Hormone replacement therapy and incidence of central nervous system tumours in the Million Women Study

We examined the relation between the use of hormone replacement therapy (HRT) and the incidence of central nervous system (CNS) tumours in a large prospective study of 1,147,894 postmenopausal women. Women were aged 56.6 years on average at entry, and HRT use was recorded at recruitment and updated, where possible, about 3 years later. During a mean follow‐up of 5.3 years per woman, 1,266 CNS tumours were diagnosed, including 557 gliomas, 311 meningiomas and 117 acoustic neuromas. Compared with never users of HRT, the relative risks (RRs) for all incident CNS tumours, gliomas, meningiomas and acoustic neuromas in current users of HRT were 1.20 (95% CI: 1.05–1.36), 1.09 (95% CI: 0.89–1.32), 1.34 (95% CI: 1.03–1.75) and 1.58 (95% CI: 1.02–2.45), respectively, and there was no significant difference in the relative risks by tumour type (heterogeneity p = 0.2). In past users of HRT the relative risk was 1.07 (95% CI: 0.93–1.24) for all CNS tumours. Among current users of HRT, there was significant heterogeneity by the type of HRT with the users of oestrogen‐only HRT at higher risk of all CNS tumours than users of oestrogen–progestagen HRT (RR = 1.42, 95% CI: 1.21–1.67 versus RR = 0.97, 95% CI: 0.82–1.16) (heterogeneity p < 0.001). Among current users of oestrogen‐only and oestrogen–progestagen HRT, there was no significant heterogeneity by duration of use, hormonal constituent or mode of administration of HRT.     

Tumors of the Central Nervous System in Korea A Multicenter Study of 3221 Cases.

The Neuropathology Study Group of the Korean Society of Pathologists conducted a nationwide collection of central nervous system (CNS) tumors to evaluate the relative frequency in Korea of CNS tumors belonging to the revised World Health Organization (WHO) classification categories. A total of 3221 histologically proven cases of CNS tumors were collected from 13 institutes between 1997 and 1998. All the cases were classified according to the revised WHO histological types and analyzed for the relative frequency, the distribution of age and sex, and location of tumors. The most frequent type of CNS tumors in Korea was meningiomas, followed by pituitary adenoma, glioblastoma, astrocytoma, and schwannoma. Among the pediatric CNS tumors, pilocytic astrocytoma, medulloblastoma, craniopharyngioma, germ cell tumors, and ependymomas were common types of tumors. Compared with a previous nationwide study, the rates for neuronal/glial tumors, glioblastoma, malignant lymphoma, and cystic lesion were increased, and the rate of embryonal tumors was decreased. The overall male to female ratio was 0.9:1, which may be attributed to the greater number of female-predominate meningiomas and pituitary adenoma. Compared with Western countries, Koreans had higher rates of pituitary adenoma and meningiomas and lower rate of gliomas. The relative frequency of CNS tumors among Koreans is very similar to that reported in Taiwan. The occurrence rates for various subtypes of CNS tumors in Korea are distinct from those in the United States and Europe and similar in many ways to those in Asian and Mexican population.     

Descriptive epidemiology of primary brain and CNS tumors: results from the Central Brain Tumor Registry of the United States, 1990-1994

The Central Brain Tumor Registry of the United States (CBTRUS) obtained 5 years of incidence data (1990-1994)--including reports on all primary brain and CNS tumors--from 11 collaborating state cancer registries. Data were available for 20,765 tumors located in the brain, meninges, and other CNS sites, including the pituitary and pineal glands. The average annual incidence was estimated at 11.5 cases per 100,000 person-years. The higher incidence of tumors in male patients (12.1 per 100,000 person-years) than in female patients (11.0 per 100,000 person-years) was statistically significant (P < 0.05); the higher incidence in whites (11.6 per 100,000 person-years) compared with blacks (7.8 per 100,000 person-years) was statistically significant (P < 0.05). The most frequently reported histologies were meningiomas (24.0%) and glioblastomas (22.6%). Higher rates for glioblastomas, anaplastic astrocytomas, oligodendrogliomas, anaplastic oligodendrogliomas, ependymomas, mixed gliomas, astrocytomas not otherwise specified, medulloblastomas, lymphomas, and germ cell tumors in male than in female patients were statistically significant (P < 0.05), with relative risks (RR) ranging from 1.3 to 3.4. Meningiomas were the only tumors with a significant excess in females (RR = 0.5). We noted higher occurrence rates in whites than in blacks for the following histologies: diffuse astrocytomas, anaplastic astrocytomas, glioblastomas, oligodendrogliomas, ependymomas, mixed gliomas, astrocytomas NOS, medulloblastomas, nerve sheath tumors, hemangioblastomas, and germ cell tumors, with RRs ranging from 1.5 to 3.4. Racial differences in occurrence rates were not observed for predominately benign meningiomas or pituitary tumors. This study represents the largest compilation of data on primary brain and CNS tumors in the United States. Standard reporting definitions and practices must be universally adopted to improve the quality and use of cancer registry data.     

Production of insulin-like growth factor-binding proteins by human central nervous system tumors.

Central nervous system (CNS) tumor cells possess specific receptors for insulin-like growth factors (IGFs) and respond to the growth-promoting effects of IGFs in cell culture. In the present study, we asked whether CNS tumors also produce IGF-binding proteins (BPs) which may modulate the effects of IGFs on CNS tumor cells. Primary cell cultures were established from 20 CNS tumors. Dot blot analysis with 125I-labeled recombinant human IGF-I revealed IGF-binding activity in serum-free conditioned medium from 5 of 7 meningiomas, 7 of 8 malignant gliomas, and 3 of 5 other CNS tumors. Specific IGF BPs in conditioned medium were characterized further by Western ligand and immunoblotting, affinity labeling, and precipitation with specific antibodies against human IGFBP-1, -2, and -3. All conditioned media tested contained an Mr 35,000 BP which was recognized by antiserum against IGFBP-2 and an Mr 24,000 BP that was not recognized by available antisera. Medium conditioned by meningiomas (and one glioma) also contained Mr 45,000 and 50,000 IGF BPs, similar in size and/or immunological properties to growth hormone-dependent BPs present in normal human serum (IGFBP-3). Ligand blotting also showed that meningiomas produce an Mr 29,000 BP; immunoblotting and immunoprecipitation of affinity-labeled IGF-BP complexes confirmed that this BP is recognized by antiserum against IGFBP-1. Immunohistochemistry with specific monoclonal antibodies demonstrated that IGFBP-1 is abundant in pathological specimens of meningiomas and that lower amounts also are detected in malignant gliomas. We conclude that human CNS tumor cells produce a variety of IGF BPs in cell culture, including several that are similar in size and immunological properties to previously characterized human IGF BPs. Immunohistochemistry with specific monoclonal antibodies against IGFBP-1 confirms that this BP is present in vivo, further supporting the concept that IGF BPs may contribute to the regulation of growth in human CNS tumors.     

脑胶质瘤的放射治疗临床研究进展

在全世界,每年约有176000例新发中枢神经系统肿瘤患者,而每年约有128000名患者死于这种疾病。脑胶质瘤约占所有中枢神经系统肿瘤中的42%,其中超过3/4的患者为恶性胶质瘤。放疗能提高大多数脑胶质瘤患者的生存期和生存质量。随着近年来放疗技术的进一步发展,脑胶质瘤术后放疗发生了很大的变化。本文将以WHO分级标准为线索,分别介绍各种脑胶质瘤放射治疗的临床研究进展。     

Occupational and residential exposure to electromagnetic fields and risk of brain tumors in adults: a case-control study in Gironde, France

The etiology of brain tumors remains largely unknown. Among potential risk factors, exposure to electromagnetic fields is suspected. We analyzed the relationship between residential and occupational exposure to electromagnetic field and brain tumors in adults. A case-control study was carried out in southwestern France between May 1999 and April 2001. A total of 221 central nervous system tumors (105 gliomas, 67 meningiomas, 33 neurinomas and 16 others) and 442 individually age- and sex-matched controls selected from general population were included. Electromagnetic field exposure [extremely low frequency (ELF) and radiofrequency separately was assessed in occupational settings through expert judgement based on complete job calendar, and at home by assessing the distance to power lines with the help of a geographical information system. Confounders such as education, use of home pesticide, residency in a rural area and occupational exposure to chemicals were taken into account. Separate analyses were performed for gliomas, meningiomas and acoustic neurinomas. A nonsignificant increase in risk was found for occupational exposure to electromagnetic fields [odds ratio (OR = 1.52, 0.92-2.51)]. This increase became significant for meningiomas, especially when considering ELF separately [OR = 3.02; 95 percent confidence interval (95% CI) =1.10-8.25]. The risk of meningioma was also higher in subjects living in the vicinity of power lines (<100 m), even if not significant (OR = 2.99, 95% CI 0.86-10.40). These data suggest that occupational or residential exposure to ELF may play a role in the occurrence of meningioma.     

Determination of RNA expression for cholecystokinin/gastrin receptors (CCKA,CCKB and CCKC) in human tumors of the central and peripheral nervous system

Gastrin (G17) belongs to the cholecystokinin (CCK) peptide family widely distributed in the brain, and we were the first to show that it significantly modulates the growth and migration features of tumor astyrocytes. Conflictual data have been published as to whether CCKA, CCKB and CCKC receptors are, or are not, present in tumors of the central and peripheral nervous system (CPNS) in general, and in gliomas in particular. In the present study we employed polymerase chain reaction (PCR) on a series of 29 CNPS tumors, including 20 gliomas (17 astrocytic and 3 oligodendroglial tumors), 4 schwannomas and 5 meningiomas to investigate whether RNAs were present or absent in the case of these CCKA, CCKB and CCKC receptors. The presence of the three CCK receptor subtypes was also assayed on three experimental models, i.e. the U373 human glioma, the C6 rat glioma and the 9L rat gliosarcoma. The data show that 9/20 (45%) of the gliomas exhibited RNAs for the CCKB receptor as did the C6 rat glioma, 13/20 (65%) RNAs for the CCKC receptor as did the U373 human glioma and the 9L rat gliosarcoma. Of the 20 gliomas, 17 (85%) expressed RNAs for either the CCKB or the CCKC receptor (or both), a feature which was also observed in the experimental models. One schwannoma and one meningioma exhibited RNAs for the CCKB receptor, while 4/4 schwannomas and 4/5 meningiomas showed RNAs for the CCKC receptor. None of the gliomas, schwannomas or meningiomas exhibited RNAs for the CCKA receptor, which were found in the 9L rat gliosarcoma model only. These data emphasize that 85% of the gliomas under study and 86% (25/29) of the tumors of the central and peripheral nervous system exhibited CCKB and/or CCKC receptors. This therefore suggests an important role for gastrin in the biological development of these tumors.     

Gliomatosis cerebri mimicking a metastatic breast cancer: Fatal outcome

Gliomatosis cerebri (GC) is defined by the World Health Organization as a neoplasm of the glial cells. It is extremely rare, and there exists only 160 documented cases since 1897. There is no known treatment and themedian survival rate is one year. The association of extracranial and CNS tumors is unusual,only three cases of breast cancer have been associatedwith gliomas and meningiomas but none with GC. Below wedescribe a case of breast cancer associated with GC andreview the anatomoclinical and radiological manifestationsof Gliomatosis Cerebri.     

Parental occupational exposure to pesticides,animals and organic dust and risk of childhood leukemia and central nervous system tumors: Findings from the International Childhood Cancer Cohort Consortium (I4C)

Parental occupational exposures to pesticides, animals and organic dust have been associated with an increased risk of childhood cancer based mostly on case–control studies. We prospectively evaluated parental occupational exposures and risk of childhood leukemia and central nervous system (CNS) tumors in the International Childhood Cancer Cohort Consortium. We pooled data on 329,658 participants from birth cohorts in five countries (Australia, Denmark, Israel, Norway and United Kingdom). Parental occupational exposures during pregnancy were estimated by linking International Standard Classification of Occupations-1988 job codes to the ALOHA+ job exposure matrix. Risk of childhood (<15 years) acute lymphoblastic leukemia (ALL; n = 129), acute myeloid leukemia (AML; n = 31) and CNS tumors (n = 158) was estimated using Cox proportional hazards models to generate hazard ratios (HR) and 95% confidence intervals (CI). Paternal exposures to pesticides and animals were associated with increased risk of childhood AML (herbicides HR = 3.22, 95% CI = 0.97–10.68; insecticides HR = 2.86, 95% CI = 0.99–8.23; animals HR = 3.89, 95% CI = 1.18–12.90), but not ALL or CNS tumors. Paternal exposure to organic dust was positively associated with AML (HR = 2.38 95% CI = 1.12–5.07), inversely associated with ALL (HR = 0.55, 95% CI = 0.31–0.99) and not associated with CNS tumors. Low exposure prevalence precluded evaluation of maternal pesticide and animal exposures; we observed no significant associations with organic dust exposure. This first prospective analysis of pooled birth cohorts and parental occupational exposures provides evidence for paternal agricultural exposures as childhood AML risk factors. The different risks for childhood ALL associated with maternal and paternal organic dust exposures should be investigated further.     

Might changes in diagnostic practice explain increasing incidence of brain and central nervous system tumors? A population-based study in Wales (United Kingdom) and the United States

BackgroundIncreasing incidence of central nervous system (CNS) tumors has been noted in some populations. However, the influence of changing surgical and imaging practices has not been consistently accounted for.MethodsWe evaluated average annual percentage change (AAPC) in age- and gender-stratified incidence of CNS tumors by tumor subtypes and histological confirmation in Wales, United Kingdom (1997-2015) and the United States (2004-2015) using joinpoint regression.FindingsIn Wales, the incidence of histologically confirmed CNS tumors increased more than all CNS tumors (AAPC 3.62% vs 1.63%), indicating an increasing proportion undergoing surgery. Grade II and III glioma incidence declined significantly (AAPC −3.09% and −1.85%, respectively) but remained stable for those with histological confirmation. Grade IV glioma incidence increased overall (AAPC 3.99%), more markedly for those with histological confirmation (AAPC 5.36%), suggesting reduced glioma subtype misclassification due to increased surgery. In the United States, the incidence of CNS tumors increased overall but was stable for histologically confirmed tumors (AAPC 1.86% vs 0.09%) indicating an increase in patients diagnosed without surgery. An increase in grade IV gliomas (AAPC 0.28%) and a decline in grade II gliomas (AAPC −3.41%) were accompanied by similar changes in those with histological confirmation, indicating the overall trends in glioma subtypes were unlikely to be caused by changing diagnostic and clinical management.ConclusionsChanges in clinical practice have influenced the incidence of CNS tumors in the United Kingdom and the United States. These should be considered when evaluating trends and in epidemiological studies of putative risk factors for CNS tumors.     

Association between brain tumors and menopausal status.

BACKGROUND: Several lines of evidence have implicated female hormones in the etiology of human brain tumors, meningiomas in particular. PURPOSE: To investigate the relationship between brain tumor development and the hormonal changes manifested during pregnancy and menopause, we analyzed data from female participants in a population-based case-control study of adult brain tumors. This study was conducted in 1987-1988 in the Rhein-Neckar-Odenwald area of the Federal Republic of Germany. METHODS: The study population consisted of 127 women with meningiomas, gliomas, and acoustic neuromas (case patients) and 233 control women who were selected from the general population and frequency-matched by age to the case patients. Information on parity, menopausal status, and previous gynecologic surgeries was obtained through a standardized questionnaire. Case patients and control subjects were compared with the use of the unconditional maximum likelihood estimation of the parameters in a logistic regression model. RESULTS: Our results were not statistically significant; nevertheless, they revealed some interesting trends. No association was found between parity and the development of any of the three histological subtypes of brain tumor (relative risk [RR] = 1.31; 95% confidence interval [CI] = 0.51-2.07). Menopausal women had a greatly reduced risk of developing meningiomas (RR = 0.58; 95% CI = 0.18-1.90), and this effect was most pronounced when menopause had been surgically induced by bilateral oophorectomy (RR = 0.12; 95% CI = 0.01-1.30). Menopausal women had a greater risk of developing gliomas or acoustic neuromas (RR = 1.77; 95% CI = 0.67-4.68), except when menopause was surgically induced, in which case the risk was reduced (RR = 0.33; 95% CI = 0.04-3.09). Oophorectomy after menopause did not appear to influence risk. CONCLUSIONS: Since the onset of menopause is accompanied by cessation of estrogen production, our results support the notion that female hormones play a role in the development of brain tumors.     

Descriptive epidemiology of CNS tumors in France: results from the Gironde Registry for the period 2000-2007

An increase in the incidence of CNS tumors has been observed in many countries in the last decades. The reality of this trend has been much debated, as it has happened during a period when computer-assisted tomography and MRI have dramatically improved the detection of these tumors. The Gironde CNS Tumor Registry provides here the first data on CNS tumor incidence and trends in France for all histological types, including benign and malignant tumors, for the period 2000-2007. Incidence rates were calculated globally and for each histological subtype. For trends, a piecewise log-linear model was used. The overall annual incidence rate was found to be 17.6/100 000. Of this rate, 7.9/100 000 were neuroepithelial tumors and 6.0/100 000 were meningiomas. An overall increase in CNS tumor incidence was observed from 2000 to 2007, with an annual percent change (APC) of +2.33%, which was explained mainly by an increase in the incidence of meningiomas over the 8-year period (APC = +5.4%), and also more recently by an increase in neuroepithelial tumors (APC = +7.45% from 2003). The overall increase was more pronounced in women and in the elderly, with an APC peaking at +24.65% in subjects 85 and over. The increase in the incidence rates we observed may have several explanations: not only improvements in registration, diagnosis, and clinical practice, but also changes in potential risk factors.     

Update on the therapeutic approaches to brain tumors

Neuro-oncology is a rapidly growing field of study. The understanding of brain tumors has expanded in pace with advances in the field of molecular biology and genetics. Diagnoses are more accurate, biopsy and surgical intervention safer, radiotherapy more focused and chemotherapy safer and better tolerated. Novel strategies based on the understanding of brain tumor biology are emerging as targeted approaches to therapy. Despite all this, only a minority of patients with certain subsets of brain tumors have experienced prolonged survival. This review focuses on the standard and emerging therapies for the two most common categories of brain tumors: gliomas and meningiomas. Primary CNS lymphoma, while a relatively rare tumor, is also included as a topic of discussion as the achievements in its treatment represent the principal strides in the evolution of neuro-oncology.     

Update on the therapeutic approaches to brain tumors

Neuro-oncology is a rapidly growing field of study. The understanding of brain tumors has expanded in pace with advances in the field of molecular biology and genetics. Diagnoses are more accurate, biopsy and surgical intervention safer, radiotherapy more focused and chemotherapy safer and better tolerated. Novel strategies based on the understanding of brain tumor biology are emerging as targeted approaches to therapy. Despite all this, only a minority of patients with certain subsets of brain tumors have experienced prolonged survival. This review focuses on the standard and emerging therapies for the two most common categories of brain tumors: gliomas and meningiomas. Primary CNS lymphoma, while a relatively rare tumor, is also included as a topic of discussion as the achievements in its treatment represent the principal strides in the evolution of neuro-oncology.     

Parathyroid adenoma and primary CNS tumors

Hyperparathyroidism onset at a young age is one feature in multiple endocrine neoplasia (MEN) type 1 and MEN type 2A cancer syndromes. There are several case reports of MEN Type 1-associated central nervous system (CNS) tumors. To determine if there is an association between parathyroid adenomas and CNS tumors, we used Swedish registry data to identify all individuals operated on for parathyroid adenomas between 1958-99 (n = 12,468). Follow-up for the occurrence of CNS tumors in these individuals was through linkage with the Swedish Cancer Registry. There were 70 observed cases of a CNS tumor diagnosed after a parathyroid adenoma, to be compared to 35 expected (standard incidence ratio [SIR] = 2.0; 95% confidence interval [CI] = 1.5-2.5). This increased risk was independent of duration of follow-up and was confined to meningiomas (SIR = 2.4, 95% CI = 1.7-3.4) and neurinomas (SIR = 3.4, 95% CI = 1.5-6.8). These results strongly indicate an association between these tumor forms that may be genetic, environmental (such as radiation) or a combination of both.     

Pediatric malignancies in neurofibromatosis type 1: A population-based cohort study

Neurofibromatosis type 1 (NF1) is a cancer predisposition syndrome with an incidence of 1:2,000. Patients with NF1 have an increased cancer risk and mortality, but there are no population-based cohort studies specifically investigating the risk of childhood malignancies. We used the Finnish NF1 cohort to analyze the incidence, risk and prognosis of malignancies in NF1 patients <20 years of age. Persons born in 1987–2011 were included, and 524 persons were followed through the files of the Finnish Cancer Registry from birth up to age 20 years. This amounted to 8,376 person years. Fifty-three patients had cancer <20 years of age, yielding a standardized incidence ratio (SIR) of 35.6. The most frequent location of pediatric cancers was the central nervous system (CNS); there were 45 cases and the SIR was 115.7. Exclusion of 22 optic pathway gliomas (OPGs) gave an SIR of 59.1 for the CNS and 21.6 for all cancers. There were nine malignant peripheral nerve sheath tumors (MPNSTs); their cumulative risk was 2.7% by age 20. No cases of leukemia were observed. NF1 patients showed considerable excess mortality with a standardized mortality ratio (SMR) of 73.1. The survival of NF1 patients with CNS tumors other than OPGs did not differ from that of non-NF1 controls (HR 0.64, 95% CI 0.23 to 1.76). In conclusion, brain tumors in childhood and MPNSTs in adolescence are malignancies of major concern in patients with NF1. The risk for myeloid malignancies may not be as high as suggested in the literature.     

Reproductive factors and the risk of brain tumors: A population-based study in Sweden

Possible associations between childbearing and the risk of brain cancer were explored in a case-control study “nested” within a large nationwide cohort defined by the Swedish Fertility Registry. Among women born between 1925–1975, 1,088 patients with meningiomas and 1,657 patients with gliomas were identified in the Swedish Cancer Registry. For every woman diagnosed with brain tumor, 5 age-matched controls were selected among those in the Fertility Registry. Relative risks were estimated by odds ratios from conditional logistic regression. Ever-parous women were at a reduced risk of glioma compared to nulliparous women, while parity was unrelated to meningioma risk. Age at first birth was unrelated to both meningioma and glioma risk. The gradient in risk between ever-parous and nulliparous women for gliomas, but not meningiomas, is difficult to explain biologically. A possible explanation is that pregnancy-induced alterations in androgen levels reduce the risk of glioma in parous women. Alternatively, childlessness may represent a marker of an occult glioma, negatively affecting fecundity. Overall, our present results do not support the notion that hormonal changes, or other physiological changes induced by childbearing, play an important role in the development of brain tumors. Int. J. Cancer 72:389–393, 1997. © 1997 Wiley-Liss, Inc.     

Body size and risk of luminal, HER2-overexpressing, and triple-negative breast cancer in postmenopausal women

Although the clinical relevance of molecular subtypes of breast cancer has been documented, little is known about risk factors for different tumor subtypes, especially the HER2-overexpressing and the triple-negative subtypes that have poor prognoses. Obesity may be differentially related to the risk of different subtypes given the various potential mechanisms underlying its association with breast cancer. We pooled two population-based case-control studies of postmenopausal breast cancer for an analysis, including 1,447 controls and 1,008 luminal (hormone receptor positive), 39 HER2-overexpressing (hormone receptor negative, HER2 positive), and 77 triple-negative (hormone receptor and HER2 negative) cases. Associations between anthropometric factors and the risk of different breast cancer subtypes were evaluated using polytomous logistic regression. Among women not currently using menopausal hormone therapy, body mass index (BMI) and weight were associated with the risk of luminal tumors [odds ratio (OR) comparing highest versus lowest quartiles, 1.7; 95% confidence interval (95% CI), 1.2-2.4 and OR, 1.7; 95% CI, 1.2-2.4, respectively] and suggestively associated with risk of triple-negative tumors (OR, 2.7; 95% CI, 1.0-7.5 and OR, 5.1; 95% CI, 1.1-23.0, respectively). Neither BMI nor weight was associated with the risk of any tumor subtype among hormone therapy users. The positive relationship between BMI and luminal tumors among postmenopausal women not using hormone therapy is well characterized in the literature. Although our sample size was limited, body size may also be related to the risk of postmenopausal triple-negative breast cancer among nonusers of hormone therapy. Given the expanding obesity epidemic, the widespread cessation of hormone therapy use, and the poor prognosis of triple-negative tumors, this novel finding merits confirmation.