Abrogated Response to Cellular Stress Identifies DCIS Associated with Subsequent Tumor Events and Defines Basal-like Breast Tumors

SummaryApproximately 15%–30% of women diagnosed with ductal carcinoma in situ (DCIS) develop a subsequent tumor event within 10 years after surgical lumpectomy. To date, little is known about the molecular pathways that confer this differential risk for developing subsequent disease. In this study, we demonstrate that expression of biomarkers indicative of an abrogated response to cellular stress predicts DCIS with worse outcome and is a defining characteristic of basal-like invasive tumors. Mechanistic studies identify the Rb pathway as a key regulator of this response. Conversely, biomarkers indicative of an intact response to cellular stress are strongly associated with a disease-free prognosis. Assessment of these biomarkers in DCIS begins to allow prediction of tumor formation years before it actually occurs

Mammographic density and risk of breast cancer by age and tumor characteristics

Introduction: Understanding whether mammographic density (MD) is associated with all breast tumor subtypes and whether the strength of association varies by age is important for utilizing MD in risk models. Methods: Data were pooled from six studies including 3414 women with breast cancer and 7199 without who underwent screening mammography. Percent MD was assessed from digitized film-screen mammograms using a computer-assisted threshold technique. We used polytomous logistic regression to calculate breast cancer odds according to tumor type, histopathological characteristics, and receptor (estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER2)) status by age (51%) versus average density (11-25%). Women ages 2.1 cm) versus small tumors and positive versus negative lymph node status (P’s < 0.01). For women ages <55 years, there was a stronger association of MD with ER-negative breast cancer than ER-positive tumors compared to women ages 55–64 and ≥65 years (Page-interaction = 0.04). MD was positively associated with both HER2-negative and HER2-positive tumors within each age group. Conclusion: MD is strongly associated with all breast cancer subtypes, but particularly tumors of large size and positive lymph nodes across all ages, and ER-negative status among women ages <55 years, suggesting high MD may play an important role in tumor aggressiveness, especially in younger women

Recent trends in hormone therapy utilization and breast cancer incidence rates in the high incidence population of Marin County, California

<p>Abstract</p> <p>Background</p> <p>Recent declines in invasive breast cancer have been reported in the US, with many studies linking these declines to reductions in the use of combination estrogen/progestin hormone therapy (EPHT). We evaluated the changing use of postmenopausal hormone therapy, mammography screening rates, and the decline in breast cancer incidence specifically for Marin County, California, a population with historically elevated breast cancer incidence rates.</p> <p>Methods</p> <p>The Marin Women's Study (MWS) is a community-based, prospective cohort study launched in 2006 to monitor changes in breast cancer, breast density, and personal and biologic risk factors among women living in Marin County. The MWS enrolled 1,833 women following routine screening mammography between October 2006 and July 2007. Participants completed a self-administered questionnaire that included items regarding historical hormone therapy regimen (estrogen only, progesterone only, EPHT), age of first and last use, total years of use, and reason(s) for stopping, as well as information regarding complementary hormone use. Questionnaire items were analyzed for 1,083 non-Hispanic white participants ages 50 and over. Breast cancer incidence rates were assessed overall and by tumor histology and estrogen receptor (ER) status for the years 1990-2007 using data from the Northern California Surveillance, Epidemiology and End Results (SEER) cancer registry.</p> <p>Results</p> <p>Prevalence of EPHT use among non-Hispanic white women ages 50 and over declined sharply from 21.2% in 1998 to 6.7% by 2006-07. Estrogen only use declined from 26.9% in 1998 to 22.4% by 2006-07. Invasive breast cancer incidence rates declined 33.4% between 2001 and 2004, with drops most pronounced for ER+ cancers. These rate reductions corresponded to declines of about 50 cases per year, consistent with population attributable fraction estimates for EPHT-related breast cancer. Self-reported screening mammography rates did not change during this period. Use of alternative or complementary agents did not differ significantly between ever and never hormone users. Of women who reported stopping EPHT in the past 5 years, 60% cited "health risks" or "news reports" as their primary reasons for quitting.</p> <p>Conclusion</p> <p>A dramatic reduction in EPHT use was followed temporally by a significant reduction in invasive and ER+ breast cancer rates among women living in Marin County, California.</p

Is zero underestimation feasible? Extended Vacuum-assisted breast biopsy in solid lesions – a blind study

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Prognosis of screen-detected breast cancers: results of a population based study

BACKGROUND: The reduced mortality rate from breast carcinoma among women offered screening mammography is demonstrated after 15–20 years of follow-up. However, the assessment of 5-year overall and event-free survival could represent an earlier measure of the efficacy of mammography screening program (MSP). METHODS: All cases of breast cancer diagnosed in the Province of Modena between years 1996 and 2000 in women aged 50 to 69 years, were identified through the Modena Cancer Registry (MCR). Stage of disease and treatment information were obtained from clinical records. All the events occurring up to June 30, 2003 were retrieved by experienced monitors. Five-year overall and event-free survival were the principal end-points of the study. RESULTS: During a 5-year period, 587 primary breast cancers were detected by the MSP and 471 primary breast cancers were diagnosed out of the MSP. The screen-detected breast cancers were smaller, more likely node negative, with low histological grade, low proliferative activity and positive receptors status. Furthermore, the breast cancer diagnosed through the MSP more frequently received a conservative surgery. The 5-year survival rate was 94% in the screen-detected group, versus 84% in the other group (p = 0.0001). The rate of 5-year event-free survival was 89% and 75% for the MSP participants and not participants, respectively (p = 0.0001). CONCLUSIONS: Our data confirm a favourable outcome of screen-detected breast cancers in terms of five-year overall and event-free survival, which reflect the good quality assurance parameters of the MSP. Finally, a cancer registry should be implemented in every area covered by screening programs

Obesity and poor breast cancer prognosis: an illusion because of hormone replacement therapy?

High body mass index (BMI) and use of hormone replacement therapy (HRT) increase the risk of postmenopausal breast cancer. It has been shown that BMI modifies the effect of HRT, as its influence is most pronounced in lean women. We investigated the influence of BMI and HRT on prognosis in 2640 postmenopausal women diagnosed with breast cancer in Sweden in 1993–1995, taking into account HRT and mammography before diagnosis. Logistic and Cox regression were used. In non-users of HRT, obese women (BMI >30) compared with normal weight women (BMI <25) had a similar prognosis (hazard ratio (HR) 1.1, 95% confidence interval (CI) 0.8–1.6), despite larger tumours found in obese women. Obese HRT users had less favourable tumour characteristics and poorer prognosis compared with normal weight women (HR 3.7, 95% CI 1.9–7.2). The influence of BMI on breast cancer prognosis was similar whether diagnosed by mammographic screening or not. We found a similar prognosis of postmenopausal breast cancer-specific death regardless of BMI in non-users of HRT, but among HRT users obesity was associated with a poorer breast cancer prognosis