Risk of subsequent breast cancer in relation to characteristics of screening mammograms from women less than 50 years of age.

This investigation was conducted to assess the predictive value of calcifications and densities in mammograms from women <50 years of age for subsequent diagnosis of breast cancer. In a population-based study, prior screening mammograms taken before age 50 in 547 women with breast cancer and 472 controls were reviewed by a single radiologist. The relative risk (RR) of subsequent breast cancer increased with the percentage of the area of the mammogram that was mammographically dense [RR in succeeding quartiles of density = 1.0, 1.7 (1.1-2.6), 3.3 (2.2-5.0), and 4.0 (2.7-6.0)]; in relation to Wolfe parenchymal pattern class P2 [RR = 3.1 (2.2-4.3)] or DY [RR = 5.6 (3.2-10.0)]; and in relation to calcifications of class 1 (pleomorphic of any distribution) or class 2 (various morphological types that are regional, grouped, clustered, segmental, or linear in distribution) [RR = 3.0 (1.4-7.1), and 1.8 (1.2-2.6), respectively]. Women with radiographically dense mammograms and class 1 or 2 calcifications were at >10- and approximately 6-fold greater risk, respectively, than women with breasts of low density and no calcifications. Densities and parenchymal patterns were most strongly associated with breast cancer being diagnosed in the next 3 years. Class 1 and 2 calcifications were most strongly predictive of an increased risk in 3-6 years. Class 1 calcifications were strongly predictive of the breast in which the subsequent cancer occurred. Women <50 years of age with class 1 or 2 calcifications or mammographically dense breasts, or both, should receive high priority for further evaluation and regular breast cancer screening.

Do thyroid disorders increase the risk of breast cancer?

The objective of this study was to determine whether thyroid disorders or treatment of such disorders affects the risk of breast cancer. Subjects aged 35-64 years were participants in the National Institute of Child Health and Human Development Women's Contraceptive and Reproductive Experiences Study, a population-based, case-control study of invasive breast cancer that was carried out at five sites in the United States. In-person interviews were completed for 4575 women (cases) with breast cancer (2953 white and 1622 black) and 4682 control women (3021 white and 1661 black). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multiple logistic regression methods. Models included adjustment for age (5-year age groups), race (white or black), and site. A history of any thyroid disorder (OR = 1.1, 95% CI = 0.9-1.2) was not associated with breast cancer risk. Only women with a history of thyroid cancer had an increased risk, but this was restricted to parous women (parous OR = 3.4, 95% CI = 1.5-8.1; nulliparous OR = 0.5, 95% CI = 0.04-5.1). Breast cancer risk was not associated with treatment for thyroid disorders. There was no statistical interaction between thyroid disorders, thyroid treatments, and race, menopausal status, or parity. We found no association between thyroid disorders or their associated treatments and the risk of breast cancer.

A genome-wide association study of early-onset breast cancer identifies PFKM as a novel breast cancer gene and supports a common genetic spectrum for breast cancer at any age.

Early-onset breast cancer (EOBC) causes substantial loss of life and productivity, creating a major burden among women worldwide. We analyzed 1,265,548 Hapmap3 single-nucleotide polymorphisms (SNP) among a discovery set of 3,523 EOBC incident cases and 2,702 population control women ages ≤ 51 years. The SNPs with smallest P values were examined in a replication set of 3,470 EOBC cases and 5,475 control women. We also tested EOBC association with 19,684 genes by annotating each gene with putative functional SNPs, and then combining their P values to obtain a gene-based P value. We examined the gene with smallest P value for replication in 1,145 breast cancer cases and 1,142 control women. The combined discovery and replication sets identified 72 new SNPs associated with EOBC (P < 4 × 10(-8)) located in six genomic regions previously reported to contain SNPs associated largely with later-onset breast cancer (LOBC). SNP rs2229882 and 10 other SNPs on chromosome 5q11.2 remained associated (P < 6 × 10(-4)) after adjustment for the strongest published SNPs in the region. Thirty-two of the 82 currently known LOBC SNPs were associated with EOBC (P < 0.05). Low power is likely responsible for the remaining 50 unassociated known LOBC SNPs. The gene-based analysis identified an association between breast cancer and the phosphofructokinase-muscle (PFKM) gene on chromosome 12q13.11 that met the genome-wide gene-based threshold of 2.5 × 10(-6). In conclusion, EOBC and LOBC seem to have similar genetic etiologies; the 5q11.2 region may contain multiple distinct breast cancer loci; and the PFKM gene region is worthy of further investigation. These findings should enhance our understanding of the etiology of breast cancer.

Association between antibiotic use prior to breast cancer diagnosis and breast tumour characteristics (United States).

OBJECTIVE: To determine if breast tumour characteristics varied by antibiotic use prior to diagnosis in 2,266 women with primary, invasive breast cancer. METHODS: Subjects were women enrolled at Group Health Cooperative, a health plan in western Washington state, for at least 1 year and diagnosed with breast cancer between 1 January 1993 and 30 June 2001. Case status, tumour features, and patient characteristics were ascertained from the Surveillance, Epidemiology, and End Results cancer registry and Group Health Cooperative electronic files. Prescription information was obtained from electronic pharmacy records. RESULTS: Compared to non-use, antibiotic use prior to breast cancer diagnosis was not associated with a less favourable tumour profile (as measured by cancer stage, grade, and size), oestrogen receptor negative tumours, or lobular histology, after controlling for age and length of enrollment. Nonetheless, while not achieving statistical significance, our results suggest that antibiotic use may be associated with less favourable breast tumour features. CONCLUSIONS: Overall, we found no association between antibiotic use and breast tumour features and no dose-response gradient. However, the results are consistent with the possibility that antibiotic use may increase the risk of less favourable tumours. Larger studies are required to further investigate this hypothesis.