bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P3-11-07: Changes in PgR and Ki-67 in residual tumour and outcome of breast cancer patients treated with neoadjuvant chemotherapy
Authors: Montagna Emilia , Bagnardi Vincenzo , Viale Giuseppe , Rotmensz Nicole , Sporchia Andrea , Cancello Giuseppe , Balduzzi Alessandra , Galimberti Viviana , Veronesi Paolo , Luini Alberto , Mastropasqua Mauro G , Casadio Chiara , Sangalli Claudia , Goldhirsch Aron , Colleoni Marco 
Published: May 2015

Abstract
PURPOSE We assessed the frequency of the change in biological features between the diagnostic biopsy and final surgery in breast cancer patients with residual disease after neoadjuvant chemotherapy. We also valued the impact of change on outcome in terms of disease free survival (DFS) and overall survival (OS)
PATIENTS AND METHODS We collected information through the institutional clinical database on all consecutive breast cancer patients treated with neoadjuvant chemotherapy at the European Institute of Oncology (EIO), Milan, Italy, between 1999 and 2011. We selected patients who did not achieved pathological complete response (pCR) at final surgery. All patients had pathological evaluation, including ER, PgR, HER2 protein and ki-67 expression performed at EIO both at diagnostic core biopsy and final surgery.
RESULTS We identified a total of 904 patients. The 5% of patients with ER positive at diagnostic biopsy had ER negative residual tumor at final surgery. For PgR expression, 67% of patients, whose tumors had a PgR&gt; 20% at diagnostic biopsy had a PgR&lt;20% at final surgery. The ki-67 expression changes from &gt;20% to &lt;20% in 40% of patients. At the multivariate analysis the decrease of PgR -immunoreactive cells correlated with improved outcome in terms of DFS (HR 0.73; CI 0.54-1.00 p 0.046). In addition, the decrease of ki-67 expression to &lt; 20% of the cells at final surgery was found to be associated with better outcome both in terms of DFS (HR 0.52; CI 0.40-0.68 p &lt;0.0001) and OS (0.45 CI 0.32-0.64 p&lt;0.0001)
CONCLUSION The decrease of PgR and Ki-67 expression after preoperative chemotherapy have a prognostic role in breast cancer patients with residual disease and should be considered in the adjuvant therapeutic algorithm.
Citation Format: Emilia Montagna, Vincenzo Bagnardi, Giuseppe Viale, Nicole Rotmensz, Andrea Sporchia, Giuseppe Cancello, Alessandra Balduzzi, Viviana Galimberti, Paolo Veronesi, Alberto Luini, Mauro G Mastropasqua, Chiara Casadio, Claudia Sangalli, Aron Goldhirsch, Marco Colleoni. Changes in PgR and Ki-67 in residual tumour and outcome of breast cancer patients treated with neoadjuvant chemotherapy [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-11-07.
Abstract P3-11-12: Vacuum assisted core-needle biopsy after neoadjuvant therapy in breast cancer to predict pathologic response
Authors: Grosse Regina , Saegenschnitter Jana , Nguyen Thi-Dao , Unverzagt Susanne , Buchmann Joerg , Kantelhardt Eva J , Papendick Nancy , Thomssen Christoph 
Published: May 2015

Abstract
Introduction: Recently published neoadjuvant breast cancer therapy trials have documented impressive pathologic complete response (pCR) rates of up to 50% and above, depending on grade, hormone receptor and HER2 status and type of therapy. The purpose of our prospective study is to examine the predictive value of a standardized vacuum assisted core-needle biopsy (VAB) of the tumor site after neoadjuvant therapy with respect to pCR status. This is a presentation of the first case series of this single institution study.
Methods: As of 2011, all patients who had completed neoadjuvant breast cancer therapy at our institution were informed about this trial regardless of their clinical response status. In case of consent, a mammography-guided VAB of the initially tagged tumor site was performed directly before the operation. In case of breast conserving surgery, mammographic wire localisation was performed immediately thereafter. Final surgery (breast conservation or mastectomy) was performed according to German guidelines. Ethical approval was obtained from the institutional review board. Pathologic complete response was defined as ypT0 ypN0.
Results: Of 70 patients completing neoadjuvant therapy, 44 consented to the trial. The pCR rate was 47% (n=21). Pre-operative VAB correctly predicted residual disease in 19 of 23 cases (82,6%). We observed incorrect prediction of pathologic response if the tagging clip was not placed centrally, or if the radiologist did not perform the VAB in the tagged area. In 3 cases of pathologic partial response (pPR), all residual tumor (DCIS) was removed by VAB. In these cases, no further malignant lesions were detected in the resulting surgical specimens.
Conclusions: Preliminary observations of this ongoing study are encouraging, although the correct prediction rate of residual disease is nowhere near the sensitivity needed to change clinical practice. However, if these results can be improved and confirmed in a larger series, it may be possible to reduce operative procedures after neoadjuvant therapy based on the results of a preoperative standardized VAB.
Citation Format: Regina Grosse, Jana Saegenschnitter, Thi-Dao Nguyen, Susanne Unverzagt, Joerg Buchmann, Eva J Kantelhardt, Nancy Papendick, Christoph Thomssen. Vacuum assisted core-needle biopsy after neoadjuvant therapy in breast cancer to predict pathologic response [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-11-12.
Abstract P3-11-13: Change of Ki-67 after long course of neoadjuvant chemotherapy as prognostic factors in patients with stage II, III triple negative breast cancer
Authors: Yang Yaewon , Kim Tae-Yong , Im Seock-Ah , Keam Bhumsuk , Lee Kyung-Hun , Han Sae-Won , Oh Do-Youn , Kim Tae-You , Moon Hyeong-Gon , Han Wonshik , Park In Ae , Noh Dong-Young 
Published: May 2015

Abstract
Background: Triple negative breast cancer (TNBC) shows poor prognosis despite their higher response rate to neoadjuvant chemotherapy (NAC). Response to NAC such as pathologic complete response (pCR) is a well-known useful prognostic marker for relapse and overall survival. Pre-chemotherapy baseline higher Ki-67 is a positive predictive marker for higher pCR rate but a negative prognostic marker for relapse free survival (RFS) and overall survival (OS). After short course of NAC, Ki-67 index changed in response to the treatment. The purpose of this study is to investigate the prognostic role of Ki-67 index change between before and after the long course of NAC in TNBC patients.
Patients and Methods: Patients with clinical stage II or III breast cancer treated with NAC at Seoul National University Hospital were enrolled and their clinicopathological findings including Ki-67 index were reviewed retrospectively. The definition of Ki-67 threshold of high was ≥14% in current study. TNBC definition was adopted from 2011 St Gallen Consensus Panel.
Results: From Jan 2009 to Dec 2010, a total of 183 patients received NAC. Among them, 46 (25.1%) were TNBC. The pCR rate (19.6% vs 9.5%, P=0.069) and the objective response rate (complete response + partial response) (76.1% vs 70.8%, P=0.153) were higher in TNBC group than in non-TNBC group. The RFS was not different between the two groups (3 year 77.3% vs 75.4%, P=0.877). The change of Ki-67 index from high (≥14%) to low (&lt;14%) was significantly associated with longer RFS in only in TNBC group. As for TNBC patients with high Ki-67 index at diagnosis, RFS of those whose Ki-67 index changed to low after NAC were significantly longer than that of whose Ki-67 index remained high (3 year RFS 87.2% vs 54.5%, P=0.036). In non-TNBC group, change of Ki-67 index was not significantly associated with RFS (P=0.245). The initial Ki-67 index itself (high vs. low) was not associated with RFS in both TNBC and non-TNBC group (P=0.726 and P=0.523 respectively).
Conclusion : The change of Ki-67 index from high to low is associated with longer RFS in TNBC. Ki-67 index change between before and after the NAC can be used for further discrimination of TNBC as a prognostic marker.
Citation Format: Yaewon Yang, Tae-Yong Kim, Seock-Ah Im, Bhumsuk Keam, Kyung-Hun Lee, Sae-Won Han, Do-Youn Oh, Tae-You Kim, Hyeong-Gon Moon, Wonshik Han, In Ae Park, Dong-Young Noh. Change of Ki-67 after long course of neoadjuvant chemotherapy as prognostic factors in patients with stage II, III triple negative breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-11-13.
Abstract P4-01-02: Prospective characterization of HER2-positive circulating tumor cells in patients with HER2-negative metastatic breast cancer
Authors: Krop Ian E , Macrae Erin , Galler Sarah R , Bischoff Farideh , Fauni Romeo , Sales Edgar , Huynh Lan , Mitchell Christine , Clarin-Tamayo Trisky , Anderson Mark , Abad Leslie , Winer Eric 
Published: May 2015

Abstract
Background: We have previously shown feasibility by CLIA validation of HER2 FISH on circulating tumor cells (CTCs). Several small retrospective studies have identified HER2 amplification in CTCs in a subset of patients (pts) with clinically HER2 negative metastatic breast cancer (MBC). While these findings potentially have profound implications for CTCs as a predictive biomarker, prospective validation and functional characterization of this subgroup is necessary.
Methods: We enrolled a prospective cohort of pts with MBC that was HER2 negative by IHC and/or FISH on all available primary and metastatic biopsies. Pts had ≥1 line of prior chemotherapy for MBC. Blood samples were collected at study entry. CTCs were enumerated based on standard criteria (Cytokeratin (CK)+/CD45- staining) as well as by FISH for HER2 using the OncoCEE-BR™ CTC test (Biocept, Incorporated). This test employs a proprietary antibody cocktail for capture followed by CK/CD45 staining, and FISH analysis directly within a microfluidic device. Samples were reported as positive if the HER2/CEP17 ratio was ≥ 2.0. HER2+ CTCs were classified into two categories: CK+/CD45-/HER2+ and CK-/CD45-/HER2-
Results: CTCs were observed in 208 out of 323 pts (64%). Median number of CTCs was 10 (range 1 to &gt; 34195). 75 pts (23%) had HER2+ CTCs, with a median number of 3 HER2+ CTCs (range 1 to 21). 36% (27/75) of these pts had CK+/HER2+ CTCs and 43% (32/75) of pts had only CK-/HER2+ CTCs. The remaining pts (21%) had both CK+/HER2+ and CK-/HER2+ CTCs present.
Conclusion: HER2 amplified CTCs are present in a subset (23%) of pts with clinically HER2-negative breast cancers. Interestingly, we observed a high prevalence of pts with only CK-/HER2 amplified CTCs (32 out of 323; 10%). The unique multi-antibody CTC capture method used here thus allows for detection of a prevalent population of CK-/HER2+ CTCs that may be largely undetected by other current adopted technologies. The functional significance of CK-/HER2+ and CK+/HER2+ CTCs in patients with clinically HER2 negative breast cancer is currently being evaluated in a prospective study with HER2-directed therapy.
Citation Format: Ian E Krop, Erin Macrae, Sarah R Galler, Farideh Bischoff, Romeo Fauni, Edgar Sales, Lan Huynh, Christine Mitchell, Trisky Clarin-Tamayo, Mark Anderson, Leslie Abad, Eric Winer. Prospective characterization of HER2-positive circulating tumor cells in patients with HER2-negative metastatic breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-01-02.
Abstract P4-02-10: Detection of H1047R and E545K PIK3CA mutations from peripheral blood in ER positive breast cancer patients
Authors: Garcia-Saenz Jose Angel , Acosta Daniel , Moreno Fernando , Ayllon Paticia , Sotelo Miguel , Caldes Trinidad , Diaz-Rubio Eduardo , Romero Atocha 
Published: May 2015

Abstract
Background: Digital polymerase chain reaction (PCR) is a new technology that enables detection and quantification of cancer DNA molecules from peripheral blood. Detecting tumor-specific mutations in circulating plasma DNA may potentially be useful to select systemic therapies for solid tumors. The aim of our study is to evaluate the feasibility of detecting PIK3CA mutations from plasma of breast cancer patients.
Methods: We have designed an allele-specific PCR assay and used a digital PCR system for the detection of PIK3CA mutations H1047R and E545K. Formalin-fixed paraffin-embedded (FFPE) tumor samples were analyzed by COBAS and by digital PCR. The matched plasma samples were then analyzed by digital PCR. Kappa Cohen’s coefficient (κ) was used to test agreement between methods
Results: 37 ER positive breast cancer and matched plasma were evaluated. 31 (84%) patients were stage IV disease. E545K mutation was detected in 4 out of 37 (11%) tumor specimens and H1047R mutation was identified in 8 out of 37 (22%) tumor samples. The proportion of observed agreement between H1047R and E545K detection in tumor samples by COBAS and digital PCR was 100%. Regarding E545K mutation assay we found that the proportion of observed agreement between mutation status in FFPE samples and circulating tumor DNA (ctDNA) was 94.6% (kappa= 0.770; Sensitivity=100%; Specificity=93.9%). In H1047R assay the proportion of observed agreement between FFPE samples and ctDNA was 83.78% (Kappa=0.561; Sensitivity=60%; Specificity=92.59%).
Conclusions: The agreement between methodologies when assessing the PIK3CA status in tumor samples was perfect. However, a moderate-to-fair agreement was found between FFPE samples and ctDNA which might be due to the heterogeneity of the disease. The methodology presented in this study is a feasible approach for PIK3CA mutation detection in blood derived samples.
Citation Format: Jose Angel Garcia-Saenz, Daniel Acosta, Fernando Moreno, Paticia Ayllon, Miguel Sotelo, Trinidad Caldes, Eduardo Diaz-Rubio, Atocha Romero. Detection of H1047R and E545K PIK3CA mutations from peripheral blood in ER positive breast cancer patients [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-02-10.
Abstract P4-02-11: Circulating methylated DNA of pregnancy-associated plasma protein A as a clinically useful biomarker in breast cancer
Authors: Sainsbury Richard , Koehler Karsten , Page Catherine , Velamakanni Saroj 
Published: May 2015

Abstract
Background: A recent report suggests that Pregnancy-Associated Plasma Protein A (PAPPA) plays a pivotal role in normal cell division and is targeted early in breast cancer development. Epigenetic silencing of PAPPA is highly prevalent in precursor lesions and invasive breast cancer, correlating with loss of PAPPA protein expression. In normal breast tissue PAPPA promoter methylation was not observed (Journal of Pathology 344-356: 2014). We sought to test the hypothesis that PAPPA promoter hypermethylation can be detected in cell-free tumour specific DNA (ctDNA) in the bloodstream of patients with metastatic breast cancer.
Methods: Plasma derived from 12 patients with metastatic breast cancer was examined for ctDNA. A semi-quantitative real-time PCR based MethyLight assay was used for detection of PAPPA methylation. Spiking experiments with breast cancer cell lines were performed to develop the assay and confirm linearity of sodium bisulfite treatment.
Results: Percentage methylated reference (PMR) values from spiking experiments with PAPPA methylated and non-methylated DNA in plasma (matrix) demonstrate good linearity for the PAPPA gene and the endogenous control Col2A. PAPPA methylation was detected in 10 out of 12 (83%) of the metastatic breast cancer samples. In stark contrast, epigenetic silencing of PAPPA was not detected in any of the plasma samples from non-cancer bearing patients (n=10).
Conclusions: Given the potential clinical impact of our data, this study is being extended to include early stage breast cancer patients with poor prognostic clinic-pathological indicators. Our proof-of-concept findings indicate that testing for PAPPA promoter methylation in ctDNA may be used as a biomarker of disseminated disease, helping clinicians with treatment decisions and adjusting those choices as conditions change. By developing and refining more sensitive techniques, PAPPA methylation testing in ctDNA could also find practical utility in breast cancer screening.
Citation Format: Richard Sainsbury, Karsten Koehler, Catherine Page, Saroj Velamakanni. Circulating methylated DNA of pregnancy-associated plasma protein A as a clinically useful biomarker in breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-02-11.
Abstract P4-04-01: A new breast cancer classification scheme based on novel classes of tumor stroma
Authors: Thompson Crista , Bertos Nicholas , Gruosso Tina , Finak Greg , Lesurf Robert , Saleh Sadiq M , Zhao Hong , Souleimanova Margarita , Meterissian Sarkis , Omeroglu Atilla , Hallett Michael T , Park Morag 
Published: May 2015

Abstract
A major challenge in cancer treatment is the heterogeneous nature of the disease. This is particularly evident in breast cancer where gene expression profiling of whole tumours has identified multiple intrinsic subtypes of breast cancer. These subtypes are associated with differential prognoses and are correlated with previously identified clinical biomarkers (i.e., ER and HER2 status) used to stratify patients for targeted therapy. Despite recent studies demonstrating that elements within the tumour microenvironment can affect breast cancer progression and outcome, and that information contained within this compartment carries significant prognostic information for patient stratification above and beyond the information supplied by the intrinsic subtypes and existing therapeutic biomarkers, a limited understanding of stromal heterogeneity across the population has hindered the development of effective prognostic tools and targeted therapies directed against these processes. Here we perform expression profiling of the microdissected tumour-associated stromal components of 49 human breast tumours, and demonstrate that stromal heterogeneity can be captured by categorization into six classes which bear distinct molecular phenotypes. These stromal classes exhibit distinct biological functions and carry prognostic information independent of existing tumor-intrinsic biomarkers and molecular breast cancer subtypes. Specific combinations of stromal class and tumour subtype are significantly over- and under-represented; furthermore, simultaneous stratification of tumors in external datasets by both tumour subtype and stroma class identifies good- and poor-outcome cohorts within four of the five molecular breast cancer subtypes. The stroma classes identified here form the basis for an improved breast cancer classification scheme which takes the contribution of the microenvironment into account.
Citation Format: Crista Thompson, Nicholas Bertos, Tina Gruosso, Greg Finak, Robert Lesurf, Sadiq M Saleh, Hong Zhao, Margarita Souleimanova, Sarkis Meterissian, Atilla Omeroglu, Michael T Hallett, Morag Park. A new breast cancer classification scheme based on novel classes of tumor stroma [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-04-01.
Abstract P4-04-21: Host response to microbes found in the tumor microenvironment and healthy adjacent tissue
Authors: Navarrete Marian , Sieling Peter A , Lee Delphine J , Chung Andrew W 
Published: May 2015

Abstract
Next generation sequencing methods have defined the bacterial microbiome in human breast milk and breast tissue, but the role of bacteria or their components in breast cancer has not been well defined. There is growing evidence in humans and animals that alterations of the gut microbiome may contribute to host susceptibility to cancer. However, the presence of bacteria at the site of the tumor microenvironment may also contribute to carcinogenesis (e.g. by promoting chronic inflammation) or immune surveillance (e.g. by stimulating antitumor pathways). Previously, we found that bacterial load in breast cancer tissue is inversely correlated to the progression of disease and that antimicrobial gene expression was comparatively higher in breast tissue from healthy subjects. Our investigation of the microbiome of breast tissue showed that overall microbiome signatures in breast cancer patients are similar when comparing their healthy adjacent tissue vs. the tumor tissue. However, our published preliminary studies did identify some differences in the abundance of specific bacteria between the two tissues. Here we investigated how those bacteria in healthy adjacent vs. tumor tissue may differentially stimulate cells found in breast tissue including breast ductal epithelium, adipocytes, and immune cells. Our preliminary data suggest that bacteria found in healthy adjacent vs. tumor tissue stimulate differential cytokine responses that may shape the local tumor microenvironment and beyond and may also contribute to local/regional immune surveillance.
Citation Format: Marian Navarrete, Peter A Sieling, Delphine J Lee, Andrew W Chung. Host response to microbes found in the tumor microenvironment and healthy adjacent tissue [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-04-21.