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PURPOSE: Data from recently trials have provided practice-changing recommendations in management of the axilla in early breast cancer (eBC). However, further controversies have been raised, resulting in heterogeneous diffusion of these recommendations. Our purpose was to obtain a better homogeneity. MATERIAL AND METHODS: In 2021, the Tuscan Breast Network (TBN) established a consensus with the aim to update recommendations in this area. We performed a literature review on axillary management in eBC patients which led to an expert Delphi consensus aiming to explore the gray areas, build consensus and propose evidence-based suggestions for an appropriate management. Thereafter, we investigate their implementation in clinical practice. RESULTS: (1) DCIS patients should have SLN biopsy only in case of mastectomy or in conservative surgery if tumor is in a location that would preclude future nodal sampling or in case of a mass; (2) ALND may be omitted for 1-2 positive SLN patients undergoing BCS in T1-2 tumors with 1-2 SLN positive, eligible for whole-breast irradiation and adjuvant systemic therapies; (3) consider the option of RNI in patients with 1-3 positive lymph nodes and one or more high-risk characteristics; (4) the population identified in 2) should NOT undergo lymph node irradiation as an alternative to axillary surgery and (5) patients with clinically (pre-operatively) positive axilla, or undergoing primary systemic therapy, or outside the criteria reported in 2) must receive additional ALND and/or RT as per local policy. CONCLUSION: This consensus provided a practical tool to stimulate local and national breast surgical and radiotherapy protocols.
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Axila , Neoplasias da Mama , Técnica Delphi , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Feminino , Biópsia de Linfonodo Sentinela , Itália , Excisão de Linfonodo , Consenso , Metástase Linfática , MastectomiaAssuntos
Neoplasias da Mama , Mamoplastia , Cirurgia Plástica , Humanos , Feminino , Neoplasias da Mama/cirurgia , Mama , Itália , Mastectomia SegmentarRESUMO
Background: Systemic inflammatory markers draw great interest as potential blood-based prognostic factors in several oncological settings. Objectives: The aim of this study is to evaluate whether neutrophil-to-lymphocyte ratio (NLR) and pan-immune-inflammation value (PIV) predict nodal pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in node-positive (cN+) breast cancer (BC) patients. Design: Clinically, cN+ BC patients undergoing NAC followed by breast and axillary surgery were enrolled in a multicentric study from 11 Breast Units. Methods: Pretreatment blood counts were collected for the analysis and used to calculate NLR and PIV. Logistic regression analyses were performed to evaluate independent predictors of nodal pCR. Results: A total of 1274 cN+ BC patients were included. Nodal pCR was achieved in 586 (46%) patients. At multivariate analysis, low NLR [odds ratio (OR) = 0.71; 95% CI, 0.51-0.98; p = 0.04] and low PIV (OR = 0.63; 95% CI, 0.44-0.90; p = 0.01) were independently predictive of increased likelihood of nodal pCR. A sub-analysis on cN1 patients (n = 1075) confirmed the statistical significance of these variables. PIV was significantly associated with axillary pCR in estrogen receptor (ER)-/human epidermal growth factor receptor 2 (HER2)+ (OR = 0.31; 95% CI, 0.12-0.83; p = 0.02) and ER-/HER2- (OR = 0.41; 95% CI, 0.17-0.97; p = 0.04) BC patients. Conclusion: This study found that low NLR and PIV levels predict axillary pCR in patients with BC undergoing NAC. Registration: Eudract number NCT05798806.
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INTRODUCTION: The constant improvement of the diagnostic process and the crescent efficacy of treatment options for Breast Cancer have led to an increase in the survival rate of patients. Thereby, it has become fundamental for Breast Care Units to deal with short-, medium-, and long-term sequelae of the disease and its treatment. Among these, changes in posture seem to have a crucial role. This review aims to collect and summarize the current knowledge on postural disorders in Breast Cancer Survivors, focusing on evaluation methods and rehabilitation protocols. EVIDENCE ACQUISITION: A systematic research was conducted on PubMed, Scopus and World of Science databases, considering all the studies published up to 2021. Case reports, case series, cross-sectional, retrospective and prospective studies were included. Narrative and Systematic reviews were excluded. EVIDENCE SYNTHESIS: After applying the eligibility criteria and bibliographic expansion, 55 articles were selected. Forty-four studies focused on the analysis and the quantification of postural abnormalities, showing a huge variability in population characteristics, valuative methods and outcome measures. Most of them are cross-sectional studies. Rehabilitation treatments have been considered in only 12 studies: all the rehabilitative treatments proved to be effective but, the heterogeneity among the evaluation methods has made a comparison impossible. Hence, we designed a complete evaluation protocol for the assessment of postural abnormalities in Breast Cancer Survivors. Our protocol has been drawn following the structure of International Classification of Functioning, Disability and Health. CONCLUSIONS: Our review pointed out the crescent interest of the current Literature on analysis and treatment of postural alterations in breast cancer survivors. Since the extreme variety of outcome measures made it impossible to give a clear indication for evaluation and treatment of this disorder, we designed a complete evaluation protocol for the assessment of postural abnormalities in breast cancer survivors, with the goal of guiding the design of new clinical trials on these subjects.
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Neoplasias da Mama , Sobreviventes de Câncer , Humanos , Feminino , Neoplasias da Mama/terapia , Estudos Transversais , Estudos Prospectivos , Estudos Retrospectivos , Revisões Sistemáticas como AssuntoRESUMO
BACKGROUND: Frailty detection with comprehensive geriatric assessment (CGA) is of pivotal importance in older patients with cancer to avoid over- or under-treatment and to detect those at increased risk for poor outcomes. Several tools have been developed to capture the complexity of frailty, but only a few were explicitly conceived for older adults with cancer. The study aimed at developing and validating a multidimensional, easy-to-use diagnostic tool for early-risk stratification in patients with cancer, called the Multidimensional Oncological Frailty Scale (MOFS). METHODS: In this single-center prospective study, we consecutively enrolled 163 older women (age ≥ 75 years) with breast cancer, screened with a G8 score ≤ 14 during the outpatient preoperative evaluation at our breast centre, as the development cohort. Seventy patients with different types of cancer admitted to our OncoGeriatric Clinic served as the validation cohort. Using stepwise linear regression analysis, we evaluated the relationship between Multidimensional Prognostic Index (MPI) and CGA items, and, finally, realized a screening tool based on the combination of the significant variables. RESULTS: The mean age of the study population was 80.4 ± 5.8 years, while the mean age of the validation cohort was 78.6 ± 6.6 years [42 women (60%)]. A composite model of the Clinical Frailty Scale, G8, and hand grip strength test showed a strong correlation with MPI (R= -0.712, p < 0.001). The MOFS accuracy in the prediction of mortality was optimal in both the development and the validation cohorts (AUC 0.82 and 0.87; p < 0.001 and 0.003, respectively). CONCLUSION: MOFS represents a new, accurate, quick-to-use frailty screening tool for stratifying the risk of mortality in geriatric cancer patients.
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BACKGROUND: Based on the volume of tissue removed, conservative surgery (BCS) cannot always guarantee satisfactory cosmetic results, unless resorting to more complex oncoplastic approaches. Investigating an alternative to optimize aesthetic outcomes minimizing surgical complexity, was the purpose of this study. We assessed an innovative surgical procedure based on the use of a biomimetic polyurethane-based scaffold intended for regenerating soft-tissue resembling fat, in patients undergoing BCS for non-malignant breast lesions. Safety and performance of the scaffold, and safety and feasibility of the entire implant procedure were evaluated. METHODS: A volunteer sample of 15 female patients underwent lumpectomy with immediate device positioning, performing seven study visits with six-month follow-up. We evaluated incidence of adverse events (AEs), changes in breast appearance (using photographs and anthropomorphic measurements), interference with ultrasound and MRI (assessed by two independent investigators), investigator's satisfaction (through a VAS scale), patient's pain (through a VAS scale) and quality of life (QoL) (using the BREAST-Q© questionnaire). Data reported are the results of the interim analysis on the first 5 patients. RESULTS: No AEs were device related nor serious. Breast appearance was unaltered and the device did not interference with imaging. High investigator's satisfaction, minimal post-operative pain and positive impact on QoL were also detected. CONCLUSIONS: Albeit on a limited number of patients, data showed positive outcomes both in terms of safety and performance, paving the way to an innovative breast reconstructive approach with a potential remarkable impact on clinical application of tissue engineering. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04131972, October 18, 2019).
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Neoplasias da Mama , Mamoplastia , Mastectomia Segmentar , Feminino , Humanos , Biomimética , Neoplasias da Mama/cirurgia , Mamoplastia/efeitos adversos , Mamoplastia/métodos , Satisfação do Paciente , Poliuretanos , Qualidade de Vida , Mastectomia Segmentar/efeitos adversos , Alicerces Teciduais , Engenharia TecidualRESUMO
BACKGROUND: Type of axillary surgery in breast cancer (BC) patients who convert from cN + to ycN0 after neoadjuvant chemotherapy (NAC) is still debated. The aim of the present study was to develop and validate a preoperative predictive nomogram to select those patients with a low risk of residual axillary disease after NAC, in whom axillary surgery could be minimized. PATIENTS AND METHODS: 1950 clinically node-positive BC patients from 11 Breast Units, treated by NAC and subsequent surgery, were included from 2005 to 2020. Patients were divided in two groups: those who achieved nodal pCR vs. those with residual nodal disease after NAC. The cohort was divided into training and validation set with a geographic separation criterion. The outcome was to identify independent predictors of axillary pathologic complete response (pCR). RESULTS: Independent predictive factors associated to nodal pCR were axillary clinical complete response (cCR) after NAC (OR 3.11, p < 0.0001), ER-/HER2+ (OR 3.26, p < 0.0001) or ER+/HER2+ (OR 2.26, p = 0.0002) or ER-/HER2- (OR 1.89, p = 0.009) BC, breast cCR (OR 2.48, p < 0.0001), Ki67 > 14% (OR 0.52, p = 0.0005), and tumor grading G2 (OR 0.35, p = 0.002) or G3 (OR 0.29, p = 0.0003). The nomogram showed a sensitivity of 71% and a specificity of 73% (AUC 0.77, 95%CI 0.75-0.80). After external validation the accuracy of the nomogram was confirmed. CONCLUSION: The accuracy makes this freely-available, nomogram-based online tool useful to predict nodal pCR after NAC, translating the concept of tailored axillary surgery also in this setting of patients.
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Neoplasias da Mama , Terapia Neoadjuvante , Axila , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Feminino , Humanos , Linfonodos , Mastectomia , Nomogramas , Biópsia de Linfonodo SentinelaRESUMO
INTRODUCTION: Monitoring how patients feel and what they experience during the care process gives health professionals data to improve the quality of care, and gives health systems information to better design and implement care pathways. To gain new insights about specific gaps and/or strengths in breast cancer care, we measure patient-reported outcomes (PROs) and patient-reported experiences (PREs) for women receiving immediate breast reconstruction (iBR). METHODS AND ANALYSIS: Prospective, multicentre, cohort study with continuous and systematic web-based data collection from women diagnosed with breast cancer, who have an indication for iBR after mastectomy treated at any Breast Unit (BU) in Tuscany Region (Italy). Patients are classified into one of two groups under conditions of routine clinical practice, based on the type of iBR planned (implant and autologous reconstruction). Patient-reported information are obtained prior to and after surgery (at 3-month and 12-month follow-up). We estimate that there are around 700 annual eligible patients.Descriptive analyses are used to assess trends in PROs over time and differences between types of iBR in PROs and PREs. Additionally, econometric models are used to analyse patient and BU characteristics associated with outcomes and experiences. PREs are evaluated to assess aspects of integrated care along the care pathway. ETHICS AND DISSEMINATION: The study has been reviewed and obtained a nihil obstat from the Tuscan Ethics Committees of the three Area Vasta in 2017. Dissemination of results will be via periodic report, journal articles and conference presentations.
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Neoplasias da Mama , Mamoplastia , Neoplasias da Mama/cirurgia , Estudos de Coortes , Feminino , Humanos , Itália , Mastectomia , Medidas de Resultados Relatados pelo Paciente , Estudos ProspectivosRESUMO
BACKGROUND: PI3K pathway hyperactivation due to PIK3CA mutations contributes to endocrine resistance, and PIK3CA is one of the most frequently mutated genes in breast cancer (BC), occurring approximately 40 % of HR+, HER2- advanced BC (ABC). Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) have changed the treatment landscape of HR+, HER2- ABC. Putative mechanisms of resistance to CDK4/6i have been identified, but limited data are available on PI3K deregulation. The present study evaluates the impact of PIK3CA mutations on CDK4/6i plus hormone therapy and evaluates potential characteristics that may suggest for a PI3K screening in patients with ABC. METHODS: ABC patients were enrolled, and 12 mL of blood were collected in EDTA tubes at baseline prior to CDK4/6i plus hormone therapy. Plasma was separated and circulating free DNA (cfDNA) was extracted. PIK3CA mutation analysis was performed on a ddPCR. Selected and analyzed mutations included: p.C420R, p.E542 K, p.E545A, p.E545D, p.E545G, p.E545K, p.Q546E, p.Q546R, p.H1047L, p.H1047R, p.H1047Y. Statistical analysis were performed to investigate the predictive power of such mutations and any association with clinical factors. RESULTS: Thirty patients were enrolled. PIK3CA mutation status at baseline was independently associated with shorter median PFS (7.44 vs 12.9 months, p = 0.01) in subject receiving CDK4/6i plus hormone therapy. PIK3CA mutations were found to be associated to Ki67 expression in primary lesions (p = 0.006). Moreover, the probability to find a PI3K mutation improved considering also the therapeutic management in previous lines of treatment (McFadden's R2 = 0.415, p = 0.004; AUC of the ROC curve = 0.914). CONCLUSION: The findings of this pilot study suggest that the presence of a PI3K mutation in liquid biopsy correlates with a worse PFS in patients with ABC receiving CDK4/6i, and that liquid biopsy is a useful tool to suggests a better tailored pharmacological intervention.
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Antineoplásicos/uso terapêutico , Neoplasias da Mama/genética , Classe I de Fosfatidilinositol 3-Quinases/genética , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Resistencia a Medicamentos Antineoplásicos/genética , Adulto , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Feminino , Humanos , Biópsia Líquida , Pessoa de Meia-Idade , Mutação , Projetos Piloto , Intervalo Livre de Progressão , Estudos RetrospectivosRESUMO
PURPOSE: The clinical introduction of a radioactive and fluorescent hybrid tracer allowed for preoperative lymphatic mapping and intraoperative real-time fluorescence tracing of the sentinel lymph node (SLN) by a single injection. The aim of this feasibility study is to evaluate the first-in-human use of the hybrid tracer by combining indocyanine green (ICG) and radiocolloid based on Nanotop compound (99mTc Nanotop) for SLN biopsy (SLNB) in breast cancer patients. METHODS: The day before surgery, ICG-99mTc Nanotop was injected periareolarly in breast cancer patients scheduled for SLNB. Planar lymphoscintigraphic (PL) and SPECT/CT images were then acquired. An intraoperative optonuclear probe was used to detect SLN gamma and fluorescent signals. The harvested SLNs were examined by hematoxylin-eosin staining, and patients were clinically evaluated 1 month after surgery. RESULTS: Twenty-one consecutive patients were enrolled. The PL and SPECT/CT techniques identified at least 1 SLN in all patients for a preoperative sentinel detection rate of 100%. SPECT/CT revealed 3 additional lymph nodes in the same nodal basin, which had not been visualized on conventional PL (κ = 0.747; P < 0.005). All 30 preoperative SLNs were localized and excised up to 16 hours after injection. The counts measured via gamma tracing showed a very strong correlation with those measured via near-infrared fluorescent tracing (P < 0.005, r = 0.964). No adverse reactions were observed. CONCLUSIONS: The SLNB technique used with the ICG-99mTc Nanotop tracer resulted to be feasible, reliable, and safe. This hybrid compound allowed us to obtain excellent performance in terms of both preoperative lymphatic mapping and intraoperative SLN detection in breast cancer patients.
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Neoplasias da Mama/patologia , Verde de Indocianina/química , Biópsia de Linfonodo Sentinela/métodos , Tecnécio/química , Adulto , Idoso , Neoplasias da Mama/diagnóstico por imagem , Estudos de Viabilidade , Feminino , Humanos , Linfadenopatia , Metástase Linfática , Pessoa de Meia-Idade , Traçadores Radioativos , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton ÚnicoAssuntos
Neoplasias da Mama , Mama , Neoplasias da Mama/cirurgia , Drenagem , Feminino , Humanos , Mastectomia , Padrões de Prática MédicaRESUMO
The inheritance of mutated suppressor genes, such as BRCA1 and BRCA2, is acknowledged as an etiological factor in hereditary breast carcinoma (HBC). Two different molecular mechanisms are possible; the Knudson's "two hits" or the gene haploinsufficiency. Etiology of sporadic breast carcinoma (SBC) is not known, although data support the possible role of the betaretrovirus Mouse Mammary Tumor Virus (MMTV). This study analyzes the presence of MMTV exogenous sequences in two representative groups of HBC and SBC, excluding any contamination by murine and retroviral material and endogenous betaretroviruses. The 30.3% of 56 SBC contained MMTV sequences, against the 4.2% of 47 HBC (p < 0.001). Cases positive for viral sequences showed the presence of p14, signal peptide of the MMTV envelope precursor. This result was expected based on the fact that HBCs, having a specific genetic etiology, do not need the action of a carcinogenetic viral agent. Moreover, the striking results obtained by comparing two groups of vastly different tumors represent an additional element of quality control: the distinction between HBC and SBC is so well-defined that results cannot be ascribed to mere coincidence. This paper strengthens the hypothesis for a viral etiology for human sporadic breast carcinoma.
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Neoplasias da Mama/virologia , Carcinoma/virologia , Vírus do Tumor Mamário do Camundongo/genética , Adulto , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Carcinoma/genética , Carcinoma/metabolismo , Genes BRCA1 , Genes BRCA2 , Genes Supressores de Tumor , Mutação em Linhagem Germinativa , Humanos , Pessoa de Meia-Idade , Proteínas Oncogênicas/metabolismoRESUMO
PURPOSE: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) improve progression-free survival (PFS) in patients with hormone receptor-positive (HR+) advanced breast cancer. However, a better knowledge of predictive biomarkers of response and resistance to CDK4/6i is needed. Therefore, the present article addresses the role of the mRNA expression of thymidine kinase 1 (TK1), CDK4, 6 and 9 in plasma-derived exosomes and their relevance in the pharmacologic activity of CDK4/6i. METHODS: Blood samples of 40 HR+/HER2- advanced breast cancer patients were collected before (T0) the administration of palbociclib plus hormonal therapy and after 3 months (T1). RNA was isolated from exosomes and analysed for the expression of TK1, CDK 4, 6 and 9 by digital droplet PCR (ddPCR). RESULTS: A higher value of TK1 copies/ml at baseline (T0) was significantly associated with the number of previous lines of chemotherapy (p = 0.009). In patients with PD, a significant increase was observed in the number of copies/ml of TK1 (p = 0.01) and CDK9 (p = 0.03) comparing T1 vs. T0 values. No significant correlations between response to treatment and clinical parameters were found at univariate analysis. High baseline CDK4 expression was significantly correlated with longer PFS in patients treated with fulvestrant + palbociclib (low versus high: 6.45 months vs. not reached, p = 0.01). CONCLUSIONS: The present study demonstrates that, in plasma-derived exosomes, high baseline CDK4 mRNA levels are associated with response to palbociclib plus hormonal therapy, while the increase in TK1 and CDK9 mRNA copies/ml is associated with clinical resistance.
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Neoplasias da Mama/genética , Quinase 9 Dependente de Ciclina/genética , Resistencia a Medicamentos Antineoplásicos , Exossomos/genética , Timidina Quinase/genética , Regulação para Cima , Adulto , Idoso , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 4 Dependente de Ciclina/genética , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Piperazinas/uso terapêutico , Piridinas/uso terapêutico , Resultado do TratamentoRESUMO
Trastuzumab is an effective therapeutic treatment for Her2-like breast cancer; despite this most of these tumors develop resistance to therapy due to specific gene mutations or alterations in gene expression. Understanding the mechanisms of resistance to Trastuzumab could be a useful tool in order to identify combinations of drugs that elude resistance and allow a better response for the treated patients. Twelve primary biopsies of Her2+/hormone receptor negative (ER-/PgR-) breast cancer patients were selected based on the specific response to neoadjuvant therapy with Trastuzumab and their whole exome was sequenced leading to the identification of 18 informative gene mutations that discriminate patients selectively based on response to treatment. Among these genes, we focused on the study of the ANKRD44 gene to understand its role in the mechanism of resistance to Trastuzumab. The ANKRD44 gene was silenced in Her2-like breast cancer cell line (BT474), obtaining a partially Trastuzumab-resistant breast cancer cell line that constitutively activates the NF-kb protein via the TAK1/AKT pathway. Following this activation an increase in the level of glycolysis in resistant cells is promoted, also confirmed by the up-regulation of the LDHB protein and by an increased TROP2 protein expression, found generally associated with aggressive tumors. These results allow us to consider the ANKRD44 gene as a potential gene involved in Trastuzumab resistance.
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Doenças Mamárias/terapia , Celulite (Flegmão)/terapia , Síndrome de Munchausen/etiologia , Tratamento de Ferimentos com Pressão Negativa , Comportamento Autodestrutivo/etiologia , Transplante de Pele/métodos , Adulto , Doenças Mamárias/cirurgia , Celulite (Flegmão)/cirurgia , Feminino , HumanosRESUMO
In this study, we determined if BRCA1 partners involved in DNA double-strand break (DSB) and mismatch repair (MMR) may contribute to breast and ovarian cancer development. Taking advantage the functional conservation of DNA repair pathways between yeast and human, we expressed several BRCA1 missense variants in DNA repair yeast mutants to identify functional interaction between BRCA1 and DNA repair in BRCA1-induced genome instability. The pathogenic p.C61G, pA1708E, p.M775R, and p.I1766S, and the neutral pS1512I BRCA1 variants increased intra-chromosomal recombination in the DNA-repair proficient strain RSY6. In the mre11, rad50, rad51, and msh6 deletion strains, the BRCA1 variants p.C61G, pA1708E, p.M775R, p.I1766S, and pS1215I did not increase intra-chromosomal recombination suggesting that a functional DNA repair pathway is necessary for BRCA1 variants to determine genome instability. The pathogenic p.C61G and p.I1766S and the neutral p.N132K, p.Y179C, and p.N550H variants induced a significant increase of reversion in the msh2Δ strain; the neutral p.Y179C and the pathogenic p.I1766S variant induced gene reversion also, in the msh6Δ strain. These results imply a functional interaction between MMR and BRCA1 in modulating genome instability. We also performed a somatic mutational screening of MSH6, RAD50, MRE11A, and RAD51 genes in tumor samples from 34 patients and identified eight pathogenic or predicted pathogenic rare missense variants: four in MSH6, one in RAD50, one in MRE11A, and two in RAD51. Although we found no correlation between BRCA1 status and these somatic DNA repair variants, this study suggests that somatic missense variants in DNA repair genes may contribute to breast and ovarian tumor development.
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Background and objectives: Cancer stem cells (CSCs) have been implicated in tumor initiation, recurrence, metastatic spread and poor survival in multiple tumor types, breast cancers included. CSCs selectively overexpress key mitochondrial-related proteins and inhibition of mitochondrial function may represent a new potential approach for the eradication of CSCs. Because mitochondria evolved from bacteria, many classes of FDA-approved antibiotics, including doxycycline, actually target mitochondria. Our clinical pilot study aimed to determine whether short-term pre-operative treatment with oral doxycycline results in reduction of CSCs in early breast cancer patients. Methods: Doxycycline was administered orally for 14 days before surgery for a daily dose of 200 mg. Immuno-histochemical analysis of formalin-fixed paraffin-embedded (FFPE) samples from 15 patients, of which 9 were treated with doxycycline and 6 were controls (no treatment), was performed with known biomarkers of "stemness" (CD44, ALDH1), mitochondria (TOMM20), cell proliferation (Ki67, p27), apoptosis (cleaved caspase-3), and neo-angiogenesis (CD31). For each patient, the analysis was performed both on pre-operative specimens (core-biopsies) and surgical specimens. Changes from baseline to post-treatment were assessed with MedCalc 12 (unpaired t-test) and ANOVA. Results: Post-doxycycline tumor samples demonstrated a statistically significant decrease in the stemness marker CD44 (p-value < 0.005), when compared to pre-doxycycline tumor samples. More specifically, CD44 levels were reduced between 17.65 and 66.67%, in 8 out of 9 patients treated with doxycycline. In contrast, only one patient showed a rise in CD44, by 15%. Overall, this represents a positive response rate of nearly 90%. Similar results were also obtained with ALDH1, another marker of stemness. In contrast, markers of mitochondria, proliferation, apoptosis, and neo-angiogenesis, were all similar between the two groups. Conclusions: Quantitative decreases in CD44 and ALDH1 expression are consistent with pre-clinical experiments and suggest that doxycycline can selectively eradicate CSCs in breast cancer patients in vivo. Future studies (with larger numbers of patients) will be conducted to validate these promising pilot studies.
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BACKGROUND: Molecular subtypes of breast cancer have been proposed since 2012. The correlation between various baseline [18F]fluorodeoxyglucose ([18F]FDG) uptake parameters, including total lesion glycolysis (TLG), and molecular subtypes of primary breast cancer lesions in patients with invasive ductal cancer will be investigated. METHODS: Staging [18F]FDG PET/CT for breast invasive ductal carcinoma were retrospectively evaluated. Breast lesions were examined for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and proliferation index (Ki-67). Breast tumors were classified into five molecular subtypes: Luminal A, Luminal B-HER2(-), Luminal B-HER2(+), HER2(+) and Basal or Triple Negative cancers. The correlations between tumor characteristics and PET semiquantitative data of primary breast lesion (SUVmean, SUVmax, Mean tumor volume (MTV), TLG) were assessed. Specific Breast Uptake Ratio (SBUR) is used as a new quantification method of breast uptake to correct for physiological background activity. RESULTS: Fifty-eight patients were included. TLG was significantly higher in triple negative group when compared with luminal A (P<0.01). Significantly higher uptake was found in triple negative lesions when compared with luminal B-HER2(-) and luminal B-HER2(+) categories using SUVmax, SUVmean and TLG (all P<0.05). Conversely, no statistically significant difference for [18F]FDG uptake was observed between all other molecular subtypes. No value of SBUR in terms of correlation with histopathological parameters was demonstrated. CONCLUSIONS: TLG was superior to SUVmax and SUVmean in differentiating between triple negative breast cancer lesions and all other molecular subtypes. SBUR was not different statistically between various molecular subtypes.
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Neoplasias da Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Feminino , Fluordesoxiglucose F18 , Humanos , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
PURPOSE: Regarding radioguided surgery, the concept of "radioguided occult lesion localization" (ROLL) is based on both preoperative interventional imaging and intraoperative radioguided detection of a clinically occult neoplastic lesion. METHODS: This methodology consists in the direct administration into the lesion of Tc-macroaggregated human albumin formed by relatively large particles retained at the injection site, which direct radioguided excisional biopsy. RESULTS: This modality has expanded from the classic application of ROLL for nonpalpable breast lesions to other tumors, such as solitary pulmonary nodules or recurrences from differentiated thyroid carcinoma. In 2011, in order to improve the classification of different radioguided surgical procedures, ROLL applications were included in the more complete concept of GOSTT (Guided intraOperative Scintigraphic Tumor Targeting). This concept was introduced to include the entire range of basic and advanced radioguided procedures necessary to supply a "road map" for the surgeon. CONCLUSIONS: The terms ROLL and GOSTT have further developed by incorporating novel modalities such as hybrid tracers for simultaneous fluorescence and radioactive signal detection and innovative navigation systems based on mixed-reality protocols.
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Neoplasias Primárias Desconhecidas/diagnóstico por imagem , Neoplasias Primárias Desconhecidas/cirurgia , Cirurgia Assistida por Computador/métodos , Humanos , Traçadores RadioativosRESUMO
BACKGROUND: The evolution in the surgical and diagnostic procedures, the attention to women's preferences, the case mix, and differences in professional practices may lead to a variability in the quality of breast cancer clinical pathway. To catch and manage this variability it is important to use valid measures. The aim of this paper is to examine the concurrent validity of the breast-conserving surgery (BCS) indicator and to provide evidence to guide the quality improvement process. METHODS: The BCS indicator was calculated using hospital discharge records (HDRs) and was validated against surgical registry (SR) data in a random sample of 336 women undergoing breast cancer surgery in 2012 in two Tuscan teaching hospitals. The concurrent validity of BCS was examined by cross-tabulating patients using the ICD-9 CM codes for breast surgery obtained from the two data sources. RESULTS: The analysis, carried out involving breast cancer professionals, highlighted that the large majority of interventions coded as "mastectomies" in HDRs are in fact reconstructing procedures, including nipple-sparing, skin-sparing and skin-reducing mastectomies in SR. These results led us to refine the old algorithm, that calculates the proportion of breast-conserving surgery over the total number of breast interventions, and reclassify breast cancer surgical procedures into three categories: conservative, reconstructive and traditional mastectomy. Based on this new classification algorithm, the percentages of (I) reconstructive interventions were 16% at Florence TH and 38.3% at Pisa TH; (II) breast-conserving interventions were respectively 72.8 and 52.1%; and (III) mastectomies 11.2 and 9.6%. After adjusting for age in a logistic regression model, the percentages of reconstructive interventions at Florence and Pisa were respectively 22 and 34% and those of breast-conserving interventions 63 and 53%. CONCLUSIONS: Our results indicate that breast cancer care indicators should be refined by distinguishing reconstructive procedures (nipple/skin-sparing surgery with implant or breast tissue expander insertion) from traditional mastectomy. The involvement of breast care professionals in the choice of indicators proved to be crucial to capture the up-to-date breast cancer surgical practice and inform the quality improvement process.