Corrections: 2009 San Antonio Breast Cancer Symposium Abstracts

Abstract

The abstracts of the 2009 CTRC-AACR San Antonio Breast Cancer Symposium were published as a Supplement to the December 15, 2009 issue of Cancer Research. The following three Late-Breaking Abstracts were accepted for presentation at the Symposium after the abstract supplement went to press:#80 Results of Chemotherapy Alone, with Sequential or Concurrent Addition of 52 Weeks of Trastuzumab in the NCCTG N9831 HER2-Positive Adjuvant Breast Cancer Trial.Perez E, Suman V, Davidson N, Gralow J, Kaufman P, Ingle J, Dakhil S, Zujewski J, Pisansky T, Jenkins R. Mayo Clinic, Jacksonville, FL; Mayo Clinic, Rochester, MN; University of Pittsburgh, Pittsburgh, PA; Seattle Cancer Center Alliance, Seattle, WA; Dartmouth Hitchcock Medical Center, Lebanon, NH; Cancer Center of Kansas, Wichita, KS; National Cancer Institute, Bethesda, MD.Background: N9831 is the only randomized phase III trial comparing safety and efficacy of the addition of trastuzumab (H) to doxorubicin and cyclophosphamide then paclitaxel (arm A: AC→T) either following (arm B: AC→T→H) or starting concurrently with paclitaxel (arm C: AC→T+H→H) for women with resected stage I to III invasive HER2+ breast cancer. The 3-year cumulative incidence of NYHA class III or IV congestive heart failure or sudden cardiac death was previously reported: 3.3% in arm C, 2.8% in arm B (Perez EA et al., JCO 2008). The comparison of AC→T to AC→T+H→H was reported in a joint analysis of N9831 and NSABP B-31 in 2005 and updated in 2007, demonstrating a 52% reduction in risk of a disease event (Romond E et al., NEJM 2005; Perez EA et al., ASCO 2007).Materials and Methods: Primary end point is disease-free survival (DFS). At the second planned interim analysis of arm A versus arm B, the O'Brien-Fleming boundary (OFB) was crossed. The NCCTG Independent Data Safety Monitoring Committee approved the release of these data as well as the data pertaining to arm B versus arm C due to slow pace of events [expected 647 events in 4-year follow-up period (f/u) versus actual 334 events in 4.5-year f/u]. Shortly thereafter, there were sufficient events to perform the first planned interim analysis of B versus C. We present the results of each of these pairwise comparisons taking into account the potential for crossover to arm C after the release of the joint analysis findings in 2005.Results: From May 2000 to April 2005, 2,448 eligible women were enrolled for the arm A (n = 1,087) versus arm B (n = 1,097) comparison. Median f/u is 5.5 years with 386 events. The addition of trastuzumab sequentially to AC→T significantly improved DFS, univariately [HR(arm B/arm A) = 0.70; 95% CI, 57–86%; log-rank P = 0.0005] and after adjusting for age, tumor size, number of positive nodes, and ER [PPH: HRadj = 0.67 (95% CI, 0.55–0.82)]. Five-year DFS was increased from 72% with AC→T to 80% with AC→T →H.From May 2000 to April 2005, 1,903 eligible women were enrolled for the arm B (n = 954) versus arm C (n = 949) comparison. Median f/u is 5.3 years with 312 events. The log-rank P value testing whether DFS differs with respect to starting time of trastuzumab was 0.019 (not crossing prespecified OFB for statistical significance). After adjusting for tumor size, number of positive nodes, and ER, HRadj (arm C/arm B) = 0.75 (95% CI, 0.60–0.94). Five-year DFS was increased from 80% with AC→T →H to 84% for AC→T+H →H.Conclusions: DFS is significantly improved with the addition of 52 weeks of H (sequentially or concurrently) to AC→ T. There is a statistically significant 33% reduction in the risk of an event with the sequential addition of H following AC→T. There is a strong trend for a 25% reduction in the risk of an event with starting H concurrently with T relative to sequentially after T. Therefore, based on a positive risk/benefit ratio, we recommend that trastuzumab be incorporated in a concurrent fashion with T chemotherapy.Acknowledgements: NIH grant CA25224, the Breast Cancer Research Foundation, and Genentech.#112 Prediction of 10-Year Chemotherapy Benefit and Breast Cancer–Specific Survival by the 21-Gene Recurrence Score (RS) Assay in Node-Positive, ER-Positive Breast Cancer—An Update of SWOG-8814 (INT0100).Albain K, Barlow W, Shak S, Hortobagyi G, Livingston R, Yeh I, Ravdin P, Bugarini R, Baehner F, Davidson N, Sledge G, Winer E, Hudis C, Ingle J, Perez E, Pritchard K, Shepherd L, Gralow J, Yoshizawa C, Allred D, Osborne C, Hayes D, for The Breast Cancer Intergroup of North America. Loyola University Chicago Cardinal Bernardin Cancer Center, Chicago, IL.Background: A low 21-gene recurrence score (RS) identifies patients with ER-positive breast cancer who do not seem to benefit from anthracycline-based chemotherapy (CAF) added to tamoxifen (T) despite positive axillary lymph nodes (Albain KS et al., Lancet Oncology, in press). However, in the low-RS group, the lack of improvement by CAF in the 64% disease-free survival (DFS) at 10 years is not considered definitive evidence against the use of chemotherapy for conventionally identified high-risk patients. We conducted new DFS prediction analyses within nodal categories by RS over 10 years and assessed whether the assay has predictive utility for breast cancer–specific survival (BCSS).Methods: RT-PCR analyses for the 21-gene RS assay were feasible in 148 patients on T from the parent trial treated and 219 on CAF followed by T, as previously described. In this update, we conducted 10-year DFS analyses within nodal categories 1–3+ and 4+ by the linear RS. For the exploratory analysis of BCSS, only deaths due to breast cancer were counted as events, censoring deaths due to other causes (such as late cardiovascular events) as well as patients alive at the last follow-up visit. The clinically used (trichotomized) RS categories of low (<18), intermediate (18–30), and high (≥31) were used for the BCSS analysis, and log-rank P values were stratified by nodes.Results: As with the previously reported 5-year DFS analysis by nodal status and linear RS, there was no apparent DFS benefit to CAF in the lower RS over 10 years for either the 1–3+ or the 4+ nodal group. Specifically (for both nodal groups), the 10-year DFS treatment curves overlapped for scores 0–10 and then started diverging at about RS = 11, although any clinically meaningful CAF benefit for DFS was not evident until much higher RS. There was no BCSS benefit from CAF in either the low-RS (log-rank P = 0.56) or the intermediate-RS (log-rank P = 0.89) category, but CAF resulted in superior BCSS in the high-RS category (log-rank P = 0.033). The 10-year estimates for BCSS for low RS were 92% (95% CI 79–97%) for T and 87% (95% CI, 76–93%) for CAF-T. In the intermediate RS, 10-year BCSS estimates were 70% (50–83%) for T and 81% (67–89%) for CAF-T; in the high RS, 10-year BCSS estimates were 54% (38–68%) for T and 73% (60–82%) for CAF-T.Conclusions: These additional exploratory analyses reinforce our initial interpretation that anthracycline-based chemotherapy does not seem to benefit patients with either 1–3 or 4 or more positive nodes over 10 years, if their tumors have a low RS. A prospective study to confirm and extend these results has been proposed. New adjuvant treatment strategies for tumors with this distinct biology should be a high research priority.Funding: This study was supported by the National Cancer Institute (NCI #8814A-ICSC) and Genomic Health, Inc.#3183 Interim Analysis of a Randomized Phase II Study of the Novel Ii-Key Hybrid HER2/Neu Peptide (AE37) Vaccine to Prevent Breast Cancer Recurrence: United States Military Cancer Institute Clinical Trials Group Study I-05.Peoples G, Perez S, Clifton G, Holmes J, Georgakopoulou K, Benavides L, Gates J, von Hofe E, Baxevanis C, Mittendorf E, Ardavanis A, Ponniah S, Papamichail M. Brooke Army Medical Center, Fort Sam Houston, TX; Saint Savas Cancer Hospital, Athens, Greece; Naval Medical Center, San Diego, CA; Antigen Express, Worcester, MA; M.D. Anderson Cancer Center, Houston, TX; Uniformed Services University of Health Sciences, Bethesda, MD.Background: CD4+ T helper peptides from HER2/neu have been evaluated in vaccine trials. The Ii-Key addition, a 4-amino-acid (LRMK) modification, increases vaccine potency when compared with unmodified class II epitopes. We present results of a prospective, randomized, single-blinded phase II clinical trial of the Ii-Key hybrid HER2/neu peptide (AE37) + granulocyte macrophage colony-stimulating factor (GM-CSF) immunoadjuvant vaccine versus GM-CSF alone in the adjuvant setting in disease-free, high-risk breast cancer (BCa) patients to prevent recurrence.Methods: Disease-free, high-risk BCa patients who have completed standard adjuvant therapy were enrolled and randomized to receive six monthly inoculations of either 500 μg of AE37 with 62.5 or 125 μg of GM-CSF (peptide group; PG) or 62.5 or 125 μg of GM-CSF alone (adjuvant group; AG). Toxicity was assessed after each inoculation using National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. Immunologic response was monitored using delayed type hypersensitivity reactions (DTH) and [3H]thymidine proliferative assays for both hybrid AE37 (LRMK+HER2/neu:776–790) and AE36 (unmodified HER2/neu:776–790) peptides. Patients were clinically, radiographically, and pathologically monitored for recurrence of BCa.Results: Thus far, 120 (49 PG, 71 AG) of the planned 200 patients have completed the primary series. The PG and AG have similar demographic/prognostic characteristics (Table 1). Toxicity profiles in the PG and AG were almost identical with no grade 4 to 5 local toxicities and no grade 3 to 5 systemic toxicities in either arm. Median DTH reaction to AE36 and AE37 increased significantly from baseline at 1 month after completion of the primary series in the PG group (AE36: 0.0 ± 0.8 to 15.3 ± 2.1 cm; AE37: 0.0 ± 0.7 to 24.5 ± 2.6 cm; P < 0.0001) and did not change in the AG group (AE36: 0.0 ± 0.5 to 0.0 ± 1.4 cm; AE37: 0.0 ± 0.7 to 0.0 ± 1.6 cm; P < 0.05). Median proliferation response to AE36 and AE37 increased significantly from baseline at 3, 6, and 12 months after the start of the vaccine series in the PG (P < 0.015) and did not change significantly in the AG. At a median follow-up of 13 months, there have been no (0.0%) recurrences in the PG (0 of 49) compared with 7.0% (5 of 71) in the AG (P = 0.08).(See Table 1.)Conclusions: The modified peptide AE37 is safe with mild toxicities observed primarily due to the GM-CSF immunoadjuvant. AE37 elicits a strong HER2/neu-specific in vivo and ex vivo immune response to the modified and unmodified peptides. Importantly, the AE37 peptide vaccine may protect against BCa recurrences.In abstract 4053, which was published in the December 15, 2009 abstract supplement to Cancer Research, three of the authors (including L.B. Jordan, the correct presenting author) were inadvertently omitted. The correct author string is provided below. The online version of the abstract has been updated to reflect this change and no longer matches the print.#4053 A Prospective Comparison of Switches in Biomarker Status between Primary and Recurrent Breast Cancer: The Breast Recurrence in Tissues Study (BRITS).Jordan LB, Purdie CA, Quinlan PR, Anderson E, Thompson AM. For the Breast Recurrence in Tissues Study (BRITS), United Kingdom.The following abstracts were printed in the SABCS abstract supplement but were withdrawn by the authors prior to the start of the Symposium:#702 Benefit from Adjuvant Trastuzumab in HER2-Negative Patients—Independent Validation of Central HER2 Assay Results from NSABP B-31. Paik S, Jeong J-H, Goldstein L, Simon R, Sneige N, Kim C, Geyer, Jr., CE, Wolmark N.#810 Upper-Body Morbidity following Breast Cancer—How Big Is the Problem? Hayes SC, Rye S, Battistutta D, Newman B.#1003 The Breast Cancer Stromal Factor and Its Clinical Impact in T1a-T1b Carcinomas. Wernicke M, Roitman P, Manfre D.#1029 Three-Dimensional Imaging Localization of Sentinel Lymph Nodes with a Handheld Gamma Probe. Britten A, Tropman D, Newey V.#1055 Preserving Fertility by Oocyte and Embryo Freezing prior to Adjuvant Chemotherapy: A Prospective Clinical Trial of Letrozole and a GnRH Agonist to Reduce Estrogen Exposure during Ovarian Stimulation. Oktay K, Turkcuoglu I, Rodriguez-Wallberg K.#1073 Adjuvant Endocrine Monotherapy with Tamoxifen or Aromatase Inhibitors for Postmenopausal Women with Breast Cancer: What Is the Economic Impact of CYP 2D6 Testing? Younis T, Rayson D, Skedgel C.#3018 Bone Marrow Micrometastasis as Correlated to Other Prognostic Factors in Breast Cancer. Saha S, Sirop S, Korant A, Chakravarty B, Arora S, Iddings D, Soni M, Wiese D.#3108 Nipple-Areolar Sparing Mastectomy via an Inframammary Fold Incision Is a Viable Option in Patients with Scarring from Prior Breast Surgery. Huston TL, Swistel AJ, Martin J, Talmor M.#3169 A Possible Association between Mammographic Density and Breast Cancer Prognosticators. Eriksson LK, Czene K, Hall P, Ploner A.#4027 Pathologic Correlation of MR Imaging Findings Close to the Invasive Ductal Carcinoma: Possible Ductal Carcinoma In situ Surrounding Index Tumor. Suh Y, Oh S, Song B, Jung S.#4028 Analysis of the Cause of Discordance between Two Radiologists on the Assessment of Radiographic Response and Progression for Subjects Enrolled in Breast Cancer Clinical Trials Employing Blinded Independent Central Review. Borradaile KL, Ford RR, O'Neal JM.#4030 Duplication of Chromosome 17 CEP Predicts for Anthracycline Benefit: A Meta-analysis of 4 Trials. Bartlett JMS, Munro A, Desmedt C, Dunn JA, Larsimont D, O'Malley FP, Cameron DA, Earl H, Poole CJ, Shepherd L, Cardoso F, Caldas C, Twelves CJ, Pritchard KI, Rea DW, diLeo A, on Behalf of the HER2/TOP2A Meta-analysis Group.#4069 Evaluation of a Common SNP Panel for Breast Cancer Risk Assessment in a Nested Case-Control Study from the Women's Health Initiative. Mealiffe ME, Stowkowski RP, Rhees BK, Prentice RL, Hinds DA.#4147 Defining a Potential Role of Adiponectin in Mammary Gland Development. Karadimos MJ, Camarillo I.#5090 A Phase II Study of Trastuzumab-DM1 (T-DM1), a Novel HER2 Antibody-Drug Conjugate, in Patients Previously Treated with Lapatinib, Trastuzumab, and Chemotherapy. Krop I, LoRusso P, Miller KD, Modi S, Yardley D, Rodriguez G, Agresta S, Zheng M, Amler L, Rugo H.#6028 Reproducibility of Random Periareolar Fine Needle Aspiration in a Multi-institutional Cancer and Leukemia Group B (CALGB) Cross-sectional Study. Seewaldt V, Wilke LG, Zalles C, Archer L, Yee L, Kulkarni S, Wood M, Garber J, Ibarra-Drendall C.#6059 Combinatorial V-D-J Diversity of TCR and IgH as a Biomarker of Early Death in Breast Cancer. Manuel M, Grives A, Rabeony T, Mouret J-F, Perez S, Blay J-Y, Caux C, Bachelot T, Pasqual N, Menetrier-Caux C.#6060 21-Gene Recurrence Score (RS) in 100 Consecutive Brazilian Patients. Schor APT, Carvalho FM, Ojopi E, Mangabeira A, Saad E, Bacchi CE.#6121 BA1 Subclass of Basal-like Breast Cancer Is Characterized by Upregulation of Interferon-Related Genes and Is Enriched for BRCA1-Associated Cancers. Ganesan S, Alexe G, Bilal E, Liu H, Bhanot G.#6164 Adiponectin-like Activities of Osmotin. Salameh TS, Sokolchik I, Haddan M, Bressan RA, Narsimham ML, Camarillo IG.The following abstracts were printed in the SABCS abstract supplement but were not presented at the Symposium:#1026 A Decision Tree to Predict Four or More Positive Axillary Lymph Nodes in Breast Cancer Patients with Positive Sentinel Node Biopsy: Determining Necessity for Regional Nodal Irradiation in the Absence of Axillary Dissection. Macrorie-Fairweather RA, Albuquerque K, Yao K, Sinacore J.#1031 Predicting Axillary Lymph Node Status Using Preoperative Ultrasound-Guided Fine Needle Aspiration Cytology of Radiologically Equivocal and abnormal Nodes. White JP, Hogan BV, Langlands F, Dall B, Horgan K.#1041 Sulindac Sulfide Selectively Induces Apoptosis of Human Breast Tumor Cells by Inhibiting PDE5A, Elevating CGMP, and Activating PKG. Tinsley HN, Gary BD, Keeton AB, Reynolds RC, Piazza GA.#1099 Final Result of Non-Anthracycline Containing Weekly Paclitaxel Plus Carboplatin Regimen as Neoadjuvant Chemotherapy for Breast Cancer. Chen X, Wu J, Shen K, Chen C, Lu J, Wu J, Shao Z, Shen Z.#1104 Estrogen Receptor Expression: Possible Predictor of Pathological Complete Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer Patients. Wu J, Shen K, Chen X, Chen C, Hu Z, Liu G, Di G, Lu J, Wu J, Shao Z, Shen Z.#1121 Breast Cancer initiating Cells Promote Chemoresistance by Pre-Activation of the DNA Damage Repair. Gong C, Yu F, Shi J, Su F, Song E.#1136 Let-7 Inverts the Chemoresistance of Breast Tumor-Initiating Cells. Yu F, Wu J, Gong C, Su F, Song E.#1151 Epigenetics Differences between Estrogen Receptor (ERS1) and Her2/neu Status in Breast Cancer Patients. Martínez-Galán J, Torres-Torres B, Ales I, Durán G, Gutierrez V, Del Moral R, Cobo M, Nuñez MI, Benavides M, Ruiz De Almodóvar M.#2018 p53 Status Splits Triple-Negative Breast Cancers in Subgroups with Distinct Predictive and Prognostic Potential Value. Alberti S, Ambrogi F, Pedriali M, Piantelli M, Patrizia Q, Nenci I, Ellis I, Boracchi P, Coradini D, Biganzoli E.#2048 Characteristics of Overall and Cause-Specific Survival Rates in Breast Cancer Patients under the Age of 40: A Population Based Study of 481,294 Cases in SEER Registry. Kim E, Thomas, Jr., C, Hoffelt C.#2065 Epidemiology of Triple-Negative Breast Cancer in China. Lin Y, Yin W, Yan T, Zhou L, Di G, Wu J, Shen Z, Shao Z, Lu J.#2071 Relationship of Age at First Live Birth, Parity and Duration of Breast Feeding with Non-Familial Breast Cancer in Pakistani Women. A Study of the Cancer Research Group Pakistan. Ahmad S, Mahmood H, Kanwal S, Mahmood A, Ahmad K, Masood M, Faheem M, Akbar N, Hafeez M.#2106 Radiofrequency Ablation in Breast Cancer. Tzoracoleftherakis EE, Sdralis EK, Maroulis JC, Ravazoula PK.#2144 Albumin-Binding and Angiogenic Domains of SPARC Located at Its C-Terminus. Knauer D, Hwang LY, Lowe C, Hwang J, Norng M, Trieu V, Desai N.#2147 Role of CTCF Poly(ADP-Ribosyl)ation in the Regulation of Apoptosis in Breast Cancer Cells. Venkatraman B, Klenova E.#2159 Mast Cells Positive to Tryptase Correlate with Angiogenesis in Early Breast Cancer. Troilo S, Patruno R, Zizzo N, Troilo P, Catino A, Gadaleta CD, Ranieri G.#3060 Genetic Polymorphisms in EGFR Gene: No Evidence for an Association with the Risk of Breast Cancer. Gorlov I, Gorlova O, Jupe E.#3099 Differences in Dielectric Properties between Malignant and Normal Breast Tissue: Preliminary Results of the MicroBlate Study. Chaudhry AS, Baruah BP, Goyal A, Kink T, Young P, Douglas-Jones A, Mansel RE.#3119 Does Having Primary Breast Reconstruction Influence Chest-Wall Radiotherapy Rates? Agusti A, Rusby J, Sundaramorthy S, Roche N, Gui G, Harris P, James S, Ross G, MacNeill F.#3124 Anti-Breast Cancer Activity of a Novel Strategy of Targeting Autophagy Induced by Pan-HDAC Inhibitor and Acetylated Hsp70. Rao R, Nalluri S, Bhalla KN.#3133 The HDAC Inhibitor TSA Inhibits Cell Proliferation, Induces Apoptosis, and Down-Regulates HER2 Protein and Gene Expression as a Single Agent and in Combination with Trastuzumab in Trastuzumab-Sensitive and -Resistant Breast Cancer Cell Lines. Radke S, Perincheri S, Schulz V, Lerner B, Kumar A, Chandrasekan L, Tuck D, Harris L.#4025 Diffusion-Weighted MRI in Predicting the Efficacy of Neoadjuvant Chemotherapy of Breast Cancer. Wu J, Shen K, Chen X, Chen C, Hu Z, Liu G, Di G, Lu J, Wu J, Shao Z, Shen Z.#4115 Radiological Assessment of the Anatomic Adequacy of Locoregional Lymphatic Radiotherapy Target Volumes for Locally Advanced Breast Cancer (LABC). Dinniwell R, Lee G, Gregorio N, Clemons M.#4132 Perioperative Suppression of Immune-Regulatory Blood Cells Predicts Wound Complications in Breast Cancer Patients. Hogan BV, Peter MB, Thorpe RF, Achuthan R, Carter CD, Horgan KM, Hughes TA.#4160 Tumor Microenvironment–Induced Gene Expression Changes in Invasive Breast Cancer Cells. Goswami S, Faigen RJ, Condeelis JS, Sun D.#5043 Identifying Symptom Clusters in Breast Cancer: Implications on Patient Quality of Life. Lis CG, Birdsall TC, Stark JJ, Cain L, Campbell K, Gilbert K, Gupta D.#5148 Intermittent Hypoxia: Potential Factor of Resistance to Endocrine Therapy. Yin W, Liu G, Di G, Shen Z, Shao Z.#6033 The Relationship between Preoperative Biomarkers of Inflammation, Clinicopathological Characteristics, and Cancer-Specific Survival in Early Breast Cancer. Obondo CA, Mansell J, Afra AMM, Doughty JC, Lannigan A, McMillan DC.#6048 Clinical and Nutritional Correlates of Survival in Breast Cancer. Lis CG, Gupta D, Dahlk S, Vashi PG, Lammersfeld CA.#6062 Interaction between Family History of Breast Cancer and the Remaining Gail Risk Factors. Ni X, Muram D.#6074 New Approach for Early Detection of Breast Cancer in Iran. Harirchi I, Mousavi SM, Keshtgar M.#6103 A Phase I-II Trial of Ispinesib, a Kinesin Spindle Protein Inhibitor, Dosed Every Two Weeks as First-Line Chemotherapy for Advanced Locally Recurrent or Metastatic Breast Cancer. Gomez H, Philco M, Pimentel P, Escandon R, Saikali K, Seroogy J, Wolff A, Conlan M.#6107 Phase II Study of the Novel Epothilone Sagopilone (ZK-EPO) in Patients with Progressive Metastatic Breast Cancer. Campone M, Dittrich C, Cufer T, Dudov A, Dao Phan P, Schmelter T, Giurescu M, Martin M.#6154 ZNF393 Is a Negative Regulator of Epithelial-Mesenchymal Transition and Metastasis in Breast Cancer. Huang Q, Gumireddy K, Li A, Gimotty PA, Klein-Szanto AJ, Showe LC, Katsaros D, Coukos G, Zhang L.#6157 Tumor Invasion and Metastasis initiated by Mir-106b in Breast Cancer by Targeting BRMS1 and RB. Pan S, Yu F, Gong C, Song E.#6165 Role of KCNMA1 in Breast Cancer Metastasis and Angiogenesis. Ningaraj NS, Khaitan D, Sankpal UT.#6166 An Alternative Splice Variant of KCNMA1 Drives Breast Cancer Metastasis and Invasion. Khaitan D, Sankpal UT, Ningaraj NS.