| 31. |
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| 32. |
- Lundgren, Katja, et al.
(author)
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Effects of cyclin D-1 gene amplification and protein expression on time to recurrence in postmenopausal breast cancer patients treated with anastrozole or tamoxifen: a TransATAC study
- 2012
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In: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-542X .- 1465-5411. ; 14:2
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Journal article (peer-reviewed)abstract
- Introduction: Gene amplification of CCND1 is observed in a subgroup of breast cancers with poor prognosis, whereas overexpression of the protein cyclin D-1 has been linked to both worse and better clinical outcome. CCND1 amplification and protein overexpression have also been associated with resistance to treatment with tamoxifen or even to a potentially detrimental effect of tamoxifen. Methods: To clarify these challenging and partly contrasting treatment predictive and prognostic links for cyclin D-1 we analysed a large cohort of postmenopausal breast cancer patients randomised to receive either adjuvant anastrozole or tamoxifen, as part of the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial. The CCND1 amplification status and protein expression of cyclin D-1 were assessed by chromogenic in situ hybridisation and immunohistochemistry, respectively, in 1,155 postmenopausal, oestrogen-receptor-positive breast cancer patients included in the TransATAC substudy. Results: Amplification of CCND1 was observed in 8.7% of the tumours and was associated with increased risk of disease recurrence (hazard ratio = 1.61; 95% confidence interval, 1.08 to 2.41) after adjustment for other clinicopathological parameters. In contrast, nuclear expression of cyclin D-1 protein was associated with decreased recurrence rate (hazard ratio = 0.6; 95% confidence interval, 0.39 to 0.92). The intensity of nuclear or cytoplasmic expression was not of prognostic value. There was no significant interaction between cyclin D-1 status and treatment efficacy, ruling out any major detrimental effect of tamoxifen in CCND1-amplified postmenopausal breast cancer. Conclusions: In summary, CCND1 amplification and low nuclear expression of cyclin D-1 predicted poor clinical outcome in postmenopausal breast cancer patients treated with either anastrozole or tamoxifen.
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| 33. |
- Meijer, Chris J. L. M., et al.
(author)
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Guidelines for human papillomavirus DNA test requirements for primary cervical cancer screening in women 30 years and older
- 2009
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 124:3, s. 516-520
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Journal article (peer-reviewed)abstract
- Given the strong etiologic link between high-risk HPV infection and cervical cancer high-risk HPV testing is now being considered as an alternative for cytology-based cervical cancer screening. Many test systems have been developed that can detect the broad spectrum of hrHPV types in one assay. However, for screening purposes the detection of high-risk HPV is not inherently useful unless it is informative for the presence of high-grade cervical intraepithelial neoplasia (CIN 2/3) or cancer. Candidate high-risk HPV tests to be used for screening should reach an optimal balance between clinical sensitivity and specificity for detection of high-grade CIN and cervical cancer to minimize redundant or excessive follow-up procedures for high-risk HPV positive women without cervical lesions. Data from various large screening studies have shown that high-risk HPV testing by hybrid capture 2 and GP5+/6+-PCR yields considerably better results in the detection of CIN 2/3 than cytology. The data from these studies can be used to guide the translation of high-risk HPV testing into clinical practice by setting standards of test performance and characteristics. On the basis of these data we have developed guidelines for high-risk HPV test requirements for primary cervical screening and validation guidelines for candidate HPV assays. (C) 2008 Wiley-Liss, Inc.
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| 34. |
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| 35. |
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| 36. |
- Trinh, T., et al.
(author)
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Background risk of breast cancer influences the association between alcohol consumption and mammographic density
- 2015
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In: British Journal of Cancer. - : NATURE PUBLISHING GROUP. - 0007-0920 .- 1532-1827. ; 113:1, s. 159-165
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Journal article (peer-reviewed)abstract
- Background: Alcohol consumption has been suggested to increase risk of breast cancer through a mechanism that also increases mammographic density. Whether the association between alcohol consumption and mammographic density is modified by background breast cancer risk has, however, not been studied. Methods: We conducted a population-based cross-sectional study of 53 060 Swedish women aged 40-74 years. Alcohol consumption was assessed using a web-based self-administered questionnaire. Mammographic density was measured using the fully-automated volumetric Volpara method. The Tyrer-Cuzick prediction model was used to estimate risk of developing breast cancer in the next 10 years. Linear regression models were used to evaluate the association between alcohol consumption and volumetric mammographic density and the potential influence of Tyrer-Cuzick breast cancer risk. Results: Overall, increasing alcohol consumption was associated with higher absolute dense volume (cm(3)) and per cent dense volume (%). The association between alcohol consumption and absolute dense volume was most pronounced among women with the highest (>= 5%) Tyrer-Cuzick 10-year risk. Among high-risk women, women consuming 5.0-9.9, 10.0-19.9, 20.0-29.9, and 30.0-40.0 g of alcohol per day had 2.6 cm(3) (95% confidence interval (CI), 0.2-4.9), 2.9 cm(3) (95% CI, -0.6 to 6.3), 4.6 cm(3) (95% CI, 1.5-7.7), and 10.8 cm(3) (95% CI, 4.8-17.0) higher absolute dense volume, respectively, as compared with women abstaining from alcohol. A trend of increasing alcohol consumption and higher absolute dense volume was seen in women at low (<= 3%) risk, but not in women at moderate (3.0-4.9%) risk. Conclusion: Alcohol consumption may increase breast cancer risk through increasing mammographic density, particularly in women at high background risk of breast cancer.
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| 37. |
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| 38. |
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| 39. |
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| 40. |
- Cuzick, Jack, et al.
(author)
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Overview of Human Papillomavirus-Based and Other Novel Options for Cervical Cancer Screening in Developed and Developing Countries
- 2008
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In: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 26, s. 29-41
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Journal article (peer-reviewed)abstract
- Screening for cervical cancer precursors by cytology has been very successful in countries where adequate resources exist to ensure high quality and good coverage of the population at risk. Mortality reductions in excess of 50% have been achieved in many developed countries; however the procedure is generally inefficient and unworkable in many parts of the world where the appropriate infrastructure is not achievable. A summary and update of recently published meta-analyses and systematic reviews on four possible clinical applications of human papillomavirus (HPV) DNA testing is provided in this article: (1) triage of women with equivocal or low-grade cytological abnormalities; (2) follow-up of women with abnormal screening results who are negative at colposcopy/biopsy; (3) prediction of the therapeutic outcome after treatment of cervical intraepithelial neoplasia (CIN), and most importantly (4) primary screening HPV DNA test, solely or in combination with Pap smear to detect cervical cancer precursors. There are clear benefits for the use of HPV DNA testing in the triage of equivocal smears, low-grade smears in older women and in the post-treatment surveillance of women after treatment for CIN. However, there are still issues regarding how best to use HPV DNA testing in primary screening. Primary screening with Hybrid Capture (R) 2 (HC2) generally detects more than 90% of all CIN2, CIN3 or cancer cases, and is 25% (95% CI): 15-36%) relatively more sensitive than cytology at a cut-off of abnormal squamous cells of undetermined significance (ASCUS) (or low-grade squamous intraepithelial lesions (LSIL) if ASC-US unavailable), but is 6% (95% CI: 4-7%) relatively less specific. Several approaches are currently under evaluation to deal with the lower specificity of HPV DNA testing as associated with transient infection. These include HPV typing for HPV-16 and -18/45, markers of proliferative lesions such as p16 and mRNA coding for the viral E6 and/or E7 proteins, with a potential clinical use recommending more aggressive management in those who are positive. In countries where cytology is of good quality, the most attractive option for primary screening is to use HPV DNA testing as the sole screening modality with cytology reserved for triage of HPV-positive women. Established cytology-based programmes should also be gradually moving towards a greater use of HPV DNA testing to improve their efficacy and safely lengthen the screening interval. The greater sensitivity of HPV DNA testing compared to cytology argues strongly for using HPV DNA testing as the primary screening test in newly implemented programmes, except where resources are extremely limited and only programmes based on visual inspection are affordable. In such countries, use of a simple HPV DNA test followed by immediate 'screen and treat' algorithms based on visual inspection in those who are HPV-positive are needed to minimise the number of visits and make best use of limited resources. A review of studies for visual inspection methods is presented. The fact that HPV is a sexually transmitted infection may lead to anxiety and concerns about sexual relationships. These psychosocial aspects and the need for more information and educational programmes about HPV are also discussed in this article. (C) 2008 Elsevier Ltd. All rights reserved.
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