Thursday, May 06, 2010
Progesterone induces adult mammary stem cell expansion : Nature
Note: in research; defining the role of progesterones
"Reproductive history is the strongest risk factor for breast cancer after age, genetics and breast density. Increased breast cancer risk is entwined with a greater number of ovarian hormone-dependent reproductive cycles, yet the basis for this predisposition is unknown..........The emerging role of MaSCs (mammary stem cells) in cancer initiation warrants the study of ovarian hormones in MaSC homeostasis. Here we show that the MaSC pool increases 14-fold during maximal progesterone levels at the luteal dioestrus phase of the mouse."
Assessing Health-Related Quality of Life in Gyneco... [Int J Gynecol Cancer. 2010] - PubMed result
Int J Gynecol Cancer. 2010 May;20(4):664-684.
Assessing Health-Related Quality of Life in Gynecologic Oncology: A Systematic Review of Questionnaires and Their Ability to Detect Clinically Important Differences and Change.
Luckett T, King M, Butow P, Friedlander M, Paris T.
*Psycho-oncology Co-operative Research Group, School of Psychology, daggerCentre for Medical Psychology and Evidence-Based Decision-Making (CeMPED), University of Sydney, Sydney, New South Wales, Australia; double daggerDepartment of Medical Oncology, Prince of Wales Hospital, Sydney, New South Wales, Australia; section signAustralia New Zealand Gynaecological Oncology Group (ANZGOG), Sydney, New South Wales, Australia; and parallelSchool of Psychology, University of Sydney, Sydney, New South Wales, Australia.
Abstract
OBJECTIVES:: Researchers wishing to assess the health-related quality of life (HRQoL) of women with gynecologic cancers have a range of questionnaires to choose from. In general, disease-, treatment-, or symptom-specific questionnaires are assumed to be better able to identify between-group differences (sensitivity) and changes over time (responsiveness) than are cancer-specific or generic questionnaires. However, little work has tested this assumption in oncology. We set out to (a) identify all multidimensional HRQoL questionnaires used in studies with women with gynecologic cancer and (b) evaluate their track records in identifying minimal clinically important differences (MCIDs), with a view to making recommendations. METHODS:: We searched MEDLINE using the term quality of life and each gynecologic cancer type, as well as the names of identified questionnaires. We used 10% of the scale range as the threshold for an MCID. RESULTS:: We identified 1 generic (SF-36/SF-12), 3 cancer-specific (European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ] C30, Functional Assessment of Cancer Therapy-General [FACT-G], and short-form Cancer Rehabilitation Evaluation System [CARES-SF]), and 1 disease-specific (QOL-Ovarian Cancer Patient Version) HRQoL questionnaires and 5 disease-specific (QLQ-OV28, FACT-O for ovarian, QLQ-CX24, FACT-Cx for cervical and FACT-V for vulvar), 1 treatment-specific (FACT and Gynecologic Oncology Group-Ntx for neurotoxicity), and 2 symptom-specific (FACT-Anemia and Functional Assessment of Chronic Illness and Therapy [FACIT]-Fatigue) modules. Twenty-seven articles reported results from 26 studies in which an MCID had been identified. The FACIT's anemia and fatigue subscales were more sensitive, and the neurotoxicity subscale more sensitive and responsive than the FACT-G on at least 1 comparison. However, we found no evidence for superior performance by the FACT-G compared with the SF-36 or EORTC and FACIT disease-specific modules versus the QLQ-C30 and FACT-G. There was also little evidence to favor EORTC versus FACIT questionnaires or vice versa. CONCLUSIONS:: The evidence we reviewed offered little support for the hypothesis that disease-, symptom-, or treatment-specific instruments are more sensitive and responsive than cancer-specific or generic questionnaires. However, conclusions were limited by the small number of head-to-head comparisons available. We summarize the clinical contexts in which each instrument identified an MCID to inform choice of questionnaire(s), sample size calculations, and interpretation of results in future studies.
Atypical identification of Lynch syndrome by immunohistochemistry and microsatellite instability analysis on jejunal adenocarcinoma
Note: abstract/free full text (pdf)
*this case describes a patient with many different cancers in the family including breast cancer, MSH6 deficiency
"LS (Lynch Syndrome) has been traditionally described in terms of earlyonset colorectal and endometrial cancers. Although this remains a confirmed association, we are learning more about the variability of LS and the prevalence of other cancers associated with this condition. The majority of cases of LS are reported to be caused by MLH1 and MSH2 gene mutations, but as evaluation for this condition becomes more widespread and routine in cases beyond the classically reported presentation, it is likely that we will come to find that the prevalence of other mismatch gene mutations is much higher than previously suspected."
Surgical Staging and Treatment of Early Ovarian Cancer: Long-term Analysis From a Randomized Trial -- Trimbos et al., 10.1093/jnci/djq149 -- JNCI Journal of the National Cancer Institute
"Abstract:
A long-term follow-up analysis of the randomized clinical trial Adjuvant Chemotherapy in Ovarian Neoplasm (ACTION) from the European Organization for Research and Treatment of Cancer was undertaken to determine whether the original results with a median follow-up of 5.5 years could be verified after longer follow-up with more events........Thus, completeness of surgical staging in patients with early ovarian cancer was found to be statistically significantly associated with better outcomes, and the benefit from adjuvant chemotherapy appeared to be restricted to patients with nonoptimal surgical staging."
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
"Commentary:
CONTEXT AND CAVEATS
Prior knowledge
Surgical Staging and Treatment of Early Ovarian Cancer: Long-term Analysis From a Randomized Trial -- Trimbos et al., 10.1093/jnci/djq149 -- JNCI Journal of the National Cancer Institute
Brief Communication
Surgical Staging and Treatment of Early Ovarian Cancer: Long-term Analysis From a Randomized Trial
Affiliations of authors: Department of Gynecology, Leiden University Medical Center, Leiden, the Netherlands (BT); Medisch Centrum Rijnmond Zuid, Rotterdam, the Netherlands (PT); EORTC Data Centre, Brussels, Belgium (PT, CC, KV, AC); Department of Obstetrics and Gynaecology, University of Brescia, Brescia, Italy (SP); Department of Medical Oncology, Erasmus Medical Center, Rotterdam, the Netherlands (MvdB); Department of Medical Oncology, Hospital Universitario San Carlos, Madrid, Spain (AC)
Correspondence to: Baptist Trimbos, MD, PhD, Department of Gynecology, Leiden University Medical Center, POB 9600, 2300RC Leiden, the Netherlands (e-mail: j.b.m.z.trimbos@lumc.nl).
A long-term follow-up analysis of the randomized clinical trial Adjuvant Chemotherapy in Ovarian Neoplasm (ACTION) from the European Organization for Research and Treatment of Cancer was undertaken to determine whether the original results with a median follow-up of 5.5 years could be verified after longer follow-up with more events. In the ACTION trial, 448 patients with early ovarian cancer were randomly assigned, after surgery, to adjuvant chemotherapy or to observation (no further treatment). The original analysis found that adjuvant chemotherapy improved recurrence-free survival but not overall survival and found in a subgroup analysis that completeness of surgical staging was an independent prognostic factor, with better recurrence-free and overall survival among those with complete (optimal) surgical staging. After a median follow-up of 10.1 years, we analyzed the more mature data from the ACTION trial and found support for most of the main conclusions of the original analysis, except that overall survival after optimal surgical staging was improved, even among patients who received adjuvant chemotherapy (hazard ratio of death = 1.89, 95% confidence interval = 0.99 to 3.60; overall two-sided log-rank test P = .05). More cancer-specific deaths were observed among nonoptimally staged patients (40 [27%] of the 147 deaths in the observation arm and 11 [14%] of the 76 deaths in the adjuvant chemotherapy arm) than among optimally staged patients (seven [9%] of the 75 deaths in the observation arm and 11 [14%] of the 76 deaths in the adjuvant chemotherapy arm) (two-sided 
2 test for heterogeneity, P = .06). Thus, completeness of surgical staging in patients with early ovarian cancer was found to be statistically significantly associated with better outcomes, and the benefit from adjuvant chemotherapy appeared to be restricted to patients with nonoptimal surgical staging.
| CONTEXT AND CAVEATS Prior knowledge In the randomized clinical trial Adjuvant Chemotherapy in Ovarian Neoplasm, 448 patients with early ovarian cancer were randomly assigned, after surgery, to adjuvant chemotherapy or to observation. After a median follow-up of 5.5 years, adjuvant chemotherapy was associated with improved recurrence-free survival but not overall survival. In a subgroup analysis, better recurrence-free and overall survival were observed among those with nonoptimal surgical staging than those with optimal staging. Study design Long-term analysis of data from this trial after a median of 10.1 years of follow-up. Contribution The long-term analysis supported most conclusions from the original analysis, except that overall survival after optimal surgical staging was improved, even among patients who received adjuvant chemotherapy. More cancer-specific deaths were observed among nonoptimally staged patients than among optimally staged patients. Implications Completeness of surgical staging among patients with early ovarian cancer was statistically significantly associated with better outcomes, and the benefit from adjuvant chemotherapy was restricted to patients with nonoptimal surgical staging. Limitations The trial was not designed to compare different surgical staging procedures. Patients could not be prospectively stratified by surgical staging category. The study had a limited sample size. Quality of life was not studied. From the Editors |
Scleroderma-like cutaneous lesions induced by paclitaxel and carboplatin for ovarian carcinoma, not a single course of carboplatin, but re-induced and worsened by previously administrated paclitaxel (Taxol)
"ABSTRACT
Scleroderma-like cutaneous lesion as an adverse event from paclitaxel and carboplatin has been reported. No report shows the occurrence of scleroderma-like cutaneous lesions from a single course of carboplatin. The patient is a 67-year-old female, administered paclitaxel and carboplatin as neoadjuvant chemotherapy. Following four courses, scleroderma-like cutaneous lesions were demonstrated. Skin biopsy corresponded to histopathological findings of scleroderma. Immunological investigation shows only antinuclear antibodies are positive. The characteristic Raynaud's phenomenon of scleroderma and hemorrhagic spots on the cuticles were not found. Postoperatively, a single course of carboplatin treatment was given. Scleroderma-like cutaneous lesions re-induced and worsened. This is the first report detailing scleroderma-like cutaneous lesions induced by previously administrated paclitaxel that worsened by carboplatin."
Discussions/paper: U.S. - JCO: Accelerated Approval and Oncology Drug Development Timelines
"Based on the US Food and Drug Administration's own standards, our findings, and the criticism of others, it is reasonable to conclude that improvements in AA processes are needed. The US Food and Drug Administration should have an open debate about AA restructuring and perhaps develop an entirely new program that better addresses the context of oncology. Public discussion, augmented by open access to relevant data, is essential."
Population-Based Study of the Risk of Second Primary Contralateral Breast Cancer Associated With Carrying a Mutation in BRCA1 or BRCA2 JCO
"The risks of subsequent contralateral breast cancer are substantial for women who carry a BRCA1/BRCA2 mutation. These findings have important clinical relevance regarding the assessment of BRCA1/BRCA2 status in patients with breast cancer and the counseling and clinical management of patients found to carry a mutation."
Curis Reports First Quarter 2010 Financial news
"Genentech also reported in April that:
-- It expects results from ongoing Phase II clinical trials of GDC-0449 in first-line metastatic colorectal in mid-2010 and in advanced ovarian cancer during the second half of 2010."
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