bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of protein phosphatase 2A subunit gene haplotypes and proliferative breast disease on breast cancer risk.
Authors: Dupont WD , Breyer JP , Bradley KM , Schuyler PA , Plummer W , Sanders ME , Page DL , Smith JR 
Published: December 2010

Abstract
Abstract #3090
Background: A large number of genes encode components of complex growth factor signaling networks and may contribute to breast cancer risk. Prominent among these candidates are protein phosphatases that counter kinases of signaling cascades. We explored the role of a set of candidate genes encoding subunits of the major cellular protein phosphatase 2A (PP2A) in a cohort of women with a history benign breast disease. Women with a history of benign proliferative breast disease are at increased risk of subsequently developing breast cancer.&#x2028; Materials and Methods: We evaluated genetic variation in a set of 49 candidate genes of signal transduction pathways for potential contributions to breast cancer risk. The study was conducted as a nested case-control investigation of a cohort of women with a history of benign breast disease. DNA prepared from the original archival benign breast biopsy was available for 301 women diagnosed with breast cancer on follow-up, and for 545 of their 602 matched controls. Controls were women who remained free of breast cancer, matched to cases in a 2:1 ratio by race, age, and year of entry biopsy.&#x2028; Results: We observed that a PP2A structural subunit gene, PPP2R1A, and two regulatory subunit genes, PPP2R2A and PPP2R5E, each appeared to modify breast cancer risk with both risk-elevating and risk-reducing genetic variants. Only PPP2R2A was significantly associated with breast cancer after correction for multiple comparisons, with significant risk and protective haplotypes (OR = 1.79, study-wide P = 0.015, and OR = 0.62, study-wide P = 0.025, respectively). These variants interact with a history of proliferative breast disease to modify risk for breast cancer. In a dose model that included all three genes, breast cancer risk ranged from a 5.1-fold decrease to a 3.9-fold increase in risk, depending on the portfolio of variants inherited by a woman (study-wide P = 0.02).&#x2028; Discussion: If confirmed by independent studies, PP2A may play a key role as a tumor suppressor in breast cancer that is able to augment as well as to nullify elevated risk associated with early benign proliferative breast disease.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3090.
Impact of BRCA mutation status on the clinical phenotype and survival of hereditary breast cancer.
Authors: Kiechle M , Engel C , Schwarz-Boeger U , Grund D , Preisler-Adams S , Crohns C , Stark S , Gadzicki D , Strunz K , Schoenbuchner I , Nestle-Kräemeling C , Kast K , Ditsch N , Schlehe B , Schmutzler R 
Published: December 2010

Abstract
Abstract #3091
Background : In a multidisciplinary program supported by the German Cancer Aid in 1996-2006 a total of 3.408 women with a family history for breast and/or ovarian cancer were genetically counselled and tested for BRCA-1 and BRCA-2 mutations.&#x2028; Methods: The mutations were detected using DHPLC and direct sequencing. The family history of breast and/or ovarian cancer was proven by collecting medical reports of family members. The statistical analysis was done using standard procedures (Kaplan-Meier-analysis, t-test, chi-square-test).&#x2028; Results: Among the women with breast cancer 566 showed a deleterious BRCA1 and 313 a BRCA2 mutation. Four women were found to have mutations in both genes and 2.525 were BRCA-1/2 negative. In accordance with the literature we found the phenotype “hormone receptor negative and grade 3” as well as the medullary subtype significantly more often in BRCA1 associated breast cancers (74% vs. 24%, 63% vs. 42% and 10% vs. 5%). The median age of onset was significantly lower in BRCA1 mutation carriers (38 yrs) compared to BRCA2 mutation carriers (45 yrs) and women tested negative for BRCA1 and BRCA2 mutations (46 yrs) as well as sporadic breast cancer cases within these families (52 yrs). The median age of the 4 women with mutations in both genes was even lower (median age 33.5 yrs). Although BRCA2 associated breast carcinomas presented in more advanced stages (N+ in 44%[118/257] compared to BRCA-1 positive in 31%[166/519], p&lt;0.01) there was no difference in overall survival between BRCA1 and BRCA2 mutation carriers. However, BRCA1 and BRCA2 negative cases showed a significantly better survival rate compared to the women with mutations (p&lt;0.0001). Women from families with early onset breast cancer (&lt;35 yrs) or bilateral breast cancer (&lt;40 yrs) had a significantly better survival (p&lt;0.0001) than women from families with a later age of onset.&#x2028; Conclusions: The BRCA mutation status has a significant impact on the clinical phenotype of hereditary breast cancer which is important for the clinical management, counselling and prevention.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3091.
Evaluation of variants in BRIP1, PALB2 and CHEK2 in a west of Ireland breast cancer cohort.
Authors: Mc Inerney NM , Miller N , Rowan A , Colleran G , Curran C , Ian T , Eli S , Michael KJ 
Published: December 2010

Abstract
Abstract #3092
Introduction&#x2028; Positive family history is the most important risk factor in breast cancer predisposition. Recent studies have identified variants in BRIP1, PALB2 and CHEK2, which have been proposed as breast cancer susceptibility genes conferring an increased relative risk of 2-4%.&#x2028; Aims&#x2028; To evaluate the role of the above variants in the West of Ireland population and to examine their potential clinical relevance.&#x2028; Methods&#x2028; Proposed candidate genetics variants in BRIP1, PALB2 and CHEK2 were interrogated in 192 patients with a high risk of familial breast cancer. Genescan analysis and direct sequencing were used to evaluate these variants. Where a variant was exhibited, it was then examined further in 990 sporadic breast cancer patients and 1016 matched non-cancer controls using KASPar genotyping technology.&#x2028; Results&#x2028; We demonstated mutations in BRIP1 and CHEK2 genes. 1 mutation was found in BRIP1 2392C→T in our 192 patients with a high risk of familial breast cancer. 5 breast cancer patients and 1 control exhibited a CHEK2110delC mutation within 990 breast cancer patients and 1016 matched non-cancer controls. Mutations previously demonstrated in PALB2 were not evident in 192 high risk patients.&#x2028; Conclusions&#x2028; We have confirmed the presence of variants in BRIP1 and CHEK2, candidate moderate penetrance genes, in breast cancer patients with a strong family history of breast cancer. This may have implications in clinical practice as our knowledge of these variants expands. The absense of PALB2 variants in patients at high genetic risk points to a low clinical significance. Our findings contribute to a better understanding of inherited breast cancer risk while helping to optimize future screening, therapeutic and prophylactic programs.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3092.
The new understanding of two-sided role of glutathione S-transferase M1 in breast cancer susceptibility.
Authors: Yu K , Di G , Wu J , Shao Z 
Published: December 2010

Abstract
Abstract #3098
[Background and purpose] Although glutathione S-transferase M1 (GSTM1) enzyme occupies a key position in biological detoxification processes by catalyzing the glutathione conjugation of carcinogens, GSTM1 gene is genetically deleted (referred as GSTM1-null or GSTM1-/-) in a high percentage of the Eurasian populations. Numerous studies have examined the association of GSTM1-/- with breast cancer yielding inconsistent results. In addition, few genetic variants in this gene have been explored. We set out to systematically evaluate the contributions of GSTM1 gene deletion/presence and common variants in GSTM1 to breast cancer, followed by functional studies.&#x2028; [Methods and Results] In the present study, we show that GSTM1-/- does confer a weak increased risk of breast cancer compared with GSTM1-present genotype, being confirmed by a meta-analysis of combining 40 related studies with the current case-control study (921 cases vs. 711 controls) of Chinese population (overall odds ratio of 1.10, 95% confidence interval: 1.04-1.15, P&lt;0.001). Unexpectedly, GSTM1 homozygous wild-type (+/+) is also associated with a risk of breast cancer compared with heterozygous (+/-) individuals on the basis of accurate classification using long-PCR-based assay. Furthermore, for the population with one allele of GSTM1 (GSTM1+/-) accounting for 30-50%, we genotype four common single nucleotide polymorphisms (SNPs) spanning GSTM1 gene and identify a functional variant g.-498C&gt;G in the putative promoter region associated with breast cancer risk. It displays that minor -498G allele is significantly more frequent in breast cancer controls than in cases (odds ratio of 0.51, 95% confidence interval: 0.30-0.86, P=0.012). This allele also leads to significantly reduced promoter activity compared to the major -498C allele. Further studies reveal the -498G can modify AP-2 binding site and decrease GSTM1 transcription. Among the three AP-2 isoforms, AP-2α provides the predominant regulation effect on this SNP.&#x2028; [Conclusions] These results indicate that the effect of GSTM1 genotypes conferring to breast cancer susceptibility is not dosage-dependent as taken for grant previously. GSTM1 has a two-sided role in breast cancer susceptibility; too high or too low expression of GSTM1 is not beneficial. We recommend that the complicated genetic predisposition of GSTM1 be considered when predicting breast cancer susceptibility using single or a panel of genetic variants.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3098.
HER2/ER subtypes associated with patient and tumor factors and predicted survival among participants in a retrospective breast cancer cohort study in Southern California.
Authors: Haque R , Press MF , Polikoff JA , Avila CC , Enger SM 
Published: December 2010

Abstract
Abstract #3099
Background: Molecular marker expression analyses have led to the identification of unique breast cancer subtypes that have clinical and prognostic importance. Using data from a large population-based breast cancer cohort, we report results examining combined HER2/neu and estrogen receptor (ER) subtype distribution in relation to patient and tumor characteristics as well as breast cancer specific survival.&#x2028; Methods: We conducted a retrospective cohort study of 1,645 female members of a large managed care organization newly diagnosed with invasive breast cancer from 1988 to 1995. We collected patient, tumor, treatment, and outcome information from medical records and electronic cancer registry files. We used immunohistochemistry techniques to evaluate gene expression of specific molecular markers including HER2/neu and estrogen receptor (ER). We examined prevalence of markers as well as odds ratios (OR) and 95% confidence intervals (CI) comparing outcomes by marker expression.&#x2028; Results: Women with HER2+/ER- tumors were more likely to have been diagnosed at a younger age (less than age 60) than women with luminal A subtype (HER2-, ER+ and/or PR+) tumors (65.5% versus 47.8%, P&lt;0.0001). A higher proportion of women with HER2+/ER- tumors were other than white race compared with women with luminal A subtype (21.8% versus 11.6%, P=0.007). Women with luminal B (HER2+, ER+ and/or PR+) or basal-like (HER2-, ER-, PR) subtype tumors were similarly more likely to be older at diagnosis and from minority backgrounds than women with luminal A subtype. Family history of breast cancer was not clearly associated with HER2/ER subtype. Women with luminal A tumors were more likely to be diagnosed with stage 1 disease than women with other tumor subtypes (luminal A: 56.3%; luminal B: 38.9%; basal-like: 38.1%; HER2+/ER-: 25.5%; P&lt;0.0001). Residual tumor in surgical margins was not associated with HER2/ER subtype. Compared with women with luminal A tumors, women with HER2+/ER- tumors were much more likely to die of their cancers overall (OR=6.5, CI=3.5-11.9), and by stage (stage 1: OR=11.5, CI=2.6-50.3; stage 2: OR=3.8, CI=1.6-9.2; stage 3/4: OR=9.0, CI=1.1-77.2). Odds of breast cancer death, overall and by stage, was also increased for women with luminal B and basal-like subtype tumors compared with women having luminal A subtype.&#x2028; Conclusions: HER2/ER subtype was clearly associated with patient as well as tumor characteristics in this large cohort of breast cancer patients. Specific tumor subtypes (HER2+/ER-, luminal B, and basal-like) were also associated with increased likelihood of dying of breast cancer. Further work is warranted to define treatment strategies by molecular subtypes.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3099.
Preference for breast cancer risk reduction hormonal therapy in women age 50-69 years attending screening mammography.
Authors: Lupichuk SM , Currie GR , Bryant HE 
Published: December 2010

Abstract
Abstract #3100
Background: It is expected that tamoxifen, raloxifene and aromatase inhibitors (AIs) will become available for the indication of breast cancer prevention in postmenopausal women. It is unknown how women weigh the benefits and disadvantages of these drugs. The aim of this study was to elicit preferences, using a discrete choice experiment (DCE), for attributes of breast cancer risk reduction hormonal therapies amongst women age 50 – 69 years who attend screening mammography.&#x2028; Methods: 500 potentially eligible women were randomly sampled from a screening mammography database (SMD). Women permitting contact from the investigators were invited to participate. Demographic and breast cancer risk factor data was collected from the SMD for participants and non-participants, and compared. The DCE was administered via a postal survey. The attributes and levels for the DCE are outlined in Table 1. A fractional factorial design and matched fold-over technique yielded 16 choice sets. Two dominant choice sets were added. For each choice set, respondents were asked to mark preference for Drug A, Drug B or Neither. The DCE was analyzed using conditional logistic regression (CLR). Regression post estimation calculations (RPECs) were used to predict chemoprevention uptake.&#x2028; &#x2028; Results: 111 women agreed to be contacted by the investigators, 94 agreed to be sent a survey and 79 returned a completed questionnaire. The proportions of participants who were nulliparous or had a predicted 5-year breast cancer risk &gt;1.66% were significantly higher than for non-participants (p&lt;0.05). No differences were found for age, education or mammographic breast density. From the CLR, all attributes, except decreased risk bone fracture, had coefficients that were significantly different from zero (p&lt;0.01) and of the expected sign. RPECs suggest that the uptake of tamoxifen, raloxifene and AIs would be 13%, 50% and 23% respectively, and that 14% would not consider chemoprevention.&#x2028; &#x2028; Conclusions: The most important attribute in women's selection of a prevention drug was breast cancer risk reduction. However, the following attributes were still important negative influences on choice: increased risk bone fracture &gt; endometrial cancer &gt; venous thromboembolic event &gt;&gt; cost. Raloxifene may be favoured if all three agents were available.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3100.
Skin thickness as a measure of breast lymphedema.
Authors: Degnim AC , Hoskin TL , Cheville AL , Miller JP , Gamble GL , Baddour LM , Donohue JH , Thomsen KM , Maloney SD , Boughey JC 
Published: December 2010

Abstract
Abstract #3103
Introduction: Lymphedema is well-known in the arm but can also occur in the breast. Diagnosis is currently non-standardized and based on clinical impression. We sought to determine if skin thickness could serve as a useful measure in the diagnosis of breast lymphedema (BLE).&#x2028; Methods: Patients undergoing unilateral non-mastectomy procedures were enrolled on this prospective clinical study preoperatively and evaluated for signs and symptoms of lymphedema in the operated breast in the postoperative period. Patients with established BLE were also studied. BLE diagnosis was independent of ultrasound findings and was based on a graded physical exam targeting clinical signs of edema and erythema. Skin thickness was measured with ultrasound at the 6 o'clock position of both breasts. Differences in skin thickness were assessed by the ratio of skin thickness in the operated and contralateral breasts, with comparison of means by two-sample t-test. Receiver operating characteristic curves were constructed to estimate the area under the curve (AUC) and to determine optimal cutpoints.&#x2028; Results: Ninety-seven women were studied; 85 were enrolled preoperatively and 12 postoperatively after a diagnosis of BLE. Median length of follow-up overall was 8 months. Of the 97 women, 46 had BLE at one or more follow-up visit with median time to first diagnosis of 3 months. Mean measured skin thickness was 2.3 ± 0.5mm in unaffected breasts and 3.2 ± 1.0 mm in operated breasts. Women with BLE had significantly greater skin thickness in the operated breast compared to the contralateral breast, with a mean skin thickness ratio of 1.83 ± 0.57 in patients with BLE compared to 1.18 ± 0.40 among those without BLE (p&lt;0.0001). Skin thickness ratio provided excellent discrimination for BLE, with an area under the curve (AUC) of 0.86. At a ratio of 1.32 or greater (32% greater skin thickness in operated versus contralateral breast), sensitivity and specificity for diagnosing BLE were 81% and 82% respectively. A single measure of skin thickness in the operated breast also correlated well with diagnosis of BLE, with skin thickness of 3.2 mm or greater demonstrating sensitivity of 78% and specificity of 82%, AUC 0.82.&#x2028; Conclusions: Breast lymphedema results in skin edema and increased skin thickness that can be quantified with ultrasound. Measuring breast skin thickness- either as a single reading or as a ratio to the unaffected breast- may be useful in the diagnosis of breast lymphedema.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3103.
Analysis of factors associated with increased psychological distress in new outpatients at the breast clinic.
Authors: Ando N , Iwamitsu Y , Kuranami M , Okazaki S , Wada M , Yamamoto K , Watanabe M , Miyaoka H 
Published: December 2010

Abstract
Abstract #3110
Objective: To determine how psychological characteristics, subjective symptoms, and a family history of breast cancer affect the mood states of outpatients with mammary gland complains at the first hospital visit.&#x2028; Participants and methods: Written consent to participate in the study was provided by 242 outpatients with mammary gland complains at Kitasato University hospital from November 2004 to January 2007. Participants either visited our hospital directly, or were referred here from another clinic. Participants were asked to complete questionnaires determining scales of the following: trait anxiety (State-Trait Anxiety Inventry-Trait; STAI-Trait), negative emotion suppression (Courtauld Emotional Control Scale; CECS), life stress events (Life Experiences Survey; LES), and mood states (Profile of Mood States; POMS) and return them either by mail or at the time of the next clinical examination. In addition, we examined subjective symptoms (lump, pain, abnormal nipple discharge, or deformed nipple) and family history of breast cancer based on answers to the interview sheet filled out by patients on their first visit to the hospital. We excluded 45 patients who submitted incomplete answers, 38 who did not reply, and 5 who were considered to be ineligible for other reasons. The analysis covered a total of 154 patients (age (years); mean=49.94, SD=12.22). Approval for this study was granted by the Institutional Review Board of Kitasato University School of Medicine and Hospital.&#x2028; Results and conclusion: We performed multiple regression analysis (forced entry method) to assess how mood states (POMS score) are affected by the following factors: age at the time of first visit, trait anxiety (STAI-Trait score), emotional suppression (CECS score), number of life stress events (LES total score), number of negative evaluations of life stress events (LES balance score), subjective symptoms, and a family history of breast cancer. We obtained a significant model (adjusted R2=0.558, p&lt;0.01) in which trait anxiety, emotional suppression, number of life stress events, and the standard partial regression coefficient of subjective symptoms were found to be statistically significant (beta=0.618, 0.111, 0.181, 0.118; p&lt;0.05, respectively). This suggests that mood states at the first visit are less positive when patients have high trait anxiety, emotional suppression, many life stress events, and subjective symptoms. In particular, trait anxiety had a particularly large impact on mood states, indicating the importance of psychological assistance.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3110.