bluuebunny/crossref_metadata_2025_split huggingface dataset:
P4-10-10: Breast Cancer Risk Factors among Asian Versus Caucasian Women with BRCA1/2 Mutations.
Authors: de Bruin MA , Kwong A , Goldstein BA , Lipson JA , Ikeda DM , McPherson LA , Sharma B , Kardashian A , Schackmann EA , Kingham KE , Mills MA , West DW , Ford JM , Kurian AW 
Published: June 2012

Abstract
Background
Prior research suggests that the prevalence and penetrance of BRCA1/2 mutations may be different in Asians compared with Caucasians. Such differences in penetrance could be related to genetic, as well as hormonal, reproductive and lifestyle factors.
Methods: Chinese and Caucasian BRCA1/2 mutation carriers were recruited from genetics clinics in Hong Kong and California. We compared personal and family history of cancer, as well as hormonal, reproductive and lifestyle exposures between racial groups. Breast density was estimated using BIRADS breast composition categories on mammogram. We analyzed DNA samples for single-nucleotide polymorphisms (SNPs) that may modify BRCA-associated cancer risk, and compared the prevalence between groups. A multivariable analysis of potential modifiers of cancer risk is underway.
Results: Forty-two Chinese women from Hong Kong and forty-nine Caucasian women from California were enrolled. BRCA1 mutations were more common in Caucasian women (63% vs. 43%, P=0.05), while BRCA2 mutations were more common among Chinese women (57% vs. 33%, P=0.02). More Chinese women had a personal history of breast cancer (91% vs. 53%) and ovarian cancer (12% vs. 4%). In contrast, significantly more Caucasian women had a family history of breast and ovarian cancer. On average, Caucasian women had higher parity, breastfed more, had less dense breasts on mammogram, and more often underwent prophylactic oophorectomy, all of which are protective against breast cancer in the general population. However, Caucasian women also consumed more alcohol and had higher average BMI. Risk associated alleles in RAD51, MAP3K1 and TOX3/TNRC9 were more common in Chinese women; risk associated alleles in FGFR2 and RASSF1 were similar in frequency between groups. Results of the multivariable analysis are pending and will be presented.
Discussion: We found notable differences between Chinese and Caucasian women in the proportion of BRCA1 versus BRCA2 mutations, and in the distribution of hormonal, reproductive and lifestyle factors, and SNPs associated with breast cancer risk. Such variations in risk-modifying factors may contribute to differences in BRCA mutation penetrance. Enhanced understanding of racial differences in BRCA1/2 mutation epidemiology may inform targeted cancer screening and prevention strategies.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-10-10.
P4-11-02: Insulin-Like Growth Factor-1 (IGF-1), Insulin-Like Growth Factor Binding Protein-3 (IGFBP-3) and Lobule Type among Women in the Nurses' Health Study II (NHS II).
Authors: Collins LC , Rice MS , Shen D , Connolly JL , Schnitt SJ , Tamimi RM 
Published: June 2012

Abstract
In a previous analysis of women enrolled in NHSII, we found that among women diagnosed with benign breast disease (BBD), those with predominant type 1/no type 3 lobules were at lower risk of subsequent breast cancer compared to women with other lobule types. Additionally, studies in animal models suggest that higher levels of IGF-1, a polypeptide hormone involved in the proliferation/differentiation of normal mammary epithelium, may inhibit involution of breast lobules. However, the interaction between IGF-1 levels and lobule types in determining breast cancer risk has not been previously evaluated. Therefore, we examined the association between IGF-1 levels and lobule type among women with BBD.
Methods: We conducted a cross-sectional study among 484 women in NHSII with biopsy-confirmed BBD between 1993–2001 who had blood samples available for determining levels of IGF-1 and IGFBP-3. A pathologist, blinded to exposure status, classified lobule type on biopsy slides according to the number of acini per lobule (type 1 &lt; 12; type 2∼50; type 3∼80 acini). Lobule type was classified into (1) predominant type 1/no type 3 lobules or (2) other lobule types. Multivariate logistic models were used to assess the associations between plasma IGF-1, IGFBP-3, and IGF-1/IGFBP-3 levels with lobule type. Models were adjusted for age, IGF-1 batch and additional potential confounders in secondary analyses.
Results: In univariate analyses, older age at biopsy, higher body mass index, postmenopausal status, nulliparity, and lower IGF-1 levels were associated with predominant type1/no type 3 lobules (p&lt;0.05). In multivariate logistic models adjusting for age, higher IGF-1 levels were associated with a decreased risk of predominant type 1/no type 3 lobules (OR quartile 4 vs. quartile 1 = 0.35, 95%CI: 0.15−0.81). Greater IGF-1/IGFBP-3 ratio was also associated with a decreased risk of predominant type1/no type 3 lobules (OR quartile 4 vs. quartile 1 = 0.24, 95%CI: 0.10−0.57).

These associations persisted, though were slightly attenuated, in models adjusting for additional potential confounders.
Conclusion: Higher IGF-1 levels and greater IGF-1/IGFBP-3 ratios are associated with a decreased risk of predominant type 1 lobules/no type 3 lobules among women with BBD in the NHSII. Whether this association contributes to the mechanism by which IGF-1 confers an elevated breast cancer risk requires further investigation.
Acknowledgements: This work was supported by T32 CA09001-35 CA124865, R01 CA050385, and the Breast Cancer Research Foundation
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-11-02.
P4-14-02: Risk Factors for Early Lymphoedema Do Not Predict Late Development of Lymphoedema.
Authors: Kilbreath SL , Beith J , Refshauge KM , Lee M-J , Ward LC 
Published: June 2012

Abstract
Background: Previously, we investigated whether an upper limb 8 week exercise program commencing 1 month after surgery was associated with higher incidence of LE. As part of that study, we investigated the risk factors for development of LE at 12 month follow-up, which was equivalent to 15 m post surgery. As LE fluctuates during the first year, our secondary aim was to identify risk factors for LE at the conclusion of the intervention and at 6 m follow-up.
Methods: Women (n=160) were recruited who had undergone breast and axillary surgery within the previous month for unilateral early stage breast cancer. Potential predictors were measured at approximately one month postoperatively after which women were randomised to the exercise or control group. Possible predictors of LE included age, BMI, side of surgery, treatments for breast cancer, physical measures of shoulder range of motion and strength, inter-limb bioimpedance ratio at each previous measurement occasion and the treatment group to which women were randomised. The outcome measure for LE was based on the inter-limb impedance ratio. Presence of LE was determined using established cut-offs for LE. The relationship of each variable to the outcome measures (i.e. presence of LE) was assessed using t-tests and correlations. Significant variables (P &lt; 0.25) were further examined with a multivariate logistic regression model.
Results: At least 10% of women developed LE: following intervention (N=15), and at 6m (N=15) and 12 m (N=20) follow-up. Risk factors for LE varied across the 3 time points (Table 1). At 12 m follow-up, the only significant risk factor was surgery on the non-dominant side. In contrast, the risk factors for LE following the intervention were allocation to the control group and commencement of taxane-based chemotherapy. At 6 m follow-up, risk factors for LE were having LE following the intervention and receiving taxane-based chemotherapy.

Conclusion: Fluctuation of LE over the first year is associated with different risk factors. For example, fluid accumulation is a common side effect of taxanes and it was therefore not surprising that there was a transient increase in LE. However, overall, we speculate that the higher risk for LE after 1 year is because of lack of use of the non-dominant affected arm. It is use of the upper limb which is likely the critical issue in this first year. Exercise was preventative while it was being undertaken; we question whether women maintained the level of exercise once the intervention concluded.
Acknowledgement: Cancer Council NSW; NBCF Australia
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-14-02.
P4-15-02: Clinical and Epidemiological Correlates of Elevated Distress Thermometer Scores in Breast Cancer Patients.
Authors: Powers K , Pappas L , Buchmann L , Anderson L , Gauchay L , Rich A , Agarwal J 
Published: June 2012

Abstract
Objectives: Distress is prevalent in breast cancer patients and can be detrimental to quality of life, performance status, treatment adherence, and satisfaction with medical care. The National Comprehensive Cancer Network (NCCN) developed the Distress Thermometer (DT) as a quick and efficient self-assessment tool for screening distress in cancer patients. While surveys estimate that between 20–40% of patients with cancer have significant levels of distress, fewer than 10% are identified and treated. Given time and monetary constraints, it is important to refine screening criteria to identify patients with elevated risk for distress. In this study, we identify clinical and epidemiological factors that are associated with an increased likelihood of elevated DT scores (≥4 and ≥7) in breast cancer patients.
Methods: We assessed 229 consecutive female patients with the DT at their initial consultation for breast cancer at the Huntsman Cancer Hospital between September 2007 and December 2008. The DT screening tool measures a global level of distress using a visual analogue scale from 0–10 in the shape of a thermometer, with zero identified as “No Distress” and ten labeled as “Extreme Distress.” The DT screening tool also includes a checklist of common emotional, family, physical, practical, and spiritual concerns with instructions for the paitent to indicate which of those concerns contributed to the distress they experienced within the past week. We chose a score ≥4 as our cutoff for a positive screen for “distress” and a score ≥7 as our cutoff for a positive screen for “extreme distress/depression” based on previous studies. Variables included in the analyses were: age, employment status, race/ethnicity, personal history of depression, family history of breast cancer, marital status, estrogen and progesterone receptor status, stage of cancer, time since diagnosis, and recurrence. Descriptive statistics and logistic regression models were used to determine associations between DT and patient data. Results: Emotional and physical concerns were associated with scores ≥4 and scores ≥7. Spiritual concerns were significantly associated with patients reporting scores ≥7. Patients who were non-Caucasian, unemployed, had a prior history of depression, who presented for recurrent disease, or who had been recently diagnosed had a higher likelihood of scores ≥4 and scores ≥7.
Conclusions: The likelihood of scoring ≥4 and ≥7 on the DT screening tool is highest during the first 30 days after receiving a breast cancer diagnosis. Four groups of patients should be targeted for aggressive screening: patients with a prior diagnosis of depression, patients presenting with recurrent disease, unemployed patients, and non-Caucasian patients. Interventions should address physical, emotional and spiritual concerns.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-15-02.
P4-16-01: Proteomic Analysis of Patient Plasma Identifies Parathyroid Hormone Related Protein (PTHrP12-48) as a Potential Biomarker of Breast Cancer Bone Metastasis.
Authors: Washam CL , Byrum SD , Leitzel K , Suhail AM , Lipton A , Suva LJ 
Published: June 2012

Abstract
Background: Bone metastasis is a devastating and often incurable phase of breast cancer progression that significantly compromises patient morbidity and mortality. Despite the well-characterized issues associated with tumor progression, there is currently no reliable method to detect or predict which patients have or are at increased risk for developing bone metastasis. In this study a validated plasma-based proteomic profile for the diagnosis of breast cancer bone metastasis was developed and a highly discriminatory protein component of the profile identified as a novel fragment of parathyroid hormone related protein (PTHrP).
Materials and Methods: Plasma samples were collected from a total of 110 breast cancer patients. The training set consisted of 38 breast cancer patients with clinical evidence of bone metastasis and 38 with no evidence of a bone metastasis from time of diagnosis to clinical outcome. The independent validation cohort consisted of 34 breast cancer patients with an unknown bone metastasis classification. The training set was analyzed using surface enhanced laser desorption time-of-flight mass spectrometry (SELDI-TOF MS) and 13 discriminatory protein peaks that contributed to a homogeneous partitioning of the training set (n = 76) in multiple statistical, bioinformatics, and machine learning modeling scenarios were identified and used to construct a RandomForest classifier for the detection of breast cancer bone metastasis (sensitivity: 100%, specificity: 100%).
Results: The diagnostic profile identified was then independently confirmed in a blinded fashion using the validation cohort (sensitivity: 97%; specificity: 82%). Importantly, the most discriminatory protein peak (m/z 4260.92 Da) in the plasma of bone metastasis patients was subsequently identified using specific immunodepletion, tryptic peptide mapping and peptide sequencing as a unique proteolytic PTHrP fragment, PTHrP(12-48). Ongoing studies are determining the biogenesis and biological activity of this unique PTHrP peptide. Discussion: Our discovery of PTHrP(12-48) as a novel plasma biomarker of breast cancer bone metastasis validates our plasma proteomic approach and provides the first direct evidence for the existence of a circulating PTHrP biomarker in breast cancer patient plasma that is associated with bone metastasis.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-16-01.
P4-16-08: Pilot Randomized Trial of De-Escalated (q12 Weekly) Versus Standard (q3-4 Weekly) Intravenous Bisphosphonates in Women with Low-Risk Bone Metastases from Breast Cancer.
Authors: Amir E , Freedman O , Carlsson L , Usmani T , Lee E , Dranitsaris G , Clemons M 
Published: June 2012

Abstract
Background: Bone-targeted agent such as bisphosphonates (BPs) can reduce skeletal complications from bone metastases but have no effect on either disease progression or survival. Despite substantial variability in the frequency and severity of skeletal complications, patients are empirically treated with BPs at the same dose and schedule irrespective of their individual risk.
Materials and Methods: A pilot, randomized, non-inferiority trial was conducted. Patients with low-risk bone metastases (serum C-telopeptide [CTx] &lt;600ng/L after at least 3 cycles of monthly IV BP) were assigned to pamidronate 90mg IV either every 3–4 weeks (control) or every 12 weeks (de-escalated). Data on serum CTx and bone alkaline phosphatase (BAP), pain scores (brief pain inventory [BPI] and functional assessment of cancer therapy-bone pain [FACT-BP]) were collected at 12 weekly intervals for 48 weeks.
Results: Fifty-four patients were approached, 44 provided consent and 38 were eligible for randomization. Median age was 55 (range 29–77) and mean baseline CTx was 319ng/L (range 10–526). Thirty-five participants (92%) completed the trial, 2 withdrew consent and one participant died. Fourteen control group participants (73.7%) and 13 experimental group participants (68.4%) maintained CTx in the low risk range (test for two proportions p=0.64). All patients not maintaining CTx in the low risk range showed evidence of both visceral and bone progression. Compared to the control group, there was a trend towards increasing CTx with time in the experimental group (p=0.10). There was no significant difference in BAP (p=0.37), BPI (p=0.21) or FACT-BP scores (p=0.59) between the two groups. Over the 48 week follow-up, two skeletal events were observed in each group.
Conclusions: Randomized trials of de-escalated BP therapy in women with low-risk bone metastases are feasible. Twelve-weekly pamidronate appears non-inferior to 3–4 weekly treatment. Larger trials are required to assess whether; 1) increasing CTx levels with de-escalated therapy will lead to higher rates of skeletal complications and 2) whether BP should be given every 3–4 weeks in patients with progressive visceral and bone disease.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-16-08.
P4-17-08: Is Cranial Magnetic Resonance Imaging (MRI) Necessary for Staging of Asymptomatic HER2−Positive Breast Cancer Patients?
Authors: Kaplan MA , Inal A , Kucukoner M , Urakci Z , Isikdogan A 
Published: June 2012

Abstract
Background
Breast cancer one of the most common tumors of the adults. Approximately 20% to 25% of all breast cancers are HER2−positive. It can be assumed that up to 30% of HER2−positive metastatic breast cancer (MBC) patients may experience brain metastasis during the course of their disease. The aim of this study to investigate that whether cranial MR is necessary for staging in asymptomatic HER2−positive breast cancer patients.
Material and metods: HER2−positive breast cancer patients without symptoms of brain metastasis included in the study. Cranial MRI was added to the staging procedures. Subgroup analysis was performed to determine risk factors for developing brain metastasis.
Results: Seventy five patients included in the study. Of whom, 71 were women (94.7%). Median age was 42.5 (22-76). Ten of the 75 patients (13.3%) had brain metastasis. The distribution rate of brain metastasis according to breast cancer stage at diagnosis was: 0% for stage I, 9.1% for stage 2, 4.3% for stage 3 and 28.6% for stage 4 (p=0.027). There was no association between presence of brain metastasis and the site of metastasis, estrogen and progesterone receptor positivity, grade, histological subgroup, menopausal status and gender.
Discussion: Brain metastasis is an important problem for breast cancer patients. Treatment strategies may vary in the presence of brain metastasis. In our study we found brain metastasis nearly one quarter of patients with metastatic HER2−positive breast cancer. Cranial MRI imaging can be performed routinely in patient with metastatic HER2−positive breast cancer patients.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-17-08.
P4-18-04: Hypofractionated Radiotherapy for Breast Ductal Carcinoma In Situ.
Authors: Hathout L , Fortin B , Vulpe H , Hijal T , Bahig H , Dubé P , Yassa M 
Published: June 2012

Abstract
Background
Conventional radiotherapy at a dose of 50 Gy in 25 fractions after breast conservative surgery is the standard treatment for ductal carcinoma in situ of the breast (DCIS). Hypofractionation is an interesting alternative for the treatment of breast cancer, providing a less intense treatment scheme for the patient. While the hypofractionated regimen of 42.5 Gy in 16 fractions has been shown to be equivalent to 50 Gy in 25 in infiltrating ductal carcinoma, few studies and no prospective study have reported results using hypofractionation in DCIS.
Materials and Methods: In this multicenter collaborative effort, we retrospectively reviewed the records of women with a diagnosis of DCIS at two Canadian institutions, treated with conservative surgery followed by hypofractionated radiotherapy (42.5 Gy in 16 fractions) to the whole breast. Tumor, patient and treatment factors were collected. Local control was evaluated using the Kaplan Meier method. Curves were compared using log rank.
Results: Between 2003 to 2008, 292 patients with DCIS underwent conservative surgery followed by hypofractionated radiation in 16 fractions for a total dose of 42.5 Gy. Treatment delivery was similar at both institutions. Mean age at diagnosis was 59 years, with 70 % of women being postmenopausal. Nuclear grade was 1–2 in 65 % of patients while 28 % had grade 3 tumors. Complete surgical excision with negative margins was achieved in 92 % of patients. Radiotherapy boost was given to 92 patients (31.5 %) at the discretion of the radiation oncologist. After a mean follow up of 3.35 years (range 1–8 years), 10 patients (3.4 %) had ipsilateral local relapse resulting in a disease-free survival (DFS) of 96 % at 4 years. The histology at recurrence was DCIS for 8 patients; infiltrative disease for one patient and one patient had an unknown histology at recurrence. Age was statistically associated with local relapse (DFS 89 % for patients under 50 years old vs 97 % for those older than 50, p=0.027). Grade was also a significant prognostic factor (DFS 98% for grade 1–2 vs 91 % for grade 3, p = 0.015). Finally, administration of boost did not have an impact on local control (DFS boost 98 % vs 95 % for no boost, p=0.44).
Discussion: Hypofractionated radiotherapy (42.5 Gy in 16 fractions) provides excellent local control for patients with DCIS undergoing breast conservative surgery. This regimen is more convenient to both patient and physician since it is less time consuming. Further work needs to be done to determine if this regimen is as effective as conventional radiotherapy in younger women (age less than 50) and those with grade 3 tumors.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-18-04.
P4-19-06: Ghrelin Expression Is Associated with Favorable Outcome in Male Breast Cancer.
Authors: Grönberg M , Nilsson C , Johansson I , Hedenfalk I , Janson ET , Fjällskog M-L 
Published: June 2012

Abstract
Background: Expression of the peptide hormones ghrelin and obestatin has previously been demonstrated in normal breast as well as in breast cancer. Interestingly, ghrelin expression has been shown to be associated with longer survival in female patients suffering from invasive breast cancer. However, the clinical implications of the expression of these peptides in male breast cancer are unclear. The aim of this study was to further investigate the role and potential clinical value of these peptides in male breast cancer.
Methods: A tissue microarray containing male breast cancer specimens from 197 patients was immunostained with antibodies directed towards the peptides. The expression of the peptides was evaluated and correlated to previously known prognostic factors in breast cancer and to the outcome. Cox regression analysis was used to assess whether these markers may predict survival of male breast cancer patients.
Results: Immunoreactivity for ghrelin and obestatin was observed in 81% and 87% of the cases, respectively. No strong correlations were found between ghrelin or obestatin expression and other known prognostic factors. Only ghrelin expression was significantly correlated to breast cancer-specific survival (HR=0.37−0.39, p=0.01−0.03) in both uni- and multivariate analyses. Reproducibility between the two readers was good to very good for both stainings with kappa values of 0.65−0.89.
Conclusions: Male breast cancer patients with tumors expressing ghrelin had 3 times lower risk for breast cancer death than those lacking ghrelin expression. Ghrelin expression is easily assessable with good reproducibility using immunohistochemistry. Further studies are needed to establish the clinical significance of ghrelin as a biomarker in breast cancer.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-19-06.