bluuebunny/crossref_metadata_2025_split huggingface dataset:
Breast cancer, dermatofibromas and arsenic.
Authors: Dantzig P 
Published: December 2010

Abstract
Abstract #4160
Background: Dermatofibromas are common benign tumors in women and breast cancer is the most common malignancy in women and an environmental etiology has been suspected in both conditions. The aim of this study is to determine if there is any relationship between the two conditions.&#x2028; Materials and Methods: 5 patients with dermatofibromas and 10 control patients(2 groups) had blood arsenic levels and their skin biopsies measured for arsenic by inductively coupled mass spectometry. Fifty randomly selected patients with breast cancer and 50 control patients were examined for the presence of dermatofibromas.&#x2028; Results: The patients with dermatofibromas had no detectable blood arsenic but the dermatofibromas were found to have an arsenic concentration of .171 micrograms/gram. One control group(5 patients) with no detectable blood arsenic had a skin concentration of .07 micrograms/gram and the other control group (5 patients) with an average blood concentration of 6 micrograms/liter had a concentration in their skin of .06 micrograms/gram. 43/50 patients with breast cancer had dermatofibromas and 32/50 had multiple dermatofibromas, compared with 10/50 control patients with dermatofibromas and only 1/50 with multiple dermatofibromas. In all breast cancer patients, the dermatofibromas preceded the breast cancer by many years though none of the patients could give an exact answer to that question.&#x2028; Conclusions: Dermatofibromas may represent a reservoir for arsenic and may interfere with the rapid excretion of arsenic resulting in prolonged exposure. Arsenic may be important to the development of dermatofibromas as shown by the proliferation of endothelial cells, the main target of arsenic toxicity, and the increased melanin and hemosiderin, the classic causes of hyperpigmentation in chronic arsenic toxicity.Dermatofibromas represent a sign of chronic arsenic exposure, a powerful environmental carcinogen, 5-20 years prior to the clinical signs of breast cancer, when the changes in the cells would first be developing. This is the first time that any link to an environmental carcinogen has been shown in breast cancer and may represent an important venue to dramatically decrease the number of cases in the future. The dermatofibroma, especially multiple dermatofibromas, represent an important cutaneous sign of women at risk for breast cancer.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4160.
Endoplasmic reticulum-associated calcium regulates taxol-induced apoptosis in breast cancer cells.
Authors: Pan Z , Gollahon L 
Published: December 2010

Abstract
Abstract #4163
Background: The body eliminates unhealthy cells through programmed cell-suicide called apoptosis. Calcium (Ca2+), one of the key regulators of cell survival, is also important in regulating apoptosis. Although the chemotherapeutic agent Taxol employs apoptosis to induce cell death in breast cancer treatment, the exact mechanism of how it induces apoptosis and the role of Ca2+ in this process remain unclear. The endoplasmic reticulum (ER), the main intracellular Ca2+ store, is newly-recognized as an important gateway in apoptosis, and possibly provides a target for Taxol.&#x2028; Objective/Hypothesis: Putting these facts together, our hypothesis is that ER Ca2+ changes induced by Taxol determine breast cancer cell susceptibility to apoptosis and thus play a key role in ER-associated apoptosis. Therefore, this study investigated whether Ca2+ changes, especially associated with the ER, were generated and related to this apoptotic event.&#x2028; Study Design and Methods: For this study, we used the MDA-MB-468 breast cancer cell line. The dynamic Ca2+ changes induced by Taxol were determined in living breast cancer cells by two methods: free cytosolic Ca2+ changes were measured using Fluo4-AM Ca2+ dye; and ER Ca2+ changes were measured by a novel Ca2+ cameleon, D1ER. After inducing and evaluating Taxol-induced apoptosis in this breast cancer cell line, the effects of different Ca2+ interfering agents on the apoptotic event were tested to determine whether Taxol-induced apoptosis is Ca2+ dependent.&#x2028; Results: Taxol has a direct effect on Ca2+ homeostasis. Taxol induces a rapid ER Ca2+ release and results in a transient increase in cytosolic Ca2+ levels. A gradual ER Ca2+ depletion developed and contributed to the final sustained cytosolic Ca2+ increase. Interfering with these Ca2+ changes inhibited the Taxol-induced apoptosis, indicating that ER Ca2+ promotes Taxol-induced apoptosis.&#x2028; Relevance: It is critical to understand the process through which the widely used anticancer agent Taxol induces apoptosis. This research addressed the question of whether intracellular Ca2+ changes play a critical or marginal role in mediating Taxol-induced apoptosis. Elucidating the role of calcium in this process will not only help to clarify the mechanism of Taxol, but also aid in more effective application of Taxol in breast cancer treatment.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4163.
Breast cancer treatment delay in African American women in Washington, DC.
Authors: Landau J , Sagy N , Young H , Alexander L , LaVerda N , Levine P , Patierno S 
Published: December 2010

Abstract
Abstract #4164
Background: Delays in follow-up after a positive breast cancer screen are thought to contribute to racial/ethnic disparities in breast cancer outcomes. The goal of this study was to determine the relative impact of self-identified race and other relevant socio-demographic and logistic variables on time to diagnosis after an abnormal mammogram, and time to first treatment after a cancer diagnosis within the context of data collection for a large research study of the effectiveness of patient navigation.&#x2028; Methods: Our sample includes 168 African-American and non-Hispanic white women with a documented invasive breast cancer diagnosis at an urban academic medical center during 2006 and 2007. The outcome variables were the number of days from abnormal mammogram to cancer diagnosis and from diagnosis to first treatment.&#x2028; Results: The median number of days to breast cancer diagnosis following an abnormal mammogram was 20.5 days for African-Americans compared to 15 days for non-Hispanic white women. Median days to first treatment after diagnosis was 21 days for African-American women compared to 16 days for non-Hispanic white women. Neither difference was statistically significant. In addition, 76% of African-American women had private insurance versus 81% of non-Hispanic white women.&#x2028; Conclusions: The identification of specific risk factors associated with a delay in diagnosis noted elsewhere in the literature and suggested in these preliminary findings could provide useful information regarding characteristics of women who are most likely to benefit from enhanced patient navigation efforts. Thus far, no statistically significant differences have been identified but the variety of factors that could contribute to the longer delay in disease management in African-American women compared to non-Hispanic white women, such as insurance status, provider location, household income, cultural issues, and other barriers to health care access, should be evaluated with a larger patient population.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4164.
The chemoresistant population of luminal subtype human breast cancer cells expresses a basal phenotype.
Authors: Kabos P , Dye WW , Elias A , Horwitz KB , Sartorius CA 
Published: December 2010

Abstract
Abstract #42
Background: We recently identified rare cells that express cytokeratin 5 (CK5+) and lack estrogen and progesterone receptors (ER– and PR–), in solid tumor xenografts derived from ER+PR+ T47D luminal A subtype human breast cancer cells (Horwitz et al, 2008 PNAS 105: 5774). These rare CK5+ cells have the capacity to re-form the majority of ER+PR+CK18+ cells in luminal tumor xenografts, and recapitulate the original tumor heterogeneity. CK5 is a marker of the poor prognosis basal-like subtype of human breast cancers. Additionally, CK5 is postulated to be a marker of stem/progenitor like cells in the human breast, and we have shown that CK5+ cells co-express the breast cancer stem cell marker CD44. We postulated that these rare basal-like CK5+ cells represent a potential chemoresistant subpopulation within luminal tumors. To test this, we used T47D and MCF7 cells, both of which have been classified by genetic profiling as luminal A (ER+PR+CK18+HER2–).&#x2028; Methods: Cells were plated at subconfluent densities in serum-containing media and treated with either vehicle or cyclophosphamide (1mM), 5-fluorouracil (150μM) or docetaxel (11nM) for 72 hours; these doses were determined to yield a one to two-log kill. Residual chemoresistant cells were fixed: i) immediately following chemotherapy, or ii) after colony repopulation for 7 days. The chemoresistant subpopulation was characterized by immunocytochemistry for markers of basal/stem and luminal phenotypes, including CK5, ER, PR, CK18, and CD44.&#x2028; Results: At baseline, as well as in controls, both cell lines were ER+PR+CK18+ and ER–PR–CK5+ cells were rare or undetectable. In response to treatment with each of the three drugs, the surviving population was enriched in ER–CK5+ cells. PR expression was variable (+/–) in CK5+ cells. These chemoresistant cells were able to repopulate colonies that expressed ER+PR+CK18+ and resembled the original cells by having a predominant luminal phenotype, with only rare/undetectable receptor negative, CK5+ basal-like cells.&#x2028; Conclusion: We conclude that luminal subtype human breast cancer cells contain a rare basal/stem-like chemoresistant subpopulation that is capable of repopulating a luminal tumor after therapy.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 42.
Intensive breast cancer screening programs including MRI influence prognosis and treatment of breast cancer among BRCA 1/2 gene mutation carriers.
Authors: Chereau E , Uzan C , Chevalier J , Bressac-de Paillerets B , Caron O , Mathieu M , Koskas M , Bourgier C , André F , Dromain C , Balleyguier C , Delaloge S 
Published: December 2010

Abstract
Abstract #5004
Background: Several studies have highlighted the potential benefit of early breast cancer (BC) diagnosis through breast MRI for high risk patients (pts). However, MRI is an expensive test with a low positive predictive value and has not been proven to reduce mortality rates in women carrying BRCA1/2 deleterious gene mutations (mut).&#x2028; At Institut Gustave Roussy, we started intensive BC screening programs for BRCA1/2 carriers (annual MRI + mammogram + bi-annual US) in 2001. The aim of this study was to compare the characteristics and prognostic features of BC in BRCA1/2 pts diagnosed inside or outside screening programs.&#x2028; Patients and Methods: All female BRCA1/2 mut carriers who have been treated for a new BC in our institution between 2001 and 2008, were entered into this study. All BRCA1/2 mut testing have been performed under the French guidelines and recommendations.&#x2028; We compared the clinico-pathological data, treatments and prognostic features between group 1 (pts diagnosed while on an intensive dedicated screening program) and group 2 (pts diagnosed outside these programs). Pts characteristics were compared using student T-test, and survival curves using Log-Rank tests.&#x2028; Results: 122 pts met the inclusion criteria: 20 in group 1, 102 in group 2. &gt; 95% of pts in group 2 were not aware of their BRCA1/2 mut at time of diagnosis. In group 1, 17 cancers were diagnosed primarily through MRI (85%), while 3 were self-detected interval BC. Pts in group 1 had tumors with significantly better prognostic factors and received less CT.&#x2028; 3-year DFS significantly differed between groups 1 (100%) and 2 (74% (IC: 64-81 (p=0.04). 3-years MFS was 100 and 80% (p= 0.08), 3-years OS was 100 and 94% (p=0.26) in groups 1 and 2.&#x2028; &#x2028; Conclusion: These early data strongly suggest an important benefit in terms of disease-free survival and treatment sparing for i. the knowledge of a BRCA1/2 mut; ii. inclusion into intensive BC screening programs including MRI.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5004.
Method of detection is a prognostic factor for outcome among women diagnosed with early stage breast cancer.
Authors: Brewster AM , Thompson PA , Cao Y , Murray JL , Stewart MM , Berry DA , Bondy ML 
Published: December 2010

Abstract
Abstract #5005
Background: The reduction in breast cancer mortality over the past several decades has been partially attributed to the impact of screening mammograms. Breast cancers detected by screening mammograms tend to be at an earlier stage than those detected as a result of symptoms. The magnitude of the impact of method of detection on breast cancer survival beyond this phenomenon, known as stage shift, is not well defined. We therefore evaluated the independent prognostic effect of method of detection among women diagnosed in early stages of disease (stage I and II breast cancers). Methods: Medical records from 2,143 women aged 40 or older with stage I and II breast cancers, treated at the M.D. Anderson Cancer Center between 1985 and 2000 were used to derive information on method of breast cancer detection, clinical and histological tumor characteristics. Cox proportional hazards models were used to estimate the hazard ratios (HR) of breast cancer recurrence and breast cancer-specific death adjusted for age at diagnosis, year of diagnosis, nuclear grade, hormone receptor status, systemic treatment and stage at diagnosis. All statistical tests were two-sided. Results: Patients ages 40-49, 50-69 and ≥70 with symptom compared to screen-detected breast cancers were statistically significantly more likely to be diagnosed with stage II versus stage I disease and were more likely to have higher nuclear grade III versus grade I tumors. Symptom-detected breast cancers were associated with an increased risk of breast cancer recurrence (HR 1.9, 95% confidence interval (CI) 1.4-2.6) and breast cancer-specific death (HR 2.0, 95% CI 1.4-3.0) than screen-detected breast cancers after adjusting for age at diagnosis, year of diagnosis, tumor size, lymph node involvement, tumor characteristics and systemic treatment. Discussion: Our data from a large cohort of breast cancer patients with long-term follow-up indicate that even among patients with early stage disease; those with symptom-detected breast cancers have a worse prognosis. Consideration should be given to including method of detection as a prognostic factor when making treatment decisions for patients with stage I and II breast cancers.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5005.
Is the incidence of breast cancer among Asian women living in the UK, higher at a younger age than that of the Caucasian women?.
Authors: Ullah MZ , Pericleous M , Jamal-Hanjani M , Pereira B , Snooks SJ , Keshtgar M , Davidson T 
Published: December 2010

Abstract
Abstract #5011
Introduction: The South Asian population comprises 3% of total UK population. An observational study showed that the Asian women living in the London boroughs of Redbridge and Camden present at a younger age with breast cancer than their Caucasian counterpart. This raises the question as to whether or not an earlier intervention with breast screening would be beneficial for this group.&#x2028; Methods: To verify our study, we audited two centres in these London boroughs. The patients with breast cancer from areas with a higher concentration of women of South Asian ethnic origin have been audited from January 2000 to December 2007 (Total 9 years). The borough of Redbridge has an Asian population of 25% from a total of 240,000 residents and Camden has an Asian population of 10.4% from a total of 198,000 residents. Data was collected from the breast units and from patient databases of King George Hospital and Royal Free hospital, London, UK.&#x2028; Results: A total of 1314(513+801) patients presented with breast cancer from January 2000 to December 2004 at King George Hospital and from January 2002 to December 2007 at Royal Free Hospital. 147(11.18%) of these patients were of South Asian origin (Indian, Pakistani, Bangladeshi, Sri Lankan) and 1149 (87.44%) were Caucasian. The age at which breast cancer was presented for the Caucasian population ranges from 25 to 99 years with a mean of 65.16 in contrast to the age for the Asian population which ranges from 31 to 78 years with a mean of 54.04.&#x2028; Conclusions: The finding of a lower mean age of incidence of breast cancer amongst South Asian women in Redbridge and Camden raises the increased possibility of breast cancer occurring among younger women of the South Asian population in general, compared to Caucasian women living in the United Kingdom. The evidence of a generally younger age of presentation of breast cancer in Asian women living in the UK suggests that more awareness of this condition is needed amongst this group. Therefore, an earlier breast screening programme will possibly increase the chances of early detection of breast cancer among this group of patients.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5011.
The value of mammography vs. physical examination in detecting a recurrent breast cancer in women with a previous diagnosis of breast cancer.
Authors: Elmadhun NY , Finlayson CA 
Published: December 2010

Abstract
Abstract #5014
Background: The value of mammography in detecting early breast cancer has been firmly established, however the benefit of mammography in detecting recurrent breast cancer has not been clearly elucidated. The purpose of this study is to determine the value of mammography versus physical examination in detecting a recurrent breast cancer in women with a previous diagnosis of breast cancer.&#x2028; Methods: This is an IRB approved retrospective chart review. Fifty-eight patients were identified from our institution's Breast Center tumor registry who were diagnosed with stage I-II breast cancer from 1973-2006 and who subsequently developed a locoregional recurrence. The method of detection of the initial breast cancer was recorded and compared to the method of detection of the recurrent breast cancer.&#x2028; Results: The mean age at the original diagnosis was 47 years (range 29-89 years). The mean time to recurrent breast cancer or second primary was 38 months (range 6-173 months). Seventeen patients (29%) were initially diagnosed with breast cancer by screening mammography. Of those 17, 3 (18%) were diagnosed with a recurrent breast cancer by mammography, and the remaining 14 by physical exam. Among the 14 patients that presented initially with a palpable breast mass and positive mammogram, 3 (21%) had recurrent breast cancer detected by mammography. Thirty-four patients (59%) initially presented with a palpable mass. Nineteen of these patients had mammograms, 5 did not have mammography, and 8 were unknown whether imaging was done. Of those 19 that had mammography, 14 were positive and 5 were negative. The 5 patients with palpable masses and negative mammograms all had mastectomies initially and their locoregional recurrence was detected by physical exam. Forty-nine patients (84%) had a clinical finding leading to the diagnosis of recurrent breast cancer and seven (12%) had recurrence identified by mammography. Two patients had unknown method of detection of recurrence. The clinical recurrences were identified in the axilla (53.4%), chest wall (12%), supraclavicular fossa (8.6%), breast (3.4%), and skin (3.4%).&#x2028; Conclusions: One-third of patients with a recurrent breast cancer had their initial cancer identified by mammography but only 12% had their recurrence identified by mammography. Fifty-nine percent of patients were initially diagnosed by physical examination and 84% of recurrence was diagnosed with physical examination. Patients whose initial cancer was visible on mammogram are likely to have a recurrence also visible on mammogram. Though mammography is useful in detecting the first early stage breast cancer, most patients present with a clinical finding when they present with the recurrent breast cancer.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5014.
Validation of OncoVue®, a new individualized breast cancer risk estimator in the Marin County, California adolescent risk study.
Authors: Dalessandri KM , Miike R , Wrensch MR , Wiencke JK , Benz CC , Pugh TW , Manjeshwar S , Jupe ER 
Published: December 2010

Abstract
Abstract #502
Background: Improved models for estimating individual breast cancer risk are urgently needed for guiding clinical decisions. The OncoVue model was developed by analysis of a large case-control study genotyped for 117 common, functional single nucleotide polymorphisms (SNPs) in candidate genes likely to influence breast carcinogenesis. Multivariate logistic regression analyses were used to develop a model employing 22 SNPs in 19 genes together with the Gail Model risk factors. In the original studies of the model building set and two independent validation sets, OncoVue exhibited improved individualized risk estimation, compared to the Gail Model alone, by correctly placing more cases and fewer controls at elevated risk. Here, we sought to examine the performance of OncoVue in women from the Marin County, California breast cancer adolescent risk factor study.&#x2028; Materials and Methods: Buccal cell DNA was isolated from 177 controls and 169 age-matched women diagnosed with breast cancer between 1997 and 1999. All samples were anonymously coded to remove case-control status and provided to InterGenetics along with all other relevant personal history information. DNAs were genotyped for the 22 SNP variants in OncoVue and combined with personal factors to calculate the risk scores for the individual participants. OncoVue scores were then returned to the Marin County study investigators who conducted the analyses using case-control status.&#x2028; Results: Positive likelihood ratios (PLR) were calculated as the proportion of patients with breast cancer with an elevated risk estimate (12%) divided by the proportion of disease-free individuals with an elevated risk estimate. For OncoVue the PLR was 2.2, whereas for the Gail Model the PLR was 0.9, demonstrating a 2.4-fold statistically significant (p=0.036) improvement. In additional comparisons using normalized control scores, OncoVue exhibited a 51% improvement compared to the Gail Model in assigning elevated risk to cases.&#x2028; Conclusion: In this blinded validation study OncoVue exhibited significantly improved performance, compared to the Gail model alone, in estimating individual risk among Marin County, California women. The improved performance of OncoVue was similar to that observed in two previous independent validation sets, thus, supporting the clinical utility of OncoVue for more accurate individualized breast cancer risk estimation.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 502.