bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P1-14-03: Overall survival results of a multicenter randomized phase II study in locally advanced breast cancer patients treated with or without neoadjuvant Trastuzumab for HER2 positive tumor (Remagus 02 trial)
Authors: Giacchetti S , Pierga J-Y , Asselain B , Delaloge S , Brain E , Espié M , Mathieu M-C , Bertheau p , de Cremoux P , Tembo O , Marty M 
Published: August 2014

Abstract
Background: Trastuzumab is indicated in neoadjuvant setting in locally advanced HER2 positive breast cancer patients (Gianni L. Lancet 2010). There is no data on the impact of the use of neoadjuvant Trastuzumab (T) compared to adjuvant T on survival.
Patients and methods: From May 2004 to October 2007, 341 stage II-III breast cancer patients were included in a phase II randomized trial and received 4 cycles (c) of epirubicin (75 mg/m2 d1)–cyclophosphamide (750 mg/m2 d1) q 3 w followed by 4 (c) of docetaxel (100 mg/m2 d1) q 3 w. Pts with HER2+++ tumor (120 pts) were randomized to receive or not neoadjuvant T combined with docetaxel. From September 2005, all pts with HER2+cancer received adjuvant T for a total of 18 c (106 pts). All pts with hormone receptors positive tumor received hormonal treatment according to menopausal status (Pierga et al BCRT 2010). We report here overall survival (OS) and disease free survival (DFS) data at 5 year and associated prognostic factors.
Results: At a median follow up of 49 months, the median DFS was not reached for the whole population and was statistically superior for the HER2 positive cancer patients treated with chemotherapy plus neoadjuvant T compared to the other groups, p = 0.018. The median OS is not reached for the whole population and is statistically higher in HER2 positive tumor group compared to HER2 negative group (p = 0.00077). For 106 HER2 positive breast cancer patients who had received one year of complete trastuzumab treatment, there was no significant difference in OS and DFS between pts who started T in neoadjuvant setting versus in adjuvant setting. DFS and OS were not significantly influenced by pathological Complete Response rate (pCR) (respectively, p = 0.22 and p = 0.56). At multivariate analysis including 6 factors (age, tumor size, clinical lymph node, ER, PgR), factors which influenced OS were tumor size (p = 0.03) and ER expression (p = 0.06) and for DFS, clinical lymph node status (p = 0.049) and PgR expression (p = 0.046).
Conclusion: pCR is not a surrogate of survival in the HER2+subgroup. HER2 positive breast cancer pts receiving trastuzumab have a significant higher OS than those with HER2 negative tumors. OS and DFS do not seem to differ between the neoadjuvant T group and the T adjuvant group.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-14-03.
Abstract P1-14-12: Response to neoadjuvant chemotherapy and prognosis of primary breast cancer according to intrinsic subtype
Authors: Kochi M , Ito M , Ohtani S , Higaki K 
Published: August 2014

Abstract
Background: Response to neoadjuvant chemotherapy of primary breast cancer differs across intrinsic subtypes and is considered as a useful surrogate indicator for prognostic prediction, while some subtype populations seems to take different course.
Methods: We classified 364 primary breast cancer patients, who received neoadjuvant chemotherapy after 2002 at our institute, to 5 intrinsic subtype groups; Luminal A type (LA), Luminal B type (LB), Luminal Her2 type (LH), Her2 type (Her2) and triple negative (TN), according to hormonal sensitivity, Her2 status, and cancer proliferation. We evaluated their pathological response to neoadjuvant chemotherapy by response criteria of Japanese Breast Cancer Society. Pathological complete response (pCR) is defined as Necrosis or disappearance of invasive cancer of breast in this study, approving residual non-invasive component of breast or axillary lymph node metastasis. We also examined disease free survival (DFS) and overall survival (OS) by each subtypes statistically, using Kaplan-Meier method and Log-rank test.
Results: Number of patients in each subtype were as follows; LA: 141 patients, LB: 41 patients, LH: 38 patients, Her2: 54 patients, and TN: 90 patients. Surveillance period is 4–105 months (median: 37 months). Most of cases in all subtypes received both anthracycline and taxane. 27 cases in LH (71.1%) and 48 cases in Her2 (88.9%) were treated with trastzumab. 7 cases in LA (5.0%), 4 cases in LB (9.8%), 9 cases in LH (23.7%), 31 cases in Her2 (57.4%), and 26 cases in TN (28.9%) achieved pCR. pCR rate was significantly high in Her2 and TN (p &lt; 0.05). LA, LB, LH showed no significant differences in DFS and OS between pCR group and non-pCR group (LA; DFS p = 0.929 OS p = 0.663, LB; DFS p = 0.189 OS p = 0.552, LH; DFS p = 0.508 OS p = 0.691). In Her2 group, pCR group tended to show better prognosis, but there were no significant differences (Her2; DFS p = 0.107, OS p = 0.343). In TN group, pCR group showed significantly better prognosis (TN; DFS p = 0.046, OS p = 0.040), which indicates the correlation between response to neoadjuvant chemotherapy and prognosis.
Conclusion: Our results indicate the correlation between response to neoadjuvant chemotherapy and prognosis in TN breast cancer.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-14-12.
Abstract P1-14-15: Recent experience of neoadjuvant chemotherapy according to breast cancer subtype: experience from a large United Kindgom teaching hospital
Authors: Rattay T , Kaushik M , Ahmed S , Shokuhi S 
Published: August 2014

Abstract
INTRODUCTION: The most recent United Kingdom (NICE, 2009) guidelines recommend neoadjuvant chemotherapy as the most appropriate initial treatment for locally advanced breast cancer followed by mastectomy. Neoadjuvant chemotherapy should also be offered to patients with early breast cancer who are considering breast conserving surgery that is not advisable at presentation. However, the evidence base is still gathering. This study reviews the recent experience of neoadjuvant chemotherapy in a large United Kingdom breast unit according to breast cancer subtype.
METHODS: Retrospective chart review of patients who received neoadjuvant chemotherapy for breast cancer at University Hospitals of Leicester between January 2008 and March 2011. Patients were identified from the unit database. Breast cancers were typed according to immunehistochemical marker profile: luminal A (ER or PR positive, HER2 negative), luminal B (ER or PR positive, HER2 positive), triple negative (ER and PR negative, HER2 negative), and HER2 positive (ER and PR negative, HER2 positive).
RESULTS: Of 2,489 new patients with breast cancer seen during the study period, 153 patients received neoadjuvant chemotherapy. 20 patients had lobular-type cancers, and the remaining 133 patients had ductal- or mixed-type histology. 101 patients had locally advanced disease and 52 patients presented as early breast cancer. 24 of all patients (15 %) achieved complete pathological response. 18 patients (12 %) never proceeded to surgery, eight of whom died during the study period. In total to date, 23 patients (15 %) have died including one death due to complications from chemotherapy. Of 120 patients initially scheduled for mastectomy, the tumor was downsized in 26 patients (22 %) so that they were able to undergo breast conserving surgery (BCS), with margins involved in six patients. The outcome of neoadjuvant chemotherapy according to breast cancer subtype is presented (Tables 1 and 2).

CONCLUSIONS: In our experience, patients receive neoadjuvant chemotherapy for breast cancer for a variety of indications. Compared to our standard population of breast cancer patients, early mortality remains relatively high, particlularly in the hormone receptor negative subtypes. BCS conversion rates were similar across breast cancer subtypes, but BCS was less likely to be successful in the Luminal A group. Luminal A cancers were also significantly less likely to achieve pCR after neoadjuvant chemotherapy. Breast cancer subtype should be taken into account when scheduling patients for neoadjuvant chemotherapy.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-14-15.
Abstract P1-15-02: Febrile neutropenia (FN) risk assessment and granulocyte colony-stimulating factor (G-CSF) guideline adherence in patients with breast cancer – results from a German prospective multicentre observational study (PROTECT)
Authors: Steffens C-C , Eschenburg H , Kurbacher C , Goehler T , Schmidt M , Eustermann H , Schaffrik M , Otremba B 
Published: August 2014

Abstract
Background: FN is a dose-limiting toxicity of chemotherapy which can affect patient (pt) outcomes. EORTC guidelines recommend G-CSF primary prophylaxis when the overall FN risk assessment is ≥20%. We evaluated risk assessment and guideline adherence (prophylaxis in high-risk pts) in clinical practice among breast cancer patients.
Methods: Eligible pts were enrolled consecutively at centres selected based on experience and geographical spread. Key inclusion criteria were diagnosis of solid tumour or lymphoma, physician-assessed overall FN risk ≥10% (chemotherapy risk plus individual risk factors per EORTC guidelines), and planned primary (PPP) or secondary (PSP) prophylaxis with pegfilgrastim. Pegfilgrastim administered &gt;3 days after chemotherapy completion was classified as therapeutic use. The primary objective was to describe the proportion of pts with an investigator-assessed overall FN risk of &gt;20% or 10–20% receiving PPP or PSP. Secondary objectives included evaluating FN incidence and chemotherapy dose reductions/delays. Data from breast cancer patients only are reported, and prophylaxis in high-risk patients was determined to evaluate guideline adherence.
Results: 1003 pts were enrolled from Nov 2007 to Sept 2010. Mean (±SD) age was 54.4 (±11.2) years, almost all pts (99%) were female. Treatment intent was deemed curative by the investigator in 91% of pts. The investigator-assessed FN risk was &gt;20% in 505 (50%) pts and 10–20% in 414 (41%) pts. Despite eligibility criteria, 84 (8%) pts were assessed by investigators as &lt;10% risk; reasons for inclusion of low-risk pts were not documented. Measured baseline patient risk factors were similar between PPP and PSP pts, and PPP and PSP pts were equally likely to receive chemotherapy with curative intent (92% vs 89%) and less likely to have received prior chemotherapy (11% vs 20%). 100 pts (10%) experienced FN, 43/680 (6%) in the PPP and 53/254 (21%) in the PSP group. 45 (4%) pts experienced FN-related dose reductions or dose delays, with 22/680 (3%) in the PPP group and 22/254 (9%) in the PSP group. In the subgroup of pts assessed as high FN risk, PPP was administered to fewer pts than planned and PSP to more pts than planned (Table).

Conclusion: Adherence to G-CSF guidelines, and reasons for differences between planned and administered prophylaxis warrants further investigation. Comparison of outcomes between prophylaxis groups should be interpreted with caution; however, FN incidence remained low with pegfilgrastim PP among breast cancer pts in German clinical practice.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-15-02.
Abstract P2-01-04: Long term independent prognostic impact of circulating tumor cells detected before neoadjuvant chemotherapy in non-metastatic breast cancer: 70 months analysis of the REMAGUS02 study
Authors: Bidard F-C , Delaloge S , Giacchetti S , Brain E , de Cremoux P , Vincent-Salomon A , Marty M , Pierga J-Y 
Published: August 2014

Abstract
Background: Circulating tumor cells (CTCs) isolated by CellSearch® from peripheral blood of metastatic breast patients have been shown as strong independent prognostic factor for progression-free and overall survival. With this technique, the REMAGUS02 prospective multicentric study was the first to report that CTC detection (≥1CTC/7.5ml) before and/or after neoadjuvant chemotherapy was independently associated with distant metastasis-free survival (DMFS, 18 months follow-up, Pierga CCR 2008) and with overall survival (OS, 36 months follow-up, Bidard Ann Oncol 2010).
Patients and Methods: In 115 non-metastatic patients diagnosed with large operable or locally advanced breast cancer, we prospectively detected CTC using the CellSearch system before and after neoadjuvant chemotherapy in the REMAGUS02 trial (Pierga, BCRT 2010). For this report, survival analyses were performed at a median follow-up of 70 months.
Results: After a median follow-up of 70 months, 20 distant metastatic relapses and 14 deaths have been observed among the 115 patients included. CTC detection before chemotherapy (in 23% of patients) is an independent prognostic factor for both DMFS [p = 0.03, relative risk (RR)=3.2] and OS [p = 0.05, RR = 3.7] in multivariate analyses, together with triple negative tumor status. At long-term, CTC detection after chemotherapy (17%) had no clear prognostic significance (p = 0.15 and 0.22, respectively). Complete pathological response as well as tumour size and all other variables tested did not appear as predictive in this model.
Conclusions: Baseline CTC detection is a new independent prognostic factor in the neoadjuvant setting, and is, in this trial, superior to pathological tumor response to predict the survival of non-metastatic breast cancer patients. We confirm therefore our previous results reported with shorter follow-up.
Supported by PHRC AOM/2OO2/02117, Pfizer inc., Roche, sanofi-aventis. ISRCTN10059974
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-01-04.
Abstract P2-01-08: Different numbers and prognostic significance of circulating tumour cells in patients with metastatic breast cancer according to immunohistochemical subtypes.
Authors: Peeters DJ , van Dam P-J , Wuyts H , Van den Eynden GG , Jeuris K , Prové A , Rutten A , Peeters M , Pauwels P , Van Laere SJ , Hauspy J , van Dam PA , Vermeulen PB , Dirix LY 
Published: August 2014

Abstract
Introduction: The enumeration of circulating tumour cells (CTCs) with the EPCAM-based CellSearch system has prognostic significance in patients with metastatic breast cancer (MBC). However, breast cancer has been shown to be a molecularly heterogeneous disease. The aim of this study was to assess potential differences in the detection and prognostic significance of CTCs according to the immunohistochemically defined molecular subtypes of breast cancer.
Methods: CellSearch CTC counts were obtained from 110 patients with MBC prior to first line systemic treatment, treated at GZA Hospitals Sint-Augustinus between november 2007 and december 2011. Clinicopathological variables were prospectively entered in a database. Based on the St-Gallen surrogate definitions of intrinsic breast cancer subtypes (Goldhirsch et al. Ann Oncol 2011), patients were divided in 5 groups: luminal A (ER/PR+, HER2−, Bloom-Richardson histological grade I-II), luminal B – HER2 negative (ER/PR+, Her2−, grade III), luminal B – HER2 positive (ER/PR+, HER2+, any grade), HER2 positive – non luminal (ER/PR−, HER2+), and triple negative (TN) (ER/PR−, HER2−). Differences in progression free survival (PFS) and overall survival (OS) according to the FDA approved prognostic cut-off of ≥5 CTC/7.5 ml blood were estimated using Kaplan Meier and Cox proportional hazard statistics.
Results: CTC were detected in 78 of 110 (71%) patients. Higher detection rates and numbers of CTC were observed in patients with luminal A and TN breast cancer as compared to patients with luminal B and HER2 positive disease. However, no differences in positivity rates were observed between molecular subtypes according to the 5 CTC prognostic cut-off point (table 1). After a median FU time of 3.1 years, 39 patients had died. In the total study population, the presence of ≥5 CTC was an independent predictor of PFS and OS in multivariate analysis (PFS: HRCTC≥5=2.236 (1.366–3.658), p = 0.001; OS: HRCTC≥5=3.180 (1.553–6.509), p = 0.002). When analyzing subgroups separately, a lower prognostic power was observed in the HER2 positive and luminal B subgroups.

Conclusion: Significant differences were observed in the detection and prognostic significance of EPCAM positive CTC according to the immunohistochemically defined breast cancer subtypes. Interestingly, CTC were detected more frequently in patients with luminal A and TN tumors. Furthermore, our data suggest a lower prognostic significance of CTC evaluation in HER2 positive patients with MBC. Our data independently confirm those reported by Giordano et al. (Ann Oncol 2010) in a large clinically uniform population of patients with MBC before the start of first-line treatment.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-01-08.
Abstract P2-04-03: A robust transgenic mouse model to study male breast cancer.
Authors: Krause S , Lurvey HL , Tobin H , Ingber DE 
Published: August 2014

Abstract
Male breast cancer accounts for about 1% of all breast cancers and even though it is a rare disease, the incidence rate has increased steadily during the past 20 years. Study of the male form of the disease has been hampered by a lack of relevant animal models as it is commonly believed that male mammary glands do not contain ducts. Female FVB C3(1)-SV40Tag transgenic mice spontaneously develop hyperplastic mammary lesions that progress to invasive mammary tumors, whereas most of the transgenic males develop prostatic hyperplasia that progresses to adenocarcinoma. However, upon closer examination, we discovered that approximately 45% of transgenic males develop mammary tumors by 40 weeks of age, often prior to developing prostate tumors. The course of male mammary development is similar to that observed in the females but with a later onset. Hyperplastic ducts form as early as 15 weeks of age and progress into DCIS-resembling tumors before developing into invasive tumors that invade locally into adipose tissue and muscle and occasionally form metastases to lung and other organs. We then examined male mammary development in the FVB background strain (wild type) and showed that all males develop mammary ducts that continue to grow and branch throughout adulthood. The morphology of these ducts was similar to that of females with a central lumen surrounded by concentric layers of luminal epithelium, myoepithelium, a basement membrane and surrounding stroma. A study of CD1 male mice confirmed that male mammary development was not specific to the FVB strain but rather, CD1 males showed similar mammary ductal development. Male mammary development in FVB wild type animals and tumor progression in the transgenic males was characterized in terms of cell proliferation, apoptosis and expression of various markers of differentiation including hormone receptor status. In summary, our results demonstrate that FVB C3(1)-SV40Tag transgenic males represent a highly robust and reproducible model for the study male breast cancer. Our long-term goal is to leverage the information we uncovered through this effort to design novel therapies for breast cancer treatment in men.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-04-03.
Abstract P2-04-06: Transgenic expression of a breast-cancer specific GATA3 mutant leads to mammary hyperplasia
Authors: Kenny PA , Chandiramani N 
Published: August 2014

Abstract
GATA3 is expressed in normal luminal breast epithelial cells and is a key transcription factor in mammary gland development. In human breast tumors, high GATA3 protein levels are associated with estrogen receptor (ER) positivity and low grade. Recent published reports indicate that somatic mutations of GATA3 occur in up to 21% of ER+ tumors. These authors suggest, but do not demonstrate, that these GATA3 mutations are loss-of-function null alleles and that GATA3 is a haploinsufficient tumor suppressor gene.
The published mutational data indicate a striking enrichment of GATA3 mutations in exons 5 and 6 (amino acids 309–443) which encode the second of two DNA binding zinc fingers. This suggests that mutant proteins lacking this zinc finger may confer a survival advantage on breast cancer cells. Given this apparently strong selective pressure for mutations in this hotspot, it seems unlikely that these mutations are loss-of-function alleles.
We explored this directly by generating a MMTV-GATA3mutant mouse which specifically expresses a mutant GATA3 protein in the mammary gland. Non-parous pubertal transgenic mice exhibit a pronounced mammary hyperplasia and have increased ductal branching compared to wildtype littermates. These data confirm that the mutant GATA3 mutations commonly found in breast cancer are not null alleles, but that they instead have a gain-of-function phenotype. We are currently evaluating the effect of mutant GATA3 on the kinetics of mammary tumorigenesis by crossing these mice to the MMTV-PyMT model.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-04-06.
Abstract P2-05-07: Comparison of hormone receptor and HER-2 expression in primary breast cancers and sentinel lymph node metastases
Authors: Rokutanda N , Horiguchi J , Takata D , Nagaoka R , Sato A , Tokiniwa H , Tozuka K , Uchida S , Takeyoshi I 
Published: August 2014

Abstract
Background: Recently, it is a hot topic that the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor type 2 (HER2) may differ between the primary tumors and the paired recurrent metastatic tumors. On the other hand, the concordance of the ER, PR, and HER2 status between the primary tumor and ipsilateral axillary lymph node metastases is reported to be high in previous study. However, in these reports, the majority of lymph nodes metastases examined are macrometastases obtained from axillary lymph node dissection. The aim of the present study is to compare the ER, PR, and HER2 status of the primary breast tumors with that of sentinel lymph node micrometastases and macrometastases.
Methods: A total of 770 breast cancer patients underwent sentinel lymph node biopsy between 2006 and 2010 at our hospital. Among them, 87 patients who had only one node positive were eligible for our study. ER, PR, and HER2 status were determined by immunohistochemistry (IHC) and/or FISH.
Result: We analyzed 76 patients with 50(66%) patients with macrometastasesn and 26 (34%) micrometastases, except 11 cases those were indeterminate for IHC. ER status of primary tumor and the paired metastatic lymph node were almost full concordance except one case, in which ER was negative in primary tumor but ER was positive in lymph node. Discordance for PR was 15.8% (n = 12). Among these, six patients had PR-positive on primary and PR-negative in lymph node while six patients had PR-negative in primary and PR-positive in lymph node. Discordance for HER2 between primary tumor and metastatic lymph node was 5.3% (n = 4). Among these, three had negative in primaries and positive in lymph nodes while one had positive in primary and negative in lymph node. A discordance between primary and lymph node in HER2, ER, or PR status was observed in 14 of 67 (18.4%) cases.
Conclusions: The concordance in HER2, ER, and PR was high between the primary tumor and sentinel lymph nodes. However some cases had discordance of receptor status and these result may cause of discordance for distant metastases or poor prognosis.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-05-07.