Purpose/Objective(s)The use of molecular profiling in breast cancer for local risk assessment and local therapy decision is not well understood. The goal of this study is to assess locoregional outcome associated with breast cancer subtype in LABC patients after surgery, systemic therapy and radiation (RT).Materials/MethodsWe retrospectively reviewed 188 consecutive patients with clinical or pathological stage III breast cancer treated at University of Miami from 1990 - 2008. Biologic subtype was approximated using receptor status: Luminal A (ER+ or PR+ and HER2-), Luminal B (ER+ or PR+ and HER2+), HER-2 (ER- and PR- and HER2+), and Basal (ER- and PR- and HER2-). Ninety-seven patients (51.6%) were classified as Luminal A, 20 (10.6%) Luminal B, 22 (11.7%) Her2, and 49 (26.1%) were Basal. All patients received RT. Mastectomy was done in 78.2% and lumpectomy in 21.8%. Axillary surgery was performed in all patients. Surgical margins were negative in 95.7%. 93.6% of the patients received chemotherapy, adjuvantly (43.1%), neoadjuvantly (23.9%) or both (26.6%). Hormone therapy was given to 53.7% of the patients. Progression free survival (PFS) and OS were estimated by the Kaplan-Meier method. The method of cumulative incidence allowing for competing risk was applied to first failure event categorized as locoregional (LRR), distant metastasis (DM), simultaneous (LRR+DM within 4 months of each other) and death NED. Local Control (LC) was defined as the complement of the combined rate of LRR and simultaneous LRR+DM failures. Log-rank test was used to compare OS and PFS by biologic subtype, Gray's test was used to compare incidence rate of failure events by biologic subtype.ResultsMedian follow-up was 46.5 months (range, 7-205). There were 37 events for PFS and 21 deaths for OS. Nine patients had LRR as their first failure, 6 had simultaneous LRR+DM, 15 had DM, and 7 died NED. Due to smaller numbers and lack of events in some groups, subtypes Luminal B and Her2 were grouped together for analysis. LC rate varied significantly by subtype. The 5-year LC was 96% for Luminal A, 92% in Luminal B/Her2, and 83.1% in Basal subtype (p = 0.045, Gray's test). The difference in PFS by subtype was marginally significant with 5-year rates of 83% in Luminal A, 85.1% in Luminal B/Her 2, and 65.4% in Basal patients (p = 0.062, log-rank test). OS varied by subtype with 5-year rates of 91.4% in Luminal A, 92.4% in Luminal B/Her2, and 71.1% in Basal patients (p = 0.032, log-rank test).ConclusionsWith a median follow-up of 46.5 months, we have demonstrated with statistical significance that Basal tumors have worse 5-year LC and OS compared to Luminal A and Luminal B/Her2 subtype. Further strategies to improve outcome in Basal tumors using radiosensitizers or dose escalation are warranted. Luminal A tumors had the best LC and OS, despite stage III disease. Purpose/Objective(s)The use of molecular profiling in breast cancer for local risk assessment and local therapy decision is not well understood. The goal of this study is to assess locoregional outcome associated with breast cancer subtype in LABC patients after surgery, systemic therapy and radiation (RT). The use of molecular profiling in breast cancer for local risk assessment and local therapy decision is not well understood. The goal of this study is to assess locoregional outcome associated with breast cancer subtype in LABC patients after surgery, systemic therapy and radiation (RT). Materials/MethodsWe retrospectively reviewed 188 consecutive patients with clinical or pathological stage III breast cancer treated at University of Miami from 1990 - 2008. Biologic subtype was approximated using receptor status: Luminal A (ER+ or PR+ and HER2-), Luminal B (ER+ or PR+ and HER2+), HER-2 (ER- and PR- and HER2+), and Basal (ER- and PR- and HER2-). Ninety-seven patients (51.6%) were classified as Luminal A, 20 (10.6%) Luminal B, 22 (11.7%) Her2, and 49 (26.1%) were Basal. All patients received RT. Mastectomy was done in 78.2% and lumpectomy in 21.8%. Axillary surgery was performed in all patients. Surgical margins were negative in 95.7%. 93.6% of the patients received chemotherapy, adjuvantly (43.1%), neoadjuvantly (23.9%) or both (26.6%). Hormone therapy was given to 53.7% of the patients. Progression free survival (PFS) and OS were estimated by the Kaplan-Meier method. The method of cumulative incidence allowing for competing risk was applied to first failure event categorized as locoregional (LRR), distant metastasis (DM), simultaneous (LRR+DM within 4 months of each other) and death NED. Local Control (LC) was defined as the complement of the combined rate of LRR and simultaneous LRR+DM failures. Log-rank test was used to compare OS and PFS by biologic subtype, Gray's test was used to compare incidence rate of failure events by biologic subtype. We retrospectively reviewed 188 consecutive patients with clinical or pathological stage III breast cancer treated at University of Miami from 1990 - 2008. Biologic subtype was approximated using receptor status: Luminal A (ER+ or PR+ and HER2-), Luminal B (ER+ or PR+ and HER2+), HER-2 (ER- and PR- and HER2+), and Basal (ER- and PR- and HER2-). Ninety-seven patients (51.6%) were classified as Luminal A, 20 (10.6%) Luminal B, 22 (11.7%) Her2, and 49 (26.1%) were Basal. All patients received RT. Mastectomy was done in 78.2% and lumpectomy in 21.8%. Axillary surgery was performed in all patients. Surgical margins were negative in 95.7%. 93.6% of the patients received chemotherapy, adjuvantly (43.1%), neoadjuvantly (23.9%) or both (26.6%). Hormone therapy was given to 53.7% of the patients. Progression free survival (PFS) and OS were estimated by the Kaplan-Meier method. The method of cumulative incidence allowing for competing risk was applied to first failure event categorized as locoregional (LRR), distant metastasis (DM), simultaneous (LRR+DM within 4 months of each other) and death NED. Local Control (LC) was defined as the complement of the combined rate of LRR and simultaneous LRR+DM failures. Log-rank test was used to compare OS and PFS by biologic subtype, Gray's test was used to compare incidence rate of failure events by biologic subtype. ResultsMedian follow-up was 46.5 months (range, 7-205). There were 37 events for PFS and 21 deaths for OS. Nine patients had LRR as their first failure, 6 had simultaneous LRR+DM, 15 had DM, and 7 died NED. Due to smaller numbers and lack of events in some groups, subtypes Luminal B and Her2 were grouped together for analysis. LC rate varied significantly by subtype. The 5-year LC was 96% for Luminal A, 92% in Luminal B/Her2, and 83.1% in Basal subtype (p = 0.045, Gray's test). The difference in PFS by subtype was marginally significant with 5-year rates of 83% in Luminal A, 85.1% in Luminal B/Her 2, and 65.4% in Basal patients (p = 0.062, log-rank test). OS varied by subtype with 5-year rates of 91.4% in Luminal A, 92.4% in Luminal B/Her2, and 71.1% in Basal patients (p = 0.032, log-rank test). Median follow-up was 46.5 months (range, 7-205). There were 37 events for PFS and 21 deaths for OS. Nine patients had LRR as their first failure, 6 had simultaneous LRR+DM, 15 had DM, and 7 died NED. Due to smaller numbers and lack of events in some groups, subtypes Luminal B and Her2 were grouped together for analysis. LC rate varied significantly by subtype. The 5-year LC was 96% for Luminal A, 92% in Luminal B/Her2, and 83.1% in Basal subtype (p = 0.045, Gray's test). The difference in PFS by subtype was marginally significant with 5-year rates of 83% in Luminal A, 85.1% in Luminal B/Her 2, and 65.4% in Basal patients (p = 0.062, log-rank test). OS varied by subtype with 5-year rates of 91.4% in Luminal A, 92.4% in Luminal B/Her2, and 71.1% in Basal patients (p = 0.032, log-rank test). ConclusionsWith a median follow-up of 46.5 months, we have demonstrated with statistical significance that Basal tumors have worse 5-year LC and OS compared to Luminal A and Luminal B/Her2 subtype. Further strategies to improve outcome in Basal tumors using radiosensitizers or dose escalation are warranted. Luminal A tumors had the best LC and OS, despite stage III disease. With a median follow-up of 46.5 months, we have demonstrated with statistical significance that Basal tumors have worse 5-year LC and OS compared to Luminal A and Luminal B/Her2 subtype. Further strategies to improve outcome in Basal tumors using radiosensitizers or dose escalation are warranted. Luminal A tumors had the best LC and OS, despite stage III disease.

3081 Background: Ix is a cytotoxic microtubule-stabilizing agent with anti-proliferative and anti-angiogenic properties. S is a multi-targeted receptor tyrosine kinase inhibitor. IX and S combination may be synergistic, since S may increase delivery of Ix to the tumor by inducing vascular normalization. Methods: Patients (pts) with advanced STs were enrolled in a phase I, dose-escalation study to assess safety, pharmacokinetics (PK), angiogenesis biomarkers and to determine the recommended phase II dose. Eligibility: age > 18, ≤ 4 prior systemic therapies (tx), ECOG PS 0-2, measurable/evaluable disease and good organ function. Treatment schedules: A (weekly Ix, 3 out of 4-weeks): starting dose 7.5 mg/m2 IV (1A), 15 mg/m2 IV (2A) and 20 mg/m2 IV (3A). Schedule B (every 3 weeks): starting dose 20 mg/m2 IV (1B), 30 mg/m2 IV (2B) and 40 mg/m2 IV (3B). In both schedules, S was given continuously starting on day 8 of cycle 1 at 37.5 mg PO daily. A standard 3 + 3 design was used and dose-limiting toxicities (DLTs) assessed in the first cycle. Results: 30 patients were enrolled. Two pts withdrew before starting tx. Baseline characteristics: median age: 61.5 (25-78); males/females: 19/9; most frequent STs: colorectal -CRC- (16), pancreas (2), prostate (2); median PS: 1; median of prior tx: 3. Number of pts evaluable for toxicity/dose escalation/efficacy: 28/23/21. One DLT was observed in schedule 3A (grade (gr) 3 DVT) and 2 in schedule 3B (gr 4 mucositis/gr 3 dehydration; gr4 neutropenia). Other gr 3 /4 AEs (non DLTs): leukopenia (18%), neutropenia (25%), lymphopenia (21%), anemia (14%), thrombocytopenia (7%), leukocytosis (4%), fatigue (25%), neuropathy (7%), mucositis (7%), nausea (7%), vomiting (4%), hyperglycemia (4%), syncope (4%), abdominal pain (4%) and GI bleed (4%). Median # of cycles (evaluable pts): 3 (range1-10). Three pts achieved PR (2 with CRC). Eight patients had SD (5 with CRC). 10 patients had PD. Conclusions: The combination of Ix and S appears to have acceptable toxicity and encouraging activity in heavily pretreated pts. The recommended phase II dose for S is 37.5 mg po daily with Ix 20 mg/m2 in Schedule A and Ix 30 mg/m2 in schedule B. Angiogenesis biomarkers and PK analyses are underway.

Pastiche scenarios draw on fiction as a resource to explore the interior ‘felt-life’ aspects of user experience and the complex social and cultural issues raised by technological innovations. This paper sets out an approach for their use, outlining techniques for the location of source material and presenting three case studies of pastiche scenario use. The first case study is an evaluation of the Apple iPod that explores the socio-cultural meanings of the technology. The second case study focuses on the participatory design of Net Neighbours, an online shopping system where volunteers shop as intermediaries for older people who do not have access to computers. The third is an in depth consideration of a conceptual design, the ‘cambadge’ a wearable lightweight web cam which, upon activation broadcasts to police or public websites intended to reduce older people's fear of crime. This design concept is explored in depth in pastiche scenarios of the Miss Marple stories, A Clockwork Orange and Nineteen Eighty-four that reflect on how the device might be experienced not only by users but also by those it is used against. It is argued that pastiche scenarios are a useful complementary method for designers to reason about user experience as well as the broad social and cultural impacts of new technologies.