Multigenic panels in breast cancer: Clinical utility and management of patients with pathogenic variants other than BRCA1/2.

Multigene panels can analyze high and moderate/intermediate penetrance genes that predispose to breast cancer (BC), providing an opportunity to identify at-risk individuals within affected families. However, considering the complexity of different pathogenic variants and correlated clinical manifestations, a multidisciplinary team is needed to effectively manage BC. A classification of pathogenic variants included in multigene panels was presented in this narrative review to evaluate their clinical utility in BC. Clinical management was discussed for each category and focused on BC, including available evidence regarding the multidisciplinary and integrated management of patients with BC. The integration of both genetic testing and counseling is required for customized decisions in therapeutic strategies and preventative initiatives, as well as for a defined multidisciplinary approach, considering the continuous evolution of guidelines and research in the field.

Long-Term Safety of Level II Oncoplastic Surgery after Neoadjuvant Treatment for Locally Advanced Breast Cancer: A 20-Year Experience.

Background: Oncoplastic surgery (OPS) reliability in the post-neoadjuvant chemotherapy (NACT) setting is still debated due to weak scientific evidences in such scenarios. Methods: Our analysis aims to report results obtained in a retrospective series of 111 patients consecutively treated with level II OPS after NACT at the Multidisciplinary Breast Center of the Fondazione Policlinico Universitario Agostino Gemelli IRCCS between 1998 and 2018. The surgical endpoints were the mean specimen volume, rates of positive margins (PMR), re-excision (RR), conversion to mastectomy (CMR), and complications (CR). The oncological endpoints were overall survival (OS), disease-free survival (DFS), and local recurrence (LR). To evaluate the impact of NACT on surgical and oncological outcomes at 302 months, we conducted a propensity score matching, pairing patients in post-NACT and upfront surgery groups. Results: The mean sample volume was 390,796 mm3. We registered a 3.6% of PMR, 1.8% RR, 0.9% CMR, 5% CR. The 10-year OS and 10-year DFS with a median follow-up of 88 months (6-302) were 79% and 76%, respectively, with an LR recurrence rate of 5%. The post-NACT group received significantly larger excised volumes and lower PMR. NACT did not affect surgical and oncological outcomes. Conclusions: Level II OPS can be considered a reliable alternative to mastectomy even in the post-NACT setting.

Young Women with Early-Stage Breast Cancer Treated with Upfront Surgery: Overview of Oncological Outcomes.

Background: Breast cancer in young women aged < 40 years is rare and often aggressive with less favorable survival rates. The lack of systematic screening, later stage at diagnosis, and a more aggressive disease biology may all contribute to their poor prognosis. Data on the best management remain conflicting, especially those regarding surgical management, either breast-conserving or mastectomy. To our knowledge, there are limited studies surrounding the treatment of young women with early breast cancer, and this analysis evaluated the oncological outcomes for those patients who underwent surgery upfront. Methods: We conducted a retrospective study including 130 young women with early breast cancer from a total of 373 consecutive patients treated with upfront surgery between January 2016 and December 2021 at our institution. Local recurrence-free survival (LR-FS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were evaluated. Results: The median follow-up was 61.1 months (range, 25-95). A total of 92 (70.8%) patients underwent breast-conserving surgery, while 38 (29.2%) patients underwent conservative mastectomy with immediate implant breast reconstruction. In total, 8 of 130 patients (6.2%) developed a local recurrence in the treated breast, an7 (5.4%) patients presented distant metastasis. Overall, two (1.6%) patients died due to breast cancer recurrence. Conclusions: The results of our study interestingly support breast-conserving surgery in young patients with early-stage breast cancer. While appropriate breast-conserving surgery can achieve favorable oncological outcomes and can always be considered a valid alternative to conservative mastectomy in upfront surgery, a younger age at diagnosis should never be used alone to choose the type of surgery.

Preventing Bone Loss in Breast Cancer Patients: Designing a Personalized Clinical Pathway in a Large-Volume Research Hospital.

BACKGROUND: We assess the impact of bone health clinical management in breast cancer (BC) patients receiving adjuvant endocrine therapy and design a personalized clinical pathway to reduce bone loss in an Italian research hospital. METHODS: The primary endpoint was to assess (through the process improvement organizational method) the clinical pathway that post-surgical BC patients prescribed with endocrine therapy undergo to prevent bone loss. The secondary endpoint was to design a personalized clinical pathway for a prompt implementation of guidelines, to assess and possibly prescribe antiresorptive therapy. RESULTS: During the first year of the execution of the new Diagnostic Therapeutic Assistance Pathway, a 60% increase in Dual-Energy X-ray Absorptiometry evaluations within 30 days and a 39.5% increase in antiresorptive therapy prescription within 90 days (since the prescription of endocrine therapy) were shown, thus increasing patients' compliance. CONCLUSION: Case managers and bone health specialists in this context can improve patients' adherence to therapies and bone health, helping physicians to expand their collaboration.

Atypical ductal hyperplasia on vacuum-assisted breast biopsy: a scoring system to predict the risk of upgrade to malignancy.

RATIONALE AND OBJECTIVES: Our multicentric study analysed clinical, radiologic and pathologic features in patients with atypical ductal hyperplasia (ADH) diagnosed with vacuum-assisted biopsy (VAB), to identify factors associated with the risk of upgrade, to develop a scoring system to support decision making. MATERIALS AND METHODS: Patients with ADH on VAB under stereotactic/tomosynthesis guidance (2012-2022) were eligible. Inclusion criteria were availability of surgical histopathological examination of the entire lesion or radiologic follow-up (FUP) ≥ 24 months. VAB results were compared with surgical pathological results or with imaging FUP evolution to assess upgrade. A backward stepwise linear regression was used to identify predictors of upgrade. The discriminatory power of the model was calculated through the area under the receiver operating curve (ROC-AUC); the Hosmer-Lemeshow test was used to assess model calibration. The points system was developed based on the selected risk factors, and the probability of upgrade associated with each point total was determined. RESULTS: 112 ADH lesions were included: 91 (91/112, 81.3%) underwent surgical excision with 20 diagnosis of malignancy, while 21 (21/112, 18.7%) underwent imaging FUP with one interval change (mean FUP time 48 months). Overall upgrade rate was 18.7% (21/112). Age, menopausal status, concurrent breast cancer, BIRADS classification and number of foci of ADH were identified as risk factors for upgrade. Our model showed an AUC = 0.85 (95% CI 0.76-0.94). The points system showed that the risk of upgrade is < 2% when the total score is ≤ 1. CONCLUSION: Our scoring system seemed a promising easy-to-use decision support tool for management of ADH, decreasing unnecessary surgeries, reducing patients' overtreatment and healthcare costs.

Magnetic seed versus skin tattoo localization of non-palpable breast lesions: a single institution cohort study.

OBJECTIVE: The objective of this retrospective study was to investigate the accuracy and feasibility of magnetic seed compared to skin tattoo in preoperative localization of impalpable breast lesions in terms of accuracy of placement, re-excision and positive margins rates, and breast/surgical specimen volume ratio. METHODS: We retrospectively analyzed 77 patients who underwent breast conservative surgery in our center from November 2020 to November 2021, with previous localization with skin tattoo or magnetic seed. RESULTS: Thirty-seven magnetic seeds were placed in 36 patients (48.6%) and 40 skin tattoos were performed in the remaining cases (51.4%). The seeds were placed correctly at the two-view mammogram acquired after the insertion in 97.6% (36/37) of cases. With both methods, 100% of the index lesions were completely removed and found in the surgical specimen. The reported re-excision rate was 0% for both groups. A significant difference was observed in the volume of breast parenchyma removed between the two groups, inferior in the seed group (p = 0.046), especially in case of voluminous breasts (p = 0.003) and small lesions (dimension < 8 mm, p = 0.019). CONCLUSIONS: Magnetic seed is a non-radioactive localization technique, feasible to place, recommended in case of non-palpable breast lesions, saving the breast parenchyma removed compared with skin tattoo, without reducing the accuracy. CLINICAL RELEVANCE STATEMENT: Our findings contribute to the current evidence on preoperative localization techniques for non-palpable breast lesions, highlighting the efficacy of magnetic seed localization for deep and small lesions. KEY POINTS: • Magnetic seed is a non-radioactive technique for the preoperative localization of non-palpable breast lesions studied in comparison with skin tattoo. • Magnetic seed is feasible to place in terms of post-placement migration and distance from the target lesion. • Magnetic seed is recommended in case of non-palpable breast lesions, saving the breast parenchyma removed without reducing the accuracy.

An Innovative Scoring System to Select the Optimal Surgery in Breast Cancer after Neoadjuvant Chemotherapy.

INTRODUCTION: The selection of surgery post-neoadjuvant chemotherapy (NACT) is difficult and based on surgeons' expertise. The aim of this study was to create a post-NEoadjuvant Score System (pNESSy) to choose surgery, optimizing oncological and aesthetical outcomes. METHODS: Patients (stage I-III) underwent surgery post-NACT (breast-conserving surgery (BCS), oncoplastic surgery (OPS), and conservative mastectomy (CMR) were included. Data selected were BRCA mutation, ptosis, breast volume, radiological response, MRI, and mammography pre- and post-NACT prediction of excised breast area. pNESSy was created using the association between these data and surgery. Area under the curve (AUC) was assessed. Patients were divided into groups according to correspondence (G1) or discrepancy (G2) between score and surgery; oncological and aesthetic outcomes were analyzed. RESULTS: A total of 255 patients were included (118 BCS, 49 OPS, 88 CMR). pNESSy between 6.896-8.724 was predictive for BCS, 8.725-9.375 for OPS, and 9.376-14.245 for CMR; AUC was, respectively, 0.835, 0.766, and 0.825. G1 presented a lower incidence of involved margins (5-14.7%; p = 0.010), a better locoregional disease-free survival (98.8-88.9%; p < 0.001) and a better overall survival (96.1-86.5%; p = 0.017), and a better satisfaction with breasts (39.8-27.5%; p = 0.017) and physical wellbeing (93.5-73.6%; p = 0.001). CONCLUSION: A score system based on clinical and radiological features was created to select the optimal surgery post-NACT and improve oncological and aesthetic outcomes.

Tibolone and Breast Tissue: a Review.

The safety profile of hormone replacement therapy (HRT) on breast is still controversial. Tibolone is an option of treatment for climacteric syndrome of postmenopausal women. Its risk profile on breast is debated. This is an updated narrative review focusing on the impact of tibolone on breast. Particularly, we will report data from major preclinical and clinical studies regarding the effects of the use of this compound on breast tissue and breast density. Moreover, we will analyze and discuss the most relevant findings of the principal studies evaluating the relationship between tibolone and breast cancer risk. Our purpose is making all clinicians who are particularly involved in women's health more aware of the effects of this compound on breast and, thus, more experienced in the management of menopausal symptoms with this drug. According to the available literature, tibolone seems to be characterized by an interesting safety profile on breast tissue.

Local Treatment of Triple-Negative Breast Cancer: Is Mastectomy Superior to Breast-Conserving Surgery?

Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer that lacks the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). TNBC accounts for about 15% of breast cancers and has a poorer prognosis as compared with other subtypes of breast cancer. The more rapid onset of this cancer and its aggressiveness have often convinced breast surgeons that mastectomy could provide better oncological results. However, there is no relevant clinical trial that has assessed differences between breast-conserving surgery (BCS) and mastectomy (M) in these patients. This population-based study aimed to investigate the distinct outcomes between conservative treatment and M in a case series of 289 patients with TNBC treated over a 9-year period. This monocentric study retrospectively evaluated patients with TNBC who underwent upfront surgery at Fondazione Policlinico Agostino Gemelli IRCCS, in Rome, between 1 January 2013 and 31 December 2021. First, the patients were divided in two groups according to the surgical treatment received: BCS vs. M. Then, the patients were stratified into four risk subclasses based on combined T and N pathological staging (T1N0, T1N+, T2-4N0 and T2-4N+). The primary endpoint of the study was to evaluate locoregional disease-free survival (LR-DFS), distant disease-free survival (DDFS) and overall survival (OS) in the different subclasses. We analyzed 289 patients that underwent either breast-conserving surgery (247/289, 85.5%) or mastectomy (42/289, 14.5%). After a median follow-up of 43.2 months (49.7, 22.2-74.3), 28 patients (9.6%) developed a locoregional recurrence, 27 patients (9.0%) showed systemic recurrence and 19 patients (6.5%) died. No significant differences due to type of surgical treatment were observed in the different risk subclasses in terms of locoregional disease-free survival, distant disease-free survival and overall survival. With the limits of a retrospective, single-center study, our data seem to indicate similar efficacy in terms of locoregional control, distant metastasis and overall survival with the use of upfront breast-conserving surgery as compared with radical surgery in the treatment of TNBC. Therefore, TNBC should not be considered to be a contraindication for breast conservation.

Endocrine Disruptors in Food, Estrobolome and Breast Cancer.

The microbiota is now recognized as one of the major players in human health and diseases, including cancer. Regarding breast cancer (BC), a clear link between microbiota and oncogenesis still needs to be confirmed. Yet, part of the bacterial gene mass inside the gut, constituting the so called "estrobolome", influences sexual hormonal balance and, since the increased exposure to estrogens is associated with an increased risk, may impact on the onset, progression, and treatment of hormonal dependent cancers (which account for more than 70% of all BCs). The hormonal dependent BCs are also affected by environmental and dietary endocrine disruptors and phytoestrogens which interact with microbiota in a bidirectional way: on the one side disruptors can alter the composition and functions of the estrobolome, ad on the other the gut microbiota influences the metabolism of endocrine active food components. This review highlights the current evidence about the complex interplay between endocrine disruptors, phytoestrogens, microbiome, and BC, within the frames of a new "oncobiotic" perspective.

Conservative Surgery in cT4 Breast Cancer: Single-Center Experience in the Neoadjuvant Setting.

BACKGROUND: The diffusion of screening programs has resulted in a decrease of cT4 breast cancer diagnosis. The standard care for cT4 was neoadjuvant chemotherapy (NA), surgery, and locoregional or adjuvant systemic therapies. NA allows two outcomes: 1. improve survival rates, and 2. de-escalation of surgery. This de-escalation has allowed the introduction of conservative breast surgery (CBS). We evaluate the possibility of submitting cT4 patients to CBS instead of radical breast surgery (RBS) by assessing the risk of locoregional disease-free survival, (LR-DFS) distant disease-free survival (DDFS), and overall survival (OS). METHODS: This monocentric, retrospective study evaluated cT4 patients submitted to NA and surgery between January 2014 and July 2021. The study population included patients undergoing CBS or RBS without immediate reconstruction. Survival curves were obtained using the Kaplan-Meyer method and compared using a Log Rank test. RESULTS: At a follow-up of 43.7 months, LR-DFS was 70% and 75.9%, respectively, in CBS and RBS (p = 0.420). DDFS was 67.8% and 29.7%, respectively, (p = 0.122). OS was 69.8% and 59.8%, respectively, (p = 0.311). CONCLUSIONS: In patients with major or complete response to NA, CBS can be considered a safe alternative to RBS in the treatment of cT4a-d stage. In patients with poor response to NA, RBS remained the best surgical choice.

Selective Axillary Dissection after Neoadjuvant Chemotherapy in Patients with Lymph-Node-Positive Breast Cancer (CLYP Study): The Radio-Guided Occult Lesion Localization Technique for Biopsy-Proven Metastatic Lymph Nodes.

(1) Background: To help to refine the accuracy of sentinel lymph node biopsy (SLNB) in breast cancer (BC) patients with biopsy-proven nodal disease prior to neoadjuvant chemotherapy (NACT), a method of marking the biopsy-proven positive LN at diagnosis to enable its removal during surgery was proposed. The aim of this study was to evaluate the accuracy of the Radio-Guided Occult Lesion Localization (ROLL) technique of biopsy-proven metastatic LN in nodal staging after NACT among node-positive BC patients. (2) Methods: Patients with invasive BC and biopsy-proven axillary metastases receiving NACT were enrolled. A clip marker was placed on the sampled LN (clipped lymph node, CLN) before NACT. Before surgery, the ROLL procedure (radioactive tracer injection into CLN under ultrasound guidance) was performed, and the CLN was surgically resected. The correspondence between the CLNs and SLNs was evaluated. The pathologic findings of the CLNs and SLN(s) were compared with remaining axillary nodes at ALND to determine false negative rates (FNRs). (3) Results: Seventy-two patients were analyzed. Surgery successfully identified the CLN in 70/72 procedures (97.2%). For 60/72 patients who underwent ALND, the FNRs dropped from 19.35% for SLNB to 3.13% for CLN biopsy. (4) Conclusions: The ROLL procedure got CLNs is accurate in axillary nodal staging after NACT in node-positive BC patients at diagnosis.

Gradients of Variation in the At-Vessel Mortality Rate between Twelve Species of Sharks and Skates Sampled through a Fishery-Independent Trawl Survey in the Asinara Gulf (NW Mediterranean Sea).

Elasmobranchs are priority species for conservation due to their rapid decline determined by the unbalanced struggle between a fragile bio-ecology and strong anthropogenic impacts, such as bycatch from professional fishing. In this context, measuring species resistance to catch of poorly selective gear is of paramount importance. During June-October 2022, five experimental fishing campaigns were carried out in the Asinara Gulf (northern Sardinia) through 35 geographically and bathymetrically representative hauls of an area between 30 and 600 m in depth. Skates prevailed over sharks in the number of species, with seven and five species, respectively. We first evaluated the status of each individual with respect to stress due to the trawl's catch using a three-graded scale. We also recorded individual biometrics (total and disk length, weight and sex, and maturity for males) on board by implementing the best practices in manipulating individuals for physiological recovery and release at sea. After capture, skates resulted in generally better conditions than sharks, although deepwater species of both groups exhibited a worse state than coastal species. The estimated vitality rates also depended on the size of the individuals. This work provides standardized data on the intermingled effect of size, species type, and inhabited depth on the resistance response of some elasmobranch species against capture by trawl fishery activities.