bluuebunny/crossref_metadata_2025_split huggingface dataset:
P2-10-04: 3D Mapping of Total Choline in Human Breast Cancer Using High-Speed MR Spectroscopic Imaging at 3T: A Feasibility Study.
Authors: Posse S , Royce M , Dayao ZR , Zhang T , Zhao C , Sillerud L , Lopez S , Casey L , Eberhardt SC , Lomo L , Lee S-J , Rosenberg R , Rajput A , Bolan P 
Published: June 2012

Abstract
PURPOSE: To assess the feasibility of quantitative high-speed MR spectroscopic imaging (MRSI) of total Choline (tCho) as an adjunct to dynamic-contrast enhanced (DCE) MRI to improve lesion characterization and monitor treatment response in patients undergoing neoadjuvant chemotherapy.
METHOD AND MATERIALS: Seven patients with biopsy-confirmed, infiltrating ductal carcinoma were studied using a clinical 3T MR scanner (Siemens Medical Solutions, Erlangen, Germany) equipped with 8- and 16-channel breast array (Hologic Inc., Bedford, MA). Measurements were performed using PRESS prelocalized 3D Proton-Echo-Planar-Spectroscopic-Imaging (PEPSI) using TR/TE=2000ms/135ms, matrix size up to 32×16x8, voxel size=1cc, and total acquisition time of 10 minutes (including water reference scan). Additional data were collected at TE 60 ms to enhance sensitivity for detecting tCho and J-coupled resonances. TE-averaging (8 steps, ΔTE: 2.5 ms) was employed to minimize gradient sideband artifacts. Quantification of tCho in reference to tissue water was performed using spectral fitting and relaxation correction.
RESULTS: Strongly elevated tCho with maximum concentration ranging from 0.3 to 4.1 mmol/kg was measured in five patients with single and multi-centric enhancing lesions larger than 2 cc volume (Table 1). The measured tCho concentration in Grade 3 tumors was higher than in lower grade untreated and treated tumors. Strong decreases in tCho concentration were measured in 2 patients undergoing neoadjuvant therapy in a follow-up scan. At short TE an additional resonance was detected that was elevated in enhancing lesions and tentatively assigned to Taurine. Two patients had lesions smaller than 2 cc with surgical clips in which tCho was not detectable due to line broadening. MRSI data sets were preferentially collected before contrast injection, since it increased spectral line width by up to 50%.
CONCLUSION: This study demonstrates feasibility of quantitatively mapping tCho in invasive breast carcinoma using high-speed MRSI. The long-term goals are to utilize high-speed MRSI as an early predictor of treatment failure in women undergoing neoadjuvant therapy (i.e. chemotherapy, endocrine therapy or biologic therapy) for breast cancer and to develop an improved screening protocol for high-risk patients. Grant support: 1RC1EB010617-01

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-10-04.
P2-12-09: Prediction of Residual Risk of Recurrence after 5 Years of Follow-Up by Clinicopathologic Variables and 4 IHC Markers: A TransATAC Study.
Authors: Sestak I , Cuzick J , Dowsett M , Salter J , Quinn E , Zabaglo L , Howell A , Buzdar A , Forbes J 
Published: June 2012

Abstract
Background
Adjuvant endocrine therapy beyond 5 years is known to be of benefit to some ER+ patients but it is unclear which patients have sufficient residual risk (RR) to merit this. We have previously shown that 4 immunohistochemical markers (ER, PgR, Ki67, HER-2), both alone and combined into the IHC4 score (Cuzick et al, JCO 2011) are significantly correlated with time to recurrence (TTR) in the overall follow up of a cohort of 1125 patients from the monotherapy arms of the Arimidex, Tamoxifen, Alone or in combination (ATAC) trial. We have now assessed the relationship of each of these parameters and common clinical variables (nodal status, grade, tumour size, age and treatment option) for predicting outcome beyond 5 years.
Material and Methods: We determined the univariate and multivariate prognostic value of clinical variables and the 4 IHC variables separately and as the IHC4 score for TTR separately in years 0–5 and 5–10 of follow up for all patients, separately for anastrozole and tamoxifen and only in the node-negative patients.
Results: Results in years 5–10 are summarized in the Table. Nodal status, tumour size and grade were at least as strong in years 5–10 as in years 0–5. Ki67 and the overall IHC4 score were the only significant IHC biomarkers related to TTR univariately in this period, but both lost significance in a multivariate model including clinical variables. There were no significant interactions with treatment. Similar results were seen for the node-negative population.
Conclusions: None of the IHC4 markers provided significant additional prognostic information in the 5–10 year period, but nodal status, tumour size and grade continued to be strong prognostic factors.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-12-09.
P2-12-10: Low TCR Diversity (Divpenia) Is a Prognosis Factor of Overall Survival in Metastatic Breast Cancer.
Authors: Manuel M , Tredan O , Bachelot T , Parmentier G , Courtier A , Rabeony T , Chabaud S , Mouret J-F , Grives A , Perez S , Clapisson G , Blay J-Y , Caux C , Pasqual N , Menetrier-Caux C 
Published: June 2012

Abstract
Background: We already showed that lymphopenia (&lt;1000 lymphocytes/μl) or CD4+ T cell lymphopenia (&lt;450/μl) detected before initiation of chemotherapy are prognostic factors for toxicity and death for metastatic breast cancer (MBC) patients. The goal of the present study was to identify the characteristics of the T cells in these lymphopenic patients. TCR diversity was investigated and tested as a prognostic factor for overall survival (OS).
Patients and methods: The ImmunTraCkeR® assay (ImmunID, Grenoble, France), which analyzes through semi quantitative multiplex-PCR the V-D-J combinatorial diversity of TCR-beta chain (TRB), was used to investigate diversity of T cell repertoire on cryopreserved blood samples from a retrospective cohort of MBC patients before chemotherapy administration (n=66). Univariate and multivariate analysis were performed. We then validated our score on a prospective cohort (n=67) using the same eligibility criteria (MBC patients before first line chemotherapy administration).
Results: Using a 33% cutoff for divpenia in our retrospective cohort (T cell diversity below 33%) (average diversity for healthy people is 70%), divpenia was associated with a median OS of 10 months vs 22 months for patients with diversity &gt;33% (logrank p value=0.04). The NDL® score (Numeration Diversity Lymphocytes representation) that combines lymphocyte numeration with TRB diversity, demonstrated that lympho-divpenia (T cell diversity below 33% and lymphopenia below lGiga/L) was associated with a poor OS compared to patients with either lymphocyte &lt;1000/μL & diversity &gt;33% or lymphocyte &gt;1000/μL & diversity &lt;33% or both lymphocyte &gt;1000/μL and diversity &gt;33% (p=0.015). In multivariate analysis, including performance status (PS), hemoglobin level, polynuclear neutrophil count (PNN), age, and liver metastasis, NDL® score was identified as an independent prognostic factor for OS. In our prospective validation cohort, NDL® score was also identified as a prognostic factors for OS (p=0,007), as well as lymphopenia (&lt;1000/μL) (p=0,0003), CD4+ lymphopenia (&lt;450/μL) (p=0,04), menopausal status (p=0,02), hormonal receptor status (estrogen receptor p=0.02; progesterone receptor p=0.002) and lung metastasis (p=0,009). In multivariate analysis, hemoglobin level was the only independent prognostic factor in this cohort.
Conclusion: We showed that Divpenia and NDL® score are prognostic factors for OS in MBC patients. In order to confirm these results, a prospective clinical trial is ongoing on a larger cohort of MBC and lung cancer patients.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-12-10.
P2-12-17: Prospective Evaluation of the Conversion Rate of HER2, ER and PR between Primary Tumors and Corresponding Metastases. CONVERTHER/GEICAM 2009–03 Study.
Authors: Martinez de Dueñas E , Lluch A , Guerrero A , Chacon JI , Perez R , Antolin S , Blancas I , Ferrer-Lozano J , Burgues O , Lopez A , Gonzalez-Angulo AM 
Published: June 2012

Abstract
Introduction: A substantial number of small studies, most retrospective, have shown variable degrees of discordance in HER2, ER and PR expression between primary and metastatic breast cancer. This may have prognostic and therapeutic implications. These discordances could be triggered by tumor somatic mutations, intratumoral heterogeneity, or technical issues with receptor assayes. In this prospective study, we centrally analyzed and determined the changes in receptor status between primary tumor and corresponding metastases.
Methods: In 32 Spanish hospitals, patients where primary tumor sample was available, were prospectively included prior to the biopsy of the presumably metastatic lesion. Determinations of ER and PR status (assessed by immuhistochemistry [IHC]) and HER2 status (IHC and FISH) were centrally and blindly performed in both primary tumor and metastases. Concordance rate between local laboratories and central laboratory receptor determinations were analyzed. We also determined whether the biopsy results modified the oncologist initial treatment strategy.
Results: A total of 236 patients were included. To today, 183 paired cases were centrally evaluated. Patients in first recurrence were 65% and the mean age was 57.2 years. Biopsy samples were taken from locoregional recurrence (25%), liver metastases (28%), bone metastases (11%), lung metastases (7%) and other locations (29%). In 6.6% of the biopsies normal tissue, benign lesion or secondary malignant neoplasm were seen. The changes in HER2, ER and PR were 17%, 26% and 35% (local lab) and 4%, 12% and 26% (central lab), respectively; and were independent of treatment given or biopsy localization. Concordance rate in HER2, ER and PR between local and central determination were 83%, 92% and 78% (kappa index 0.58, 0.80 and 0.55), respectively. Changes in receptor status lead to a modification in medical management in 16% of patients.
Conclusions: A remarkable discordance in receptor status, especially in the hormonal receptors, was found between primary tumor and metastases that implies a change in medical management in 16% of patients. These discordances were reduced but remained after performing in a high-quality central laboratory, so that they could only be partly explained by technical discrepancies in receptor assessments.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-12-17.
P2-12-27: Simply Adding Together the Diameters of Tumor Foci in Patients with Multicentric or Multifocal Disease Does Not Add Any Additional Prognostic Information: An Analysis from NCIC CTG MA.12 Randomized Placebo-Controlled Trial of Tamoxifen after Adjuvant Chemotherapy in Pre-Menopausal Women with Early Breast Cancer.
Authors: Hilton JF , Dong B , Bouganim N , Chapman J-AW , Arnaout A , O'Malley F , Nielsen T , Gelmon K , Yerushalmi R , Levine M , Bramwell V , Whelan T , Pritchard KI , Shepherd L , Clemons M 
Published: June 2012

Abstract
Background: A common clinical conundrum in breast cancer management is whether pathologic T stage in women with multicentric or multifocal disease should be taken as the diameter of the largest focus or as the sum of all foci in the breast. Most staging systems, such as the American Joint Committee on Cancer (AJCC), simply use the largest tumor focus for staging. We examine here the impact of alternate methods of estimating tumour size including measures of total tumor size, volume and surface area.
Materials & Methods: NCIC CTG MA.12 is a randomized placebo-controlled trial of tamoxifen after adjuvant chemotherapy for pre-menopausal women with early breast cancer. Median follow up is 9.7 years. Pathologically reported patient tumor dimensions for up to 3 foci were utilized to examine the effects of tumor size on Breast-Cancer-Free-Interval (BCFI), defined as the time from randomization until recurrence (defined as first local, regional, distant, or contralateral invasive tumor or DCIS). Tumor size was estimated as 1) pathologic T stage as per AJCC criteria; 2) largest dimension of largest tumor focus (cm); 3) sum of largest dimension(s) of tumor foci (cm); 4) sum of surface area(s) of tumor foci (cm2), and 5) sum of volume of tumor foci (cm3). Step-wise forward unstratified Cox regression was used to assess the different effects of tumor size. Results: This study accrued 672 patients, 43% with T1 tumors, 51% with T2 tumors, and 6% with T3/T4 tumors; 25% were node negative and 56% had 1–3 positive lymph nodes. 75% were locally determined to have hormone receptor positive tumors. A higher number of involved lymph nodes was associated with significantly shorter BCFI (p&lt;0.0001). None of pathologic T stage (p=0.14), largest dimension of largest tumor size (p=0.14), sum of largest dimensions of tumor foci (p=0.24), sum of surface area (p=0.38), and sum of volume of foci (p=0.51) were significantly associated with BCFI. Likewise, lymphovascular invasion (p=0.08), grade (p=0.14), nor administration of anthracycline therapy (p=0.08) were associated with BCFI.
Discussion: In the MA.12 population of pre-menopausal women randomized to either tamoxifen or placebo, the sole factor significantly associated with BCFI was nodal status. No measure of tumor size in unifocal or multicentric/multifocal tumors impacted BCFI. The findings of this mature data set suggest that simply adding together the diameters of tumors in patients with multicentric or multifocal disease did not add any additional prognostic information.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-12-27.
P2-12-30: Pre-Operative Haematological Markers and Prognosis in Early Breast Cancer.
Authors: Cordiner RL , Mansell J , Obondo C , Angerson WJ , Lannigan A , McMillan D , Wilson CR , Doughty JC 
Published: June 2012

Abstract
Background
Systemic inflammation may influence survival in women with breast cancer. Both the platelet lymphocyte ratio (PLR) and the neutrophil lymphocyte ratio (NLR) have been shown to be associated with survival in a number of solid tumours. The aim of this study was to assess the role of PLR and NLR in survival of women with early breast cancer.
Methods: Women diagnosed with early breast cancer at two centres between 2003 and 2006 were included. All women had measured white cells, neutrophils, lymphocytes and platelets. NLR and PLR were calculated. Cox regression survival analysis was performed with breast cancer specific survival used as the primary end point. Significant associations of NLR and PLR with pathological variables was assessed using the Chi squared test.
Results: 707 women were included with a median follow up of 3.7yrs. On univariate analysis neither NLR (HR 1.08, 95% CI 0.66−1.79) or PLR (HR 0.96, 95% CI 0.58−1.59) were significantly associated with breast cancer specific survival. An increased PLR was found to be associated with significantly fewer grade 1 tumours (P&lt;0.05) but no other significant associations with pathology was demonstrated for either PLR or NLR.
Conclusions: This study would suggest that the NLR and PLR are not prognostic of survival in women with early breast cancer.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-12-30.
P2-13-03: Comparative Assessment of 636 Women at Risk for Hereditary Breast Cancer within 3 Public Hospitals: The Consortium of Underserved BRCA Testers.
Authors: Beattie MS , Ganschow P , Gabram-Mendola S , Wilson A , Joseph G , Lee R , Loranger K , Stanislaw C , Seelaus C , Farrell R , Trim L , DelPozo S , Luce J 
Published: June 2012

Abstract
Background: Underserved women at risk for Hereditary Breast and Ovarian Cancer (HBOC) are confronted with many unique challenges, such as barriers to accessing appropriate genetic testing and counseling services and decreased resources, that place them at increased cancer risk. It is unclear whether these high-risk women are appropriately referred for genetic counseling and what their genetic test results demonstrate due to minimal practice-based evidence. To study this population, and to establish an infrastructure to further explore long-term outcomes, we formed the Consortium of Underserved BRCA testers in October 2010 from: San Francisco General Hospital (SF), Stroger Hospital of Cook County (Chicago), and Grady Memorial Hospital (Atlanta).
Methods: Using common clinical and research protocols and mixed methods analysis, we examined and compared referral patterns, demographics, and BRCA test results between sites. We used chart reviews and common data collection instruments to gather and pool data. Using descriptive and comparative statistics, we examined similarities and differences between Consortium sites.
Results: SF's program began 9 years ago, Chicago's began 6 years ago, and Atlanta's began 3 years ago. Medicaid funding for BRCA testing has been available in SF since 2011, in Chicago since 2009, and is not yet available in Atlanta. P values were all &lt;0.05 for comparing referral sources between sites. Each site uses unique referral tools and systems. For example, in SF, a family history screening questionnaire is administered during mammography; in Chicago, an extensive primary care network has been educated to provide appropriate referrals; in Atlanta, a pedigree assessment tool is employed by referring clinics.

Conclusions: Despite differences in referral patterns and Medicaid funding, underserved women at all 3 public hospital sites had similar BRCA positive rates, which are in line with positive rates from University Cancer Centers. We believe this relates to the availability of genetic counseling services and a similar testing threshold at each site. The large and ethnically diverse population of this Consortium can serve as a valuable resource for researchers and clinicians. We plan to follow this cohort prospectively to study clinical outcomes and medical decisions after BRCA testing in underserved families at risk of HBOC.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-13-03.
P2-13-05: Breast Cancer, BRCA Mutations and Attitudes Regarding Pregnancy and Preimplantation Genetic Diagnosis.
Authors: Litton JK , Etzel CJ , Jackson MA , Muse KI , Turco D , Schover LR , Theriault RL , Mattair D , Lu KH , Hortobagyi GN , Arun BK 
Published: June 2012

Abstract
Background: Breast cancer is associated with treatment-related infertility and has been demonstrated to be a major concern for premenopausal survivors. Detection of a BRCA deleterious mutation may also affect attitudes regarding future childbearing. Preimplantation genetic diagnosis (PGD) allows women to use in vitro fertilization (IVF) to implant only those embryos without a BRCA mutation. The ability to test the fetus for BRCA mutations is also available through amniocentesis and chorionic villus sampling (CVS). The objective of this study was to evaluate attitudes about childbearing and fertility in women being evaluated for a BRCA mutation. Methods: Women with childbearing potential who were referred to the Clinical Cancer Genetics Clinic to be evaluated for a BRCA mutation were invited to participate in this survey. The questionnaire was administered prior to genetic counseling. A follow-up was administered after the BRCA results were disclosed. The survey queried participants regarding their attitudes on fertility, pregnancy as it may relate to cancer and the potential of a BRCA mutation. Other questions detailed attitudes regarding IVF, PGD, and CVS in these instances. Descriptive statistics were used. Results: One hundred and twenty-eight women completed pre-questionnaires and to date 76 have completed post results disclosure questionnaires. The mean age was 33 (range 21–44) with 69.5% with a diagnosis of breast cancer, 39.8% received chemotherapy and 60.9% already had at least 1 biological child. A future child was desired by 45.3% although 53.1% worried that their children would have an increased risk of cancer. Regarding PGD, although only 30.9% (38/123) said that they would use PGD, 80.2% felt that the testing should be available to families with inherited cancers. Regarding fetal testing via amniocentesis or CVS, 29.7% would have the fetus tested and 7% would consider termination if a genetic mutation was identified. Additionally, 69.5% felt it was important to receive fertility counseling and treatment at the same place where they receive their cancer care. To date 8 women have been diagnosed with a BRCA1 mutation and 4 with a BRCA2 mutation. When asked similar questions after their genetic results were disclosed, 2 women who had previously stated they would not use PGD changed their mind. Conclusions: Future pregnancies are important to many breast cancer survivors. BRCA mutation carriers have the option to have children without passing on their genetic risk for cancer. Although few would use these interventions, a large majority felt it was important to have information about these choices and to have options for fertility preservation options addressed at the center where cancer care is delivered.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-13-05.
P2-13-08: A Retrospective Study on Surveillance Behaviour and Prophylaxis after Genetic Testing for Hereditary Breast and Ovarian Cancer among High-Risk Chinese Females.
Authors: Kwong A , Chu ATW 
Published: June 2012

Abstract
Background
Research in the West has shown that the uptake rates of surveillance and prophylaxis may be different in BRCA mutation carriers and non carriers and this may vary between different ethnicities. To date there is limited comprehensive data available for the behavioural pattern of Asian cohorts. The present on-going study is the first to investigate the behavioural impact and medical compliance of Chinese high risk females who had undergone BRCA1/2 genetic testing up to 1.5 years after genetic testing.
Methods: 88 females with personal or family breast and/or ovarian cancer history who had BRCA1/2 genetic testing performed by the Hong Kong Hereditary Breast Cancer Family Registry were surveyed by a face-to-face or telephone interview. Sociodemographic information, genetic test results, pre-and post-testing surveillance practice, chemoprevention methods used and attitudes towards clinical management were obtained. Retrieval of medical records was performed using a prospective database.
Results: 39 carriers and 49 noncarriers of a BRCA 1/2 mutations were interviewed. 82.1% of carriers and 79.6% noncarriers had breast and/or ovarian cancer prior to testing. The uptake rate of breast surveillance by eligible carriers (85.2%) and noncarriers (71.1%) remained high after knowing the test results. 12.8% and 15.4% of the eligible carriers had prophylactic contralateral mastectomy and salpingo-oophorectomy respectively, while 5.1% chose to have both procedures within 1.5 years of knowing the genetic test result. Significantly more carriers (85.7%) than noncarriers (49%) underwent ovarian surveillance (p= 0.004). 25.6% of carriers and 26.5% of noncarriers with breast cancer history chose Western chemoprevention methods, while no carriers without breast cancer history chose such methods. 34.7% of carriers (30.8% of noncarriers) used Chinese herbal medicine as complementary prevention treatment after knowing the genetic test result. Clinicians’ advice was perceived as the major reason of choosing a particular surveillance or preventative strategy.
Conclusions: As population-based breast screening is unavailable in Hong Kong, the relatively high uptake rate of breast screening among noncarriers may be the result of enhancement in health-consciousness due to prior personal or family cancer experience. Proper education by clinicians is crucial to increase uptake of high risk screening. Traditional Chinese herbal medicine methods are commonly used as a form of prevention. A longitudinal prospective study will contribute to the understanding of attitude-change towards clinical management of this Chinese population who may have different cultural beliefs.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-13-08.