bluuebunny/crossref_metadata_2025_split huggingface dataset:
PD04-03: Sexual Dysfunction in Premenopausal Women with Breast Cancer: Prevalence and Severity.
Authors: Goldfarb SB , Dickler M , Patil S , Jia R , Sit L , Damast S , Carter J , Kaplan J , Hudis C , Basch E 
Published: June 2012

Abstract
Background: Sexual dysfunction is reported after chemotherapy and endocrine therapies. However, the prevalence and severity of sexual dysfunction in premenopausal women undergoing therapy for both local and metastatic disease is not well defined. This study was performed in order to understand the impact of contemporary breast cancer treatment on the prevalence and severity of sexual health in premenopausal women.
Methods: We developed a survey that includes a previously validated questionnaire, the Female Sexual Function Index (FSFI), as well as an established measure of health-related quality of life (the EuroQol EQ-5D), and disease-specific items to characterize sexual dysfunction and its causes based on literature review and expert consultations. Anonymous administration of the surveys was conducted in outpatient clinic waiting areas of the Breast Cancer Center at Memorial Sloan-Kettering Cancer Center (MSKCC), under an IRB waiver of consent.
Results: 372 consecutively approached premenopausal women with breast cancer of any stage, undergoing treatment were each queried once. The mean age was 47. 87% reported current or past hormonal treatment, and 86% reported current or past chemotherapy (76% adjuvant; 24% for metastatic disease). Sexual dysfunction attributed to breast cancer or its treatment, defined as an FSFI score &lt;26, was reported by 75% of respondents with a mean score of 16.3. Among these women, 79% of patients considered their sexual symptoms to be bothersome, with 51% noting moderate or severe levels of bother (score &gt;=5/10). In a multivariate analysis, metastatic disease, development of amenorrhea from cancer treatment, antidepressant use and poorer overall health were each significantly associated with worse FSFI scores. Lower FSFI scores were also significantly associated with worse health-related quality of life.
Conclusion: Sexual dysfunction is prevalent in premenopausal women treated for breast cancer and should be discussed with patients as a potential adverse effect of therapy. Assessment of sexual symptoms throughout treatment and beyond may facilitate the use of potential interventions such as lubricants, dilators, treatment modification and counseling.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD04-03.
PD05-05: Meta Analysis of Discordant HER2 Status in Matched Primary and Metastatic Breast Cancer.
Authors: Richter S , Zandvakili A 
Published: June 2012

Abstract
Background: The status of HER2 amplification in breast cancer is an important prognostic and predictive indicator. Only those tumors exhibiting HER2 overamplification are candidates for HER2 targeted therapy. It remains controversial how accurately HER2 status of primary tumors reflects HER2 status in distant metastases. Discordance between primary and metastatic tumors can impact significantly on patient management and suitability for HER2 targeted therapies in the setting of recurrent distant disease.
Methods: A literature search of the PubMed database was performed to identify all primary studies comparing HER2 status in matched primary and distant metastatic tumors between January 2005 and February 2011. Review and data extraction was performed by two independent reviewers. Eligible studies evaluated HER2 status by current ASCO guidelines. Studies comparing paired primary and axillary lymph nodes or synchronous primaries and metastases were excluded. Weighted pooled estimates were calculated.
Results: The original search strategy retrieved 1703 studies for which there were 62 eligible studies for full evaluation. Metastatic sites included bone, brain, lung and liver. Traztuzumab was received in three studies. Weighted summary estimate for negative to positive discordance was 23% (95% CI, 16.0-28%). Positive to negative discordance had a weighted summary estimate of 4% (95% CI, 0.0-6%).
Discussion: Meta analysis of studies adhering to ASCO guidelines for HER2 status determination revealed a significant rate of change to HER2 positive metastatic disease in HER2 unamplified primary breast cancers. This data suggests that nearly one quarter of patients may be denied the benefit of HER2 targeted therapy if HER2 primary status alone is used a the sole measure in determining therapeutic options upon distant recurrence.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD05-05.
PD05-06: Determination of HER2 Status with Analysis of Plasma DNA by Digital PCR in Patients with Metastatic Breast Cancer.
Authors: Graeser MK , Gevensleben H , Smith IE , Ashworth A , Turner NC 
Published: June 2012

Abstract
Background. A small proportion of originally HER2 negative primary breast cancers relapse with HER2 amplified disease. Identification of these cancers is important as these patients may benefit from HER2 targeting therapies. A proportion of free plasma DNA originates from the cancer, and accurate determination of HER2 copy number in plasma DNA has the potential to non-invasively determine HER2 status in patients with metastatic breast cancer. Digital PCR can differentiate small increases in DNA concentration with a much higher degree of accuracy than conventional quantitative PCR, and here we assess the potential of plasma DNA digital PCR to determine HER2 status.
Methods. We examined a cohort of 44 patients with metastatic breast cancer treated at the Royal Marsden Hospital who had received a median of 1.5 prior courses of chemotherapy for recurrent disease; 34 patients had ER positive and 9 HER2 positive (all 3+ positive HercepTest) disease as determined on biopsy of recurrent disease in 16 patients and original primary cancer in 28 patients. Following informed consent, plasma samples were taken, free plasma DNA was extracted and concentration determined with LINE1 quantitative PCR. We designed a custom HER2 copy number TaqMan MBG-probe (Applied Biosystems) and two chromosome 17 peri-centromeric control probes TUFMP1 and UBBP4, avoiding known SNPs and regions of normal copy number variation. Digital PCR was performed in 384 well format on a 7900HT Fast RT-PCR system, with copy number ratio determined using the Poisson distribution.
Results. HER2 Digital PCR assay was initially tested on DNA from 9 HER2 amplified cell lines. HER2/UPPB4 ratio was increased in 9/9 HER2 amplified cell lines, and HER2/TUFMP1 in 7/9 due to co-amplification of the 17q peri-centromeric DNA in 2 cell lines. Dilution experiments with SKBR3 DNA in non-amplified DNA demonstrated sensitivity down to ∼1% levels. We selected HER2/UBBP4 digital PCR for examination of patient samples. Plasma DNA Digital PCR HER2/UBBP4 ratios differed substantially between HER2 non-amplified (mean 1.047, SD 0.149, median 1.046, range 0.70−1.264), and HER2 amplified cancers (median 2.231, range 1.138−7.89, p&lt;0.001). Digital PCR HER2 ratios had a high diagnostic accuracy with ROC curve AUC 0.967 (95% CI 0.585−0.997). With a threshold Digital PCR HER2 ratio of 1.3 the test had 100% specificity and 89% sensitivity, with negative predictive value 97%. The single miscalled HER2 amplified patient had a low tumour burden. Results of a test set using sequential probability ratio test analysis will be presented at the conference.
Conclusions: Plasma DNA Digital PCR accurately determined HER2 status in patients with metastatic breast cancer. Analyses of plasma DNA have the potential to replace biopsy sampling of metastatic disease to guided targeted therapy.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD05-06.
PD06-10: Breast Cancer Patient Distress Associated with Difficulties Navigating the Costs Associated with Care: Results from a National Education Program.
Authors: Ahmed I , Gubin A , Champion L , Harvey A , Amsellem M 
Published: June 2012

Abstract
Compounding the stressors related with a diagnosis of breast cancer can be the associated direct and indirect costs of cancer care. To address this need, the Cancer Support Community (CSC) in 2009 developed an evidence-based, professionally-led national education workshop for cancer patients and caregivers entitled Frankly Speaking About Cancer: Coping with the Cost of Care. As part of this workshop, participants completed a survey describing their experiences coping with the cost of cancer care. To date, responses from 465 participants (representing 46 workshops) have been analyzed. Of those participants, 105 are women diagnosed with breast cancer. Though workshop participants were affected by a wide variety of cancer diagnoses, half of those with cancer attending the workshop (50%) were affected by breast cancer. No significant differences between breast cancer patients and individuals with other cancers were found. Analyses are based on responses from breast cancer patients only. Participants’ pre-workshop rating of their understanding about the financial aspects of their breast cancer care was low (m =2.8, s.d.=1.0) and was significantly less than their level of knowledge post-workshop (m =4.1, s.d.=0.7, p &lt;.05).
Most attendees (72.8%) reported experiencing some degree of emotional distress from trying to manage cancer care costs, and nearly one-third of attendees (30.1%) reported significant distress. Most (64.8%) reported that their healthcare team did not discuss financial aspects of care with them. Of attendees whose team did discuss it with them, typically it was a social worker, physician, or nurse. Of those who had this discussion, only 34% reported that this information was actually useful to them. Not surprisingly then, attendees reported they have looked elsewhere for information about managing the costs of care, such as patient support organizations (40.2%), the Internet (43.5%), and other patients (41.3%).
A positive to arise from the workshop is that most participants (69.9%) reported the intention to discuss financial aspects of their care with their healthcare team based on what they had learned from the workshop. Intention to have this discussion with their healthcare team was both positively correlated with having experienced emotional distress about the cost of their care (r=.29, p &lt;.05) as well as negatively correlated with their level of pre-workshop knowledge about financial issues in breast cancer care (r=-.28, p &lt;.05).Taken together, these data highlight significant obstacles that individuals face in receiving meaningful information relevant to managing the costs associated with cancer care.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD06-10.
PD07-02: Docetaxel Is Superior to Paclitaxel Given Every Three Weeks in Post Operative Patients with Node-Positive Breast Cancer: Results of the Final Analyses of the NSAS-BC (National Surgical Adjuvant Study of Breast Cancer) 02 Trial from Japan.
Authors: Watanabe T , Kuranami M , Inoue K , Masuda N , Aogi K , Ohno S , Iwata H , Mukai H , Uemura Y , Ohashi Y 
Published: June 2012

Abstract
Background: Four cycles of doxorubicin plus cyclophosphamide (4-AC) followed by four cycles of a taxane is widely used for postoperative chemotherapy in breast cancer (BC). Concern about relatively rare, but life-threatening toxicity of anthracyclines such as heart failure and secondary leukemia has promoted research to seek anthracycline-free regimens. Since 1990's when taxanes were introduced, docetaxel (DTX) is used interchangeably with paclitaxel (PTX) for the treatment of BC, but they may differ more than initially anticipated. We conducted this trial to test two hypotheses: (1) Eight cycles of a taxane is not inferior to 4-AC followed by four cycles of a taxane; (2) one taxane is superior to the other.
Methods: Eligibility included a diagnosis of clinical stage I-IIIA and axillary node-positive BC, an age younger than 71 years and with performance status of 0 to 1. Patients were randomly assigned to receive either one of the following regimens;ACP: 4-AC (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 q3w x 4) followed by 4-PTX (175 mg/m2 q3w x 4)ACD: 4-AC followed by 4-DTX (75 mg/m2 q3w x 4)8-PTX: PTX (175 mg/m2 q3w x 8)8-DTX: DTX (75 mg/m2 q3w x 8)
Comparisons included PTX vs. DTX (ACP + 8-PTX vs. ACD + 8-DTX) and +AC vs. -AC (ACP + ACD vs. 8-PTX + 8-DTX). The primary endpoint was disease-free survival (DFS), and the secondary endpoints include overall survival (OS). The trial was powered to prove the non-inferiority of +AC to -AC (threshold hazard ratio 1.32) in terms of DFS. DFS was also compared between PTX and DTX to determine any superiority.
Results: A total of 1,060 eligible patients were accrued at 84 centers between December 2001 and April 2006. There were 348 DFS events and 166 deaths after a median followup of 72.2 months. DTX was superior to PTX in terms of both DFS (Hazard ratio(HR) 0.76; 95% Confidence Interval(CI) 0.62−0.95, p=0.012) and OS (HR 0.72;95%CI 0.53−0.97, p=0.033). -AC was not inferior to +AC with respect to DFS (HR: 1.21, 90% CI 1.01−1.44). Among the four arms, 8-PTX alone resulted in poorer DFS (compared with ACP, HR 1.42 95%CI 1.07−1.89).

Nausea and vomiting were more frequent with +AC than -AC. Edema and febrile neutropenia were more frequent with DTX than PTX. The incidence of sensory neuropathy was higher with PTX than DTX and it lasted for more than one year of the end of PTX treatment.
Conclusions: When AC, PTX and DTX were given every three weeks, both DFS and OS were better in the arms including DTX than in those including PTX. AC followed by a taxane can be replaced by 8-DTX.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD07-02.
PD08-08: Preclinical Efficacy of the Combination of Met and Src Family Kinase Inhibitors in Triple-Negative Breast Cancer.
Authors: Gartner EM , Kim EMH , Choi L , Boerner J 
Published: June 2012

Abstract
Background: Epidermal growth factor receptor (EGFR), although overexpressed in almost 60% of all triple-negative breast cancers, has yet to be identified as an effective therapeutic target for the treatment of the disease. We have previously shown in cell culture models of triple-negative breast cancer that primary resistance to EGFR tyrosine kinase inhibitors through ligand-independent phosphorylation can be overcome by co-inhibiting EGFR with either Met or Src family kinases (SFKs). We also demonstrated that inhibiting Met kinase activity reduced EGFR and c-Src phosphorylation and inhibiting SFK reduced EGFR phosphorylation. Taken together, these data suggest that EGFR, Met and SFKs regulate the activity of each other through transphosphorylation. This process of transphosphorylation, or crosstalk, allows for the continued activation of key signaling proteins required for proliferation and transformation. Here we demonstrate that inhibiting both Met and SFKs decreases cell viability and eliminates the need for inhibition of EGFR tyrosine kinase activity, as the autophosphorylation sites of EGFR were lost with the combination treatment.
Methods: Seven triple-negative (SUM102, SUM149, SUM229, SUM1315, BT20, BT549, MDA-MB-231), two HER2+ (SUM190 and SKBr3), and two ER/PR+ (MCF7 and T47D) breast cancer cell lines were used to test the efficacy of the combination of Met and SFK inhibitors, Arq-197 and dasatinib, respectively. Cell viability after drug treatment was assessed by MTT assays. IC50 values were calculated and drug synergy calculations were performed. Transphosphorylation was measured by immunoblotting using phospho-specific antibodies. Apoptosis was characterized by immunoblotting.
Results: All seven triple-negative breast cancer cell lines demonstrated decreased cell viability with the combination of Arq-197 and dasatinib when compared with either drug alone. In contrast, none of the HER2+ or ER/PR+ breast cancer cell lines had any additional loss of viability with the combination treatment. We found that the interactions between Arq-197 and dasatinib were synergistic in several of the breast cancer cell lines. Specifically, in one such cell line (BT20), the combinatorial index values were less than 1.0. Interestingly, in this cell line, the tyrosine phosphorylation levels on residues 1068 and 992 of EGFR were significantly altered with the combination treatment and activation of apoptotic proteins, including PARP, occurred.
Conclusions: These data demonstrate that two tyrosine kinases, known to be downstream of EGFR activation, interact to promote resistance to EGFR inhibitors. However, inhibiting both Met and SFKs was sufficient to decrease cell viability and stimulate apoptosis in triple-negative breast cancer cells. Further studies to validate the relevance of these findings are ongoing.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD08-08.
PD10-04: Exploration of the Relationship between Loss of PTEN and BRCA1 Expression in Triple Negative Breast Carcinoma.
Authors: Jones N , Velasco V , Reault M , Dapremont V , Gastaldello B , Rouault A , Bonnet F , Debled M , Tunon de Lara C , Longy M , MacGrogan G , Sevenet N 
Published: June 2012

Abstract
Based on the mechanism of action of PARP inhibitors, BRCAness breast and ovarian cancers could be defined as the optimal group of tumours to target with such drugs. As the BRCAness phenotype is not fully defined at present, a surrogate phenotype of triple negative breast cancer (TNBC) has been proposed. Results of recent clinical trials involving PARP inhibitors in the context of TNBC do not demonstrate a significant improvement in overall survival or progression free survival, partly due to the inaccurate selection of certain tumours. Data from cell culture studies suggests that loss of PTEN expression could be a marker of PARP inhibitor sensitivity.
Materials and Methods: A retrospective study of 160 TNBC resected at Institut Bergonie between 1989 and 2010 was undertaken. Inclusion criteria were: ER & PR immunohistochemcial (IHC) negativity (&lt;10% tumour cells positive), non-amplification of HER2 (IHC score 0, 1, or 2 with negative FISH analysis) and an invasive ductal carcinoma resected before chemotherapy. For some familial cases, germline BRCA1 mutation screening had been performed in a diagnostic setting and was accompanied by genetic counselling. PTEN IHC, point mutation and gross rearrangement screening, along with BRCA1 expression and promoter methylation analysis (through real-time PCR and bisulfite treatment, respectively) and 53BP1 IHC were undertaken on this series of TNBC.
Results: Twenty percent of sporadic and familial TNBC demonstrated reduced BRCA1 expression with a greater than 7 fold reduction in expression. Almost half of tumours demonstrated a complete loss of PTEN expression as assessed by IHC, with a deleterious PTEN point mutation identified in 5% of cases. Although a slight correlation is observed between the complete loss of PTEN and a reduction in BRCA1 expression, a complete overlap of these two alterations was not observed; tumours with reduced BRCA1 expression do not always demonstrate complete negativity on PTEN IHC and certain tumours displaying complete negativity on PTEN IHC do not show a reduction in BRCA1 expression. Full immunohistochemical characterization of the tumour series (ER, PR, HER2, AR, CK5/6 & EGFR) together with the results of PTEN, BRCA1 and 53BP1 analyses will be presented. Conclusion
These results suggest that at present, loss of PTEN expression is not a suitable surrogate marker for tumours with reduced BRCA1 expression. This should be borne in mind for ancillary studies of clinical trials involving PARP inhibitors in the treatment of breast tumours and further investigation is warranted.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD10-04.
S1-6: Characterization of Breast Cancer Distant Metastasis Based on Outcome over Time Using a Gene Expression Profiling Approach and Identification of Pathway Activities of Late Relapse.
Authors: Saghatchian M , Mittempergher L , Michiels S , Casinius S , Glas A , Lazar V , Roepman P , Dessen P , Benz S , Piccart M , Delaloge S , van't Veer L 
Published: June 2012

Abstract
Background
Previous reports have described the use of microarrays to assess the molecular classification of human breast cancers and defined new subgroups based on gene expression that are relevant to patient management through their ability to predict metastatic relapse and survival relapse. However, different mechanisms may be associated with the development of early and late distant metastases. With the hypothesis that tumors may lead to early or distant metastases based on their intrinsic biological initial features, we aimed at defining molecular profiles for several subgroups of patients based on their outcome over time.
Material and methods
Breast primary tumors were selected from retrospective series of patients with frozen material available. These series include patients of all ages, LN- and LN+; Estrogen or Progesteron-receptor positive, Her2-negative, no adjuvant treatment, with a follow-up of more than 10 years (y) for the control group or distant metastatic relapse as first event (DM) for the study group (n=144). Patients tumors were classified in 4 groups: no relapse at 10 y (M0), DM before 3 y (M0-3, n=30), DM between 3 and 7 y (M3-7), DM after 7 y (M7+). Samples were collected in 2 different institutions (NKI series for identifying the signature and IGR series for validation). Gene expression analysis of breast tumor samples was performed using custom-made Agilent 44K high-density microarrays and hybridized against the Mammaprint® reference pool (MRP). Tumors were also assessed for their Mammaprint® status, wound-healing signature status and their intrinsic subtypes based on the Blueprint® signature. Moreover, we identified the pathway-level activities of the patient groups using PARADIGM.
Results and Discussion
For the NKI series, A subset of 144 samples was included based on the selection criteria: 57 M0, 31 M0-3, 25 M3-7, 31 M7+.
None of the 3 previously mentioned signatures correctly identified M0 vs. M7+ patients.
In order to identify a predictive signature of late relapse (after 7y) we considered M0 and M7+ MammaPrint-Low Risk patients and we split them in a training (n=41) and in a test (n=23) sets.
A 73-gene signature was able to classify M7+ patients with 75% of sensitivity and 66% of specificity on the test set. DM after 7yr showed significant activation of pathway related to inflammatory response and angiogenesis.
Detailed results and validation results on the independent IGR series will be presented at the meeting.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr S1-6.