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G Gasparini

Publications and source records attributed to G Gasparini.

At least 109 records · Page 6Linked to original sources

[Areas of isodensity and functional pulmonary computerized tomography].

Computed Tomography scanners can be calibrated to provide reproducible measurements for the quantitative analysis of lung density. We measured in square centimeters the pulmonary density areas for each interval of values expressed in Hounsfield Units and obtained some histograms representing the "respiratory curves" for full inspiration and full expiration. The study population had been divided into three groups according to their clinical conditions. Group A: 12 normal subjects, aged 20-40, non-smokers; Group B: 23 patients, aged 40-65, smokers, asymptomatic or slightly asthmatic; Group C: 19 patients, aged 55-75 hospitalized with chronic obstructive pulmonary disease. The respiratory curves obtained at full expiration appeared to be completely different in the three groups resulting more significant than those obtained at full inspiration. We conclude that the histograms obtained by measuring the pulmonary density areas in full expiration at preselected intervals of HU values can be useful as a screening test as well as to quantify pulmonary emphysema.

Adult↗

Predictive and prognostic markers in a series of patients with head and neck squamous cell invasive carcinoma treated with concurrent chemoradiation therapy.

It has been proposed that diverse anticancer drugs and radiation therapy may induce a mode of cell death with the characteristics of apoptosis. Since apoptosis is under the control of several oncogenes, we analyzed the expression of the protein encoded by the proto-oncogenes bcl-2 and p53. Furthermore, we studied cell proliferation [using PC-10 mAb to proliferating cell nuclear antigen (PCNA)] and vascularization [using the CD-31 mAb and by counting intratumoral microvessel density (IMD)] using immunocytochemistry. A series of 73 patients with clinical stage II-IV squamous cell invasive carcinoma of the head and neck (H&N) were treated with concurrent chemoradiation therapy (cisplatin, 80 mg/m2, versus carboplatin, 375 mg/m2, three times every 3 weeks and a total dose of radiation therapy of 64 Gy in 6-8 weeks). We correlated the expression of these markers, determined prior to treatment, with response to the therapy and prognosis. Bcl-2 protein was expressed in 37.4% of the carcinomas (25/67 evaluable), and it was not significantly associated with any other feature studied. Forty (56. 4%) of the 71 carcinomas evaluable for p53 were p53 positive; the median IMD was 38 microvessels/field at the hot spot (range, 18-80), and the median percentage of nuclei labeled by the PC-10 mAb was 50% (range, 0-95%). In the univariate analysis, regional lymph node negativity (P = 0.016), good performance status (PS) (PS >/= 90; P = 0.044), bcl-2 positivity (P = 0.070), and low vascularization (P = 0. 085) were significantly associated with a higher probability of complete remission. In the multivariate analysis (final model), only IMD (continuous variable; P = 0.045) and PS (P = 0.017) retained significance. As far as prognosis is concerned, in the univariate analysis, patients with tumors with low histological grading (grades 1-2; P = 0.006), p53 negative (P = 0.09), bcl-2 positive (P = 0.08), and high PCNA labeling (P = 0.06) had a significantly better disease-free survival. In the multivariate analysis, only grading (P = 0.003) and p53 (P = 0.04) retained significance for disease-free survival. For overall survival, in the univariate analysis, the following markers were significantly prognostic when only deaths due to progression are considered: response to therapy (P = 0.00001), PS (P = 0.04), nodal status (P = 0.028), PCNA (P = 0.04), p53 (P = 0. 08), and grading (P = 0.01). In the multivariate analysis, only patients who achieved complete response (P = 0.00002), high PCNA values (P = 0.002), and low histological grading (P = 0.01) retained a statistically significant probability of better overall survival. Our results suggest that in this series of H&N cancer patients the markers capable of predicting response to therapy are distinct from those associated with prognosis, once the remission has been achieved. This information is potentially useful to the clinician for developing a more rational therapeutic approach for H&N cancer patients eligible for concurrent chemoradiation therapy.

Adult↗

Expression of bcl-2 protein predicts efficacy of adjuvant treatments in operable node-positive breast cancer.

The proto-oncogene bcl-2 encodes a protein that inhibits apoptosis, a common mechanism of cell death caused by hormone and chemotherapy. We have analyzed bcl-2 protein expression by immuno-cytochemistry in primary node-positive breast cancers in two groups of patients (for a total of 180 cases). One group received adjuvant hormone therapy, the other chemotherapy (cyclophosphamide, methotrexate, and fluorouracil), and both groups were followed for a median time of 63 months. We compared our findings with conventional clinicopathological indicators [menopausal status, number of axillary nodes, histological grade, tumor size and type, estrogen receptor (ER), and progesterone receptor] and with p53 protein expression. bcl-2 protein was present in 65% of the carcinomas (117/180) and it was significantly associated with ER and progesterone receptor and inversely associated with p53 in both the groups of patients treated with adjuvant chemotherapy and tamoxifen. In patients treated either with adjuvant chemotherapy or tamoxifen, relapse-free survival at 5 years was significantly better among patients with bcl-2-positive tumors than in those with bcl-2 negative ones (P = 0.05 and 0.02, respectively). As far as overall survival is concerned, patients with bcl-2-positive tumors had a significantly better outcome in the group treated with adjuvant chemotherapy (P = 0.03). Multivariate analyses were performed for the two treatment groups. In the group treated with tamoxifen, lack of expression of ER and of bcl-2 was the only significant and independent predictor for poor relapse-free survival (P < 0.01). A number of nodes above 3 was the only significant and independent predictor for poor overall survival (P < 0.01). In the cyclophosphamide-methotrexate-fluorouracil-treated group, bcl-2 absence was significant for poor overall survival (P = 0.02) as well as a number of nodes above 3 (P = 0.04) and a tumor size above 2 cm (P = 0.05). For poor relapse-free survival only a number of nodes above 3 (P < 0.01) and progesterone negativity (P = 0.02) were significant and independent predictors of a higher probability of relapse. Thus, in contrast to in vitro data on drug resistance, bcl-2 expression was associated with better outcomes in patients treated with hormone and chemotherapy. Overall, these results suggest that expression of bcl-2 protein and the number of metastatic lymph nodes are independent features predictive of clinical outcome in patients with node-positive breast cancer, irrespective of the type of adjuvant treatment. The determination of bcl-2 protein may prove to be a useful tool to distinguish patients for whom conventional forms of adjuvant therapy are beneficial from those with bcl-2 negative and ER-negative tumors for whom novel therapeutic strategies are needed.

Adult↗

Cell kinetics in human breast cancer: comparison between the prognostic value of the cytofluorimetric S-phase fraction and that of the antibodies to Ki-67 and PCNA antigens detected by immunocytochemistry.

The determination of cell proliferation is one of the more widely used tools for assessing prognosis. However, additional research in this field is warranted because today there are several methodological procedures available for monitoring cell kinetics and it has still not been established which is the most reliable marker of proliferation and which possesses the greatest prognostic value. We performed this study in a series of primary invasive breast cancers to compare the prognostic value of S-phase fraction (SPF) by flow cytometry, the most widely used method for detecting proliferation at present, with that of antibodies to Ki-67 and PC-10 to proliferating-cell nuclear antigen (PCNA) detected by immunocytochemical methods. A significant linear relationship was observed only between SPF and Ki-67. In univariate analysis SPF and Ki-67 values, nodal status, histological grading and peritumoral lymphatic-vessel invasion were significant predictors of relapse-free survival (RFS). As far as overall survival (OS) is concerned, only SPF, Ki-67 and nodal status were significantly associated with the risk of death. PCNA had no prognostic value for either RFS or OS. In multivariate analysis only SPF and nodal status retained a significant and independent prognostic value. Neither the cell-kinetics parameters assessed by immunocytochemistry (i.e. Ki-67 and PCNA) nor histological grading were independent prognosticators. In conclusion, our results provide evidence that the determination of SPF by flow cytometry was the strongest cell-kinetics marker used to assess prognosis in this series of breast cancers. However, different and novel markers of cell kinetics need to be compared in larger series in order to identify the best one.

Breast Neoplasms↗

A multiparametric study on the prognostic value of epidermal growth factor receptor in operable breast carcinoma.

Epidermal growth factor receptor (EGFR) is a potentially useful new biological prognostic and predictive indicator in human breast cancer. Additional research on EGFR is warranted to enhance our information on: i) the method of choice for its detection and quality control issues; ii) its association with novel pathobiological markers of prognosis; iii) its prognostic value in multivariate analysis; and iv) its capability to predict response to hormone therapy and, in the future, to biological treatments using antibodies against the specific receptor or its ligands. In the present study we update previous data on EGFR status, determined immunocytochemically, by prolonging the period of observation up to 5 years and by including, in the multivariate analysis, several new biological indicators. The main results obtained are: i) EGFR is weakly associated with Ki-67 score (p = 0.073) and with p53 expression (p = 0.06); ii) EGFR is a significant indicator for recurrence (p < 0.01 and odds ratio of 2.82) but not for death (p = 0.27 and odds ratio of 1.49); iii) the prognostic power of EGFR is enhanced when combined with the knowledge of S-phase fraction; and iv) in multivariate analysis on relapse-free survival, EGFR and S-phase fraction (likelihood ratio test = 26.40; p < 0.01), c-erB-2 protein and p53 mutant protein expression (likelihood ratio test = 5.94; p = 0.05), cathepsin D (likelihood ratio test = 9.78; p < 0.01), and nodal status (likelihood ratio test = 7.32: p < 0.01) are significant and independent prognostic factors in early-stage breast carcinoma. This new information could be of help for a more rational approach in the use of EGFR as a marker in future clinical research.

Age Factors↗

Determination of epidermal growth factor receptor provides additional prognostic information to measuring tumor angiogenesis in breast carcinoma patients.

Recent studies have shown that women with invasive breast carcinoma having high microvessel density (MVD) (a measure of tumor angiogenesis) or epidermal growth factor receptor (EGFR) expression have increased risk for metastasis and/or decreased survival. To determine if MVD and EGFR expression provide additive prognostic information, we analyzed these two prognostic indicators in the primary invasive breast carcinomas from 165 consecutive patients, who were followed for a median of 51 months. Univariate analysis showed a highly significant (p < 0.001) association of MVD with overall and relapse-free survival in all patients, including both node-negative and node-positive groups (see JNCI 84:1875-1887, 1992). For EGFR, although univariate analysis suggested that women with tumors showing EGFR expression relapsed earlier and, perhaps, died earlier, the differences were not statistically significant. Multivariate analysis, in contrast, revealed that determination of EGFR did provide significant additional information to that already provided by MVD for predicting relapse-free survival in all women (p = 0.001) and in the subset of node-positive women (p = 0.007). Among node-negative women, however, the contribution of EGFR expression in predicting relapse-free survival was not significant (p = 0.12). Likewise, EGFR measurement did not provide significant additional information beyond that of MVD alone for predicting overall survival. Thus, EGFR provides additional prognostic information to determination of MVD, but only for relapse-free survival in node-positive women with invasive breast carcinoma.

Adult↗

Vinorelbine in pre-treated advanced head & neck squamous cell carcinoma. A phase II study.

BACKGROUND: There are few moderately active single-agents for the treatment of recurrent or metastatic head & neck cancer. Thus, the identification of novel active agents is warranted. We performed the present phase II trial to evaluate activity and toxicity of vinorelbine (VNB) in previously treated patients with advanced head & neck cancer. PATIENTS AND METHODS: 16 patients entered the study, 15 of whom were evaluable. The main characteristics were: M/F = 14/1; median age of 58 yrs (18-67); median PS (Karnofsky score) of 70 (60-100); primitive tumor sites were: oropharynx in 5; larynx in 4, hypopharynx in 3, rhynopharynx in 2, and oral cavity in 1 patient; initial clinical stage was IV in 9, III in 4 and II in 2 patients. Previous treatments were: cisplatinum with concurrent radiotherapy in 6 and cisplatinum + fluorouracil (for at least 2 cycles) in 9 patients. VNB was given at the dose of 20 mg/m2 i.v. infusion for 1 hr, weekly, for a minimum of 8 doses. Response and toxicity were evaluated after at least 8 doses of VNB. RESULTS: Overall, 139 courses of VNB were given (median 9, range 8-19). Objective responses were: partial response in 1 patient (6%); stable disease, lasting at least 2 months, in 4 patients (27%) and progression in the other 10 patients (67%). Three patients had a one week delay in subsequent courses due to severe hematological toxicity. Toxicities observed were: leucopenia of grade IV (W.H.O.) in 2 patients and of grade I-II in 12 patients; granulocytopenia of grade III in 1 patient and of grade IV in 2 patients; grade I-II anemia in 4 patients; grade II phlebitis in 3 patients; grade II constipation in 2 patients, grade I-II peripheral neuropathy in 3 patients, grade I-II nausea and vomiting in 4 patients, and grade II stomatitis in 2 patients. CONCLUSIONS: VNB, in this series of heavily pre-treated patients with head & neck cancer, did not reveal an antitumor activity of interest.

Adult↗

Nitroglycerin infusion during upright tilt: a new test for the diagnosis of vasovagal syncope.

The aim of our present study was to assess the value of nitroglycerin infusion during upright posture as a new provocative test for diagnosis of vasovagal syncope. To this purpose 40 patients with unexplained syncope (17 men and 23 women, mean age 47 years) and 25 asymptomatic control subjects with negative baseline head-up tilt underwent two other tilting tests, one during nitroglycerin infusion and one during isoproterenol infusion. The protocol of the nitroglycerin test consisted of a maximum of five successive stages of 5 minutes in the supine position plus 10 minutes 80-degree upright tilt at progressively increasing infusion rates (increments of 0.86 microgram/kg/hr every stage). During the nitroglycerin test a positive response (syncope in association with sudden hypotension and bradycardia) occurred in 21 (53%) patients with unexplained syncope, an exaggerated response (minor symptoms in association with slowly increasing hypotension alone) occurred in 10 (25%), a negative response in 9 (22%), and drug intolerance in 0. During the isoproterenol test these percentages were 25%, 25%, 32%, and 18%, respectively. Only 2 (8%) control subjects had a positive response to nitroglycerin test and 2 (8%) to isoproterenol test. Thus the nitroglycerin test seems to be a useful alternative tool for diagnosis of vasovagal syncope; it is equally specific but more sensitive and feasible than the isoproterenol test.

Adult↗

c-erbB-3 and c-erbB-2 protein expression in node-negative breast carcinoma--an immunocytochemical study.

The type I growth factor receptor family has been found to play an important role in the control of normal growth and differentiation. Moreover, the epidermal growth factor receptor and the c-erbB-2 oncogene seem to be implicated in the pathogenesis and behaviour of several cancers, including breast cancer. c-erbB-3 is a new member of the type I receptor family for which there is currently little information available on its expression in neoplastic tissues, and on its possible prognostic significance. This study was undertaken to define the prognostic value of c-erbB-3 expression in a series of node-negative breast cancer (NNBC) patients when compared, by multivariate analysis, with expression of the c-erbB-2 protein and conventional clinicopathological features. cerbB-3 was recognised by the novel monoclonal antibody RTJ1, whereas c-erbB-2 was detected by the polyclonal antibody 21N, using immunocytochemical methods. We found that overexpression of c-erbB-3 occurs frequently in NNBC. Overall, 138 of 212 carcinomas (65%) had some degree of membrane RTJ1 staining, and 28 (13%) showed strong and generalised positivity ( ). Twenty-four per cent of carcinomas had membrane 21N staining, and 12% presented strong and generalised positivity ( ). c-erbB-3 protein expression was significantly associated only with that of c-erbB-2 (P = 0.05), whereas 21N positivity was significantly associated with small tumour size (P = 0.02) and ductal histotype (P = 0.04). No significant correlation between expression of either receptor proteins or relapse-free survival was observed after a median follow-up of 63 months. Applying multivariate analysis, only tumour size approached significance. Our results indicate that analysis of expression of c-erbB-3 and c-erbB-2 alone do not seem to be useful in identifying patients with NNBC at different risk of relapse or death.

Adult↗

Vinorelbine is an active antiproliferative agent in pretreated advanced breast cancer patients: a phase II study.

PURPOSE: To evaluate the efficacy and toxicity of single-agent vinorelbine (VNB), a semisynthetic vinca alkaloid, in patients with breast cancer previously treated with other chemotherapeutic regimens for metastatic disease. PATIENTS AND METHODS: Sixty-seven of 70 patients with assessable disease entered onto the study were assessable. The main characteristics were as follows: median age, 60 years (range, 41 to 77); median performance status (PS; Karnofsky score), 90 (range, 60 to 100); and number of previous chemotherapeutic regimens given--one in 17, two in 27, three in eight, four in two, and five in one patient. The dominant sites of metastasis were viscera in 40, bone in 16, and soft tissues in 11 patients. VNB was administered beginning with the dose of 20 mg/m2 by 60-minute intravenous (iv) infusion weekly, with a dose escalation up to 25 mg/m2 if the first four courses were well tolerated. The treatment was continued until disease progression. RESULTS: Overall, 845 courses of VNB were given (median, 10; range, eight to 33). Objective responses were as follows: complete response (CR) in three (4.5%), partial response (PR) in 21 (31.2%), stable disease (SD) in 20 (30%), and progressive disease (PD) in 23 patients (34.3%). Twenty-four of 67 assessable patients obtained a major objective response (CR or PR, 36%; 95% confidence interval [Cl], 24% to 47%). Thirty-three percent of patients had a > or = 33% reduction of dose-intensity (DI). The median time to progression was 18 weeks. The drug was active in patients pretreated with either cyclophosphamide, methotrexate, and fluorouracil (CMF) or anthracyclines. The most relevant toxicity observed was myelosuppression: 17 (25%) and 19 patients (28%) had World Health Organization grade III, and six (9%) and six patients (9%) had grade IV leukopenia and granulocytopenia, respectively; two (3%) and two patients (3%) had grade III and IV anemia, respectively. Nonhematologic toxicities were phlebitis (grade II or III in 15 patients), alopecia (grade I or II in 16), nausea and vomiting (grade II or III in 15), diarrhea (grade II in two), constipation (grade II or III in 16), stomatitis (grade II or III in 13), peripheral neuropathy (grade II in seven), and asthenia (grade II in five). CONCLUSION: This study shows that VNB is an effective and well-tolerated agent in pretreated patients with advanced breast cancer. This drug does not seem to present cross-resistance with previous CMF or anthracycline regimens. Future clinical trials should be designed to prove whether the inclusion of VNB in combination chemotherapy regimens, or whether an enhancement of its dose-intensity using bone marrow growth factors, is able to improve further the efficacy of this drug in breast carcinoma.

Adult↗

Tumor microvessel density, p53 expression, tumor size, and peritumoral lymphatic vessel invasion are relevant prognostic markers in node-negative breast carcinoma.

PURPOSE: To determine the absolute and relative value of microvessel density (MVD), p53 and c-erbB-2 protein expression, peritumoral lymphatic vessel invasion (PLVI), and conventional prognosticators in predicting relapse-free (RFS) and overall survival (OS) rates in patients with node-negative breast carcinoma (NNBC). PATIENTS AND METHODS: We monitored 254 consecutive patients with NNBC for a median of 62 months. Intratumoral MVD was measured after microvessels were immunostained using anti-CD31 antibody. p53 and c-erbB-2 protein and hormone receptors were also determined immunocytochemically. Results were analyzed by both univariate and multivariate statistical analysis. RESULTS: Univariate analysis showed that MVD was significantly predictive of both RFS (odds ratio [OR], 8.30; P = .0001) and OS (OR, 4.50; P = .012) when tested as a continuous or dichotomous variable. Likewise, tumor size (OR, 3.16; P = .0012), PLVI (OR, 4.36; P = .0009), estrogen receptor (ER) status (OR, 2.35; P = .016), progesterone receptor (PR) status (OR, 2.00; P = .017), and expression of p53 protein (OR, 2.82; P = .004) were significantly associated with RFS. Tumor size (OR, 3.80; P = .0038) and expression of p53 protein (OR, 2.58; P = .024) were significantly associated with OS by univariate analysis. Multivariate analysis showed that MVD (P = .0004), p53 protein expression (P = .0063), tumor size (P = .0144), and PLVI (P = .0033) were all significant and independent prognostic factors for RFS. However, only tumor size (P = .004) and MVD (P = .047) were independent predictors for OS. c-erbB2 expression was not associated with outcome by either univariate or multivariate analysis. CONCLUSION: MVD, p53 expression, PLVI, and tumor size are independent prognostic indicators of recurrence, which are useful in selection of high-risk NNBC patients who may be eligible to receive adjuvant therapies.

Adult↗

[Imposing "calcium milk" lithiasis in giant hydronephrosis].

The authors report a quite unusual case of "milk of calcium renal Stone" in unilateral giant Hydronephrosis. Radiographic, sonographic, intravenous urographic and TC aspects are described and prominence il given to morphostructural information obtained through digital image techniques of pyeloureteral zone junction and of "milk of calcium renal Stone". The authors discuss the pathogenesis of the renal Stone type and emphasize the convenience of investigative acts to clear up the ethio-pathogenetic role of pyeloureteral infections.

Adult↗

[The National Workshop on Defecography: anorectal deformities with a functional origin (prolapse, intussusception, rectocele)].

The nonoperative treatment--i.e., rubber band ligation and sclerotherapy--of mucous rectal prolapse, rectocele and intussusception is much less expensive than conventional surgery (Lit. 325,000 vs. 6,500,000, p < 0.0001 on the average). Symptom relief, however, has been reported in 0 to 57% of cases only, according to current literature. A possible cause is represented by improper management from misdiagnosis, relying on clinical findings only, overestimating mucous prolapse in 36.37% of cases and underestimating intussusception in 14.22% of cases (with respect to defecography). Defecography is a cost-effective method (average cost: Lit. 37,000) potentially reducing failure rate after the surgical repair of rectal prolapse.

Ambulatory Surgical Procedures↗

Intratumoral microvessel density and p53 protein: correlation with metastasis in head-and-neck squamous-cell carcinoma.

Squamous-cell carcinoma of the head and neck includes a heterogeneous group of tumours of the upper air and food passages for which prognosis is difficult to assess. In fact, patients in comparable stages may have diverse clinical courses and responses to similar treatments. In order to better define the prognosis of each patient there is therefore a need to identify novel biological markers which reflect more accurately growth rate, progression and metastatic potential of each tumour. We assessed whether metastases correlate with microvessel counts (i.e. intratumoral vascularity) using the CD-31 monoclonal antibody (MAb) and p53 mutant protein expression, determined in the primary by immunocytochemical methods in 70 patients with locally advanced head and neck cancer. Patients were treated with concurrent chemo-radiotherapy; 50 of these presented loco-regional node metastasis at diagnosis whereas 3 cases, initially node-negative, developed distant metastasis during the period of observation. No feature was predictive for objective response to treatment. The overall mean and median blood vessel density at "hot spots" was 37.42 and 36, respectively, and 57% of the tumours expressed p53 mutant proteins. These 2 biological markers were significantly associated. Patients with metastases (loco-regional and distant) had a significantly higher mean blood-vessel density than those without tumour spread. Also, patients with p53-positive (+/++) tumours had a significantly higher incidence of metastasis than those with negative ones. Multivariate analysis showed that both vascularity and stage, but not p53 expression, are significant and independent predictors of metastasis in this series.

Adult↗

Evaluating the potential usefulness of new prognostic and predictive indicators in node-negative breast cancer patients.

The incidence of breast cancer is increasing in all Western countries. Due both to a more widespread public education and to early diagnosis by mammography screening programs, the percentage of patients with node-negative breast cancer has gone up to 70%. Thus, node-negative breast cancer is a major public health problem and, consequently, clinical research in this setting is an expanding field. A recent overview analysis confirmed the results of five prospective randomized clinical trials suggesting that systemic adjuvant therapy can benefit node-negative breast cancer patients. Because of the heterogeneity of node-negative breast cancer, it is reasonable to attempt to avoid excessive treatment morbidity and costs by using selective prognostic markers to identify patients at high risk for disease recurrence who are eligible for postsurgical systemic adjuvant therapy. It is also desirable to use predictive markers in selecting the therapy to which each patient is more likely to respond. The need for additional prognostic and predictive factors has led to identification of a plethora of potentially useful markers. As a result, the selection of patients at different risks of developing node-negative breast cancer and the choice for appropriate therapy remain difficult and confusing for the clinician. Moreover, the majority of studies have examined new markers individually rather than by multivariate analysis and retrospectively rather than prospectively. Thus, there are also important methodologic biases in such studies. This analysis consists of (a) defining the clinical "problem," (b) defining the terms of prognostic and predictive factors, (c) suggesting more appropriate laboratory and clinical approaches to properly evaluate a new indicator, (d) identifying the subsets of patients in whom the use of new prognosticators is warranted and of particular importance, and (e) providing some direction for future research on this topic. Our ultimate goals are to facilitate the understanding of node-negative breast cancer prognostic markers among clinicians, to help them select the most appropriate indicator for specific situations, and to recommend methodology for future research.

Adult↗