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Background and Objectives: The association between endometriosis and breast cancer still remains controversial. The aim of this study was to investigate the different subtypes of breast cancer, immunohistochemical markers, hormone receptors, and ki67 proliferation indexes in patients with and without endometriosis and/or adenomyosis. Materials and Methods: All patients with endometriosis and breast cancer were enrolled. Women with endometriosis and breast cancer (Group BC+EN+) were compared to patients with breast cancer without endometriosis (group BC+EN-) and those with endometriosis without breast cancer (group BC-EN+). General population characteristics and histological and immunohistochemical subtypes of breast cancer were compared between groups. Results: Our study included 41 cases affected by both endometriosis and/or adenomyosis and breast cancer (Group BC+EN+) that were matched (1:2) with 82 patients affected only by breast cancer (group BC+EN-) and 82 patients affected only by endometriosis and/or adenomyosis (group BC-EN+). Group BC+EN+ presented a higher percentage of ER receptor expression (83% vs. 70%, p = 0.02), as well as lower values of Ki 67% (15% vs. 24%, p < 0.0001) and HER2+ (9.8% vs. 28%, p = 0.022). These findings were more evident when comparing patients with premenopausal status, while in postmenopausal patients, this difference was no longer significant. Regarding endometriosis, no statistical differences were observed in type or specific localization of the disease among the groups with and without breast cancer. Conclusions: Patients with endometriosis presented lower aggressive breast cancer rates with higher values of ER% and lower values of Ki 67 and HER2neu+. The type and severity of endometriotic diseases seemed not to influence breast cancer occurrence.
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Neoplasias da Mama , Endometriose , Humanos , Feminino , Endometriose/complicações , Neoplasias da Mama/complicações , Pessoa de Meia-Idade , Adulto , Antígeno Ki-67/análise , Adenomiose/complicações , Receptores de Estrogênio/análise , Receptor ErbB-2/análise , Imuno-Histoquímica , Receptores de Progesterona/análise , Receptores de Progesterona/metabolismo , IdosoRESUMO
Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) and Breast Implant-Associated Squamous Cell Carcinoma (BIA-SCC) are emerging neoplastic complications related to breast implants. While BIA-ALCL is often linked to macrotextured implants, current evidence does not suggest an implant-type association for BIA-SCC. Chronic inflammation and genetics have been hypothesized as key pathogenetic players, although for both conditions, the exact mechanisms and specific risks related to breast implants are yet to be established. While the genetic alterations in BIA-SCC are still unknown, JAK-STAT pathway activation has been outlined as a dominant signature of BIA-ALCL. Recent genetic investigation has uncovered various molecular players, including MEK-ERK, PI3K/AKT, CDK4-6, and PDL1. The clinical presentation of BIA-ALCL and BIA-SCC overlaps, including most commonly late seroma and breast swelling, warranting ultrasound and cytological examinations, which are the first recommended steps as part of the diagnostic work-up. While the role of mammography is still limited, MRI and CT-PET are recommended according to the clinical presentation and for disease staging. To date, the mainstay of treatment for BIA-ALCL and BIA-SCC is implant removal with en-bloc capsulectomy. Chemotherapy and radiation therapy have also been used for advanced-stage BIA-ALCL and BIA-SCC. In-depth characterization of the tumor genetics is key for the development of novel therapeutic strategies, especially for advanced stage BIA-ALCL and BIA-SCC, which show a more aggressive course and poor prognosis.
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Implantes de Mama , Neoplasias da Mama , Carcinoma de Células Escamosas , Linfoma Anaplásico de Células Grandes , Mutação , Humanos , Neoplasias da Mama/genética , Feminino , Implantes de Mama/efeitos adversos , Linfoma Anaplásico de Células Grandes/etiologia , Linfoma Anaplásico de Células Grandes/genética , Linfoma Anaplásico de Células Grandes/diagnóstico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/diagnósticoRESUMO
Immune checkpoint inhibitors (ICIs) have a modest clinical activity when administered as monotherapy against breast cancer (BC), the most common malignancy in women. Novel combinatorial strategies are currently being investigated to overcome resistance to ICIs and promote antitumor immune responses in a greater proportion of BC patients. Recent studies have shown that the BC abnormal vasculature is associated with immune suppression in patients, and hampers both drug delivery and immune effector cell trafficking to tumor nests. Thus, strategies directed at normalizing (i.e., at remodeling and stabilizing) the immature, abnormal tumor vessels are receiving much attention. In particular, the combination of ICIs with tumor vessel normalizing agents is thought to hold great promise for the treatment of BC patients. Indeed, a compelling body of evidence indicates that the addition of low doses of antiangiogenic drugs to ICIs substantially improves antitumor immunity. In this review, we outline the impact that the reciprocal interactions occurring between tumor angiogenesis and immune cells have on the immune evasion and clinical progression of BC. In addition, we overview preclinical and clinical studies that are presently evaluating the therapeutic effectiveness of combining ICIs with antiangiogenic drugs in BC patients.
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Neoplasias da Mama , Neoplasias , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Inibidores da Angiogênese/uso terapêutico , Imunoterapia , Microambiente TumoralRESUMO
Despite the screening program, breast cancer is the commonest cause of cancer death in women in the industrialized world. In this study, we investigate the correlation among poorly differentiated carcinoma, epithelial to mesenchymal transition (EMT) phenomenon, and expression of NF-kB, Sonic Hedgehog (SHH), K-RAS, and PTX3 in breast cancer in 100 breast biopsies. Samples were classified as follows: 30 benign lesions (BL), 30 ductal infiltrating carcinomas low grade (MLG1), and 40 ductal infiltrating carcinomas high grade (MLG3). Expression of vimentin, CD44, ß-catenin, NF-kB, SHH, K-RAS, CD44, and PTX3 was studied by immunohistochemistry. The different rate of cells with vimentin, nuclear ß-catenin, and CD44 expression in MLG3 as compared with MLG1 and BL suggested that the process of de-differentiation of breast cancer cells could be related to the EMT. Our results showed a significant increase in NF-kB signal in MLG3 (2.33 ± 0.77) with respect to MLG1 (1.26 ± 0.55) and BL (0.86 ± 0.52). SHH expression appeared low in BL (1.00 ± 0.41) and homogenously widespread in MLG1 (1.23 ± 0.63) and MLG3 (1.56 ± 0.54). An important increase in K-RAS signal was observed in MLG3 compared to that in BL (2.20 ± 0.69 vs 0.82 ± 0.59). As regards PTX3, we observed a strong expression in MLG3 (2.00 ± 0.78) with respect to BL (0.58 ± 0.55) and MLG1 (1.53 ± 0.76). The recurring expression of NF-kB, SHH, K-RAS, and PTX3 in vimentin- and CD44-positive breast cancer cells allows to speculate that breast cells acquire the ability to express these molecules in concomitance to EMT phenomenon.
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Biomarcadores Tumorais/biossíntese , Neoplasias da Mama/genética , Proteína C-Reativa/biossíntese , Proteínas Hedgehog/biossíntese , Proteínas Proto-Oncogênicas p21(ras)/biossíntese , Componente Amiloide P Sérico/biossíntese , Biomarcadores Tumorais/genética , Neoplasias da Mama/patologia , Proteína C-Reativa/genética , Caderinas/biossíntese , Caderinas/genética , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Proteínas Hedgehog/genética , Humanos , Receptores de Hialuronatos/biossíntese , Receptores de Hialuronatos/genética , NF-kappa B/biossíntese , NF-kappa B/genética , Prognóstico , Proteínas Proto-Oncogênicas p21(ras)/genética , Componente Amiloide P Sérico/genética , Vimentina/biossíntese , Vimentina/genéticaRESUMO
Aim: The main challenge during breast-conserving surgery (BCS) is to obtain clear margins, especially in patients with ductal carcinoma in situ (DCIS) due to the absence of well-defined nodules. Many surgical approaches have been used in an attempt to reduce the positive margin rate. The aim of this retrospective study is to compare the cavity shave margin technique with standard surgery and the intraoperative evaluation of surgical margins. Methods: This is a single-center retrospective study analyzing margin status, need for re-excision, and surgical time in a cohort of 227 patients who underwent surgery from September 2016 to September 2022. Results: In patients subjected to cavity shaving, we reported a significant reduction in positive margins of 17.1% versus 28.7% (p-value = 0.042). Also, a difference in terms of surgical re-excision was reported as p-value = 0.039 (12.4% versus 23.8%, respectively, for the cavity shave and control group). In the multivariate analysis, intraoperative evaluation of the margins was a risk factor for margins re-excision (Wald = 4.315, p = 0.038, OR: 2.331 [95% CI: 1.049-5.180]). Surgical time was lower in patients subjected to cavity shaves (p = 0.024), and the relative mean time was 68.4 min ± 37.1 min in the cavity shave group versus 93.9 min ± 40.6 min in the control group. Conclusion: The cavity shave margin technique in conserving breast surgery results in a reduction in positive margin rate, surgical re-excision, and operative time.
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The current surgical guidelines recommend an optimal margin width of 2 mm for the management of patients diagnosed with ductal carcinoma in situ (DCIS). However, there are still many controversies regarding re-excision when the optimal margin criteria are not met in the first resection. The purpose of this study is to understand the importance of surgical margin width, re-excision, and treatments to avoid additional surgery on locoregional recurrence (LRR). The study is retrospective and analyzed surgical margins, adjuvant treatments, re-excision, and LRR in patients with DCIS who underwent breast-conserving surgery (BCS). A total of 197 patients were enrolled. Re-operation for a close margin rate was 13.5%, and the 3-year recurrence was 7.6%. No difference in the LRR was reported among the patients subjected to BCS regardless of the margin width (p = 0.295). The recurrence rate according to margin status was not significant (p = 0.484). Approximately 36.9% (n: 79) patients had resection margins < 2 mm. A sub-analysis of patients with margins < 2 mm showed no difference in the recurrence between the patients treated with a second surgery and those treated with radiation (p = 0.091). The recurrence rate according to margin status in patients with margins < 2 mm was not significant (p = 0.161). The margin was not a predictive factor of LRR p = 0.999. Surgical re-excision should be avoided in patients with a focally positive margin and no evidence of the disease at post-surgical imaging.
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BACKGROUND/AIM: Ductal carcinoma in situ is considered a local disease with no metastatic potential, thus sentinel lymph node biopsy (SLNB) may be deemed an overtreatment. SLNB should be reserved for patients with invasive cancer, even though the risk of upstaging rises to 25 %. We aimed to identify clinicopathological predictors of post-operative upstaging in invasive carcinoma. METHODS: We retrospectively analyzed patients with a pre-operative diagnosis of DCIS subjected to breast surgery between January 2017 to December 2021, and evaluated at the Breast Unit of PTV (Policlinico Tor Vergata, Rome). RESULTS: Out of 267 patients diagnosed with DCIS, 33(12.4 %) received a diagnosis upstaging and 9(3.37 %) patients presented with sentinel lymph node (SLN) metastasis. In multivariate analysis, grade 3 tumor (OR 1.9; 95 % CI 1.2-5.6), dense nodule at mammography (OR 1.3; 95 % CI 1.1-2.6) and presence of a solid nodule at ultrasonography (OR 1.5; 95 % CI 1.2-2.6) were independent upstaging predictors. Differently, the independent predictors for SLNB metastasis were: upstaging (OR 2.1.; 95 % CI 1.2-4.6; p = 0.0079) and age between 40 and 60yrs (OR 1.4; 95 % CI 1.4-2.7; p = 0.027). All 9 patients with SLN metastasis received a diagnosis upstaging and were aged between 40 and 60 years old. CONCLUSION: We identified pre-operative independent predictors of upstaging to invasive ductal carcinoma. The combined use of different predictors in an algorithm for surgical treatments of DCIS could reduce the numbers of unnecessary SLNB.
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Algoritmos , Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Intraductal não Infiltrante , Metástase Linfática , Humanos , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Estudos Retrospectivos , Pessoa de Meia-Idade , Carcinoma Intraductal não Infiltrante/cirurgia , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/secundário , Carcinoma Ductal de Mama/cirurgia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/secundário , Adulto , Idoso , Biópsia de Linfonodo Sentinela/métodos , Prognóstico , Seguimentos , Mamografia , Mastectomia , Estadiamento de NeoplasiasRESUMO
Background: The SOUND study demonstrated that an axillary de-escalation may be sufficient in locoregional and distant disease control in selected early breast cancer (EBC) patients. To establish any preoperative variables that may drive sentinel lymph node biopsy (SLNB) omission, a study named sentinel omission risk factor (SOFT) 1.23 was planned. Methods: A single-center retrospective study from a prospectively maintained database was designed, aiming at underlying preoperative prognostic factors involved in sentinel lymph node (SLN) metastasis (lymph node involvement (LN+) vs. negative lymph node (LN-) group). Secondary outcomes included surgical room occupancy analysis for SLNB in patients fulfilling the SOUND study inclusion criteria. The institutional ethical committee Area Territoriale Lazio 2 approved the study (n° 122/23). Results: Between 1 January 2022 and 30 June 2023, 160 patients were included in the study and 26 (%) were included in the LN+ group. Multifocality, higher cT stage, and larger tumor diameter were reported in the LN+ group (p = 0.020, p = 0.014, and 0.016, respectively). Tumor biology, including estrogen and progesterone receptors, and molecular subtypes showed association with the LN+ group (p < 0.001; p = 0.001; and p = 0.001, respectively). A total of 117 (73.6%) patients were eligible for the SOUND study and the potential operating room time saved was 2696.81 min. Conclusions: De-escalating strategies may rationalize healthcare activities. Multifactorial risk stratification may further refine the selection of patients who could benefit from SLNB omission.
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Axila , Neoplasias da Mama , Biópsia de Linfonodo Sentinela , Humanos , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Biópsia de Linfonodo Sentinela/métodos , Idoso , Metástase Linfática , AdultoRESUMO
BACKGROUND/AIM: In the context of surgical de-escalation in early breast cancer (EBC), this study aimed to evaluate the contrast enhancement ultrasound (CEUS) sentinel lymph node (SLN) procedure as a non-invasive axillary staging procedure in EBC in comparison with standard SLN biopsy (SLNB). PATIENTS AND METHODS: A subanalysis of the AX-CES study, a prospective single-arm, monocentric phase 3 study was performed (EudraCT: 2020-000393-20). The study included patients with EBC undergoing upfront surgery and SLN resection, with no prior history of locoregional treatment, and weighing between 40-85 kg. All patients underwent the CEUS SLN procedure as a non-invasive axillary staging procedure, with CEUS SLN accumulation marked using blue dye. After the CEUS SLN procedure, all patients underwent the standard mapping procedure. Data on success rate, systemic reactions, mean procedure time, mean surgical procedure, mean procedure without axillary staging, CEUS SLN appearance (normal/pathological), SLN number, and concordance with standard mapping procedure were collected. RESULTS: After the CEUS SLN procedure, 29 LNs among 16 patients were identified and marked. In all cases, CEUS SLN revealed at least one LN enhancement. Six (37.50%) LNs were defined as pathological after the CEUS SLN procedure. Definitive staining of CEUS SLN pathology revealed metastatic involvement in four (66.67%) of the cases. Two SLNs were identified during the CEUS SLN procedure; however, owing to the low disease burden, no change in the surgical plan was reported. CONCLUSION: The CEUS SLN procedure shows promise as a technique for non-invasive assessment of the axilla, potentially enabling safe axillary de-escalation in EBC by estimating the axillary disease burden.
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Axila , Neoplasias da Mama , Meios de Contraste , Estadiamento de Neoplasias , Biópsia de Linfonodo Sentinela , Hexafluoreto de Enxofre , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Feminino , Meios de Contraste/administração & dosagem , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , Biópsia de Linfonodo Sentinela/métodos , Hexafluoreto de Enxofre/administração & dosagem , Ultrassonografia/métodos , Microbolhas , Metástase Linfática/diagnóstico por imagem , Linfonodo Sentinela/patologia , Linfonodo Sentinela/diagnóstico por imagem , Linfonodo Sentinela/cirurgia , AdultoRESUMO
Background: Resection of additional tissue circumferentially around the cavity left by lumpectomy (cavity shave) was suggested to reduce rates of positive margins and re-excision. Methods: A single center retrospective study which analyzed margins status, re-excision, and surgical time in patients who underwent breast conserving surgery and cavity shave or intraoperative evaluation of resection margins. Results: Between 2021 and 2023, 594 patients were enrolled in the study. In patients subjected to cavity shave, a significant reduction in positive, focally positive, or closer margins was reported 8.9% vs. 18.5% (p = 0.003). No difference was reported in terms of surgical re-excision (p < 0.846) (5% vs. 5.5%). Surgical time was lower in patients subjected to cavity shave (<0.001). The multivariate analysis intraoperative evaluation of sentinel lymph node OR 1.816 and cavity shave OR 2.909 were predictive factors for a shorter surgical time. Excluding patients subjected to intraoperative evaluation of sentinel lymph node and patients with ductal carcinoma in situ, patients that underwent the cavity shave presented a reduced surgical time (67.9 + 3.8 min vs. 81.6 + 2.8 min) (p = 0.006). Conclusions: Cavity shaving after lumpectomy reduced the rate of positive margins and it was associated with a significant reduction in surgical time compared to intraoperative evaluation of resection margins.
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Carcinoma Intraductal não Infiltrante , Margens de Excisão , Mastectomia Segmentar , Humanos , Carcinoma Intraductal não Infiltrante/cirurgia , Linfadenopatia , Duração da Cirurgia , Estudos RetrospectivosRESUMO
BACKGROUND: The identification of women at high risk of breast cancer (BC) is crucial for personalized screening strategies. Pathogenic and likely pathogenic variants (PVs/LPVs) in susceptibility risk genes explain part of the individual risk. Moreover, a polygenic background, summarized as a polygenic risk score (PRS), contributes to the risk of BC and may modify the individual risk in carrier and non-carrier members of BC families. METHODS: We performed a retrospective pilot study evaluating PRS in women from a subset of high- (BRCA1 and BRCA2) and moderate-risk (PALB2 and ATM) BC families. We included PVs/LPVs carriers and non-carriers and evaluated a PRS based on 577,113 BC-associated variants. Using BOADICEA, we calculated the adjusted lifetime BC risk. RESULTS: Our data showed that in BRCA1/BRCA2 carriers, PVs have a major role in stratifying the lifetime risk, while PRS improves risk estimation in non-carriers of these families. A different scenario may be observed in PALB2 and ATM families where PRS combined with PV/LPV carrier status gives a more informative lifetime risk. CONCLUSIONS: This study showed that in BC families, the PRS might help to quantify the weight of the genetic familial background, improving the individual risk stratification and contributing to personalized clinical management for carrier and non-carrier women.
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Background: Improving prognosis of BC patients has drawn the attention of health care professionals on disease related long-term side effects and on the multiple treatments BC patients must undergo. Despite advances in procedures, surgery still has multiple detrimental effects, including pain, edema, and limited mobility. For this reason, fostering adapted physical activity (APA) and healthy lifestyle (including a balanced diet and weight management) should become an everyday purpose of healthcare professionals. Fencing may be a well-suited activity to counteract fatigue, pain, and limited arm mobility. Method and analysis: The FENICE study is a mono-center, randomized clinical trial targeting women with BC stages I-III within four weeks from BC surgery. Participants in the control arm will receive the usual recommendations based on the good clinical practice guidelines. In the study arm, participants will be treated with the usual clinical and therapeutic recommendations together with APA and correct lifestyle suggestions. Objective: The primary objective of the study is to compare whether implementation of APA and healthy lifestyle in BC patient after surgery will result in an overall improvement of physical and mental status. Conclusion: Fencing and its early application in postoperative period may represent a feasible strategy to be implemented in the rehabilitation journey of BC patients. Ethics and dissemination: The study protocol FENICE has been approved by an Italian Ethics Committee on May 2023 (R.S 100.23 5th May 2023).
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Climate change is a global issue that has had significant impacts on public health and healthcare policy worldwide. The direct impact of climate change on healthcare has been associated with extreme weather events, resulting in a higher demand for disaster management resources and reduced healthcare access. Moreover, the increase of zoonotic spillover effects has increased the risk of transmission of different diseases, including COVID-19. The healthcare industry alone is responsible for 4.4% of greenhouse gas global emissions. The surgical theatre is a resource-intense healthcare activity and a major carbon emitter, thus surgical processes require rethinking. This article proposes the introduction of environmental-related outcome measures in clinical trials, which will associate highest clinical standards to a reduced impact of care on climate change. Breast cancer care may represent a model disease for the implementation of evidence-based protocols, such as Green Breast Surgery, aiming to optimize the carbon footprint of care without affecting oncological and non-oncological outcomes. Physicians and healthcare workers worldwide should be aware of the importance of addressing environmental issues in healthcare policy, implementing programs to reduce their carbon footprint, and contributing to a more sustainable future.
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Neoplasias da Mama , COVID-19 , Humanos , Feminino , Pegada de Carbono , Mudança Climática , Neoplasias da Mama/cirurgia , Medidas de Resultados Relatados pelo PacienteRESUMO
BACKGROUND/AIM: Breast cancer (BC) is the most prevalent oncological diagnosis worldwide. Molecular subtyping has provided valuable insights for treatment decisions, but challenges remain in adjuvant treatment for hormone receptor (HR)-positive/HER2-negative luminal BC (LBC). Multigene markers like Oncotype DX have emerged to provide more precise prognostic information. This study aimed to evaluate the influence of gene expression panels on fear of cancer recurrence (FCR), quality of life (QoL), and healthcare-related greenhouse emissions. PATIENTS AND METHODS: A monocentric retrospective analysis was conducted using a prospective database of patients undergoing Oncotype DX. QoL assessments were performed using the Short Breast Health Perception Questionnaire (BHPQ) and Life Satisfaction Questionnaire (LSQ-32). Reductions in hospital visits and travel distance were analyzed. RESULTS: Twenty-eight patients underwent Oncotype DX testing. Of these, 17.85% received adjuvant chemotherapy based on the recurrence score (RS). The implementation of Oncotype DX resulted in a significant reduction in hospital visits, travel distance, and healthcare-related greenhouse gas emissions. QoL assessments using BHPQ and LSQ-32 showed lower levels of FCR and improved QoL in various domains for patients who received hormone therapy (HT) alone. CONCLUSION: The implementation of Oncotype DX in clinical practice has the potential to reduce overtreatment, decrease healthcare-related greenhouse gas emissions, and improve QoL. Lower levels of FCR and improved QoL were observed in patients who received HT-only based on the RS score.
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Neoplasias da Mama , Gases de Efeito Estufa , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Qualidade de Vida , Estudos Retrospectivos , Gases de Efeito Estufa/análise , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/tratamento farmacológico , Receptores de Estrogênio/metabolismo , Prognóstico , Perfilação da Expressão Gênica/métodos , Fatores Socioeconômicos , HormôniosRESUMO
Here, we present the case of a 47-year-old woman diagnosed with luminal B breast cancer subtype and provide an in-depth analysis of her gene mutations, chromosomal alterations, mRNA and protein expression changes. We found a point mutation in the FGFR2 gene, which is potentially hyper-activating the receptor function, along with over-expression of its ligand FGF20 due to genomic amplification. The patient also harbors somatic and germline mutations in some mismatch repair (MMR) genes, with a strong MMR mutational signature. The patient displays high microsatellite instability (MSI) and tumor mutational burden (TMB) status and increased levels of CTLA-4 and PD-1 expression. Altogether, these data strongly implicate that aberrant FGFR signaling, and defective MMR system might be involved in the development of this breast tumor. In addition, high MSI and TMB in the context of CTLA-4 and PD-L1 positivity, suggest the potential benefit of immune checkpoint inhibitors. Accurate characterization of molecular subtypes, based on gene mutational and expression profiling analyses, will be certainly helpful for individualized treatment and targeted therapy of breast cancer patients, especially for those subtypes with adverse outcome.
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Triple-negative breast cancer (TNBC) is the most aggressive subtype of mammary carcinoma. Here, we describe a case of an 81-year-old female diagnosed with ductal triple negative breast cancer with a germline pathogenic variant in BReast CAncer gene2 (BRCA2). Genetic testing also revealed the presence of four somatic mutations in the ephrin type-A receptor 3 (EphA3), TP53, BRCA1-associated protein (BAP1), and MYB genes. The BRCA2, TP53, and BAP1 gene mutations are highly predictive of a defective homologous recombination repair system and subsequent chromosomal instability in this patient. Coherently, the patient displayed a strong homologous recombination deficiency signature and high tumor mutational burden status, which are generally associated with increased probability of immune neoantigens formation and presentation, and with tumor immunogenicity. Analysis of immune checkpoint revealed high expression of programmed cell death ligand 1 (PD-L1), programmed cell death ligand 2 (PD-L2), programmed death 1 (PD1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA 4), suggesting that the patient might likely benefit from immunotherapies. Altogether, these findings support an unveiled link between BRCA2 inactivation, HR deficiency and increased expression of immune checkpoints in TNBC. This clinical case highlights the importance of screening TNBC patients for genetic mutations and TMB biomarkers in order to predict the potential efficacy of immunotherapy.
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BACKGROUND/AIM: Sentinel lymph node (SLN) procedures have gained popularity in early breast cancer thanks to the reduction of surgical side-effects. The standard SLN mapping procedure uses 99mTc-nanocolloid human serum albumin with/without blue dye; limitations include logistical challenges and adverse reactions. Recently, contrast-enhanced ultrasound (CEUS) using sulfur hexafluoride has emerged as a promising technique for SLN mapping. Our study aimed to compare the CEUS technique with the standard isotope method. MATERIALS AND METHODS: AX-CES, a prospective, monocentric, single-arm phase-3 study was designed (EudraCT: 2020-000393-20). Inclusion criteria were histologically diagnosed early breast cancer eligible for upfront surgery and SLN resection, bodyweight 40-85 kg, and no prior history of ipsilateral surgery or radiotherapy. All patients underwent CEUS prior to surgery and blue dye injection was performed in areas with contrast accumulation. After the experimental procedure, all patients underwent the standard mapping procedure and SLN frozen section assessment was performed. Data on the success rate, systemic reactions, mean procedure time, CEUS appearance, SLN number, and concordance with standard mapping procedure were collected. RESULTS: Among 16 cases, a median of two SLNs were identified during CEUS. In all cases, at least one SLN was identified by CEUS (100%). In six cases, SLNs were classified during CEUS as abnormal, which was confirmed by definitive staining in four cases. After the standard mapping technique, in 15 out of the 16 cases (87.50%), at least one SLN from the standard mapping procedure was marked with blue dye in the CEUS procedure. In our series, sensitivity and specificity of SLN detection by CEUS were 75% and 100%, respectively. CONCLUSION: CEUS is a safe and manageable intraoperative procedure. When compared with standard techniques, US appearance during CEUS may provide additional information when associated with histological assessment.
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Neoplasias da Mama , Linfonodo Sentinela , Feminino , Humanos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Meios de Contraste , Linfonodos/diagnóstico por imagem , Linfonodos/cirurgia , Linfonodos/patologia , Microbolhas , Estudos Prospectivos , Linfonodo Sentinela/diagnóstico por imagem , Linfonodo Sentinela/cirurgia , Linfonodo Sentinela/patologia , Biópsia de Linfonodo Sentinela/métodos , Hexafluoreto de EnxofreRESUMO
BACKGROUND/AIM: Despite an aging population, there is no consensus regarding ductal carcinoma in situ (DCIS) treatment for elderly women. Breast surgery can be well tolerated even in elderly patients. The aim of this study is to evaluate the surgical management of DCIS in elderly patients. PATIENTS AND METHODS: We retrospectively analyzed patients with DCIS from 2016 to 2022 at our Breast Unit and divided our population according to age. RESULTS: Out of 231 patients with DCIS, 45 (19.5%) were elderly. The Charlson comorbidity index and American Society of Anesthesiology (ASA) score was significantly higher in the elderly (p<0.001 for both). Among the elderly, 10 (22.2%) patients received upstaging diagnoses, versus 18 (9.7%) in the control (p=0.048). Twelve (26.7%) of the elderly patients underwent sentinel lymph node biopsy, versus 93 (50%) in the control group (p=0.005). No difference was reported between groups in terms of breast conserving surgeries performed. A higher incidence of surgeries performed using local anesthesia was reported in the elderly group (p=0.041). Thirty-day surgical complications, according to Clavien-Dindo, did not show significant differences. CONCLUSION: Despite higher comorbidity and ASA score, breast surgery is safe and feasible in elderly patients. Due to the higher risk of upstaging to invasive ductal carcinoma, surgery should be performed but sentinel lymph node biopsy should be omitted, owing to the low risk of lymph node metastasis and lower use of adjuvant treatments.
Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Intraductal não Infiltrante , Humanos , Feminino , Idoso , Carcinoma Intraductal não Infiltrante/cirurgia , Carcinoma Intraductal não Infiltrante/patologia , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela , Metástase Linfática , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/patologiaRESUMO
BACKGROUND/AIM: Among postoperative complications in breast surgery, postoperative hematoma is the most common occurrence. While mostly self-limited, in some cases surgical revision is mandatory. Among percutaneous procedures, preliminary studies demonstrated the efficacy of vacuum-assisted breast biopsy (VAB) in evacuating postprocedural breast hematomas. However, no data are available regarding VAB evacuating postoperative breast hematomas. Therefore, the present study aimed to investigate the efficacy of the VAB system in evacuating postoperative and postprocedural hematoma, symptom resolution, and avoidance of surgery. PATIENTS AND METHODS: From January 2016 to January 2020, patients with ≥25 mm symptomatic breast hematomas developed after breast-conserving surgery (BCS) and percutaneous procedures were retrospectively enrolled from a perspective-maintained database. Hematoma maximum diameter, estimated hematoma volume, total procedure time, and visual analog scale (VAS) score before ultrasound (US) vacuum-assisted evacuation (VAEv) were recorded. At one-week VAS score, residual hematoma volume, and complications were recorded. RESULTS: Among 932 BCSs and 618 VAB procedures, a total of 15 late postoperative hematomas were recorded (9 after BCS and 6 after VAB). Preoperative median diameter was 43.00 (35.50-52.50) mm and median volume 12.60 (7.35-18.30) mm3 Regarding VAEv, median time recorded was 25.92 (21.89-36.81) min. At one week, the median hematoma reduction was 83.00% (78.00%-87.5%) with a statistically significant VAS reduction (5.00 vs. 2.00; p>0.001). No surgical treatment was needed and only one case of seroma occurred. CONCLUSION: VAEv represents a promising safe, time and resource-sparing treatment modality for the evacuation of breast hematomas, potentially decreasing the rate of reoperation after surgery.
Assuntos
Neoplasias da Mama , Mama , Humanos , Feminino , Estudos Retrospectivos , Mama/patologia , Biópsia por Agulha/métodos , Hematoma/etiologia , Hematoma/cirurgia , Biópsia Guiada por Imagem/métodos , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologiaRESUMO
BACKGROUND/AIM: Awake surgery has become a valid alternative to general anesthesia in many surgery fields. This technique played a very important role during the COVID-19 period. The growing use of this technique has many advantages. We performed a systematic review to study the potentialities of awake breast surgery. MATERIALS AND METHODS: We searched Pubmed, Embase, and Cochrane library database and retrieved a total of 109 records. Forty-nine of them were excluded as unsuitable. Finally, we selected a total of 12 records concerning different types of studies for topic appropriateness. Three reviewers reviewed independently each record. RESULTS: Five articles analyzing the sustainability of awake surgery during the COVID-19 period were selected. In addition, one article analyzing the impact on the immune system and six articles and eight case reports analyzing anesthetic techniques were also selected. The studies analyzing awake breast surgery during the COVID-19 period showed advantages in terms of sustainability and length of hospitalization. The study analyzing the immune response after awake breast surgery showed lesser lymphocyte response than the general anesthesia group. The studies analyzing anesthetic techniques in awake breast surgery showed that the nerve blocks allow good level of safety and postoperative pain control. CONCLUSION: The awake breast surgery and fast track implementation shortened hospital stays and reduced costs, without influencing the surgical results. Furthermore, awake breast surgery reduced surgical stress compared to general anesthesia. Among the various anesthetic techniques, nerve blocks are the most advantageous in terms of safety and efficacy compared to epidural anesthesia.