bluuebunny/crossref_metadata_2025 huggingface dataset:
CtIP, a BRCA1 binding protein, is a transcriptional corepressor of estrogen receptor α.
Authors: Ludes-Meyers JH , Wu M , Aldaz C
Published: December 2010

Abstract #606

The role of estrogen and estrogen receptor (ER) transcriptional regulation in breast carcinogenesis is indisputable. In the last few years there has been dramatic progress in understanding how receptor transcriptional coactivator and corepressor complexes operate.  We demonstrated that CtIP (CtBP interacting protein) is downregulated in tamoxifen resistant breast cancer lines. Furthermore, CtIP protein expression correlates with response to neo-adjuvant endocrine therapy and patients with progressive disease express lower CtIP protein in their primary breast carcinomas than those who respond. CtIP expression directly correlates with ER alpha expression, and inversely correlates with disease free survival and breast cancer metastasis. Importantly, silencing endogenous CtIP confers tamoxifen resistance in tamoxifen sensitive breast cancer cells and re-expression restored tamoxifen sensitivity in resistant breast cancer cells (Wu et al. Molec. Cancer Res. 2007; 5: 1285-1295). Our findings indicate that CtIP silencing is a novel mechanism for the development of tamoxifen resistance in breast cancer.  CtIP interacts with the BRCT domains of BRCA1 where most mutations occur in familial BRCA1 breast cancers. CtIP also interacts with the transcriptional corepressor CtBP. Emerging evidence suggests that CtIP is involved in transcriptional repression and may be a tumor suppressor gene. We hypothesize that CtIP plays a key role in repression of ER transcription and such repressive function is linked to the inhibitory growth effects exerted by tamoxifen. We further speculate that CtIP inhibition of ER transcription is mediated by its ability to bridge BRCA1 with CtBP to form a transcriptional corepressor complex able to modulate ER activity via the interaction between BRCA1 and ER and that CtIP is in fact required for BRCA1 to exert its transcriptional repression activity on ER. We will present our work showing that CtIP, BRCA1 and CtBP form a multiprotein complex, that requires CtIP, and associates with ER in breast cancer cells. More importantly, we will show that BRCA1, CtIP and CtBP associate with ER on the ER-dependent promoter of the pS2 gene in the absence of ligand. Stimulation by ligand leads to dissociation of the complex and ER-dependent gene expression. Furthermore, silencing CtIP expression using RNAi in E2-starved MCF-7 cells led to an increase of basal transcription of the pS2 gene. CtIP was also observed to repress E2 stimulation of ERE-luciferase in transfected MCF-7 cells. We are currently characterizing the role of the CtIP corepressor complex in ER-transcriptional activity. We will present the results of our efforts to identify specific ER-dependent promoters repressed by the CtIP corepressor. In addition, we will present results of studies aimed at characterizing CtIP-specific changes in chromatin remodeling and ER-cofactor recruitment at ER-dependent promoters.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 606.
p53 mutations to predict efficacy of alkylating-containing regimen: a metaanalysis of four different clinical trials.
Authors: Lehmann-Che J , André F , Desmedt C , Giacchetti S , Sotiriou C , Turpin E , Espié M , Marty M , Piccart M , Pusztai L , De Thé H
Published: December 2010

Abstract #6064

Background. The predictive value of p53 mutations for efficacy of anthracycline-based chemotherapy is matter of controversy. Inconsistencies among studies could be related to the heterogeneous use of alkylating agents in combination with anthracyclines in different studies. We examined the predictive value of p53 mutations in four different series of breast cancer patients treated with preoperative anthracycline-based chemotherapy including different doses of cyclophosphamide (C).  Patients and Methods. All patients had stage II-III breast cancer and received anthracycline-containing chemotherapies. A total of 352 patients were included in four different clinical studies : 65 patients with estrogen receptor (ER)-negative cancers treated with single agent epirubicine (E) (100 mg/m2/3w x 4) in the TOP trial (R1), 52 patients treated with FAC (500 mg/m2 C, 5-FU and 50 mg/m2 doxorubicin/3w x 6) (R2), 96 patients treated with EC-T (75mg/m2 E and 750 mg/m2 C/3w x 4 followed by 100mg/m2 docetaxel/3w x 4) (R3) and 139 patients treated with dose-dense EC (1200mg/m2 C and 75 mg/m2 E/2w x 6) (R4). Before therapy, p53 status was determined in all tumors by yeast functional complementation (FASAY) assay. After chemotherapy, all patients underwent surgery. Pathologic complete response (pCR) was defined as no residual invasive tumour cells in breast and lymph nodes.  Results. P53 mutations were more frequently observed in the 128 ER-neg compared to ER-pos cancers (78% vs 29.4%). In p53 mutated tumours, the pCR rate increased with the dose-intensity of C. Conversely, in p53 wild type tumours, pCR rates decreased.    Focusing on ER-neg, p53 mutated tumors, the pCR rates rose from 11%, 6%, 32% to 52% in R1, R2, R3 and R4 groups. The R1 and R4 regimen, differing only in C dose intensity, showed marked differences in pCR in ERneg tumors.    Conclusions: Increasing doses of C do not seem to improve pCR rates in P53 wild type tumours, raising the possibility of antagonism with anthracycline in this group. On the other hand, in ER-neg, p53 mutant tumors, inclusion of dose-intense C seems to significantly increase pCR rates.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6064.
Response to neoadjuvant chemotherapy in patients with triple negative breast cancer.
Authors: Abe E , Hayashi N , Yoshida A , Hamaoka T , Yagata H , Tsugawa K , Tsunoda-Shimizu H , Suzuki K , Nakamura S
Published: December 2010

Abstract #6069

Background:  Triple negative breast cancer (TNBC) is defined by the lack of estrogen receptor(ER), progesterone receptor (PR), and human epidermal growth factor receptor2 (HER-2) expression. TNBC has poor outcome due to no specific therapeutic agents. But TNBC includes two major phenotypes, basal-like and non basal-like phenotypes. Basal-like phenotype has poor prognosis and is associated with positive expression of basal markers. We compared response to neoadjuvant chemotherapy between patients with TNBC and non-TNBC, in addition, basal-like and non basal-like phenotype.  Material and Methods:  We retrospectively reviewed a total of 1948 operated patients with a diagnosis of primary breast cancer from November 2002 to December 2006 at St. Luke's International Hospital. 369 (18.9%) patients received neoadjuvant chemotherapy. Clinical and pathological response rates, survival measurements and relapse rates were compared between patients with TNBC and non-TNBC. Clinical response was determined by MRI or CT which was performed before and after neoadjuvant chemotherapy. Histopathological parameter(ER, PGR, HER-2, nuclear grade, mitosis) were confirmed from the specimens of needle biopsy performed before treatment. The specimens were also stained with basal markers (cytokeratin 5/6 and EGFR) to identify basal-like phenotype in TNBC. Basal-like phenotype was defined by the expression of CK5/6 and/or EGFR in >10% of tumor cells.  Results:  Fifty-four of 369 patients (14.6%) had TNBC. Progressive disease (PD) rate was significantly higher in patients with TNBC than those patients with non-TNBC (20.7% v 2.3%).And pathologic complete response rate (pCR) was also higher in patients with TNBC than those patients with non-TNBC (17% v 9.6%).14of 48 patients (29.1%) was diagnosed as Basal-like phenotype in TNBC. Clinical response rate for basal-like phenotype was worse than non basal-like phenotype (42.9% v 67.6%). Furthermore, both disease free survival and overall survival for basal-like subtype were significantly worse than non basal-like phenotype (p<0.05).Other parameters including age, histological grade, and tumor size were not significant for response to neoadjuvant chemotherapy.  Conclusions:  Patients with TNBC have higher PD rate but also pCR rate to treatment compared with non TNBC. Furthermore, basal-like phenotype could predict poor prognosis.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6069.
Breast cancer molecular classification using immunohistochemical surrogate markers predicts response to neoadjuvant chemotherapy.
Authors: Bhargava R , Goldman F , Beriwal S , Dabbs DJ , Johnson R , Brufsky AM , Lembersky BC , Ahrendt GM
Published: December 2010

Abstract #6071

Complete pathologic response (pCR) to neo-adjuvant chemotherapy (NACT) is seen in 45% of "ERBB2" and "basal-like" group of tumors using gene expression profiling (Rouzier et al. Clin Cancer Res. 2005;11:5678-5685).  We hypothesized that a similar response could be predicted using the immunohistochemical (IHC) surrogate markers estrogen receptors (ER), progesterone receptors (PR) and HER2. ER and PR were scored using a semi-quantitative scoring method (modified "H-score") with a dynamic range of 0-300. HER2 was considered positive only if 3+ by IHC or amplified (HER2 to chromosome 17 ratio of >2.2) by FISH. These markers were used to classify 358 tumors treated with NACT into the following 6 groups: luminal A (LUMA; ER score 200 or higher, HER2 negative); ERBB2 (ER and PR score 10 or less, HER2+); triple negative (TN; ER and PR score 10 or less, HER2 negative); luminal A-HER2 hybrid (LAHH; ER score 200 or higher, HER2+); luminal unclassified HER2 negative (LUHN; ER or PR score 11-199, HER2 negative); luminal unclassified HER2 positive (LUHP; ER or PR score 11-199, HER2+). pCR was defined as absence of invasive carcinoma in the post therapy resection specimen along with lack of carcinoma within regional lymph nodes.  pCR and average tumor size reduction was much higher in ERBB2 and TN group of tumors compared to the other classes (p<0.05).    Trastuzumab was part of NACT regimen in 6 ERBB2 tumors of which 5 (83%) showed pCR. In contrast, 10 patients with LUHP and LAHH tumors (ER/PR+ and HER2+ tumors) received trastuzumab, of which none showed pCR.  Conclusions: pCR to NACT is generally limited to "ERBB2" and "TN" tumors. This response can be predicted with similar (to expression profiling) accuracy using IHC surrogate markers. Sub-division of ER+ tumors into LUMA, LUHN, LAHH, and LUHP demonstrates subtle differences between these groups with respect to pCR and tumor size reduction and confirms that NACT is less effective in all ER+ tumors. Among all HER2+ tumors, trastuzumab treatment is much more effective in ERBB2 tumors.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6071.
TIMP-1 and responsiveness of estrogen receptor negative breast cancer to preoperative epirubicin and cyclophosphamide with or without gefitinib.
Authors: Hertel PB , Brünner N , Jørgensen LA , Petersen MB , Ingvar C , Jacobsen EH , Sætersdal AB , Tuxen MK , Nielsen BS , Mouridsen HT , Ejlertsen B
Published: December 2010

Abstract #6072

Background: Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) is a naturally occuring proteinase inhibitor, which inhibits most matrix metalloproteinases. It has previously been reported that high levels of tumor TIMP-1 is associated with lack of clinical benefit from anthracycline based chemotherapy in metastatic breast cancer and preliminary data suggest that this is also true for adjuvant treatment. Plasma TIMP-1 has also been shown to predict response to endocrine therapy in patients with metastatic breast cancer. No data regarding TIMP-1 response to neo-adjuvant treatment exists.  Material and Methods: NICE (1839IL/0712) is a randomized phase II trial, assigning 144 patients per protocol with primary operable estrogen receptor negative breast cancer and tumor ≥ 2 cm to either four cycles of EC (epirubicin 90 mg/m2 and cyclophosphamide 600 mg/m2) plus placebo or EC plus gefitinib 250 mg daily. The primary endpoint was pCR (no invasive residual) at surgery and secondary endpoints were complete (CR) and overall objective (OR) tumor response rates (CR+PR) assessed by palpation, mammography and ultrasonography (the last prevailed in case of disagreements). Plasma TIMP-1 levels were measured (blinded and in duplicates) before and after preoperative EC using a validated enzyme-linked immunosorbent assay.  Results: 'pCR was attained by 8/71 patients in the EC + gefitinib group and 8/73 patients in the EC + placebo group, and OR by 50 patients in each treatment group. The addition of gefitinib to pre-operative EC was not associated with any significant benefit, thereby justifying pooling of the 2 groups of patients. TIMP-1 ranged from 55.1 to 519 ng/ml, median 126.8 ng/ml at baseline. Patients who obtained pCR had numeric higher plasma TIMP-1 values than non-responders (155.2ng/ml against 139.9 ng/ml, p=0.35). Dichotomizing patients by the plasma TIMP-1 median showed, that patients with elevated TIMP-1 had a numeric increased likelihood of obtaining pCR and OR: Patients with plasma TIMP-1 above the median had a numeric higher pCR rate (6.6% against 4.4%; odds ratio 1.60, p=0.39), and OR (51.0% against 49.0%; odds ratio 1.20, p=0.61). A small decline in TIMP-1 was observed after four cycles of EC (median difference 4.5, 25% and 75% quartile of -28.6 and 27.9, p=0.85) and the change was nearly the same in responders as in non-responders.  Conclusion: This study could not demonstrate a predictive role of pre-treatment plasma TIMP-1 in neo-adjuvant chemotherapy for primary breast cancer. A change in plasma levels of TIMP-1 during 4 cycles of EC was not associated with response to the treatment.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6072.
Serum biomarker analysis in a phase II study of irinotecan in refractory metastatic breast cancer (MBC).
Authors: Moreno-Aspitia A , Anderson KS , Reinholz MM , Lipton A , Carney W , Dueck AC , Lafky JM , Fitch TR , Hillman DW , Perez EA
Published: December 2010

Abstract #6074

Objective: To analyze blood-serum biomarkers (HER2, EGFR, uPA, and TIMP-1) for prediction of response to treatment in conjunction with Study 96-32-55, a multicenter phase II trial assessing the efficacy and tolerability of two irinotecan schedules in anthracycline- or taxane-refractory MBC patients.  Methods: MBC patients who experienced disease progression after one to three chemotherapy regimens, including at least one anthracycline- or taxane-based regimen, were randomly assigned to irinotecan in 6-week cycles comprising 100 mg/m2 weekly for 4 weeks, then a 2-week rest or 240 mg/m2 every 3 weeks. During this study the serum samples from each patient were collected at a possibility of three time points; prior to treatment, at the first occurrence of response, and at completion of or withdrawal from treatment. Response prediction was analyzed using predetermined elevated/non-elevated serum biomarker cutoffs. Percentage changes from baseline to first response and disease progression were analyzed.  Results: In the weekly arm, the objective response (CR+PR) rate was 23% (95% CI, 13% to 37%), and in the every-3-weeks arm, the objective response rate was 14% (95% CI, 6% to 26%). Serum biomarker levels were determined for HER2, EGFR, uPA, and TIMP-1 prior to treatment for 91 patients. Of these 91 patients, 17 had serum measurements at first response, and 38 had serum measurements at their completion of study due to disease progression. Only 7 patients had serum-levels collected at all three event-points. The baseline levels of sHER2, EGFR, uPA, and TIMP-1 were not different among responders and non-responders (Fisher's Exact p=0.41, 0.26, 0.68, 0.75). sHER2 level increased by 20.6% from baseline to disease progression (p=0.01). TIMP-1 level was 15.2% lower than baseline at first response (p=0.03), 16.5% higher than baseline at disease progression (p=0.01), and for 7 patients with all three event-point measures, TIMP-1 was 21.8% lower than baseline at first response and was 22.3% higher than baseline at disease progression (p=0.02, 0.04).  Conclusions: In this study, serum levels of HER2, EGFR, uPA, and TIMP-1 do not appear to be predictive of response. However, interpretation of the data is compromised due to limited availability of serum at all 3 points. Serum HER2 appears higher at disease progression than at baseline. Serum TIMP-1 appears to decrease from baseline to first response, and then appears to increase at disease progression.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6074.
Lifestyle, weight history, nutrition and breast cancer among non-gene carriers: a case-control study.
Authors: Ghadirian P , Bissonauth V , Maugard C , Robidoux A , Narod SA
Published: December 2010

Abstract #6084

We conducted a nested case-control study of 280 French-Canadian women with breast cancer who were non-gene carriers (BRCA) and 280 women without cancer who were also non-gene carriers. A validated lifestyle questionnaire and a food frequency questionnaire were administered to obtain relevant information. It was found that age at the time the subjects reached maximum body mass index (BMI) was significantly associated with breast cancer risk [OR=2.83; 95% CI: (2.34-2.81)]. In addition, a significant association was noted between maximum weight gain at age 20 years [OR=1.68; 95% CI: (1.10-2.58)], 30 years [OR=1.96; 95% CI: (1.46-3.06)], and 40 years [OR=2.50; 95% CI: (1.72-3.97)] and breast cancer risk. Women who smoked more than 9 pack-years of cigarettes had a higher risk of breast cancer [OR=1.59; 95% CI: (1.57-2.87)]. Subjects who engaged in moderate physical activity had a 52% decreased risk of breast cancer [OR=0.48; 95% CI: (0.31-0.74)], but this was not evident for vigorous physical activity. It was observed that total energy intake was significantly associated with breast cancer risk [OR=2.54; 95% CI: (1.67-3.84)]. Women who drank more than 8 cups of coffee per day had 40% more chance of developing breast cancer [OR=1.40 (95% CI: (1.09-2.24)]. Subjects who consumed more than 9 grams of alcohol (ethanol) per day had the highest risk of breast cancer [OR=1.55 (95% CI: (1.02-2.37)]. None of the other nutrients and dietary components was significantly associated with non-gene carrier breast cancer risk. This study suggests that BMI, maximum weight gain during the second, third and fourth decades, smoking, total energy intake, and high intake of both alcohol and coffee may increase the risk of breast cancer among non-gene carrier French-Canadian women, while moderate physical activities may reduce the risk.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6084.
Breast brachytherapy in the United States: how is this emerging modality being incorporated into the care of older breast cancer patients?.
Authors: Smith GL , Shih YT , Xu Y , Giordano SH , Smith BD , Buchholz TA
Published: December 2010

Abstract #6087

Introduction: Several studies have demonstrated the potential value of brachytherapy in the treatment of breast cancer, either as local boost irradiation, or alone as accelerated partial breast irradiation, after breast conserving surgery (BCS). In 2002, the Food and Drug Administration approved the first balloon-based brachytherapy delivery system, signaling the beginning of broader incorporation of partial breast irradiation into breast cancer treatment. While subsequent studies have been seeking to define the patient population that will derive optimal clinical benefit from breast brachytherapy, this treatment option has remained widely available for use in a variety of settings. However, no prior study has described the frequency of breast brachytherapy use in the US. In a population-based cohort of older breast cancer patients, we characterized utilization of breast brachytherapy across the nation at the inception of this era.  Methods: A cross-sectional sample from a national Medicare database identified 37,323 beneficiaries (age≥65) with newly diagnosed invasive breast cancer treated with BCS in 2003. ICD-9 and CPT codes indicated receipt of external beam radiotherapy (EBRT) and brachytherapy. Percent use by state, region, age, and race was compared using Pearson χ2.  Results: Across the nation, 73% of older patients were treated with any radiotherapy after BCS. Of these patients, 97% were treated with EBRT alone, 3% with brachytherapy alone, and <1% with EBRT plus brachytherapy boost. For patients treated with brachytherapy, 98% received interstitial therapy and 2% intracavitary therapy. Though percent utilization of brachytherapy modalities ranged from 1% to 4% across different locations in the US, no statistically significant variation was detected by state (P=0.62) or by region (P=0.32). In addition, brachytherapy use did not differ by race (P=0.63) or age (P=0.59).  Conclusions: At the inception of the era in which partial breast irradiation was becoming incorporated into the care of breast cancer patients, only a small percentage of all patients received breast brachytherapy across the US. As contemporary data become available, future studies may seek to trace how this new treatment strategy is becoming more widely integrated into routine breast cancer treatment.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6087.
Increased incidence of breast cancer among young women: reality or overestimation?.
Authors: Freitas-Júnior R , Freitas NM , Curado M , Martins E , Queiroz GS , Rahal RS
Published: December 2010

Abstract #6088

Background: a story is going around that there has been a large increase in the incidence of breast cancer among young women, but there is very little scientific information regarding such an occurrence in developing countries. This study had the aim of investigating the incidence of breast cancer among young women (up to 39 years), and comparing this with other age groups. Patients and methods: this was a retrospective study using the database of the Population-based Cancer Registry of Goiania, State of Goias, Brazil, covering the years 1988-2003. Cases of breast cancer that occurred in Goiania were analyzed. The incidence was calculated according to age groups: up to 39 years, 40 to 59 years and 60 years and over. The values were adjusted for sex and age, in accordance with Segi's worldwide population (1960). Results: Over this period, 3,310 new cases were recorded. The standardized incidence was 2.89/100,000 in 1988 and increased to 6.37/100,000 in 2003 (R2 = 0.72) for the group aged up to 39 years (p<0.001). For the group from 40 to 59 years, the incidence was 14.39/100,000 in 1988 and 41.70/100,000 in 2003 (R2 = 0.87; p<0.001). For the group aged 60 years and over, it was 17.62/100,000 and 28.49/100,000, respectively (R2 = 0.75; p<0.001). Conclusions: The incidence of breast cancer among young women in the city of Goiania has been increasing significantly, although this increase is less pronounced than in the other age groups.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6088.
A clinico-pathological analysis of breast cancer patients with a family history.
Authors: Hojo T , Kinoshita T , Kikuyama M , Nakano E , Akashi S , Khono T , Ando M , Katsumata N , Fujiwara Y
Published: December 2010

Abstract #6090

Background: It has been said that the high incidence of breast cancer within family lines could be investigated efficiently from genetic and environmental aspects. There could be a strong enough relationship between various carcinogenic factors and these family members. In this study, we examined the clinical and pathological characteristics of breast cancer among patients with a family history.  Patients and Methods: We put the definition of 'Positive for a family history (FH+)' for patients who had one or more members within three generations apart from the proband. Patients with family history of breast cancer were selected out of 10506 patients who were treated in our hospital between 1962 and 2007.  Results: There were 1272 cases in FH+ and 9234 cases in 'Negative for a family history (FH-)' group. Distribution within the family line showed the highest percentage for sisters at 37%, aunts at 25% and a mother at 25%. The family history positive breast cancer patients were around 5% in 1960-1970 although the number increased up to 18% in 2007. There was similar increasing pattern in Europe and America. The survival rate had no significant difference between FH+ and FH- statistically, but the trend was toward a better prognosis in FH+ cases. There was no relationship between family history and body mass index (BMI). The outbreak of contralateral breast cancer of FH+ was significantly higher than FH-. FH+ patients had significantly higher prevalence of a mastopathy compare to FH- patients. As for the history of other cancer species, the FH+ breast cancer patients within first generation apart from the proband had significantly higher chances compared to FH- patients.Conclusion: The breast cancer patients with family history require more detail examinations especially for the development of contralateral breast cancer. Also carcinomatous examinations are important other than breast cancer to those patients who are in the first generation apart from the proband.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6090.
Survival outcome is similar for first-line chemotherapy with capecitabine or taxane for metastatic breast cancer.
Authors: Kimmick GG , Camacho F , Wei W , Balkrishnan R , Anderson R
Published: December 2010

Abstract #6091

Background: Capecitabine is often offered as first-line treatment option for metastatic breast cancer (MBC). In this study, we compare characteristics of and survival among women prescribed capecitabine or taxane monotherapy as first-line chemotherapy for MBC.  Methods: Women receiving first-line chemotherapy for MBC from 1998 to 2005 were identified from the North Carolina tumor registry linked with Medicaid and Medicare claims records, and were followed through the end of 2005 with survival data from the National Death Index. T-tests and Chi-square tests were used to compare baseline charactistics between patients who received first-line chemotherapy with capecitabine versus taxane (paclitaxel or docetaxel). Overall survival was examined as average months survived post-diagnosis of metastases using Cox proportional hazard modeling. The following variables were included in the models: age, race, comorbidity, insurance coverage, hormone receptor (HR) status, time from diagnosis of metastases to first-line chemotherapy, trastuzumab use, time from initial diagnosis to metastasis, receipt of adjuvant chemotherapy or hormonal therapy, and year of first-line chemotherapy.  Results: There were 257 patients with MBC starting first-line chemotherapy with capecitabine (n=71) or a taxane (n=186). Statistically significant differences between patients treated with capecitabine versus taxane were seen for the following baseline characteristics: insurance coverage, such that women in the taxane group were more likely insured by Medicare only; time from initial diagnosis to recurrence was longer in the capecitabine group; time from metastases to first-line chemotherapy was longer in the capecitabine group. The unadjusted 1-year overall and cancer-specific survival rates were longer for the taxane treated group than for the capecitabine treated group: 72% vs 59%, p=0.002, and 75% and 63%, p=0.01. In multivariate analysis, treatment received was not associated with overall or cancer-specific survival after adjustment for baseline differences in the populations. Factors significantly associated with increased overall and cancer-specific survival were positive HR status (HR 0.65, p=0.01; HR 0.60, p=0.005), greater time from metastases until 1st line chemotherapy (for each additional month: HR 0.95, p 0.0001; HR 0.96, p=0.0004), and earlier year of 1st line chemotherapy (for each previous year compared to successive year 2005-1998: HR 0.86, p=0.022; HR 0.86, p=0.03).  Conclusions: In this population-based study, women who received capecitabine as first-line treatment for MBC were more often insured by Medicaid, had a longer disease free interval and time to first-line chemotherapy from diagnosis of metastases. In multivariate analysis, however, first-line capecitabine and taxane for MBC yielded similar survival outcomes.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6091.
Clinical outcomes of obese low socioeconomic status women diagnosed with invasive breast cancer.
Authors: Quispe DR , Quispe ME , Runhua S , Amanda SW , Gary BV
Published: December 2010

Abstract #6092

Background: Obesity a possible risk factor for breast cancer development, may along with low socioeconomic status (LSES) influence breast cancer outcomes. Louisiana a state with the second highest level of poverty has an obesity prevalence above 25%. The Feist-Weiller Cancer Center (FWCC) provides oncology care to the majority of LSES patients (pts) in the nothern half of the state. This study examines if there is a difference in clinical outcomes in obese patients with invasive breast cancer treated at FWCC.  Methods: The electronic medical records of pts with histologically proven invasive breast cancer diagnosed between 1981-2006 at FWCC were reviewed. Pts with Stage IV breast cancer at diagnosis were excluded. Data on insurance, race, body mass index at diagnosis (BMI), stage, disease free interval (DFI) and survival time was analyzed. National Institutes of Health criteria was used to stratify pts into normal weight (NW)[ BMI <25 kg/m2], overweight (OW) [BMI 25-30 kg/m2], and obese (OB)[BMI >30 kg/m2]. LSES was defined as pts who were either uninsured or received Medicaid assistance. Differences in DFI and Overall survival (OS) were analyzed by BMI.  Results: 647 pts were analyzed, 49% were obese and 29% were overweight. 47% were African Americans and 53% were Caucasians. 49% had LSES (22% uninsured and 27% received Medicaid). Obese pts were more likely to be African American (58%; p<0.001), LSES (57%; p=0.003), with Stage III breast cancer at diagnosis (23%; p=0.003) and to develop contralateral breast cancer after the initial diagnosis (10%; p=0.003). One hundred seventy three (27%) pts relapsed (90 obese and 82 non obese) and 74 (11%) deaths occurred (37 obese and 40 non obese). Obese pts had a shorter median DFI (56 months) in comparison with NW and OW pts (67 months and 70 months, respectively) however this difference was not statistically significant (p=0.43). Regarding OS, there were no statistically significant differences between BMI groups. In multivariate analysis using Cox regression model, after adjusting for race, SES, stage at diagnosis, menopausal status, age at diagnosis, smoker status, obesity remains as a none significant predictor of time to relapse. (HR=1.3; p=0.12)  Conclusion: Our results suggest that African American race, low socioeconomic status, stage III at diagnosis and contralateral breast cancer occurrence are associated with obesity at diagnosis of invasive breast cancer. In our patient population, obesity did not appear to contribute to increase risk of relapse or shorter OS.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6092.
Who calls the breast care nurses – the rich, the poor or the poorly?.
Authors: Chaudhry A , Massey E , Roe T , Price R , Scarrott S , Chan C
Published: December 2010

Abstract #6094

Introduction: Breast care nurses (BCNs) are valuable members of the team; they provide advice, counselling and act as patients' advocates. We have previously demonstrated the worth of BCNs in our UK centre1 and the high number of calls they receive from patients and family. In this study, we investigate factors that might influence call rates from individual patients. We have examined the effect of patient age, prognosis and social deprivation on demand for this service.  Methods: Our BCNs collect prospectively daily call sheets. These sheets include hospital number, age, type of call (phone or face to face), duration of call, purpose of call and outcome. We have examined breast nurse call sheets over a six-month period. The patients' home zip codes were also collected and allocated to the correct electoral ward (small geographical areas with average population of 5500). Using data from the UK National Census in 2000, information on social status was derived from the patients' zip codes and given as the Index of Multiple Deprivation (ID2000). The ID2000 has both an ID2000 score and ID2000 ranking for different electoral wards across England. Low ID2000 scores and high ID2000 rankings correspond to areas of affluence. Prognostic information was derived using the Nottingham Prognostic Index (NPI). The data were analysed by Spearman rank correlation using Statview 5.0 (SAS Inc) software comparing call rate to age, NPI and ID2000 scores & rankings.  Results: During a six-month period, 1188 patients contacted the breast cancer nurse specialists in the NHS and private setting. 204 (17.1%) patients contacted their BCN once; 228 (19.1%) twice; 264 (22.2%) three times and 492 (41.4%) of patients called four times or more.  Analysis by Spearman rank correlation of number of calls against age (Rho = -0.009, p=0.90), NPI (Rho = 0.068, p=0.40), ID2000 scores (Rho = 0.058, p=0.41) & ID20000 rank (Rho = -0.060, p=0.40) show no evidence of a relationship between age, prognosis or deprivation and the need to access BCNs.  Conclusions: The BCNs provide a valuable service to patients with breast cancer. This support continues throughout the individual patient's cancer journey. In Gloucestershire, the need for support appears to be independent of age, prognosis and social status.  1 Counselling women with breast cancer - whose line is it anyway?  F G Court, S Scarrott, M Cassidy-Gray, A Thomas, S Vestey, J Bristol, M Ghilchik, H Y Chan  Abstract 6045 - SABCS 2007.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6094.
Obesity a significant risk factor for contralateral breast cancer ocurrence.
Authors: Quispe ME , Quispe DR , Shi R , Sun AW , Burton GV
Published: December 2010

Abstract #6097

Background: The health consequences of obesity are significant and it's effect on breast cancer outcomes are now being recognized. Several risk factors for contralateral breast cancer recurrence included age, lobular histology, genetic abnormalities and no prior adjuvant systemic therapy. This study's objective was to define the risk of contralateral breast cancer in obese patients following treatment for primary breast cancer.  Methods: The electronic medical records of pts with histologically proven invasive breast cancer diagnosed between 1981 from 2006 were reviewed. Patients with Stage IV at diagnosis were excluded. Intrammamary breast cancer recurrence was defined as a new diagnosis of invasive or in-situ breast cancer at least 6 months after the diagnosis of primary invasive breast cancer, and it was classified as ipsilateral or contralateral breast cancer. Data on insurance, race, body mass index at diagnosis (BMI) and disease free interval (DFI) was analyzed. National Institutes of Health criteria was used to stratify pts as obese (BMI >30 kg/m2). Differences in DFI were analyzed by BMI.  Results: Of the 647 pts who were diagnosed with invasive breast cancer, 72 pts (11%) had intrammamary breast cancer recurrence, (28 ipsilateral and 44 contralateral). Pts with contralateral breast cancer in comparison with pts with ipsilateral breast cancer were more likely to be obese at diagnosis (64% vs 25%; p=0.001), to have a higher mean age at diagnosis (51 years vs 46 years; p=0.04) and to have primary breast cancer with ER positive status (67% vs 39%; p=0.05). In univariate analysis, obesity is a significant predictor of contralateral breast cancer. (HR =1.97; p=0.04). In multivariate analysis using Cox regression model, after adjusting for race, menopausal status, stage and SES, age at diagnosis and BMI remain statistically significant predictors for contralateral breast cancer (age at diagnosis: HR=1.09; p=0.006; BMI: HR=4.9; p=0.004).  Conclusions: In this relatively small patient group, obesity represent a significant risk factor for contralateral breast cancer occurrence. Additional studies are needed to further define the impact of obesity in breast cancer outcomes.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6097.
Triple-negative breast cancer and obesity in a rural Appalachian population.
Authors: Vona-Davis L , Rose DP , Hazard H , Partin J , Adkins F , Hobbs G
Published: December 2010

Abstract #6099

Background: Our objective was to determine the clinico-pathological features of triple-negative (estrogen, progesterone and HER-2 receptor negative) breast cancer and their relationship to obesity in women drawn from a population with one of the highest obesity rates in the United States.  Methods: This retrospective study involved 620 white patients with invasive breast cancer in West Virginia. Hospital tumor registry, charts, and pathology records provided age at diagnosis, tumor histologic type, size, and nodal status, and receptor status. Body mass index (BMI) was calculated and a value of ≥30 considered indicative of obesity.  Results: Triple-negative tumors occurred in 117 (18.9%) of the 620 patients, most often in association with invasive ductal carcinomas. Patients with triple-negative tumors were younger than those with other receptor types, 44.5% and 26.7%, respectively, being diagnosed before age 50 years (P = 0.0004). The triple-negative tumors were larger (P = 0.0003), most notably in the younger women, but small tumors (<2.0 cm) were more often accompanied by lymph node metastases. Obesity was present in 49.6% of those with triple-negative tumors, but only 35.8% of those with non-triple-negative tumors (P = 0.0098). Lymph node metastases were more frequently associated with T2 tumors in obese patients (P = 0.032) regardless of their receptor status.  Conclusions: Triple-negative breast cancers within a white, socioeconomically-deprived, population occurred in younger women, with later stage at diagnosis, and in association with obesity. The elevated adipokine production which is present in obesity may exert tumor proliferative and angiogenic effects that contribute to an aggressive phenotype.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6099.
Modelling the cost-effectiveness of first, second and third generation polychemotherapy regimens in women with early breast cancer who have differing prognoses.
Authors: Campbell H , Epstein D , Griffin S , Sculpher M , Manca A , Bloomfield D , Yarnold J , Bliss J , Johnson L , Earl H , Poole C , Hiller L , Dunn J , Rea D , Hopwood P , Barrett-Lee P , Ellis P
Published: December 2010

Abstract #6106

Purpose: To use individual patient data from three sequential large UK randomised trials to facilitate an integrated comparison of the cost-effectiveness of three generations of chemotherapy plus a no treatment option. The ABC trial compared CMF versus no chemo (1991 patients), NEAT trial Epirubicin-CMF versus CMF (2391 patients) and TACT FEC-Docetaxel vs FEC or epi-CMF (4162 patients)  Methods: The model estimates lifetime costs and Quality-Adjusted Life Years (QALYs). Model inputs include transition probabilities which are estimated from a longitudinal observational study using parametric survival models incorporating characteristics such as number of positive lymph nodes, ER status, grade and tumour size that allow analyses to be conducted for women with differing baseline prognoses. The effects of each chemotherapy regimen on preventing recurrence are taken from the above UK trials and are assumed to be additive on the log scale to facilitate previously untested comparisons. Costs and utility decrements associated with chemotherapy, its toxicity, and type of recurrent disease, are informed from the trial data and published literature. A secondary analysis is performed by basing the effects of each chemotherapy regimen on published meta-analyses based on individual level data that include RCTs conducted in a range of multi-national settings.  Results: For a woman aged 50 years with 1 positive node, grade 2 tumour size 2cm, ECMF is expected to be the most cost-effective regimen. However, the cost-effectiveness of the chemotherapy options varies between women with different risk factors. On the basis of the results of the TACT trial, 3rd generation chemotherapy is not cost-effective, but including evidence of the relative risk of recurrence from non-UK trials, particularly those with ER- and HER2+ phenotype, may alter this conclusion.  Indicative lifetime costs and QALYs for a woman aged 50 years, with 1 positive node, grade 2 tumor size 2cm, with and without ER+ are shown:        Conclusions: Evaluating the cost-effectiveness of chemotherapy regimens in women with early breast cancer who have differing prognoses is feasible using an integrative synthesis and model. Thought does, however, need to be given to how best present cost-effectiveness results when there are differing levels of baseline risk.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6106.
Cost-effectiveness of anastrozole versus tamoxifen as adjuvant therapy in early breast cancer (EBC) – a German health economic analysis.
Authors: Lux MP , Benedict A , Buchholz S , Woeckel A , Harbeck N , Kreienberg R , Kaufmann M , Beckmann MW , Jonat W , Hadji P , Distler W , Raab G , Tesch H , Weyers G , Schneeweiss A , Possinger K
Published: December 2010

Abstract #6109

Background: The non-steroidal aromatase inhibitor (AI) anastrozole is superior to tamoxifen in terms of efficacy and safety in the adjuvant treatment of postmenopausal patients with hormone receptor-positive (HR+) early breast cancer (EBC). The aim of the current study was to evaluate the cost-effectiveness of anastrozole versus tamoxifen from the German health care perspective.  Methods: A probabilistic Markov model was developed using data from the published literature and expert opinion to project trial outcomes to 25 years based on a cohort of 1000 postmenopausal women with HR+ EBC. Resource use data and costs were obtained from standard sources and expert opinion. Utility scores for the different heath states were obtained from a patient-based utility study using the standard gamble technique. Results were expressed as incremental cost-effectiveness ratios (ICERs) per quality adjusted life-years (QALYs) gained. Costs and benefits were discounted at 5% annually.  Results: Total costs over the 25 year period for anastrozole and tamoxifen were €12,422 and €6,757, respectively. The cost per life year (LY) for anastrozole compared to tamoxifen was €24,822/LY gained. The ICER of anastrozole compared to tamoxifen was €21,050/QALY gained (95% CI €9,841 - €62,344). The result remained robust to all parameters tested in the sensitivity analysis. Cost-effectiveness probability curves indicated a >90% probability that the cost per QALY gained with anastrozole would be <€42,000.  Conclusions: In this model, five years of adjuvant anastrozole is a cost-effective treatment alternative to tamoxifen in postmenopausal women with HR+ EBC from the German health care perspective.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6109.
High-dose chemotherapy with autologous stem-cell support versus standard-dose chemotherapy: meta-analysis of individual patient data from 6 randomized metastatic breast cancer trials.
Authors: Berry DA , Ueno NT , Johnson MM , Lei X , Smith DA , Caputo J , Yancey LJ , Bregni M , Demirer T
Published: December 2010

Abstract #6113

Background: The role of high-dose chemotherapy (HDC) with autologous hematopoietic stem-cell transplantation for metastatic breast cancer has not been well defined. The statistical power of the available trials has limited precision for determining whether HDC has any benefit for this indication, or for any subset of patients.  Methods: Individual patient data from the 6 known randomized trials were merged into a single database. The primary endpoint was overall survival (OS): time from randomization to death. The secondary endpoint was progression-free survival (PFS). Cox proportional hazards regression compared the effect of HDC vs standard-dose chemotherapy (SDC) on PFS and OS adjusted for age, trial and hormone receptor (HmR) status (positive if either estrogen (ER) or progesterone (PgR) receptor positive), and other variables. Among the subset analyses considered were by age, HmR status, number metastatic sites, and soft tissue metastases.  Results: A total of 846 patients (433 HDC, 413 SDC) had median follow-up of 1.9 years. Median age was 47 years (range 23 to 65). Preliminary analyses show that after adjusting for age and trial, HDC significantly prolonged OS (hazard ratio (HR) 0.86; 95%CI 0.73-1.00; p=0.05) and PFS (HR 0.73; 95%CI 0.63-0.84; p<0.0001). Mean improvement (out to 8 yrs) was 4 months for both OS and PFS. Both age (p=0.023) and soft tissue disease (p=0.0025) had statistically significant interactions with treatment for OS, but neither remain significant after adjusting for multiple comparisons.  Conclusions: HDC may have a modest benefit on OS that may be greater in patients younger than 50 years. However, we were not able to draw firm conclusions about age or other subset analyses.   

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6113.
Ixabepilone plus capecitabine improves overall survival in symptomatic patients with metastatic breast cancer previously treated with anthracycline and taxane in 2 large phase III studies.
Authors: Conte P , Roche H , Perez E , Sparano J , Xu B , Jassem J , Peck R , Mukhopadhyay P , Hortobagyi G
Published: December 2010

Abstract #6114

Introduction:  Symptomatic patients (pts) with performance status (KPS) 70-80 with locally advanced or metastatic breast cancer (MBC) have worse prognosis than pts with good performance status and are often excluded from clinical trials. Ixabepilone (ixa), the first in a new class of antineoplastic agents, showed clinical benefit in 2 large clinical trials in combination with capecitabine (C) in MBC pts with tumors resistant to (study 046; JCO; 2007) or pretreated with anthracycline (A) and taxane (T) (study 048). In 048, ixa + C, compared to C alone, showed significant increases in PFS (HR 0.79 [0.69-0.90] and ORR (43% vs 29%). A trend toward increased OS was seen in 048 (HR 0.90 [0.78-1.03]) and 046 (HR 0.90 [0.77-1.05]) which did not reach statistical significance. In 046 and 048 trials, a survival benefit was seen with ixa + C in a predefined analysis in a subset of symptomatic KPS 70-80 pts (HR: 0.75 [0.58-0.98], 0.76 [0.60-0.96], respectively). We present a predefined pooled analysis of clinical outcomes in symptomatic pts from both studies to better evaluate the treatment effect in this subset.  Methods:  1973 pts with MBC previously treated with an A and T were randomized in phase III trials 046 and 048 to receive ixa (40mg/m2 IV over 3h Q3w) + C (1000mg/m2 PO BID x14d Q3w) or C alone (1250mg/m2 PO BID x14d Q3w). 606 pts from the 2 studies were KPS 70-80. Study outcomes included ORR, PFS and OS.  Results:  ORR, PFS and OS favored ixa + C in this pt population.    In asymptomatic pts (KPS 90-100), similar improvement was observed in PFS and ORR; no benefit in OS was seen. Incidence of key treatment related grade 3/4 AEs for ixa + C in this subset of pts was similar to the overall population.  Conclusions:  In the pooled analysis, ixa + C demonstrates a survival benefit (2.8 mo) for symptomatic pts (KPS 70-80) failing A and T, which was consistently seen in this pt population in the individual studies as well, indicating that symptomatic pts can benefit from management of their disease and achieve overall clinical benefit with ixa combination.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6114.