Chemoprevention of breast cancer Cuzick, Jack
Women's Health,
2006-November-01, 20061100, 2006-Nov, 2006-11-00, 20061101, Volume:
2, Issue:
6
Journal Article, Book Review
Peer reviewed
Open access
Trials with tamoxifen have clearly shown that estrogen receptor-positive breast cancer risk can be reduced at a late stage in the natural history with prophylactic agents. Approximately half of the ...cases were prevented. The current challenge is to achieve this or better efficacy, and reduce side effects. A recent trial found that the selective estrogen receptor modulator raloxifene has similar efficacy to tamoxifen but fewer side effects. Long-term Phase III trials are currently underway studying two aromatase inhibitors. Results from other studies suggest that these agents have a better side-effect profile and may prevent 70-80% of receptor-positive breast cancers. New agents are needed for receptor-negative breast cancer and several possibilities are currently under investigation.
There has been a noticeable shift in discussions about cervical cancer, moving from prevention to elimination. Interventions such as FASTER, human papillomavirus (HPV) vaccination and HPV screening ...are innovative intervention strategies which can be utilized to begin a path to elimination. To explore the feasibility of the FASTER strategy, an evaluation was carried out in eight primary health-care centers within the Tlalpan Health-Jurisdiction of Mexico City between March 2017 and August 2018. A mixed methods approach was used to evaluate three components: infrastructure, patient acceptability, and health-care professionals' perceptions. This included checklists of requirements for the infrastructure rollout of FASTER and interviews with women and health-care professionals. Nearly all (93%) of the 3,474 women aged 25-45 years accepted HPV vaccination as part of a combined vaccination and screening program. The main reason for acceptance was prevention, while having doubts about the vaccine's benefits was the main reason for refusal. Most of the 24 health-care professionals had a positive opinion toward HPV vaccination and identified the need to increase dissemination, inform the population clearly and concisely and currently extend the age range for vaccination. The evaluation of eight primary health-care centers showed they had the necessary infrastructure for the development of a joint HPV prevention strategy, but many centers required improvements to become more efficient. Together these findings suggest that although HPV vaccine acceptance was high, there is the need to increase education and awareness among potential vaccine recipients and health-care professionals to implement the FASTER strategy.
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Background: Obesity is an adverse prognostic factor in BC. Mixed results are reported for the relative efficacy of AIs compared to tamoxifen (T) in obese ER+ BC patients. Our ...purpose was to conduct a meta-analysis of adjuvant randomised trials of AIs vs T assessing the impact of body mass index (BMI). Methods: We identified four studies evaluating BMI and endocrine therapy. Of these, 3 were randomised (non-steroidal AIs vs T) and were evaluable for the aggregation of results for DFS and OS in our meta-analysis. We extracted published data from ATAC, ABCSG-12 and BIG01-98, analyzed according to standard meta-analytic techniques. Results: A total of 11,383 patients were included in our study. BMI>25 is associated with reduced disease free survival (DFS) and a trend towards worse overall survival (OS) (Table 1). A significantly shorter DFS was seen for patients with BMI>25 treated with an AI while a trend was seen for OS. Reduced relative efficacy was seen for DFS for AIs compared to T for BMI<25 (HR=0.78; 95%CI 0.66- 0.91; p=0.002) and a trend for BMI>25 (HR=0.85; 95%CI 0.70- 1.02; p=0.08). The test for interaction was not significant (p=0.48), with similar results for OS for BMI<25 (HR=0.79; 95%CI 0.63-0.9; p=0.009) and BMI>25 (HR=0.98; 95%CI 0.61-1.60; p=0.95). The test for interaction was not significant (p=0.37). Notably, significant heterogeneity in patients treated with anastrozole and a BMI>25 did not allow a comparison between anastrozole and letrozole. Conclusions: BMI>25 has a negative prognostic effect in BC. AIs demonstrate improved outcomes in normal weight BC patients (BMI<25). Obesity was associated with observed relative reduced efficacy of AIs; however, we were not able to detect a significant interaction between BMI and treatment effect. Further analyses into the differing impact of type of AIs on BC outcomes in obese patients are warranted. Table: see text
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Background: Most postmenopausal women with node positive HR+ EBC receive adjuvant chemotherapy. We hypothesized that a molecular-based characterization of residual risk after ...endocrine therapy using the ROR score and IS may identify node-positive patient subgroups with limited long-term recurrence risk after endocrine therapy better than clinical-pathological risk assessment by clinical treatment score (CTS) alone. Methods: Long-term follow-up and tissue samples were obtained from 2,485 postmenopausal HR+ patients from the ABCSG-8 (N=1,478) and transATAC (N=1,007) trials. The PAM50 test was conducted on RNA extracted from paraffin blocks using the NanoString nCounter Analysis system. The ability of ROR, IS and ROR-defined risk groups (ROR-RG) to add prognostic information to CTS was assessed by the likelihood ratio test in a prospectively defined analysis plan. Results: Patients in the combined data set were grouped by the number of positive nodes into 1 (N1), 2 (N2), or 2 or 3 (N2-3),Baseline hazards for these subgroups were similar in the two trials. ROR score, IS and ROR-RG added statistically significant prognostic information (10-year distant recurrence risk) beyond CTS in all groups. In patients with one positive node, the absolute 10-year risk of distant recurrence was 6.6% 95% CI: 3.3%-12.8% in the PAM-50-low risk group (40% of patients) and 8.4 % 5.3%-13.3% in the Luminal A subgroup (69% of patients). Conclusions: The results of this combined analysis demonstrate that a significant proportion of N1 EBC patients have very limited long term recurrence risk and suggest the same for some N2 patients. The PAM50 ROR score, IS and ROR-RG reliably provide additional prognostic information beyond CTS and may be useful in deciding which women with node-positive HR+ EBC can be spared adjuvant chemotherapy. Table: see text
We investigated if methylation of candidate genes can be useful for predicting prostate cancer (PCa) specific death.
Methylation of PITX2, WNT5a, SPARC, EPB41L3 and TPM4 was investigated in a 1:2 ...case-control cohort comprising 45 men with cancer of Gleason score ≤ 7 who died (cases), and 90 men who were alive or died of other causes with survival time longer than the cases (controls). A univariate conditional logistic regression model was fitted by maximizing the likelihood of DNA methylation of each gene versus the primary end point.
A 10% increase in methylation of PITX2 was associated with PCa related death with OR 1.56 (95% CI: 1.17-2.08; p = 0.005).
Our study strengthens prior findings that PITX2 methylation is useful as a biomarker of poor outcome of PCa and in addition we also suggest that it may be particularly useful in men with low Gleason score.
The finding that cervical cancer only occurs in women infected with specific, “high-risk” types of the human papillomavirus (HPV) has led to the development of novel, non-cytology-based cervical ...cancer prevention strategies. We now have sensitive molecular methods for detecting HPV that dramatically improve our ability to detect high-grade cervical cancer precursor lesions. Perhaps more importantly, prophylactic HPV vaccines have been developed that are protective against cervical cancer precursors caused by HPV 16 and 18. In the Spring of 2006, over 100 experts in HPV, cervical cancer screening, and vaccination worked together to define how best to incorporate HPV DNA testing and the HPV vaccines into cervical cancer prevention efforts. In this summary, we summarize the opinions of this expert group on how these advances can be introduced to provide the maximum benefit to women and to reduce the global burden of cervical cancer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
HPV DNA testing is known to be much more sensitive than cytology, but less specific. A range of HPV and related tests in 858 women referred for colposcopy because of an abnormal smear were evaluated ...to compare the performances of these tests. This article compared the Abbott test to other tests which had been previously evaluated. This test was a real true test for 14 high-risk HPV types. The Abbott test was found to be highly sensitive for cervical intraepithelial neoplasia grade 3 or worse (CIN3+) (98.9%) with a specificity of 31.5%. These numbers were comparable with the Qiagen HC2 test, the Roche Linear Array and Amplicor tests, and the Gen-Probe APTIMA test. Differences between these tests appeared to be related mostly to the choice of cutoff level. An added feature of the Abbott test was the provision of type specific results for HPV 16 and 18. J. Med. Virol. 82: 1186-1191, 2010.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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67
Background: Prostate cancer outcomes are variable and difficult to predict. Improved tools are needed to appropriately match treatment to a patient’s risk of progression. We ...developed and validated a multivariate model to predict disease−specific mortality (DSM) by combining clinical parameters (CAPRA score) with a score based on measuring the expression level of cell cycle progression (CCP) genes. Methods: A multivariate prediction model was trained using patients from 4 retrospective cohorts with median clinical follow up of 7.6 years. We used 200 men from the UK diagnosed after TURP, 353 from Scott & White and 388 from UCSF treated with radical prostatectomy, and 118 men from Durham VA treated with EBRT. CCP score was derived from fixed tumor tissue (biopsy or surgical resection). Outcome was either time from treatment to biochemical recurrence (US cohorts) or time from diagnosis to disease specific mortality (UK cohort). The model was validated for predicting time from diagnosis to DSM in 180 men from the UK diagnosed by needle biopsy with clinically localized prostate cancer and managed conservatively (mean/median CAPRA score = 6). Results: A model combining CAPRA with CCP score was fit in the training set by a Cox Proportional Hazards analysis stratified by cohort. The Combined score was defined as 0.39*CAPRA+0.57*CCP score. There were no significant interactions between cohort and CAPRA or CCP score. This suggests that both CCP score and CAPRA confer similar prognostic information regardless of cohort composition, treatment, or specific outcome. In the validation cohort the Combined score was highly prognostic (HR= 2.27, 95%CI: (1.63, 3.16), p = 1.2 x 10−7). By likelihood ratio testing, the Combined score was a better predictor of DSM than CAPRA alone (p = 0.0028). The c−index of the Combined score was 0.75, which was an improvement over CAPRA (c−index 0.71). Conclusions: This multivariate model predicts DSM in a conservatively treated cohort. The model provides prognostic information beyond clinical variables, and can be used to help differentiate aggressive from indolent cancer at diagnosis.
Summary In the United Kingdom (UK), T- and Z-scores are usually calculated using reference ranges derived from United States (US) populations. In the UK arm of a recent randomised trial ...(International Breast Cancer Intervention Study II (IBIS-II)), substantially, fewer women than expected were recruited into the osteopenic graphic removed and osteoporotic (T-score <−2.5) arms of the study. The comparison with data from two independent studies showed that UK women aged >45 years with a typical body mass index of 28 kg m⁻² have spine and hip bone mineral density (BMD) 0.6 standard deviation higher than their US counterparts. Introduction Dual energy X-ray absorptiometry (DXA) is widely used for the diagnosis of osteoporosis and to investigate the effect of pharmacological treatments on BMD. In both routine and research settings, it is important that DXA results are correctly interpreted. Methods T- and Z-scores for the first 650 UK Caucasian women enrolled in the IBIS-II study were compared with data from two independent studies of unrelated, unselected UK Caucasian women: (1) 2,382 women aged 18 to 79 recruited to the Twins UK Adult Twin Registry; (2) 431 women aged 21 to 84 with no risk factors for osteoporosis recruited at Guy's Hospital. All DXA measurements were performed on Hologic densitometers. Subjects were divided into six age bands, and T- and Z-scores were calculated using the manufacturer's US reference range for the spine and the National Health and Nutrition Examination Survey III reference range for the femoral neck and total hip. Results The overall mean Z-scores for the IBIS-II, Twin, and Guy's groups were: spine: +0.61, +0.29, +0.33; femoral neck: +0.42, +0.36, +0.45; total hip: +0.65, +0.38, +0.39 (all p < 0.001 compared with the expected value of 0). The mean body weight of subjects in the three studies was 74.4, 65.5, and 65.4 kg, respectively. Analysis revealed a highly significant relationship between Z-score and weight at each BMD site with a slope of 0.03 kg⁻¹. Conclusions In general, US spine and hip reference ranges are not suitable for the calculation of Z-scores in UK women. For some research study designs, the differences may significantly influence the pattern of subject recruitment.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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