The socioeconomic impact of cancer on patients and their relatives: Organisation of European Cancer Institutes task force consensus recommendations on conceptual framework, taxonomy, and research directions.

Loss of income and out-of-pocket expenditures are important causes of financial hardship in many patients with cancer, even in high-income countries. The far-reaching consequences extend beyond the patients themselves to their relatives, including caregivers and dependents. European research to date has been limited and is hampered by the absence of a coherent theoretical framework and by heterogeneous methods and terminology. To address these shortages, a task force initiated by the Organisation of European Cancer Institutes (OECI) produced 25 recommendations, including a comprehensive definition of socioeconomic impact from the perspective of patients and their relatives, a conceptual framework, and a consistent taxonomy linked to the framework. The OECI task force consensus statement highlights directions for future research with a view towards policy relevance. Beyond descriptive studies into the dimension of the problem, individual severity and predictors of vulnerability should be explored. It is anticipated that the consensus recommendations will facilitate and enhance future research efforts into the socioeconomic impact of cancer and cancer care, providing a crucial reference point for the development and validation of patient-reported outcome instruments aimed at measuring its broader effects.

Molecular diagnosis of bloodstream infections in onco-haematology patients with PCR/ESI-MS technology.

OBJECTIVES: Onco-haematological patients are prone to develop infections, and antibiotic prophylaxis may lead to negative blood cultures. Thus, the microbiological diagnosis and subsequent administration of a targeted antimicrobial therapy is often difficult. The goal of this study was to evaluate the usefulness of IRIDICA (PCR/ESI-MS technology) for the molecular diagnosis of bloodstream infections in this patient group. METHODS: A total of 463 whole blood specimens from different sepsis episodes in 429 patients were analysed using the PCR/ESI-MS platform, comparing the results with those of blood culture and other clinically relevant information. RESULTS: The sensitivity of PCR/ESI-MS by specimen (excluding polymicrobial infections, n = 25) in comparison with blood culture was 64.3% overall, 69.0% in oncological patients, and 59.3% in haematological patients. When comparing with a clinical infection criterion, overall sensitivity rose to 74.7%, being higher in oncological patients (80.0%) than in haematological patients (67.7%). Thirty-one microorganisms isolated by culture were not detected by IRIDICA, whereas 42 clinically relevant pathogens not isolated by culture were detected moleculary. CONCLUSIONS: PCR/ESI-MS offers a reliable identification of pathogens directly from whole blood. While additional studies are needed to confirm our findings, the system showed a lower sensitivity in onco-haematological patients in comparison with previously reported results in patients from the Intensive Care Unit.

HER-2/neu status and response to CMF: retrospective study in a series of operable breast cancer treated with primary CMF chemotherapy.

PURPOSE: Primary chemotherapy brings the opportunity for an early and accurate assessment of response and offers an ideal model to search for new predictors of response. HER-2/neu is one of the most studied genes for this purpose. PATIENTS AND METHODS: Her-2/neu was tested in a non-randomized series of 300 patients with operable breast carcinomas treated with primary CMF. Response was assessed by mammography. Disease-free survival (DFS) and overall survival (OS) were calculated after a mean follow-up of 116 months. Statistical analysis was performed to study the association between HER-2/neu status and response to CMF. RESULTS: Overexpression/amplification was found in 23.66% cases. Univariate analysis showed that response was similar in HER-2/neu positive and negative tumors (51.38 vs. 47.36%, P = 0.6). Triple negative tumors (ER, PR and HER-2/neu negative) presented the highest response rate (64.9%). By multivariate analysis, response was significantly correlated to higher nuclear grade and negative estrogen receptor status (P = 0.02 and 0.007, respectively). Patients with HER-2/neu positive tumors presented shorter survival rates (P = 0.06). Patients with response to CMF showed a better survival over non-responders independent of Her-2/neu status. Patients with the combination of response to CMF and Her-2/neu negative tumors presented the best outcome. On the other hand, the association of no response to CMF and positive Her-2/neu score was statistically related to poor DFS and OS. CONCLUSIONS: CMF indication is independent of Her-2/neu status.

Predictive value of HER-2 and Topoisomerase IIalpha in response to primary doxorubicin in breast cancer.

AIM: To study the predictive role of HER-2 and Topoisomerase IIalpha (TOP2A) in response to primary doxorubicin. METHODS: Two hundred and thirty-two patients with operable breast cancer were treated with doxorubicin prior to surgery. ER, PgR, grade, Ki-67 and HER-2 status were prospectively assessed. HER-2 overexpression was evaluated with immunohistochemistry; positive cases were then studied for gene copy number of HER-2, TOP2A and chromosome 17 centromere by chromogenic in situ hybridisation. Clinical response was assessed by mammography. Pathological response was evaluated as the percentage of tumour replaced by changes due to chemotherapy. RESULTS: HER-2 amplification was associated with clinical response (p=0.04). ER and PgR negativity, high Ki-67 and HER-2 amplification significantly correlated to pathological response (p<0.05). Tumours with coamplification of HER-2 and TOP2A showed a higher percentage of pathological changes (p=0.6). However, in the multivariate analysis for complete pathological response, ER negativity and high Ki-67 index were the only parameters that maintained statistical significance. CONCLUSION: HER2 and Topoisomerase IIalpha amplification failed to show an association with pathological response to doxorubicin, whereas ER negativity and a high proliferation rate were predictive of complete pathological response to this regime.

Primary chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil in operable breast carcinoma.

BACKGROUND: Primary chemotherapy (PC) is becoming an accepted practice to treat large tumors to avoid mastectomies and as a surrogate of outcome. METHODS: A series of 305 patients with tumors >3 cm with T2-3N0-1M0 classification were treated with a multimodal approach that consisted of 3 courses of primary cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) followed by appropriate local treatment and 3 more courses of CMF or 4 courses of doxorubicin. Response was assessed by mammography. RESULTS: The overall response rate was 48% (a 3% pathologic complete response rate). Conservative surgery was achieved in 79.64% of the patients with a low rate of local disease recurrences (5%). Toxicity was minimal. With a median follow-up of 104 months, the 8-year disease-free survival (DFS) rate was 57.63% and the 8-year overall survival (OS) was 67.65%. The DFS and OS rates for patients with a clinical response were significantly longer, i.e., 70% (P=0.0048) and 90% (P=0.0042), respectively. CONCLUSIONS: PC with CMF was feasible. A high rate of breast-conservative surgery was achieved. The current results stressed the value of PC to increase conservative surgery and as a predictor of outcome.

Algorithm for the diagnosis of HER-2/neu status in breast-infiltrating carcinomas.

Determination of HER-2/neu overexpression/amplification is becoming increasingly important. The aim of this study is to elaborate an algorithm for the diagnosis of Her-2/neu status in breast-infiltrating carcinomas. Three hundred five breast-infiltrating carcinomas were selected to determine HER-2/neu overexpression by immunohistochemistry with two different methods: the monoclonal antibody CB11 and the HercepTest. Fluorescence in situ hybridization (FISH) was performed in a subgroup of those cases. Time-consuming and reagent costs were calculated for each of the procedures. HER-2/neu overexpression was found in 16% and 33% of the tumors with the monoclonal antibody (mAb) CB11 and with the HercepTest, respectively. There were 50 cases with immunohistochemical discordant results; most of them were HercepTest score 2+/mAb CB11 negative (37/50). Of those cases, only 27% presented gene amplification. The algorithm consisted of testing all the specimens with the mAb CB11 for selection of positive cases, negative cases are confirmed with the HercepTest, and FISH is performed only in those cases with immunohistochemical discordant results. The algorithm rate of HER-2/neu positivity in our series was 22%. Time and costs are reduced by 60% and 41%, respectively, compared to FISH. The use of the algorithm is feasible, accurate, and cost-effective in relation to FISH.

Pathologic changes related to CMF primary chemotherapy in breast cancer. Pathological evaluation of response predicts clinical outcome.

The pathologic changes associated to response to primary chemotherapy in a series of 303 operable breast cancers are evaluated and correlated to patients' follow-up (interval free of disease and survival). In our series, the incidence of microscopic changes related to chemotherapy is 43.9%. Tumor replacement by loose fibrosis is the most common pathologic event. In most cases, the intensity of fibrotic change is proportional to the degree of clinical-mammographic reduction of the tumor mass. However, some discrepancies exist in the sense of absence of microscopic changes in cases of well-documented mammographic reduction as well as in cases without clinical reduction but with large areas of chemotherapy-related fibrosis. The presence of pathologic response is significantly associated with better survival rate.

Churg-Strauss syndrome involving the breast: a rare cause of eosinophilic mastitis.

Churg-Strauss syndrome is a rare immunoallergic disorder that usually affects lungs, skin and nervous system. The clinical and radiological findings of Churg-Strauss disease involving the breast are reported and attention is drawn to the fact that, although uncommonly, the breast can be involved by immunological diseases.