Joerger M.,Cancer Registry St. Gallen Appenzell |
Joerger M.,Cantonal Hospital |
Thurlimann B.,Cantonal Hospital |
Savidan A.,Cancer Registry St. Gallen Appenzell |
And 12 more authors.
Journal of Geriatric Oncology | Year: 2013
Objectives: The primary objective of this population-based study is to describe the patterns of care of elderly patients with breast cancer (BC), and evaluate potential causative factors for the decrease in BC-specific survival (BCSS) in the elderly. Patients and Methods: We included all or representative samples of patients with newly diagnosed BC from seven Swiss cancer registries between 2003 and 2005 (n=4820). Surgical and non-surgical BC treatment was analyzed over 5 age groups (<65, 65 to <70, 70 to <75, 75 to <80 and ≥80. years), and the predictive impact of patient age on specific treatments was calculated using multivariate logistic regression analysis. Results: The proportion of locally advanced, metastatic and incompletely staged BC increased with age. The odds ratio for performing breast-conserving surgery (BCS) in stages I-II BC (0.37), sentinel lymph node dissection (SLND) in patients with no palpable adenopathy (0.58), post-BCS radiotherapy (0.04) and adjuvant endocrine treatment (0.23) were all in disfavor of patients ≥80. years of age compared to their younger peers. Only 36% of patients ≥80. years of age with no palpable adenopathy underwent SLND. In the adjusted model, higher age was a significant risk factor for omitting post-BCS radiotherapy, SLND and adjuvant endocrine treatment. Conclusions: This study found an increase in incomplete diagnostic assessment, and a substantial underuse of BCS, post-BCS radiotherapy, SLND and adjuvant endocrine treatment. in elderly patients with BC. There is a need for improved management of early BC in the elderly even in a system with universal access to health care services. © 2012 Elsevier Ltd.
Crocetti E.,Clinical and Descriptive Epidemiology Unit |
Caldarella A.,Clinical and Descriptive Epidemiology Unit |
Ferretti S.,Ferrara Cancer Registry |
Ardanaz E.,Navarra Public Health Institute |
And 37 more authors.
Breast | Year: 2013
Purpose: Biological markers are crucial factors in order to differentiate female breast cancers and to determine the right therapy. This study aims at evaluating whether testing for biomarkers for female breast cancer has similar frequency and characteristics across and within countries. Methods: Population-based cancer registries of the Association for cancer registration and epidemiology in Romance language countries (GRELL) were asked to complete a questionnaire on biomarkers testing. The data collected referred to invasive female breast cancer cases diagnosed between 2004 and 2009. The investigation focused on 1) the overexpression and amplification of the human epidermal growth factor receptor 2 oncogene (HER2); 2) the expression of oestrogen (ER) and progesterone (PgR) receptors; and 3) the proliferation index (PI). Weighted percentages, the heterogeneity among and within countries, and the correlation between responses and calendar years were evaluated. The study was based on 19,644 breast cancers. Results: Overall, 85.9% of the cases were tested for HER2, 91.8% for both ER and PgR, and 74.1% for proliferative markers. For HER2 and ER-PgR, the frequency of testing increased from 2004 to 2009. Testing varied among countries (HER2 from 82.0% to 95.9%, ER-PgR from 89.3% to 98.9%, PI from 10% to 92%) and also within the same country (e.g. HER2 in Italy from 51% to 99%) as well as within single cancer registries. The most relevant differences were in the scores for positive/negative/not clearly defined HER2 (e.g. HER2 was defined positive if IHC 3+ in 21/33 registries), and in the cut-off of positive cells for ER/PgR (from >0% to >30%) and PI positivity (from >0% to >20%). Conclusions: Biological markers are widely tested in the Romance language countries; however, the parameters defining their positivity may vary, raising concerns about homogeneity in breast cancer classification and treatment. © 2013 Elsevier Ltd.
Molinari F.,Institute of Pathology |
Felicioni L.,University of Chieti Pescara |
Buscarino M.,University of Turin |
De Dosso S.,Oncology Institute of Southern Switzerland |
And 16 more authors.
Clinical Cancer Research | Year: 2011
Purpose: KRAS mutations represent the main cause of resistance to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MoAbs) in metastatic colorectal cancer (mCRC). We evaluated whether highly sensitive methods for KRAS investigation improve the accuracy of predictions of anti-EGFR MoAbs efficacy. Experimental Design: We retrospectively evaluated objective tumor responses in mCRC patients treated with cetuximab or panitumumab. KRAS codons 12 and 13 were examined by direct sequencing, MALDITOF MS, mutant-enriched PCR, and engineered mutant-enriched PCR, which have a sensitivity of 20%, 10%, 0.1%, and 0.1%, respectively. In addition, we analyzed KRAS codon 61, BRAF, and PIK3CA by direct sequencing and PTEN expression by immunohistochemistry. Results: In total, 111 patients were considered. Direct sequencing revealed mutations in codons 12 and 13 of KRAS in 43/111 patients (39%) and BRAF mutations in 9/111 (8%), with almost all of these occurring in nonresponder patients. Using highly sensitive methods, we identified up to 13 additional KRAS mutations compared with direct sequencing, all occurring in nonresponders. By analyzing PIK3CA and PTEN, we found that of these 13 patients, 7 did not show any additional alteration in the PI3K pathway. Conclusions: The application of highly sensitive methods for the detection of KRAS mutations significantly improves the identification of mCRC patients resistant to anti-EGFR MoAbs. ©2011 AACR.
Sant M.,Fondazione IRCCS Instituto Nazionale dei Tumori |
Allemani C.,Fondazione IRCCS Instituto Nazionale dei Tumori |
Tereanu C.,Fondazione IRCCS Instituto Nazionale dei Tumori |
De Angelis R.,Instituto Superiore Of Sanita |
And 54 more authors.
Blood | Year: 2010
Changing definitions and classifications of hematologic malignancies (HMs) complicate incidence comparisons. HAEMACARE classified HMs into groupings consistent with the latest World Health Organization classification and useful for epidemiologic and public health purposes. We present crude, age-specific and age-standardized incidence rates for European HMs according to these groupings, estimated from 66 371 lymphoid malignancies (LMs) and 21 796 myeloid malignancies (MMs) registered in 2000-2002 by 44 European cancer registries, grouped into 5 regions. Age-standardized incidence rates were 24.5 (per 100 000) for LMs and 7.55 for MMs. The commonest LMs were plasma cell neoplasms (4.62), small B-cell lymphocytic lymphoma/chronic lymphatic leukemia (3.79), diffuse B-cell lymphoma (3.13), and Hodgkin lymphoma (2.41). The commonest MMs were acute myeloid leukemia (2.96), other myeloproliferative neoplasms (1.76), and myelodysplastic syndrome (1.24). Unknown morphology LMs were commonest in Northern Europe (7.53); unknown morphology MMs were commonest in Southern Europe (0.73). Overall incidence was lowest in Eastern Europe and lower in women than in men. For most LMs, incidence was highest in Southern Europe; for MMs incidence was highest in the United Kingdom and Ireland. Differences in diagnostic and registration criteria are an important cause of incidence variation; however, different distribution of HM risk factors also contributes. The quality of population-based HM data needs further improvement. © 2010 by The American Society of Hematology.
Stiller C.A.,University of Oxford |
Trama A.,Instituto Nazionale dei Tumori |
Brewster D.H.,Scottish Cancer Registry |
Verne J.,Public Health England |
And 100 more authors.
Cancer Epidemiology | Year: 2014
Kaposi sarcoma (KS) is a virus-related malignancy which most frequently arises in skin, though visceral sites can also be involved. Infection with Kaposi sarcoma herpes virus (KSHV or HHV-8) is required for development of KS. Nowadays, most cases worldwide occur in persons who are immunosuppressed, usually because of HIV infection or as a result of therapy to combat rejection of a transplanted organ, but classic Kaposi sarcoma is predominantly a disease of the elderly without apparent immunosuppression. We analyzed 2667 KS incident cases diagnosed during 1995-2002 and registered by 75 population-based European cancer registries contributing to the RARECARE project. Total crude and age-standardized incidence rate was 0.3 per 100,000 per year with an estimated 1642 new cases per year in the EU27 countries. Age-standardized incidence rate was 0.8 per 100,000 in Southern Europe but below 0.3 per 100,000 in all other regions. The elevated rate in southern Europe was attributable to a combination of classic Kaposi sarcoma in some Mediterranean countries and the relatively high incidence of AIDS in several countries. Five-year relative survival for 2000-2002 by the period method was 75%. More than 10,000 persons were estimated to be alive in Europe at the beginning of 2008 with a past diagnosis of KS. The aetiological link with suppressed immunity means that many people alive following diagnosis of KS suffer comorbidity from a pre-existing condition. While KS is a rare cancer, it has a relatively good prognosis and so the number of people affected by it is quite large. Thus it provides a notable example of the importance of networking in diagnosis, therapy and research for rare cancers. © 2014 Elsevier Ltd.
Miranda C.,Foundation Medicine |
Nucifora M.,Institute of Pathology |
Molinari F.,Institute of Pathology |
Conca E.,Instituto Nazionale dei Tumori IRCCS Foundation |
And 9 more authors.
Clinical Cancer Research | Year: 2012
Purpose: Gastrointestinal stromal tumors (GIST) are characterized by gain-of-function mutations in KIT/ PDGFRA genes leading to a constitutive receptor activation which is well counteracted by imatinib. However, cases in which imatinib as first-line treatment has no effects are reported (primary resistance). Our purpose is to investigate alterations in downstream effectors, not reported so far in mutated GIST, possibly explaining the primary resistance to targeted treatments. Experimental Design:Twoindependent naive GIST cohorts have been analyzed for KIT,PDGFRA, KRAS, and BRAF mutations by direct sequencing. Cell lines expressing a constitutively activated and imatinibresponding KIT, alone or in combination with activated KRAS and BRAF, were produced and treated with imatinib. KIT receptor and its downstream effectors were analyzed by direct Western blotting. Results: In naive GISTs carrying activating mutations in KIT or PDGFRA a concomitant activating mutation was detected in KRAS (5%) or BRAF (about 2%) genes. In vitro experiments showed that imatinib was able to switch off the mutated receptor KIT but not the downstream signaling triggered by RAS-RAF effectors. Conclusions: These data suggest the activation of mitogen-activated protein kinase pathway as a possible novel mechanism of primary resistance to imatinib in GISTs and could explain the survival curves obtained from several clinical studies where 2% to 4% of patients with GIST treated with imatinib, despite carrying KIT-sensitive mutations, do not respond to the treatment. ©2012 AACR.