Search PubMed⌕ Search

Biomedical subjects

Jack Cuzick

Publications and source records attributed to Jack Cuzick.

At least 19 recordsLinked to original sources
PubMed2007

Increased cardiovascular mortality more than fifteen years after radiotherapy for breast cancer: a population-based study.

BACKGROUND: Breast radiotherapy as practised in the 1970s and 1980s resulted in significant myocardial exposure, and this was higher when the left breast was treated. It has been proposed that this difference might result in greater cardiovascular mortality following irradiation of the left breast when compared with the right. METHODS: All cases of female breast cancer diagnosed between 1971 and 1988 and recorded on the Thames Cancer Registry database were followed up to the end of 2003 to identify cases who had died from ischaemic heart disease (IHD) or any cardiovascular disease (CVD). A proportional hazards regression analysis was performed, stratified by time since diagnosis, using as the baseline group those women with right-sided disease who did not receive radiotherapy, and adjusting for age at diagnosis. RESULTS: A total of 20,871 women with breast cancer were included in the analysis, of which 51% had left-sided disease. Mortality at 15+ years after diagnosis was increased in recipients of left-breast radiotherapy compared to non-irradiated women with right-sided breast cancer, both for IHD (hazard ratio 1.59; 95% confidence interval 1.21-2.08; p = 0.001) and all CVD (hazard ratio 1.27; 95% confidence interval 1.07-1.51; p = 0.006). When irradiated women with left-sided breast cancer were compared with irradiated women with right-sided breast cancer, cardiovascular mortality at 15+ years after diagnosis was raised by around 25% (IHD: hazard ratio 1.23; 95% confidence interval 0.95-1.60; p = 0.114; CVD: hazard ratio 1.25; 95% confidence interval 1.05-1.49; p = 0.014). CONCLUSION: We have found an elevation in cardiovascular mortality more than 15 years after breast radiotherapy in women diagnosed with breast cancer between 1971 and 1988. The risk was greater following irradiation of the left breast compared with the right. This confirms that radiotherapy as practised in the 1970s and 1980s has resulted in significant long-term cardiac toxicity. In absolute terms, the increase in cardiovascular mortality induced by radiotherapy may be substantial, as these mortality events are relatively common.

Aged↗
PubMed2007

HPV triage for low grade (L-SIL) cytology is appropriate for women over 35 in mass cervical cancer screening using liquid based cytology.

In the experimental arm of a randomised trial, women were tested both for liquid-based cytology and human papillomavirus (HPV) DNA and referred for colposcopy if cytology was ASCUS (atypical cells of undetermined significance) or more severe. We considered those with ASCUS (757) or LSIL (low-grade squamous intraepithelial lesions) (485) and a valid HPV test who received colposcopy. We computed sensitivity, specificity and ROC curves with different values of relative light units (RLU, that are related to viral load) as cut off, using cervical intraepithelial neoplasia grade 2 or more severe (CIN2+) at blind histology review as the endpoint. The area under the receiver operating characteristic (ROC) curve was significantly less among women aged 25-34 years than in those older, both considering ASCUS/AGUS (atypical glandular cells of undetermined significance) (p=0.0355) and LSIL (p=0.0009). At age 35-60 the curves for ASCUS and LSIL were similar, while at age 25-34 the area under the curve for LSIL was significantly less than for ASCUS (p=0.0084). With LSIL cytology, specificity of Hybrid Capture 2 with 2 RLU cut-off was 35.0% (95%CI 28.4-42.1) at age 25-34 and 64.5% (95%CI 58.3-70.3) at age 35-60. In conclusion, triaging by HPV testing performed better in women aged over 35 years than those younger. For older women, HPV triaging should also be considered for managing those with LSIL cytology.

Adult↗
PubMed2006

Overview of the European and North American studies on HPV testing in primary cervical cancer screening.

Several studies suggest that HPV testing is more sensitive than cytology in primary cervical screening. These studies had different designs and were reported in different ways. Individual patient data were collected for all European and North American studies in which cytology was routinely performed and HPV testing was included as an additional parallel test. More than 60,000 women were included. The sensitivity and specificity of HPV testing were compared with routine cytology, both overall and for ages <35, 35-49 and 50+. The age-specific prevalence of high risk HPV (hr-HPV) was also analysed. HPV testing was substantially more sensitive in detecting CIN2+ than cytology (96.1% vs. 53.0%) but less specific (90.7% vs. 96.3%). The sensitivity of HPV testing was similar in all studies carried out in different areas of Europe and North America, whereas the sensitivity of cytology was highly variable. HPV sensitivity was uniformly high at all ages, whereas the sensitivity of cytology was substantially better in women over the age of 50 than in younger women (79.3% vs. 59.6%). The specificity of both tests increased with age. Positivity rates for HPV testing in women without high-grade CIN were region dependent. These results support the use of HPV testing as the sole primary screening test, with cytology reserved for women who test HPV positive. Large demonstration projects are needed to fully evaluate this strategy.

Adolescent↗
PubMed2006

Chapter 29: Knowledge gaps and priorities for research on prevention of HPV infection and cervical cancer.

The recognition that human papillomavirus (HPV) infection is the necessary cause of cervical cancer brought new prevention paradigms in screening and HPV immunization. We now face many questions about how to implement an ambitious evidence-based agenda for cervical cancer prevention. Much is known about the epidemiology and natural history of HPV infection but several key variables remain to be elucidated. Research on HPV transmission requires new study designs to provide useful insights into preventive strategies. HPV testing has carved a niche in clinical practice but to consolidate its role in screening still requires evidence of long-term benefit. The rapidly evolving field of HPV diagnostics has contributed useful information concerning the value of HPV typing. Other screening methods hold promise in specific settings. The decade-long process that brought HPV vaccines to the doorstep of public health application is over. Many questions remain concerning long-term efficacy, correlates of protection, age of vaccination, and delivery. As vaccination makes inroads as a cancer control strategy, screening practices must be reformulated to maximize the synergy between primary and secondary prevention. Research on how to achieve an efficient combination of these modalities is yet to begin, but mathematical models have provided a useful road map for field-testing of promising algorithms. Daunting questions loom large concerning delivery of vaccines to those populations that need it the most. The field of HPV and cervical cancer prevention has never been so multi-disciplinary. A new era has begun and the challenges are many.

Female↗
PubMed2006

Chapter 30: HPV vaccines and screening in the prevention of cervical cancer; conclusions from a 2006 workshop of international experts.

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.

Female↗
PubMed2006

Influence of hormone replacement therapy on tamoxifen-induced vasomotor symptoms.

PURPOSE: Tamoxifen is an effective drug, but its role in prevention is limited by its adverse effect profile. Non-life-threatening adverse effects, such as vasomotor symptoms, have an important influence in its use for prevention. Vasomotor symptoms were evaluated according to follow-up time, severity, and use of hormone replacement therapy (HRT) in a retrospective analysis. PATIENTS AND METHODS: In the International Breast Cancer Intervention Study-I study, 7,154 women at increased risk of breast cancer were randomly assigned to either tamoxifen 20 mg/d or placebo for 5 years. Women gave detailed information on any vasomotor symptoms at each 6-month follow-up visit. RESULTS: Hot flushes were reported more often in the tamoxifen group than in the placebo group (70.6% v 57.1%, respectively; odds ratio, 1.80; 95% CI, 1.63 to 1.99). Severe hot flushes were more strongly related to tamoxifen. In the tamoxifen arm, more women taking HRT at entry experienced hot flushes in the first 6 months than those who did not take HRT (60.8% v 49.2%, respectively; P = .09). In contrast, women on placebo taking HRT at entry experienced fewer hot flushes than women who stopped HRT (22.9% v 34.3%, respectively; P = .03). Furthermore, for women who first began HRT in the first 6 months of the trial compared with women who did not begin HRT, HRT seemed to be much more effective in controlling hot flushes in months 6 to 12 in the placebo arm (47.9% v 20.4%, respectively) than in the tamoxifen arm (51.4% v 39.0%, respectively). CONCLUSION: HRT use at entry or during the trial was not effective in alleviating hot flushes for women in the tamoxifen arm. Our retrospective study suggests that estrogen-based HRT has limited effectiveness among women receiving tamoxifen.

Adult↗
PubMed2006

Impact of chemotherapy regimens prior to endocrine therapy: Results from the ATAC (Anastrozole and Tamoxifen, Alone or in Combination) trial.

BACKGROUND: The 33-month median follow-up of the ATAC (anastrozole and tamoxifen, alone or in combination) trial showed a potential interaction between anastrozole and previous chemotherapy; however, this was much smaller at 47 months' median follow-up. When the effects of different chemotherapy regimens were evaluated at that time, the apparent interaction was limited to patients who had received cyclophosphamide, methotrexate, and 5-fluorouracil (CMF). METHODS: In this retrospective analysis of 68-month data, we investigated the impact of prior chemotherapy, including different chemotherapy regimens, on time to recurrence. The chemotherapy regimens were 1) CMF only; 2) anthracycline-containing regimens (anthracycline or anthracycline and CMF); and 3) other chemotherapy regimens, including taxane-containing combinations. RESULTS: No evidence was found for an interaction between prior chemotherapy and anastrozole (hazard ratio [HR] 0.89 vs. 0.74 for those with or without prior chemotherapy, respectively; P = .21 for interaction). For those with prior chemotherapy, the HR of anastrozole when compared with that of tamoxifen shifted from 0.98 (95% confidence intervals [CI], 0.76-1.28) at 47 months' median follow-up to 0.89 (95% CI, 0.71-1.12) at 68 months' median follow-up and was closer to the overall treatment effect (HR, 0.79; 95% CI, 0.70-0.90). No differences according to type of chemotherapy were seen, and a benefit for anastrozole was also now apparent for patients receiving prior CMF (HR, 0.89; 95% CI, 0.63-1.24). CONCLUSIONS: On the basis of the 5-year Completed Treatment Analysis, the ATAC trial does not indicate that the relative treatment benefits of anastrozole differ significantly between patients who received prior chemotherapy and those who did not.

Aged↗
PubMed2006

Chapter 10: New dimensions in cervical cancer screening.

Human papillomavirus (HPV) testing has clearly demonstrated a higher sensitivity but somewhat lower specificity than cytology. However, there are still issues regarding how best to use it in primary screening. In countries where cytology is of good quality, the most interesting possibility for primary screening is to use HPV testing as the sole screening modality with cytology reserved for triage of HPV-positive women. In countries with a less established infrastructure, however, use of HPV alone would also be attractive, although rapid, simple tests followed by immediate treatment are needed to minimize the number of visits and make best use of limited resources. Several approaches to deal with the lower specificity of HPV testing are also examined. These include HPV typing with a different management strategy for HPV-16 and -18/45, use of viral load to exclude infections unlikely to be associated with > or =CIN-2, and markers of proliferative lesions such as p16 and mRNA or cell-cycle markers such as cdc6 or the mcm5 proteins. Micro-array studies offer the prospect of discovering new, better DNA- or RNA-based diagnostics. The fact that HPV is a sexually transmitted infection may lead to anxiety and concerns about sexual relationships and these issues are also discussed. Ongoing HPV studies are identified and briefly reviewed.

Female↗
PubMed2006

Quality of life of postmenopausal women in the ATAC ("Arimidex", tamoxifen, alone or in combination) trial after completion of 5 years' adjuvant treatment for early breast cancer.

The impact of treatment on health-related quality of life (HRQoL) is an important consideration in the adjuvant treatment of operable breast cancer. Here we report mature HRQoL outcomes from the ATAC trial, comparing anastrozole with tamoxifen as primary adjuvant therapy for postmenopausal women with localized breast cancer. Patients completed the Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire plus endocrine subscale (ES) at baseline, 3 and 6 months, and every 6 months thereafter. Baseline characteristics in the HRQoL sub-protocol were well balanced between the anastrozole (n = 335) and tamoxifen (n = 347) groups in the primary analysis population. As with previously published results at 2 years, there was no statistically significant difference in the Trial Outcome Index of the FACT-B, the primary endpoint of the study, between treatments at 5 years. There were no statistically significant differences between treatment groups in ES total scores. Consistent with the 2-year analysis, there were differences between treatment groups in patient-reported side effects: diarrhea (anastrozole 3.1% vs. tamoxifen 1.3%), vaginal dryness (18.5% vs. 9.1%), diminished libido (34.0% vs. 26.1%), and dyspareunia (17.3% vs. 8.1%) were significantly more frequent with anastrozole compared to tamoxifen. Dizziness (3.1% vs. 5.4%) and vaginal discharge (1.2% vs. 5.2%) were significantly less frequent with anastrozole compared to tamoxifen. In this, the first report of HRQoL over 5 years of initial adjuvant therapy with an aromatase inhibitor, we conclude that anastrozole and tamoxifen had similar impacts on HRQoL, which was maintained or slightly improved during the treatment period for both groups.

Anastrozole↗
PubMed2006

Chapter 20: Issues in planning cervical cancer screening in the era of HPV vaccination.

Human Papillomavirus (HPV) vaccines will likely have an impact as a preventive strategy for cervical cancer. Screening for precancerous lesions cannot be discontinued because vaccination will not protect against HPV types not included in the first generation of vaccines. Moreover, protection for the target types, 16 and 18, which are responsible for most cases of cervical precancerous lesions and cancer, and 6 and 11, which are responsible for a substantial proportion of low-grade lesions, cannot be expected to be absolute, and the likely implementation of HPV vaccination in young women will not impact older groups initially. Cervical cancer control programs will need to be re-evaluated because the addition of HPV vaccination will make the existing approach of high-frequency screening by cytology too costly and inefficient for most public health budgets. Simply making cytology screening less frequent may not be a viable strategy in light of potential problems that may plague cytology performance in conditions of low lesion prevalence. HPV testing has the performance characteristics that would make it an ideal primary screening test in such conditions. Cytology should be reserved for triage of HPV-positive cases because it is more likely to perform with sufficient accuracy in high-prevalence conditions. Another advantage of using HPV testing as a primary screening tool is the opportunity to create infection registries that can link test results from the same women over time, thus allowing an efficient and low-cost strategy to monitor long-term protection among vaccinated women.

Female↗
PubMed2006

Human papillomavirus testing and liquid-based cytology: results at recruitment from the new technologies for cervical cancer randomized controlled trial.

BACKGROUND: Although testing for human papillomavirus (HPV) has higher sensitivity and lower specificity than cytology alone for detecting cervical intraepithelial neoplasia (CIN), studies comparing conventional and liquid-based cytology have had conflicting results. METHODS: In the first phase of a two-phase multicenter randomized controlled trial, women aged 35-60 years in the conventional arm (n = 16,658) were screened using conventional cytology, and women in the experimental arm (n = 16,706) had liquid-based cytology and were tested for high-risk HPV types using the Hybrid Capture 2 assay. Women in the conventional arm were referred to colposcopy with atypical cells of undetermined significance (ASCUS) or higher and those in the experimental arm were referred with ASCUS or higher cytology or with a positive (> or = 1 pg/mL) HPV test. Sensitivity and positive predictive value (PPV) for detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) were calculated. RESULTS: The screening methods and referral criterion applied in the experimental arm had higher sensitivity than that in the conventional arm (relative sensitivity = 1.47; 95% confidence interval [CI] = 1.03 to 2.09) but a lower PPV (relative PPV = 0.40; 95% CI = 0.23 to 0.66). With HPV testing alone at > or = 1 pg/mL and at > or = 2 pg/mL, the gain in sensitivity compared with the conventional arm remained similar (relative sensitivity = 1.43, 95% CI = 1.00 to 2.04 and relative sensitivity = 1.41, 95% CI = 0.98 to 2.01, respectively) but PPV progressively improved (relative PPV = 0.58, 95% CI = 0.33 to 0.98 and relative PPV = 0.75, 95% CI = 0.45 and 1.27, respectively). Referral based on liquid-based cytology alone did not increase sensitivity compared with conventional cytology (relative sensitivity = 1.06; 95% CI = 0.72 to 1.55) but reduced PPV (relative PPV = 0.57; 95% CI = 0.39 to 0.82). CONCLUSIONS: HPV testing alone was more sensitive than conventional cytology among women 35-60 years old. Adding liquid-based cytology improved sensitivity only marginally but increased false-positives. HPV testing using Hybrid Capture 2 with a 2 pg/mL cutoff may be more appropriate than a 1 pg/mL cutoff for primary cervical cancer screening.

Adult↗
PubMed2006

Bone versus breast density.

The common link with oestrogen levels suggests that bone mineral density and mammographic density might also be linked. One study found weak support for this, but another study failed to provide confirmation. Overall, the relationship is very weak, if it exists at all. Other factors such as weight-bearing exercise, which have opposing impacts on these variables, may have a more dominant effect.

Bone Density↗
PubMed2006

The prevention, detection, and management of breast cancer.

The reduction in the incidence of contralateral breast cancer in women treated with adjuvant tamoxifen provided a model for prevention using endocrine agents. Oestrogen-receptor-positive cancer can be prevented with tamoxifen, but side effects limit its clinical utility, and the risk-benefit ratio is not sufficiently high to routinely recommend tamoxifen as a preventive agent. Agents being evaluated in prevention trials include raloxifene and the aromatase inhibitors; these are expected to be at least as effective as tamoxifen and to have fewer side effects. Core needle biopsy (providing histological information) and high-resolution breast ultrasound enhance preoperative assessment of breast cancer. Mammography remains the only screening test shown to reduce breast cancer deaths in randomised trials. Magnetic resonance imaging may have a role in screening women with inherited mutations of the breast cancer genes. Sentinel lymph node biopsy accurately assesses lymph node status and is associated with less morbidity than axillary dissection. Where the biopsy is negative (no histologic evidence of metastases), no further axillary treatment is necessary. Breast reconstruction after mastectomy can produce good cosmetic results, especially where autologous tissue is used. Myocutaneous flaps using latissimus dorsi or transverse rectus abdominus muscles are increasingly popular. Adjuvant trastuzumab therapy in patients whose tumours overexpress HER2 (growth factor receptor) can reduce recurrence rates and improve survival. Neoadjuvant endocrine therapy (as an initial treatment before surgery) is an underutilised treatment in postmenopausal women with oestrogen-receptor-positive large operable or locally advanced cancers. It makes more patients suitable for surgery and offers others the choice of breast conservation.

Antibodies, Monoclonal↗
PubMed2006

Anastrozole as an adjuvant endocrine treatment for postmenopausal patients with breast cancer: emerging data.

The Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial compared the efficacy and safety of anastrozole versus tamoxifen versus the combination as initial adjuvant treatment for early breast cancer in over 9,000 postmenopausal women. Analyses at 33 and 47 months median follow-up showed that anastrozole significantly prolonged disease-free survival and time to recurrence and reduced the incidence of contralateral breast cancer compared with tamoxifen. Results of the completed treatment analysis at 68 months median follow-up confirmed the earlier findings, showing that the absolute difference in disease-free survival continued to increase beyond completion of treatment. Mature safety data from the ATAC trial show that, overall, anastrozole has a favorable safety profile compared with tamoxifen. In the absence of current data on further follow-up or the outcome of trials investigating proactive sequencing of endocrine therapies, we present a model based on several trials, including ATAC. This model suggests that using an aromatase inhibitor as initial adjuvant therapy is a better option than switching to an aromatase inhibitor after >/=2 years of tamoxifen. The relative toxicities of the three approved third-generation aromatase inhibitors, anastrozole, letrozole, and exemestane, are discussed. These data suggest that long-term safety profiles may differ between aromatase inhibitors, although comprehensive comparative data for letrozole and exemestane versus tamoxifen are lacking.

Anastrozole↗