bluuebunny/crossref_metadata_2025_split huggingface dataset:
P2-12-23: How Should We Assess Tumour Size (T Stage) in Patients with Multicentric/Multifocal Breast Cancer? Results from the NCIC CTG MA.5 Randomized Trial of CEF vs. CMF in Pre-Menopausal Women with Node Positive Breast Cancer.
Authors: Bouganim N , Dong B , Hilton JF , Chapman J-AW , Arnaout A , O'Malley F , Nielsen T , Gelmon K , Yerushalmi R , Levine M , Bramwell V , Whelan T , Pritchard KI , Shepherd L , Clemons M 
Published: June 2012

Abstract
Background
A common clinical conundrum in breast cancer management is whether pathologic T stage in women with multicentric or multifocal disease should be taken as the diameter of the largest focus or as the sum of all foci in the breast. Most staging systems, such as the American Joint Committee on Cancer (AJCC), simply use the largest tumour focus for staging. We examine here the impact of alternate methods of estimating tumour size including measures of total tumour size, volume and surface area.
Methods: NCIC CTG MA.5 is a randomized trial of CEF versus CMF in pre-menopausal women with node positive breast cancer.
Median follow up is 10 years. Pathologically reported patient tumour dimensions for up to 3 foci were utilized to examine the effects of tumour size on Breast-Cancer-Free-Interval (BCFI). BCFI is defined as the time from randomization until recurrence: first local invasive or DCIS, regional, distant, contralateral invasive or DCIS. Tumour size was estimated as 1) pathologic T stage as per AJCC criteria; 2) largest dimension of largest tumour focus (cm); 3) sum of largest dimension(s) of tumour foci (cm); 4) sum of surface area(s) of tumour foci (cm2), and 5) sum of volume of tumour foci (cm3). Step-wise forward unstratified Cox regression was used to assess the different effects of tumour size.
Results: This study accrued 710 patients, 37% with T1 tumours, 52% with T2 tumours and 9% with T3 tumours; 61% had 1 to 3 positive lymph nodes. 59% hormone receptor positive. Higher pathologic T stage (p=0.001) and greater surface area (p=0.02) were associated with shorter BCFI, as was lymphovascular invasion (p=0.03), and # of lymph nodes involved (p&lt;0.0001). Administration of anthracycline therapy led to significantly longer BCFI (0.003). The sum of largest tumour sizes (p=0.33) and sum of tumour volume (p=0.34) were not significantly associated with BCFI. Additionally, when the less complete locally reported tumour grade data were included, higher tumour grade was associated with shorter BCFI (p&lt;0.0001).
Conclusions: Consideration of multicentric and multifocal disease was an important adjunct to standard pathologic tumour size as was estimation of tumour surface area in this chemotherapy trial of node positive premenopausal women. However, simply adding together the diameters of tumours in patients with multicentric or multifocal disease did not add any additional prognostic information in this high risk patient population.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-12-23.
P2-14-08: Hormone Receptor Status and Breast Cancer Survival among Hispanic and Non-Hispanic White Women over 10 Years of Follow-Up.
Authors: Denkhoff SR , Baumgartner KB , Yang D , Pinkston CM , Baumgartner RN 
Published: June 2012

Abstract
Introduction: The joint presence or absence of expression of estrogen receptor (ER+/−), progesterone receptor (PR+/−), and Her2neu (Her2+/−) is now widely used to define the hormone receptor (HR) phenotype of breast tumors. HR phenotype influences breast cancer etiology, response to treatment and survival, which may vary by ethnic group. The triple negative phenotype (TNT: ER-/PR-/Her2-) is associated with the poorest survival and is more common in African American than white women. Few studies have assessed how HR status differs by Hispanic (H) versus non-Hispanic white (NHW) ethnicity in relation to survival.
Methods: We analyzed data from the New Mexico site of the ‘Health, Eating, Activity and Lifestyle’ (HEAL) study for breast cancer mortality over 10 years of follow-up by HR phenotype and ethnicity for 126 H and 408 NHW women with invasive (I-IIIA), first primary breast cancer. Kaplan Meier curves were used to describe differences in survival by ethnicity and HR phenotype (ER+/PR+/Her2+, referent; ER+/PR+/Her2-; ER-/PR-/Her2+; and ER-/PR-/Her2-). Hazard ratios were estimated using Cox regression models stratified by phenotype and ethnicity, adjusting for age at diagnosis, stage, and diagnosis of another cancer (yes/no).
Results: Kaplan Meier (KM) analysis indicated that the TNT phenotype was associated with poorer survival, particularly during the first 5 years, although the difference was not statistically significant after 10 years of follow-up (p=0.36). The prevalence of TNT was higher in H (10.3%) than NHW (6.6%) women, and H also tended to poorer survival than NHW women (p=0.17). In multivariate-adjusted models, women with a TNT phenotype had a 26% increased risk of death (HR=1.26 95% CI 0.62−2.6). In NHW women, the risk was 12% (HR=1.12 95% CI 0.43−2.9). Among H women, those with a TNT phenotype had a 17% increased risk of death (HR=1.17 95% CI 0.35−3.8) while those with ER-/PR-/Her2+ had a 46% increase (HR= 1.46 95% CI 0.40−5.3).
Discussion: Although this analysis is limited by small numbers, the results suggest that H women may have worse 10-year survival rates than NHW women and that women with TNT have a higher risk of death regardless of ethnicity. These differences in survival could be due to a higher rate of recurrence or issues related to treatment. This study suggests that there is an ethnic disparity in survival by HR subtypes that should be examined in a larger population based study.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-14-08.
P2-15-02: Are We Performing More Mastectomies on Women Diagnosed with Invasive Breast Cancer?
Authors: Lo MCI , Hariri B , Gandamihardja T , Lewis J , Hogben K 
Published: June 2012

Abstract
Introduction: Surgical management of breast cancer has changed over the past several decades; breast-conserving surgery has become widely accepted. Mastectomies, however, are still being performed as part of the management of breast cancer. The aim of this study was to investigate the indications for mastectomy in women with invasive breast cancer within our institution.
Method: A systematic review of all new patients with invasive breast cancer treated with surgical intervention at our breast unit in the years 2000, 2005 and 2009 was performed. Using our databases, patient demographics, tumour characteristics and reasons for mastectomy were examined. Screen-detected and symptomatic patients were included in the study. Patients excluded were those with incomplete data and recurrent breast cancer.
Results: A total of 584 patients (F:M, 576:8); with cancer types which included invasive ductal carcinoma (n=501, 84%), invasive lobular carcinoma (n=51, 9%), invasive tubular carcinoma (n=27, 5%) and sarcomas (n=5, 1%) were studied.

Conclusion: In our institution, the majority of patients with screen-detected invasive breast cancer fulfilled the criteria to have breast-conserving surgery; mastectomy rate for screen-detected cancers remained stable. However, we found that in the symptomatic patient group, there was an increase in mastectomy rate from 16% (n=170) in 2000 to 52% (n=225) in 2009. Despite this trend, our results were still in keeping with the national standard as illustrated by the National Cancer Intelligence Network, where they noted that in 2006, 52% of symptomatic patients with invasive breast cancer underwent mastectomy in the United Kingdom.
The reason for a higher mastectomy rate in symptomatic patients compared to screen-detected patients in 2009 is multifactorial. We found that a larger proportion of symptomatic patients presented with larger tumours and tumours which were multifocal in nature. Other factors which may have contributed included more accurate estimation of tumour size by imaging (e.g. MRI) and patient choice.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-15-02.
P2-16-14: Skin Sparing Mastectomy and Immediate Latissimus Dorsi Flap Reconstruction: Patient Reported Outcome and Factors Affecting the Highest Patient Satisfaction.
Authors: Kim Z , Kang S-G , Lee J , Kim SY , Lim CW , Lee MH 
Published: June 2012

Abstract
Background: Skin sparing mastectomy (SSM) and immediate breast reconstruction (IBR) with latissimus dorsi (LD) flap is a tailored surgical procedure for breast cancer patients. In this study the oncologic safety, morbidities, and aesthetic results of SSM and LD IBR, as regards to patient satisfaction, were assessed.
Material and Methods: Between March 2000 and February 2011, single surgeon performed SSM and IBR for 145 patients. Eighty-five patients completed the patient satisfaction survey, and 65 patients with SSM and LD IBR were included. The patients were divided into 2 groups according to their degree of satisfaction, and a stratified analysis was performed.
Results: The mean age of the patients was 48.4 years (range, 21–74), and the pathologic results were infiltrating ductal carcinoma (n=48, 73.8%), ductal carcinoma in situ (n=15, 23.1%), and others (n=2, 3.1%). After a mean follow-up of 34 months (range, 1.6−89.9) no local recurrence occurred, and there were no skin necrosis or LD flap loss. Donor site morbidities were seroma (n=8, 12.3%), scarring (n=8, 12.3%), and back pain (n=6, 9.2%).

Fifty patients (76.9%) were satisfied with their surgical outcomes, and 40% reported their degree of satisfaction as excellent. Breast symmetry (P&lt;0.001), nipple cosmesis (P&lt;0.001), surgeon assessment (P&lt;0.001), observer assessment (P&lt;0.001), and visual difference of bilateral breasts (P=0.021) were factors that affected the highest patient satisfaction.

Conclusion: The present study demonstrated that our SSM and LD IBR was oncologically safe, and was associated with low morbidity rates. LD flap per se, without a prosthetic implant, could sufficiently produce a high level of patient satisfaction. Accurate surgical techniuqes and careful consideration for breast symmetry and nipple cosmesis would be the key to meet the patient's expectations and enhanced quality of life.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-16-14.
P2-18-06: Conventional Trastuzumab Is an Antagonist of Natural Killer Cells: Making the Case for Fucose-Depleted Trastuzumab.
Authors: Listinsky JJ , Siegal GP , Listinsky CM 
Published: June 2012

Abstract
The discovery of the HER2 receptor and later the development of trastuzumab (an anti-HER2 antibody) were major advances leading toward the treatment of a significant proportion of human breast cancers. Trastuzumab (Herceptin®) is a humanized monoclonal IgG1 whose discrete antitumor effects are exerted through the 2 main components of the antibody. Trastuzumab's FAB portion binds to the HER2 extracellular domain, interrupting HER2 signaling. The FC portion then engages the activating receptor (FcγRIIIa) on an effector cell, usually a natural killer (NK) cell and instigates a lytic attack via antibody-dependent cellular cytotoxicity (ADCC).
The value of trastuzumab in breast cancer therapy is well established, but, there are limitations to the drug's effectiveness. These include: (1) unresponsive tumors with low or equivocal HER2 expression; (2) de novo (primary) resistance to therapy in over 50% of patients with HER2−positive tumors; (3) frequent emergence of secondary resistance often after short exposure periods; (4) competition of plasma IgG proteins with antibodies for binding to the activating FC receptors on NK cells; and (5) the high cost of trastuzumab treatment, raising concerns for the economic sustainability of this form of therapy.
Trastuzumab and other therapeutic antibodies share a structural feature that is critical to their effectiveness: a specific oligosaccharide which is covalently linked to the FC region at asparagine 297 (Asn297) in each of the 2 heavy chains. This oligosaccharide, a mannosyl-chitobiose core, is “core-fucosylated” with a single α-L-fucose (fucose) sugar attached via an α(1,6) linkage. In 2002, Shields et al. developed a novel form of trastuzumab which lacked core fucose in the Fc region [J Biol Chem 2002; 277: 26733–40]. When compared to conventional trastuzumab, the fucose-depleted trastuzumab was 43-fold more potent in provoking ADCC against HER2−expressing human breast cancer cells in vitro. Subsequent studies with several monoclonal antibodies have elucidated the role of core fucose in inhibiting ADCC, by reducing the affinity of trastuzumab's Fc portion for the activating FC receptors located on effector cells. The superior ADCC effect of fucose-depleted trastuzumab has now been demonstrated in vivo [Junttila TT et al., Cancer Res 2010; 70: 4481–4489].
We review both in vitro and in vivo evidence from multiple laboratories (working with trastuzumab, rituximab and other therapeutic antibodies) to argue that fucose-depleted trastuzumab offers several potential advantages over conventional trastuzumab. Such advantages in clinical use, we postulate, include (1) treatment of patients with trastuzumab-resistant tumors, (2) treatment of patients with equivocal or low expression of HER2, and (3) decreased cost of treatment.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-18-06.
P3-01-07: A Murine Xenograft Model for the Study of Ciclooxygenase-2 Expression and Function in Human Breast Cancer.
Authors: Solano AR , Orlando UD , Garona J , Ripoli GV , Duarte AB , Maloberti PM , Avagnina MA , Alonso DF , Gomez DE , Podesta EJ 
Published: June 2012

Abstract
BACKGROUND: ciclooxygenase-2 (COX-2) has been suggested as a necessary component of the cellular and molecular mechanisms behind breast cancer cell motility and invasion The potential therapeutic benefit of COX-2 inhibitors in a range of cancers is being seen as a great promise however, there have been recent concerns about potential cardiotoxicity. Thus, there is an urgency to develop new inhibitors exhibiting a better risk/benefit ratio.
Acyl-CoA synthetase 4 (ACSL4), belongs to a five-member familyof enzymes that esterifies mainly arachidonic acid into acyl-CoA. We have provided first-time evidence demonstrating that, ACSL4 is the key enzyme that regulates the induction of COX-2, the production of prostaglandin E2 (PGE2) and the proliferation and metastatic potential of breast cancer cells. Therefore, the aim of the study was the development of an in vivo model of human breast tumor xenografts for the study of the regulation of COX-2 expression and action.
RESULTS: stable transfection of MCF-7 cells with ACSL4 cDNA under the control of tetracycline (MCF-7 Tet-off-ACSL4) resulted in a significant increase in the expression of COX-2. The increment in COX-2 expression registered in MCF-7 Tet-off-ACSL4 cells is accompanied with an increase in the production of PGE2, and the proliferation and metastatic potential of cancer cells. Next, we tested whether the injection of MCF-7 Tet-off/ACSL4 cells into nude mice resulted in tumor development.
The results of those experiments demonstrate that MCF-7 Tet-off/ACSL4 cells develop into murine mammary tumors whereas cells transfected with the MCF-7 Tet-off empty vector did not. Interestingly, treatment of nude mice with tetracycline resulted in tumor growth inhibition. The results show that the sole transfection of ACSL4 results in a phenotype change that endows the cells with the capacity to develop into tumors when injected into nude mice. Tumor volume (TV) at day 70 reached 468.4 ± 189.3mm3. Treatment with tetracycline reduced TV to 189.3 ± 65.9mm3 (p&lt;0.05). The growth rate between days 45–70 was 12.30 mm3/day. Tumors were classified as Basal-like subtypes.
We have also observed an inhibition of proliferation and migration of MDA-MB-231 cell cultures when exposed to a combination of ACSL4 and COX-2 inhibitors. Interestingly, the compounds assayed markedly reduced cell proliferation and migration at concentrations that are less effective when used alone. These results point to an effect that has the advantage of exposing the cells to lower drug concentrations.
CONCLUSION: Based on our results, we hypothesize that ACSL4 and COX-2 could constitute potential therapeutic targets for the control of tumor growth. Our animal model of mammary tumors constitutes a proper platform for the study of those therapies.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-01-07.
P3-01-13: Leptin Modulates the Response to Tamoxifen Treatment in ER-Positive Breast Cancer Cell Lines.
Authors: Yom CK , Han W , Kim S-W , Kim DW , Kang E , Noh D-Y 
Published: June 2012

Abstract
Obesity is known to a risk factor for breast cancer in postmenopausal women. Leptin is a potent adipokine which mainly produced by adipose tissue and leptin signaling plays a significant role in tumor development and invasion of breast cancer. In recent study, leptin induced aromatase gene expression, elevating aromatase activity and increasing estrogen synthesis in MCF-7 cell. Leptin was also able to enhance estrogen receptor α (ERα)-dependent transcription by decreasing ERα ubiquitination and degradation. And this imply that lepin may play some role on hormone resistancy of ER-positive breast cancer. The aims of this study is to evaluate whether leptin modulates the effect on tamoxifen treatment in estrogen receptor (ER)-positive breast cancer cell.
At first, we examined leptin and Leptin receptor(Ob-R) expression by western blot assay in various breast cancer cells and cell proliferation by cell viability assay in combination with leptin and tamoxifen under estradiol (E2) treatment. And we analyzed the effect of leptin on the response of tamoxifen treatment in ER-positive breast cancer cells and which result from activation of ERK1/2 and STAT3 signaling pathway in leptin treatment.
We used the MCF-7 (ER+/Leptin +/Ob-R+) cell and T-47D (ER+/ Leptin +/Ob-R-)cell to compare the effect of leptin according to Ob-R status. Leptin had the proliferative effect on MCF-7 comparing to control and T-47D cells. But leptin had no additional effect on both cells in combination with tamoxifen or E2. Interestingly, Leptin had an inhibitory effect on tamoxifen especially in high E2 (20 nM) setting in both MCF-7 and T-47D cells. In cell signaling, when leptin was added to combination treatment of E2 and tamoxifen, the total- and phospho- of ERK1/2 was more activated than combination without leptin in MCF-7. In case of STAT3, activation of total- and phospho-STAT3 were relatively remarkable comparing to combination without leptin, when the three agents are combined to treatment in MCF-7. On the contrary, in T-47D cell, when leptin added to combination of E2 and tamoxifen, leptin relatively induced the activation of total ERK1/2 comparing to combination of E2 and tamoxifen without leptin. But this result was not shown in phospho-ERK1/2 signaling. In STAT3 signaling, same results was noted in T-47D.
We concluded that leptin interfere with the anti-estrogenic effects of tamoxifen under E2 condition both in MCF-7 and in T-47D ER-positive breast cancer cells through activation not only Ob-R but also crosstalk other signaling system. These results imply that inhibition of leptin expect to enhance the hormone response in ER-positive breast cancer, and therefore, to be the promising way to overcome hormonal resistance.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-01-13.
P3-05-06: Progression of Breast Cancer Molecular Subtypes through Different Clinical Stages.
Authors: Ciruelos EM , Castaneda CA , Andrés E , Gomez HL , Castellano D , Mendiola C , Manso L , Ghanem I , Farfan C , Cortes-Funes H 
Published: June 2012

Abstract
Purpose : Molecular classification of breast cancer (BC) through immunohistochemistry classifies patients globally in 4 subtypes with similar features and prognosis. The present study was designed to compare features of BC subtypes in early versus locally advanced clinical stages. A secondary objective was compare molecular subtypes of the primary vs recurrences.
Methods : The study included 1621 patients with non-metastatic invasive BC that were consecutively diagnosed at Hospital Universitario 12 de Octubre, Madrid, between 1997 and 2007. Luminal A was defined as ER+ and PR+, HER2−negative and Ki67 &lt; 14%. Luminal B was defined as PR-negative, HER2−positive or ki67≥14%. HER2 was defined as ER and PR-negative, and HER2−positive.Triple negative (TN) were tumors with ER, PR and HER2 -negativity. Clinicopathological characteristics and outcomes were retrospectively reviewed. Variables were compared with the X2 test, and survival curves were evaluated with Kaplan-Meier method.
Results : Most patients were diagnosed as T1 (48%) and T2 (39.7%) clinical stages, and classified as Luminal B (49%) and Luminal A (29%). GIII frequency increased from T1 to T3-4 in Luminal A (p=0.002), and Luminal B (p=0.051) subtypes, but not in HER2 (p=0.867) or TN (p=0.53).

Molecular subtypes carry significant different prognosis (DFS and OS) in all T stages except for T1a cases. When T3-4 and T1 stages of the same molecular subtype were compared, a significant shorter DFS were found for more advanced stages in the Luminal A (p=0.0002), Luminal B (0.0001) and TN (0.0017), but not for HER2 (p=0.54) subtype. And, similar results were found for OS.
We compared molecular subtypes in the primary tumor and in the metastatic site in 83 cases (excluding contralateral recurrences) and found change of phenotype in 54% of the cases. Changes from Luminal A to a more aggressive phenotype were more frequent than in the opposite situation (14 vs 2 cases).
Conclusion : Despite the molecular classification of early-stage BC that classifies patients in well-defined prognostic subgroups, tumors are continuously changing and tumor behavior becomes more aggressive through progression. Therefore, even tumors with favorable phenotype could loss their good prognosis in locally advanced stages. Obtention of tumor tissue at metastatic sites is also mandatory to a better selection of systemic therapies in relapsed patients.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-05-06.