bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P2-05-20: Validation and comparison of CS-IHC4 score with a nomogram based on Ki67 index, Adjuvant! Online, and St. Gallen risk stratification to predict recurrence in early Hormone Receptor (HR)-positive breast cancers
Authors: Park YH , Im S-A , Cho EY , Ahn JH , Woo SY , Kim S , Keam B , Lee JE , Han W , Nam SJ , Park IA , Noh D-Y , Yang JH , Ahn JS , Im Y-H
Published: August 2014

Background: Recently, the information in the IHC score was reported to be similar to that in the 21-gene Genomic Health recurrence score (GHI-RS). The aim of this study is to develop a nomogram based on Ki67 index to predict recurrence and to validate the nomogram by comparison with CS-IHC4 as well as Adjuvant! Online and St. Galen risk stratification. In addition, we validated our nomogram with external cohort.

Methods: We retrospectively analyzed the clinicopathologic characteristics and outcomes of 1,070 postoperative HR-positive breast cancer patients between 2004 and 2007 at the Samsung Medical Center to determine recurrence-free survival (RFS). We constructed nomogram using Cox proportional hazard model and validated externally in a cohort of 1,028 at Seoul National University Hospital. A prognostic model that used classical variables, Adjuvant! Online, St. Gallen risk stratification, and the four IHC markers (IHC4 score) were created and assessed in our cohort by LR-χ2 test using the bootstrapping method.

Results: Nomogram showed an area under the receiver operating characteristic curve (AUC) of 0.70 (95% CI, 0.62–0.75) in the training set. The validation set showed a good discrimination with an AUC of 0.65 (95% CI, 0.58–0.72). In LR-χ2 test, the nomogram score was found to be more informative than the IHC4 with CS (LR-χ2 4.0539 [df1], 95% CI; 0.1038–8.004 for CS-IHC4 + nomogram score vs. CS-IHC4).

Prognostic significance was more prominent in N1 diseases than in the others (LR-χ2 4.199, 95% CI; 1.496–6.902 for CS-IHC4 + nomogram score vs. CS-IHC4).

However, Adjuvant! Online and St. Galen risk stratification did not show any definitive additional prognostic value.

Conclusions: We developed and validated a nomogram based on Ki67 index in external patients' cohort. It was compared with CS-IHC4 in our patients' cohort in early HR-positive breast cancers. This study implicates the amount of prognostic information contained in the nomogram is superior to that in the CS-IHC4 score.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-05-20.
Abstract P2-06-06: Integrating multiple molecular profiles with pathways to learn sub-type specific interactions with PARADIGM
Authors: Sedgewick AJ , Vaske CJ , Benz SC
Published: August 2014

High-dimensional omics profiling provides a detailed molecular view of individual breast cancers. We extended the Paradigm algorithm, a pathway analysis method for combining multiple omics data types with curated interactions on 7132 genes, to learn the strength and direction of curated interactions. Using only a single dataset, the 568 samples from the TCGA breast cancer cohort, we found strong high-throughput support for the majority of curated interactions. Gene set enrichment found that targets of the strongest interactions were significantly enriched for apoptosis and cell morphogenesis, and that strong regulators were significantly associated with phosphorylation. Within the TCGA breast cancer cohort the interactions some of the strongest support centered around ER alpha, IL23, GREB1, AKT1, and p53. We also assessed different strength between breast cancer subtypes, and found interactions associated with the MYC pathway and the ER alpha network to be among the most differential between basal and luminal A subtypes. Finally, we extended the method to assess the contextual dependence of interactions and found significant correlation between FOXM1 and JUN in regulation of CDK1.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-06-06.
Abstract P2-08-02: The large scale structure of the HER-2/neu amplicon in breast cancer
Authors: Pauletti G , Anderson L , Rong H-M , Yu J , Slamon DJ
Published: August 2014

Classical models of gene amplification envision chromosomally localized focal amplicons encompassing the immediate contiguous chromosomal regions flanking the driver gene. We present evidence that this is not the case for the HER2/neu amplicon in human breast cancer. Using a large panel of HER-2/neu positive cell lines, we observed that the HER-2/neu amplicon is made up of DNA segments mapping at different positions along chromosome 17. Sub-regions were subsequently re-amplified with the creation of condensed array of shorter amplicons. In addition, we show involvement of other chromosomes. The massive inter and intra-chromosomal reshuffling associated with amplified HER-2/neu containing sequences not only shed new light on the mechanism of gene amplification in human cancer but also have significant clinical implications for developing new targeted therapies and for combating drug resistance in this important subtype of breast cancer.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-08-02.
Abstract P2-09-06: The structure design and biological activities of inhibitory peptides, which block the interactions among polycomb repressive complex 2
Authors: LI KK , Luo L , Kong X , Li L , Luo C
Published: August 2014

Polycomb repressive complex (PRC2) contains several proteins, including embryonic ectoderm development (EED), suppressor of zeste 12 (SUZ12) and enhancer of zeste homolog 2 (EZH2). Excessive EZH2 concentrations have been reported as a marker of aggressive breast cancer and associated with invasion and cancer progression. EZH2 levels were elevated in patients with invasive breast carcinoma relative to normal or atypical hyperplasia. Except for the C-terminal SET domain, which functions as a histone-lysine N-methyltransferases, EZH2 has an N-terminal alpha helix region, which forms tight complex with EED protein. The in vivo enzymatic activity of EZH2 relies on and be tightly regulated by the interaction with EED. We designed series of artificial peptides trying to block the interaction between EZH2 and EED. By using label-free surface plasmon resonance (SPR) technology, the dynamic binding capacities of these peptides were tested. There were 3 leading structures standing out from the screening of more 80 peptides. After several round of co-crystal structure based optimization, the binding capacity of one inhibitor was reached to several nM levels, which indicated the availability for being a drug candidate. Finally, the biological activities of the inhibitory peptides were tested in several breast cancer cell lines. The PRC2 inhibitory peptides in this study are the first time reported PRC2 targeting epigenetic molecules with biological activity in breast cancer.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-09-06.
Abstract P2-10-04: The Mammostrat Test is an Effective Tool to Stratify Patient Samples Previously Characterized as Intermediate by the Oncotype Dx Test
Authors: Bloom KJ , Kyshtoobayeva A , Hilaire L , Gutekunst K
Published: August 2014

Mammostrat is a well validated, 5-antibody immunohistochemistry (IHC) based assay initially developed to assess the risk of recurrence in patients with early stage estrogen receptor (ER) positive breast cancer. Recent data from the TEAM trial demonstrated that Mammostrat predicted distant relapse free survival (DRFS) for both exemestane and tamoxifen-exemestane treated patients irrespective of nodal status and chemotherapy. OncoType Dx® is a recurrence assay frequently used by oncologists to aid in the selection of early stage breast cancer patients who may benefit from adjuvant chemotherapy. It is currently unclear whether patients whose tumors demonstrate an intermediate risk score should receive chemotherapy. We sought to determine if tumors with intermediate OncoType Dx® scores would be clearly classified as high or low risk with the Mammostrat assay.

Formalin fixed paraffin embedded tissue blocks were retrieved from 143 patients whose tumor were previously assessed as intermediate with the OncoType Dx® assay (Genomic Health, Redwood City, Ca). Six serial 5 micron sections were cut from the tissue block. One section was stained with H&E and the remaining five sections were stained with the Mammostrat antibodies, NDRG1 (AGI-3-3-12E clone, Clarient, Aliso Viejo, CA), TRMT2A (AGI-2-33-12E clone, Clarient, Aliso Viejo, Ca), P53 (D07 clone, Dako, Carpenteria, CA), CEACAM (S0235 08/28/06 clone, Clarient, Aliso Viejo, CA)and SLC7A5 (AGI-1-108-2E clone, Clarient, Aliso Viejo, CA). Slides were reviewed by a single pathologist (KJB) using previously published Mammostrat criteria and a risk score of low, moderate or high was generated.

Of the 143 tumors, 62 (43%) were classified as low risk, 51 (36%) were classified as high risk and 30 (21%) were classified as moderate risk. Thus, 113 (79%) cases were defined as either low risk or high risk by the Mammostrat assay.

The Mammostrat assay reclassified 79% of OncoType Dx® intermediate tumors into a clear high risk or low risk category. Based on data from the TEAM trial, node negative patients categorized as low risk by Mammostrat had a 5 year DRFS of 96%, while data from the NSABP-B20 trial showed that patients categorized as high risk by the Mammostrat assay derived a significant benefit from adjuvant chemotherapy. Mammostrat may be an effective tool to aid oncologists and patients in treatment decisions when Oncotype Dx® classifies a tumor as intermediate risk.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-04.
Abstract P2-10-05: Continuous association of a 200-gene prognostic risk score with probability of neoadjuvant chemotherapy response and translation from fresh frozen to FFPE tissue for clinical use.
Authors: van Laar R , DiPaola J , Carbaugh H , Murphy T , DiRamio A , Flinchum R , Brown N , Albino T
Published: August 2014

BreastPRS is a suite of complimentary gene signatures that resolves several of the significant limitations of current gene expression signatures in breast cancer. Notably, BreastPRS can accurately provide prognosis prediction, histological grade resolution and molecular subtyping of invasive breast cancer. The 200-gene prognostic component was previously validated in an independent retrospective series of 1,016 previously published fresh-frozen breast cancers and has now been applied to data from over 6,000 patients.

In part one of this study, a meta-analysis of 890 previously published neoadjuvant treated breast cancer patients was performed. A highly significant association was observed between prognosis risk group (high vs low), continuous risk score (0–100), and a patient's probability of achieving complete pathologic response with neoadjuvant chemotherapy. Data from both fine-needle-aspirate and biopsy tissue were included in the cohort. Notably, fewer than 10% of patients with the lowest (most favorable) pre-treatment BreastPRS prognosis scores achieve pCR. Probability of pCR was observed to increase steadily to over 40% for individuals with the highest prognosis scores.

In part two of the analysis, 50 paired fresh-frozen and FFPE tumors were profiled on whole genome microarrays containing all three signatures, in a CLIA-certified high throughput genomics laboratory. Results will be presented that highlight the consistency of the prognosis, grade and subtype signatures in clinically relevant FFPE tissue.

This suggests that BreastPRS, in addition to identifying 10-year recurrence risk, histologic grade and molecular subtype, may enable physicians to determine a patients benefit from receiving neoadjuvant chemotherapy with more granularity than current clinical or genomic methods.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-05.
Abstract P2-10-21: Prognostic value of estrogen receptor status in women with synchronous or metachronous breast cancers
Authors: Huo D
Published: August 2014

Background: Estrogen receptor (ER) is an important prognostic and predictive factor for breast cancer (BC) patients. For women with two primary breast cancers, however, estrogen receptor status measured at the two tumors is not always the same, either due to tumor heterogeneity, or because of limited reproducibility of receptor assays. For women with metachronous breast cancers, it is unclear if estrogen receptor status of previous cancer has prognostic value. For women with synchronous breast cancers, it is important to know if inconsistent receptor status predicts worse clinical outcome.

Methods: Data on ER status of two primary breast cancers were obtained from the Surveillance, Epidemiology, and End Results program 1990–2009. We used piecewise proportional hazard Cox models to examine the joint effect of ER statuses of two tumors on overall survival or disease-free survival. Hazard ratio (HR) and 95% confidence interval (CI) were calculated, after adjusting for age, stage, race/ethnicity, histology, grade, and treatments in Cox models. Synchronous and metachronous cases were analyzed separately.

Results: There are 12,285 patients with synchronous breast cancers; 81.2% had both tumors being ER positive, 10.2% had one tumor being ER positive but the other being ER negative, and 5.6% had both tumors being ER negative. As shown in the Table, patients with inconsistent ER status (heterogeneity) had worse short-term survival rate than patients with double ER positive tumors. Among the 14,470 patients with metachronous breast cancers, 60.2% had two ER+ tumors, 13.8% had two ER− tumors, 11.8% had ER status changing from negative to positive, and 14.1% had ER status changing from positive to negative. In addition to ER status of the index cancer, ER status of the first cancer has independent prognostic value in predicting both short-term and long-term outcome (p = 0.0002).

Conclusions: Our study found that estrogen status of previous cancer has independent prognostic value for women with metachronous breast cancers. We also found that inconsistency in ER status between two tumors predicts worse survival for women with synchronous breast cancer. These findings suggest that heterogeneity or change in estrogen receptor expression in patients with two breast cancers should be considered during decision making on treatment or counseling on prognosis.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-21.
Abstract P2-10-26: Association between circulating tumor cells and molecular breast cancer subtypes
Authors: Gang N , Haibo W , Funian L , Chen L , Xiaoyi L , Xingang W , Zhidong L
Published: August 2014

Background and Objective: Circulating tumor cells (CTCs) provide crucial information for the management of breast cancer patients. CTCs analysis can be used as a liquid biopsy approach for prognostic and predictive purposes in breast and other cancers. Several contradictory results presented about the breast cancer subtypes of CTCs recently. The aim of this study was therefore to analysis the association between the CTCs and molecular breast cancer subtypes.

Methods: Blood samples were obtained from 143 breast cancer patients admitted to Breast Surgery Department, Affiliated Hospital of Medical College, Qingdao University. CTCs were detected by using immunomagnetic enrichment and a commercial kit, based on RT-PCR, was used to characterize CTCs. The expression of ER, PR, HER2 was detected by immunohistochemistry. The molecular subtypes were defined as: luminal A (ER+ and/or PR+, HER2−), luminal B (ER+ and/or PR+, HER2+), TNBC (ER−, PR−, HER2−), and HER2+, (ER−, PR−, and HER2+). The relations between the positive rate of CTCs and clinicopathological characteristics of primary tumor and molecular subtypes of breast cancer patients were analyzed.

Results: Overall positive rate of CTCs was 39.8% (57/143). The positive rate of CTCs in patients with Luminal A, Luminal B, HER2+ and TNBC subtype was 33.8% (26/77), 47.1% (8/17),50.0% (6/12) and 45.9%(17/37). There was significant difference in positive rate of CTCs by different molecular subtypes (P = 0.0415), especially at different AJCC stages (P = 0.004). The positive rate of CTCs in patients with Luminal A subtype was significantly lower than patients with the others breast cancer subtypes (p = 0.0387).

Conclusion: Our study suggests that presence of CTCs was more frequently found in patients with HER2+ and Luminal B subtypes. The presence of CTCs in patients with TNBC subtype was not as high as we wished. Theoretically, the positive rate of CTCs in TNBC subtype should be higher than that of others subtypes for being more aggressive histologically features and having increased potential to be invasive. One possible explanation for this might because of lacking epithelial markers expression and epithelial-mesenchyme transition (EMT) characteristics, CTCs of TNBC subtype are missed when using the standard EpCAM-based method. Shortage of patient's number was another possible reason. Further research on the Association between CTCs and molecular breast cancer subtypes will contribute to a better understanding of the biology of metastatic development in cancer patients.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-26.
Abstract P2-10-28: The Prognostic Index, KiGE, Combining Proliferation, Histological Grade and Estrogen Receptor Status Challenges Gene Profiling – A Study in 1,854 Chemo-Naïve Women with N0/N1 Primary Breast Cancer.
Authors: Strand C , Bak M , Borgquist S , Chebil G , Falck A-K , Fjällskog M-L , Grabau D , Hedenfalk I , Jirström K , Klintman M , Malmtröm P , Olsson H , Rydén L , Stål O , Bendahl P-O , Fernö M
Published: August 2014

Purpose: The aim was to validate the prognostic value of a previously defined index (CAGE), combining proliferation (Cyclin A), histological grade, and estrogen receptor (ER) in different subsets of primary breast cancer patients. In the present study, Ki67 was included in the index (KiGE) instead of cyclin A, since it is the generally accepted proliferation marker in clinical routine.

Patients and methods: 1,854 chemo-naive patients with primary breast cancer were included. The low KiGE group consisted of histological grade 1 cases and grade 2 cases which were ER-positive and had low Ki67 expression. High KiGE consisted of all other cases.

Results: The KiGE index separated patients into groups with different prognosis. In multivariate analysis, KiGE was significantly associated with disease-free survival, when adjusted for age at diagnosis, tumor size and adjuvant endocrine treatment (hazard ratio: 3.5, 95% confidence interval: 2.6–4.7, P<0.0001).

Conclusion: We have validated a prognostic index based on proliferation (Ki67), histological grade and ER, for identification of a low-risk group of patients with N0/N1 primary breast cancer. For this low-risk group, with a five-year distant disease-free survival of 92%, adjuvant chemotherapy will have limited effect and may be avoided. The KiGE index, based on clinically used factors, may challenge the more expensive gene expression profiles.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-28.
Abstract P2-10-30: Expression of lipid metabolism genes in contralateral unaffected breast associated with estrogen receptor status of breast cancer
Authors: Wang J , Scholtens D , Holko M , Ivancic D , Lee O , Hu H , Chatterton RT , Khan SA
Published: August 2014

Background: Risk biomarkers that are specific to ER subtypes of breast cancer would help developing distinct prevention strategies. The contralateral unaffected breast of women with unilateral breast is a good model for defining subtype specific risk as women with ER− primary tumor are at high risk for subsequent ER− tumor in contralateral breast.

Methods: We performed random fine needle aspiration of unaffected breast of cases. RNA samples from 30 subjects (15 ER+ and 15 ER−) were used for Ilumina expression array analysis. Findings were validated by qRT-PCR using independent sample set consisted of 36 subjects (12 ER+, 12 ER−, and 12 standard risk healthy controls).

Results: Gene array studies identified 18 genes with significant higher expression in ER− case samples, 8 of which were associated with lipid metabolism. This pattern was confirmed by qRT-PCR in the same samples and in the 24 cases of validation set. When compared to the healthy controls, significant over-expression of 4 genes (DHRS2, HMGCS2, HPGD, ACSL3) was observed in ER− cases, with significant lower expression of UGT2B11 and APOD in ER+ cases, and decreased expression of UGT2B7 in both subtypes.

Conclusion: Differential expression of lipid metabolism genes my be involved in the risk for subtypes of breast cancer, which might be potential biomarkers of ER specific breast cancer risk.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-30.
Abstract P2-10-36: Analysis of biomarker expression and biological subtype in primary tumour, corresponding lymph node and distant metastasis with 5-year follow-up
Authors: Falck A-K , Ferno M , Bendahl P-O , Chebil G , Olsson H , Rydén L
Published: August 2014

Background: Biological variation in genotype and phenotype of primary breast cancer explains the heterogeneity of the disease and subsequent outcome. Choice of treatment is routinely based on the biomarker expression of the primary tumour with regard to estrogen- (ER) and progesterone (PR) receptor status, human epidermal growth factor receptor 2 (HER2) status and the proliferation marker Ki67, individually. Recently, gene expression profiling and subsequent immunohistochemical studies have identified biologically distinct subtypes by using a combination of biomarkers which have been shown to be of prognostic value beyond the previous known. However, tumour progression theories propose a change in biomarker expression during development from primary tumour to distant metastasis with implications on choice of therapy. The aim of this study was to compare biomarker expression individually and according to biological subtype between tumour samples from primary tumour, lymph node metastasis and distant metastasis from the same patient.

Material and methods: From an original cohort of 569 patients with primary breast cancer, tissue microarrays were constructed from archival tissue blocks of primary tumour (n = 521), paired lymph node metastasis (n = 147) and biopsies from distant metastasis (n = 42). The samples were evaluated by two independent pathologists. The individual biomarker expression as well as subtype classification (Luminal A: ER+ and/or PR+, Ki67≤ 20% and HER2−. Luminal B: ER+ and/or PR+, Ki67> 20% and/or HER2+. HER2 type: ER/PR−, HER2+. Basal-like: ER/PR−, HER2−, CK5/6+ and/or EGFR+) were compared between primary tumour, lymph node metastasis and distant metastasis. Survival outcome were estimated using the Kaplan-Meier method and log rank test. The primary end-point was distant disease-free survival (DDFS).

Results: Distribution according to subtype.

The molecular subgroups in the primary tumours were associated with statistically significant prognostic information by log-rank test (p = 0.005) validating luminal A as a subgroup with excellent prognosis. More detailed survival analysis comparing expression of biomarkers between primary tumour, lymph node metastasis and distant metastasis will be presented.

Conclusion: Prognostic information can be obtained by subtype classification using routine-based biomarker analysis in the primary tumour. Preliminary data suggest that the subtype distribution is associated with a worse prognostic profile in the lymph node- and distant metastasis. Detailed survival analysis will be presented at the meeting.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-36.
Abstract P2-10-37: Long-term prognosis of early breast cancer in a population-based cohort with a known BRCA1/2 mutation status.
Authors: Nilsson MP , Werner Hartman L , Idvall I , Kristoffersson U , Olsson H , Johansson O , Borg Å , Loman N
Published: August 2014

Background: The impact of germline BRCA1/2 mutations on breast cancer prognosis and treatment is currently not clear. We investigate how different factors, including BRCA1/2 mutation status, correlate with long-term outcome in early breast cancer in a population-based cohort.

Methods: As previously reported, all women in the Southern Health Care Region in Sweden with breast cancer diagnosed before age 41 years between 1990 and 1995 (n = 262) were contacted in 1996 and offered mutation analysis of the BRCA1 and BRCA2 genes. Mutation analysis was performed on 234 of them, the others were excluded from further studies. 23 pathogenic mutations were found; 18 in BRCA1 and 5 in BRCA2. We will now present data on tumor and patient characteristics, treatment and long-term follow-up for the patients from this population-based cohort. Three patients have declined further study follow-up and were therefore excluded. Six patients had metastatic breast cancer at the time diagnosis (one of them a BRCA2 mutation carrier) and are also excluded, leaving 225 in the present analysis.

Results: Among the 225 cases estrogen receptor (ER) status is known for 191 (49% ER+, 51% ER−); histologic grade for 169 (24% grade I; 33% grade II; 43% grade III); stage for 225 (36% stage I, 44% stage II, 20% stage III); type of surgery, adjuvant systemic treatment and postoperative radiotherapy for 225. In the cohort, 46% received adjuvant or neoadjuvant chemotherapy, whereas 15% were given adjuvant endocrine therapy. There is complete follow-up > 10 years for 205 and present vital status for 224.

Of the 225 women, 128 (57%) have had a local, regional or distant recurrence of breast cancer (contralateral breast cancer not included) at the date of last follow-up. One hundred and six patients (47%) have died, 98 of whom from breast cancer and 2 from presumably radiation-induced malignancies caused by postoperative radiotherapy. Thirteen of the 22 BRCA1/2 mutation carriers (59 %) have died, all from breast cancer. Of the 9 mutation carriers that are alive today, 3 have had an in-breast tumor recurrence and 3 have had a contralateral breast cancer; the 3 women that have had neither have all performed bilateral prophylactic mastectomy as well as prophylactic salpingo-ooforectomy.

Data on how the long-term prognosis of early breast cancer is correlated to BRCA1/2 mutation status, adjuvant treatment, stage at diagnosis, histologic grade and ER status of the tumor will be presented.

Conclusion: Women with early breast cancer in this cohort from the early 90ies had a poor long-term prognosis. The prognosis for women diagnosed with early breast cancer today is likely to be better, thanks to more modern chemotherapy regimens, endocrine and targeted treatments. The prognostic significance of BRCA1/2 mutation status will be further analyzed.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-37.
Abstract P2-10-41: The prediction of invasion in ductal carcinoma in situ: developing prediction model and validation
Authors: Lee SK , Kim M , Nam SJ , Lee JE , Yang J-H
Published: August 2014

Background: The aim of the study was to determine factors and develop the model that predict the risk of invasion in patients with ductal carcinoma in situ (DCIS) diagnosed by preoperative biopsy.

Methods: We selected 497 patients underwent surgical treatment for preoperatively diagnosed DCIS of the breast between 1997 and 2009. Multivariate analysis was used to identify relevant clinical, radiological and pathological factors that may predict upstaging. A prediction model was developed based on significant factors and measured using the area under the receiver operating characteristics (ROC) curve. This prediction model was subsequently validated using the dataset of 149 cases who were diagnosed with DCIS preoperatively between 2010 and 2012.

Results: Of 24.75%, there was an upstaging to the invasive cancer. We found that larger size (≥1.5cm) of DCIS was most significant factor, followed by palpable lesion on physical examination, no expression of estrogen receptor (ER)/progesterone receptor (PR), high nuclear grade, non-cribriform subtype and absence of necrosis significantly associated with presence of invasion.

The prediction model with these factors showed that excellent predictive accuracy (the area under the ROC curve= 0.851, 95% CI: 0.817–0.881) and showed similar findings in the validation data set (AUC = 0.868, 95% CI: 0.800–0.916). After ranking the significant factors, we selected 4 factors to simplify the model. This simple model also showed good prediction power (AUC = 0.821, 98% CI: 0.784–0.854).

Conclusion: We developed the prediction model to predict upstaging in patients diagnose with DCIS preoperatively based on 4 most significant factors. By this prediction model, we suggest the axilla exploration with SLNB in case of DCIS with more than 1.5 cm size, palpable lesion, no expression of HR and high NG to avoid 2nd operation.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-41.
Abstract P2-11-02: Perception and practice of reproductive specialists towards fertility preservation of young breast cancer patients
Authors: Shimizu C , Kato T , Tamura N , Asada Y , Hiroko B , Mizota Y , Yamamoto S , Fujiwara Y
Published: August 2014

Background: The potential for infertility caused by treatment is one of the important quality-of-life issues in young breast cancer (YBC) patients. Insufficient communication and partnership between oncologists and reproductive specialists has been identified as a major barrier to meeting their needs. However, the perception of reproductive specialists towards fertility preservation (FP) of YBC has not been evaluated.

Objective: To investigate the perception and needs of reproductive specialists towards FP of YBC patients.

Methods: A cross-sectional survey was developed and sent to 423 certified reproductive specialists registered to the Japan Society for Reproductive Medicine to self-evaluate their perceptions and practices regarding FP in YBC patients.

Results: Two hundred reproductive specialists (47%) responded to the survey.

99% responded that reproductive specialists should be engaged in FP of YBC patients. 46% responded that cancer treatment is more important than childbirth even if the patient was recurrence-free five years after primary treatment. 83% responded that they would like to treat YBC patients. Respondents affiliated with private clinics were more likely to accept both fertilized egg and unfertilized egg preservation than those affiliated with academic or general hospitals (p < 0.01). 58% responded that ovulation induction methods should be modified in YBC patients. The choice of ovulation induction methods varied both in non-cancer women and YBC patients, however, the frequency of the use of letrozole was significantly higher (p < 0.01) and that of LHRH-agonist short protocol was significantly less (p < 0.05) in the management of breast cancer patients than in the practice of non-cancer women. 70% of the reproductive specialists responded that they were anxious in treating YBC patients. Concerns for greater or unknown risk of disease recurrence (66%), insufficient knowledge about breast cancer (47%), and lack of patient's spouse/partner (24%) were identified as major barriers in supporting FP for YBC patients.

Conclusion Reproductive specialists recognize the needs of FP in YBC patients and are willing to participate and support care for YBC. Affiliation of reproductive specialists was related to positive attitude towards to egg preservation. Various concerns regarding FP among reproductive specialists indicate the need for evidence that supports the safety of FP for YBC patients and guidelines that facilitate the practice and communication of oncologists and reproductive specialists.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-11-02.
Abstract P2-11-14: Symptoms, Physical Impairments, and Function in Breast Cancer Patients with Negative Axillary Lymph Nodes
Authors: Kesarwala AH , Pfalzer LA , O'Meara WP , Stout NL
Published: August 2014

Purpose/Objective(s): Breast cancer (BC) patients are recommended for post-operative regional nodal radiation therapy (RNRT) based on the number of positive axillary lymph nodes (LN). While RNRT is recommended for patients with 4 or more positive LN, it remains controversial in patients with 1–3 positive LN. For these patients, consideration of anticipated functional impairments often guides decision making, but these considerations are confounded by the inseparable effects of disease in and treatment of the axilla. The purpose of this analysis is to investigate the effect of various therapies on functional impairments in BC patients without axillary disease.

Materials/Methods: 166 women were diagnosed with BC between 2001–05 and enrolled and treated in a prospective surveillance physical therapy program. 110 had zero positive axillary LN on either sentinel LN biopsy or axillary LN dissection and were analyzed for this report. Participants' upper extremity (UE) range of motion, strength, and limb volume were assessed pre-operatively and at 1, 3, 6, 9, and 12+ months post-operatively by a physical therapist. Limb volume was assessed using infrared optoelectronic perometry. At 12+ months, overall health status, UE symptoms and function, and physical activity levels were reported using standardized questionnaires. Chi-square tests and one-way ANOVA analyses were used to determine significance between groups (p ≤ 0.05).

Results: Of these 110 patients, 34 received mastectomy without RT, 21 received mastectomy with RNRT, 10 received lumpectomy alone, and 45 received lumpectomy with whole breast tangent RT. No significant differences were found between groups with regard to stage, ER/PR status, and number of dissected LN. Rates of lymphedema, cording, and seroma were not significantly different between groups. By 12+ months post-operatively, there were no differences in shoulder abduction, shoulder flexion, internal rotation, or external rotation between groups. No differences were seen between groups in self-reported fatigue, UE swelling or weakness, arm stiffness, or ability to climb stairs.

Conclusions: Functional impairments represent an important category of morbidity for BC survivors and should be considered in pre-treatment decision making. In patients without axillary disease, post-operative RNRT or whole breast tangent RT may not contribute significantly to impairment over the first year of treatment when a prospective surveillance physical therapy program is part of the plan of care. Additional research is needed to assess longer-term changes and the impact of radiation in the context of the aggregate effect of disease burden combined with other BC treatment modalities.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-11-14.
Abstract P2-11-17: Pilot Study to Evaluate a Home-based Exercise and Weight Loss Intervention on Cardiopulmonary Fitness and Markers of Breast Cancer Risk in Postmenopausal Breast Cancer Survivors
Authors: Burnett D , Klemp JR , Porter C , Schmitz KJ , Fabian CJ , Kluding P
Published: August 2014

Background: BrCa survivors have an estimated 4-fold increase in risk for developing cardiovascular disease compared to women never treated for breast cancer and a nearly 3-fold increase in breast cancer mortality in women with an exercise capacity (VO2max) less than 28mL kg−1 min−1. Cardiac events are the second most common cause of death in long-term breast cancer (BrCa) survivors.

Purpose: We conducted a study to investigate the effects of standard exercise or structured exercise on targeted cardiovascular outcomes during a home-based diet and exercise intervention for breast cancer survivors.

Method: Cross-sectional within- and between-group design. A total of 19 breast cancer survivors, average age of 52.6+/−9.3, were enrolled in the study. A convenient sample was enrolled into two exercise groups receiving either: standard (150 minutes per week of usual care (exercise without instruction) cardiovascular exercise + resistance training) or structured (150 minutes per week of gradual increased intensity cardiovascular exercise + resistance training) exercise instruction along with a group based behavioral weight loss intervention. All participants underwent baseline and 17 week assessments including maximal exercise testing (VO2max and minutes on the treadmill), measurements of body composition (weight, BMI, % body fat), and assessment of quality of life.

Results: We report on the 16 participants who completed the baseline and 17 week assessments (9 = Standard Exercise Group; 7 = Structured Exercise Group). The structured exercise group exhibited significantly greater improvements in measures of cardiorespiratory fitness: VO2max (p = 0.05) and duration on treadmill (p = 0.02). No significant differences were noted for all other cardiorespiratory fitness testing outcomes. Significant improvements from baseline to 17 weeks were seen across both groups for all measures of body composition. Lean body mass did not significantly change from baseline to 17 weeks in both groups. There were no significant between group differences for change in body composition.

Conclusion: In this study, both standard exercise and structured exercise improved CR fitness measured by VO2max, but the structured exercise group experienced significantly greater improvements.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-11-17.
Abstract P2-12-02: Comorbidities and patient-reported cognitive function among women with stage I-II breast cancer randomized to hormonal therapy (HT) alone versus chemotherapy followed by hormonal therapy (C+HT) treated on the Trial Assigning IndividuaLized Options
Authors: Wagner Lynne I , Gray Robert , Sledge George , Whelan Tim , Hayes Daniel , Geyer Charles , Dees E Claire , Cella David , Sparano Joseph A
Published: August 2014

Withdrawn by Author

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-12-02.
Abstract P2-12-07: A review of clinical endpoints and use of quality-of-life outcomes in phase III metastatic breast cancer clinical trials
Authors: Tatla R , Landaverde D , Victor C , Miles D , Verma S
Published: August 2014

Background: The management of metastatic breast cancer (MBC) is often considered to be palliative, with most interventions intended to relieve disease symptoms, minimize treatment effects and prolong patient survival. The impact of disease and treatment on a patient's functional abilities has led to the emphasis of incorporating quality of life (QoL) measures into clinical trials. The primary objective of this study is to evaluate phase III clinical trials in MBC, and assess the inclusion of QoL as an endpoint, in addition to conventional progression and survival endpoints.

Methods: A structured PubMed search was conducted to identify phase III clinical trials published between Jan. 1990 and Aug. 2011, which evaluated systemic treatment in MBC patients. Data pertaining to treatment regimens, study endpoints and clinical findings were collected, with a particular focus on progression-based (PB), overall survival (OS), and QoL endpoints. The instrument(s) used in evaluating QoL were also noted (when applicable).

Results: Of 520 publications identified, 122 phase III MBC clinical trials met the inclusion criteria. Of these studies, 98.4% and 95.9% included PB and OS respectively, as clinical endpoints, while QoL was assessed in only 46 (37.7%) studies. 14 instruments were identified as QoL measurement tools among these studies, with EORTC QLQ-C30 and FACT-B accounting for 54.7% of the instruments used. While the inclusion of QoL was not associated with the significance of PB results, there was an association between the inclusion of QoL and OS results, with 59% of significant OS studies and 32% of non-significant OS studies including QoL as a clinical endpoint (p = 0.016). When stratified by treatment arm, it was found that studies favouring standard therapy were more likely to include QoL (75%, p = 0.045), compared to those favouring the intervention (56%), and those without significant differences (32%).

Conclusions: Although the importance of QoL is often emphasized in MBC management and treatment decisions, only one-third of identified phase III clinical trials included an assessment of QoL. About half of these trials showed no statistically significant differences in QoL endpoint; of note, instruments of varying validity were utilized. There needs to be greater emphasis on the evaluation of QoL, with the use of standard and validated QoL tools in MBC clinical trials, especially as we increasingly focus on progression-based endpoints.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-12-07.
Abstract P2-12-14: Use of the MD Anderson Symptom Inventory to Screen for Depression in Breast Cancer
Authors: Kvale EA , Azuero CB , Azuero A , Fisch M , Ritchie C
Published: August 2014

Background: The prevalence of depression among breast cancer patients is estimated to be twice that in the general population, is linked to diminished quality of life and impaired adherence to therapy. Depression is frequently underdiagnosed or misdiagnosed in this population. Efficient screening for depression is central to patient-centered care and enhanced clinical outcomes for breast cancer patients.

Purpose: To evaluate the use of a commonly utilized symptom assessment instrument as a screen to enhance identification of breast cancer patients experiencing depression.

Methods: Data from a longitudinal surveillance database in outpatient supportive and palliative care were utilized, 174 breast cancer patient contacts were evaluated. Patients completed both the MD Anderson Symptom Inventory (MDASI) and the 9-item Patient Health Questionnaire (PHQ-9) as components of a routinely collected patient-reported outcomes battery. Performance of the MDASI (using the 1–10 Depression question) in identifying cases of depression (defined as a score ≥ 15 on the PHQ-9) was determined using receiver operating characteristic (ROC) analysis.

Results: Data were available on 174 patient contacts. When scored as a continuous measure, the MDASI performed well with an area under the ROC curve of 0.87 (95% confidence interval [CI], 0.81–0.94). An MDASI cutoff score of >= 6 provided a sensitivity of 73% (95% CI, 58%–88%), a specificity of 80% (95% CI, 74%–87%), a positive predictive value (PPV) of 46%, and a negative predictive value (NPV) of 93%.

Conclusion: The “depression” component of the MDASI as a screening instrument for depression in breast cancer patients yields suboptimal sensitivity and specificity for use as a screening tool. Further efforts to evaluate subsequent iterations of the MDASI and combinations of elements in the MDASI that may enhance performance are indicated.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-12-14.
Abstract P2-12-15: Understanding the complex non face-to-face interventions delivered by the clinical nurse specialists in metastatic breast cancer.
Authors: Warren M , Mackie D , Leary A
Published: August 2014

Introduction: Despite improving survival rates in breast cancer, globally one third of patients diagnosed with primary breast cancer will go onto develop metastatic breast cancer. In recent years treatment for metastatic breast cancer in the United Kingdom has moved to the ambulatory setting using treatments such as, oral chemotherapies, oral biological and bisphosphonate therapies meaning telephone consultation and clinical management, pivotal to confluent care.

Research Objectives: To determine the number and complexity of incoming telephone calls, the stage of the metastatic breast cancer disease pathway for example at diagnosis, treatment, follow-up, and palliative care, the nursing interventions, outcomes and the reason for contact from patients and carers.

Rationale: Previous studies demonstrate much of the clinical work of the clinical nurse specialist is delivered via the telephone. The rationale of this study was to examine the complexity of non face-to-face patient interaction with the metastatic breast cancer clinical nurse specialist.

Method: A prospective study conducted over a 1 – month period at a United Kingdom National Health Service Foundation Hospital Trust. Data was collected by two clinical nurse specialists on incoming calls using Excel and a bespoke interrelational structured query database. These data were then mined using standard data mining techniques and pattern recognition techniques.

Results: The study collected 28 days of data. 229 patient and carer telephone contacts were recorded. Most calls were from patients (62.5%). Incoming calls resulted in the delivery of 1282 interventions, a mean of six interventions per call (range1-8) and clustered into four areas: meeting information needs (29%), symptom management (26%), psychological/social issues (33%) and other issues (12%). The incoming telephone work accounted for 63 h which represented 30% of the total working time of the clinical nurse specialist. Calls primarily originated from patients who were in the follow-up phase (43% of calls), a group usually thought to prefer self management.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-12-15.
Abstract P2-13-04: Superior efficacy of anastrozole to tamoxifen as adjuvant therapy for postmenopausal patients with hormone-responsive breast cancer. Efficacy results of long-term follow-up data from N-SAS BC 03 trial
Authors: Imoto S , Osumi S , Aogi K , Hozumi Y , Mukai H , Iwata H , Yokota I , Yamaguchi T , Ohashi Y , Watanabe T , Takatsuka Y , Aihara T
Published: August 2014

Background: Aromatase inhibitors have been shown to be superior to tamoxifen as adjuvant therapy in postmenopausal patients with hormone-responsive breast cancer. Here we report the efficacy results of long-term follow-up data from N-SAS BC 03 trial (UMIN CTRID: C000000056), in which anastrozole was compared to tamoxifen in hormone-responsive postmenopausal early breast cancer patients who had taken tamoxifen for 1—4 years out of a total of 5 years of treatment as adjuvant therapy.

Patients and methods: Out of a total of 706 recruited patients, 696 patients (tamoxifen group, n=345; anastrozole group, n=351) were used as the full analysis set for the present study. The log-rank test was used to compare the two groups in terms of disease-free survival (DFS) and relapse-free survival (RFS), Kaplan-Meier estimates were calculated. The treatment effects were estimated by Cox's proportional hazard model and were expressed as hazard ratios, with associated 95% confidence intervals (CIs).

Results: After a median follow-up of 76.1 months, (range: 1.3–110 months), the unadjusted hazard ratio was 0.87 (95%Cl 0.60–1.26; log-rank p = 0.457) for DFS and 0.77 (95%Cl 0.49–1.22; log-rank p = 0.266) for RFS, both in favor of anastrozole. The estimated hazard ratio (95%CIs) for DFS and for RFS until each time point (right censored data) was as follows: until 30 months: 0.54 (0.30–0.98) and 0.48 (0.23–0.98), until 42 months; 0.65 (0.40–1.06) and 0.53 (0.29–0.97), until 54 months: 0.77 (0.50–1.19) and 0.63 (0.37–1.06), until 66 months: 0.82 (0.55–1.24) and 0.72 (0.44–1.17), until 78 months: 0.83 (0.57–1.23) and 0.73 (0.46–1.17), respectively. The hazard ratios (95%CIs) for DFS and for RFS until 36 months were 0.72 (95%Cl 0.43–1.22) and 0.58 (95%Cl 0.30–1.12), and those after 36 months were 1.06 (95%Cl 0.62–1.81) and 0.98 (95%Cl 0.51–1.88), respectively.

Conclusion: Superior efficacy of anastrozole to tamoxifen in the Japanese population was suggested over a long-term follow-up period. It was the greatest early after switching from tamoxifen and then decreased thereafter.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-13-04.