NUOVI STRUMENTI DIAGNOSTICI E NUOVE PROSPETTIVE PER LA SALUTE DELL\u2019OSSO

Sebbene l'osso trabecolare rappresenti solo il 20% dello scheletro, la resistenza dell\u2019osso \ue8 fortemente influenzata, oltre che dalla densit\ue0, anche dalla micro-architettura della struttura trabecolare. Un metodo diagnostico innovativo di recente introduzione, BESTEST\uae, mediante il BSI (Bone Structure Index) misura la risposta elastica alle sollecitazioni da parte della struttura ossea, ricavata da simulazioni di carico condotte con metodi ingegneristici su una biopsia virtuale del paziente, ottenuta da radiogrammi planari dell'epifisi prossimale della mano. I risultati dell\u2019esame sono espressi in termini statistici, BSI_T-score e BSI_Z-score, di significato analogo ma non correlati a quelli utilizzati in densitometria. \uc8 ben noto che i regolatori ipofisari, gli inibitori dell'aromatasi e il tamoxifene nelle donne in pre-menopausa e i chemioterapici hanno tutti un impatto negativo sulla salute delle ossa poich\ue9, bloccando l'attivit\ue0 degli estrogeni o degli androgeni, aumentano il turnover osseo portando ad un rischio crescente di fratture. L'incidenza globale del rischio di fratture nei pazienti in trattamento ormonale per carcinoma mammario varia dall'1,37% all'11%. In questo lavoro, vengono discussi i risultati preliminari ottenuti nella valutazione del BSI_T-score in 100 pazienti di sesso femminile sottoposte a trattamento per carcinoma del seno. I risultati dimostrano che la micro-architettura ossea \ue8 effettivamente influenzata dal trattamento oncologico e che il BESTEST\uae pu\uf2 fornire un prezioso aiuto alla densitometria nella valutazione di queste alterazioni, specialmente quando associate a fratture. Questo studio preliminare fornisce inoltre una base razionale per ulteriori e pi\uf9 approfondite indagini sull'uso di questa nuova tecnica, rapida e sicura, per monitorare l'effetto delle terapie contro il cancro della mammella sulle alterazioni della micro-architettura ossea

A New Genetic Risk Score to Predict the Outcome of Locally Advanced or Metastatic Breast Cancer Patients Treated With First-Line Exemestane: Results From a Prospective Study

Currently there are no reliable biomarkers to predict outcome of exemestane treatment. We designed a prospective study to investigate whether constitutive genetic background might affect response to therapy. In a population of 302 advanced breast cancer patients treated with exemestane we showed that a 5-polymorphism-based genetic score could be used to identify patients with different risks of progression and death.Introduction: Approximately 50% of locally advanced or metastatic breast cancer (MBC) patients treated with first-line exemestane do not show objective response and currently there are no reliable biomarkers to predict the outcome of patients using this therapy. The constitutive genetic background might be responsible for differences in the outcome of exemestane-treated patients. We designed a prospective study to investigate the role of germ line polymorphisms as biomarkers of survival. Patients and Methods: Three hundred two locally advanced or MBC patients treated with first-line exemestane were genotyped for 74 germ line polymorphisms in 39 candidate genes involved in drug activity, hormone balance, DNA replication and repair, and cell signaling pathways. Associations with progression-free survival (PFS) and overall survival (OS) were tested with multivariate Cox regression. Bootstrap resampling was used as an internal assessment of results reproducibility. Results: Cytochrome P450 19A1-rs10046TC/CC, solute carrier organic anion transporter 1B1-rs4149056TT, adenosine triphosphate binding cassette subfamily G member 2-rs2046134GG, fibroblast growth factor receptor-4-rs351855TT, and X-ray repair cross complementing 3-rs861539TT were significantly associated with PFS and then combined into a risk score (0-1, 2, 3, or 4-6 risk points). Patients with the highest risk score (4-6 risk points) compared with ones with the lowest score (0-1 risk points) had a median PFS of 10 months versus 26.3 months (adjusted hazard ratio [AdjHR], 3.12 [95% confidence interval (CI), 2.18-4.48]; P < .001) and a median OS of 38.9 months versus 63.0 months (AdjHR, 2.41 [95% CI, 1.22-4.79], P = .012), respectively. Conclusion: In this study we defined a score including 5 polymorphisms to stratify patients for PFS and OS. This score, if validated, might be translated to personalize locally advanced or MBC patient treatment and management

Bone Structure Evaluation : Perspectives in Oncology

Early phase endocrine-expansive breast and prostate cancers are treated with post-operative adjuvant hormonal therapies and chemotherapeutic drugs that have a negative impact on bone heath, blocking estrogen or androgen activity and increasing bone turnover leading to a progressively higher risk of fractures. At present, DXA monitoring of bone loss is widely recommended in prostate and breast cancer patients, but most fractures occur in patients whose DXA result falls outside the osteoporosis ranges, indicating that DXA might not be the elective exam for evaluating the degree of fracture risk in terms of microarchitecture alterations. The recently introduced Bone Structure Index (BSI) gives an indication of the quality of the bone structure. In this work, we discuss the preliminary results obtained in the evaluation of the BSI in female patients undergoing breast cancer treatment

Metronomic oral vinorelbine in advanced breast cancer and non-small-cell lung cancer: current status and future development

Metronomic chemotherapy (mCT), a frequent administration of low-dose chemotherapy, allows prolonged treatment duration and minimizes the toxicity of standard-dose chemotherapy. mCT has multiple actions against cancer cells including inhibition of angiogenesis and modulation of the immune system. A number of studies lend support to the clinical efficacy of mCT in advanced breast cancer and non-small-cell lung cancer. However, further evidence is necessary to describe the optimal use of mCT and to identify suitable patients. Oral vinorelbine has emerged as a promising metronomic treatment in patients with metastatic breast cancer and non-small-cell lung cancer and is the only orally available microtubule-targeting agent. This paper reviews current evidence on metronomic oral vinorelbine, discusses its management and defines a suitable patient profile on the basis of a workshop of Italian experts

Predictive Factors of Lapatinib and Capecitabine Activity in Patients with HER2-Positive, Trastuzumab-Resistant Metastatic Breast Cancer: Results from the Italian Retrospective Multicenter HERLAPAC Study.

BACKGROUND:There are no validated predictive markers for lapatinib and capecitabine in patients with trastuzumab-resistant HER2 positive metastatic breast cancer. METHODS:Data of 148 consecutive patients treated with lapatinib and capecitabine from March 2007 to December 2013 were collected from 13 Italian institutions. Estimates of progression-free survival (PFS) and overall survival (OS) were obtained with the Kaplan-Meier method and compared with logrank test. The association of clinicopathological variables and the outcome was studied by binary logistic regression analysis and Cox proportional hazard analysis. RESULTS:At a median follow-up of 41 months, median PFS and OS were 7 and 21 months, respectively. Patents with a PFS longer than 7 months had a significantly longer OS, compared with patients with a PFS equal to or shorter than 7 months (36 vs 15 months; p<0.001). Multivariate analysis revealed the benefit of lapatinib-based therapy in terms of PFS and OS was significantly associated with time-to-progression (TTP) on prior first-line trastuzumab-based therapy. In particular, each additional month on first-line trastuzumab based therapy was associated with a reduction in hazard of progression and death after the initiation of lapatinib-based therapy of 2% and 4%, respectively. CONCLUSIONS:A longer TTP to first line trastuzumab seems to predict a prolonged PFS and OS with subsequent lapatinib and capecitabine