bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P1-10-09: Access to HER2 Testing in Early Stage Breast Cancer (ESBC) in a Single Payor, Public Healthcare System — Ontario (ON), Canada
Authors: Ferrusi IL , Trudeau M , Earle C , Leighl NB , Pullenayegum E , Cascagnette P , Marshall DA.
Published: April 2011

Background: In ON, testing for HER2 overexpression in ESBC was approved, along with trastuzumab (T) treatment with chemotherapy for HER2 positive (IHC = 3 or FISH ≥2.0) tumors in 2005. Guidelines for testing and treatment must be met for provincial T reimbursement. To study adherence to HER2 testing and T utilization guidelines in ESBC, we first describe patient access to HER2 testing by age, tumor, stage, urbanicity and income. Methods: A population-based retrospective cohort of ESBC patients diagnosed in 2006 and 2007 was identified using the Ontario Cancer Registry and for whom ≥1 pathology report was available from Cancer Care Ontario (CCO). All BC-related pathology reports were individually reviewed to identify early stage, resected, primary BC. Information was collected on surgical procedure, TN stage, histologic grade, receptor status (ER/PR) and HER2 test provision. Linkage to other administrative databases provided income quintile, urban vs. rural residence and institution of diagnosis. Odds ratios were calculated to determine association of HER2 testing with any pathologic or socioeconomic factors. Results: The 2-year cohort contains 13,430 ESBC patients, 60% of which had breast conserving surgery. 29,746 (2.2/patient) pathology reports were reviewed. 13% of the cohort had rural residences, and 95% were alive at end of follow-up. Age at diagnosis was distributed as: 5% < 40 years, 18% 40-49 years, 25% 50-59 years, 24% 60- 69 years, 18% 70-79 years and 10% ≥80 years. Stage at diagnosis was: 35% stage I, 32% stage II, 10% stage III and 22% stage unknown after removing all stage IV. No differences in HER2 testing were observed for patients across income quintiles (P>0.3550). Patients ≥80 years (P<0.0001) and <40 years (p=0.0074) had significantly lower odds of receiving ≥1 HER2 test than patients 40-49 years. ESBC of higher histologic grade had significantly greater odds (P<0.0001) of ≥1 HER2 test compared to grade I ESBC. Patients from rural areas had lower odds of HER2 testing compared to urban patients (P<0.0001). Conclusions: For the 2 years 2006-2007: 13,430 ESBC patients were identified from the OCR for which ≥1 pathology report was available from CCO. Age, stage at diagnosis, and surgical procedure were representative of an ESBC population. HER2 testing was universally available per Ontario policy, but not all reports were submitted to CCO. The odds of having a documented HER2 test were not affected by income, but testing was more likely to be documented for high grade tumours and less likely to be documented for the youngest and oldest women and those with rural residence. Pathology reports missing from CCO are being sought. Adherence to guidelines for testing, treatment with T and cardiac monitoring during treatment will be assessed.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-10-09.
Abstract P1-11-04: A Phase II Preoperative Trial of Concurrent Trastuzumab and Paclitaxel without Anthracycline in HER2-Positive Operable Breast Cancer
Authors: Sato T , Hayashida T , Takahashi M , Sakata M , Jinno H , Hirose S , Mukai M , Kitagawa Y.
Published: April 2011

Background

Concurrent trastuzumab with paclitaxel/fluorouracil, epirubicin, and cyclophosphamide (P/FEC) chemotherapy as neoadjuvant treatment revealed the high pathologic complete response (pCR) rate of 54.5% (Buzdar, 2007). Deregulation of the phosphatidylinositol 3-kinase (PI3K) pathway either through loss of PTEN or mutation of the catalytic subunit alpha of PI3K (PIK3CA) might confer resistance to trastuzumab. The objective of this study was to determine the efficacy of concurrent administration of trastuzumab and paclitaxel wtihout anthracycline as preoperative chemotherapy. The correlation between deregulation of PI3K and resistance to trastuzumab was also investigated. Patients & methods

Patients with HER2-positive, operable breast cancer received 12 cycles of weekly paclitaxel (80 mg/m2) and trastuzumab (4mg/kg loading dose then 2 mg/kg) for 12 weeks before surgery. PTEN status was evaluated by immunohistochemistry. PTEN staining intensity scores was recorded on an integer scale from 0 to 2+ (0; no staining, 1+; reduced staining, and 2+; equal staining as compared to the internal control). Sequencing of PIK3CA exons 9 and 20 was done by PCR amplification and direct sequencing. pCR was defined as no residual invasive carcinoma in the breast. Results

Twenty-eight patients were enrolled and assessable for clinical and pathologic responses. The overall response rate was 92.9%, including a complete response in 13 patients and a partial response in 13 patients. The pCR rate was 53.6% (15/28). Twenty-three patients (82.1%) underwent breast concerving surgery. Progesteron receptor (PgR) status was significantly correlated with pCR (p=0.025). Eight of 24 patients (33.3%) were scored PTEN negative. PIK3CA mutations were identified in 4 of 13 patients (30.8%). There was no significant difference in pCR rate and PTEN loss/PIK3CA mutation.

Correlation of PgR status and pCR

Conclusions

These data indicate that the combination of trastuzumab and paclitaxel without anthracycline is effective preoperative chemotherapy with high pCR rate. PTEN loss and/or PIK3CA mutation were not useful predictors of resistance to trastuzumab.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-11-04.
Abstract P1-11-08: A Multicenter Prospective Phase II Trial of Neo-Adjuvant (FEC 100)/Cisplatin-Docetaxel with or without Trastuzumab in Locally Advanced Breast Cancer. Gulf Oncology Research Group (G0RG-001)
Authors: AL-Tweigeri TA , Alsayed AA , Ibrahim MM , Ashaur WM , Jaafar HN , Abulkhair OA , Al-Abdulkarim HA , Khalid HKH , Alawadi SA , Ajarim DS.
Published: April 2011

BACKGROUND: To evaluate the efficacy and safety profile of the (FEC100) followed by cisplatin/docetaxel with or without trastuzumab as primary chemotherapy for patients with locally advanced breast cancer (LABC T2> 4cm, N0-2, M0).

METHODS: Eighty (80) patients with LABC (T2-T4, No-N2, M0) received 4 cycles of FEC (100) followed by 4 cycles of cisplatin/docetaxel, followed by definitive surgery and locoregional radiotherapy with or without hormonal therapy. Patients with HER2 positive received trastuzumab concurrently with cisplatin docetaxel for a total of 8 cycles (for a total of 6 months). The primary end point was pathologic complete response (pCR) in breast and/or axilla for HER2 negative and HER2 positive. RESULTS: Seventy nine (79) patients were evaluable for analysis: median age: 43yrs, Premenopausal: 83%, median tumor size: 7.0cm (≥4 - 10), Stage IIB: 24% and IIIA/IIIB: 76%, both ER/PR positive: 56%, Her2/neu (3+) by IHC staining: 39%. Clinical response was 65% complete response and 28% partial response. Breast conserving surgery was performed in: 10 % and MRM in: 90%.Three (3) patients suffered an asymptomatic and reversible decrease in left ventricular ejection fraction. Pathological complete response (pCR) can b summarized as follow: Overall pCR in breast: 37%, in Axilla: 65%, Breast and axilla: 33%. In patients with HER2 Negative: pCR in breast: 19%, in Axilla: 56%, Breast and axilla: 17%.In patients with HER2 positive: pCR in breast: 65%, in Axilla: 77%, Breast and axilla: 58%.Overall the DFS & OS at 3 years were 88% and 98% respectively.

CONCLUSIONS: This sequential combination is a safe, feasible and active combination, which associated with high clinical and pathologic response rates, the addition of trastuzumab increased pCR rate in HER2 positive tumors with promising and encouraging outcomes, further investigation of this combination are warranted.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-11-08.
Abstract P1-11-09: Predictive Response Factors (PRF) in an Open, Non-Randomized, Phase II Study of a Combination of Bevacizumab (BZ) and Sequential Chemotherapy as Preoperative Treatment in Patients with Operable HER-2 Negative Breast Cancer (BC)
Authors: Sanchez Rovira P , de la Haba J , Fernandez M , Segui MA , Llombart A , Anton A , Sanchez A , Aranda E.
Published: April 2011

Introduction: Association of BZ to chemotherapy in BC improves time to progression of advanced disease. However limited studies are still available for primary treatment, and PRF are not still clearly determined, above all in HER-2 negative patient subgroup receiving antiangiogenic therapy. Objetives: To determine percentage of pathological Complete Responses (pCR) in patients diagnosed of locally advanced BC who receive neoadjuvant sequential therapy in association with BZ, as well as to determine the PRF and perform differential analysis of treatment resistant genes.

Material/Methods: 72 patients were included in ML20382 clinical trial. Treatment was 4 cycles of doxorubicin/cyclophosphamide 60/600 mg/m2 x 21 days, followed by 4 cycles of BZ 15 mg/kg + docetaxel 75 mg/m2 x 21 days. Median age was 46 years. Stage classification was 20.8% IIA, 43.1% IIB, 23.6% IIIA, 8.3% IIIB, 4.2% IIIC. Median tumor size was 4.75 cm. 68.1% showed axillary affectation and 80.6% were hormone-receptor positive. Clinical evaluation was done by mammography and mammary ultrasound and/or NMR. Tumor samples were collected before treatment and after surgery for analysis of VEGF, VEGFR, EGFR, pAKT, pMAPK, pTEN, HIF, IGF and differential analysis of gene expresion.

Results: 66 patinets evaluated for histopathological response, resulting in 24. 2% of pCR (CI 95%, 14.5-36.4). Multivariate analysis shows a significant increase of responses in ER-negative patients. Treatment was well tolerated, with haematological toxicity G3-4 for 22% of patients (12.5% of neutropenic fever as most noteworthy toxicities). Most relevant non-haematologycal toxicity was mucositis G3 for 19.4% and hypertension for 1.4%. Preliminary analysis shows VEGFr and KISS1 amplification entail a tendency of a lower pCR rate (8.7% and 6.25% respectively).

Conclusions: Addition of BZ in preoperative treatment (AC+D) permits a high pCR rate with an adequate safety profile in a subgroup with a median of T>4cm and predominantly ER+. Definitive results about amplification analysis of KISS1, VEGFR and Angiotensin 1 Rc, RNA and proteonomic expression will be presented.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-11-09.
Abstract P1-11-19: Prognostic Significance of Ki67 Index after Neoadjuvant Chemotherapy for Human Breast Cancer
Authors: Tanei T , Shimomura A , Shimazu K , Nakayama T , Kim SJ , Tamaki Y , Noguchi S.
Published: April 2011

Purpose: The Ki67 index (cell proliferation marker) has recently been attracting considerable attention as a prognostic factor in breast cancer, but the prognostic significance of Ki67 after neoadjuvant chemotherapy (NAC) has hardly been studied.

Experimental Design: Primary breast cancer patients (n=102) treated with NAC (sequential paclitaxel 12 cycles (q1w) and 5-FU/epirubicin/cyclophosphamide 4 cycles (q3w)) were recruited for this study. In the patients who did not achieve pathological complete response (pCR) after NAC. we evaluated the expression of Ki67, estrogen receptor (ER), progesterone receptor (PR), breast cancer resistant protein (BCRP) and P-glycoprotein were determined by immunohistochemistry, and HER2 was determined by FISH in tumor tissues obtained before and after NAC. Therefore the association of these proteins with patient prognosis (relapse-free survival) was examined.

Results: pCR was achieved in 30 (29.4%) of the 102 patients. In the remaining 72 non-pCR patients, the Ki67 index significantly (P<0.001) decreased after NAC, and the Ki67 index after but not before NAC, was significantly associated with patient prognosis (P=0.022). Multivariate analysis showed that the Ki67 index after NAC was a marginally significant (P=0.05) prognostic factor and that other biomarkers including ER, PR, BCRP, and P-glycoprotein either before or after NAC were not significant.

Conclusions: Ki67 after but not before NAC, is prognostic for breast cancer patients, and may be clinically useful for the prediction of prognosis for patients who do not achieve pCR after NAC. On the other hand, BCRP and P-glycoprotein either before or after NAC are unlikely to be useful as prognostic factors for such patients.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-11-19.
Abstract P1-11-21: Effectiveness Analysis of Neoadjuvant Treatment by Using 4FE100C vs 6FE100C in Patients with Advanced Breast Cancer
Authors: Ramirez-Torres N , Perez-Puentes A , Astudillo-de la Vega H
Published: April 2011

Objective: To detect the difference in the effectiveness of 6 FE100C as neoadjuvant chemotherapy (NCT) vs 4 FE100C and set the duration.

Method. Forty-eight consecutive cases per group from January 2003 to December 2007 were registered. Patients received cyclophosphamide 500 mg/m2, epirubicin 100 mg/m2 and 5-fluorouracil 500 mg/m2 (FE100C) with 4 or 6 cycles every 21 days. They were followed by surgery and radiotherapy.

Results In the analysis, the number of the largest cycle was a predictor in clinical response. Theobjective complete clinical and partial response (cCR+cPR) was 62.5% and 87.5% with 4 FE100C and 6 FE100C respectively (p <0.003); the clinical benefit was better with six FE100C with a complete response rate (cCR) of 35.4% (CI 95%: 22% −48%, n=17). The distribution of best complete pathologic response (CPR) for 6 FE100C was significantly better than for 4 FE100C (20.8% vs.12.5%, p = 0.044). The most clinically important difference in gastrointestinal toxicity caused by 6 FE100C was the effect of mild to moderate vomiting (52.4% vs. 39% for 4 FE100C, p = 0.001); the severe leukopenia (2.43% vs. 1.56%, p= 0.401) and moderate anemia (2.08% vs. 0.52%, p = 0.142) for 6 FE100C and 4 FE100C respectively. There was no significant difference between regimens. The toxicity of the nausea, alopecia and hematologic toxicity in the effect of peripheral leukocyte count and platelet presented no significant difference between regimens. The moderate anemia was rescued with blood transfusion and severe leukopenia with filgastrim. There was no cardio toxicity, thrombocytopenia or other serious events.

Conclusion: Both regimens were similar for the incidence of gastric toxicity and hematologic toxicity. The scheme of six FE100C was well tolerated in patients with LABC. It was confirmed a significant improvement in the pCR and cCR with intensified epirubicin dose (100mg/m2) for 6 cycles without granulocyte colony-stimulating factor.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-11-21.
Abstract P1-11-22: Bisphosphonates and Pathologic Complete Response to Neoadjuvant Chemotherapy in Patients with Breast Cancer
Authors: Chavez-Mac Gregor M , Brown EN , Lei X , Hsu L , Meric-Bernstam F , Litton J , Mittendorf EA , Valero V , Hortobagyi GN , Gonzalez-Angulo AM.
Published: April 2011

Purpose: Several studies have suggested that bisphosphonates have antitumor effects and that their use may have a potential benefit on recurrence and survival in patients with primary breast cancer. In a retrospective study, we sought to evaluate whether the use of bisphosphonates increased the rates of pathological complete response (pCR) in breast cancer patients receiving taxane and anthracycline-based neoadjuvant chemotherapy. Methods: We identified from our database 1449 breast cancer patients receiving taxane and anthracycline-based neoadjuvant chemotherapy between 1995 and 2007 at M.D. Anderson Cancer Center. Among the entire cohort, we identified by chart review those patients that while receiving chemotherapy also received bisphosphonates for a different indication (osteopenia or osteoporosis). Primary outcome was the proportion of patients achieving a pCR. Groups were compared using the chi-squared test. A multivariable logistic regression model was fit to examine the relationship between the use of bisphosphonates and pCR. An exploratory survival analysis using the Kaplan-Meier method was performed; groups were compared using the log-rank test.

Results: From the 1449 patients included, 39 (2.7%) received bisphosphonates at the time of neoadjuvant chemotherapy.66.7% received alendronate, 28.2% risedronate and 5.1% ibandronate. Those receiving bisphosphonates were older (P<.001) and less likely to be obese (P=.04). The pCR rate was 26% in the bisphosphonate group and 16% in the non- bisphosphonate group (P=.11). After adjusting for potential confounding variables, patients treated with bisphosphonates tended to have higher rates of pCR (OR 2.16 95% CI 0.89-5.25); however the difference did not reach statistical significance. With a median follow up of 55 months (3-145) there were 412 recurrences and 359 deaths. There were no differences on 5-year PFS (71% vs 80%; P=.28) or 5-year OS (77% vs 82%; P=.42) between the two groups.

Conclusions: In this cohort of patients, the concurrent use of bisphosphonates at the time of neoadjuvant chemotherapy was not associated with significant increased rates of pCR. The observed estimates suggest a positive effect; however, it is possible that the small proportion of patients receiving bisphosphonates affected the power to detect a statistically significant difference. To fully test the hypothesis, additional, well-powered prospective studies to evaluate the potential use of bisphosphonates as antitumor agents used in the neoadjuvant setting are warranted.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-11-22.
Abstract P1-13-08: A Cross-Sectional Study Evaluating Bone Quantity and Quality in Women with Bone Metastases from Breast Cancer
Authors: Freedman OC , Amir E , Cheung AM , Hu H , Lee E , Dranitsaris G , Clemons MJ.
Published: April 2011

Background: Approximately 1/3 of patients with metastatic breast cancer (MBC) and bone disease will sustain a skeletal related event (SRE) despite use of a bisphosphonate; there is therefore an urgent unmet need in this large population to better assess individual SRE risk and develop more effective bone protective agents. Using novel tools to assess bone quality may help guide individual patient treatment choices as well as future trial design.

Materials and Methods: Women with MBC and bone metastases were recruited. Baseline bone assessments were performed using dual-energy X-ray absorptiometry (DXA) [areal bone mineral density (BMD) and vertebral fracture assessment (VFA)], high-resolution peripheral quantitative computed tomography (HR-pQCT), and serum markers of bone turnover [serum CTX and bone-specific alkaline phosphatase (BAP)]. Risk factors for osteoporosis and fractures were then recorded. Results: 49 baseline assessments were completed. Mean age and body mass index were 53.6 (range 30-80) and 27 (range 17-45) respectively. One in four women had an ECOG 2-3, and 24% had a clinical fracture since the diagnosis of MBC. 94% had estrogen positive disease, 11% were HER2+. 53% had prior radiation therapy to bone; 90% received bisphosphonate therapy. Bone assessments are outlined in the Table. Vertebral compression deformity (VCD) using the novel technique of VFA was most strongly associated with clinical fracture (p = 0.003).

Discussion: Prospective evaluation of individual SRE risk will enable improved patient-centred care and allow more rational use of bone targeted therapies. VFA is a novel tool that may better inform treatment decisions and choice of agents in women with MBC. Future follow-up of these patients will help determine the optimal assessment modality.

Bone quantity and quality assessments

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-13-08.
Abstract P1-13-09: Marked Inhibition of Both Invasion and Proliferation by Zoledronic Acid and the Epidermal Growth Factor Receptor Inhibitor Gefitinib in a Bone-Seeking Clone of Breast Cancer
Authors: Oda M , Iwaya K , Yamada K , Kaise H , Ogata A , Kimura F , Kobayashi T , Matsubara O , Yoneda T , Kouno N.
Published: April 2011

Background: Zoledronic acid (Zol) is the most potent inhibitor of bone resorption in bisphosphonates. In order to examine whether the inhibitory effect is involved in the mechanism of bone metastasis in breast cancer, a bone-seeking clone was examined. It was established by repeated sequential passages of metastatic cells from bone in nude mice and in vitro, and it exclusively metastasizes to bone with larger osteolytic lesions than MDA-MB-231 parental cells. Recent findings indicate that epidermal growth factor (EGF) signaling is also an important mediator of bone metastasis. We examined the synergistic effects of gefitinib on the proliferation and invasion of a bone-seeking clone compared with MDA-MB-231. Materials and Methods: The cellular proliferation was estimated using WST-1. Migration in the matrigel in a Boyden chamber was applied to the invasion assay.

Results: Treatment with 1 µM of Zol reduced 51% of cell proliferation in the bone-seeking clone; however, the inhibited rate was 37% in MDA-MB-231. The migration was also inhibited with 10 µM of Zol (bone-seeking clone: 69% reduction, MDA-MB-231: 54% reduction). The reduction rates of both assays by Zol treatment were significantly higher in the bone-seeking clone than in MDA-MB-231. Treatment with 10 µM of Zol plus 1 µM of gefitinib resulted in a proliferation reduction rate of 27% compared to that with 10 µM Zol treatment in the bone-seeking clone and no reduction in MDA-MB-231.

The migration reduction rate was 88% in the bone-seeking clone and no reduction in MDA-MB-231.

There was a significant difference between the bone-seeking clone and MDA-MB-231 in the reduction rates of both cellular proliferation and migration. Although the effect of gefitinib was synergistic with that of Zol in the bone-seeking clone, it was not clear in MDA-MB-231.

Conclusion: There appear to be at least two independent signaling pathways that occur in osteolytic bone metastasis. One is involved in the bone resorption of bisphosphonates, and the other is an EGFR signaling pathway. Clinically, the combination of Zol and gefitinib is suggested to be a strong therapy specific to bone metastasis.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-13-09.
Abstract P1-14-02: Different Outcomes in Breast Cancer (BC) Patients with CNS Metastases According to IHC Phenotype
Authors: Gómez HL , Vigil CE , Cruz WR , Neciosup SP , Pinto JA , Suazo JF , Mas LA , Doimi FF , Falla MJ , Vallejos CS.
Published: April 2011

Background: Phenotype plays an important role in BC biology and outcome. We evaluated the characteristics and outcomes of clinical stages I-III BC patients with recurrence according to the IHC phenotype: ER or PR+/HER2-; HER2+ (regardless the ER and PR status) and triple negative (ER-/PR-/HER2-), to determine the influence of phenotype in the SNC recurrence.

Methods: We reviewed 1,232 clinical stage I-III BC treated at INEN (2000-2002). Phenotypes were categorized by IHC into [ER+ and/or PR+, HER2-], [ER-, PR-, HER2-] and [HER2+ (regardless ER/PR status)]. Patients were classified in 3 risk groups (recursive partitioning analysis [RPA]; Gaspar et al. Int J Radiat Oncol Biol Phys 1997;37:745) according to 4 criteria: those with Karnofsky Performance Status (KPS) less than 70 (Class III), those with a KPS of or more, aged less than 65, with a controlled primary, no other systemic metastases (Class I), all other patients (Class II). We used Kaplan-Meier estimates for comparing CNS-free metastases survival and survival after CNS recurrence according to IHC phenotype or classes.

Results: A median follow-up of 7.6 years; 416 (33.8%) patients had local, regional or distant disease dissemination, and 454 (36.9%) deaths were registered. In total, 62 (5.0%) patients developed CNS metastases (60 cases of cerebral and 2 of meningeal metastases), 36 (2.9%) of whom had developed CNS metastases as the site of first recurrence. 12 (2.1%), 31 (7.7%) and 19 (7.5%) were ER or PR+/HER2-, HER2+ and triple negative, respectively. CNS metastases free survival shown significant differences between ER or PR+/HER2-, HER2+ and Triple negative (97.3%, 89.6% y 90.5%, respectively; P<0.001). Main multivariate predictive factor was IHC phenotype (P<0.001), using [ER or PR+/HER2-] as reference, other phenotypes were expressed by hazard ratios (HR); [HER2+] (HR=3.8, 95%CI; 1.9 - 7.4), triple-negative (HR=4.0, 95%CI; 1.9-8.4). In regard to the RPA groups, 3 (4.9%) were class I, 28 (45.9%) class II and 30 (49.2%) class III. Median survival after CNS recurrence was 12.9, 6.1 and 2.8 for RPA Class I,II and III, respectively]; however there was not significant differences (p=0.085). In the multivariate analysis for OS after SNC metastases, only phenotype was significant and Triple Negative have the higher risk (HR=2.064; IC95% 0.94 — 4.531; P=0.023), Risk groups have not significant effect (P=0.088).

Phenotype and outcome

Conclusion: IHC phenotype is a strong risk factor for outcome; triple negative, and Class III breast cancer patients present a shorter time to CNS recurrence and survival after CNS recurrence than other IHC phenotypes and other risk groups.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-14-02.
Abstract P1-14-03: New Breast Cancer Recursive Partitioning Analysis (RPA) Prognostic Index in Patients with Newly Diagnosed Brain Metastases
Authors: Niwinska A , Murawska M
Published: April 2011

Purpose: To analyze survival of 441 patients with breast cancer and brain metastases including prognostic factors related to patient, cancer and type of treatment. To present a new Breast Cancer Recursive Partitioning Analysis (RPA) prognostic index for patients with newly diagnosed brain metastases as a guide in clinical decision making. Methods and Materials: A group of 411 patients with breast cancer and brain metastases treated in one institution between the years 2003-2009 was assessed. Factors significant for univariate analysis were included into recursive partitioning analysis (RPA).

Results: Median survival from brain metastases in the entire group was 7 months. Three prognostic classes of new Breast Cancer RPA prognostic index were selected. Median survival of patients within prognostic class I, II and III was 29 months, 9 months and 2.4 months, respectively (P<0.0001). Class I included patients with 1 or 2 brain metastases, without extracranial metastases or with controlled extracranial metastases and with Karnofsky performance status (KPS) of 100. Class III included patients with multiple brain metastases with KPS of <=60. Class II included all other cases. Conclusions: Breast Cancer RPA prognostic index is a simple and valuable tool for usage in clinical practice. It can quickly select patients who required aggressive treatment (neurosurgery, stereotactic radiosurgery, systemic therapy) and those in whom corticoids and best supportive care, often even without whole-brain radiotherapy, is the most reasonable option. Individual approach is required for patients from prognostic class II.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-14-03.
Abstract P1-17-02: Outcome after Locoregional Recurrence in Patients with Inflammatory Breast Cancer
Authors: Patel HJ , Li J , Gonzalez-Angulo AM , Strom E , Perkins GH , Tereffe W , Yu T-K , Hoffman K , Smith BD , Lucci A , Valero V , Buchholz TA , Woodward W.
Published: April 2011

Purpose: High rates of locoregional recurrence (LRR) have been reported in spite of comprehensive tri-modality therapy for patients with inflammatory breast cancer (IBC). The aim of this study was to examine the prognosis of patients who have experienced LRR after treated primary IBC. Methods:

We retrospectively reviewed information for 124 IBC patients who experienced a LRR seen in our institution from 1990-2008. 63 patients had simultaneous distant disease (DM) +/−3 months of LRR (simLRR),

5 patients had LRR > 3 months subsequent to DM, while 56 patients had isolated LRR >3 months prior to DM (isLRR). Overall survival (OS) was calculated from date of recurrence using the Kaplan-Meier method. Results:

Median time to LRR from diagnosis was 13 months (interquartile range 8-21 months). Median survival after LRR was 15 months. 2-yr OS was 46%. Regarding the primary tumors, 23% were estrogen receptor positive (ER+), 33% were HER2-neu positive (H2N+), 81% had lymph vascular space invasion (LVSI), and 83% were grade 3. Comparing isLRR and simLRR cohorts, median survival was 18 months vs. 10 months and 2 yr-OS was 66% vs. 28%, respectively. ER+ and H2N+ primary status predicted for longer 2 yr OS among patients with simLRR but not among isLRR patients. (simLRR, ER+ 57% vs. ER-19% p = 0.02, H2N+ 45% vs. H2N-17% p = 0.01; IsLRR ER+ vs. ER-92% vs. 55% p = 0.15, H2N+ 86% vs. H2N-57% p = 0.11). LVSI was not prognostic in either group and Grade 3 primary trended towards worse outcome among isLRR cohort only, Grade 2 83% vs. Grade 3 64% P = 0.08. Molecular subtyping using ER and H2N status to group tumors demonstrates basal subtype in the primary tumor compared to H2N, luminal B and luminal A is associated with significantly worse 2 yr OS after isLRR (43% vs. 88%, 82%, and 83%, P = 0.04) and simLRR (13% vs. 34%, 80%, 32% P = 0.005) respectively. Conclusions:

Forty-five% of LRR occurred as isolated first events. LRRs generally occur within 2 years after primary IBC treatment and are associated with poor outcomes even as first events. Basal subtype predicts for worse overall survival regardless of distant disease.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-17-02.
Abstract P2-02-04: MRI Findings and Outcomes in an Underserved Breast Cancer Population Screened with BRCA Testing
Authors: Tang S , Fahed E , Azadi A , Ricker C , Larsen L , Lee S , Jain P , Spicer D , Tripathy D.
Published: April 2011

Background: Patients with breast cancer and a familial risk and/or BRCA 1 or 2 mutations are at high risk of contralateral breast cancer and ipsilateral recurrence. While MRI screening is recommended for patients with BRCA mutations, and MRI staging for breast cancer is being increasingly used, the outcomes of such testing are not well described, especially in underserved populations. At Los Angeles County Hospital (LAC) for the last 3 years, we have enacted a program of genetic counseling and testing based standard guidelines as well as MRI evaluation of all patients newly diagnosed with breast cancer. LAC serves a population that includes a high number of indigent patients, primarily Hispanic (60%) and Asian (15%). Methods: We undertook a retrospective evaluation of all patients seen at LAC from March 2008 to March 2010 who underwent genetic counseling/testing and MRI as preoperative assessment for histologically documented breast cancer or followup after cancer treatment. IRB approval was obtained to extract data for this analysis. Demographic information along with clinical presentation, MRI and mammography results, additional imaging results, biopsy and surgical procedure and corresponding pathology data were obtained through the review of electronic medical records and clinic charts.

Results: A total of 90 patients had both genetic testing and MRI reports available. The median age of all tested patients was 41 years. Ethnicity was 78% Hispanic, 9% Asian, 7% African American, 2% Caucasian and 4% other. BRCA mutation was seen in 20 cases (22%), 12 BRCA-1, 8 BRCA-2, 4 variants of unknown significance, and 66 had no mutation. Breast mass or other symptoms were the mode of detection in 89% of the overall cohort, and 81% in mutation carriers. The index lesion was visible on MRI in 78% and by mammogram in 82% of all patients. Ipsilateral MRI showed 7 abnormal non-index findings in 6 patients (7%); 6 of 7 lesions biopsied showed cancer. In the contralateral breast, 7 abnormalities were noted on MRI, but only 5 were amenable to biopsy as 2 could not be visualized by any means on follow up, and 1 showed cancer. Interestingly, only one of the 13 patients with abnormal findings carried a mutation (BRCA-1) and this patient did not have cancer on contralateral lesion biopsy. Mastectomy was performed in 91% and 78% of patients with and without mutation. Conclusions: Screening, counseling and testing for BRCA mutations is feasible in an underserved population, with a 22% mutation identification rate. MRI detected 5 non-index ipsilateral cancers and one contralateral cancer among 90 patients, with none of the detected cancers among the 20 mutation carriers. While MRI staging may be effective at detecting additional cancers in this underserved and high familial risk population, this appears to be independent of BRCA status.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-02-04.
Abstract P2-02-09: The Effect of Breast-MRI in Work-Up of Primary Operable Breast Cancer
Authors: Huttenhuis J , Bourez R , Faneyte I , Kouwenhoven E.
Published: April 2011

Background: Breast magnetic resonance imaging (MRI) is becoming an often-utilized examination in the preoperative planning for breast cancer. However, it is not yet accepted as a routine examination for all breast cancer patients due to the lack of data regarding whether breast MRI has any effect on recurrence or survival.

Aim: The aim of this study is to evaluate the effect of MRI on surgical management in operable breast cancer.

Methods: From April 2008 till January 2010 consecutive primary operable breast cancer patients had a preoperative breast-MRI in addition to regular mammography and ultrasonography. Additional lesions newly found by MRI were evaluated with a target ultrasound and if needed biopsied. Moreover MRI tumor size was compared to mammographic and ultrasonographic tumor size.

Blinded for MRI results and the performed surgical plan, surgical management based on traditional radiological work-up was determined retrospectively by 2 surgeons. Change of surgical plan by MRI was subsequently analysed. Accuracy of MRI based surgical plan was evaluated by comparing definitive pathology.

Results Hundred ninety eight consecutive patients were analyzed. Median age was 59 years (23-82). Additional ipsilateral and contralateral suspicious lesions were detected by MRI in 53 patients (27%). Twenty two patients had additionally target-ultrasonography: 5 lesions were not found, 4 lesions had benign aspect. Five out of 13 biopsied patients had second breast cancer, 3 patients had contralateral breast cancer and 2 patients had multicentric breast cancer. In 31 patients no further evaluation was performed because the new focus was supposed to be a satellite (n=12) or mastectomy was already chosen to be done (n=19). There was a change in surgical plan due to MRI results in 35 of 198 patients (18%), all of whom received more extensive surgery than previously planned: in 17 patients mastectomy was performed instead of lumpectomy, 15 patients had a more extensive lumpectomy. Three patients had contralateral surgery for breast cancer.

In 24 patients (69%) MRI based surgical plan was confirmed by definitive pathology. In 11 patients MRI overestimated tumor size or misinterpreted a satellite lesion.

Conclusion. Breast MRI contributes to a significantly change of surgical plan. However, false-positive findings are frequent. Therefore, in unselected primary operable breast cancer patients routine implementation of breast MRI is not right away justified.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-02-09.
Abstract P2-02-12: Utility of Targeted Sonography Using Real-Time Virtual Sonography (RVS) for Breast Lesions That Were Suspicious on MRI
Authors: Nakano S , Fujii K , Yorozuya K , Yoshida M , Kousaka J , Mouri Y , Fukutomi T , Ishiguchi T.
Published: April 2011

PURPOSE : MRI-detected suspicious breast lesions that are not expected from previous MMG or sonography, are detectable initially on MRI in 48% maximum. Therefore, biopsy is required for definitive diagnosis of MRI-detected lesions. Although MRI-guided biopsy is often necessary, sonographically guided biopsy after targeted sonography is more broadly available and less time-consuming and costly. The aim of this study was to verify the utility of targeted sonography using Real-time Virtual Sonography (RVS) for the identification of MRI-detected suspicious lesions.

METHOD AND MATERIALS : From 196 breast MRI examinations, all MRI-detected suspicious lesions and subsequent biopsy were identified between February 2006 and December 2009. All patients were examined using MMG, sonography, MRI and RVS that could synchronize a sonography image and the MRI cutaway images of the same site to be displayed in real time using magnetic navigation system. Following the conventional dynamic enhanced image, MRI was obtained on a 1.5-T imager in the supine position using a flexible body surface coil in order to achieve the same position as in sonography. We searched all cases for MRI-detected suspicious lesions and investigated targeted sonography with or without RVS in identifying the lesions.

RESULTS : Of the 196 patients, MRI-detected suspicious lesions were detected in 55 (28%) patients. A total of 67 suspicious lesions in 55 patients comprised this analysis. Of the study lesions, 24 (36%) were malignant and 43 (64%) were benign. Overall mean lesion size was 6.7mm. A total of 46 (69%) mass lesions were identified, compared with 16 (24%) foci and 5 (7%) nonmasslike lesions. 18 (27%) lesions were detected in targeted sonography without RVS and were revealed as cancers in eight, benign lesions in 10. In contrast, 60 (90%) lesions were detected in targeted sonography with RVS and were revealed as cancers in 21, benign lesions in 39. Although seven (10%) lesions were not detected with RVS, all lesions were able to project enhanced MRI information onto a body surface correctly as we checked ultrasound form images without the use of large-scale equipment.

CONCLUSION: The present results suggest that targeted sonography with RVS appears to be not time consuming technique which can identify a large part of MRI-detected suspicious lesions.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-02-12.
Abstract P2-03-01: An Investigation of Factors Influencing Real-Time Tissue Elastography Score
Authors: Nishiyama Y , Sakaguchi U , Matsushita K
Published: April 2011

[Purpose]

At 32nd SABCS, we reported that Real-time Tissue Elastography (EG) score was useful in the examinations of mass-forming breast lesions. The results suggested that a possibility of being invasive carcinoma may practically be ruled out when a mass-forming breast lesion scored 1 or 2 on EG. Because the stiffness is relatively visualized in EG, it is possible that the score is influenced by the state of the patient's breast. We examined the factors influencing EG scores in mass-forming breast lesions. [Subject and Method]

EG scores of 502 patients with breast lesions (150 malignant, 352 benign) whose tissues were diagnosed histopathologically from October 2007 to December 2009 were studied. The hardness was scored on a scale 1 to 5 on Tsukuba elasticity scoring system. [Results]

In the 502 cases of mass-forming breast lesions there was a significantly higher score for non-invasive carcinoma and invasive carcinoma than for benign lesions (< 0.0001). No difference in score was observed in a comparison of the location (lateral quadrants, medial quadrants) of the mass-forming lesion. There were significantly lower scores (< 0.0001) in 10 mm in diameter or smaller when comparing three groups of tumor mass diameters: 10 mm in diameter or smaller, 11-20 mm, and 21-30 mm. When the breast density of two groups were examined, “almost entirely fat or scattered fibroglandular tissue” group and “heterogeneously dense or extremely dense” group, there were significantly low scores in the “heterogeneously dense or extremely dense” group (< 0.0001). When the two groups divided by median area of the mammography were examined, there were significantly low scores in the larger breast group (< 0.0001). Although in the total cases examined, all cases were benign in score 1, 6% were malignant in score 2 (5 cases non-invasive carcinoma, 4 cases invasive carcinoma). When 3 cases in which pathology results of the surgical specimen were obtained were examined among the 4 cases of invasive carcinoma, widespread intraductal spread was observed in the surrounding invasive carcinoma. [Conclusion]

Through this investigation we ascertained that EG scores are influenced by lesion size and the state of the patient's breast. In addition, care must be taken given the possibility of low scores in invasive carcinoma with widespread intraductal spread.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-03-01.
Abstract P2-06-17: Biological Study of the Effects of GW572016 (Lapatinib) in Ras/Raf/MAK and PI3K/Akt Signaling Pathways in HER2 Positive Ductal Breast Carcinoma in Situ (DCIS)
Authors: Estevez LG , Suarez A , Calvo I , Ugidos L , Miró C , Durán H , Quijano Y , Herrero M , López-Ríos F , Hidalgo M.
Published: April 2011

Background: DCIS is a heterogeneous disease, with increasing incidence. Up to 37% of DCIS overexpress HER2. Lapatinib is a tyrosine kinase inhibitor that directly inhibits HER2 receptor signaling by blocking the receptor's kinase activity. This work tested the hypothesis that Lapatinib inhibits Ras/Raf/MAK and PI3K/AKT signaling in HER2 positive DCIS.

Patients and Methods: Patients with HER2 positive (FISH rate >2.2) DCIS diagnosed by core needle biopsy with low risk of having a hidden invasive component were eligible. Neoadjuvant Lapatinib 1500mg daily was administered for 4 weeks prior to surgical resection. EGFR was analyzed by FISH in the biopsy specimen. Ki67, PTEN, AKT, pAKT and pERK were evaluated by IHQ. PI3KCA mutations were screened at exons 9 and 20 by PCR. Apoptosis was analyzed by TUNEL assay. All biological markers were measured before and after Lapatinib treatment. Results: Eleven pts with HER2 positive DCIS have been included to date. Median FISH amplification was 7 (range 2, 70-14). Evaluation pre-Lapatinib showed that: none of the pts had EGFR amplification; six pts (54%) had a Ki67 >25%; pAKT was overexpressed in 3 pts (27%) and pERK in 2 pts (18%); PTEN was deleted in 3 pts (27%). PI3KCA mutations were detected in only 1 pt (9%). After Lapatinib treatment, 9 pts were evaluable. We observed a trend for inactivation of the Ras/Raf/MAK signaling pathway in 7 pts (70%) patients. Interestingly, 3 of these pts had paradoxical activation of PI3K/Akt suggesting a compensatory feed back loop. One out of these 3 pts has PTEN deleted. In addition, 3 pts (33%) showed an increase in the apoptotic index. Conclusions: In our study, four weeks of Lapatinib against HER2 positive DCIS resulted in inactivation of Ras/Raf/MAK pathway; however an activation of the PI3K/Akt was seen as the same time in 3 pts. Nevertheless this trend needs to be confirmed with the inclusion of more pts.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-06-17.
Abstract P2-06-19: Transferrin Receptor (CD71) Identifies Poor Response to Tamoxifen in Oestrogen Receptor Positive Breast Cancer Patients
Authors: Nicholson RI , Habashy HO , Gee JM , Finlay P , Farrow L , Jasani B , Barrett-Lee P , Robertson JF , Ellis IO.
Published: April 2011

Background: CD71 is involved in the cellular uptake of iron and is expressed on cells with high proliferation. Interestingly, we have Interestingly, we shown that its expression is associated with elevated tumour proliferation, shortened breast cancer specific survival and worsened outlook in ER+ adjuvant tamoxifen treated early breast cancer patients (Habashy et al, 2010). Here we extend our studies of the relationship between CD71 and tamoxifen outcome by study of an exploratory series of patients where endocrine response was directly assessable.

Material and Methods: CD71 (clone 10F11 antibody; Abcam, Cambridge, UK) and proliferation (MIB1) immunohistochemistry were performed as described in Habashy et al (2010) on 87 formalin fixed paraffin-embedded breast cancers. These were obtained from patients within the Nottingham Tenovus Multiple Antibody Study who had received systemic tamoxifen therapy for locally advanced primary carcinoma or metastatic disease or for recurrence after surgery alone. All had lesions assessable for response quality at 6 months, with survival and duration of antihormone response measured from initiation of antihormone to death or progression on therapy respectively. 48 tumours were classified as ER+ and 39 ER-. Results: Within this tamoxifen treated series, 68/87 patients were deemed positive for CD71 (plasma membrane and cytoplasmic), showing HScore values >=5. In the ER+ subgroup, a greater clinical response rate to tamoxifen was seen in CD71 — tumours (10 CR/PR, 3 S and 2 P) versus their CD71+ counterparts (CR/PR, 11 S and 16 P, p=0.015). CD71 positivity was associated with a significantly shortened time to progression and death (Kaplan Meier Test, p=0.026 and p=0.005 respectively). Examination of the proliferation marker MIB1 in ER+ tumours revealed a positive association with CD71 expression (Spearman's Test, p=0.01). In ER-patients, comprising predominantly progressive disease on tamoxifen therapy, CD71 status showed no impact on either time to progression of the disease or death.

Discussion: The present study extends our novel findings relating CD71 expression to loss of response to tamoxifen in ER+ breast cancer and reveals CD71 associates with increased tumour cell proliferation in clinical disease. Whether CD71 plays a causative role in the direction of these events and can be targeted to improve endocrine response requires to be ascertained.

Habashy HO et al, 2010, Breast Cancer Research and Treatment 119:283-293

Abd El-Rehim DM et al, 2005, Int J Cancer 116: 340-350

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-06-19.