bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P3-06-16: Predictive biomarker of pathologic complete response to neoadjuvant chemotherapy in triple negative breast cancer
Authors: Kim T , Han W , Moon H-G , Noh D-Y 
Published: August 2014

Abstract
Neoadjuvant chemotherapy has been considered valuable beyond its role in facilitating conservative surgery and improving prognosis associated with pathologic complete response. Predictive factors of response would help to assess the expected individual benefit of this treatment. Bcl-2 and p53 have been mostly investigated predictive biomarker for the efficacy of chemotherapy in breast cancer, however, studies documenting predictive significance of biomarkers in triple negative breast cancer(TNBC) are limited by low n values of patients. Furthermore, studies did not provide consistent result to conclude about predictive value of biomarkers. There is no unique explanation to date to account for such inconsistencies across studies. In the present study, the two most studied inhibitors of apoptosis, the bcl-2 and p53, have been evaluated to assess whether they may play a role in modulating response to triple negative breast cancer to neoadjuvant chemotherapy. From January 2003 to December 2011, 187 patients presenting T1-4 N0-3 M0 primary TNBC were submitted to two different chemotherapeutic regimens before surgery. The first 154 received the doxetaxel/doxorubicin regimen, the remaining 33 were submitted to doxorubicin and cyclophosphamide followed by doxetaxel. The expression of p53, bcl-2 was evaluated in TNBC specimens obtained at diagnosis by core needle biopsy and at postchemotherapy surgery. Overall pathologic complete response(pCR) occurred in 43 of the 187 cases(23%). The pCR rate was superimposable in the patient subgroups with bcl-2-positive or –negative primary tumors. Conversely, p53 expression was significantly associated with higher pCR rate(19.5 vs 73.2%; p = 0.026; in patients with p53- and p53+ breast cancer). In a multivariate regression analysis, after adjusting for tumor and node status, treatment administered, p53 status maintained an independent predictive role for pCR.[relative risk(RR)=6.247, 95% confidence interval (CI)=0.9–39.1] In our homogeneous patient population, pCR was not associated with initial clinical stage, nodal status as well as other clinicopathologic factors. The status of the p53, which is mutated in a high percentage of breast tumors, is a predictive factor for cytotoxic drug activity. By contrast, bcl-2 failed to be related to chemotherapy activity.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-06-16.
Abstract P3-06-29: Change of circulating tumor cells before and after neoadjuvant chemotherapy in patients with primary breast cancer
Authors: Horiguchi J , Takata D , Rokutanda N , Nagaoka R , Tokiniwa H , Tozuka K , Sato A , Kikuchi M , Oyama T , Takeyoshi I 
Published: August 2014

Abstract
Background: Circulating tumor cells (CTCs) in peripheral blood may represent the possible presence of early tumor dissemination. However, relatively few studies were designed to investigate the change of CTC status by adjuvant chemotherapy in operable breast cancer patients.
Patients and methods: Peripheral blood (7.5ml) was collected from 95 patients with stage II/III breast cancer before neoadjuvant chemotherapy (NAC). NAC consisted of anthracycline and paclitaxel chemotherapy and additional trastuzumab treatment for patients with HER2-positive tumors.
Results: The average age of patients was 52.6 year old (median 52.0). One or more CTCs were detected in 18 (18.9%) of 95 patients. CTCs were detected in 6 (12.0%) of 50 patients with clinical stage II disease and 12 (26.7%) of 45 patients with clinical stage III disease. According to tumor subtypes, CTCs were detected in 5 (17.9%) of 28 patients with hormone receptor (HR)-positive and HER2-negative tumors (L subtype), 3 (12.5%) of 24 patients with HR-positive and HER2-positive tumors (L-H subtype), 4 (22.2%) of 18 patients with HR-negative and HER2-positive tumors (H subtype), and 6 (24.0%) of 25 patients with HR-negative and HER2-negative tumors (TN subtype). After NAC, 17 (94.4%) of 18 patients who were CTC-positive before chemotherapy changed into negative status. 30 (31.6%) of 95 patients had a pathologic complete response (pCR) after NAC. There was no correlation between CTC status before NAC and pathological response. At the median follow up of 27 months, distant metastasis was observed in 9 patients (9.5%). Patients with clinical stage III, TN subtype, or non-pCR had a significantly worse disease-free survival (DFS). However, CTC status before NAC was not a significant prognostic factor.
Conclusion: NAC has a significant impact on CTC status irrespective of tumor subtypes. CTC status before NAC was not a significant prognostic factor in this study. The reason of which may be that most of patients showing positive for CTCs before NAC have changed into negative after NAC.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-06-29.
Abstract P3-06-33: Effect of trastuzumab-based therapy on serum activin A levels in metastatic breast cancer.
Authors: Zubritsky LM , Ali SM , Leitzel K , Koestler W , Fuchs E-M , Costa L , Knight R , Laadem A , Sherman ML , Lipton A 
Published: August 2014

Abstract
Background: Only half of HER2-positive metastatic breast cancer patients will respond to first-line trastuzumab-containing therapy, but of these, most will progress within a year. Trastuzumab resistance remains a continuing clinical problem, and better biomarkers and therapies are needed. Activin A is a TGF-beta superfamily member that regulates cell proliferation, apoptosis, differentiation, and immune response. We have previously reported that higher pretreatment serum activin A level predicted reduced progression-free survival (PFS) and overall survival (OS) to first-line trastuzumab, independent of age, line of therapy, CA 15–3, and hormone receptor status (ASCO Ab ID 607, 2012).
Methods: Serum activin A was measured using ELISA (R&D Systems, Minneapolis, MN) in 60 metastatic breast cancer patients before and 1 month after starting first-line trastuzumab-containing therapy. PFS and OS were analyzed using the Kaplan-Meier method and Cox modeling with both continuous and dichotomous (median) serum activin A analyses.
Results: Pretreatment serum activin A levels had a median of 629 pg/mL and an inter-quartile range of 406 to 1791 pg/mL. There was no significant change in activin A levels between pretreatment and one month after starting trastuzumab therapy. Median activin A level at one month was 655 pg/mL, with an inter-quartile range of 405 to 1517 pg/mL. 83% of patients who had low pretreatment activin A levels (below median) had low activin levels at one month, and 83% who had high activin levels (above median) at baseline had high activin A levels at one month. Patients who had high activin A levels at baseline and one month had the worst outcome for both PFS (HR 3.9; median 134 days vs.776 days; p &lt; 0.0001) and OS (HR 6.7; p &lt; 0.0001) when compared to patients with low activin A levels which remained low at one month.
Conclusions: Higher pretreatment and 1 month post-treatment serum activin A predicted for reduced PFS and overall survival in metastatic breast cancer patients treated with first-line trastuzumab-containing therapy. Trastuzumab-based therapy did not have a significant effect on activin A levels at one month. Patients with persistently high activin A levels had significantly worsened outcomes compared to those with low activin A levels. Serum activin A deserves further study to select patients most likely to respond to activin A-targeted therapy.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-06-33.
Abstract P3-07-07: Incidence and survival among breast cancer patients in the United States by race and stage diagnosis: an analysis of national registry data 2000–2009
Authors: Lang K , Huang H , Namjoshi M , Federico V , Menzin J 
Published: August 2014

Abstract
BACKGROUND: This study evaluated incidence and survival among breast cancer (BC) patients in the United States during 2000–2009, by race and stage at diagnosis.
METHODS: The Surveillance, Epidemiology, and End Results (SEER) Program SEER*Stat Database was used for this analysis. SEER is an epidemiologic surveillance system consisting of population-based tumor registries designed to track cancer incidence and survival in the US. The registries routinely collect information on incident cancer cases in areas that represent approximately 25% of the US population. We evaluated age-adjusted (to the 2000 US standard population) incidence (number of cases per 100,000 population), and 1- and 5-year survival among newly diagnosed female breast cancer patients during 2000–2009, by cancer stage (localized, regional, distant and unknown/unstaged) and race (White, Black, Other [American Indians/Alaska Natives or Asians/Pacific Islanders]).
RESULTS: A total of 543,539 cases of female BC were reported to SEER during 2000–2009, with 452,047 cases among Whites (W), 54,310 cases among Blacks (B), and 37,182 among other races (O). The overall incidence was highest for Whites (130.2 per 100,000 population), followed by Blacks (120.1) and other races (59.6–93.2). Similarly, incidence of localized BC was highest among Whites (81.1), followed by Blacks (63.0) and other races (35.4–58.7). Blacks had the highest incidence of regional (43.6 vs. 18.8–40.1), distant (9.7 vs. 3.7–6.0), and unknown stage of BC (3.8 vs. 1.6–3.0) compared to Whites and other races. Incidence of localized BC decreased slightly for Whites (average annual change −0.4%) during 2000–2009; however it increased for all other groups (1.4–1.8%). Incidence of distant BC increased for all races (W: 1.0%, B: 2.3%, O: 3.1–3.8%). Blacks had the lowest one-year and five-year survival for localized, regional and distant BC.

One-year and five-year survival rates were relatively stable during 2000–2009 for regional and localized BC (annual average change: −0.6% to 0.7%), for all races. For distant BC, Blacks had least improvement during 2000–2009 in one-year survival (annual average change 0.03%, vs. 0.6% for Whites and 3.6% for other races), and decreasing five-year survival (annual average change −5.4% vs. 2.2% for Whites and 1.7% for other races).
CONCLUSIONS: Based on US population-based registry data, Blacks had higher incidence of more advanced breast cancer and lower long-term survival for all stages of BC. There is considerable room to improve survival rates for patients with regional and distant BC, especially among Blacks. Further studies evaluating the survival experience of later-stage BC patients based on other key factors, such as age, socioeconomic status, treatment patterns, and tumor characteristics (e.g. ER/HER2 status) are warranted.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-07-07.
Abstract P3-07-11: Retrospective database review of outcomes in invasive lobular carcinoma and invasive ductal carcinoma of the breast
Authors: Shih Y-C , Dillon P 
Published: August 2014

Abstract
Background. Invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) are histologically distinct breast cancer subtypes. While ILC and IDC have similar disease-free survival (DFS) and overall survival (OS), the patterns of metastatic recurrence are suspected to differ due to differing adhesion markers.
Methods. Retrospective review of a cohort of breast cancer patients treated at a tertiary academic medical center from May 1999 to April 2012 was performed. Demographic, pathologic, treatment and follow-up data were collected from a cancer database and the institutional medical records.
Results. There were 179 ILC and 358 IDC (1:2 stage-matched) patients in the study period. Mean age (59 vs. 58 years), gender, race (88% vs. 80% Caucasian), menopause state (71% vs. 66% post-menopausal), and family history (48% vs. 42% positive for breast cancer) were similar in the two groups. Median follow-up was 4.7 years. ILC patients had more negative mammograms upon diagnosis (6.8% vs. 1.4%, p = 0.001), and their breast cancers were more likely to be hormone-receptor-positive/HER2-negative (90% vs. 69%, p &lt; 0.00001). The recurrence rate was the same between ILC and IDC. ILC recurred more often in the abdominal cavity (24.3% vs. 4.1%, p = 0.001), and it recurred similarly to IDC in other sites (bone, lung, liver, central nervous system, and local). Both groups received similar treatments, including number of surgical resections (1.3), positive margins (17%), breast-conservation rate (42% in ILC vs. 49% in IDC), systemic treatment (91% vs. 88%), and taxane use during chemotherapy (71% vs. 69%). The DFS (10.6 vs. 11.4 years), OS (10.2 vs. 11.9 years), and breast-cancer-specific OS (11 vs. 13 years) were not statistically different. In a subgroup analysis, stage IV ILC patients had worse overall survival than stage IV IDC patients (2.9 vs. 6.8 years, p = 0.039). On multivariate analysis, age, stage of disease, hormone receptor status, and systemic therapy were associated with survival, but histology was not.
Conclusions. Compared to ductal breast cancers, lobular breast cancers recur more often in the abdominal cavity. Both ILC and IDC have comparable surgical and medical treatment outcomes, including resection number, positive margin of resection, breast conservation rate, recurrence rate, and survival.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-07-11.
Abstract P3-08-04: Impact of CYP3A variation on estrone levels and breast cancer risk
Authors: Ross GM , Johnson N , Orr N , Walker K , Gibson L , Folkerd E , Haynes B , Palles C , Coupland B , Shoemaker M , Jones M , Broderick P , Sawyer E , Kerin M , Tomlinson I , Zvelebil M , Chilcott-Burns S , Tomczyk K , Simpson G , Willianson J , Hillier S , Houlston R , Swerdlow A , Ashworth A , Dowsett M , Peto J , dos Santos I , Fletcher O 
Published: August 2014

Abstract
Background: Epidemiological studies provide strong evidence for a role of endogenous sex steroids in the etiology of breast cancer. Our aim was to identify common variants in genes involved in sex steroid synthesis or metabolism that were associated with premenopausal hormone levels and breast cancer risk.
Methods: We measured urinary estrone glucuronide (E1G) and pregnanediol glucuronide (PG) using a protocol specifically developed to account for cyclic variation in hormone levels during the menstrual cycle, plasma sex hormone-binding globulin (SHBG) and androgenic precursors in up to 763 healthy premenopausal women. We genotyped 642 single nucleotide polymorphisms (SNPs) in these women; a single SNP was further tested for association with breast cancer risk in data from 10,551 breast cancer case patients and 17,535 control subjects. All statistical tests were two-sided.
Results: rs10273424 mapping approximately 50kb centromeric to the cytochrome P450 3A (CYP3A) cluster (7q22.1) was associated with a 21.8% reduction in E1G levels (P = 2.7 × 10−9) and a modest reduction in breast cancer risk in cases diagnosed at or before age 50 (OR = 0.91; P = 0.03) but not older cases (odds ratio (OR) = 1.01; P = 0.82). A rare non-synonymous SHBG SNP was associated with reduced plasma SHBG levels.
Conclusions: Genetic variation in non-coding sequences flanking the CYP3A locus contributes to variance in premenopausal E1G levels and breast cancer risk in younger cases. Since CYP3A4, the most predominantly expressed CYP3A gene, is responsible for metabolism of endogenous and exogenous hormones and hormonal agents such as tamoxifen, used in the treatment of breast cancer this association may have wider implications.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-08-04.
Abstract P3-10-02: Modulation of mRNA and miRNAs by the novel histone deacetylase inhibitor, CG-1521 disrupts cytokinesis in SUM149PT inflammatory breast cancer cells
Authors: Chatterjee N , Tenniswood MPR 
Published: August 2014

Abstract
Inflammatory breast cancer (IBC) comprises only 2.0% of all breast cancer cases; however it accounts for 8.0% of breast cancer-specific deaths. IBC is highly aggressive, appears at a younger age, and is more difficult to treat than the common forms of breast cancer. By the time the disease is diagnosed, IBC is usually stage 3 and has already metastasized to neighboring lymphatics. Though many tumors are p53 wild type and/or Her2 positive, the median overall survival among women with IBC is less than 4 years even with aggressive multimodal therapy. To develop IBC-specific therapies, we have compared the effects of two hydroxamic acid histone deacetylase (HDAC) inhibitors, Trichostatin A (TSA) and CG-1521 on the biology of the triple negative SUM149PT IBC cell line. In these cells, CG-1521 and TSA induce dose (0–10 µM) and time dependent (0–96 h) increases in the proportion of cells undergoing cell cycle arrest and cell death, in the presence or absence of 17β-estradiol. To identify the genomic targets of CG-1521, we have performed concurrent microarray analyses of mRNA and miRNA expression followed by qPCR validation. In SUM149PT cells, CG-1521 modulates the expression of approximately 935 transcripts: 341 of these transcripts are up-regulated and 594 are down-regulated after 48h of treatment. Gene ontology analysis demonstrates that many of the down-regulated mRNA transcripts encode proteins that are associated with the spindle assembly checkpoint, chromosome segregation and microtubule based processes including KIF4, PRC1, AURKB and KIF23 (MKLP-1). Strikingly, many genes in these ontologies are potentially targeted by a small number of miRNAs (miR-22, miR-1207-5p & miR-494) which are significantly up-regulated by CG-1521, suggesting that the ability of CG-1521 to down-regulate the transcripts associated with spindle formation and cytokinesis may be significantly modulated by miRNA expression. Immunofluorescence microscopy demonstrates that treatment of SUM149PT cells with CG-1521 results in the appearance of elongated midzone structures visualized by phalloidin staining, similar to the phenotype seen by others after siRNA-mediated knockdown of KIF4 in HeLa cells. These data suggest that CG-1521 affects the central mitotic spindle formation, disrupts furrow formation and abscission, arresting the cells in cytokinesis ultimately leading to cell death. Whether these effects are solely mediated through transcriptional mechanisms or whether CG-1521 also directly affects the activity of these proteins through acetylation remains to be determined. Nevertheless, the data show that histone deacetylase inhibitors induce cell death in IBC cells, and suggest that these small molecules may be useful addition to the armamentarium as adjuvants for the treatment of IBC.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-10-02.
Abstract P3-11-01: Matched-pair analysis of patients with male and female breast cancer
Authors: Kim M , Lee SK , Choi M-Y , Kim S , Kim J , Jung SP , Bae SY , Kil WH , Lee JE , Nam SJ 
Published: August 2014

Abstract
Purpose: Male breast cancer (MBC) is extremely rare, accounting for less than 1% of all malignancies in men and only 1% of all breast carcinomas. The treatment and surveillance guidelines on male breast cancers are less recognized. The aim of this study is to evaluate our single institution's experience with MBC over the past 15 years and to contrast differences between female and MBC.
Methods: MBC diagnosed from 1994 to 2010 at the Department of Surgery, Samsung Medical Center (Seoul, Korea) was retrospectively analyzed. Clinical data and tumor characteristics were examined. Each MBC was matched with female counterparts by 1:N varied matching ratio that showed accordance in seven variables (year of diagnosis, age, tumor stage, nodal stage, tumor grade, estrogen receptor(ER), progesterone receptor(PR)).
Results: 39 male/184 female matched-pairs were available for analysis. The median duration of follow-up was 3.8 years. The median age of MBC patients was 50 years and the median size of tumor was 2.0cm. The proportion of positivity of ER and PR status was 97.4% and 84.6%, respectively. Despite of higher positive rate of hormone receptor, the rate of hormone therapy in MBC patients was significant lower than female conterpart (p = 0.002). Men and women with breast cancer had similar disease-free survival (DFS) and disease-specific overall survival (DSS). Five MBC patients had a recurrence during follow up period and 4 of them were expired. The 10-years DFS was 73.1% in men and 80.5% in women (p = 0.348). The 10-years DSS was 74.1% in men and 87.1% in women, respectively (p = 0.207).
Conclusion: This study showed no disease free and overall survival differences between male and female breast cancer patients and revealed that gender is no predictor for survival in breast cancer. Male patients receive obviously less adjuvant treatment compared their female matched patients. It would be better to do more aggressive treatment in MBC to improve the survival outcome.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-11-01.
Abstract P3-11-04: Male breast cancer: Overall survival in a single institution.
Authors: Bello MA , Bergmann A , Costa CRA , Pinto RR , Millen EC , Thuler LCS , Bender PFM 
Published: August 2014

Abstract
Background: Male breast cancer is an uncommon disease and the therapy is mainly based on what is know from female breast cancer. Objective: To investigate the clinicopathologic characteristics of male breast cancer and the overall survival in a single institution.
Methods: The clinical data and survival status of 75 male breast cancer treated in a Brazilian public cancer hospital from 2000 to 2009 were collected. The association with clinicopathological characteristics and overall survival was analyzed using Kaplan-Meier curves and the Cox proportional hazards regression (enter method) was used to assess survival differences after adjusting for confounders. The study was approved by National Cancer Institute Research and Ethics Committee (number 128/11).
Results: The median patient age was 64 years (range 33–86). Estrogen receptor (ER) was positive in 58 (77.3%) patients, while progesterone receptor (PR) were positive in 47 (62.7%). Histology type was ductal infiltrant carcinoma for 57 (76.0%) and 51 (68.0%) patients underwent surgery. The median follow-up period was 43,1 months (range 2.7–147.8). The median survival from the diagnosis of breast cancer was 97.0 months (95%CI 53.6 −140.4) with a 61.7% 5-year overall survival (OS). In the final Cox regression model, independent factors associated with increased risk of death were metastasis at diagnosis (HR = 18.1; 95%CI: 5.9–55.2), ≥ 65 years old (HR = 4.3; 95%CI: 1.7–10.5); tumor stages ≥ IIb (HR = 3.5; 95%CI: 1.3–9.7) and smoking (HR = 1.6; 95%CI: 1.04–2.6).
Conclusions: Invasive ductal carcinoma is the main pathologic type. The median survival from the diagnosis of breast cancer was 97.0 months and metastasis at diagnosis, patient age, tumor stage and smoking are independent prognostic factors.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-11-04.