PubMed Health⌕ Search

Biomedical subjects

Per Hall

Publications and source records attributed to Per Hall.

At least 19 recordsLinked to original sources
PubMed2025

A Swedish genome-wide haplotype association analysis identifies novel candidate loci associated with endometrial cancer risk.

Genome-wide association studies [GWAS] have identified a limited number of endometrial cancer risk loci by analyzing single nucleotide polymorphisms [SNPs]. We hypothesized that analyzing haplotypes rather than SNPs could provide novel and more detailed information on genetic cancer susceptibility loci. To examine the association of a SNP or haplotype with endometrial cancer risk we performed a two-stage haplotype GWAS. The discovery GWAS included a sub-cohort of 1,116 Swedish endometrial cancer cases and 5,021 controls from previously published GWAS data. A sliding window analysis was employed with window sizes of 1-25 SNPs using a logistic regression model. The Swedish haplotype analysis identified 15 novel candidate risk loci (2q31.1, 4p16.1, 4p15.31, 6q13, 7p21.1, 9p13.3, 10q26.3, 11q21, 12q13.11, 13q12.11, 15q13.3, 16q24.3, 19q13.32, 20p12.3 and 22q13.2) with OR ranging from 1.6 to 3.3 and p-values from 4.25 × 10-8 to 9.86 × 10-15. A second replication haplotype analysis of the Swedish novel loci was performed using two cohorts from Belgium and Germany. In spite of small sample sizes in the replication cohorts, there was still support for most loci with positive ORs. In addition, the findings in the two European cohorts motivates further studies to search for founder haplotypes. These novel findings suggested that endometrial cancer loci, identified through haplotype analysis, conferred a higher risk compared to previous single-variant GWAS.

Humans↗
PubMed2007

Leukemia following breast cancer: an international population-based study of 376,825 women.

PURPOSE: To quantify long-term temporal trends in the excess absolute risk (EAR) of secondary leukemia among breast cancer (BC) survivors, using multivariate analyses to evaluate the effects of subtype, age at BC diagnosis, attained age, and calendar year. PATIENTS AND METHODS: We identified 376,825 1-year survivors of BC within 4 nationwide, population-based cancer registries in Sweden, Denmark, Finland, and Norway (1943-2001). Estimates of EAR (per 100,000 person-years) were modeled using Poisson regression methods and cumulative risks calculated using a competing risk model. RESULTS: A total of 687 non-chronic lymphocytic leukemias (EAR = 9.05; 95% confidence interval (CI) = 7.5-10.7) was reported. Significantly elevated risks were observed for the first time for chronic myeloid leukemia (CML) (EAR = 2.06; 95% CI = 1.3-2.9) and acute lymphoblastic leukemia (ALL) (EAR = 0.62; 95% CI = 0.2-1.1), in addition to acute myeloid leukemia (AML) (EAR = 5.00; 95% CI = 3.9-6.2). Excesses of CML, ALL, AML and all leukemias combined persisted over 25 years after BC diagnosis. For all leukemias, EAR decreased with increasing calendar year (P = 0.04) of BC diagnosis. Risk for all leukemia and AML by calendar year of BC diagnosis depended on age at diagnosis. For women diagnosed with BC after 1985, the 10-year cumulative risk of leukemia for those diagnosed before and after age 50 was small, 0.10% and 0.14%, respectively. CONCLUSIONS: Although secondary leukemia is a rare event, BC survivors experience statistically significant excesses for at least 25 years after diagnosis, including CML and ALL. Decreasing leukemia risks in recent calendar years likely reflect changes in treatment.

Adult↗
PubMed2007

Gene expression in 16q is associated with survival and differs between Sørlie breast cancer subtypes.

We have investigated the relationship between gene expression and chromosomal positions in 402 breast cancer patients. Using an overrepresentation approach based on Fisher's exact test, we identified disproportionate contributions of specific chromosomal positions to genes associated with survival. Our major finding is that the gene expression in the long arm of chromosome 16 stands out in its relationship to survival. This arm contributes 36 (18%) and 55 (11%) genes to lists negatively associated with recurrence-free survival (set to sizes 200 and 500). This is a highly disproportionate contribution from the 313 (2%) genes in this arm represented on the used Affymetrix U133A and B microarray platforms (Bonferroni corrected Fisher test: P < 2.2 x 10(-16)). We also demonstrate differential expression in 16q across tumor subtypes, which suggests that the ERBB2, basal, and luminal B tumors progress along a high grade-poor prognosis path, while luminal A and normal-like tumors progress along a low grade-good prognosis path, in accordance with a previously proposed model of tumor progression. We conclude that important biological information can be extracted from gene expression data in breast cancer by studying non-random connections between chromosomal positions and gene expression. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.

Breast Neoplasms↗
PubMed2006

Effect of ATM, CHEK2 and ERBB2 TAGSNPs and haplotypes on endometrial cancer risk.

Family history of endometrial cancer increases the risk of developing the disease, but it is still largely unknown which germ-line genetic factors are involved in the aetiology of endometrial cancer. In a Swedish population-based case-control study including 705 cases and 1565 controls, we examined common variation in the ATM, CHEK2 and ERBB2 genes in relation to endometrial cancer risk overall, restricted to tumours of certain characteristics or stratified by various endometrial cancer risk factors. We genotyped a large number of single-nucleotide polymorphisms (SNPs) in the genes and selected seven haplotype-tagging SNPs (tagSNPs) in ATM, six tagSNPs in CHEK2 and seven tagSNPs in ERBB2 that could predict common variants and haplotypes (frequency > or =0.03) in each gene with R(2) > or = 0.8. We included the tagSNPs or their haplotypes as explanatory variables in unconditional logistic regression models adjusted for age. Our results indicated an increased risk of developing endometroid endometrial cancer for homozygous carriers of the rare allele (AA) of a tagSNP (rs4987886) in CHEK2 (P = 0.005) when contrasted with GG carriers. We also found a decreased endometrial cancer risk among non-smoking carriers of a haplotype in ATM (P = 0.0007) and among carriers of a haplotype in CHEK2, who had experienced menopause below 49 years of age (P = 0.0009) compared with non-carriers of these haplotypes. We found no effect of genetic variation in ERBB2 on endometrial cancer risk. In conclusion, it is possible that common variants in the ATM and CHEK2 genes, in interaction with oestrogen-related exposures, are involved in endometrial cancer aetiology.

Age Factors↗
PubMed2006

Ethnic differences in the time trend of female breast cancer incidence: Singapore, 1968-2002.

BACKGROUND: From 1968 to 2002, Singapore experienced an almost three-fold increase in breast cancer incidence. This increase appeared to be different across the three main ethnic groups: Chinese, Malays and Indians. This paper used age-period-cohort (APC) modelling, to determine the effects of age at diagnosis, calendar period, and birth cohort on breast cancer incidence for each ethnic group. METHODS: This study included all breast cancer cases (n = 15,269) in the three ethnic groups, reported to the Singapore Cancer Registry from 1968 to 2002 between the ages 25 to 79. Age-specific fertility rates from the Department of Statistics were used to explore the role of fertility. RESULTS: In the 1970s, Indian women had the highest age-standardized breast cancer but by the mid-1980s the highest rates were seen among the Chinese. Remarkable differences were seen in the age-specific incidence rates by ethnic groups. After age 49, the incidence rates for the Chinese and Malays leveled off whereas it continued to rise in the Indians. While our analyses provided some evidence that an age-drift model described the trend seen in the Indians, age-period-cohort model and age-cohort model had the best fit for the Chinese and Malays aged 25 to 79 respectively. Overall, Chinese and Malay women born in later cohorts were at increased risk of developing breast cancer relative to their counterparts in the earlier cohorts. The three ethnic groups experienced similar changes in their fertility in the 1970s, which likely explained much of the increase in their breast cancer incidence but not the ethnic differences. There was a stronger inverse association between total fertility rate and pre-menopausal breast cancer incidence in the Chinese and Malays than the Indians. CONCLUSION: The observed dissimilarity among ethnic groups suggests ethnic differences in exposure or response to certain risk factors. It is likely that longer and subtler differences in childbearing trends and other risk factors may further explain these ethnic differences.

Adult↗
PubMed2006

Genetic reclassification of histologic grade delineates new clinical subtypes of breast cancer.

Histologic grading of breast cancer defines morphologic subtypes informative of metastatic potential, although not without considerable interobserver disagreement and clinical heterogeneity particularly among the moderately differentiated grade 2 (G2) tumors. We posited that a gene expression signature capable of discerning tumors of grade 1 (G1) and grade 3 (G3) histology might provide a more objective measure of grade with prognostic benefit for patients with G2 disease. To this end, we studied the expression profiles of 347 primary invasive breast tumors analyzed on Affymetrix microarrays. Using class prediction algorithms, we identified 264 robust grade-associated markers, six of which could accurately classify G1 and G3 tumors, and separate G2 tumors into two highly discriminant classes (termed G2a and G2b genetic grades) with patient survival outcomes highly similar to those with G1 and G3 histology, respectively. Statistical analysis of conventional clinical variables further distinguished G2a and G2b subtypes from each other, but also from histologic G1 and G3 tumors. In multivariate analyses, genetic grade was consistently found to be an independent prognostic indicator of disease recurrence comparable with that of lymph node status and tumor size. When incorporated into the Nottingham prognostic index, genetic grade enhanced detection of patients with less harmful tumors, likely to benefit little from adjuvant therapy. Our findings show that a genetic grade signature can improve prognosis and therapeutic planning for breast cancer patients, and support the view that low- and high-grade disease, as defined genetically, reflect independent pathobiological entities rather than a continuum of cancer progression.

Algorithms↗
PubMed2006

Suicide after breast cancer: an international population-based study of 723,810 women.

Few studies have examined long-term suicide risk among breast cancer survivors, and there are no data for women in the United States. We quantified suicide risk through 2002 among 723,810 1-year breast cancer survivors diagnosed between January 1, 1953, and December 31, 2001, and reported to 16 population-based cancer registries in the United States and Scandinavia. Among breast cancer survivors, we calculated standardized mortality ratios (SMRs) and excess absolute risks (EARs) compared with the general population, and the probability of suicide. We used Poisson regression likelihood ratio tests to assess heterogeneity in SMRs; all statistical tests were two-sided, with a .05 cutoff for statistical significance. In total 836 breast cancer patients committed suicide (SMR = 1.37, 95% confidence interval [CI] = 1.28 to 1.47; EAR = 4.1 per 100,000 person-years). Although SMRs ranged from 1.25 to 1.53 among registries, with 245 deaths among the sample of US women (SMR = 1.49, 95% CI = 1.32 to 1.70), differences among registries were not statistically significant (P for heterogeneity = .19). Risk was elevated throughout follow-up, including for 25 or more years after diagnosis (SMR = 1.35, 95% CI = 0.82 to 2.12), and was highest among black women (SMR = 2.88, 95% CI = 1.44 to 5.17) (P for heterogeneity = .06). Risk increased with increasing stage of breast cancer (P for heterogeneity = .08) and remained elevated among women diagnosed between 1990 and 2001 (SMR = 1.36, 95% CI = 1.18 to 1.57). The cumulative probability of suicide was 0.20% 30 years after breast cancer diagnosis.

Adult↗
PubMed2006

Risk of brain tumors associated with exposure to exogenous female sex hormones.

The etiology of brain tumors is largely unknown. Prior observations have implicated gender-specific hormones in the pathogenesis of these tumors. In a population-based case-control study, the authors identified all women aged 20-69 years who had been diagnosed with meningioma or glioma during 2000-2002 in four regions of Sweden. Controls were randomly selected from the study base. Detailed information on hormone usage, including use of hormonal contraceptives, hormonal treatment for gynecologic problems, and hormone replacement therapy, was collected from 178 meningioma cases, 115 glioma cases, and 323 controls. Data were analyzed using unconditional logistic regression, adjusting for age, residential area, education, and parity. An increased relative risk of meningioma was found among postmenopausal women for ever use of hormone replacement therapy, with an odds ratio of 1.7 (95% confidence interval: 1.0, 2.8). Women who had used long-acting hormonal contraceptives (subdermal implants, injections, or hormonal intrauterine devices) had an increased risk of meningioma; the odds ratio for at least 10 years of use was 2.7 (95% confidence interval: 0.9, 7.5). Hormone usage was not associated with glioma risk in this study. The findings suggest that the use of female sex steroids may increase the risk of meningioma.

Adult↗
PubMed2006

Hormone-replacement therapy influences gene expression profiles and is associated with breast-cancer prognosis: a cohort study.

BACKGROUND: Postmenopausal hormone-replacement therapy (HRT) increases breast-cancer risk. The influence of HRT on the biology of the primary tumor, however, is not well understood. METHODS: We obtained breast-cancer gene expression profiles using Affymetrix human genome U133A arrays. We examined the relationship between HRT-regulated gene profiles, tumor characteristics, and recurrence-free survival in 72 postmenopausal women. RESULTS: HRT use in patients with estrogen receptor (ER) protein positive tumors (n = 72) was associated with an altered regulation of 276 genes. Expression profiles based on these genes clustered ER-positive tumors into two molecular subclasses, one of which was associated with HRT use and had significantly better recurrence free survival despite lower ER levels. A comparison with external data suggested that gene regulation in tumors associated with HRT was negatively correlated with gene regulation induced by short-term estrogen exposure, but positively correlated with the effect of tamoxifen. CONCLUSION: Our findings suggest that post-menopausal HRT use is associated with a distinct gene expression profile related to better recurrence-free survival and lower ER protein levels. Tentatively, HRT-associated gene expression in tumors resembles the effect of tamoxifen exposure on MCF-7 cells.

Breast Neoplasms↗
PubMed2006

Linkage disequilibrium mapping of CHEK2: common variation and breast cancer risk.

BACKGROUND: Checkpoint kinase 2 (CHEK2) averts cancer development by promoting cell cycle arrest and activating DNA repair in genetically damaged cells. Previous investigation has established a role for the CHEK2 gene in breast cancer aetiology, but studies have largely been limited to the rare 1100delC mutation. Whether common polymorphisms in this gene influence breast cancer risk remains unknown. In this study, we aimed to assess the importance of common CHEK2 variants on population risk for breast cancer by capturing the majority of diversity in the gene using haplotype tagging single nucleotide polymorphisms (tagSNPs). METHODS AND FINDINGS: We analyzed 14 common SNPs spanning 52 kilobases (kb) of the CHEK2 gene in 92 Swedish women. Coverage evaluation indicated that these typed SNPs would efficiently convey association signal also from untyped SNPs in the same region. Six of the 14 SNPs predicted well both the haplotypic and single SNP variations within CHEK2. We genotyped these six tagSNPs in 1,577 postmenopausal breast cancer cases and 1,513 population controls, but found no convincing association between any common CHEK2 haplotype and breast cancer risk. The 1100delC mutation was rare in our Swedish population--0.7% in cases and 0.4% in controls--with a corresponding odds ratio for carriers versus noncarriers of 2.26 (95% confidence interval, 0.99-5.15). Estimates of the population frequency and the odds ratio of 1100delC indicate that our sample is representative of a Northern European population. CONCLUSIONS: Notwithstanding the involvement of the CHEK2 gene in breast cancer aetiology, we show that common polymorphisms do not influence postmenopausal breast cancer risk.

Aged↗
PubMed2006

Sex of first child and breast cancer survival: a population-based study.

Previous reports on the influence of the sex of a child and prognosis of a subsequent breast cancer have been conflicting. We took advantage of a number of large and good quality, nationwide Registries in Sweden to evaluate the prognostic value of the sex of the first child in breast cancer. A population-based cohort of 32,003 women born after 1935 and diagnosed with primary breast cancer between 1958 and 1997 was generated by linking a number of Swedish registries including Swedish Cancer Registry, Cause of Death Registry, Swedish Generation Registry and the Registry of Population and Population changes. Of these, 4,251 were nulliparous, 2,732 had only a boy and 2,497 had only a girl prior to diagnosis. We used this subpopulation to quantify the association between the sex of the first child and breast cancer-specific mortality, using the Cox proportional hazards. Sex of the child did not significantly influence the prognosis of breast cancer. Stratifying by age and adjusting for age at diagnosis, calendar period, time since last birth and age at first child did not alter the results. Our study, the largest up to date, failed to identify evidence to support the proposed association between the sex of the first child and breast cancer survival. Given the previous reports that advocated taking sex of the first child into consideration in making decisions related to breast cancer therapy, our findings are reassuring and clinically important.

Adult↗
PubMed2006

Menopausal hormone therapy and other breast cancer risk factors in relation to the risk of different histological subtypes of breast cancer: a case-control study.

INTRODUCTION: Breast cancers of different histology have different clinical and prognostic features. There are also indications of differences in aetiology. We therefore evaluated the risk of the three most common histological subtypes in relation to menopausal hormone therapy and other breast cancer risk factors. METHODS: We used a population-based case-control study of breast cancer to evaluate menopausal hormone therapy and other breast cancer risk factors for risk by histological subtype. Women aged 50 to 74 years, diagnosed with invasive ductal (n = 1,888), lobular (n = 308) or tubular (n = 93) breast cancer in Sweden in 1993 to 1995 were compared with 3,065 age-frequency matched controls randomly selected from the population. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for ductal, lobular, and tubular cancer. RESULTS: Women who had used medium potency estrogen alone were at increased risks of both ductal and lobular cancer. Medium potency estrogen-progestin was associated with increased risks for all subtypes, but the estimates for lobular and tubular cancer were higher compared with ductal cancer. We found OR 5.6 (95% CI 3.2-9.7) for lobular cancer, OR 6.5 (95% CI 2.8-14.9) for tubular cancer and OR 2.3 (95% CI 1.6-3.3) for ductal cancer with > or =5 years use of medium potency estrogen-progestin therapy. Low potency oral estrogen (mainly estriol) appeared to be associated with an increased risk for lobular cancer, but the association was strongest for short-term use. Reproductive and anthropometric factors, smoking, and past use of oral contraceptives were mostly similarly related to the risks of the three breast cancer subtypes. Recent alcohol consumption of > 10 g alcohol/day was associated with increased risk only for tubular cancer (OR 3.1, 95% CI 1.4-6.8). CONCLUSION: Menopausal hormone therapy was associated with increased risks for breast cancer of both ductal and lobular subtype, and medium potency estrogen-progestin therapy was more strongly associated with lobular compared with ductal cancer. We also found medium potency estrogen-progestin therapy and alcohol to be strongly associated with tubular cancer. With some exceptions, most other risk factors seemed to be similarly associated with the three subtypes of breast cancer.

Adenocarcinoma↗
PubMed2006

Clinically significant prognostic factors for differentiated thyroid carcinoma: a population-based, nested case-control study.

BACKGROUND: Different scoring systems currently are being used to stratify patients with differentiated thyroid carcinoma (DTC) into risk groups. DTC is usually subdivided into papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC). The objective of the current study was to identify those factors that predict long-term unfavorable prognosis and to evaluate the predictive accuracy of the TNM staging system. METHODS: The authors conducted a nested case-control study within the cohort of all patients (n=5123) diagnosed with DTC in Sweden between 1958-1987 who survived at least 1 year after diagnosis. One control, matched by age at diagnosis, gender, and calendar period, was randomly selected for each case (patients who died of DTC). All patients were classified at the time of diagnosis according to the TNM staging system. The effect of prognostic factors on DTC mortality was evaluated using conditional logistic regression. RESULTS: Patients with widely invasive FTC experienced a significantly higher mortality compared with PTC patients. The grade of differentiation was found to influence mortality significantly. Patients with TNM Stage IV disease had a higher mortality rate compared with patients with Stage II disease (odds ratio [OR]=9.1; 95% confidence interval [95% CI], 5.7-14.6). Patients with lymph node metastases experienced a higher mortality (OR=2.5; 95% CI, 1.6-4.1) and patients with distant metastasis at the time of diagnosis were found to have a nearly 7-fold higher mortality rate (OR=6.6; 95% CI, 4.1-10.5). Incomplete surgical excision was associated with higher mortality, particularly in patients with Stage I disease. CONCLUSIONS: In the current study, the following were found to be clinically significant prognostic factors for patients with DTC: histopathologic subgroup, TNM staging including lymph node metastases and distant metastases, and completeness of the surgical excision.

Adenocarcinoma, Follicular↗
PubMed2006

Acute myeloid leukemia following Hodgkin lymphoma: a population-based study of 35,511 patients.

Treatments for Hodgkin lymphoma are associated with large relative risks of acute myeloid leukemia (AML), but there are few estimates of the excess absolute risk (EAR), a useful measure of disease burden. One-year Hodgkin lymphoma survivors (N = 35,511) were identified within 14 population-based cancer registries in Nordic countries and North America from January 1, 1970, through December 31, 2001. We used Poisson regression analysis to model the EAR of AML, per 10,000 person-years. A total of 217 Hodgkin lymphoma survivors were diagnosed with AML (10.8 expected; unadjusted EAR = 6.2; 95% confidence interval = 5.4 to 7.1). Excess absolute risk for AML was highest during the first 10 years after Hodgkin lymphoma diagnosis but remained elevated thereafter. In subsequent analyses, adjusted for time since Hodgkin lymphoma diagnosis and presented for the 5-9 year interval, the EAR was statistically significantly (P < .001) larger in patients diagnosed with Hodgkin lymphoma at age 35 years and older than in those diagnosed before 35 years of age. The EAR of AML declined statistically significantly after 1984 (7.0 to 4.2 and 16.4 to 9.9 in the < 35 and > or = 35 age groups, respectively), which may be associated with modifications in chemotherapy.

Adult↗
PubMed2006

p53 Mutation analysis in breast tumors by a DNA microarray method.

The p53 gene acts as a regulator of cell growth and DNA repair in normal cells; inactivation of the gene seems to lead to cancer. It is the most commonly mutated gene in human cancers, and a high-throughput sequencing method is needed for cancer etiology studies using large sample sets. In our population-based case-control study of breast cancer, the p53 gene was amplified by PCR for 392 subjects from seven hospitals in Western New York using the Affymetrix GeneChip technology. One hundred thirty-eight (35%) of the breast tumors had p53 mutations, of which 88% were located in exons 5 to 8. New hotspots were identified at codons 179, 195, 196, 213, 217, 249, 254, 278, 281, and 298, and previously reported hotspots were found at codons 175, 248, and 273. Manual sequencing for exons 5 to 9 of the p53 gene was done for 139 tumors to validate the Affymetrix assay. The two methods had 100% concordance for mutations detectable by the Affymetrix assay. We also successfully assayed paraffin-embedded breast and lung tumors from as early as 1958 and employed a nested PCR strategy to improve weak PCR amplification. To have statistical power, the investigation of gene environment interactions and cancer requires a large number of tumor analyses, which are frequently only available from archived tissue from multiple sources. We have shown the utility of the Affymetrix GeneChip method under these challenging conditions and provided new data for the mutational spectra of breast cancer in a population-based study.

Breast Neoplasms↗
PubMed2006

Genomic instability and prognosis in breast carcinomas.

BACKGROUND: We recently reported that DNA content of breast adenocarcinomas, cytometrically assessed by diploid (D), tetraploid (T), and aneuploid (A) categories, can be further divided into genomically stable and unstable subtypes by means of the stemline scatter index (SSI). The aim of the present study was to survey the clinical correlates and the prognostic value of the SSI in a consecutive series of 890 breast cancer patients. RESULTS: Genomically stable subtype had a significantly better survival compared with the unstable subtype within each ploidy category: D (P = 0.04), T (P = 0.008), and A (P = 0.004). By contrast, no statistically significant difference in survival was observed between the D, T, and A categories within the stable (P = 0.23) and unstable subtypes (P = 0.12). Among A tumors, the unstable subtype tended to be larger, more frequently estrogen- and progesterone-receptor negative, and to be of higher grade compared with the stable subtype. Stable D tumors tended to have lower grade than the unstable subtype, but among the D and T tumors, genomic instability was not associated with receptor status. Within the Elston grade 3, lymph node-positive or estrogen receptor-positive subgroups, patients with stable tumors had significantly better survival compared with unstable tumors (P = 0.01, 0.002, and 7.2E-5, respectively). CONCLUSIONS: The SSI contributes supplementary biological and clinical information in addition to ploidy information alone. Objective classification of breast adenocarcinomas into stable and unstable subtypes is a useful prognostic indicator independent of established clinical factors.

Adult↗
PubMed2006

Risk factors for hormone receptor-defined breast cancer in postmenopausal women.

The effect of classic breast cancer risk factors on hormone receptor-defined breast cancer is not fully clarified. We explored these associations in a Swedish population-based study. Postmenopausal women ages 50 to 74 years, diagnosed with invasive breast cancer during 1993 to 1995, were compared with 3,065 age frequency-matched controls. We identified 332 estrogen receptor (ER-) and progesterone receptor (PR-) negative, 286 ER+PR-, 71 ER-PR+, 1,165 ER+PR+, and 789 tumors with unknown receptor status. Unconditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI). Women ages >or=30 years, compared with those ages 20 to 24 years at first birth, were at an increased risk of ER+PR+ tumors (OR, 1.5; 95% CI, 1.2-1.8) but not ER-PR- tumors (OR, 1.1; 95% CI, 0.8-1.6). Women who gained >or=30 kg in weight during adulthood had an approximately 3-fold increased relative risk of ER+PR+ tumors (OR, 2.7; 95% CI, 1.9-3.8), but no risk increase of ER-PR- tumors (OR, 1.0; 95% CI, 0.5-2.1), compared with women who gained <10 kg. Compared with never users, women who used menopausal estrogen-progestin therapy for at least 5 years were at increased risk of ER+PR+ tumors (OR, 3.0; 95% CI, 2.1-4.1) but not ER-PR- tumors (OR, 1.3; 95% CI, 0.7-2.5). In conclusion, other risk factors were similarly related to breast cancer regardless of receptor status, but high age at first birth, substantial weight gain in adult age, and use of menopausal estrogen-progestin therapy were more strongly related to receptor-positive breast cancer than receptor-negative breast cancer.

Aged↗