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1.
Biosensors (Basel) ; 13(6)2023 May 25.
Article in English | MEDLINE | ID: mdl-37366941

ABSTRACT

Neurotransmitter release is important to study in order to better understand neurological diseases and treatment approaches. Serotonin is a neurotransmitter known to play key roles in the etiology of neuropsychiatric disorders. Fast-scan cyclic voltammetry (FSCV) has enabled the detection of neurochemicals, including serotonin, on a sub-second timescale via the well-established carbon fiber microelectrode (CFME). However, poor chronic stability and biofouling, i.e., the adsorption of interferent proteins to the electrode surface upon implantation, pose challenges in the natural physiological environment. We have recently developed a uniquely designed, freestanding, all-diamond boron-doped diamond microelectrode (BDDME) for electrochemical measurements. Key potential advantages of the device include customizable electrode site layouts, a wider working potential window, improved stability, and resistance to biofouling. Here, we present a first report on the electrochemical behavior of the BDDME in comparison with CFME by investigating in vitro serotonin (5-HT) responses with varying FSCV waveform parameters and biofouling conditions. While the CFME delivered lower limits of detection, we also found that BDDMEs showed more sustained 5-HT responses to increasing or changing FSCV waveform-switching potential and frequency, as well as to higher analyte concentrations. Biofouling-induced current reductions were significantly less pronounced at the BDDME when using a "Jackson" waveform compared to CFMEs. These findings are important steps towards the development and optimization of the BDDME as a chronically implanted biosensor for in vivo neurotransmitter detection.


Subject(s)
Biofouling , Diamond , Microelectrodes , Serotonin , Boron , Carbon Fiber , Neurotransmitter Agents
2.
ESMO Open ; 7(6): 100634, 2022 12.
Article in English | MEDLINE | ID: mdl-36493602

ABSTRACT

BACKGROUND: The Meet-URO score allowed a more accurate prognostication than the International Metastatic RCC Database Consortium (IMDC) for patients with pre-treated metastatic renal cell carcinoma (mRCC) by adding the pre-treatment neutrophil-to-lymphocyte ratio and presence of bone metastases. MATERIALS AND METHODS: A post hoc analysis was carried out to validate the Meet-URO score on the overall survival (OS) of patients with IMDC intermediate-poor-risk mRCC treated with first-line nivolumab plus ipilimumab within the prospective Italian Expanded Access Programme (EAP). We additionally considered progression-free survival (PFS) and disease response rates. Harrell's c-index was calculated to compare the accuracy of survival prediction. RESULTS: Overall the EAP included 306 patients, with a median follow-up of 12.2 months, median OS was not reached, 1-year OS was 66.8% and median PFS was 7.9 months. By univariable analysis, both the IMDC score and the two additional variables of the Meet-URO score were associated with either OS or PFS (P < 0.001 for all comparisons). The four Meet-URO risk groups (G) had 1-year OS of 92%, 72%, 50% and 21% for G2 (29.1% of patients), G3 (28.8%), G4 (33.0%) and G5 (9.1%), respectively. OS was significantly shorter in each consecutive G (P = 0.001 for G3, P < 0.001 for both G4 and G5 compared to G2). Similarly, Meet-URO Gs 2-5 showed decreasing median PFS and response rates. The Meet-URO score showed the highest c-index for both OS (0.73) and PFS (0.67). Limitations include the post hoc nature of this analysis and the lack of a comparative arm to assess predictive value. CONCLUSION: The Meet-URO score appeared to show better prognostic classification than the IMDC alone in patients with mRCC at IMDC intermediate-poor risk treated with first-line nivolumab and ipilimumab.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/secondary , Nivolumab/pharmacology , Nivolumab/therapeutic use , Ipilimumab/pharmacology , Ipilimumab/therapeutic use , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Prospective Studies , Retrospective Studies
4.
ESMO Open ; 6(3): 100118, 2021 06.
Article in English | MEDLINE | ID: mdl-33984678

ABSTRACT

BACKGROUND: Reliable and affordable prognostic and predictive biomarkers for urothelial carcinoma treated with immunotherapy may allow patients' outcome stratification and drive therapeutic options. The SAUL trial investigated the safety and efficacy of atezolizumab in a real-world setting on 1004 patients with locally advanced or metastatic urothelial carcinoma who progressed to one to three prior systemic therapies. PATIENTS AND METHODS: Using the SAUL Italian cohort of 267 patients, we investigated the prognostic role of neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) and the best performing one of these in combination with programmed death-ligand 1 (PD-L1) with or without lactate dehydrogenase (LDH). Previously reported cut-offs (NLR >3 and NLR >5; SII >1375) in addition to study-defined ones derived from receiver operating characteristic (ROC) analysis were used. RESULTS: The cut-off values for NLR and SII by the ROC analysis were 3.65 (sensitivity 60.4; specificity 63.0) and 884 (sensitivity 64.4; specificity 67.5), respectively. The median overall survival (OS) was 14.7 months for NLR <3.65 [95% confidence interval (CI) 9.9-not reached (NR)] versus 6.0 months for NLR ≥3.65 (95% CI 3.9-9.4); 14.7 months for SII <884 (95% CI 10.6-NR) versus 6.0 months for SII ≥884 (95% CI 3.7-8.6). The combination of SII, PD-L1, and LDH stratified OS better than SII plus PD-L1 through better identification of patients with intermediate prognosis (77% versus 48%, respectively). Multivariate analyses confirmed significant correlations with OS and progression-free survival for both the SII + PD-L1 + LDH and SII + PD-L1 combinations. CONCLUSION: The combination of immune-inflammatory biomarkers based on SII, PD-L1, with or without LDH is a potentially useful and easy-to-assess prognostic tool deserving validation to identify patients who may benefit from immunotherapy alone or alternative therapies.


Subject(s)
Carcinoma, Transitional Cell , Lung Neoplasms , Urinary Bladder Neoplasms , Urologic Neoplasms , Biomarkers , Humans , Immunotherapy , Italy , Prognosis , Urologic Neoplasms/diagnosis , Urologic Neoplasms/therapy
5.
ESMO Open ; 6(2): 100078, 2021 04.
Article in English | MEDLINE | ID: mdl-33735802

ABSTRACT

BACKGROUND: To stratify the prognosis of patients with programmed cell death-ligand 1 (PD-L1) ≥ 50% advanced non-small-cell lung cancer (aNSCLC) treated with first-line immunotherapy. METHODS: Baseline clinical prognostic factors, the neutrophil-to-lymphocyte ratio (NLR), PD-L1 tumour cell expression level, lactate dehydrogenase (LDH) and their combination were investigated by a retrospective analysis of 784 patients divided between statistically powered training (n = 201) and validation (n = 583) cohorts. Cut-offs were explored by receiver operating characteristic (ROC) curves and a risk model built with validated independent factors by multivariate analysis. RESULTS: NLR < 4 was a significant prognostic factor in both cohorts (P < 0.001). It represented 53% of patients in the validation cohort, with 1-year overall survival (OS) of 76.6% versus 44.8% with NLR > 4, in the validation series. The addition of PD-L1 ≥ 80% (21% of patients) or LDH < 252 U/l (25%) to NLR < 4 did not result in better 1-year OS (of 72.6% and 74.1%, respectively, in the validation cohort). Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2 [P < 0.001, hazard ratio (HR) 2.04], pretreatment steroids (P < 0.001, HR 1.67) and NLR < 4 (P < 0.001, HR 2.29) resulted in independent prognostic factors. A risk model with these three factors, namely, the lung immuno-oncology prognostic score (LIPS)-3, accurately stratified three OS risk-validated categories of patients: favourable (0 risk factors, 40%, 1-year OS of 78.2% in the whole series), intermediate (1 or 2 risk factors, 54%, 1-year OS 53.8%) and poor (>2 risk factors, 5%, 1-year OS 10.7%) prognosis. CONCLUSIONS: We advocate the use of LIPS-3 as an easy-to-assess and inexpensive adjuvant prognostic tool for patients with PD-L1 ≥ 50% aNSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Antibodies, Monoclonal, Humanized , B7-H1 Antigen , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/drug therapy , Humans , Lung , Lung Neoplasms/diagnosis , Lung Neoplasms/drug therapy , Prognosis , Retrospective Studies
6.
Clin Transl Oncol ; 22(11): 2130-2135, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32232716

ABSTRACT

PURPOSE: To identify patients with metastatic urothelial cancer (mUC) unlikely to benefit from immune-checkpoint inhibitors (ICIs). METHODS/PATIENTS: We explored the predictive and prognostic values of baseline neutrophil-to-lymphocyte ratio (NLR), with cut-offs ≥ 3 and ≥ 5, and of a urothelial immune prognostic index (UIPI, based on increased NLR and LDH), on 146 patients. RESULTS: NLR and UIPI significantly predicted progressive disease and progression-free survival with both cut-offs (p = 0.0069, p = 0.0034, p = 0.0160, p = 0.0063; p < 0.001, p = 0.021, p = 0.014, p = 0.026; for NLR-3, NLR-5, UIPI-3, UIPI-5, respectively) and overall survival when NLR cut-off was ≥ 5 (p = 0.03 and p = 0.024, for NLR-5 and UIPI-5, respectively). CONCLUSIONS: NLR-5 deserves prospective validation to identify mUC patients with poor prognosis following ICIs.


Subject(s)
Immune Checkpoint Inhibitors/therapeutic use , L-Lactate Dehydrogenase/blood , Lymphocytes , Neutrophils , Urologic Neoplasms/drug therapy , Urothelium/pathology , Adult , Aged , Biomarkers , Female , Humans , Male , Middle Aged , Urologic Neoplasms/immunology , Urologic Neoplasms/mortality
7.
Clin Transl Oncol ; 22(6): 844-851, 2020 Jun.
Article in English | MEDLINE | ID: mdl-31392645

ABSTRACT

BACKGROUND: In most cases, T790M EGFR-positive NSCLC patients receiving osimertinib developed "non-drugable" progression, as the patients with common EGFR-sensitizing mutations were treated with first-line osimertinib. In both settings, chemotherapy represents the standard treatment and local ablative treatments (LATs) are potential useful options in the case of oligo-progression. METHODS: We conducted a study on "post-progression" (pp) outcomes of T790M EGFR-positive NSCLC patients treated with osimertinib, according to the therapeutic strategy applied: osimertinib beyond progression (± LATs), "switched therapies" or best supportive care only (BSC). RESULTS: 144 consecutive patients were evaluated: 53 (36.8%) did not received post-progression treatments (BSC), while 91 (63.2%) patients received at least 1 subsequent treatment; 50 patients (54.9%) received osimertinib beyond disease progression [19 (20.9%) of them with adjunctive LATs] and 41 (45.1%) a switched therapy. Median ppPFS (progression-free survival) and median ppOS (overall survival) of patients who received osimertinib beyond progression vs. switched therapies were 6.4 months vs. 4.7 months, respectively [HR 0.57 (95% CI 0.35-0.92), p = 0.0239] and 11.3 months vs 7.8 months, respectively [HR 0.57 (95% CI 0.33-0.98), p = 0.0446]. Among patients who received osimertinib beyond progression with and without LATs median ppPFS was 6.4 months and 5.7 months, respectively [HR 0.90 (95% CI 0.68-1.18), p = 0.4560], while median ppOS was 20.2 months and 9.9 months, respectively [HR 0.73 (95% CI 0.52-1.03), p = 0.0748]. At the univariate analysis, the only factor significantly related to the ppPFS was the therapeutic strategy in favor of osimertinib beyond progression (± LATs). Moreover, the only variable which was significantly related to ppOS at the multivariate analysis was osimertinib beyond progression (± LATs). CONCLUSION: Our study confirmed that in clinical practice, in case of "non-druggable" disease progression, maintaining osimertinib beyond progression (with adjunctive LATs) is an effective option.


Subject(s)
Acrylamides/therapeutic use , Aniline Compounds/therapeutic use , Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , ErbB Receptors/genetics , Lung Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Combined Modality Therapy , Disease Progression , ErbB Receptors/antagonists & inhibitors , Female , Health Knowledge, Attitudes, Practice , Humans , Italy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Male , Middle Aged , Mutation , Survival Analysis , Treatment Outcome
8.
Clin Transl Oncol ; 21(6): 790-795, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30448956

ABSTRACT

PURPOSE: Metronomic oral vinorelbine (MOV) could be a treatment option for unfit patients with advanced non-small cell lung cancer (NSCLC) based on its safety profile and high patient compliance. METHODS: We retrospectively collected data on 270 patients [median age 76 (range 48-92) years, M/F 204/66, PS 0 (27)/1 (110)/≥ 2 (133), median of 3 serious comorbidities] with stage IIIB-IV NSCLC treated with MOV as first (T1) (67%), second (T2) (19%) or subsequent (T3) (14%) line. Schedules consisted of vinorelbine 50 mg (138), 40 mg (68) or 30 mg (64) three times a week continuously. RESULTS: Patients received an overall median of 6 (range 1-25) cycles with a total of 1253 cycles delivered. The overall response rate was 17.8% with 46 partial and 2 complete responses and 119 patients (44.1%) experienced stable disease > 12 weeks with an overall disease control rate of 61.9%. Median overall time to progression was 5 (range 1-21) months [T1 7 (1-21), T2 5.5 (1-19) and T3 4 (1-19) months] and median overall survival 9 (range 1-36) months [T1 10 (1-31), T2 8 (1-36) and T3 6.5 (2-29) months]. Treatment was extremely well tolerated with 2% (25/1253) G3/4 toxicity (mainly G3 fatigue and anemia) and no toxic deaths. We observed the longer OS 14 (range 7-36) months in a subset of squamous NSCLC patients receiving immunotherapy after metronomic oral vinorelbine. CONCLUSION: We confirmed MOV as an extremely safe treatment in a large real world population of advanced NSCLC with an interesting activity mainly consisting of long-term disease stabilization. We speculate the possibility of a synergistic effect with subsequent immunotherapy.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Agents, Phytogenic/administration & dosage , Carcinoma, Large Cell/drug therapy , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Squamous Cell/drug therapy , Lung Neoplasms/drug therapy , Vinorelbine/administration & dosage , Adenocarcinoma/pathology , Administration, Metronomic , Aged , Aged, 80 and over , Carcinoma, Large Cell/pathology , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Squamous Cell/pathology , Female , Follow-Up Studies , Humans , International Agencies , Lung Neoplasms/pathology , Male , Middle Aged , Palliative Care , Remission Induction , Retrospective Studies , Survival Rate
9.
Nanotechnology ; 28(44): 445402, 2017 Nov 03.
Article in English | MEDLINE | ID: mdl-28809757

ABSTRACT

We report on the fabrication of ZnO nanorod (NR)-based flexible piezoelectric nanogenerators (PENGs) on carbon paper (CP). Structural investigations indicate that the ZnO NRs grew well along the porous CP surface. Optical investigation shows that the crystal quality of the ZnO NRs on the CP was comparable to that of NRs grown on Si substrate. As the molar concentration increased from 10-70 mM, the output voltage and current increased consistently from 3.6-6.8 V and 0.79-1.45 µA, respectively. The enhancements of the voltage and current were attributed to the enhanced accumulation of the potentials generated by the increased number of ZnO NRs in the PENG devices. Therefore, the porous CP enhanced the PENG performance due to the higher surface area, and provided a super-flexible self-powering platform.

11.
Breast Cancer Res Treat ; 163(2): 295-302, 2017 06.
Article in English | MEDLINE | ID: mdl-28289852

ABSTRACT

PURPOSE: The aim was to evaluate the role of tumor-infiltrating lymphocytes (TIL) in predicting molecular response after preoperative endocrine or cytotoxic treatment for HR+/HER2- patients who do not achieve a pathological complete response. METHODS: Stromal (Str) TIL were centrally evaluated on samples from diagnostic core-biopsies of HR+/HER2- patients included in two prospective randomized trials: the LETLOB trial (neoadjuvant endocrine-based treatment) and the GIOB trial (neoadjuvant chemotherapy-based treatment). Pre- and post-treatment Ki67 was centrally assessed. RESULTS: StrTIL were evaluable in 111 cases (n = 73 from the LETLOB trial and n = 38 from the GIOB trial). Median StrTIL was 2%. Patients with high StrTIL (StrTIL ≥10%, n = 28) had more frequently breast cancer of ductal histology (p = 0.02), high grade (p = 0.049), and high Ki67 (p = 0.02). After neoadjuvant endocrine treatment (LETLOB cohort), a significant Ki67 suppression (p < 0.01) from pre- to post-treatment was observed in both the low and high StrTIL groups. High StrTIL patients achieve more frequently a relative Ki67 suppression ≥50% from baseline as compared to low StrTIL patients (55 vs. 35%, p non significant). After neoadjuvant chemotherapy (GIOB cohort), a significant Ki67 suppression was observed only for low StrTIL patients (Wilcoxon p = 0.001) and not in the high StrTIL group (p = 0.612). In this cohort, the rate of patients achieving a relative Ki67 suppression ≥50% from baseline was significantly higher in the low vs high StrTIL group (64% vs 10%, p = 0.003). Geometric mean Ki67 suppression was evaluated in each cohort according to StrTIL: the lowest value (-41%) was observed for high StrTIL cases treated with chemotherapy. CONCLUSIONS: This hypothesis-generating study suggests that in HR+/HER2- breast cancer StrTIL at baseline may influence the achievement of a molecular response after neoadjuvant treatment. Further evaluation in large studies is needed, and interaction with the type of treatment warrants to be explored.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Lymphocytes, Tumor-Infiltrating/pathology , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/metabolism , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Chemotherapy, Adjuvant , Female , Humans , Lapatinib , Letrozole , Middle Aged , Neoadjuvant Therapy , Nitriles/administration & dosage , Prospective Studies , Quinazolines/administration & dosage , Receptor, ErbB-2/metabolism , Receptors, Cell Surface/metabolism , Treatment Outcome , Triazoles/administration & dosage
12.
Ann Oncol ; 23(4): 815-22, 2012 Apr.
Article in English | MEDLINE | ID: mdl-21948814

ABSTRACT

BACKGROUND: Based on the high chemosensitivity of germ-cell tumors (GCTs), the concept of high-dose chemotherapy (HDCT) has been developed worldwide and investigated through many clinical trials. It has been carried out in different clinical settings, ranging from resistant or absolute refractory disease to chemosensitive relapse. HDCT with stem-cell support has been also explored as a part of first-line strategy for poor-prognosis patients. PATIENTS AND METHODS: Our review summarized results from clinical trials evaluating the role of HDCT in patients with advanced GCTs. So far available data were obtained through a Medline search of English-language literature. RESULTS: Several phase II trials and retrospective series have shown a possible benefit for GCT patients with recurrent disease as well as in first-line setting. Despite these results, data derived from randomized phase III studies failed to demonstrate any survival advantage for HDCT over conventional chemotherapy. CONCLUSIONS: The role of HDCT in GCTs remains controversial. We need new prospective studies based on prognostic factors with multiple transplants of carboplatin and etoposide as the preferred high dose regimen. At present, based mainly on retrospective and phase II studies, HDCT may represent a therapeutic option for patients with primary refractory disease or for those with a second or further relapse.


Subject(s)
Neoplasm Recurrence, Local/drug therapy , Neoplasms, Germ Cell and Embryonal/drug therapy , Stem Cell Transplantation , Drug Resistance, Neoplasm , Humans , Neoplasm Recurrence, Local/diagnosis , Neoplasm Recurrence, Local/mortality , Neoplasms, Germ Cell and Embryonal/diagnosis , Neoplasms, Germ Cell and Embryonal/mortality , Prognosis , Randomized Controlled Trials as Topic , Salvage Therapy
13.
Radiol Med ; 113(7): 1018-28, 2008 Oct.
Article in English, Italian | MEDLINE | ID: mdl-18779931

ABSTRACT

PURPOSE: The aim of this study was to demonstrate the effectiveness of interventional techniques in the palliative management of painful extraspinal bone metastases. MATERIALS AND METHODS: Cementoplasty alone or in combination with radiofrequency (RF) ablation was performed in 14 skeletal extravertebral segments in 13 patients with ages ranging from 50 to 74 (average 67) years. The primary tumours were myeloma (n=5), renal carcinoma (n=5), hepatocellular carcinoma (n=2) and bladder carcinoma (n=2). Metastases were located at the acetabulum (n=4), femur (n=5), humerus (n=1), scapula (n=2) and iliac bone (n=2). The clinical indication was a pain intensity score >4 on the visual analogue scale (VAS) partially or totally refractory to analgesic medication. Clinical evaluation was based on clinical and neurological conditions before and immediately after the procedure and during the follow-up. RESULTS: Technical success was achieved in all cases. Ten patients were treated by cementoplasty alone and four cases by cementoplasty combined with RF ablation. After treatment, all patients experienced improved symptoms, as demonstrated by the VAS score, which remained constant during follow-up. All patients were followed for between 2 and 14 (average 6.1) months. We had one major complication in a patient who developed an abscess, which was treated by percutaneous drainage. CONCLUSIONS: In our experience, cementoplasty alone for small lesions or combined with RF ablation in larger lesions is an effective and safe therapy in the palliative management of painful extraspinal bone metastases.


Subject(s)
Bone Cements/therapeutic use , Bone Neoplasms/secondary , Bone Neoplasms/surgery , Catheter Ablation , Aged , Bone Neoplasms/diagnosis , Bone Neoplasms/diagnostic imaging , Carcinoma, Hepatocellular/secondary , Carcinoma, Renal Cell/secondary , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Kidney Neoplasms/pathology , Liver Neoplasms/pathology , Magnetic Resonance Imaging , Male , Middle Aged , Multiple Myeloma/secondary , Pain Measurement , Palliative Care , Time Factors , Tomography, X-Ray Computed , Treatment Outcome
15.
Cancer Lett ; 168(1): 31-6, 2001 Jul 10.
Article in English | MEDLINE | ID: mdl-11368874

ABSTRACT

The human androgen receptor (AR) gene contains a highly polymorphic CAG repeat in exon 1 that is inversely correlated with AR transcriptional activity in vitro. Several studies have shown that fewer CAG repeats are associated with an increased risk as well as more aggressive forms of prostate cancer. More recently, AR allele length was also inversely correlated with the histological grade of breast cancer, but no association was found between the AR-CAG polymorphism and the risk of either breast or ovary cancer. On the contrary, it was proposed that a longer CAG repeat sequence might be associated with an increased risk of breast cancer in BRCA1 mutation carriers, thus suggesting a different role of the AR-CAG polymorphism in sporadic and inherited breast cancers. With the intent of better understanding the role of the AR-CAG polymorphism as a cancer risk modifier, we defined the AR genotype of 151 patients (101 with breast and 50 with ovary cancer) belonging to high-risk breast/ovary cancer families. No difference in CAG repeat length was found between either breast and ovary cancer patients or age at diagnosis of both tumors. These results were also confirmed in a sub-group of 47 breast cancer cases, that either carried a BRCA gene mutation (11 cases) or were identified by very stringent operational criteria as hereditary breast cancers. Even though a substantially larger sample size would be required to reach conclusive evidence, our findings suggest that the AR-CAG polymorphism does not act as a modifier of tumor onset or tumor phenotype in breast/ovarian cancer families.


Subject(s)
Breast Neoplasms/genetics , Ovarian Neoplasms/genetics , Polymorphism, Genetic , Receptors, Androgen/genetics , Repetitive Sequences, Nucleic Acid , Alleles , Family Health , Female , Genotype , Humans , Mutation , Phenotype , Risk Factors
16.
Cancer Treat Rev ; 27(5): 295-304, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11871866

ABSTRACT

Women in general have a 10% risk of developing breast cancer and a 2-3% chance of ovarian cancer in their life-times. Mutations in BRCA-1 and BRCA-2 are present in only a small portion (5-10%) of all breast cancers. Carriers of mutations in these genes have a greater risk of cancer, especially before menopause in the case of BRCA-1 carriers. In addition, their risk of contralateral breast cancer is significantly higher than for the general population (4.2-53% vs. 2%). The grade of contralateral tumours in these patients is more aggressive. BRCA-2 hereditary breast cancer seems more heterogeneous than the BRCA-1 phenotype, and not clearly different from sporadic forms. However, since 20-30% of carriers of BRCA mutations never develop breast or ovarian cancer, there must be other 'risk modifiers'. Survival is better for carriers of hereditary ovarian cancer. Patients with these mutations are referred for genetic counselling, a complex process which includes: an informative dialogue between the proband and the geneticist, drawing up a family history, informed consent, evaluation of risk, genetic testing and possible involvement of healthy family members.


Subject(s)
Breast Neoplasms/genetics , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Breast Neoplasms/pathology , Breast Neoplasms/psychology , Female , Genetic Counseling , Genetic Predisposition to Disease/genetics , Humans , Medical Oncology/trends , Mutation , Prognosis
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