Role of mammography screening as a predictor of survival in postmenopausal breast cancer patients

We examined the effect of population-based screening programme on tumour characteristics by comparing carcinomas diagnosed during the prescreening (N=341) and screening (N=552) periods. We identified screen detected (N=224), interval (N=99) and clinical cancer (N=229) cases. Median tumour size and proportion of axillary lymph node negative cases were 1.5 cm and 65% in the screen detected group, 2.0 cm and 44% in cases found outside the screening, and 3.2 cm and 41% in the cases from the prescreening period. Survival of the breast cancer patients was 66% (95% CI, 60–71%) in the prescreening era group and 73% (95% CI, 66–78%) in the screening era group after 10 years of follow-up. In the screening era group the survival of the screen detected cases was 86% (95% CI, 80–90%) and that of the clinical cancer cases 73% (95% CI, 66–78%) after 10 years. In multivariate analysis the risk of breast cancer death was not significantly different between the prescreening and screening periods (HR 0.82; 95% CI 0.59–1.12, P=0.21). Detection by screening was not an independent prognostic factor in multivariate analysis (HR 0.75; CI 95% 0.50–1.12; P=0.17)

Neurological symptoms and natural course of xeroderma pigmentosum

We have prospectively followed 16 Finnish xeroderma pigmentosum (XP) patients for up to 23 years. Seven patients were assigned by complementation analysis to the group XP-A, two patients to the XP-C group and one patient to the XP-G group. Six of the seven XP-A patients had the identical mutation (Arg228Ter) and the seventh patient had a different mutation (G283A). Further patients were assigned to complementation groups on the basis of their consanguinity to an XP patient with a known complementation group. The first sign of the disease in all the cases was severe sunburn with minimal sun exposure in early infancy. However, at the time the diagnosis was made in only two cases. The XP-A patients developed neurological and cognitive dysfunction in childhood. The neurological disease advanced in an orderly fashion through its successive stages, finally affecting the whole nervous system and leading to death before the age of 40 years. Dermatological and ocular damage of the XP-A patients tended to be limited. The two XP-C patients were neurologically and cognitively intact despite mild brain atrophy as seen by neuroimaging. The XP-G patients had sensorineural hearing loss, laryngeal dystonia and peripheral neuropathy. The XP-C patients had severe skin and ocular malignancies that first presented at pre-school age. They also showed immunosuppression in cell-mediated immunity. Neurological disease appears to be associated with the complementation group and the failure of fibroblasts to recover RNA synthesis following UV irradiation, but not necessarily to the severity of the dermatological symptoms, the hypersensitivity of fibroblasts to UVB killing or the susceptibility of keratinocytes to UVB-induced apoptosis

The influence of socio-economic and surveillance characteristics on breast cancer survival: a French population-based study

Survival data on female invasive breast cancer with 9-year follow-up from five French cancer registries were analysed by logistic regression for prognostic factors of cancer stage. The Kaplan–Meier method and log-rank test were used to estimate and compare the overall survival probability at 5 and 7 years, and at the endpoint. The Cox regression model was used for multivariate analysis. County of residence, age group, occupational status, mammographic surveillance, gynaecological prevention consultations and the diagnosis mammography, whether within a screening framework or not, were independent prognostic factors of survival. Moreover, for the same age group, and only for cancers T2 and/or N+ (whether 1, 2 or 3) and M0, the prognosis was significantly better when the diagnosis mammography was done within the framework of screening. Socio-economic and surveillance characteristics are independent prognostic factors of both breast cancer stage at diagnosis and of survival. Screening mammography is an independent prognostic factor of survival

Long-term prognosis of breast cancer detected by mammography screening or other methods

Introduction Previous studies on breast cancer have shown that patients whose tumors are detected by mammography screening have a more favorable survival. However, little is known about the long-term prognostic impact of screen-detection. The purpose of the current study was to compare breast cancer-specific long-term survival between patients whose tumors were detected in mammography screening and those detected by other methods. Methods Breast cancer patients diagnosed within five specified geographical areas in Finland in 1991-92 were identified (n=2,936). Detailed clinical, treatment and outcome data as well as tissue samples were collected. Women with in situ carcinoma, distant metastases at the primary diagnosis and women who were not operated were excluded. Main analyses were made with exclusions of patients with other malignancy or contralateral breast cancer followed by to sensitivity analyses with different exclusion criterias. Median follow-up time was 15.4 years. Univariate and multivariate analysis of breast cancer-specific survival were performed. Results Of patients included in the main analyses (n=1,884) 22% (n=408) were screen-detected and 78% (n=1,476) were detected by other methods. Breast cancer-specific 15-year survival was 86% for patients with screen-detected cancer and 66% for patients diagnosed by other methods (p<0.0001, HR=2.91). Similar differences in survival were also observed in women at screening age (50-69 years) as well as in clinically important subgroups, such as patients with small tumors ([less than or equal to]1cm in diameter) and without nodal involvement (N0). Women with breast cancer diagnosed by screening mammography had a more favorable prognosis compared to those diagnosed outside of screening program following adjustments according to patient age, tumor size, axillary lymph node status, histological grade and hormone receptor status. Significant differences in the risk of having future contralateral breast cancer according to method of detection was not observed . Conclusions Breast cancer detection in mammography screening is an independent prognostic factor in breast cancer and is associated with a more favorable survival also in long-term follow-up.BioMed Central open acces

Age-Related Neuronal Degeneration: Complementary Roles of Nucleotide Excision Repair and Transcription-Coupled Repair in Preventing Neuropathology

Neuronal degeneration is a hallmark of many DNA repair syndromes. Yet, how DNA damage causes neuronal degeneration and whether defects in different repair systems affect the brain differently is largely unknown. Here, we performed a systematic detailed analysis of neurodegenerative changes in mouse models deficient in nucleotide excision repair (NER) and transcription-coupled repair (TCR), two partially overlapping DNA repair systems that remove helix-distorting and transcription-blocking lesions, respectively, and that are associated with the UV-sensitive syndromes xeroderma pigmentosum (XP) and Cockayne syndrome (CS). TCR–deficient Csa−/− and Csb−/− CS mice showed activated microglia cells surrounding oligodendrocytes in regions with myelinated axons throughout the nervous system. This white matter microglia activation was not observed in NER–deficient Xpa−/− and Xpc−/− XP mice, but also occurred in XpdXPCS mice carrying a point mutation (G602D) in the Xpd gene that is associated with a combined XPCS disorder and causes a partial NER and TCR defect. The white matter abnormalities in TCR–deficient mice are compatible with focal dysmyelination in CS patients. Both TCR–deficient and NER–deficient mice showed no evidence for neuronal degeneration apart from p53 activation in sporadic (Csa−/−, Csb−/−) or highly sporadic (Xpa−/−, Xpc−/−) neurons and astrocytes. To examine to what extent overlap occurs between both repair systems, we generated TCR–deficient mice with selective inactivation of NER in postnatal neurons. These mice develop dramatic age-related cumulative neuronal loss indicating DNA damage substrate overlap and synergism between TCR and NER pathways in neurons, and they uncover the occurrence of spontaneous DNA injury that may trigger neuronal degeneration. We propose that, while Csa−/− and Csb−/− TCR–deficient mice represent powerful animal models to study the mechanisms underlying myelin abnormalities in CS, neuron-specific inactivation of NER in TCR–deficient mice represents a valuable model for the role of NER in neuronal maintenance and survival