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Biomedical subjects

Ian S Fentiman

Publications and source records attributed to Ian S Fentiman.

At least 19 recordsLinked to original sources
PubMed2006

Breast-conserving treatment with or without radiotherapy in ductal carcinoma-in-situ: ten-year results of European Organisation for Research and Treatment of Cancer randomized phase III trial 10853--a study by the EORTC Breast Cancer Cooperative Group and EORTC Radiotherapy Group.

PURPOSE: The European Organisation for Research and Treatment of Cancer conducted a randomized trial investigating the role of radiotherapy (RT) after local excision (LE) of ductal carcinoma-in-situ (DCIS) of the breast. We analyzed the efficacy of RT with 10 years follow-up on both the overall risk of local recurrence (LR) and related to clinical, histologic, and treatment factors. PATIENTS AND METHODS: After complete LE, women with DCIS were randomly assigned to no further treatment or RT (50 Gy). One thousand ten women with mostly (71%) mammographically detected DCIS were included. The median follow-up was 10.5 years. RESULTS: The 10-year LR-free rate was 74% in the group treated with LE alone compared with 85% in the women treated by LE plus RT (log-rank P < .0001; hazard ratio [HR] = 0.53). The risk of DCIS and invasive LR was reduced by 48% (P = .0011) and 42% (P = .0065) respectively. Both groups had similar low risks of metastases and death. At multivariate analysis, factors significantly associated with an increased LR risk were young age (< or = 40 years; HR = 1.89), symptomatic detection (HR = 1.55), intermediately or poorly differentiated DCIS (as opposed to well-differentiated DCIS; HR = 1.85 and HR = 1.61 respectively), cribriform or solid growth pattern (as opposed to clinging/micropapillary subtypes; HR = 2.39 and HR = 2.25 respectively), doubtful margins (HR = 1.84), and treatment by LE alone (HR = 1.82). The effect of RT was homogeneous across all assessed risk factors. CONCLUSION: With long-term follow-up, RT after LE for DCIS continued to reduce the risk of LR, with a 47% reduction at 10 years. All patient subgroups benefited from RT.

Adult↗
PubMed2006

Insight into the treatment of cancer in older patients: developments in the last decade.

In the last decades there has been an increased interest in the treatment of elderly cancer patients and a change in attitude of both clinicians and their patients has occurred. Drugs are now available that might be considered "elderly-friendly" and the enormous advances in surgical procedures and supportive treatments over the recent years have enabled adverse effects to be minimized. A Geriatric Assessment is increasingly used as a tool to define those patients who are more suitable for aggressive chemotherapy or, on the contrary, palliative treatment. For almost all cancers, older patients are better treated today than they were in the past, even though we are still far from optimal management. Despite the perceived barriers to including elderly patients in clinical trials, there are few data to support excluding them. We must not permit increased age in cancer patients to continue to be an important and independent risk factor for receiving inadequate care.

Age Factors↗
PubMed2006

Male breast cancer.

Occurrence of male breast cancer, a rare disease, peaks at age 71 years. Familial cases usually have BRCA2 rather than BRCA1 mutations. Occupational risks include high temperature environments and exhaust fumes, but electromagnetic fields have not been implicated. Hyperoestrogenisation resulting from Klinefelter's, gonadal dysfunction, obesity, or excess alcohol, all increase risk as does exposure to radiation, whereas gynaecomastia does not. Presentation is usually a lump or nipple inversion, but is often late, with more than 40% of individuals having stage III or IV disease. Most tumours are ductal and 10% are ductal carcinoma in situ. Surgery is usually mastectomy with axillary clearance or sentinel node biopsy. Indications for radiotherapy, by stage, are similar to female breast cancer. Because 90% of tumours are oestrogen-receptor-positive, tamoxifen is standard adjuvant therapy, but some individuals could also benefit from chemotherapy. Hormonal therapy is the main treatment for metastatic disease, but chemotherapy can also provide palliation. National initiatives are increasingly needed to improve information and support for male breast cancer patients.

Aged↗
PubMed2006

The insulin-like growth factor system and mammographic features in premenopausal and postmenopausal women.

High levels of circulating insulin-like growth factor-I (IGF-I) and its major binding protein (IGFBP-3) at premenopausal ages have been associated with an increased breast cancer risk. We conducted a cross-sectional study (215 premenopausal women and 241 after natural menopause) nested within the Guernsey prospective studies to examine the relationship between the IGF system and mammographic features of the breast. The mammographically dense area in the breast increased with increasing serum levels of IGF-I (P for linear trend, P(t) = 0.05), IGF-II (P(t) = 0.08), and IGFBP-3 (P(t) = 0.01) only in premenopausal women. IGF-II and IGFBP-3 serum levels were associated with increases in the mammographically lucent area in both premenopausal (P(t) = 0.01 and 0.04, respectively) and postmenopausal women (P(t) < 0.001 for both), but these associations were no longer statistically significant after adjustment for body mass index and waist circumference. Neither the IGF-I/IGFBP-3 nor the IGF-II/IGFBP-3 molar ratio was associated with any of these mammographic features. The number of A alleles at a polymorphic locus in the promoter region of the IGFBP-3 gene was associated with increasing mean IGFBP-3 levels in both premenopausal (P(t) = 0.01) and postmenopausal (P(t) <0.001) women but not with mammographically dense area. These results support the hypothesis that the IGF system may affect the amount of mammographically dense tissue in premenopausal women, possibly by promoting cell proliferation and inhibiting apoptosis in the fibroglandular tissue. The findings also show strong relations between IGF-II and IGFBP-3 levels and the amount of mammographically lucent tissue, reflecting the associations between body adiposity and amount of fat tissue in the breast and between body adiposity and circulating levels of these growth factors.

Adult↗
PubMed2006

Is axillary clearance the standard of care for breast cancer patients with sentinel node involvement?

Sentinel node biopsy (SNB) has become accepted for staging the axilla in early breast cancer with avoidance of axillary lymph node dissection (ALND) in patients with negative SNB. For those with positive SNB, the standard surgical management is ALND; however, this approach is increasingly being challenged. The central problem is that it is not possible to preoperatively predict whether the SNB will be positive, and it is even more difficult to determine the likelihood of nonsentinel node positivity. Various histopathological features indicate increased risk of nonsentinel node metastasis, including size of SNB metastasis, presence of lymphovascular invasion, multifocality, number of involved sentinel nodes and, conversely, the number of negative sentinel nodes. These features have been combined to produce predictive nomograms but, understandably, these still lack precision. Presently, the decision to avoid ALND will depend upon both the clinician and the patient's impression of risk, but if either requires assurance that no residual axillary disease remains, a completion clearance will be required.

Axilla↗
PubMed2005

Mammographic features and subsequent risk of breast cancer: a comparison of qualitative and quantitative evaluations in the Guernsey prospective studies.

Mammographic features are known to be associated with breast cancer but the magnitude of the effect differs markedly from study to study. Methods to assess mammographic features range from subjective qualitative classifications to computer-automated quantitative measures. We used data from the UK Guernsey prospective studies to examine the relative value of these methods in predicting breast cancer risk. In all, 3,211 women ages > or =35 years who had a mammogram taken in 1986 to 1989 were followed-up to the end of October 2003, with 111 developing breast cancer during this period. Mammograms were classified using the subjective qualitative Wolfe classification and several quantitative mammographic features measured using computer-based techniques. Breast cancer risk was positively associated with high-grade Wolfe classification, percent breast density and area of dense tissue, and negatively associated with area of lucent tissue, fractal dimension, and lacunarity. Inclusion of the quantitative measures in the same model identified area of dense tissue and lacunarity as the best predictors of breast cancer, with risk increasing by 59% [95% confidence interval (95% CI), 29-94%] per SD increase in total area of dense tissue but declining by 39% (95% CI, 53-22%) per SD increase in lacunarity, after adjusting for each other and for other confounders. Comparison of models that included both the qualitative Wolfe classification and these two quantitative measures to models that included either the qualitative or the two quantitative variables showed that they all made significant contributions to prediction of breast cancer risk. These findings indicate that breast cancer risk is affected not only by the amount of mammographic density but also by the degree of heterogeneity of the parenchymal pattern and, presumably, by other features captured by the Wolfe classification.

Adult↗
PubMed2004

Melatonin and breast cancer: a prospective study.

BACKGROUND: Experimental data from animals suggest a protective role for the pineal hormone melatonin in the etiology of breast cancer, but results from the few retrospective case-control studies that examined the association in humans have been inconsistent. To determine whether low levels of endogenous melatonin are associated with an increased risk for developing breast cancer, we conducted a prospective nested case-control study among British women. METHODS: Concentrations of 6-sulfatoxymelatonin, the main metabolite of melatonin in urine and a validated marker of circulating melatonin levels, were measured by radioimmunoassay in 24-hour urine samples collected from women shortly after enrollment in the prospective Guernsey III Study. Levels of 6-sulfatoxymelatonin were compared among 127 patients diagnosed with breast cancer during follow-up and among 353 control subjects, matched for age, recruitment date, menopausal status, and day of menstrual cycle for premenopausal women or number of years postmenopausal for postmenopausal women. Associations were examined by analyses of covariance and conditional logistic regression. All tests of statistical significance were two-sided. RESULTS: No statistically significant differences in urinary 6-sulfatoxymelatonin concentrations were observed between women who developed breast cancer and control subjects among premenopausal or postmenopausal women (P=.8 and P=.9, respectively). When data from premenopausal and postmenopausal women were combined in a multivariable analysis adjusted for potential confounders and grouped into three categories defined by 6-sulfatoxymelatonin tertiles of control subjects, the level of 6-sulfatoxymelatonin excreted was not statistically significantly associated with the risk of breast cancer (odds ratio [OR] for breast cancer = 0.95, 95% confidence interval [CI] = 0.55 to 1.65, comparing the middle category with the lowest category of 6-sulfatoxymelatonin concentration, and OR = 0.99, 95% CI = 0.58 to 1.70, comparing the highest category with the lowest category). CONCLUSION: We found no evidence that the level of melatonin is strongly associated with the risk for breast cancer.

Adult↗
PubMed2004

Caesium(137) implant as sole radiation therapy for operable breast cancer: a phase II trial.

BACKGROUND AND PURPOSE: Clinical trials have indicated the need for irradiation of the tumour-bearing quadrant in patients with operable breast cancer treated by conservation therapy even under circumstances where there has been complete pathologic clearance. The aim of this phase II trial was to replace whole breast irradiation with brachytherapy to the tumour bed. PATIENTS AND METHODS: A series of 50 patients with operable breast cancers measuring <==4 cm diameter were treated by combination therapy comprising tumour excision axillary clearance and synoperative insertion of a rigid implant to the tumour bed. The implant was after-loaded with medium dose rate Cs(137) sources giving a dose of 45 Gy in daily four fractions of about 6 h duration. No external beam radiotherapy was given. RESULTS: After a median follow-up of 6.3 years, of the 49 evaluable patients, 80% were alive without relapse. Of the 9 patients (18%) who developed a breast relapse, the site of recurrence was in the index quadrant in 7 cases (78%). Of the series, 26 (81%) gave a subjective rating of cosmetic outcome which was excellent or good. Objectively the treated breast was deemed to be normal in 11 (42%) and abnormal in 15 (58%). CONCLUSIONS: This phase II study suggests that in a selected group of patients with early breast cancer, external whole breast radiotherapy can be replaced by interstitial irradiation to the tumour bed without compromising local disease control and giving an excellent or good cosmetic outcome in the majority of cases.

Adult↗
PubMed2004

Pathogenesis of breast carcinoma.

Breast cancer usually develops after a series of epithelial changes in the terminal ductolobular unit. There are multiple benign causes of breast lumps, the majority of which are not associated with an increased risk of breast cancer. Histological changes of pre-malignancy such as atypical hyperplasia and in situ carcinoma can be identified, and these are indications for either close surveillance or further surgery. At the time of diagnosis, breast cancers can be staged both clinically and pathologically, and this facilitates international comparisons of results of treatment.

Breast Diseases↗
PubMed2004

Pathology of breast carcinoma.

The pathologist examines biopsy material obtained at surgery or preoperatively by core biopsy to make a definitive diagnosis of malignancy and to determine the type and grade of the tumour. Additional prognostic information is provided to the clinician, and this includes the true tumour size and the relative contribution of the in situ and invasive components. Other important factors include multifocality, vascular invasion and the presence and extent of axillary nodal metastases. For optimal use of this important information, close cooperation between the members of the multidisciplinary team is essential.

Adult↗