Search

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.

No abstract available

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.

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.

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 retros

Background: Conservative mastectomy with immediate prosthetic breast reconstruction (IPBR) is an oncologically accepted technique that offers improved esthetic results and patient quality of life. Traditionally, implants have been placed in a submuscular (SM) plane beneath the pectoralis major muscle (PMM). Recently, prepectoral (PP) placement of the prosthesis has been increasingly used in order to avoid morbidities related to manipulation of the PMM. The aim of this study was to compare outcomes of SM vs. PP IPBR after conservative mastectomy in patients with histologically proven breast cancer treated with neoadjuvant chemotherapy (NAC). Methods: In this retrospective observational study, we analyzed two cohorts of patients that underwent mastectomy with IPBR after NAC in our institution from January 2018 to December 2021. Conservative mastectomy was performed in 146 of the 400 patients that underwent NAC during the study period. Patients were divided into two groups based on the positioning of implants: 56 SM versus 90 PP. Results: The two cohorts were similar for age (mean age 42 and 44 years in the SM and PP group respectively) and follow-up (33 and 20 months, respectively). Mean operative time was 56 min shorter in the PP group (300 and 244 min in the SM and PP group). No significant differences were observed in overall major complication rates. Implant loss was observed in 1.78% of patients (1/56) in the SM group and 1.11% of patients (1/90) in PP group. No differences were observed between the two groups in local or regional recurrence. Conclusions: Our preliminary experience, which represents one of the largest series of patients undergoing PP-IPBR after NAC at a single institution documented in the literature, seems to confirm that PP-IPBR after NAC is a safe, reliable and effective alternative to traditional SM-IPBR with excellent esthetic and oncological outcomes; it is easy to perform, reduces operative time and minimizes complications related to manip

no Abstract available

Background: The modern concept of lymphatic transfer includes vascularised lymph node transfer (VLNT), lymphatic vessels transfer (lymph interpositional flap transfer, LIFT) and lymphatic system transfer (vascularised lymph nodes and afferent lymphatics, LYST). The aim of this paper was to report our experience with different types of lymphatic transfer. Patients and Method: From June 2016 to June 2020, 30 consecutive patients affected by extremity lymphedema and 15 patients affected by post-traumatic lower extremity soft tissue defects, underwent lymphatic transfer (VLNT, LYST or LIFT). All cases were preoperatively evaluated by both high frequency and ultra-high frequency ultrasound. Flap features were recorded, as well as qualitative and quantitative outcomes at 1 year postoperative. Results: The mean postoperative lymphedema index reduction was 7.2 ± 5.7 for upper extremity and 20.7 ± 7.1 for lower extremity. No dismission of compression garments occurred, 12 patients (26%) referred more stable results of physical treatment and 1 case showed a 1-class compression reduction. All the LIFTs aimed as preventive did not develop post-traumatic lymphedema. In all cases of distal placement of VLNT and/or LYST, patients were dissatisfied with the aesthetic appearance of reconstruction, while no donor site scar disappointment was referred. Conclusion: When LVA is not feasible, LTT may represent a valid treatment option. This report was aimed at comprehensively describing and assessing how different lymphatic tissue transfer modalities may fulfil the different reconstructive needs of lymphedema patients.

The prevention of chemotherapy-induced alopecia still represents an urgent need for every day clinical practice. In this regard, this prospective single-center study included breast cancer (BC) patients who underwent a scalp cooling device (Dignicap®) during (neo)adjuvant chemotherapy with the aim to evaluate the efficacy and safety of this device in preventing alopecia. One hundred and seventy-eight patients (median age 43 years) were enrolled. The chemotherapy regimen included anthracycline and taxane-based chemotherapy (68.1%), docetaxel and cyclophosphamide (25.8%), anthracycline and taxane-based plus carboplatin (3.9%), and paclitaxel alone (2.2%). In 25.3% of cases, a dose dense schedule was used. Overall, the success rate was 68.0%: 100% in paclitaxel alone, 87.0% in docetaxel-cyclophosphamide, 59.5% in anthracycline and taxane, and 71.4% in the sequential regimen plus carboplatin group (anthracycline and taxane-based chemotherapy versus taxane-based chemotherapy, p ≤ 001. No difference in terms of hair preservation between dose-dense or standard schedule was found (p = 0.557). Early discontinuation of the scalp cooling was observed in 50 patients (28.1%). Although 138 patients (77.5%) experienced adverse events, 70.2% of patients were satisfied with this device. In conclusion, this large prospective study confirmed the helpful effect of the scalp cooling system in preventing alopecia in BC patients also undergoing sequential anthracyclines and taxane-based chemotherapy.

No abstract available

Not available

Background: Triple-negative breast cancer (TNBC) is a very heterogeneous disease. Several gene expression and mutation profiling approaches were used to classify it, and all converged to the identification of distinct molecular subtypes, with some overlapping across different approaches. However, a standardised tool to routinely classify TNBC in the clinics and guide personalised treatment is lacking. We aimed at defining a specific gene signature for each of the six TNBC subtypes proposed by Lehman et al. in 2011 (basal-like 1 (BL1); basal-like 2 (BL2); mesenchymal (M); immunomodulatory (IM); mesenchymal stem-like (MSL); and luminal androgen receptor (LAR)), to be able to accurately predict them. Methods: Lehman’s TNBCtype subtyping tool was applied to RNA-sequencing data from 482 TNBC (GSE164458), and a minimal subtype-specific gene signature was defined by combining two class comparison techniques with seven attribute selection methods. Several machine learning algorithms for subtype prediction were used, and the best classifier was applied on microarray data from 72 Italian TNBC and on the TNBC subset of the BRCA-TCGA data set. Results: We identified two signatures with the 120 and 81 top up- and downregulated genes that define the six TNBC subtypes, with prediction accuracy ranging from 88.6 to 89.4%, and even improving after removal of the least important genes. Network analysis was used to identify highly interconnected genes within each subgroup. Two druggable matrix metalloproteinases were found in the BL1 and BL2 subsets, and several druggable targets were complementary to androgen receptor or aromatase in the LAR subset. Several secondary drug–target interactions were found among the upregulated genes in the M, IM and MSL subsets. Conclusions: Our study took full advantage of available TNBC data sets to stratify samples and genes into distinct subtypes, according to gene expression profiles. The development of a data mining approach to acquire a large amo

We read with interest the article of Francesca Maria Plutino entitled "A peculiar case of Paget's disease of the breast" and would like to make some considerations about this particular topic 1. Mammary Paget's Disease (MPD) or Paget's disease of the breast is an uncommon pathology which accounts for less than 5% of breast cancers 1-3. MPD occurs with alterations of the nipple-areolar complex (NAC) such as redness, eczema, bleeding ulceration and usually itching 1-3. In the era of personalized care, a careful multidisciplinary management is mandatory to optimize the results and minimize the risk of overtreatment 4; an adequate knowledge of the MPD, surgical skills and use of appropriate adjuvant therapies allow to reduce the risk of local recurrence and improve the aesthetic outcomes and patient's quality of life; however, a successful work can be more easily achieved thanks to the repetitive performance of some standardized tasks, such as 5: - an accurate radiological preoperative assessment with mammography and ultrasonography is important to identify associated glandular lesions; an underlying breast carcinoma (in situ and/or invasive) may be present up to about 80% to 90% of MPD although often without an evident breast mass or mammographic abnormality (2,5); therefore, all patients with MPD should also perform a magnetic resonance imaging to detect possible underlying occult breast carcinoma and define the true extent of disease 5,6; - a pathological diagnosis should be early established by nipple scrape cytology when a MPD is clinically suspected; full-thickness punch or wedge biopsy of the NAC may be necessary to accurately diagnose MPD; the histological examination must detect malignant intraepithelial carcinoma cells, also known as "Paget cells", in the epidermis of the NAC 2,3; a needle biopsy is also required for any suspicious glandular lesion identified by imaging and associated with MPD 5; - a multidisciplinary "Surgery Board" is mandatory to select the

Oncoplastic level II breast-conserving surgery (OPS2) allows for wider excisions than standard breast-conserving surgery, but the literature on this technique in the treatment of DCIS is scarce. This study compares OPS2 to conservative mastectomy (CM) in patients undergoing surgery for large DCIS. The clinical, radiological, surgical, and post-operative data of 147 patients who underwent either CM or OPS2 for large DCIS between 2007 and 2021 were retrospectively reviewed. The surgical, oncological, and patient-reported outcomes (PRO) were analyzed and compared between the two groups. The surgical outcomes were similar, in terms of margin involvement (p = 0.211), complication rate (p = 0.827), and re-excision rate (p = 1). The rate of additional surgery for cosmetic optimization was significantly lower in the OPS2 group: only 1 (1.8%) patient required surgical adjustments versus 24 (26.4%) patients in the CM group (p < 0.001). The mean hospital stay was lower in the OPS2 group (p < 0.001). The oncological outcomes did not differ between the two groups (p = 0.662). The PRO analysis showed better outcomes in the OPS2 group, which achieved statistical significance in the sexual well-being module (p = 0.015). Skin sensitivity loss was also significantly lower in the OPS2 group (p < 0.001). When feasible, OPS2 should be considered in the treatment of large DCIS, as it is safe and shows high levels of patient satisfaction.

Introduction: Paget’s disease (PD) represents 1%–3% of all breast cancers and mostly occurs in postmenopausal women. Multiple studies have confirmed that breast-conserving surgery (BCS) followed by radiotherapy is a safe option for patients with in situ or invasive PD, ensuring local control and survival rates similar to those achieved with mastectomy. Materials and methods: We retrospectively analyzed 115 patients affected by PD treated in our institution between January 2000 and May 2021. Median age at diagnosis was 60 years and median follow-up was 82 months; 69 patients were treated with BCS and 46 were treated with modified radical mastectomy or skin-sparing mastectomy. Results: At histological examination, 59 patients (59/115, 51.0%) had an underlying invasive carcinoma; in 11 patients (11/115, 9.0%), only PD was found. In 45 patients (45/115, 40.0%), only noninvasive cancer was found. Nine patients (9/115, 7.8%) developed a local recurrence, 7 patients (7/115, 6.0%) are alive with distant metastasis, and 10 patients (10/115, 8.6%) died. Discussion: In our series, no statistically significant differences were shown between PD alone, PD associated with in situ cancer, and PD with invasive cancer, regardless of the surgical procedure. BCS followed by radiotherapy appears to be an effective and safe option for patients with PD. Conclusion: PD is a rare form of breast cancer and, in half of the cases, is associated with an invasive carcinoma. Separating our sample into three subgroups based on tumor histology, there were no significant differences in terms of LC, DFS, and OS rate in patients treated with different types of surgery. This study presents some limitations due to its retrospective nature and being confined to a single institution.

Background. Immediate breast reconstruction is recommended for eligible patients undergoing mastectomy, raising the issue of economic sustainability of both mastectomy and breast reconstruction performed within the same hospitalization, as opposed to two surgical procedures in two different hospitalizations. Study design. A retrospective analysis was conducted to compare economic sustainability of mastectomies with or without immediate breast reconstruction. Methods. Economic data on hospitalizations for mastectomy in a Teaching Hospital between 1 January 2019 and 31 March 2021 were analyzed to assess their sustainability. Results. 338 admissions were selected (63.9% with immediate breast reconstruction (CI 99%: 57.2% to 70.6%). Compared to mastectomy alone, mastectomy with immediate breast reconstruction had higher cost of € 2,245 (p < 0.001), with operating rooms and devices as main cost drivers. Current reimbursements rates (which are the same for mastectomy alone and for mastectomy with immediate breast reconstruction) led to an average loss of € 1,719 for each mastectomy with immediate breast reconstruction. Conclusion. Current DRGs reimbursement rates for hospital admissions for breast cancer surgery do not guarantee immediate breast reconstruction’s economic sustainability. DRGs system should be revised, or other solutions as bundled payment should be implemented in the light of the costs of innovation in healthcare, considering mastectomy and breast reconstruction steps in a path of linked actions aimed at improving patients’ health.

Oncoplastic surgery level II techniques (OPSII) are used in patients with operable breast cancer. There is no evidence regarding their safety and efficacy after neoadjuvant chemotherapy (NAC). The aim of this study was to compare the oncological and aesthetic outcomes of this technique compared with those observed in mastectomy with immediate breast reconstruction (MIBR), in post-NAC patients undergoing surgery between January 2016 and March 2021. Local disease-free survival (L-DFS), regional disease-free survival (R-DFS), distant disease-free survival (D-DFS), and overall survival (OS) were compared; the aesthetic results and quality of life (QoL) were evaluated using BREAST-Q. A total of 297 patients were included, 87 of whom underwent OPSII and 210 of whom underwent MIBR. After a median follow-up of 39.5 months, local recurrence had occurred in 3 patients in the OPSII group (3.4%), and in 13 patients in the MIBR group (6.1%) (p = 0.408). The three-year L-DFS rates were 95.1% for OPSII and 96.2% for MIBR (p = 0.286). The three-year R-DFS rates were 100% and 96.4%, respectively (p = 0.559). The three-year D-DFS rate were 90.7% and 89.7% (p = 0.849). The three-year OS rates were 95.7% and 95% (p = 0.394). BREAST-Q highlighted significant advantages in physical well-being for OPSII. No difference was shown for satisfaction with breasts (p = 0.656) or psychosocial well-being (p = 0.444). OPSII is safe and effective after NAC. It allows oncological and aesthetic outcomes with a high QoL, and is a safe alternative for locally advanced tumors which are partial responders to NAC.

BACKGROUND: Treatment of de-novo metastatic breast cancer is usually centered around systemic therapy, with local therapy (surgery and radiation therapy) largely reserved for palliation in patients with significant symptoms from primary tumor. The efficacy of locoregional treatment like surgery and/or radiotherapy is still controversial and the debate about surgical resection of primary tumor (PT) in de novo metastatic breast cancer (MBC) patients persists. METHODS: All patients with de-novo MBC undergone surgical treatment between January 2015 and January 2020 at the Multidisciplinary Breast Center of the IRCCS A. Gemelli University Polyclinic Foundation in Rome were included in this study. The primary endpoint was overall survival (OS) after PT resection, the secondary endpoint was progression free survival (PFS). The survival analyses were done using Kaplan-Meier method. Patients and tumor characteristics were analyzed in an exploratory modality in order to identify prognostic factor. RESULTS: Forty-five patients received resection of the primary breast cancer (26 mastectomy and 19 breast conserving surgery). Median age of diagnosis was 53 years old (range 25-75 years old). Median follow-up was 25.67 months. The median OS was not reached with 75% of patients alive over 2 years from PT resection. The median PFS was not reached with 64% of patients alive over 2 years from PT resection. For both PFS and OS only the triple negative (TN) immunophenotype appears to be a prognostically unfavorable factor in multivariate analysis. CONCLUSIONS: In view of the low number of disease progression events and deaths, although our results are preliminary, surgical treatment of primary breast cancer in metastatic setting seems to be an option after systemic therapies in luminal and HER2 positive breast cancer. Randomized prospective trials for each immunophenotype are necessary in order to confirm this evidence.

No abstract available

The diagnosis of breast cancer (BC) during pregnancy is uncommon. It has varied among different studies from 1:10,000 to 1:3000 of all pregnancies, with a median age of 33 years. Pregnancy-associated BC represents a challenge in terms of clinical management to guarantee both maternal and fetal security in choosing the right treatment. This situation is complex and requires a multidisciplinary approach, including the surgeon, anesthesiologist, oncologist, radiotherapist, psychologist, and maternal–fetal medicine specialist. In the present review, we examined the management of pregnancy-associated BC, focusing on pathophysiologic background, risk factors, diagnosis, staging procedures, anesthesia, surgical management, and systemic treatment.

No abstract available

Sarcopenia is a geriatric syndrome characterized by losses of quantity and quality of skeletal muscle, which is associated with negative outcomes in older adults and in cancer patients. Different definitions of sarcopenia have been used, with quantitative data more frequently used in oncology, while functional measures have been advocated in the geriatric literature. Little is known about the correlation between frailty status as assessed by comprehensive geriatric assessment (CGA) and sarcopenia in cancer patients. We retrospectively analyzed data from 96 older women with early breast cancer who underwent CGAs and Dual X-ray Absorptiometry (DXA) scans for muscle mass assessment before cancer treatment at a single cancer center from 2016 to 2019 to explore the correlation between frailty status as assessed by CGA and sarcopenia using different definitions. Based on the results of the CGA, 35 patients (36.5%) were defined as frail. Using DXA Appendicular Skeletal Mass (ASM) or the Skeletal Muscle Index (SMI=ASM/heightˆ2), 41 patients were found to be sarcopenic (42.7%), with no significant difference in prevalence between frail and nonfrail subjects. Using the European Working Group on Sarcopenia in Older People (EWGSOP2) definition of sarcopenia (where both muscle function and mass are required), 58 patients were classified as “probably” sarcopenic; among these, 25 were sarcopenic and 17 “severely” sarcopenic. Only 13 patients satisfied both the requirements for being defined as sarcopenic and frail. Grade 3-4 treatment-related toxicities (according to Common Terminology Criteria for Adverse Events) were more common in sarcopenic and frail sarcopenic patients. Our data support the use of a definition of sarcopenia that includes both quantitative and functional data in order to identify frail patients who need tailored treatment.

No abstract available

BACKGROUND: Nipple-sparing mastectomy (NSM) with immediate prosthetic breast reconstruction (IPBR) is an oncologically accepted technique that allows to improve aesthetic results and patient quality of life. Traditionally, implant for reconstruction have been placed in a submuscolar (SM) plane, beneath the pectoralis major muscle (PMM). Recently, prepectoral (PP) placement of prosthesis is increasingly used in order to avoid morbidities related to manipulation of PMM. The aim of the present study was to report our experience with 209 NSMs and IPBR using a prepectoral approach and polyurethane-coated implant without acellular dermal matrices (ADMs). METHODS: A retrospective review of breast cancer patients who underwent NSM followed by PP - IPBR from January 2018 to April 2021 was performed. Data were recorded in order to evaluate operative details, major complications and oncological outcomes. Aesthetic results and patient quality of life were measured by a specific “QOL assessment PRO” survey. RESULTS: Two hundred and nine patients (269 breasts) with PP - IPBR after NSM were included. Mean age was 47 (25-73) years and median follow-up was 14 (1-40) months. A simultaneous contralateral implant-based mammoplasty of symmetrization after unilateral NSM was carried out in six of 149 (4%) patients. Implant loss was observed in three of 209 patient (1.44%); two of 209 (0.96%) patients developed a full-thickness NAC necrosis that required excision. During follow-up one local relapse (0.48%) and two regional nodes recurrences (0,96%) was observed. Patient satisfaction, assessed using a personalized QOL Assessment PRO survey, in term of aesthetic results, chronic pain, shoulder dysfunction, sports activity, sexual and relationship life and skin sensibility, was excellent. CONCLUSIONS: Our experience shows that PP-IPBR using polyurethane-coated implant after NSM is a safe, reliable and effective alternative to traditional IPBR with excellent aesthetic outcomes and high patien

Neoadjuvant chemotherapy is increasingly being employed in the management of breast cancer patients. Efforts and resources have been devoted over the years to the search for an optimal strategy that can improve outcomes in the neoadjuvant setting. Today, a multidisciplinary approach with the application of evidence-based medicine is considered the gold standard for the improvement of oncological results and patient satisfaction. However, several clinical complications and psychological issues due to various factors can arise during neoadjuvant therapy and undermine outcomes. To ensure that health care needs are adequately addressed, clinicians must consider that women with breast cancer have a high risk of developing “unmet needs” during treatment, and often require a clinical intervention or additional care resources to limit possible complications and psychological issues that can occur during neoadjuvant treatment. This work describes a multidisciplinary model developed at “Fondazione Policlinico Universitario Agostino Gemelli” (FPG) in Rome in an effort to optimize treatment, ease the application of evidence-based medicine, and improve patient quality of life in the neoadjuvant setting. In developing our model, our main goal was to adequately meet patient needs while preventing high levels of distress.

Background: Worldwide, breast cancer (BC) is the most common malignancy in the female population. In recent years, its diagnosis in young women has increased, together with a growing desire to become pregnant later in life. Although there is evidence about the detrimental effect of chemotherapy (CT) on the menses cycle, a practical tool to measure ovarian reserve is still missing. Recently, anti-Mullerian hormone (AMH) has been considered a good surrogate for ovarian reserve. The main objective of this paper is to evaluate the effect of CT on AMH value. Methods: A systematic review and meta-analysis were conducted on the PubMed and Scopus electronic databases on articles retrieved from inception until February 2021. Trials evaluating ovarian reserves before and after CT in BC were included. We excluded case reports, case-series with fewer than ten patients, reviews (narrative or systematic), communications and perspectives. Studies in languages other than English or with polycystic ovarian syndrome (PCOS) patients were also excluded. AMH reduction was the main endpoint. Egger’s and Begg’s tests were used to assess the risk of publication bias. Results: Eighteen trials were included from the 833 examined. A statistically significant decline in serum AMH concentration was found after CT, persisting even after years, with an overall reduction of -1.97 (95% CI: -3.12, -0.82). No significant differences in ovarian reserve loss were found in the BRCA1/2 mutation carriers compared to wild-type patients. Conclusions: Although this study has some limitations, including publication bias, failure to stratify the results by some important factors and low to medium quality of the studies included, this metanalysis demonstrates that the level of AMH markedly falls after CT in BC patients, corresponding to a reduction in ovarian reserve. These findings should be routinely discussed during oncofertility counseling and used to guide fertility preservation choices in young women befo

No abstract available

Normal breast tissue undergoes great variations during a woman’s life as a consequence of the different hormonal stimulation. The purpose of the present study was to examine the hormonal receptor expression variations according to age, menstrual cycle, menopausal state and body mass index. To this purpose, 49 tissue samples of normal breast tissue, obtained during surgery performed for benign and malignant conditions, were immunostained with Estrogen (ER), Progesterone (PR) and Androgen receptors (AR). In addition, Ki67 and Gross Cystic Disease Fluid Protein were studied. The data obtained revealed a great variability of hormone receptor expression. ER and AR generally increased in older and post-menopausal women, while young women presented a higher proliferative rate, evaluated with Ki67. PR increase was observed in women with BMI higher than 25. The different hormonal receptor expression could favor the development of breast cancer.

Background: In the present study, we evaluated the prognostic value of TILs as well their relation with clinicopathological factors in patients affected by HER-2 positive breast cancer. Methods: We evaluated 47 patients with a histologically confirmed diagnosis of invasive breast carcinoma showing an immunohistochemically confirmed (score 3+) amplification of the c-erbB-2 gene for the presence of TILs and categorized in three predefined groups of low (0-10% immune cells in stromal tissue within the tumor), intermediate (11-40%), and high TILs (>40%). Results: Low, intermediate and high TILs were found in 17/47 (36%), 23/47 (49%) and 7/47(15%) cases, respectively. It was found that 6/47 cases treated with adjuvant chemotherapy plus trastuzumab underwent progression of the disease; none of these cases exhibited high TILs. It was found that 12/47 patients with a prognostically unfavorable stage of III and IV showed low and intermediate levels of TILs, while high TILs were never observed. A significant association between intermediate/high-levels of TILs, elevated KI 67 index and hormone receptors nuclear staining was observed. High concordance in TILs distribution was observed between preoperative breast biopsies and surgical samples. Conclusions: We observed a positive correlation between the TILs and the response to both adjuvant and neoadjuvant treatments in HER-2 positive BC. High TILs were also related to increased KI-67 index and to the expression of hormone receptors.

No abstract available

Clinical trials in cancer treatment are imperative in enhancing patients’ survival and quality of life outcomes. The lack of communication among professionals may produce a non-optimization of patients’ accrual in clinical trials. We developed a specific platform, called “Digital Research Assistant” (DRA), to report real-time every available clinical trial and support clinician. Healthcare professionals involved in breast cancer working group agreed nine minimal fields of interest to preliminarily classify the characteristics of patients’ records (including omic data, such as genomic mutations). A progressive web app (PWA) was developed to implement a cross-platform software that was scalable on several electronic devices to share the patients’ records and clinical trials. A specialist is able to use and populate the platform. An AI algorithm helps in the matchmaking between patient’s data and clinical trial’s inclusion criteria to personalize patient enrollment. At the same time, an easy configuration allows the application of the DRA in different oncology working groups (from breast cancer to lung cancer). The DRA might represent a valid research tool supporting clinicians and scientists, in order to optimize the enrollment of patients in clinical trials. User Experience and Technology The acceptance of participants using the DRA is topic of a future analysis.

Background: The aim of this study was to compare outcomes of immediate prosthetic breast reconstruction (IPBR) using traditional submuscular (SM) positioning of implants versus prepectoral (PP) positioning of micropolyurethane-foam-coated implants (microthane) without further coverage. Methods: We retrospectively reviewed the medical records of breast cancer patients treated by nipple-sparing mastectomy (NSM) and IPBR in our institution during the two-year period from January 2018 to December 2019. Patients were divided into two groups based on the plane of implant placement: SM versus PP. Results: 177 patients who received IPBR after NSM were included in the study; implants were positioned in a SM plane in 95 patients and in a PP plane in 82 patients. The two cohorts were similar for mean age (44 years and 47 years in the SM and PP groups, respectively) and follow-up (20 months and 16 months, respectively). The mean operative time was 70 min shorter in the PP group. No significant differences were observed in length of hospital stay or overall major complication rates. Statistically significant advantages were observed in the PP group in terms of aesthetic results, chronic pain, shoulder dysfunction, and skin sensibility (p < 0.05), as well as a trend of better outcomes for sports activity and sexual/relationship life. Cost analysis revealed that PP-IPBR was also economically advantageous over SM-IPBR. Conclusions: Our preliminary experience seems to confirm that PP positioning of a polyurethane-coated implant is a safe, reliable and effective method to perform IPBR after NSM.

Clinical trials in cancer treatment are imperative in enhancing patients’ survival and quality of life outcomes. The lack of communication among professionals may produce a non-optimization of patients’ accrual in clinical trials. We developed a specific platform, called “Digital Research Assistant” (DRA), to report real-time every available clinical trial and support clinician. Healthcare professionals involved in breast cancer working group agreed nine minimal fields of interest to preliminarily classify the characteristics of patients’ records (including omic data, such as genomic mutations). A progressive web app (PWA) was developed to implement a cross-platform software that was scalable on several electronic devices to share the patients’ records and clinical trials. A specialist is able to use and populate the platform. An AI algorithm helps in the matchmaking between patient’s data and clinical trial’s inclusion criteria to personalize patient enrollment. At the same time, an easy configuration allows the application of the DRA in different oncology working groups (from breast cancer to lung cancer). The DRA might represent a valid research tool supporting clinicians and scientists, in order to optimize the enrollment of patients in clinical trials. User Experience and Technology The acceptance of participants using the DRA is topic of a future analysis.

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.

Sarcopenia is a geriatric syndrome characterized by losses of quantity and quality of skeletal muscle, which is associated with negative outcomes in older adults and in cancer patients. Different definitions of sarcopenia have been used, with quantitative data more frequently used in oncology, while functional measures have been advocated in the geriatric literature. Little is known about the correlation between frailty status as assessed by comprehensive geriatric assessment (CGA) and sarcopenia in cancer patients. We retrospectively analyzed data from 96 older women with early breast cancer who underwent CGAs and Dual X-ray Absorptiometry (DXA) scans for muscle mass assessment before cancer treatment at a single cancer center from 2016 to 2019 to explore the correlation between frailty status as assessed by CGA and sarcopenia using different definitions. Based on the results of the CGA, 35 patients (36.5%) were defined as frail. Using DXA Appendicular Skeletal Mass (ASM) or the Skeletal Muscle Index (SMI=ASM/heightˆ2), 41 patients were found to be sarcopenic (42.7%), with no significant difference in prevalence between frail and nonfrail subjects. Using the European Working Group on Sarcopenia in Older People (EWGSOP2) definition of sarcopenia (where both muscle function and mass are required), 58 patients were classified as “probably” sarcopenic; among these, 25 were sarcopenic and 17 “severely” sarcopenic. Only 13 patients satisfied both the requirements for being defined as sarcopenic and frail. Grade 3-4 treatment-related toxicities (according to Common Terminology Criteria for Adverse Events) were more common in sarcopenic and frail sarcopenic patients. Our data support the use of a definition of sarcopenia that includes both quantitative and functional data in order to identify frail patients who need tailored treatment.

Sentinel lymph node biopsy (SLNB) following neoadjuvant treatment (NACT) has been questioned by many studies that reported heterogeneous identification (IR) and false negative rates (FNR). As a result, some patients receive axillary lymph node dissection (ALND) regardless of response to NACT, leading to a potential overtreatment. To better assess reliability and clinical significance of SLNB status on ycN0 patients, we retrospectively analyzed oncological outcomes of 399 patients treated between January 2016 and December 2019 that were either cN0-ycN0 (219 pa-tients) or cN1/2-ycN0 (180 patients). The Endpoints of our study were to assess, furthermore than IR: oncological outcomes as Overall Survival (OS); Distant Disease Free Survival (DDFS); and Regional Disease Free Survival (RDFS) according to SLNB status. SLN identification rate was 96.8% (98.2% in patients cN0-ycN0 and 95.2% in patients cN+-ycN0). A median number of three lymph nodes were identified and removed. Among cN0-ycN0 patients, 149 (68%) were confirmed ypN0(sn), whereas regarding cN1/2-ycN0 cases 86 (47.8%) confirmed an effective downstaging to ypN0. Three year OS, DDFS and RDFS were significantly related to SLNB positivity. Our data seemed to confirm SLNB feasibility following NACT in ycN0 patients, furthermore reinforcing its predictive role in a short observation timing.

Background: During the 2016 Assisi Think Tank Meeting (ATTM) on breast cancer, the panel of experts proposed developing a validated system, based on rapid learning health care (RLHC) principles, to standardize inter-center data collection and promote personalized treatments for breast cancer. Material and Methods: The seven-step Breast LArge DatabasE (BLADE) project included data collection, analysis, application, and evaluation on a data-sharing platform. The multidisciplinary team developed a consensus-based ontology of validated variables with over 80% agreement. This English-language ontology constituted a breast cancer library with seven knowledge domains: baseline, primary systemic therapy, surgery, adjuvant systemic therapies, radiation therapy, followup, and toxicity. The library was uploaded to the BLADE domain. The safety of data encryption and preservation was tested according to General Data Protection Regulation (GDPR) guidelines on data from 15 clinical charts. The system was validated on 64 patients who had undergone post-mastectomy radiation therapy. In October 2018, the BLADE system was approved by the Ethical Committee of Fondazione Policlinico Gemelli IRCCS, Rome, Italy (Protocol No. 0043996/18). Results: From June 2016 to July 2019, the multidisciplinary team completed the work plan. An ontology of 218 validated variables was uploaded to the BLADE domain. The GDPR safety test confirmed encryption and data preservation (on 5000 random cases). All validation benchmarks were met. Conclusion: BLADE is a support system for follow-up and assessment of breast cancer care. To successfully develop and validate it as the first standardized data collection system, multidisciplinary collaboration was crucial in selecting its ontology and knowledge domains. BLADE is suitable for multi-center uploading of retrospective and prospective clinical data, as it ensures anonymity and data privacy.

Background: Artificial Intelligence (AI) is increasingly used for process management in daily life. In the medical field AI is becoming part of computerized systems to manage information and encourage the generation of evidence. Here we present the development of the application of AI to IT systems present in the hospital, for the creation of a DataMart for the management of clinical and research processes in the field of breast cancer. Materials and methods: A multidisciplinary team of radiation oncologists, epidemiologists, medical oncologists, breast surgeons, data scientists, and data management experts worked together to identify relevant data and sources located inside the hospital system. Combinations of open-source data science packages and industry solutions were used to design the target framework. To validate the DataMart directly on real-life cases, the working team defined tumoral pathology and clinical purposes of proof of concepts (PoCs). Results: Data were classified into “Not organized, not ‘ontologized’ data”, “Organized, not ‘ontologized’ data”, and “Organized and ‘ontologized’ data”. Archives of real-world data (RWD) identified were platform based on ontology, hospital data warehouse, PDF documents, and electronic reports. Data extraction was performed by direct connection with structured data or text-mining technology. Two PoCs were performed, by which waiting time interval for radiotherapy and performance index of breast unit were tested and resulted available. Conclusions: GENERATOR Breast DataMart was created for supporting breast cancer pathways of care. An AI-based process automatically extracts data from different sources and uses them for generating trend studies and clinical evidence. Further studies and more proof of concepts are needed to exploit all the potentials of this system.

Breast conserving surgery has become the standard of care and is more commonly performed than mastectomy for early stage breast cancer, with recent studies showing equivalent survival and lower morbidity. Accurate preoperative lesion localization is mandatory to obtain adequate oncological and cosmetic results. Image guidance assures the precision requested for this purpose. This review provides a summary of all techniques currently available, ranging from the classic wire positioning to the newer magnetic seed localization. We describe the procedures and equipment necessary for each method, outlining the advantages and disadvantages, with a focus on the cost-effective preoperative skin tattoo technique performed at our centre. Breast surgeons and radiologists have to consider ongoing technological developments in order to assess the best localization method for each individual patient and clinical setting.

Acellular dermal matrices are biological materials of porcine, bovine, or human origin used as scaffold for reconstructive purpose in plastic surgery; these materials are well-tolerated and safely integrated in host tissues without causing resorption, contracture, and encapsulation thanks to their low antigenicity. Recently, human acellular dermal matrix has been used as a filler in breast-conserving surgery to improve aesthetic results. Adequate knowledge of biomaterials properties, appropriate skill, and careful compliance with some specific recommendations are mandatory in order to optimize outcomes and obtain a work of success.

The diagnosis of breast cancer (BC) during pregnancy is uncommon. It has varied among different studies from 1:10,000 to 1:3000 of all pregnancies, with a median age of 33 years. Pregnancy-associated BC represents a challenge in terms of clinical management to guarantee both maternal and fetal security in choosing the right treatment. This situation is complex and requires a multidisciplinary approach, including the surgeon, anesthesiologist, oncologist, radiotherapist, psychologist, and maternal–fetal medicine specialist. In the present review, we examined the management of pregnancy-associated BC, focusing on pathophysiologic background, risk factors, diagnosis, staging procedures, anesthesia, surgical management, and systemic treatment.

No abstract available

No abstract available

No abstract available

A correlation between phenotypical tumor characteristics, quantitative classical immunohistochemistry (IHC), and recurrence score (RS) from Oncotype DX results was used to develop a decision supporting system for clinical use. We created a freely available nomogram based on quantitative IHC results that allows prediction of RS ≤ 25 or ≤ 20. Prospective studies will test this application in clinical practice.

Background: Androgen receptor (AR) has been described to play a prominent role in male breast cancer (MBC). It maps on chromosome X, and recent reports indicate that X-chromosome polysomy is frequent in MBC. Since the response to anti-androgen therapy may depend on AR polysomy and on its overexpression similarly to prostate cancer, the aim of the present study was to investigate the DNA methylation level of AR and its coregulators, especially those mapped on the X-chromosome, that may influence the activity of AR in MBC. Methods: The DNA methylation level of AR, MAGEA2, MAGEA11, MAGEC1, MAGEC2, FLNA, HDAC6, and UXT, mapped on the X-chromosome, was evaluated by quantitative bisulfite-NGS. Bioinformatic analysis was performed in a Galaxy Project environment using BWA-METH, MethylDackel, and Methylation Plotter tools. The study population consisted of MBC (41 cases) compared with gynecomastia (17 cases). Results: MAGEA family members, especially MAGEA2, MAGEA11, MAGEC, and UXT and HDAC6 showed hypomethylation of several CpGs, reaching statistical significance by the Kruskal–Wallis test (p < 0.01) in MBC when compared to gynecomastia. AR showed almost no methylation at all. Conclusions: Our study demonstrated for the first time that MAGEA family members mapped on the X-chromosome and coregulators of AR are hypomethylated in MBC. This may lead to their overexpression, enhancing AR activity.

Oncoplastic surgery (OPS) has demonstrated its superiority above traditional breast conserving surgery, but is still struggling to consolidate its role in breast cancer therapeutic protocols mainly because of contrasting scientific evidences and reduced follow-up results available. The objective of our contribution is to analyze results obtained with 381 patients consecutively treated in our Multidisciplinary Breast Center by means of level II OPS between January 1998 and January 2018 for unilateral, primary breast cancer. Surgical endpoints were mean specimen weight and volume, mean diameter of main lesion (MLD), rates of positive margins (PMR), re-excision (RR), conversion to mastectomy (CMR), complications (CR) and oncological endpoints as overall survival (OS), disease-free survival (DFS), and local recurrence rate (LR). About 29.1% were treated for multifocal/multicentric disease, and 29.1% previously underwent neo-adjuvant chemotherapy (NACT). Regarding surgical techniques, 53.0% of patients received “inverted T” and 30.1% “J” mammoplasties, whereas 13.6% underwent “round block,” 2.3% “Grisotti,” and 1% “batwing” techniques. Regarding surgical outcomes, mean specimen weight was 215 g (50-2157) and volume 345 mm3 (21-7980). MLD 23 mm, PMR 7.6%, RR 3.6%, CMR 1.6%, and CR 5.8%. With a mean follow-up of 118 months, oncological outcomes were: OS 93.7%, DFS 82.3%, LR 4.4%. In conclusion, our analysis confirmed level II OPS reliability even for longer follow-up timing and in difficult situations as multifocal disease or after NACT.

No abstract available

No abstract available

No abstract available