Clinical Outcomes of HER2-Negative Metastatic Breast Cancer Patients in Italy in the Last Decade: Results of the GIM 13-AMBRA Study.

GIM 13-AMBRA is a longitudinal cohort study aimed at describing therapeutic strategies and the relative outcome parameters in 939 HER2-ve MBC patients. Taxanes-based regimens, or taxanes + targeted agents, mainly Bevacizumab, were the preferred first choice in both Luminal (30.2%) and TNBC (33.3%) patients. The median PFS1 was 12.5 months (95% CI 16.79-19.64), without any significant difference according to subtypes, while the median Time to first Treatment Change (TTC1) was significantly lower in TNBC patients (7.7 months-95% CI 5.7-9.2) in comparison to Luminal A (13.2 months, 95% CI 11.7-15.1) and Luminal B patients (11.8 months, 95% CI 10.3-12.8). PFS2 was significantly shorter in TNBC patients (5.5 months, 95% CI 4.3-6.5 vs. Luminal A-9.4, 95% CI 8.1-10.7, and Luminal B-7.7 95% CI 6.8-8.2, F-Ratio 4.30, p = 0.014). TTC2 was significantly lower in patients with TNBC than in those with the other two subtypes. The median OS1 was 35.2 months (95% CI 30.8-37.4) for Luminal A patients, which was significantly higher than that for both Luminal B (28.9 months, 95% CI 26.2-31.2) and TNBC (18.5 months, 95% CI 16-20.1, F-ratio 7.44, p = 0.0006). The GIM 13-AMBRA study is one of the largest collections ever published in Italy and provides useful results in terms of time outcomes for first, second, and further lines of treatment in HER2- MBC patients.

Everolimus Plus Exemestane in Advanced Breast Cancer: Safety Results of the BALLET Study on Patients Previously Treated Without and with Chemotherapy in the Metastatic Setting.

BACKGROUND: The BALLET study was an open-label, multicenter, expanded access study designed to allow treatment with everolimus plus exemestane in postmenopausal women with hormone receptor-positive metastatic breast cancer progressed following prior endocrine therapy. A post hoc analysis to evaluate if previous chemotherapy in the metastatic setting affects the safety profile of the combination regimen of everolimus and exemestane was conducted on the Italian subset, as it represented the major part of the patients enrolled (54%). PATIENTS AND METHODS: One thousand one hundred and fifty-one Italian patients were included in the present post hoc analysis, which focused on two sets of patients: patients who never received chemotherapy in the metastatic setting (36.1%) and patients who received at least one chemotherapy treatment in the metastatic setting (63.9%). RESULTS: One thousand one hundred and sixteen patients (97.0%) prematurely discontinued the study drug, and the main reasons reported were disease progression (39.1%), local reimbursement of everolimus (31.1%), and adverse events (AEs) (16.1%). The median duration of study treatment exposure was 139.5 days for exemestane and 135.0 days for everolimus. At least one AE was experienced by 92.5% of patients. The incidence of everolimus-related AEs was higher (83.9%) when compared with those that occurred with exemestane (29.1%), and the most commonly reported everolimus-related AE was stomatitis (51.3%). However, no significant difference in terms of safety related to the combination occurred between patients without and with chemotherapy in the metastatic setting. CONCLUSION: Real-life data of the Italian patients BALLET-related cohort were an adequate setting to state that previous chemotherapy did not affect the safety profile of the combination regimen of everolimus and exemestane. IMPLICATIONS FOR PRACTICE: With the advent of new targeted agents for advanced or metastatic breast cancer, multiple lines of therapy may be possible, and components of the combined regimens can overlap from one line to another. Thus, it is important to assess even the potential of cumulative and additive toxic effects among the drugs. Previous chemotherapy did not affect the safety profile of the combination regimen of everolimus and exemestane. The continuous monitoring of the safety signals of this drug combination from general clinical practice is important, in particular for stomatitis.

Retinal metastasis regression with eribulin in a heavily pretreated breast cancer patient.

The authors present the case of a heavily pretreated young woman with retinal and brain metastases from breast cancer who was successfully treated with eribulin. Eribulin was given at 1.1 mg/m(2) on day 1 and 8, every 3 weeks for a total of 12 courses. A significant reduction in the size of brain and retinal lesions was achieved after three cycles. The treatment was continued for 12 cycles, with a good profile of tolerability. In this clinical case, eribulin demonstrated to be active on brain and retinal metastases from breast cancer, although preclinical data showed limited ability to cross the blood-brain barrier.

Expression of stemness genes in primary breast cancer tissues: the role of SOX2 as a prognostic marker for detection of early recurrence.

The events leading to breast cancer (BC) progression or recurrence are not completely understood and new prognostic markers aiming at identifying high risk-patients and to develop suitable therapy are highly demanded. Experimental evidences found in cancer cells a deregulated expression of some genes involved in governance of stem cell properties and demonstrated a relationship between stemness genes overexpression and poorly differentiated BC subtypes. In the present study 140 primary invasive BC specimens were collected. The expression profiles of 13 genes belonging to the OCT3/SOX2/NANOG/KLF4 core circuitry by RT-PCR were analyzed and any correlation between their expression and the BC clinic-pathological features (CPfs) and prognosis was investigated. In our cohort (117 samples), NANOG, GDF3 and SOX2 significantly correlated with grade 2, Nodes negative status and higher KI67 proliferation index, respectively (p=0.019, p=0.029, p= 0.035). According to multivariate analysis, SOX2 expression resulted independently associated with increased risk of recurrence (HR= 2,99; p= p=0,004) as well as Nodes status (HR=2,44; p=0,009) and T-size >1 (HR=1,77; p=0,035). Our study provides further proof of the suitable use of stemness genes in BC management. Interestingly, a prognostic role of SOX2, which seems to be a suitable marker of early recurrence irrespective of other clinicopathological features.

The impact of anemia on quality of life and hospitalisation in elderly cancer patients undergoing chemotherapy.

AIM OF THE STUDY: at present, there is very little data available about the impact of anemia on elderly cancer patient's quality of life (QoL). Most of the acquired knowledge has been derived from small studies selected for primary site cancer. This observational study investigates the association between hemoglobin (Hb) level and comprehensive geriatric assessment variables: Cancer Linear Analog Scale (CLAS), Activities of Daily Living (ADL), Mini-Mental State Examination (MMSE) in elderly cancer patients undergoing chemotherapy (CT). METHODS: we enrolled 586 elderly cancer patients undergoing CT who were evaluated at baseline and every 3-4 weeks for at least 12 weeks. The correlation between Hb level changes and the examined index changes were performed using Pearson correlation analysis and a multivariate analysis was performed using a logistic regression model. RESULTS: both univariate and multivariate analyses at baseline showed that Hb values are related to ECOG performance status (PS), stage of disease and self-reported QoL. Hb level variation significantly correlated with CLAS and ADL changes measured at baseline and after 12 weeks. This correlation is highly significant in patients with Hb< 11g/dl. Multivariate analysis showed that Hb change of at least 1g/dl was the only independent predictor of a better quality of life, when assessed by using the CLAS and ADL questionnaire (p<0.05). Moreover the median time of hospitalisation was found to be significantly lower in patients showing higher Hb level (Hb ≥ 11g/dl) (p=0.037). CONCLUSIONS: the findings of this study seem to provide adequate support for the correlation between anemia and elderly cancer patient's QoL. Interestingly, we reported an association between anemia and the length of hospitalisation in this setting of patients. However, the above results do need to be confirmed by further prospective trials.

Polymorphisms in genes involved in DNA repair and metabolism of xenobiotics in individual susceptibility to sporadic diffuse gastric cancer.

BACKGROUND: Gastric cancer is the second highest cause of cancer mortality in the world, despite declining rates of incidence in many industrialized countries. We carried out a case-control study to evaluate whether polymorphisms of DNA repair and glutathione S-transferase (GST) genes modulate the risk of developing diffuse gastric cancer. METHODS: ERCC1 118 T/C, XRCC1 399 G/A, XPD 312 G/A, XPD 751 A/C, XRCC3 241 C/T, MS 919 A/G, GSTP1 105 A/G, GSTM1-null/positive and GSTT1-null/positive genotypes were obtained for a series of 126 Helicobacter pylori-negative diffuse gastric cancer patients and 144 Helicobacter pylori-negative controls sampled from the population of Marche, an area with high gastric cancer risk in central Italy. RESULTS: GSTP1 105 A/G and GSTP1 105 G/G genotypes were identified as protective factors, with odds ratio (OR) of 0.4 (95% CI 0.17-0.81, p=0.01) and OR=0.58 (95% CI 0.33-1, p=0.05), respectively. GSTT1-null genotype was identified as a protective factor, with OR=0.48 (95% CI 0.22-0.99, p=0.04). There was no significant difference between cases and controls for XPD 751 A/C, ERCC1 118 T/C, XRCC3 241 C/T, XRCC1 399 G/A, XPD 312 G/A, GSTM1-null/positive and MS 919 A/G polymorphisms. CONCLUSIONS: This study suggests that GSTP1 105A/G and GSTT1-null/positive genotypes might be associated with a reduced risk for sporadic diffuse gastric cancer. Clin Chem Lab Med 2007;45:822-8.

Desmoplastic small round cell tumour: a description of two cases and review of the literature.

BACKGROUND: Desmoplastic small round cell tumour (DSRCT) is a recently described neoplasm, typically occurring in adolescent and young males. It usually shows an aggressive behaviour, presents in the abdomen, often with diffuse peritoneal implants. It has been demonstrated to be a chemosensitive tumour, generally with short-lasting response and poor survival gain from systemic chemotherapy. The authors report two additional cases of DSRCT and review the available medical literature. PATIENTS AND METHODS: Two young males with intra-abdominal DSRCT were treated with a first-line chemotherapy including carboplatin, doxorubicin and etoposide. RESULTS: Both of the patients obtained a partial response after first-line chemotherapy. The first patient started, subsequently, CD34+ stem cell mobilisation with high-dose cyclophosphamide (7 g/m(2)) in order to perform high-dose chemotherapy, but CD34+ cell count was insufficient to practice leukapheresis; he died 34 months after the diagnosis because of progression of the disease. The second patient underwent cytoreductive surgery, but progressed 2 months later despite second-line treatment; he died 16 months after the diagnosis. CONCLUSION: This experience confirms that DSRCT may be considered a chemosensitive tumour, highly aggressive, with short-lasting response to chemotherapy. Anyway, the recent literature suggests that multidisciplinary treatment including chemotherapy, surgery and radiation might be the proper approach to this rare malignancy.