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Currently, an in vivo spontaneous model of estrogen dependent, tamoxifen sensitive breast cancer does not exist. We show here the characterization of the M05 mammary tumor that appeared spontaneously in a 1-year-old virgin female BALB/c mouse in our animal facility. The M05 tumor is a semi-differentiated adenocarcinoma that expresses estrogen and progesterone receptors. When it was transplanted to either male or ovariectomized female mice it did not grow. Moreover, ovariectomy or treatment with tamoxifen of tumor bearing mice led to a halt in tumor growth. Treatment of ovariectomized mice that had been inoculated with the M05 tumor showed that only estradiol, but not progesterone, promoted the re-growth of the tumor. Finally, after passage nine, tumor growth was achieved in male and ovariectomized female mice suggesting that the tumor had progressed to hormone independence. However, like often found in the clinic, expression of estrogen and progesterone receptors was maintained. This model mimics the biology of estrogen receptor positive breast cancer in humans and presents itself as an invaluable tool for the study of endocrine resistance in a physiologically relevant setting.  相似文献   

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BACKGROUND: Several recent studies suggest that adequate dietary folate may attenuate the risk of breast cancer associated with intake of alcohol. We examined whether the putative benefit extends to women with a family history (FH) of breast cancer using a cohort of 33,552 postmenopausal women aged 55-69 years in 1986. METHOD: Folate and alcohol intake was estimated from a food frequency questionnaire completed at baseline. Folate was categorized as upper 50th, 31st-50th, 11th-30th, and <10th percentiles. Alcohol use was initially classified into three levels; never drinkers, less than the median and greater than the median. Subsequent models collapsed levels of intake to any versus none. Occurrence of breast cancer was determined through linkage to the Iowa SEER registry. Multivariate-adjusted relative risks (RR) and 95% confidence intervals (CI) were estimated through Cox proportional hazards regression, stratified on FH using non-drinkers with high folate and no FH as the referent group. RESULTS: Through 14 years, 1823 incident cases were identified, 308 among FH+ women. Among FH- women, low folate was not a risk factor among non-drinkers (RR = 0.96, CI = 0.73-1.26), but was among drinkers (RR = 1.40, CI = 1.05-1.86). Drinkers with high folate were not at elevated risk (RR = 1.03, CI = 0.89-1.19). Among FH+ women, low folate was a risk factor among drinkers (RR = 2.21, CI = 1.43-3.41) and non-drinkers (RR = 2.39, CI = 1.36-4.20). Further, drinkers with high folate remained at increased risk (RR = 1.67, CI= 1.30-2.14). However, FH+ women with high folate who did not drink alcohol had no elevated risk. CONCLUSION: These results suggest that folate may attenuate the risks of postmenopausal breast cancer associated with family history, but only if alcohol use is avoided or minimized.  相似文献   

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In this cross‐sectional population‐based study, we assessed the incidence of advanced breast cancer based on screening attendance. Women from the Netherlands Cancer Registry were included if aged ≥49 years and diagnosed with breast cancer between 2006 and 2011, and data were linked with the screening program. Cancers were defined as screen‐related (diagnosed <24 months after screening) or nonscreened (all other breast cancers). Two cut‐offs were used to define advanced breast cancer: TNM‐stage (III–IV vs 0–I–II) and T‐stage alone (≥15 mm vs <15 mm or DCIS). The incidence rates were adjusted for age and logistic regression was used to compare groups. Of the 72,612 included women diagnosed with breast cancer, 44,246 (61%) had screen‐related breast cancer. By TNM stage, advanced cancer was almost three times as likely to be at an advanced TNM stage in the nonscreened group compared with the screen‐related group (38 and 94 per 100,000, respectively; OR: 2.86, 95%CI: 2.72–3.00). By T‐stage, the incidence of advanced cancer was higher overall, and in nonscreened women was significantly higher than in screened women (210 and 169 per 100,000; OR: 1.85, 95%CI: 1.78–1.93). Data on actual screening attendance showed that the incidence of advanced breast cancer was significantly higher in nonscreened women than in screened women, supporting the expectation that screening would cause a stage shift to early detection. Despite critical evaluations of breast cancer screening programs, our data show that breast cancer screening is a valuable tool that can reduce the disease burden in women.  相似文献   

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Objective: To determine whether a telephone counseling program can improve psychosocial outcomes among breast cancer patients post‐treatment. Methods: A randomized trial was conducted involving 21 hospitals and medical centers, with assessments (self‐administered questionnaires) at baseline, 12 and 18 months post‐enrollment. Eligibility criteria included early stage diagnosis, enrollment during last treatment visit, and the ability to receive the intervention in English. Endpoints included distress (Impact of Event Scale), depression (Center for Epidemiologic Studies Depression Scale), and two study‐specific measures: sexual dysfunction and personal growth. The control group (n=152) received a resource directory for breast cancer; the intervention group (n=152) also received a one‐year, 16 session telephone counseling program augmented with additional print materials. Results: Significant intervention effects were found for sexual dysfunction at 12 (p=0.03) and 18 months (p=0.04) and personal growth (12 months: p=0.005; 18 months: p=0.03). No differences by group were found in mean scores for distress and depression, with both groups showing significant improvement at 12 and 18 months (all p values for within‐group change from baseline were ?0.003). However, when dichotomized at cutpoints suggestive of the need for a clinical referral, the control group showed virtually no change at 18 months, whereas the intervention group showed about a 50% reduction in both distress (p=0.07) and depression (p=0.06). Conclusions: Telephone counseling may provide a viable method for extending psychosocial services to cancer survivors nationwide. Copyright © 2010 John Wiley & Sons, Ltd.  相似文献   

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Nearly a decade ago, researchers identified a potential interaction between tamoxifen and strong CYP2D6 inhibitors, including several frequently used antidepressants. Based on evidence available at that time, a United States Food and Drug Administration advisory committee recommended tamoxifen’s label be changed in October 2006, noting that postmenopausal women with estrogen receptor-positive breast cancer who are poor CYP2D6 metabolizers by genotype or drug interactions may be at increased risk of cancer recurrence. The impact of accumulating drug risk information on antidepressant use is unknown. We conducted a retrospective, longitudinal cohort study of 13,205 women aged 50–95 with breast cancer initiating tamoxifen between July 2004 and December 2009. We evaluated trends in strong, moderate, and weak CYP2D6-inhibitor antidepressants and tamoxifen co-prescribing and factors associated with ongoing strong inhibitor use. A propensity score matched control group (aromatase inhibitor initiators) was used to estimate changes in co-prescribing, accounting for secular trends. In each month, approximately 24 % of tamoxifen and aromatase inhibitor users were prescribed antidepressants. Among women using tamoxifen and antidepressants, 34 % used strong inhibitors between 2004 and 2006 versus 15 % in 2010. Strong inhibitor use decreased more among tamoxifen users than aromatase inhibitor users (difference-in-differences [DD] ?0.09; 95 % confidence interval [CI] ?0.15, ?0.03). Weak inhibitor use increased among tamoxifen users from 32 % between 2004 and 2006 to 52 % in 2010, more rapidly than among aromatase inhibitor users (DD 0.15; CI 0.08, 0.23). The factor most strongly associated with strong inhibitor and tamoxifen co-prescribing after 2006 was prior strong inhibitor use (RR 4.73; CI 3.62–6.18). In conclusion, there were substantial declines in strong CYP2D6-inhibitor use among tamoxifen users following dissemination of information suggesting a potential for increased risk with co-prescribing. Whether patients and providers will continue to avoid strong inhibitor antidepressants is yet to be seen, but clinicians appear to be responsive to drug interaction risk information in this setting.  相似文献   

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Background and objective  

A high educational level has been found to be a risk factor of breast cancer. However, it is not clear whether such association persists after adjustment for individual risk factors of breast cancer such as parity in Iranian women.  相似文献   

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Previous studies have reported that the prevalence of ER-negative tumors in breast cancer patients is much higher in black women than in white women in the US. Herein, we examine whether the proportion (prevalence) in Africa-born black breast cancer patients residing in the US is similar to those in US-born black patients. We obtained information on invasive female breast cancers diagnosed during 1996-2008 in 17 Surveillance Epidemiology and End Results cancer registries according to select place of birth: Western-Africa-born, Eastern-Africa-born, Jamaica-born, and US-born blacks and US-born whites. The majority of Western-Africa-born and Eastern-Africa-born blacks were from Nigeria (64?%) and Ethiopia (74?%), respectively. We examined group variations in ER status using Chi-squared tests and the prevalence of ER-negative tumors in Africa-born blacks compared to US-born blacks, expressed as prevalence ratio (PRR), using multivariable regression models. The prevalence of ER-negative tumors significantly varied from 22.0?% (n?=?41/186) in Eastern-Africa-born to 32.9?% (n?=?47/143) in Western-Africa-born blacks. After adjustment for differences in age at diagnosis and other covariates, compared to US-born blacks, the prevalence was similar in Western-Africa-born (PRR?=?0.87; 95?% CI 0.70-1.08) and Jamaica-born blacks (PRR?=?0.88; 95?% CI 0.74-1.03), but significantly lower in Eastern-Africa-born blacks (PRR?=?0.58; 95?% CI 0.44-0.75). Notably, the ER-negative prevalence in Eastern-Africa-born black was comparable to the US-born whites with breast cancer. Our findings highlight the heterogeneity of breast cancer among black women in the US, which should be considered in future studies of hormone receptor status in these women.  相似文献   

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Background  

Neo-adjuvant chemotherapy is an integral part of multi-modality approach in the management of locally advanced breast cancer and it is vital to predict the response in order to tailor the regime for a patient. The common final pathway in the tumor cell death is believed to be apoptosis or programmed cell death and chemotherapeutic drugs like other DNA-damaging agents act on rapidly multiplying cells including both the tumor and the normal cells by following the same common final pathway. This could account for both the toxic effects and the response. Absence or decreased apoptosis has been found to be associated with chemo resistance. The change in expression of apoptotic markers (Bcl-2 and Bax proteins) brought about by various chemotherapeutic regimens is being used to identify drug resistance in the tumor cells. A prospective clinical study was conducted to assess whether chemotherapy induced toxic effects could serve as reliable predictors of apoptosis or response to neo-adjuvant chemotherapy in patients with locally advanced breast cancer.  相似文献   

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This study sought to examine the relationships between decisional role (preferred and assumed) at time of surgical treatment (baseline), congruence between assumed role at baseline and preferred role 3 years later (follow-up), and quality of life at follow-up. Two hundred and five women diagnosed with breast cancer completed the decisional role preference scale at baseline and follow-up, and the EORTC QLQ-C30 at follow-up. A statistically significant number of women had decisional role regret, with most of these women preferring greater involvement in treatment planning than was afforded them. Women who indicated at baseline that they were actively involved in choosing their surgical treatment had significantly higher overall quality of life at follow-up than women who indicated passive involvement. These actively involved women had significantly higher physical and social functioning and significantly less fatigue than women who assumed a passive role. Quality of life was significantly related to reports of experienced involvement in treatment decision making, but not to reports of preferred involvement, or congruence between preferred and experienced involvement.  相似文献   

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