bluuebunny/crossref_metadata_2025_split huggingface dataset:
P2-12-13: Topoisomerase 2 alpha (TOP2A) RNA Expression Provides Prognostic Information in Hormone Receptor Positive Breast Cancer That Is Complementary to a Simulated Algorithm for Recurrence Score.
Authors: Sparano JA , Goldstein LJ , Davidson NE , Sledge, Jr GW , Gray R 
Published: June 2012

Abstract
Background
We have previously reported that TOP2A RNA expression was prognostic in patients with operable estrogen receptor (ER) positive breast cancer treated with anthracycline containing adjuvant chemotherapy plus endocrine therapy in trial E2197, and provided complementary prognostic information in those who had a mid-range Recurrence Score (RS) (Sparano et al. Clin Cancer Res 2009; 15; 7693). The purpose of this analysis was to provide additional evidence regarding this observation.
Methods: We evaluated TOP2A RNA expression in 4 independent data sets individually and in a pooled analysis including all data. We also used an algorithm to simulate the Oncotype DX Recurrence Score (SimRS). The analysis included 752 patients with early stage breast cancer that was ER-positive, HER2−negative defined by gene expression. Results are expressed as the hazard ratio (HR) for estimates of the effect of a one standard deviation increase in the value of the log gene expression (x + 1SD vs. x) as a continuous function. Five-year relapse free survival (RFS) rates were also evaluated for patients with a mid-range SimRS for high vs. low TOP2A expression (above vs. below the median, which was prognostic in E2197). The distribution of SimRS was categorized to be concordant with the distribution of actual RS in E2197 (47%, 34%, 19%, respectively for RS &lt;18 - low, 18–30 - intermediate, &gt;31 - high).
Results: The HR for models including TOP2A alone and joint models including TOP2A and SimRS are shown in the table.

TOP2A expression was significantly associated with recurrence in all 4 datasets when evaluated individually (HR 1.56, p&lt;0.0001 in pooled analysis), and 2 of 4 datasets individually when adjusted for SimRS (HR 1.26, p=0.003 in pooled analysis). SimRS was significantly prognostic when adjusted for TOP2A individually in 3 of 4 datasets (HR 1.44, p&lt;0.0001 in pooled analysis). For those with an intermediate SimRS, five year RFS rates were significantly higher in 2 datasets individually for high vs. low TOP2A expression (HR 1.82, p=0.007 in pooled analysis).
Conclusions: This analysis provides additional evidence that TOP2A expression provides prognostic information in patients with ER-positive, HER2−negative disease, a population known to have low incidence of TOP2A gene alterations. These findings also suggest that TOP2A expression provides information that is complementary to RS, and may be useful for identifying high risk subjects who have a mid-range RS. These findings require prospective validation in other prospective or prospective-retrospective trials using the actual rather than simulated RS.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-12-13.
P2-12-16: HER2 Expression Is the Major Risk Factor for Recurrence in pT1a-b,N0 Breast Cancer: A French Regional Population-Based Study of 671 Patients.
Authors: Rouanet P , Daures JP , Roger P , Mathieu A , Romieu G , Cretin J , Barneon G , Granier M , Maran-Gonzalez A , Thibault S , Boissiere F , Bibeau F 
Published: June 2012

Abstract
Background: To evaluate the prognostic impact of HER2 overexpression in patients with pT1a-b, node negative, breast cancers.
Patients and Methods: A population of1127 patients whose diseases were staged as pT 1a-b, pN0 and who were treated in the Languedoc-Roussillon (ONCO LR Southern French regional network) from 1999 to 2004, was identified. 95% of patients had conservative management, no patient received adjuvant trastuzumab, 5% received chemotherapy and 80% anti-estrogen endocrine therapy. HER 2 status was retrospectively assessed by immunohistochemistry in 671 patients (122 pT1a/549 pT1b). Kaplan-Meier method was used to estimate disease-free survival (DFS). Cox proportional hazard models were used to determine associations between HER2 status and disease-free survival adjusting on variables significantly linked to it.
Results: 9-year Overall survival was 95%. HER2 overexpression (3+) was observed in 5.2% of the patients (n=35).
HER2 3+ category was most frequently identified in the following sub groups: pT1a lesion (12.3% vs 3.6%; p: 0.0001), mastectomies (14% vs 4.4%; p:0.023), Grade 2–3 (91% vs 50%; p&lt;0.0001), estrogen receptor (ER) negative (−) tumors (57% vs 30%; p&lt;0.0001), progesterone receptor (PR) - tumors (74% vs 42%; p: 0.0002). HER2 3+ was less frequent with adjuvant hormonal treatment (43% vs 80%; p&lt;0.0001). 33 relapse (5%) were observed with a median follow-up of 6.4 years (range, 0.3 to 9.9 years). The 5-year DFS rates were 78% and 95% in patients with HER2−positive and HER2−negative tumors, respectively (p:0.017).
According to the immunohistochemical phenotype DFS5 were 95%, 94%, 85%, 73.6% for ER+/PR+/HER2− (n:502/75%), ER-/PR-/ HER2− (n:134/20%), ER+/PR+/HER2 3+ (n:15/2%) and ER-/PR-/ HER2 3+ tumors (n:20/3%), respectively (p:0.02).
In univariate analysis, HER2 positive tumors (p:0.017), phenotype classification (p:0.02) and adjuvant treatment (p:0.013) were significant prognostic factors. In multivariate analysis, only patients with HER2 3+ tumors had higher risks of recurrence (hazard ratio [HR], 2.41; 95% CI: [1.06−5.53]; p&lt;0.05) than those with HER2 -tumors.
Discussion: Node-negative, pT1a-b, breast cancer patients overexpressing HER2 have a significant risk of recurrence at 6 years median follow-up. In our series of small breast tumors, HER2 status seems to be a better prognostic factor than ER status. In patients with hormone receptor-positive diseases, HER2 positivity is associated with a worse DFS despite an anti-estrogen treatment.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-12-16.
P2-12-32: Association between Progranulin (GP88) Expression and Recurrence Risk for Breast Cancer Patients with Estrogen Receptor Positive Invasive Ductal Carcinoma.
Authors: Serrero G , Hawkins DM , Ioffe O , Bejarano P , Phillips JT , Head JF , Elliott RL , Godwin AK , Weaver J , Yue B 
Published: June 2012

Abstract
Purpose: GP88 (progranulin) is a critical player of breast tumorigenesis for estrogen receptor positive (ER+) breast cancer. Pathological studies showed that GP88 was expressed in invasive ductal carcinoma (IDC), but not in normal mammary tissue, benign lesions or lobular carcinoma. The present study examines GP88 prognostic significance in association with recurrence risk for patients with ER+ IDC.
Patients and Methods: Two retrospective multi-site clinical studies examined GP88 expression by immunohistochemistry (IHC) analysis in paraffin-embedded tumor tissues in correlation with patients’ survival outcomes. The training study established a GP88 cut-off value associated with decreased disease-free (DFS) and overall (OS) survivals. The validation study verified the GP88 cut-off value and compared GP88 prognostic information with other prognostic factors in multivariate analysis.
Results: GP88 expression is associated with a statistically significant increase in recurrence risk for ER+ IDC patients. The training study established that GP88 3+ score by IHC analysis was associated with decreased DFS (p=0.0004) and OS (p=0.0036). The independent validation study verified that GP88 3+ score for the high risk group and demonstrated that GP88 3+ score was associated with a 5.9-fold higher hazard of disease recurrence and a 2.5-fold higher mortality hazard compared to patients with tumor GP88&lt;3+. GP88 remained an independent risk predictor after considering age, nodal status, tumor size, tumor grade, progesterone receptor expression, treatment and disease stage.
Conclusion: Our training and validation studies demonstrate that the survival factor GP88 is a prognostic biomarker, predictive of recurrence risk and increased mortality for ER+ IDC patients, independent from other prognostic factors. These results provide support for measuring GP88 tissue expression for newly diagnosed early stage breast cancer patients.
This work was supported by grants R43CA124179, and U01CA113916 from the National Cancer Institute, grants 07-2007-064 and 02-2010-010 from the Avon Foundation for Women.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-12-32.
P2-13-04: Testing Women with Invasive Lobular Breast Cancer for BRCA Mutations.
Authors: Turco DL , Elsayegh N , Litton J , Hortobagyi GN , Arun B 
Published: June 2012

Abstract
Background: Infiltrating lobular carcinoma (ILC) is the second most common type of invasive breast cancer behind infiltrating ductal carcinoma (IDC). ILC makes up approximately eight percent of all invasive lesions. In addition, the mixed ductal and lobular carcinoma histology makes up approximately seven percent of all invasive diagnoses.
There are several biologic differences that are demonstrated by ILC compared to other common pathologies. They are more frequently bilateral and multicentric. They tend to be seen in women slightly older than the average age of diagnosis and are usually ER positive. It is also known that individuals with a genetic predisposition have an increased risk to develop breast cancers. Women with a mutation in their CDH1 gene have up to a 39% chance to develop ILC. The majority of hereditary breast cancer is caused by germ line mutations in the BRCA1 and BRCA2 genes. Women with a mutation in their BRCA1 or BRCA2 gene have up to an 87% risk to develop an invasive breast cancer, however, the presence of ILC in this population has not been well defined. Therefore, the aim of this study is to evaluate the rate of germline BRCA mutations in a cohort of patients both with pure ILC, as well as mixed ILC/IDC.
Methods: A retrospective chart review revealed one hundred and sixty nine women with ILC and mixed ILC/IDC who underwent genetic testing for mutations in the BRCA1 and BRCA2 genes through the Clinical Cancer Genetics Program at M. D. Anderson Cancer Center. Women are referred for genetic testing using referral guidelines based on the NCCN guidelines, this usually involves a personal history of early onset breast cancer and/or a family history of breast and/or ovarian cancer.
Results: Out of the 169 patients, 19 (11.24%) were found to have a germline mutation in their BRCA1 or BRCA2 gene. A significant majority (73.7%) of these patients were BRCA2 positive. Five women tested for a variant of uncertain significance. The average age of diagnosis for the cohort was 55.6 years (range 30–87); while the average age of diagnosis for a positive patient was 49.4 years (range 30–72). Of the 62 women with pure ILC, 5 (8.06%) were positive for a BRCA gene mutation. Historically, out of all the patients with breast cancer referred and tested through the Clinical Cancer Genetics Program, approximately 15% test positive, and research shows that in the general population, 7–10% of breast cancer patients will test positive.
Conclusions: while the positivity rates between the cohorts are not statistically significant, we have shown that patients with a BRCA mutation can develop ILC in addition to the more commonly seen IDC. We suggest that patients continue to be referred for genetic counseling according to the NCCN guidelines, regardless of the pathology of their tumor.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-13-04.
P2-13-11: Follow Up of BRCA1/2 Carriers: The Spectrum of Cancer Diagnoses in Healthy at Risk Individuals (HTR), and in Cancer Survivors (CS).
Authors: Clara AI , Costa CS , Silva J , Marques JC , Moura C , André S , Luís A , Bento S , Opinião A , Rodrigues P , Machado P , Fragoso S , Santos S , Vaz F 
Published: June 2012

Abstract
Introduction and Objective: Data from long term follow up of BRCA1/2 carriers is scarce and is mainly related to BRCA1 women. Our multidisciplinary program targets both women and men for counselling towards BRCA1/2 screening and inclusion in clinical follow up. In here we review all cancer diagnoses observed in our BRCA1/2 cohort during follow up.
Methods: Review of individual records of BRCA1/2 carriers registered from January 2000 to December 2010. Follow up was calculated since BRCA1/2 post-test counselling until the last visit to the Clinic. All new cancer diagnoses and preventive surgeries were registered.
Results: Two-hundred and fifty nine BRCA1/2 carriers (206 females and 53 males) were diagnosed with BRCA1/2 mutations (42 BRCA1 and 217 BRCA2). Medium follow up for all population is 25 months (1-98). At the date of initial BRCA1/2 diagnosis 99 women and 14 men were CS.
Female population: Eighty-eight female CS had been previously diagnosed with breast cancer (18 bilateral cases), 18 with ovarian cancer, and 1 with biliary tract cancer. Preventive surgeries in the CS female population were: bilateral adnexectomy (33 pts) and prophylactic contralateral mastectomy (10 pts). In this CS female population, new cancers, during follow up were: Contralateral breast cancer (4 cases), peritoneal cancer (2 cases in pts with previous prophylactic surgery) and skin non-melanoma cancers (2 cases). In female HTR, 23 preventive bilateral adnexectomies and 20 bilateral mastectomies were performed. Cancer diagnoses during follow up were: breast (11), peritoneum (1 in a pt with previous prophylactic surgery), gastric (1) and M3 leukemia (1). Global failure of prophylactic adnexectomy, so far (CS+HTR): 3/56 (5%).
Male population: The medium age for male CS is 73 yrs and for male HTR is 52 yrs. Male CS had mostly been previously diagnosed with BC (12; 4 bilateral) and prostate cancer (4). Other previous cancers: gastric (2), skin (2: 1Melanoma, 1 non-Melanoma), colorectal (1). One BRCA2 man with gynecomastia and prostate cancer was submitted to reduction mastectomy, as a preventive surgery. During follow up, we diagnosed second and third cancers in male CS: breast (2), prostate (6) and gastric (1). Only 1 male HTR was diagnosed with cancer: skin non-melanoma.
Conclusion: The proportion of second and third cancer diagnoses in the male BRCA2 CS population is higher than in the female BRCA1/2 CS population. Small numbers and the availability of preventive surgery for women influence this observation. No data from preventive mastectomy exists for males (we have one case). The low frequency of cancer in male HTR may be due to younger age and other unknown modifier factors. Longer follow is needed.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-13-11.
P2-15-01: Surgical Patterns of Care after Magnetic Resonance Imaging in the Academic Setting in Patients with Operable Breast Cancer Treated with Neoadjuvant Systemic Therapy: A Secondary Analysis of TBCRC 017.
Authors: De Los Santos J , Cantor A , Mcguire K , Golshan M , Meric-Bernstam F , Horton J , Nanda R , Amos K , Forero A , Hudis C , Meszoely I , Hwang S 
Published: June 2012

Abstract
Background: Neoadjuvant chemotherapy is increasingly used to downstage locally advanced tumors, test new regimens, and improve chances of breast conservation. In parallel, use of breast MRI for surgical planning and as a potential response biomarker has also increased along with an observed increase in mastectomy rates. This secondary analysis reports surgical patterns of care across 8 NCI comprehensive cancer centers in women receiving both neoadjuvant therapy and breast MRIs.
Methods: 770 women from 8 institutions were retrospectively identified as having received neoadjuvant systemic therapy with MRI done before and after systemic treatment. Univariate and multivariate analyses of covariates associated with surgical management were performed. Within MRI complete response or not, the Jonckheere-Terpstra Test (JTT) was used to test for a trend in mastectomy rate by T stage.
Results: Surgical data was available on 763/770 patients. Table 1 lists MRI response by pretreatment imaging size and final breast surgery. Distribution of pretreatment imaging-defined T stage was as follows: T1 66 (8%), T2 436 (57%), T3 230 (30%), and T4 36 (5%). 347/763 (45%) patients received breast conserving surgery and 416/763 (55%) had a mastectomy. 58% vs 43% (p=0.0003) of those with an incomplete vs complete MRI response had a mastectomy, respectively. Univariate logistic regression analysis of covariates significantly associated with use of mastectomy included ER- status (p=0.01), incomplete MRI response (p=0.0003), higher T stage (p&lt;0.0001), chemotherapy regimen (p=0.006), younger age (p&lt;0.0001), and institution (p=0.002); all except chemotherapy regimen and institution remained independent predictors of mastectomy on multivariate analysis. Patients with larger baseline T stage and an incomplete response on MRI (P&lt;0.001) were more likely to undergo mastectomy. Overall, breast conservation was low (262/495, 53%) of all T1-T2 patients, especially in the T1 subset (26/65, 40%).
Conclusions: In a contemporary group of women treated with preoperative chemotherapy at NCI designated cancer centers and with available pre/post MRI, we observed a lower frequency of breast conservation as compared to historical data from prospective randomized trials. Larger tumor size at baseline was associated with higher mastectomy rates. However, even among those with a complete MRI response, 43% had a mastectomy. In addition to clinical response and MRI findings, factors not examined here (e.g., BRCA status, education level, and patient/provider preference) may influence the decision-making process and deserve further evaluation.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-15-01.
P2-15-09: Prospective Randomized Comparison of Conventional Instruments and the Harmonic Focus® Device in Breast-Conserving Therapy for Primary Breast Cancer.
Authors: Böhm D , Kubitza A , Lebrecht A , Schmidt M , Kölbl H 
Published: June 2012

Abstract
Background: In recent years, surgeons have utilized Harmonic instruments to perform breast cancer resection. Retrospective and prospective studies have demonstrated that the use of this surgical device for mastectomy and axillary dissection can reduce perioperative blood loss, seroma formation, and duration and total amount of drainage. No study has analyzed the feasibility of Harmonic instruments in breast-conserving surgery. We conducted a prospective, randomized clinical trial comparing Harmonic instrument and conventional surgery in the performance of breast conserving surgery and axillary procedures to determine differences in surgical procedures, postoperative outcome, and complications.
Methods: One hundred and forty seven patients with operable breast cancer who underwent breast-conserving surgery at a single institution between December 2009 and March 2011 were included in the analysis. Surgery was performed in 73 patients with the Harmonic Focus® device and in 74 with scissors and electrocautery. Charts were reviewed for patient demographics, histopathologic reports, surgical procedures, length of stay, volume and duration of postoperative drainage, complications such as seroma and hematoma formation, and postoperative pain.
Results: We found a statistically significant difference in size of resected breast tissue (p&lt;0.001), postoperative serum hemoglobin (p=0.001), volume (p&lt;0.001) and duration (p&lt;0.001) of breast drainage, volume (p&lt;0.001) and duration (p=0.001) of axillary drainage, intramammary (p=0.04) and axillary (p=0.006) seroma formation, subjective (p=0.012) and objective (p&lt;0.001) postoperative pain, and length of hospital stay (p=0.002) in favor of the Harmonic surgical device.
Discussion: This is the only study comparing the Harmonic instrument with traditional surgery in both breast conserving surgery and axillary procedures. From this study, we conclude that despite higher costs, the Harmonic device is safe to use and provides key benefits in intraoperative technique, postoperative outcome, and rate of complications in breast cancer surgery.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-15-09.
P2-16-16: Nipple Sparing Mastectomy and Immediate Breast Reconstruction: Critical Appraisal of Five Year, Single Centre Outcomes.
Authors: Westbroek D , Karat I , Min-Hui H , Gukas I , Daoud R , Laidlaw IJ 
Published: June 2012

Abstract
Background
Approximately 5,000 patients undergo breast reconstruction annually in the United Kingdom ( 2:1 ratio of immediate versus delayed respectively). Whilst skin sparing mastectomy is an accepted modality for local control in appropriately selected patients, nipple preservation remains controversial. In over 1,800 peer reviewed nipple sparing mastectomy (NSM) cases, the local event rate attributable to NAC preservation following NSM (therapeutic and prophylactic) is 0.16% with no evidence of deleterious impact on disease free survival. This study aims to evaluate in a selected cohort of patients, the oncological safety and aesthetic outcome of nipple- sparing mastectomy and immediate breast reconstruction (IBR). We highlight the surgical technique used and propose in/exclusion criteria.
Material and Methods: Patients were identified retrospectively from our Institution's electronic patient records and WinPath™ database by searching clinical codes corresponding to NSM & IBR, performed by the senior authors (IJL and RD) between January 2004 and December 2008. Pre-operative selection criteria included: 100% pre-operative lesion characterisation; 5mm margin acceptance; submission of separate nipple core specimens for paraffin block histological assessment and re-excision of all involved/close margins. Follow-up data was verified from patients’ case notes, histo- pathological review and standardised photographic views. Endpoints include: local recurrence rate, disease free survival, peri-operative NAC subcutaneous tissue loss and validated aesthetic outcome measures.
Results*: 84 patients underwent NSM & IBR for invasive disease. The mean age was 52.1 years and a median follow-up of 38 months. IBR utilised autologous tissue (latissimus dorsi or transverse rectus abdominus musculocutaneous flaps) with/without implant prosthesis. There was one case of local recurrence (1.2%) in a patient who declined re-excision of close/involved margins and no recorded breast cancer related deaths. Peri-operative complication rates were within the national mastectomy breast reconstruction audit outcome guidelines.
Conclusion: In this cohort of patients, nipple sparing mastectomy and immediate breast reconstruction achieves comparable oncological outcomes with excellent aesthesis relative to traditional ablative procedures for local control. Nipple preservation although not evaluated independently does enhance cosmetic outcomes.
*(Preliminary analysis)
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-16-16.