Ilaria Ardoino

Axillary dissection versus no axillary dissection in older patients with T1N0 breast cancer: 15-year results of a randomized controlled trial.

Objective:To assess the role of axillary dissection in older breast cancer patients with a clinically clear axilla. Background:Axillary dissection, once standard treatment for breast cancer, is associated with considerable morbidity. It has been substituted by sentinel node biopsy with dissection only if the sentinel node is positive. We aimed to determine whether axillary surgery can be omitted in older women, thereby sparing them morbidity, without compromising long-term disease control. Methods:We carried out a randomized clinical trial on 238 older (65–80 years) breast cancer patients, with clinically N0 disease of radiographic diameter 2 cm or less. Patients were randomized to quadrantectomy with or without axillary dissection. All received radiotherapy to the residual breast but not the axilla; all were prescribed tamoxifen for 5 years. Main outcome measures were overall survival and breast cancer mortality. We also assessed overt axillary disease in those who did not receive axillary dissection. Results:After 15 years of follow-up, distant metastasis rate, overall survival, and breast cancer mortality in the axillary dissection and no axillary dissection arms were indistinguishable. The 15-year cumulative incidence of overt axillary disease in the no axillary dissection arm was only 6%. Conclusions:Older patients with early breast cancer and a clinically clear axilla treated by conservative surgery, postoperative radiotherapy, and adjuvant tamoxifen do not benefit from axillary dissection. This study was registered at clinicaltrials.gov (ID NCT00002720).

Histology-specific nomogram for primary retroperitoneal soft tissue sarcoma.

This study was conducted to develop a histology‐specific nomogram to predict postoperative overall survival (OS) at 5 and 10 years in primary retroperitoneal soft tissue sarcoma (STS).

Recurrence and mortality dynamics for breast cancer patients undergoing mastectomy according to estrogen receptor status: different mortality but similar recurrence.

(Cancer Sci 2010; 101: 826–830)

Recurrence and mortality according to Estrogen Receptor status for breast cancer patients undergoing conservative surgery. Ipsilateral breast tumour recurrence dynamics provides clues for tumour biology within the residual breast

Backgroundthe study was designed to determine how tumour hormone receptor status affects the subsequent pattern over time (dynamics) of breast cancer recurrence and death following conservative primary breast cancer resection.MethodsTime span from primary resection until both first recurrence and death were considered among 2825 patients undergoing conservative surgery with or without breast radiotherapy. The hazard rates for ipsilateral breast tumour recurrence (IBTR), distant metastasis (DM) and mortality throughout 10 years of follow-up were assessed.ResultsDM dynamics displays the same bimodal pattern (first early peak at about 24 months, second late peak at the sixth-seventh year) for both estrogen receptor (ER) positive (P) and negative (N) tumours and for all local treatments and metastatic sites. The hazard rates for IBTR maintain the bimodal pattern for ERP and ERN tumours; however, each IBTR recurrence peak for ERP tumours is delayed in comparison to the corresponding timing of recurrence peaks for ERN tumours. Mortality dynamics is markedly different for ERP and ERN tumours with more early deaths among patients with ERN than among patients with ERP primary tumours.ConclusionDM dynamics is not influenced by the extent of conservative primary tumour resection and is similar for both ER phenotypes across different metastatic sites, suggesting similar mechanisms for tumour development at distant sites despite apparently different microenvironments. The IBTR risk peak delay observed in ERP tumours is an exception to the common recurrence risk rhythm. This suggests that the microenvironment within the residual breast tissue may enforce more stringent constraints upon ERP breast tumour cell growth than other tissues, prolonging the latency of IBTR. This local environment is, however, apparently less constraining to ERN cells, as IBTR dynamics is similar to the corresponding recurrence dynamics among other distant tissues.

Inside ST-elevation myocardial infarction by monitoring concentrations of cardiovascular risk biomarkers in blood.

BACKGROUND No information is available on the optimal sampling time to catch the highest increase for biomarkers whose elevation after ST-elevation myocardial infarction (STEMI) is prognostic for adverse events. This study aimed to investigate release kinetics and peak times of cardiac troponin I (cTnI), C-reactive protein (CRP), B-type natriuretic peptide (BNP), chromogranin A (CgA) and cystatin C (CyC) in STEMI patients undergoing primary percutaneous coronary intervention (PPCI). METHODS Blood concentrations of cTnI, CRP, BNP, CgA and CyC were measured before and 6 h, 24 h, and 48 h after PPCI in 84 STEMI patients. The averaged trajectory of marker kinetics was estimated by multivariable regression models adjusted for patient characteristics and orthogonal polynomials were used to describe related releases. RESULTS From the estimated kinetics cTnI peaked at 10 h from symptoms, BNP at 28 h and CRP within 30 h. CyC concentrations did not change, whereas CgA concentrations increased from 6 to 48 h after PPCI. The amount of BNP release was found to be affected by the interaction between gender and age: females<75 years had BNP concentrations fourfold higher than males. CONCLUSIONS According to different release kinetics a single blood sampling for measuring all biomarkers is not recommended.

p53 status identifies triple-negative breast cancer patients who do not respond to adjuvant chemotherapy

Genomic analysis and protein expression assimilate triple-negative breast cancers (TNBC) with basal-like breast tumors. TNBCs, however, have proved to encompass also tumors with normal-like phenotype and known to have favorable prognosis and to respond to chemotherapy. In a recent paper, we have provided evidence that p53 status is able to subdivide TNBCs into two distinct subgroups with different outcome, and consistent with basal- and normal-like phenotypes. Based on this finding, we explored the contribution of p53 status in predicting the response to adjuvant CMF or CMF followed doxorubicin chemotherapy of a group of TNBC patients. Results indicated that TNBC patients with a p53-positive tumor had a shorter relapse-free and overall survival than patients carrying a p53-negative TNBC, corroborating our hypothesis about the relationship between TNBC phenotype (basal-like versus normal-like) and p53 status as predictor of response to anthracycline/CMF-based chemotherapy.

Ipsilateral breast tumour recurrence (IBTR) dynamics in breast conserving treatments with or without radiotherapy

Purpose: To study whether ipsilateral breast tumour recurrence (IBTR) dynamics are modified by post-operative radiotherapy (RT). Methods and materials: The hazard rate for IBTR was analysed in a database from patients undergoing breast conserving surgery with or without post-operative radiotherapy within randomised clinical trials from the Milan Cancer Institute. Results: The hazard rate for IBTR presents a bimodal pattern. Post-operative radiotherapy, in addition to reducing IBTR incidence from 24.5% to 5.8% at 10 years, causes more than a one year delay in its clinical manifestation. Distant metastasis dynamics are not modified by radiotherapy administration. Conclusions: In the light of a biology-based model of breast cancer metastasis development, IBTR peak delay most likely originates in a more prolonged dormancy time that, in turn, is related to local microenvironment conditions. Present clinical findings suggest that, besides a direct killing effect on residual tumour cells, microenvironmental modifications may play a major role in RT effectiveness.

Defining Aging Phenotypes and Related Outcomes: Clues to Recognize Frailty in Hospitalized Older Patients

Background Because frailty is a complex phenomenon associated with poor outcomes, the identification of patient profiles with different care needs might be of greater practical help than to look for a unifying definition. This study aimed at identifying aging phenotypes and their related outcomes in order to recognize frailty in hospitalized older patients. Methods Patients aged 65 or older enrolled in internal medicine and geriatric wards participating in the REPOSI registry. Relationships among variables associated to sociodemographic, physical, cognitive, functional, and medical status were explored using a multiple correspondence analysis. The hierarchical cluster analysis was then performed to identify possible patient profiles. Multivariable logistic regression was used to verify the association between clusters and outcomes (in-hospital mortality and 3-month postdischarge mortality and rehospitalization). Results 2,841 patients were included in the statistical analyses. Four clusters were identified: the healthiest (I); those with multimorbidity (II); the functionally independent women with osteoporosis and arthritis (III); and the functionally dependent oldest old patients with cognitive impairment (IV). There was a significantly higher in-hospital mortality in Cluster II (odds ratio [OR] = 2.27, 95% confidence interval [CI] = 1.15-4.46) and Cluster IV (OR = 5.15, 95% CI = 2.58-10.26) and a higher 3-month mortality in Cluster II (OR = 1.66, 95% CI = 1.13-2.44) and Cluster IV (OR = 1.86, 95% CI = 1.15-3.00) than in Cluster I. Conclusions Using alternative analytical techniques among hospitalized older patients, we could distinguish different frailty phenotypes, differently associated with adverse events. The identification of different patient profiles can help defining the best care strategy according to specific patient needs.

Evaluation of a possible direct effect by casein phosphopeptides on paracellular and vitamin D controlled transcellular calcium transport mechanisms in intestinal human HT-29 and Caco2 cell lines

Intestinal cells are continuously exposed to food whose components are able to modulate some of their physiological functions. Among the bioactive food derivatives are casein phosphopeptides (CPPs), coming from the in vitro or in vivo casein digestion, which display the ability to form aggregates with calcium ions and to increase the uptake of the minerals in differentiated intestinal human HT-29 and Caco2 cells. Since extracellular calcium is a known inactivator of the TRPV6 channel, which is also involved in the colon cancer progression, the present study aims to determine a possible modulation by CPPs of the molecular structures responsible for paracellular and/or transcellular calcium absorption in these two cell lines. The paracellular calcium transport was determined by TEER measurements in Caco2 cells and by Lucifer Yellow flow in HT-29 cells. The possible modulation of transcellular calcium absorption machinery by CPPs was investigated by determining the mRNA expression for both the TRPV6 calcium channel and the VDR receptor in 1,25(OH)₂D₃ pre-treated undifferentiated/differentiated cells. The results obtained point out that: (i) CPPs do not affect paracellular calcium absorption; (ii) 1,25(OH)₂D₃ increases the TRPV6 mRNA expression in both types of cells. In the case of HT-29 cells this is the first determination of the presence of the TRPV6 channel; (iii) CPPs per se are not able to affect the VDR and TRPV6 mRNA expression; (iv) CPP administration does not affect the TRPV6 mRNA expression in 1,25(OH)₂D₃ pre-treated HT-29 cells and Caco2 cells. Unlike peptides coming from the digestion of cheese whey protein digest, the digestion of milk casein produces peptides with no effects on TRPV6 calcium channel expression, though the same peptides are able to determine a calcium uptake by the intestinal cells.

Significance of ipsilateral breast tumor recurrence after breast conserving treatment: role of surgical removal

OBJECTIVE To analyze the pattern over time (dynamics) of further recurrence and death after ipsilateral breast tumor recurrence (IBTR) in breast cancer patients undergoing breast conserving treatment (BCT). METHODS A total of 338 evaluable patients experiencing IBTR were extracted from a database of 3,293 patients undergoing BCT. The hazard rates for recurrence and mortality throughout 10 years of follow-up after IBTR were assessed and were compared to the analogous estimates associated to the primary treatment. RESULTS In a time frame with the time origin at the surgical treatment for IBTR, the hazard rate for further recurrence displays a bimodal pattern (peaks at the second and at the sixth year). Patients receiving mastectomy for IBTR reveal recurrence and mortality dynamics similar to that of node positive (N+) patients receiving mastectomy as primary surgery, apart from the first two-three years, when IBTR patients do worse. If the patients with time to IBTR longer than 2.5 years are considered, differences disappear. CONCLUSIONS The recurrence and mortality dynamics following IBTR surgical removal is similar to the corresponding dynamics following primary tumor removal. In particular, patients with time to IBTR in excess of 2.5 years behave like N+ patients following primary tumor removal. Findings may be suitably explained by assuming that the surgical manoeuvre required by IBTR treatment is able to activate a sudden growing phase for tumor foci most of which, as suggested by the systemic model of breast cancer, would have reached the clinical level according to their own dynamics.