bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P1-09-12: Dose dense adjuvant chemotherapy in patients with early breast cancer: Differential treatment effects according to composite index of benefit
Authors: Puglisi F , Ceppi M , Cognetti F , De Placido S , Bruzzi P , De Laurentiis M , Bisagni G , Cavazzini G , Durando A , Turletti A , Valle E , Montemurro F , Barni S , Ardizzoni A , Gamucci T , Colantuoni G , Del Mastro L 
Published: March 2017

Abstract
Background In patients with node-positive early breast cancer (EBC), dose-dense adjuvant chemotherapy improves disease-free survival (DFS) compared with standard interval chemotherapy. The GIM2 trial supports the value of dose-dense chemotherapy and suggests that the benefit is present in patients with hormone receptor-negative or hormone receptor-positive tumours (Del Mastro et al. Lancet 2015). In order to individualize decision making, there is a need to examine the absolute treatment effects of dose dense chemotherapy according to patient and tumor characteristics.
Patients and Methods The randomized phase III GIM2 trial enrolled 2091 patients. The primary endpoint was DFS. A continuous, composite measure of treatment benefit for each patient was determined from a Cox model incorporating potential predictive factors (age: 25-40/41-55/56-71; histological grade: 1+2/3; hormonal receptor status: positive/negative). Subpopulation treatment effect pattern plot methodology was used to reveal differential treatment effects on DFS according to composite index. The study focused on patients with HER2–negative disease (N=1287).
Results On average, the magnitude of benefit with dose dense chemotherapy versus standard chemotherapy ranged widely across different subpopulations, as quantified by the composite measure of relevant variables. The highest benefit was observed in patients with high grade, hormone receptor-negative disease (hazard ratio for DFS 0.44, 95% CI 0.23-0.83). Of note, a relevant benefit was observed also in patients with high grade, hormone receptor-positive disease (hazard ratio for DFS 0.74, 95% CI 0.50-1.09).
Conclusion The absolute improvement in DFS with dose dense adjuvant chemotherapy is substantial in some patients with node-positive HER2-negative breast cancer, particularly those regarded as having high index risk (hormone receptor-negative, high grade disease). Interestingly, a significant effect of dose dense chemotherapy was observed also in patients with hormone receptor-positive, high grade disease.
Citation Format: Puglisi F, Ceppi M, Cognetti F, De Placido S, Bruzzi P, De Laurentiis M, Bisagni G, Cavazzini G, Durando A, Turletti A, Valle E, Montemurro F, Barni S, Ardizzoni A, Gamucci T, Colantuoni G, Del Mastro L. Dose dense adjuvant chemotherapy in patients with early breast cancer: Differential treatment effects according to composite index of benefit [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-09-12.
Abstract P1-11-05: Influence of race and age on mastectomy rates in women with stage I, hormone-sensitive breast cancers: A SEER-based study
Authors: Bazan JG , Bittoni MA , Fisher JL , White JR 
Published: March 2017

Abstract
Background: Breast conserving therapy (lumpectomy [L] and breast radiotherapy [RT]) results in equivalent cancer control outcomes in comparison to mastectomy (M) for early stage breast cancer (BC) based on randomized controlled trials (RCT). Since 2004, RCT support that L alone without RT yields equivalent survival and acceptable local regional outcomes in women ≥70 years old with stage I (T1N0) hormone-sensitive (HS) BC on endocrine therapy. Based on this, we hypothesized that M rates should decrease substantially in this low risk elderly population and sought to examine the influence of race on M rates in this group and how these trends compare to younger aged Stage I HS patients.
Methods: We used the Surveillance Epidemiology and End Results (SEER) registry data to conduct this study. We included women with T1N0 HS BC classified as either ER-positive or PR-positive from 2000-2012 divided into 2 age groups [elderly (≥70 years old) and non-elderly (20-69 years old)] and 3 race groups [white, black, and Asian-Pacific-Islander/American Indian/Alaskan Native (API)]. We compared M rates in women diagnosed before 2004 compared to those diagnosed from 2005-2012. Statistical analyses were performed using differences in proportions (p&lt;0.05 considered statistically significant).
Results: 261,079 women met the study criteria (N=87,009 elderly; N=174,070 non-elderly). In elderly Stage I HS BC, a 5.2% reduction in the M rate is seen: 32.6% before 2004 to 27.4% after 2004 (p&lt;0.0001). M rates remained higher (with less reduction) in elderly Black (30.8 %) and API (33.6 %) vs. White (26.8%) [p&lt;0.0001 for White vs. Black and for White vs. API]. In non-elderly Stage I HS BC, after 2004 M rates increased from 29.2% to 31.8% (p&lt;0.0001). Non-elderly white women had the largest absolute increase in M rates (31.2% vs. 28.5%, p&lt;0.0001) followed by API women (35.1% vs. 37.1%, p=0.0222). M rates did not change after 2004 in non-elderly black women (31.7% vs. 31.7%, p=0.9953).
Conclusions: In patients with favorable stage I HS BC, M rates have decreased only modestly in elderly women since 2004 when L alone w/o RT was established as appropriate treatment. In comparison, M has increased since 2004 in non-elderly women. These trends are driven mostly by white women in both the elderly and non-elderly. Further research is needed to identify why M, which is associated with higher cost and morbidity than L alone, has not changed substantially in elderly very favorable BC, particularly for non-whites.
Citation Format: Bazan JG, Bittoni MA, Fisher JL, White JR. Influence of race and age on mastectomy rates in women with stage I, hormone-sensitive breast cancers: A SEER-based study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-11-05.
Abstract P2-01-13: Can axillary lymph node clearance be avoided in women with node positive breast cancer receiving primary chemotherapy?
Authors: Chowdhury MHR , Thillai K , Lucey A , Michalarea V , Mera A , Karapanagiotou E , Sandri I , Mansi J 
Published: March 2017

Abstract
Background
For patients who receive primary chemotherapy for their early breast cancer the current practice for lymph node positive (LN) disease at presentation is in transition, with a drive towards sentinel LN biopsy (SLNB) rather than axillary node clearance (ANC) for patients who achieve a good response to primary chemotherapy. Boileau et al initially reported that approximately 30% of patients could potentially avoid clearance, but with a recommendation for further evaluation before including SLNB in guidelines for biopsy proven node-positive disease prior to primary chemotherapy for early breast cancer.
Methods
This was a retrospective single centre study. Examining the records of all patients who had received primary chemotherapy between January 2010 and October 2014.
Patients were identified through the Guy's Breast Cancer Database and chemotherapy prescribing system. To fully assess the LN status, all patients were cross-referenced with the electronic notes on our electronic noting system (MOSAIQ), radiology on Patient Archiving and Communication System (PACS) and histology on our Electronic Patient Record (EPR).
Results:
1526 patients were identified, of whom 156 underwent primary chemotherapy. 111 patients had suspicious nodes on imaging (ultrasound and/or MRI) and underwent LN biopsy. 69 patients had positive nodes pre-chemotherapy. 28 of these 69 patients (40.6%) had negative nodes at ANC, of these 14 (50%) had complete pathological complete response (pCR) in their primary tumour(s) of whom 12 (86%) had radiological CR prior to surgery. Of the 41 who remained positive only three achieved pCR of their primary tumour after chemotherapy.
22 patients were LN positive post primary chemotherapy, despite having been identified as initially LN negative. Of these 9 had a negative pre chemotherapy biopsy, and only 1 of these 22 patients had a pCR.
Discussion:
We have confirmed that ANC may be avoided in selected patients with LN involvement at presentation. In our series over 40% could have had SLNB instead. Factors supporting this approach include those patients who have an excellent radiological response to primary chemotherapy. Conversely, 22 of 87 (25%) had positive LN after chemotherapy having been initially thought to be LN negative at presentation, highlighting the possible need for multiple nodal sampling prior to chemotherapy as well as further nodal assessment after chemotherapy for complete staging.
Citation Format: Chowdhury MHR, Thillai K, Lucey A, Michalarea V, Mera A, Karapanagiotou E, Sandri I, Mansi J. Can axillary lymph node clearance be avoided in women with node positive breast cancer receiving primary chemotherapy? [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-01-13.
Abstract P2-01-15: Clinical application of multimodal fluorescent-radioactive system in advanced breast cancer patients with neoadjuvant therapy; interim analysis for 65 patients
Authors: Lee S , Jung S-Y , Kim S-K , Lee ES , Lee MH , Park SJ , Kang H-S , Lee KS , Park IH , Sim SH , Kim Y , Kwon Y , Joo J , Kang SH 
Published: March 2017

Abstract
Purpose
This study aimed to evaluated the identification rate and operation time of sentinel lymph node biopsy (SLNB) by a multimodal fluorescent-radioactive system (MFS) using a mixture of indocyanine green (ICG), radioisotope (RI) compared with the RI alone in advanced breast cancer patients with neoadjuvant therapy.
Methods
In this phase II randomized study, we enrolled 65 patients with advanced breast cancer with neoadjuvant therapy. Then, they received SLNB with either MFS or RI. We compared the identification rate, operation time of SLNB and number of sentinel lymph nodes. We also evaluated the safety. We analyzed the data of 65 patients for interim analysis.
Results
The mean age of the MFS group and RI group was 51.7 and 45.9 years (p=0.024), respectively. There were no differences in histopathological characteristics, including tumor size, node positivity, and hormone receptor status between two groups. The radiologic study showed the clinically complete response in axillary lymph nodes after neoadjuvant therapy. In MFS group, sentinel lymph nodes (SLNs) were identified in 30 patients and we could not identify the SLNs in one patient. In RI group, we identified the SLNs in 33 patients and also could not identify them in one patient. (p=0.947). The average numbers of SLNs in the MFS and RI group were similar. (2.32±1.10 vs. 2.18 ± 1.57, respectively; p=0.668) The operation time of SLNB was similar in the each group (11.65 ± 6.49 vs. 9.47 ± 6.26, respectively, p= 0.174) There were no complication, including allergic reactions, skin staining or necrosis.
Conclusions
This study is the randomized trial that compared MFS using ICG and RI and the conventional RI method for SLNB in the advanced breast cancer with neoadjuvant therapy. The multimodal fluorescent-radioactive system is a feasible and safe method for SLNB for the breast cancer patients with neoadjuvant therapy. We will evaluate the 130 patients for final analysis.
Citation Format: Lee S, Jung S-Y, Kim S-K, Lee ES, Lee MH, Park SJ, Kang H-S, Lee KS, Park IH, Sim SH, Kim Y, Kwon Y, Joo J, Kang SH. Clinical application of multimodal fluorescent-radioactive system in advanced breast cancer patients with neoadjuvant therapy; interim analysis for 65 patients [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-01-15.
Abstract P2-01-24: Evaluating lymph node ratio (LNR) as a prognostic indicator in node-positive breast cancer
Authors: Kelliher A , Boyce M , Donnellan E , O Connor D , Murphy C , Bird B 
Published: March 2017

Abstract
Purpose: To determine whether LNR can provide additional prognostic information to pN staging in node-positive breast cancer patients.
Methods: We previously reported on the utility of LNR as a prognostic indicator in lymph node-positive early breast cancer. We present an updated analysis with a prolonged median follow-up of 85 months. A retrospective review of original histopathology reports was undertaken in a sample group of 214 patients diagnosed with node-positive breast cancer between January 2000 and January 2011. The LNR was defined as the number of positive lymph nodes divided by the total number of lymph nodes (LNs) removed. LNR cut off points were divided into low (≤0.14), intermediate (0.15-0.39) and high (≥0.40) by trichotomy. Patients were also divided into three groups based on nodal status in accordance with the AJCC staging system. Those with 1-3 positive nodes were classified as pN1, those with 4-9 positive nodes were pN2 and those with 10 or more positive nodes were classified as pN3. Overall survival (OS) and invasive Disease Free Survival (iDFS) were calculated using the Kaplan Meier Method.
Results: The mean age at diagnosis was 58 (SD=12) years. The median follow-up time was 85 months. The 5-year OS and iDFS for node-positive patients were 80% and 70%, respectively. The mean number of lymph nodes examined was 15.2 (SD=6.6) and the mean number of positive nodes was 5.3 (SD=6.1).
When patients were stratified according to LNR groupings OS was 80% in the low LNR group, decreasing to 67% in the intermediate LNR group and 47% in the high LNR group (p&lt;0.0001). Similarly, iDFS in the low LNR group was 71% decreasing to 57% in the intermediate LNR group and 42% in the high LNR group (p&lt;0.0009).
Conclusions: These updated results from a cohort of patients with lymph node-positive early breast cancer at a median follow-up of over 7 years confirms the utility of LNR as a prognostic indicator. Univariate and multivariate analyses to assess the ability of LNR to discriminate risk in addition to AJCC nodal grouping will be presented.
Citation Format: Kelliher A, Boyce M, Donnellan E, O Connor D, Murphy C, Bird B. Evaluating lymph node ratio (LNR) as a prognostic indicator in node-positive breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-01-24.
Abstract P2-01-26: Validation of a Chinese nomogram with a Dutch breast cancer population: Excellent prediction of the probability of axillary lymph node metastasis
Authors: Qiu S-Q , Aarnink M , van Maaren MC , Dorrius M , Koffijberg H , van Dam GM , Siesling S 
Published: March 2017

Abstract
Background: In the era of precision medicine, the surgical management of axillary lymph nodes (ALN) should be patient-tailored. Omission of sentinel lymph node biopsy (SLNB) is possible in patients with early breast cancer and very low or very high probability of ALN metastasis. Recently, we developed a nomogram to predict the probability of ALN metastasis in breast cancer patients based on clinicopathological parameters including ultrasound using a Chinese patient dataset1. In this study the nomogram performance was validated in an independent Dutch population from one hospital.
Methods: Data of 170 Dutch patients with a successful SLNB or axillary lymph node dissection were collected. A lymph node containing either micro- or macrometastatic disease was considered as a positive lymph node. Performance of the nomogram was assessed by calculating the area under the receiver-operator characteristic (ROC) curve (AUC). False-negative rates (FNRs) and false-positive rates (FPRs) at several different predictive cut-off points were calculated.
Results: There were 69 (40.6%) patients having a positive ALN. The AUC for the nomogram was 0.84 (95% confidence interval 0.78-0.90) compared with 0.86 in the Chinese validation population, showing excellent discrimination of the model. The FNR and FPR of the model were 10.2% and 0% for the predicted probability cut-off points of 14.5% and 90%, respectively.
Table 1 False-negative rates (FNRs) and false-positive rates (FPRs) of the nomogram at different predictive cut-off pointsPredicted rishPatient number and percentage (%)Number of patients with positive ALNFNR (%)&lt; 14.5%59 (34.7)610.2&lt; 20%79 (46.5)1113.9 Number of patients with negative ALNFPR (%)&gt; 70%27 (15.9)13.7&gt; 90%18 (10.6)00ALN: axillary lymph node
This means that omission of SLNB is possible for patients with a predictive probability of less than 14.5% or higher than 90%, which accounts for 45.3% of all patients in this study.
Conclusions and future perspectives: In this study, the Chinese nomogram showed excellent performance in predicting the probability of ALN metastasis in an independent Dutch population. A multicentre validation of this nomogram in large Dutch patient population (&gt;2500 patients) is ongoing.
Reference
1.Qiu S-Q, Zeng H-C, Zhang F, et al. A nomogram to predict the probability of axillary lymph node metastasis in early breast cancer patients with positive axillary ultrasound. Sci Rep 2016; 6: 21196.
Citation Format: Qiu S-Q, Aarnink M, van Maaren MC, Dorrius M, Koffijberg H, van Dam GM, Siesling S. Validation of a Chinese nomogram with a Dutch breast cancer population: Excellent prediction of the probability of axillary lymph node metastasis [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-01-26.
Abstract P2-01-36: Ex vivo shear-wave elastography of axillary lymph nodes predicting nodal metastasis in patients with primary breast cancer: A pilot study
Authors: Lim JW , Lee HW , Park JT , Ahn SG , Jung J 
Published: March 2017

Abstract
Objective: To evaluate the feasibility of shear-wave elastography using breast ultrasonography in identifying metastasis of removed sentinel lymph nodes during the operation for treatment of breast cancer.
Background: Conventional method for identification of sentinel nodal metastasis is time and cost consuming. The optimal method for identification of nodal status is important.
Methods: Excised sentinel lymph nodes during the operation were prospectively examined with the elastography. Metastatic status of lymph nodes was confirmed with permanent histology. Only macrometastasis was regarded as positive. Elastic values measured by the ex vivo elastography and nodal characteristics were analyzed to correlate with nodal metastasis.
Results: A total of 274 lymph nodes harvested from 68 breast cancer patients at Gangnam Severance Hospital from May 2014 to April 2015 were included this study. There was the difference of elastic values between nodes with and without metastasis (mean stiffness, 41.6 kPa and 17.4 kPa, P &lt; 0.001). Mean sizes of metastatic nodes (range 0.36-2.59 cm) were significantly larger than that of non-metastatic nodes (1.0 cm versus 0.75 cm, P &lt; 0.001). Moreover, there was a correlation between the size of metastatic nodes which ranged from 0.7 to 21.5 mm with a median of 7 mm and nodal stiffness (correlation coefficient of mean stiffness, r = 0.431). The area under the receiver operating characteristic curve (AUC) by the mean stiffness was 0.794. The combination of size of nodes, mean stiffness and ratio made AUC of 0.856.
Conclusions: In our study, ex vivo shear-wave elastography of sentinel lymph nodes was a feasible method to predict metastasis. Through the validation study, ex vivo elastography could be helpful to determine metastasis of sentinel lymph nodes during the operation.
Keywords Breast cancer; Elastography; Lymph node metastasis.
Citation Format: Lim JW, Lee HW, Park JT, Ahn SG, Jung J. Ex vivo shear-wave elastography of axillary lymph nodes predicting nodal metastasis in patients with primary breast cancer: A pilot study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-01-36.
Abstract P2-02-01: Identifying the remaining causes of hereditary breast cancer
Authors: Campbell IG , Trainer AH , Devereux L , James PA , Rowley S , Li N 
Published: March 2017

Abstract
Identifying the missing hereditary factors of familial breast cancer could have a major and immediate impact on reducing breast cancer risk in these family members.
Up to 1,325 candidate breast cancer predisposition genes, identified through exome sequencing of BRCAx families, were sequenced in index cases of up to 4,000 BRCAx families and 4,000 cancer free women from the LifePool study in Australia.
Interrogation of the data to refine the highest priority candidates is ongoing, but it is noteworthy that known (PALB2) or suspected (MRE11A) moderately penetrant breast cancer genes showed enrichment of loss of function (LoF) mutations in this dataset. Conversely, some other recently proposed breast cancer genes (BRIP1 and RINT1) did not show a significantly higher LoF mutation frequency in the cases compared to controls. Based on the number of LoF mutations leading candidates include NTHL1 (12 cases versus 4 controls) and ALKBH1 (7 cases versus 2 controls) which are each important members of the base excision repair and direct nucleotide repair pathways. We examined other genes in the base excision and direct repair pathways that were on our sequencing capture design and observed a significant enrichment of potentially deleterious mutations in 12 genes (NTHL1, OGG1, APEX1, APEX2, NEIL1, NEIL2, NEIL3, MUTYH, MPG, ALKBH1, ALKBH2, ALKBH3): Among the 1,638 cases and 1,654 controls analysed to date, 76 LoF variants were detected in these genes among the cases versus 47 LoF variants among the controls (p=0.007). Based on the overall distribution of variants between cases and controls the probability of selecting 12 genes with such enrichment from the 1,325 genes screened was less than 1 in 200.
Our data implicates rare mutations in base excision and direct DNA repair pathways genes as moderate-penetrance breast cancer susceptibility alleles.
Citation Format: Campbell IG, Trainer AH, Devereux L, James PA, Rowley S, Li N. Identifying the remaining causes of hereditary breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-02-01.