of tracer and nuclear medicine units. Among existing alternative tracers, SentiMag® , which uses superparamagnetic iron oxide particles, can represent a valid option for SNB. We conducted a paired, prospective, multicentre study to evaluate the non-inferiority of SentiMag® vs. 99m Tc. The primary end point was the detection rate (DR) per patient. The study sample consists of 193 women affected by breast carcinoma with negative axillary assessment. The concordance rate per patients between 99m Tc and SentiMag® was 97.9%. The DR per patient was 99.0% for 99m Tc and 97.9% for SentiMag® . SentiMag® appears to be non-inferior to the radiotracer and safe. While 99m Tc remains the standard, SentiMag® DR appears adequate after a minimum learning curve. In health care settings where nuclear medicine units are not available, SentiMag/Sienna+® allows effective treatment of breast cancer patients.

Does thyroid peroxidase provide an antigenic link between thyroid autoimmunity and breast cancer?

Women with breast cancer (BC) and antithyroid peroxidase (TPO) autoantibodies (TPOAb) have a better prognosis than women lacking TPOAb. Sera from women with TPOAb displayed immunoreactivity to BC tissue by immunofluorescence that was not apparent in women without TPOAb. We hypothesize a BC/thyroid shared antigen that provides a target for humoral or cell-mediated immune activity; candidates include the sodium/iodide symporter (expressed in thyroid and BC), cross-reacting epitopes in TPO and lactoperoxidase (LPO) or TPO itself. As the association is with TPOAb, we investigated TPO expression in BC, breast peritumoral tissue (PT), other tissues (tumoral and not) and thyroid as positive control. Transcripts for known and novel TPO isoforms were detected in BC (n = 8) and PT (n = 8) but at approximately 10(4) -fold lower than in thyroid while in non-BC tumors (n = 5) they were at the limit of detection. TPO was expressed also in adipose tissue (n = 17), 10(3) -fold lower than in thyroid. Full length TPO (Mr 105-110 kDa) was detected in Western blots in the majority of examined tissues; preabsorption of the TPO antibody with recombinant TPO (but not LPO) reduced the signal, indicating specificity. The same occurred with some lower molecular weight bands, which could correspond to smaller TPO transcript isoforms, present in all samples. In conclusion, TPO is weakly expressed in BC and other tissues; this could partly explain the high frequency and protective role of TPOAb in BC patients. Further studies will investigate tissue specificity, function and immunogenicity of the novel TPO variants (some BC-specific) identified.

Quality of life and satisfaction of patients after oncoplastic or traditional breast-conserving surgery using the BREAST-Q (BCT module): a prospective study.

INTRODUCTION: The oncoplastic conservative surgery was developed as a natural evolution of traditional surgery, attempting to improve the therapeutic and aesthetic outcomes where tumor resection could be followed by not-adequate results. Our primary aim is to evaluate how patient satisfaction and quality-of-life after conservative oncoplastic surgery, using BREAST-Q (BCT Module), change pre- and post-operatively. The secondary aim is to compare patient-reported outcome after oncoplastic or traditional conservative surgery. PATIENTS AND METHODS: We enrolled 647 patients who underwent traditional conservative surgery or oncoplastic surgery from January 2020 to December 2022. Only 232 women (35.9%) completed the BREAST-Q questionnaire on a web-based platform, at the preoperative phase and 3 months after treatment. RESULTS: The average score of "Psychosocial well-being" and "Satisfaction with Breasts" 3 months after surgery showed a statistically significant improvement, while the average score for "Physical well-being: Chest" at 3 months showed a worsening compared to the baseline. "Sexual well-being" did not show statistically significant change. A significant difference between the post-operative outcome of oncoplastic surgery and traditional surgery was observed only for Physical well-being (better for traditional surgery). CONCLUSIONS: The study showed significant improvement in patient-reported outcomes 3 months after the surgery, except for physical discomfort that increases especially after oncoplastic surgery. Furthermore, our data, as well as many others, point to the appropriateness of using OCS where there is an effective indication, while the perspective of patients cannot find significant superiority over TCS in any of the areas analyzed.

PROMs in post-mastectomy care: Patient self-reports (BREAST-Q™) as a powerful instrument to personalize medical services.

One of the goals of immediate breast reconstruction (IBR) is to satisfy the patient's outcome. Recent studies therefore tended to focus on the patient's perception of the care and on the impact on quality of life using patients-reported-outcome-measures (PROMs), able to measure the health status directly without the clinician's interposition. We present a preliminary prospective study on 333 patients who underwent mastectomy with IBR in a two-year period, in a single Italian centre, using a dedicated PROMs, the BREAST-Q™, to determine the patient's satisfaction. We studied two groups of IBR: Group A (two-step with tissue-expander) and Group B (one-step: prosthesis/mesh) and conducted a pre- and post-operative comparison for each group to evaluate score-gain over time, and a group-score comparison to determine whether differences were significant between reconstruction types. Two-hundred-and-nine were actually enrolled and 132 completed all the questionnaires. The response rate was 62.8% and the compliance rate (completion of all the questionnaires) was 63.1%. In both groups all the analyzed domains worsened comparing the pre and post-operative period; the differences were statistically significant only for physical and sexual-wellbeing. In the comparison between the two groups, none of the detected differences reached the statistical significance. According to our experience, we can state that PROMs could improve the health concept redefining the variables to be monitored even if data is still insufficient to draw any definitive conclusion. PROMs can help surgeons and patients decide the most appropriate surgery for a particular patient-profile and to identify those who require further support.

An integrated approach with homeopathic medicine and electro-acupuncture in anaesthesiology during breast cancer surgery: Case reports.

This study investigates the effect of a combination of homeopathic medicine and electro-acupuncture in two patients with breast cancer and severe liver disease who could not receive standard anaesthesia therapy due to liver problems. Specifically, measurable and quantifiable parameters were used to evaluate whether an integrated approach-consisting of electro-acupuncture and a homeopathic medicine diluted above Avogadro's limit (that is, above a potency of 12CH) during the pre-surgical, surgical and post-surgical phases--can improve general well-being of a patient undergoing breast cancer surgery. In breast cancer surgery, we employed an integrated approach consisting of induction with hypnotics and muscle relaxants, followed by maintenance with anaesthetic gas, combined with a homeopathic treatment (Arnica montana 15CH and Apis mellifica 15CH) before and after surgery and an electro-acupuncture treatment performed in the pre- and post-surgical phases without any analgesic/pain relieving medications. Both of the patients treated with the integrated approach improved their overall condition without need for other common pain relieving medicines. Additionally, thanks to their rapid awakening, the patients were not relocated to a protected area and the hospitalization was shorter. A multidisciplinary approach incorporating homeopathic medicine and electro-acupuncture can be a solution for patients who need or ask about a different and/or safer alternative to the standard treatment. This approach can offer a safe, much less expensive, non-invasive and viable alternative for such cases. Moreover it can be useful for an opioids free anesthesia.

The role of clinicopathologic and molecular prognostic factors in the post-mastectomy radiotherapy (PMRT): a retrospective analysis of 912 patients.

OBJECTIVE: To assess the association of clinicopathologic and molecular features with loco-regional recurrence (LRR) in post-mastectomy breast cancer patients with or without adjuvant radiotherapy (PMRT). PATIENTS AND METHODS: We retrospectively reviewed data of patients undergone to mastectomy followed or not by PMRT between January 2004 and June 2013. The patients were divided according to clinicopathologic and molecular sub-classification features. LRR and Cancer Specific Survival (CSS) were calculated using the Kaplan-Meier method; the prognostic factors were compared using long-rank tests and Cox regression model. RESULTS: A total of 912 patients underwent to mastectomy of whom 269 (29.5%) followed by PMRT and 643 (70.5%) not; among the PMRT group, 77 underwent to the chest wall (CW) and 202 to the chest wall and lymphatic drainage (CWLD) irradiation. The median follow-up was 54 months (range, 3-118). No significant difference in terms of LRR and CSS was found between non-PMRT and PMRT group (p=0.175; and p=0.628). The multivariate analysis of LRR for patients who did not undergo PMRT showed a significant correlation with the presence of extracapsular extension (ECE) (p=0.049), Ki-67>30% (p=0.048) and triple negative status (p=0.001). In the PMRT group, triple negative status resulted as the only variable significantly correlated to LRR (p=0.006) at the multivariate analysis and T-stage also showed a trend to significance (p=0.073). Finally, no difference in LRR control was shown between CW and CWLD-PMRT (p=0.078). CONCLUSIONS: After mastectomy ECE, a cut off of Ki-67>30% and triple negative status were strictly correlated with LRR regardless of clinicopathologic stage. PMRT has a positive impact in decreasing LRR in patients with this molecular profile. Besides, CW might represent a valid option for patients with one to three positive nodes.

Hand-assisted laparoscopic low anterior resection: initial experience with a new procedure.

BACKGROUND: Laparoscopic low anterior resection for rectal cancer has never gained wide acceptance among general surgeons, mainly due to the technical difficulties encountered during pelvic dissection. It has therefore been stated that these patients should undergo open rather than laparoscopic surgery. Hand-assisted laparoscopic surgery (HALS) is a new technique that has the potential to overcome many of the existing limitations of pure laparoscopy. In the treatment of rectal cancer, HALS could reproduce an operative setting similar to that of the open approach. METHODS: To assess the technical feasibility of hand-assisted laparoscopic low anterior resection for rectal cancer and evaluate potential benefits and drawbacks of this new procedure, a pilot study was conducted at a university hospital on 16 consecutive patients during a 12-month period. Only patients with extraperitoneal rectal cancer were included in this series. Patients' clinical data, operative time, conversion rate, complications, and early outcome measures were prospectively examined. RESULTS: There were 9 men and 7 women. The average +/- SD operation time was 238 +/- 38 min. Conversion to open surgery was never required. Ten of 16 patients were off pain medication on the third postoperative day. Eight were able to walk the day after surgery. Three minor postoperative complications were recorded. Mean postoperative stay for patients without complications was 5.6 +/- 1.4 days. CONCLUSION: From a technical standpoint, the reported hand-assisted procedure makes pelvic dissection during laparoscopic low anterior resection almost equivalent to the laparotomic operation. The incision for hand access that is needed with this technique does not seem to compromise the quick recovery of patients undergoing purely laparoscopic procedures.

Laparoscopic living donor nephrectomy in Italy: a national profile.

BACKGROUND: There are no data concerning the national experience with laparoscopic live donor nephrectomy (LLDN) in Italy. A survey was therefore conducted in May 2003 to establish current practice patterns and to describe the outcome of this procedure. METHODS: A self-administered questionnaire was mailed to the 37 Italian kidney transplant centers. Items covered each center's attitude toward LLDN, number of cases performed, and the outcome of donors and recipients. RESULTS: The return rate was 100%. The surveyed centers performed 4818 kidney transplants between January 2000 and May 2003, including 401 (8.3%) from living donors of whom 113 (28.2%) used grafts retrieved by laparoscopy. Despite an absolute increase in the number of living donors, the occurrence of a similar trend in cadaveric donation did not significantly change the overall living donor rate. Sixty-eight percent of LLDNs were done at only two centers. There was no mortality or graft loss and only a minor morbidity related to LLDN. Italian transplant surgeons showed a positive attitude toward LLDN; only a few of those not performing it had no plans to begin an LLDN program. CONCLUSIONS: Three years after the first national case, LLDN had not yet change the living donor rate, although an increasing number of donor nephrectomies were now performed by laparoscopy. Overall the results with the new technique are encouraging, although the pattern of diffusion of LLDN between different areas is heterogeneous and will demand continuous efforts on training programs in laparoscopic techniques for transplant surgeons.

Plasma exchange for polyradiculoneuropathy following kidney transplantation: a case report.

We describe a case of polyradiculoneuropathy (PRN) following living donor kidney transplantation, without clinical evidence of preexisting infection. In this study plasma exchange treatment resulted 6 days later in improvement in extremity weakness and paresthesias in the upper and lower extremities. Total neurological recovery was obtained 3 months after the onset of symptoms.

Laparoscopic and hand-assisted laparoscopic live donor nephrectomy.

Renal grafts from living donors represent an important source of organs, particularly for young patients with chronic renal failure. Laparoscopic donor nephrectomy is a relatively new technique, which has the potential to increase the pool of available kidney grafts by removing some disincentives to live donation. The technique used for left kidney donation at our center, the first to introduce laparoscopic live donor nephrectomy in Italy, is described in this report. To further reduce warm ischemia time, the kidney is preloaded inside the extraction bag and 2 staplers are used to transect the renal artery and vein. The spread of the new technique in our country and in the rest of Europe is likely to raise the issue of training in laparoscopic surgery for transplant surgeons.