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Background: Patients (pts) with breast cancer treated with neo-adjuvant therapy on clinical trials are often asked to consent to pre-treatment and on-treatment research biopsies. There is increasing interest in obtaining tissue samples at similar time points in pts treated with neo-adjuvant therapy outside of clinical trials. However, medical oncologists’ (MOs) attitudes towards approaching pts about research biopsies in this setting are unknown. Methods: Three hundred and nine academic breast MOs identified from websites of the National Cancer Institute (NCI) – designated cancer centers were asked to complete a survey either by paper or online. Eligible MOs (MOs who saw breast cancer pts and who saw pts >4 hours/week.) were asked to predict what proportion of their pts with newly diagnosed, non-metastatic breast cancer would consent to research purposes only biopsies (RPOBs) i.e., biopsies with no clinical benefit to pt. Median values are reported. Two-sided Fisher’s exact test was used to compare categorical variables using a α level of .05. Results: Of 221 (101F,85M, 5 unknown) MOs who completed the survey, 30 MOs were ineligible (response rate=221/309,72%). Median age was 50 (Range 33-80). Median years of oncology experience was 15 (Range 1-45). MOs predicted that 14%, 63% and 21% of their pts would definitely/probably, maybe, probably not/definitely not consent to a RPOB of the breast. Forty-one percent, 34%, 19%, 3% of MOs were very comfortable, somewhat comfortable, somewhat uncomfortable, and very uncomfortable asking pts to consent to RPOBs respectively. The only factor associated with increased comfort discussing an RPOB was MOs’ years in practice. MOs with fewer years (15 years) (Adjusted RR=1.2, p =0.02). Gender, number of pts enrolled onto clinical trials, and MOs with pts who had research biopsies in the last 3 months was not associated with increased comfort. MOs who were more comfortable in approaching pts for RPOBs were associated with estimating a larger proportion of their pts as willing to undergo RPOB. For example, nearly one third of MOs who were very comfortable with approaching pts for RPOBs estimated that greater than 50% of their pts would consent to research biopsies. In contrast, nearly all the MOs who were very uncomfortable with approaching pts for RPOBs estimated that less than 25% of their pts would consent to research biopsies. The 3 most common reasons why MOs were reluctant to consent pts for a RPOB include pain/discomfort of a biopsy (59%), risk of a biopsy procedure complication, (44%), and inconvenience to the pt (33%). Conclusions: Academic breast MO’s predicted that fewer than 1 in 5 women with newly diagnosed, non-metastatic breast cancer would definitely or probably agree to a request for an RPOB outside of the context of a therapeutic trial, and approximately one-quarter of MOs expressed discomfort in approaching pts for such procedures. Our results have important implications regarding the feasibility of such research efforts, and identify potential barriers to target for intervention. Citation Format: Davinia SE Seah, Sarah Scott, Hao Guo, Julie Najita, Ruth Lederman, Elizabeth Frank, Jessica Sohl, Zsofia Stadler, Stuart G Silverman, Jeffrey Peppercorn, Eric P Winer, Steve E Come, Nancy U Lin. Attitudes of medical oncologists towards research breast biopsies in patients with newly diagnosed stage I-III breast cancer not enrolled in a clinical trial [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-17-01. more...

Background: There is increasing interest in studying tissue from patients (pts) with metastatic breast cancer (MBC). Historically, limited tissue has been available. Possible barriers to research biopsies (bx) include pt and provider opinions; the contribution of each factor is unknown. Methods: 309 academic breast medical oncologists (MOs) identified from the websites of each of the National Cancer Institute - designated cancer centers were invited to complete either a self-administered paper or online survey. Eligible MOs (MOs who saw breast cancer pts and who saw pts 4 hours/week.) were asked to predict what proportion of their pts with MBC would consent to additional bx (ABs, additional bx performed with a clinically indicated bx) or research purposes only bx(RPOBs, research bx performed as a standalone procedure). They were also asked about their comfort levels in asking pts with MBC to consider participating in ABs or RPOBs for various organs. Median values are reported. Two-sided Fisher's exact test was used to compare categorical variables using a a level of .05. Results: 191 (101F,85M, 5 unknown) eligible MOs completed the survey. 29 MOs were ineligible (response rate = 191/280,68%). Median age was 50 (Range 33-80). Median years of oncology experience was 15 (Range 1-45). MOs predicted that 90%, 75%, 70% and 50%, of their pts would definitely/probably consider ABs of blood, skin, breast, or liver respectively. MOs predicted that 90%, 60%, 33%, and 20% of their pts would definitely/probably consider RPOBs of blood, skin, breast, or liver. 98% (95% CI 96%-100%), 96% (95% CI 92%-98%), 93% (95% CI 88%-96%) and 70% (95% CI 63%-77%) of MOs were very/somewhat comfortable asking pts for an AB of blood, skin, breast and liver respectively. 98% (95% CI 95%-99%), 93% (95% CI 89%-96%), 78% (95% CI 72%-84%) and 50% (95% CI 43%-58%) of MOs were very/somewhat comfortable asking pts to participate in a RPOB of blood, skin, breast and liver respectively. No demographic characteristics (eg. sex, age) were associated with MOs’ comfort levels of asking pts to have an AB of blood, skin and breast. Factors associated with increased comfort discussing an AB of the liver were: age < 50 years (p = 0.01), in practice for < 15 years (p = 0.01), ≥ 1 pt enrolled on clinical trials per month (p = 0.02), or having pts who had undergone bx for research in prior 3 months (p MOs with ≥ 4 patients enrolled on clinical trials/month or whose pts had undergone research bx in the past 3 months were more likely to feel comfortable asking pts to have a RPOB of the breast (p The 3 most common reasons why MOs were reluctant to refer pts for participation in an AB include risk of a bx procedure (n = 128, 67%), pain/discomfort of a bx (n = 125, 65%), and logistical barriers (n = 42, 22%). These reasons are similar for RPOB; risk of a bx procedure, (n = 137, 72%), pain/discomfort of a bx (n = 134, 70%), and inconvenience to pt (time involved, travel, etc) (n = 58, 30%). Conclusions: Many MOs predict that the majority of their MBC pts will consider ABs of various organs. However, this decreases with RPOBs, particularly as the procedure becomes more invasive. More research is needed to understand factors that may influence MOs’ comfort levels asking pts to participate in such studies. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-19-01. more...

Background: In the era of molecularly targeted therapy, developing an understanding of the molecular basis of cancer is a principal or secondary goal of many research studies. For this reason, studies collecting tissue for research purposes are increasingly common. Understanding patients' attitudes towards research biopsies may lead to improvement in accrual to research biopsy studies. Methods: Patients with metastatic breast cancer from two academic and two community hospitals completed a self-administered paper survey consisting of 29 questions in clinic to evaluate their willingness to consider providing additional biopsies (additional biopsy performed with a clinically indicated biopsy) and research purposes only biopsies (RPOB) (research biopsy performed as a stand alone procedure). Results: 160 patients (n = 80 academic, n=80 community) completed the survey, with a response rate of 98%. As expected, demographic variables differed between sites, with patients from academic sites likely to be younger (p = 0.01), more educated (p = 0.002), employed (p = 0.01), have prior trial participation (P In univariate analyses of patients' willingness to have additional biopsies, patients in academic sites were more likely to agree to additional biopsies than those at community sites (RR = 1.2, 95% CI 1.0–1.5, p = 0.03). Statistically significant differences based on demographic characteristics such as age, education, marital status, prior trial participation, number of prior biopsies, and travel time were not observed. For RPOB, patients having had more prior biopsies were less likely to consider research biopsies (RR = 0.6, 95% CI 0.4–1.0, p = 0.03). The following variables did not reach statistical significance: type of practice, age, education, marital status, prior trial participation, and travel time. Patients' willingness in both academic and community sites to consider RPOB declined with more invasive biopsies. Although differences were observed, none were statistically significant between academic and community; skin (56%, 65%), bone marrow (30%, 27%), breast (43%, 49%) or liver (24%, 19%). Of the 13/160 (8%) patients who would not consider additional biopsies, the most common reasons cited included pain or discomfort (n = 8/13, 62%), risk of biopsy (n = 8/13, 62%) and anxiety related to the biopsy (n = 6/13, 46%). Of the 37/160 (23%) patients who would not consider RPOB, the most common reasons cited included pain or discomfort (n = 23/37, 62%), risk of biopsy (n = 15/37, 41%) and inconvenience of the procedure to the patient (n = 13/37, 35%). Conclusions: The majority of patients in this study indicated they would consider research biopsies, with a larger proportion willing to consider additional biopsies; patients seen at academic hospitals were more likely to consider additional biopsies compared to those seen at community hospitals. Breast cancer patients' willingness to undergo research biopsies may be higher than generally expected by clinicians and may not be the primary barrier to obtaining research biopsies. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-16-04. more...

Background Patients (pts) with (w/) node-negative HER2−positive BCA have a higher risk of recurrence than those with node-negative HER2−negative disease. Several randomized trials have shown the benefit of chemotherapy (most with an anthracycline) and trastuzumab (H) for pts with node-positive and high-risk node-negative BCA. However, the benefit of chemotherapy and H needs to be further explored in the node-negative group. Due to the 2–4% risk of symptomatic congestive heart failure (CHF) with an anthracycline-based treatment (Rx) followed by H, we set out to conduct a study of a taxane-based Rx with H in a node-negative population. Design: This is a single arm, multicenter, phase II study of paclitaxel (T) (80 mg/m2) and trastuzumab (H) x 12 weekly (w) (4 mg/kg load →2 mg/kg) → H x 52 w (2 mg/kg weekly or 6 mg/kg q 3 w). Pts with HER2−positive BCA (IHC 3 + or FISH amplified at ≥ 2.0) with negative nodes (micrometastasis later allowed) and with a tumor size ≤ 3 cm were enrolled. The primary endpoint is disease-free survival. Secondary endpoints include the incidence of G 3/4 left ventricular systolic dysfunction or congestive heart failure (CHF). Pts had serial left ventricular ejection fraction (LVEF) monitored at baseline (BSLN), and at month (mo) 3, mo 6, and mo 12 w/a multigated acquisition scan or echocardiogram. H was held for significant asymptomatic (Asx) LVEF ↓ (10-15% ↓ from BSLN and < lower limit of normal or ≥ 16% ↓ from BSLN), and H was stopped for CHF. Results: From 10-9-2007 to 9-3-2010, 406 pts were enrolled. The median (med) age was 55 years (range 23–84 years); 118/406 (29%) had hypertension and 30/406 (7%) had diabetes. As of 6-1-2011, 307 are reported as off Rx of which 261 have completed protocol therapy; 99 remain on therapy. To date, 100%, 94%, 84%, and 83% of pts had LVEF monitoring at BSLN, mo 3, mo 6, and mo 12. The med LVEF at BSLN was 65% (range 50%-81%), at mo 3 was 64% (range 45%-81%), at mo 6 was 64% (range 45%-81%), and at mo 12 was 65% (range 37%-90%). Two pts had CHF; 1 pt had CHF at mo 11 (LVEF was 55% at BSLN and 37% w/CHF event) and 1 pt had CHF at mo 6 (LVEF was 66% at BSLN and 49% w/CHF event). To date, 13 pts had H held for significant Asx LVEF ↓; details on those who had appropriate LVEF recovery and had H restarted will be provided. All patients will have completed 12 mo of Rx by October 2011, and an accurate report of the incidence of CHF will be available. Conclusion: This represents the cardiac report of pts receiving TH as adjuvant Rx for node-negative (micrometastasis allowed) HER2 positive BCA. Both the CHF events and number of pts w/H hold due to significant Asx ↓ LVEF appear low. Overall, the serial med LVEFs remain stable throughout the 12 mo of Rx. Final data on all 406 pts will be available in December 2011. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-18-02. more...

Background We evaluated the safety and efficacy of L+T in pts with 0–2 prior lines of chemotherapy (CT) for HER2+ MBC. In the context of this phase II trial, we evaluated metabolic response by FDG-PET and explored the relationship between metabolic response and clinical outcomes. Methods: Pts with measurable, HER2+ MBC were eligible. Cohort 1: No prior T, L, or CT +T for MBC, and >1 yr from adjuvant T, if received. Cohort 2: 1–2 prior lines of CT for MBC, including T, or relapse within 1 yr of adjuvant T. Pts received L 1,000 mg QD + T (2 mg/kg weekly or 6 mg/kg Q3W). Staging studies were done with CT or MRI at baseline (BL) and every 2 cycles (1 cycle=4 weeks [wks]). Objective response was assessed by local investigator according to RECIST 1.0. FDG-PET/CT was performed at BL, Wk 1, and Wk 8 per NCI guidelines. Central quality assurance, review, and analysis were performed on FDG-PET studies. Up to 5 target lesions were identified on BL FDG-PET images based on hypermetabolic uptake. Percent change in the summed maximum standardized uptake value (SUVmax) of target lesions was calculated at Wk 1 or Wk 8, compared to BL. Metabolic response was assessed according to EORTC criteria for % change in SUVmax (progressive disease [PD]: ≥25% increase; partial response [PR]: ≥25% decrease; stable disease [SD]: Results: 87 pts were registered to the study. Of these, one pt did not begin protocol therapy and one pt did not have MBC on further testing, and are not included. 81/85 pts had FDG-PET data at Wk 1; 75/85 had data at Wk 8. Metabolic PR at Wk 1 was observed in 28/39 (72%) pts in Cohort 1 and 20/42 (48%) pts in Cohort 2. Metabolic PR at Wk 8 was observed in 27/34 (79%) pts in Cohort 1 and 18/41 (44%) pts in Cohort 2. Wk 1 and Wk 8 metabolic responses were similar. In cohort 1, 18/28 (64%) pts who achieved Wk 1 metabolic PR had clinical benefit by RECIST. Of pts with Wk 1 metabolic SD, 2/9 (22%) had clinical benefit. In cohort 2, 9/20 (45%) pts who achieved Wk 1 metabolic PR had clinical benefit; 5/22 (23%) who achieved Week 1 metabolic SD had clinical benefit. Exploratory analysis of progression-free survival (PFS) showed that pts in Cohort 1 who achieved Wk 1 metabolic PR experienced a median PFS of 9.3 months ([mos]; 95% CI 5.6−22.3); for pts with metabolic SD, median PFS was 1.9 mos (95% CI 0.8−5.5). For pts in Cohort 2, Wk 1 metabolic PR was associated with median PFS of 5.6 mos (95% CI 3.7−7.8), whereas for pts with metabolic SD, median PFS was 3.7 mos (95% CI 1.8−5.5). Conclusions: L+T is associated with a high rate of early and sustained metabolic response by FDG-PET. Exploratory analyses suggest that metabolic PR may be associated with clinical benefit and longer PFS. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-09-07. more...

Background: Women with HER2-positive metastatic breast cancer (MBC) can have clinical responses to multiple lines of anti-HER2 therapy. However, it is unknown whether these patients will derive further clinical benefit following treatment with the novel antibody-drug conjugate trastuzumab-MCC-DM1 (T-DM1), which has significant activity in trastuzumab-refractory breast cancer. Methods: We retrospectively identified patients treated with T-DM1 monotherapy on clinical trials for HER2-positive MBC at Dana-Farber Cancer Institute and characterized clinical outcomes during subsequent lines of anti-HER2 therapy. Response was determined by an independent and blinded radiology review using modified RECIST 1.1 criteria without confirmatory scans; patients without radiologic assessment were considered non-responders. Duration of therapy was defined from initiation of therapy until treatment discontinuation, and for patients continuing on therapy, times were censored at date of last visit; analysis was performed using Kaplan-Meier estimates. Results: We identified 23 patients treated on protocol-based therapy with single-agent TDM-1 and report on the 20 patients who had discontinued protocol, and hence, T-DM1 therapy. All patients received trastuzumab in the metastatic setting prior to initiation of T-DM1, with a median number of 6 (range 1-14) prior regimens. Most (75%) were taken off study secondary to progressive disease and the remainder discontinued therapy for toxicity. Of these 20 patients, 75% (15 of 20) received further therapy with or without anti-HER2 agents after concluding T-DM1; reasons for not receiving additional treatment after T-DM1 include death (3) and interruption of therapy due to physician or patient request (2). The majority (12 of 15; 80%) of patients treated beyond T-DM1 received a regimen containing either trastuzumab and/or lapatinib at some point during their course. Partial response to either first-or second-subsequent line(s) of therapy was seen in 5 of 15 (33%) treated patients, including 33% (4 of 12) who received a regimen containing trastuzumab and/or lapatinib (Figure 1). Three patients did not have radiographic assessments; however, all 3 demonstrated clinically stable disease (as determined by review of clinical data) to first treatment after T-DM1. Median duration of therapy to first-subsequent regimen after T-DM1 was 5.5 months. Of the 9 patients that received a second-subsequent regimen, the median duration of therapy to the second-subsequent treatment was 6.4 months. Conclusions: In heavily pretreated HER2-positive MBC patients, prior exposure to T-DM1 does not exhaust the potential benefit of ongoing anti-HER2 therapy with trastuzumab and/or lapatinib-based regimens. Maximum Decrease in Target Lesion Diameter Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-14-08. more...

Background: Circulating tumor cells (CTCs) with evidence of HER2 amplification can occur in patients (pts) with clinically HER2 negative metastatic breast cancer. While these findings potentially have profound implications for CTCs as a biomarker for treatment, prospective validation and characterization of this subgroup is necessary. Methods: We created a prospective cohort of pts with metastatic breast cancer that were HER2 negative by IHC and/or FISH on all available primary and metastatic biopsies. Blood samples were collected at study entry and then again at ≥ 3 weeks if available. CTCs were enumerated by a modification of the Veridex CellSearch Profile kit. FISH was performed on each CTC sample and reported as positive if the HER2/CEP17 ratio was ≥ 2.0. Analyses are descriptive. Results: 66 pts were consented for study and this report includes the 65 pts with detectable CTCs. Median number of CTCs was 226 (range 112 to > 3000). At initial testing, 23 pts (35%) had HER2 positive CTCs, median HER2:CEP17 ratio of 3.4. 50% (11 of 22) of the pts with lobular or ductal/lobular histology had HER2 amplified CTCs, compared to only 27% (10 of 36) of patients with ductal histology. Women with ER positive disease had HER2 positive CTCs in 40% of cases (20 of 49) compared to 19% of ER negative pts (3 of 16). To assess concordance of HER2 amplification of CTCs over time, 34 pts consented to be retested at a median 5.9 weeks after initial screening (range 3.3 - 17 weeks) and all but 1 had detectable CTCs. Baseline characteristics of these 34 pts were similar to the original population, with HER2 amplified CTCs detected in 35% (12 of 34) pts at initial screening. HER2 positive CTCs were concordant at time of retesting in 83% (10 of 12) pts; the 2 women with discordant CTCs were receiving HER2 directed therapy. Of the pts with HER2 negative CTCs at initial screening, 81% (17 of 21) continued to have HER2 negative CTCs at time of retesting. Conclusion: We observed a higher prevalence of HER2 positive CTCs among pts with ER positive disease and evidence of lobular histology. The presence of HER2 positive CTCs is concordant over time in the majority of pts. The functional significance of HER2 positive CTCs in patients with clinically HER2 negative breast cancer will be tested in a prospective study with HER2−directed therapy. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD05-07. more...

Observational studies have demonstrated a 30-50% lower risk of disease-specific and overall mortality in physically active breast and colorectal cancer patients as compared to sedentary individuals. However, there have been no randomized trials looking at the impact of physical activity on cancer outcomes, and the optimal design of such a trial is not yet well-defined. The Active After Cancer Trial (AACT) is a multicenter feasibility study designed to evaluate the ability of a telephone-based intervention to increase physical activity in patients with breast and colorectal cancer. Methods: Sedentary (reporting less than 60 minutes/week of recreational activity) individuals with stage I-III breast or colorectal cancer were eligible for enrollment after completion of all adjuvant chemotherapy and radiation. Participants were randomized 1:1 to a centralized telephone coaching intervention, with a target goal of 180 minutes/week of physical activity, or to a usual care control group. Intervention participants received an average of 10 telephone contacts over 16-weeks. Initial calls focused upon building self-efficacy and later calls concentrated upon relapse prevention and maintenance of exercise behaviors. Participants underwent assessment of physical activity behaviors (7-Day Physical Activity Recall), fitness (6-Minute Walk Test), physical functioning (EORTC QLQ C-30), fatigue (FACIT) and exercise self-efficacy at baseline and 16 weeks after enrollment. Results: One hundred and twenty-one patients were enrolled through 10 Cancer and Leukemia Group B (CALGB) institutions; 100 patients had breast cancer and 21 had colorectal cancer. Average age was 54.3, 74% of patients had received chemotherapy and mean time since completion of adjuvant treatment was 24 months. Participants randomized to the exercise group experienced significant improvements in fitness and physical functioning as compared to controls. Table. Baseline measures and change (post-minus pre) scores in intervention and control patients (±SD) Intervention participants also reported a doubling in minutes of weekly physical activity, but this was not a significant increase compared to controls. Conclusions: Sedentary breast and colorectal cancer survivors can be enrolled in a physical activity intervention. A centralized telephone coaching intervention successfully increased fitness and physical functioning, although self-reported exercise time was not significantly changed. A large-scale clinical trial within the co-operative groups is feasible. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD08-09. more...

Abstract #3137 Background: The epitholones are a new class of antineoplastic agents which are microtubule inhibitors with low susceptibility to several mechanisms of drug resistance. Ixabepilone (BMS-247550, aza-epothilone B) has demonstrated efficacy as monotherapy or in combination with capecitabine (in anthracycline- and taxane-pretreated metastatic breast cancer) and has recently been approved for use in refractory breast cancer. A multicenter NCI-sponsored study was conducted to analyze the safety and efficacy of the combination of ixabepilone with trastuzumab in patients with metastatic HER2-positive breast cancer. Methods: This phase II nonrandomized study enrolled two cohorts of patients. Cohort 1 received no prior chemotherapy or trastuzumab for metastatic disease and cohort two received one or two prior trastuzumab-containing regimens for metastatic disease. Patients in each cohort received the same treatment regimen of ixabepilone and trastuzumab. Patients received ixabepilone 40 mg/m2 as a 3-hour continuous infusion on day 1 of a 21-day cycle plus trastuzumab once every 21 days. For the initial treatment of trastuzumab, patients received 8 mg/kg IV, and for all subsequent trastuzumab treatments 6 mg/kg. Treatment was continued until disease progression or unacceptable toxicity. Endpoints included response rate (RR), time to progression (TTP), toxicity, and predictive biomarkers. Results: 39 women entered the study (median age 51, range 29-74) with 15 patients in cohort 1 and 24 patients in cohort 2. A median of 7 cycles of therapy were administered in each cohort. In cohort 1, there were 12 partial responses (PR), and 1 patient with stable disease for 5 months (SD). In cohort 2, there were 8 PRs and 9 patients with SD. Across both cohorts, the overall RR was 51%, with a clinical benefit rate (CR + PR + SD for at least 6 months) of 56%. Treatment-related toxicities included neuropathy (grade ≥2, 55%), myalgias (grade ≥2, 20%), anemia (grade ≥2, 18%), neutropenia (grade ≥2, 23%), and elevated transaminases (grade ≥2, 10%). There were no episodes of grade 2 or higher cardiac toxicity. Biomarker data will be presented. Conclusion: This represents the first study of the combination of ixabepilone with trastuzumab for the treatment of metastatic HER2-positive breast cancer. These results suggest that the combination has an encouraging response rate as first- and subsequent- line therapy for metastatic breast cancer. Clinically significant neuropathy was the major toxicity, and appeared to be cumulative. Based on these results, further evaluation of ixabepilone plus trastuzumab is warranted. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3137. more...

Abstract #4124 Background: Vaccination with tumor cells engineered to secrete granulocyte-macrophage colony stimulating factor (GM-CSF) generates potent, specific, and long-lasting anti-tumor immunity in multiple tumor models. At DF/HCC, over 100 patients with melanoma, ovarian cancer, and lung cancer have been vaccinated. These studies have led to the identification of targets of immune-mediated tumor destruction. Here, we present analysis on the safety, feasibility, and biologic activity of an autologous GM-CSF-secreting breast cancer vaccine. Methods:27 patients with metastatic breast cancer have undergone tumor procurement for vaccine from malignant pleural effusions (23), ascites (1), tumor nodules (2), lymph node (1), and 12 patients have received vaccine. Cells were transduced with a replication defective adenoviral vector encoding GM-CSF, irradiated, and GM-CSF secretion was measured by ELISA. Patients were required to have received at least one prior chemotherapy for metastatic disease and have an ECOG performance status 0-1. Vaccine was delivered s.c. and i.d. weekly for three weeks, then every other week. Immune monitoring included skin biopsies of vaccine sites, measurement of leukocyte populations, and proteomic-based assessment of antibody responses. Results: Sufficient viable tumor cell yields for vaccination were obtained from all patients, with cellular yields ranging from 1.1-679 x 106 cells and viabilities ranging from 71-100%. Dose levels were based on cellular yield, ranging from 105 -107 cells/dose. The average yield of GM-CSF was 838 ng/106 cells/24 hrs (range: 24.4-5696), higher than the average yields for lung cancer and melanoma. Vaccinated patients were 34-69 years, and received 3-23 vaccines. 9 patients had progressive disease after 3-10 vaccines (1-4 months). One patient had stable disease after 23 vaccines (11 months), resumed vaccination at 16 months for progression and remains on study. One other patient remains on study, and one patient did not have measurable disease. Toxicities related to treatment include grade I/II local injection-site reactions, grade I/II inflammation at tumor sites as well as grade I/II fatigue, fever, nausea, and edema. Skin biopsies of vaccination sites revealed mild-moderate infiltration of lymphocytes, granulocytes, and macrophages. Conclusion: Breast cancer cells can be harvested in sufficient number for autologous vaccine production from solid tumor as well as from malignant effusions. Autologous vaccination can induce coordinated immune responses with limited toxicity. The proteomic-based identification of antigen-specific immune responses following vaccination will be presented. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4124. more...