bluuebunny/crossref_metadata_2025_split huggingface dataset:
P5-13-03: Correlation of Clinical and Molecular Findings with Pathologic Response to Preoperative Lapatinib and Trastuzumab, Separately or in Combination, Prior to Neoadjuvant Chemotherapy for HER2 Positive Breast Cancer.
Authors: Holmes FA , Espina V , Liotta LA , Chang JC , Nagarwala YX , Danso M , McIntyre K , Osborne CR , Krekow LK , Gagnon RC , Mahoney JM , O'Shaughnessy JA 
Published: June 2012

Abstract
Background
15% of curative HER2−positive patients (pts) treated with standard trastuzumab (T)-based chemotherapy regimens recur. Our prior report (ASCO 2011 #506 using only data from paired samples N=49) identified major pathways of resistance: autophagy, stem cell, extracellular matrix, and phospho epitopes on FOXO, STAT5, EGFR.
Aim: To collect proteomic and microarray data from baseline biopsies and identify molecular correlates of pathologic complete response (pCR).
Methods: Randomized, open label, phase II. Eligibility: biopsy-proven HER2 positive stage II, III invasive breast cancer, healthy. After informed consent, pt randomized to T or Lapatinib (L) or both (T+L) for 2 weeks (wk) then continue same anti-HER2 agent with standard chemotherapy (FEC75 IV every 3 wk then Paclitaxel 80 mg/m2 wk x 12) then surgery. Research biopsy before and 2 wks after anti-HER2 agent analyzed by reverse phase protein microarray (RPMA) from laser capture microdissected cells, RNA expression microarray, and in-vitro stem cell studies. PCR in breast is no invasive tumor. ITT is Intent to Treat (all treated pts). Pathways identified by analytes (n=42): autophagy (Beclin 1, LC3B, ATG5), stem cell (CD44, Mushashi, E-Cadherin, Beta Catenin), extracellular matrix (Integrin, MMP). Additional informative analytes: phosphorylated HER3, IGFR1.
Results: 100 pts treated: T=33, L=34, T+L=33. % pCR- ITT: ER pos/ER neg by arm: T = 40%/67%; L = 21%/50%; T+L = 58%/50%. Baseline RPMA samples N= 65 (T = 22; L= 25; T+L = 18). A) Specific analytes contributory to outcome by arm by Random Forest analysis: T: Beta Catenin Ser 33/37/Thr 41, EGFR Tyr1045. L: MMP14, E-Cadherin, LC3B, Integrin alpha5 B1, Stat 5 Tyr 694, IGFR Tyr 1131/1146, Erk Thr 202/Tyr204, NFKB Ser536, FOXO Thr24, HER3 Tyr1289. T+L: cerb2, EGFR, Met Tyr1235, CD44, E-Cadherin. B) Statistically significant endpoint ratios from network analysis that strongly correlate with pCR: T: HER3 Tyr1289/Beclin 1; PTENser380/ERK Thr202/Tyr204; GSK3B Ser21-9/Stat5 Tyr694; p70S6 Thr389/LC3B; p7026 Thr389/MMP9; FOXO Thr24-32/NFKB Ser536; Beta Catenin Ser 33–37 Thr41/LC3B. L: EGFR Tyr1045Beclin1; cerb2/Beclin1; HER3 Tyr1289/Beclin1; PI3K/FOXO Thr24,32; IRS1 Ser612/Beclin1; Mushashi/IRS1 Ser612. T+L: only 4 pts no pCR. C) Microarray analysis confirms the critical role of extracellular matrix and autophagy.
Discussion: These findings support the concept that NO-pCR tumors can engage a diverse set of strategies to achieve cell survival in the face of therapy. The molecular correlates of response found in this small, underpowered study provide candidates for future patient stratification studies and generate insights for combination therapy.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-13-03.
P5-13-11: PTEN and Tau-Protein Expression: Predictive Value of Poor Response to Trastuzumab Plus Paclitaxel in Patients with HER2−Positive Breast Cancer.
Authors: Koo DH , Ahn J-H , Yoon DH , Kim S-B , Lee HJ , Kong KY , Son BH , Ahn SH , Jung KH 
Published: June 2012

Abstract
Backgrounds: Trastuzumab-based chemotherapy has been an active treatment in patients (pts) with HER2−positive breast cancer; however, primary and secondary resistance has occurred in pts treated with trastuzumab (H) alone or in combination with chemotherapy. Material and Methods: Biomarkers were searched using tissue microarrays (TMA) in the HER2−positive breast cancer pts treated with H and paclitaxel (P) combination chemotherapy between October 2004 and August 2010. Tumor blocks of 101 pts were analyzed for VEGF, IGF-1R, p-Akt, beta-III tubulin, CD44, Tau-protein, p27 and PTEN by immunohistochemical (IHC) analysis. Eight biomarkers were assessed to investigate the correlation with the clinical outcomes, including response rate (RR), progression free survival (PFS), and overall survival (OS).
Results: With a median follow-up duration of 21.7 months (range, 9.1−55.2 months), 101 pts received H+P chemotherapy in neoadjuvant setting (n=36, 35.6%) and recurrent or metastatic setting (n=65, 64.4%). Median age was 48 (range, 19–83 years), and the majority of pts (n=95, 94.1%) had good performance status. Premenopausal pts and hormone receptor-negative pts were 48 (47.5%) and 52 (51.5%), respectively. The median cycle of H+P chemotherapy was six (range, H 1–43; P 1–21). Overall RR was 68.3% (n=69) including complete response with 7 pts, and PFS and OS were significantly longer in pts responsive to H+P chemotherapy compared with non-responsive patients (PFS, p=0.001; OS, p=0.015). Although VEGF, IGF-1R, p-Akt, beta-III tubulin, CD44, p27 and PTEN status by IHC were not significantly associated with response to H+P chemotherapy, Tau-protein showed a trend of association without statistical significance (RR, 46.2% vs. 71.6%, p=0.066). Among 13 pts with high Tau protein expression, 9 pts with both high Tau-protein and low PTEN level showed statistically significant lower RR compared with other 92 pts (22.2% vs. 72.8%; p=0.002). None of the biomarkers was related to PFS and OS in pts with recurrent or metastatic disease, and to pathologic complete response in pts after H+P chemotherapy as neoadjuvant therapy.
Conclusion: Our data showed that both low PTEN level and high Tauprotein expression were significantly associated with poor response to H+P chemotherapy in patients with HER2−positive breast cancer.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-13-11.
P5-14-08: Impact of Progesterone Receptor Semiquantitative Immunohistochemical Result on Oncotype DX® Recurrence Score: A Quality Assurance Study of 1078 Cases.
Authors: Bhargava R , Dabbs DJ 
Published: June 2012

Abstract
Background: The oncotype DX® recurrence score (RS) is predominantly dependent on estrogen and progesterone receptor content of the tumor, proliferation and HER2 status. We have previously shown (Mod Pathol. 2008;21:1255–1261) that using a regression equation that incorporates the above along with tumor grade components is capable of estimating the RS [RS=13.424+5.420 (nuclear grade) +5.538 (mitotic count) −0.045 (ER immunohistochemical score) −0.030 (PR immunohistochemical score) +9.486 (HER-2/neu)]. Subsequent studies have also shown similar findings including a few that suggests an even more important role for progesterone receptor. In order to identify the role of semiquantitative progesterone receptor immunohistochemical (IHC) result in a simplistic manner, we evaluated the PR IHC score (H-score) for different categories of RS (low, intermediate, and high) within each tumor grade (I, II, III).
Design: As a continuing quality assurance program at our institution, all cases sent for oncotype DX® testing that have available tumor grade, and RS were included in this study. Hormone receptor results at our institution are reported using an H-score like method which details the percentage of positive cells showing none, weak, moderate, or strong staining. The score is given as the sum of the percent staining multiplied by an ordinal value corresponding to the intensity level (0=none, 1=weak, 2=moderate, 3=strong). With four intensity levels, the resulting score ranges from 0 (no staining in the tumor) to 300 (diffuse intense staining of the tumor).
Results: A total of 1078 cases were analyzed (see table below).

Conclusions: Within each grade, PR IHC score is inversely related to the RS. The dramatic impact of PR IHC score on RS is noteworthy. If PR IHC score is combined with traditional histopathologic features (nuclear grade, mitotic activity score), and other IHC variables (ER IHC score, HER2 status, Ki-67 labeling index), then a tumor's risk of recurrence and need for chemotherapy can be reasonably estimated. Oncotype DX® test may not be necessary in more than half of cases that are currently sent for testing.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-14-08.
P5-14-24: The Long Term Prognostic Impact of Real-Time Quantitative RT-PCR Detection of Cytokeratin 19 mRNA in Preoperative Bone Marrow Aspirates of Early Breast Cancer Patients.
Authors: Punie K , Wynendaele W , Clement P , Paridaens R , Christiaens M-R , Jacobs B , Wildiers H 
Published: June 2012

Abstract
Purpose: Several studies have evaluated the prognostic effect of bone marrow micrometastases at the time of surgery in early breast cancer, but few studies have long term outcome data. We report here a cohort with more than ten years follow-up.
Materials and methods: 131 patients with primary operable invasive breast cancer were enrolled in the protocol from February 1998 to September 1999. Bone marrow aspirates, obtained from the iliac crest or the sternum, were analyzed with real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) for the presence of cytokeratin 19 (CK19) mRNA. All patients received standard therapy and follow-up. After a median follow-up of 133 months, data about disease recurrence (invasive disease free survival, IDFS) and survival (breast cancer specific survival (BCSS) and overall survival (OS)) were collected. A control group consisted of archived cDNA samples from 38 patients with hematological malignant antecedents in complete remission and without known gene arrangements. The upper limit of the 95% confidence interval of the level of CK19 positive cells is this group was used as cut-off (260 cytokeratin 19+ cells / 5 × 106 leucocytes) to determine bone marrow status in breast cancer patients.
Results: 69 bone marrow samples from breast cancer patients (52,7 %) were considered CK19 positive. IDFS was 60.9 % and 79 % for CK19+ and CK19- patients, respectively (log-rank p-value = 0,036). When CK19 was evaluated as a continuous variable, IDFS also correlated significantly with the level of CK19 mRNA in bone marrow aspirates (p-value = 0,019). Except for lymph node status (ANOVA linear regression p-value = 0.022), there was no significant correlation between the level of CK19+ cells in the bone marrow and classical prognostic factors (pathological tumor stage, tumor size, differentiation grade, hormonal receptor status).
In multivariate Cox-regression analysis correcting for tumor size, differentiation grade, lymph node status, hormone receptor status, tumor stage and treatment modalities (surgical procedure, chemotherapy, radiotherapy and antihormonal therapy), the CK19 bone marrow status still was a significant predictor of IDFS. (p-value = 0.042)
Differences in BCSS (78 % of CK19 + patients and 84 % of CK19 — patients) and OS (75 % in CK 19 + patients and 74 % in CK 19 — patients) were not statistically significant. (log rank p-values 0.087 and 0.883, respectively).
Conclusion: This study demonstrates the long term (&gt;ten years) prognostic effect of CK19 mRNA detection with RT-PCR in the bone marrow of operable breast cancer patients.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-14-24.
P5-15-03: Development of a Patient Decision Aid for Women 70 Years and Older with Stage I, Hormonally Sensitive, Breast Cancer Considering Adjuvant Treatment Post-Lumpectomy.
Authors: Szumacher E , Wong J , D'Alimonte L , Angus J , Paszat L , Metcalfe K , Whelan T , Llewellyn-Thomas H 
Published: June 2012

Abstract
Background: Decision Aids (DA) are developed with the intent to support people in making specific and deliberate choices by improving information transfer about different outcomes. Previous research has shown that DAs can increase patient knowledge regarding treatment options, reduce decisional conflict, and increase patient satisfaction with the decision-making process. However, no DAs have been developed to help older breast cancer patients decide whether or not to undergo adjuvant RT. We developed and tested a DA for older women with stage I,ER/PR positive breast cancer considering adjuvant treatment post-lumpectomy and we examined its impact on treatment decision-making process.
Methods and Materials: A DA was developed and evaluated in three steps following the Ottawa Decision Aid Framework: 1) Needs assessment (N=16); 2) Pilot I, to examine the DA's acceptability (N=12); and 3) Pilot II, a pre-test post-test (N=38) with older women with ER/PR responsive breast cancer post-lumpectomy who were receiving adjuvant RT. Measures included questionnaires to assess patient's satisfaction with the DA, patients’ self-reported decisional conflict (DC), level of distress, treatment-related knowledge, and choice predisposition
Results: The DA is a booklet that details each adjuvant treatment option's benefits, risks and side-effects tailored to their clinical profile; includes a value clarification exercise; and steps to guide them towards their own treatment decision. All women felt the DA was helpful and informative. Compared with baseline scores, patients had a statistically significant (p &lt; .05) reduction in DC (adjusted mean difference [AMD], −7.18; 95% confidence interval [CI], −13.50 to 12.59); increased clarity of the treatment benefits and risks (AMD, −10.86, CI, −20.33 to 21.49; and improved general treatment knowledge (AMD, 8.99, CI, 2.88 to 10.28) after using the DA. General trends were also reported in patient's choice predisposition scores suggesting potential differences in treatment decision after DA use. Discussion: This study provides evidence that this DA may be a helpful educational tool for this group of women. The quality of care for older breast cancer patients may be enhanced by using a tailored DA to help the patient be informed of their treatment options and to prepare for decision-making.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-15-03.
P5-17-01: Evaluation of Psychosocial Distress in Main Care-Givers of Patients with Metastatic Breast Cancer Who Receive Treatment in a Community Based Oncology Group Practice.
Authors: Weide R , Feiten S , Friesenhahn V , Heymanns J , Kleboth K , Mergenthaler U , Thomalla J , van Roye C , Köppler H 
Published: June 2012

Abstract
Introduction: It is well-known that people who care for patients with a metastatic carcinoma are exposed to an above-average level of psychosocial distress. No data are available concerning the distress of main care-givers of female patients with metastatic breast cancer, who are treated in a community based oncology group practice.
Methods: Standardized cross-sectional survey of main care-givers and patients with metastatic breast cancer who were treated in a community based oncology group practice in Germany between 04/2010-03/2011. Psychosocial distress of the patients and their main care-givers were evaluated using the German versions of the Distress Thermometer (DT) and the Problem List (PL). In addition anxiety and depression of the main care-givers were assessed using the Hospital Anxiety and Depression Scale (HADS-D).
Results: 83 female patients with a median age of 65 (41-93) were interviewed. 6% did not have a main care-giver, 7% indicated that they needed no support, 48% reported one main care-giver and 39% several. Partners (60%), children (47%), siblings (11%) and friends (10%) were the most important care-givers. 47% of patients preferred visiting the practice in companion with their care-givers. The patients’ median score on the DT was 5 (0-10), with 34% scoring above cut-off (&gt; 5) for psychosocial distress. 52 main care-givers (61% male, 39% female) with a median age of 57.5 (41-86) were interviewed. The relationships to the patients were as follows: partners 62%, children 27%, mothers, siblings and friends each with 4%. The main care-givers themselves were supported by partners (54%), children (21%) friends (17%) and siblings (8%), 23% did not receive any support. The median score on the DT was 5 (0-10), with 44% scoring above cut-off (&gt; 5) for psychosocial distress. According to the HADS-D 37% (cut-off ≥ 8) of the care-givers reported anxiety, with a mean score of 6.6 (0-14). 15% could be regarded as depressed (cut-off ≥ 8), with a mean score of 4.1 (0-15).
Conclusions: The main care-givers are distressed even more than the patients themselves. 37% of care-givers reported anxiety; depression can be observed too, but less frequently in 15%. Both issues should be addressed by healthcare professionals.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-17-01.
P5-19-04: Results of a Randomized Phase II Study Demonstrate Benefit of Platinum-Based Regimen in the First-Line Treatment of Triple Negative Breast Cancer (TNBC).
Authors: Fan Y , Xu BH , Yuan P , Wang JY , Ma F , Ding XY , Zhang P , Li Q , Cai RG 
Published: June 2012

Abstract
Background: It is supposed that triple negative breast cancer (TNBC) may be more sensitive to DNA damage agents such as platinum. This study was designed to compare platinum-based regimen (docetaxel plus cisplatin) with non-platinum-based regimen (docetaxel plus capecitabine) in the first-line treatment of advanced triple negative breast cancer patients.
Patients and Methods: This was a single-institution, randomized phase II clinical trial. Eligible TNBC women with first relapse or metastasis who had measurable disease were randomized (1:1) to receive either TP regimen (docetaxel 75mg/m2 plus cisplatin 75mg/m2 intravenous infusion day 1) or TX regimen (docetaxel 75mg/m2 intravenous infusion day 1 plus capecitabine 1000mg/m2 bid, two weeks on, one week off) every 3 weeks for up to 6 cycles, until disease progression, unacceptable toxicity or patient consent withdrawal. The primary endpoint was objective response rate (ORR) and secondary endpoints included progression free survival (PFS), overall survival (OS) and safety profile. To detect a difference of 0.35 in response rate between groups with a power of 80% and 2-sided significance level at 0.05, there should be at least 26 patients in each group. As of Jun 1st, 2011, 53 patients had been randomized and evaluated.
Results: After a median follow-up of 24 months, the results showed much higher response rate in TP group than TX group although the clinical benefit rate was not significantly different. PFS was more than doubled in TP group compared with TX group. Overall survival was also statistically improved. G3/4 vomiting was merely observed in 3 patients from TP group. On the contrary, only patients in TX group (5/26) reported G2/3 Hand-Foot Syndrome. No differences were found in hematological and other non-hematological toxicities.

Conclusions: Although it is a small sample size phase II study, it strongly suggested that cisplatin-contained TP regimen improved patient outcome, as measured by ORR, CBR, PFS and OS, compared with non-cisplatin-based TX regimen in the first-line treatment of advanced TNBC patients. This is the first prospective study to show superiority of cisplatin over capecitabine in TNBC. Together with additional ongoing clinical trials comparing platinum with other chemotherapeutic agents in various settings, the role of platinum in TNBC can be further elucidated.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-19-04.
P5-20-01: Patient Valuation of Reduced Risk of Side Effects during Treatment for Metastatic Breast Cancer.
Authors: Lalla D , McLaughlin T , Brammer M , Bramley T , Bare A , Carlton R 
Published: June 2012

Abstract
Background
Chemotherapy treatment for metastatic breast cancer (MBC) has shown significant benefits in survival for breast cancer patients. However, chemotherapy is associated with several side effects that have a significant impact on patients’ quality of life. The objective of this analysis was to quantify the value patients with MBC place on reduced risk of treatment side effects.
Methods: A willingness to pay (WTP) survey was developed to assess metastatic breast cancer patients’ willingness to pay for a reduction in the risk of breast cancer treatment side effects. The survey assessed patients’ WTP for a 25%, 50% and 100% reduction in the risk of all side effects. Patients were also asked to select the side effect they would pay the most to avoid. Additionally, the survey collected demographic information such as treatment regimen, age, race/ethnicity, region, employment status, and insurance type.
Results: The survey was completed by 202 metastatic breast cancer patients. Most survey respondents were white (94%), married (62%), and over the age of 51 (78%). Most patients were covered by private insurance (67%) or Medicare (24%). Of the 58% of respondents who remembered paying out of pocket for their last treatment, the average out of pocket payment was $459. Survey respondents were willing to pay an extra $1,886, $3,837 and $7,794 for a 25%, 50% and 100% reduction in the risk of all side effects, respectively. Hair loss (28%), pain (17%) and nausea (15%) were selected most often as the side effect respondents would pay the most to avoid.
Discussion: Chemotherapy for MBC is associated with several adverse events that patients would like to avoid or reduce such as hair loss, pain, nausea and neutropenia. This analysis demonstrates patients with MBC place a significant value on reducing the risk of side effects and are willing to pay 4.2 times for a treatment devoid of side effects as compared to a treatment with a 25% reduction in the risk of treatment side effects.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-20-01.
P5-23-04: Gonadotrophin-Releasing Hormone Analogues for Ovarian Function Preservation in Women with Premenopausal Breast Cancer Undergoing Adjuvant Chemotherapy: A Systematic Review and Meta-Analysis.
Authors: Cruz MRS , Motta E , Silva EMK , Bernardo SG , Atallah AN 
Published: June 2012

Abstract
Background: Breast cancer, the most common female malignancy, is also the most frequent tumor in women of reproductive age. Young women with breast cancer usually present adverse prognostic features and higher rates of recurrence when compared with their older counterparts. Adjuvant chemotherapy is usually recommended for this group of patients and premature ovarian failure (POF) is a potential complication.
Material and Methods: We conducted a systematic search in MEDLINE, EMBASE, Cochrane Systematic Reviews databases and ***ClinicalTrials.gov from their inception until June 2011. The search was conducted to include published peer-reviewed studies on the issue of fertility preservation in women with breast cancer undergoing adjuvant chemotherapy. The search terms were tailored individually for each database to include the following Medical Subject Headings (MeSH) and text words: gonadotropin releasing hormone, breast neoplasms, drug therapy, premature ovarian failure and fertility. No language restriction was applied. We also searched for additional studies by reviewing the reference lists of retrieved articles, and studies presented in abstract form were also located in this manner. The main outcomes were return of spontaneous menstruation, ovulation and pregnancy rate.
Results: We found 8 RCTs that met the inclusion criteria. Data were extracted from 3 RCTs. Data were only available for resumption of ovulation. There were no data available for markers of ovarian function, rate of ovulation and pregnancy. The rate of women with spontaneous menstruation demonstrated a statistically significant difference in favor of the use of GnRH-a (OR 3.11;95% CI, 2.04-472). Discussion: Use of GnRH concomitant to adjuvant chemotherapy in premenopausal breast cancer women aiming to reduce rates of POF has been subject of controversy during the last decade. Evidence from recently presented RCTs suggests there is a benefit of GnRH for ovarian function protection in this setting.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-23-04.