C Van Poznak

Incidence, risk factors, and outcomes of osteonecrosis of the jaw: integrated analysis from three blinded active-controlled phase III trials in cancer patients with bone metastases

BACKGROUND Osteonecrosis of the jaw (ONJ) has been reported in patients receiving bisphosphonates for metastatic bone disease. ONJ incidence, risk factors, and outcomes were evaluated in a combined analysis of three phase III trials in patients with metastatic bone disease receiving antiresorptive therapies. PATIENTS AND METHODS Patients with bone metastases secondary to solid tumors or myeloma were randomly assigned to receive either s.c. denosumab (120 mg) or i.v. zoledronic acid (4 mg) every 4 weeks. On-study oral examinations were conducted by investigators at baseline and every 6 months. Oral adverse events were adjudicated by an independent blinded committee of dental experts. RESULTS Of 5723 patients enrolled, 89 (1.6%) patients were determined to have ONJ: 37 (1.3%) received zoledronic acid and 52 (1.8%) received denosumab (P = 0.13). Tooth extraction was reported for 61.8% of patients with ONJ. ONJ treatment was conservative in >95% of patients. As of October 2010, ONJ resolved in 36.0% of patients (29.7% for zoledronic acid and 40.4% for denosumab). CONCLUSIONS In this combined analysis of three prospective trials, ONJ was infrequent, management was mostly conservative, and healing occurred in over one-third of the patients. Educating physicians about oral health before and during bone-targeted therapy may help reduce ONJ incidence and improve outcomes.BACKGROUND Osteonecrosis of the jaw (ONJ) has been reported in patients receiving bisphosphonates for metastatic bone disease. ONJ incidence, risk factors, and outcomes were evaluated in a combined analysis of three phase III trials in patients with metastatic bone disease receiving antiresorptive therapies. PATIENTS AND METHODS Patients with bone metastases secondary to solid tumors or myeloma were randomly assigned to receive either s.c. denosumab (120 mg) or i.v. zoledronic acid (4 mg) every 4 weeks. On-study oral examinations were conducted by investigators at baseline and every 6 months. Oral adverse events were adjudicated by an independent blinded committee of dental experts. RESULTS Of 5723 patients enrolled, 89 (1.6%) patients were determined to have ONJ: 37 (1.3%) received zoledronic acid and 52 (1.8%) received denosumab (P = 0.13). Tooth extraction was reported for 61.8% of patients with ONJ. ONJ treatment was conservative in >95% of patients. As of October 2010, ONJ resolved in 36.0% of patients (29.7% for zoledronic acid and 40.4% for denosumab). CONCLUSIONS In this combined analysis of three prospective trials, ONJ was infrequent, management was mostly conservative, and healing occurred in over one-third of the patients. Educating physicians about oral health before and during bone-targeted therapy may help reduce ONJ incidence and improve outcomes.

Abstract P6-14-01: Effect of Denosumab Versus Zoledronic Acid Treatment in Patients with Breast Cancer and Bone Metastases: Results from the Extended Blinded Treatment Phase

Background: Denosumab is a fully human monoclonal antibody which inhibits RANKL, a key mediator of osteoclast activity. Results from the primary analysis of this pivotal phase 3 trial showed that denosumab was superior to zoledronic acid (ZA) in delaying the time to first on-study skeletal-related events (SRE) in patients with breast cancer and bone metastases. We now report results including an additional 4 months of blinded treatment. Methods: Randomized patients received either subcutaneous (SC) denosumab (120 mg) and intravenous (IV) placebo or IV ZA (4 mg, adjusted for renal function) and SC placebo every 4 weeks. No dose adjustments were made for SC denosumab. All patients were advised to take daily calcium (≥500 mg) and vitamin D (≥400 IU) supplements. The primary endpoint was time to first on-study SRE (predefined as pathologic fracture, radiation or surgery to bone, or spinal cord compression). Time to first and subsequent SRE (multiple event analysis) and safety endpoints were also evaluated. Analyses for the extended treatment phase are considered exploratory. Results: Overall, 2046 patients enrolled: 1026 were randomized to denosumab and 1020 were randomized to ZA. Denosumab was superior to ZA in delaying the time to first on-study SRE by 18%, and the time to first and subsequent on-study SRE by 22% (Table). The median time to first on-study SRE was 5 months longer for the denosumab group (32.4 months) than the ZA group (27.4 months). Overall survival and disease progression were similar for both treatment groups. Similar percentages of subjects reported adverse events (AEs; 96.2% denosumab, 97.4% ZA) and serious AEs (47.9% denosumab, 50.2% ZA). Positively adjudicated cases of osteonecrosis of the jaw were reported in 2.5% (n=26) of denosumab-treated patients and 1.8% (n=18) of ZA-treated patients (P=0.29). Hypocalcemia was reported by 62 (6.1 %) patients in the denosumab group and 37 (3.7%) patients in the ZA group. Conclusion: Among patients with breast cancer and bone metastases, denosumab was superior to ZA in delaying or preventing SREs, and continued treatment with denosumab resulted in a median time to first SRE that was 5 months longer than treatment with ZA. Denosumab, with its novel mode of action, may represent a potential treatment option for patients with breast cancer and bone metastases without the need for dose adjustment or renal monitoring. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-14-01.

Managing cancer treatment-induced bone loss: 24-month results from the Study of Anastrozole with the Bisphosphonate RisedronatE (SABRE).

Abstract #1137 Aim: To investigate the management of bone health in postmenopausal women with early breast cancer (BCA) scheduled to receive anastrozole.
 Methods: Postmenopausal women with hormone receptor-positive early BCA were assigned to 1 of 3 strata depending on their pre-existing risk of fragility fracture. Patients (pts) with a bone mineral density (BMD) T-score Results : BMD changes at 24 months are shown in the table. In M, a significant difference in favor of the A+R group compared with the A+P group was seen for both lumbar spine and total hip (both p Conclusions: In postmenopausal women at risk for fragility fracture receiving adjuvant anastrozole for BCA, the addition of risedronate at doses established for preventing and treating osteoporosis resulted in favorable affects in BMD over 24 months.
 Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1137.

Abstract P2-18-09: TBCRC 013: A prospective analysis of the role of surgery in stage IV breast cancer

Background: Retrospective studies suggest that primary breast surgery is associated with improved overall survival (OS) in Stage IV breast cancer. TBCRC 013 is a multi-center prospective registry study evaluating the role of surgery for the primary tumor in Stage IV disease. Methods: From 7/09 - 4/12, 128 eligible pts from 14 sites were enrolled in two cohorts (A: Stage IV with intact primary tumor (n = 112); B: metastases (mets) within 3 months of primary surgery (n = 16)). Baseline patient and tumor characteristics, and surgery of the primary were correlated with 2yr overall survival (OS) using log rank, Kaplan Meier and Cox regression for all patients. Comparisons were also made between cohorts A and B and within cohort A stratified by response to systemic therapy. Responders included those with any response (partial,complete) or stable disease at distant sites. Results: Median pt age was 52yrs(21-79) and median primary tumor size 3.2cm(0.7-15). Phenotypes were ER+ 106 (83%), HER2neg 91(71%), and triple neg 10(8%). 60(47%) had bone-only mets. The only significant baseline difference between cohorts A and B was the presence of palpable nodes (A:62% vs B:0%, p Conclusions: In this prospective registry study, patients diagnosed with mets within 3 months of primary breast surgery have an improved 2yr OS. When all pts having surgery (A + B) are examined, surgery is associated with improved OS on MVA, but when limited to Arm A responders, elective surgery does not improve OS. Given that the number of Arm A responders is small, results from the prospective randomized trial will be needed to address this question. These data also demonstrate that the need for surgical palliation of the primary tumor is uncommon in the modern era. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-18-09.

Abstract OT1-1-11: TBCRC 022: Phase II Trial of Neratinib for Patients with Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast cancer and Brain Metastases

Background: 1/3 of women with metastatic HER2+ breast cancer will develop central nervous system (CNS) metastases yet evidence-based treatments for women with progressive CNS disease are limited. Neratinib is an irreversible inhibitor of erbB1, HER2, and erbB4 which has promising activity in HER2+ breast cancer. Preclinical evidence suggests it may cross the blood brain barrier. Trial Design: This is a multicenter, phase II, open-label study of neratinib for patients with HER2+ breast cancer and brain metastases. Neratinib is administered at 240 mg orally daily during a 28 day cycle. Two cohorts will be enrolled: Cohort 1 will enroll 40 patients with progressive CNS disease; cohort 2 will enroll ≤5 patients who are candidates for surgical excision of intracranial disease. Surgical candidates receive neratinib 7–21 days preoperatively and resume postoperatively. All patients are re-staged every 2 cycles. Those who develop non-CNS progression have an option to extend therapy with trastuzumab+neratinib. Circulating tumor cells (CTC) are collected at baseline and progression; neurocognitive testing, HADS and EORTC QLQ30/BN20 measures are administered at baseline, cycle 2, cycle 3, and progression (cohort 1). Intracranial tumor, cerebrospinal fluid (CSF), and plasma are collected at surgery (cohort 2). Specific Aims: The primary endpoint is CNS objective response rate (ORR) by composite criteria. Additional endpoints include: non-CNS ORR, progression-free survival, overall survival (OS), site of 1st progression, and toxicity. Correlative and exploratory endpoints include association of CTC count and OS and longitudinal neurocognitive function and quality of life. In an exploratory analysis (cohort 2), we will quantify neratinib concentrations in CSF, intracranial tissue, and plasma and examine associations with response. Eligibility: Patients must have confirmed HER2+ metastatic disease with ≥1 parenchymal brain lesion measuring ≥10 mm that is new or progressed after completing ≥1 line of standard CNS-directed treatment (cohort 1) or CNS disease that is amenable for surgery, including those without prior CNS treatments (cohort 2). Additional eligibility criteria (cohorts 1,2) include: adequate performance status and end organ/marrow function, and ejection fraction ≥50%. Any number of prior lines of therapy is allowed, including prior lapatinib. Statistical Methods: Cohort 1 has a 2-stage design with up to 40 patients. CNS ORR is defined as ≥50% reduction in sum volume of CNS target lesions, without evidence of new lesions, progression of non-target CNS lesions, non-CNS disease progression, worsening neurological symptoms, or increase in corticosteroids. CNS lesion measurements are performed centrally by the Harvard Tumor Imaging Metrics Core. If 1/18 patients have a CNS response in the 1st stage, another 22 patients will enroll. With this design, if ≥5 of 40 patients achieve a CNS response, the drug will be deemed worthy of future study. This 2-stage design has 92% power to distinguish between a true CNS ORR of 20% and a null of 6% (one-sided type I error rate=9%). Accrual: Accrual has begun. Target=45 (cohort 1=40, cohort 2=5) Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT1-1-11.

Bone Mineral Density (BMD) Changes at 1 Year in Postmenopausal Women Who Are Not Receiving Adjuvant Endocrine Therapy for Breast Cancer (BCA).

Background: Adjuvant therapy for breast cancer (BCA) may be associated with an increased risk for osteoporosis. This prospective, observational study evaluates BMD changes in postmenopausal women undergoing adjuvant chemotherapy (CTX) for early stage BCA, in the absence of endocrine therapy.Methods: Women who have been postmenopausal for at least 5 years, and who were recently diagnosed with Stage 0-III BCA were eligible to undergo serial BMD if adjuvant endocrine therapy was not recommended. Study BMDs were performed at baseline, 1 and 2 years. All patients (pts) were counseled on calcium, vitamin D and weight bearing exercise. This study was designed to assess serial changes in BMD in the individual and to compare changes in those treated with CTX to those who received no systemic therapy (observation). The study was closed prior to reaching target sample size due to slow accrual.Results: Sixteen pts enrolled. Eleven pts received CTX with a dose dense anthracycline and taxane containing regimen and 5 pts received no systemic adjuvant therapy. Twelve pts, median age 63 (range 52-80), have completed the 1 year assessment and are reported here. Two pts treated with CTX and 1 pt on observation were on bisphosphonates at study entry. Baseline BMD mean in gm/cm2 at the lumbar spine (LS) was 1.112 (range 0.807-1.389) and total hip (TH) was 0.989 (range 0.760-1.213). At 1 year, mean BMD at LS was 1.078 (range 0.767-1.347) and TH was 0.956 (range 0.753-1.210). For all 12 pts at 1 year, the individual BMD changes in LS & TH BMD ranged from 10% loss to 2% gain, with 8 of the 9 CTX treated pts losing 1-10% of BMD and the 3 pts on observation staying within 2% of baseline. The mean dosage of dexamethasone used during CTX by the 9 CTX pts was 230 mg (range 156-288mg). The 3 observation pts had no exposure to steroids during the parallel time period.Conclusions: This prospective, observational study supports the hypothesis that adjuvant CTX, and/or its supportive medications, may be associated with acute changes in BMD in postmenopausal women. Patient follow up continues.Funded by Susan G. Komen for the Cure POP0402593 Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1066.

Zoledronic acid increases the prevalence of medication-related osteonecrosis of the jaw in a dose dependent manner in rice rats (Oryzomys palustris) with localized periodontitis

Objective Investigate role of dose/duration of zoledronic acid (ZOL), a powerful anti-resorptive (pAR), on prevalence of medication-related osteonecrosis of the jaw (MRONJ) in rice rats (Oryzomys palustris), a species with natural susceptibility to food impaction-induced localized periodontitis (FILP). We hypothesize that ZOL induces MRONJ lesions in rice rats with FILP, and that the prevalence of MRONJ rises with increasing dose and duration of ZOL treatment. Methods We performed a toxicology experiment with clinically-relevant doses of ZOL in female rats (N = 230) fed standard (STD) rodent chow. At age 4 weeks (baseline), 12 rats were necropsied. The rest were randomized into five groups that began to receive 0, 8, 20, 50 or 125 µg/kg ZOL IV/q 4 weeks. After 12, 18, 24 and 30 weeks, subgroups (N = 9–16) from each of the dose groups were necropsied. High-resolution macroscopic photos of all jaw quadrants were given a gross quadrant grade (GQG) (0–4 or MRONJ) that classified FILP lesion severity and determined presence of gross MRONJ. Quadrants with GQG ≥ 1 were examined histopathologically. Logistic regression analysis (ZOL dose/duration) of MRONJ prevalence was completed. Results We found: 1) 75% of 0 µg/kg ZOL rats developed FILP lesions; 2) baseline rats and rats treated with 0 µg/kg ZOL had no MRONJ; 3) 29 gross MRONJ cases were identified; 4) all gross MRONJ cases were confirmed histopathologically by the observation of exposed necrotic bone, and 53 new cases were discovered (total = 82); 5) ZOL dose (P < 0.001), but not duration (P = 0.326), was a significant predictor of MRONJ prevalence; 6) 13% prevalence of gross MRONJ among all rats, with 22% prevalence among rats exposed to ZOL oncologic doses (20–125 µg/kg); 7) 38% prevalence of histopathologic MRONJ among all rats, with 73% prevalence among rats exposed to ZOL oncologic doses. Conclusions This is the first experiment to show a dose response relationship between clinically relevant doses of ZOL and MRONJ prevalence.

Abstract P5-23-02: Quality of life (QoL) in male breast cancer (BC): Prospective study of the EORTC10085/TBCRC029/BIG2-07/NABCG International male BC program

Introduction: Male BC is a rare disease (dx) for which management is extrapolated from trials in female BC. Comprehensive prospective data about QoL in men with BC could inform treatment. The international Male BC Consortium conducted a prospective registry of male BC patients of all stages who newly presented to a participating center between October 2013 and February 2017. A QoL substudy was conducted as part of this registry at most participating sites. Methods: Informed consent for participation in the QoL substudy was requested from new enrollees. Those who consented were asked to complete a survey including the EORTC QLQ-C30 and BR23 (breast cancer specific module), adapted by replacing female-specific items with male-specific sexual activity/function items from the prostate module (PR25). Outcomes were scored according to standard EORTC QLQ procedures on a 0-100 scale (with higher scores on QoL/functioning scales representing better QoL and functioning, and higher scores on symptom scales representing worse symptoms). Forms were analyzed centrally by EORTC. In order to compare to female BC, we used reference data from 2782 mixed age (62% under age 60) women with BC (of whom 1,147 had recurrent or metastatic dx, and 464 had stage 1-2 dx) reported in the EORTC QLQ-C30 Reference Values manual (2008). Results: A total of 557 men were enrolled in EORTC10085, 445 at sites participating in the QoL substudy. Consent forms were received from 422/445 (95%) for the substudy. Baseline survey (required to be completed within 30 days of enrollment) compliance was 85% (359/422). Median age at diagnosis was 67 years. There were 111 men (45%) with node-positive M0/MX dx and 27 men (8%) with M1 dx. Their median global health status score at baseline was 75 (IQR 67-83), higher than that documented historically in female BC (67, with IQR 50-83, in both the 2782 women with mixed stage and the subgroup of 464 with stage 1-2 tumors). The participating men9s median social functioning score was 100 (IQR 67-100), also higher than the 83.3 (IQR 67-100) reported in mixed stage female BC patients, though no different than the 100 (IQR 67-100) found in women with stage 1-2 dx. Men9s most commonly reported symptoms included fatigue (median score 13.9, IQR 0-33), insomnia (median score 0, IQR 0-33), and pain (median score 0, IQR 0-33), for which women9s median scores were 33 (IQR 11-44), 33 (IQR 0-33), and 17 (IQR 0-50) with mixed stage dx, and 22 (IQR 0-33), 33 (IQR 0-33), and 17 (IQR 0-33) with stage 1-2 dx. Men9s median sexual activity score was 33.3 (IQR 0-50), with less sexual activity reported by older patients and men with M1 dx. In those who were sexually active, median sexual function score was 83 (IQR 75-92), with no difference by age or stage. Conclusions: QoL and symptom burden in male BC patients appears no worse (and possibly better) than that in female patients. Future analyses of 1- and 5-year surveys from this study will assess the impact of specific treatments on changes in symptoms and QoL over time. These data will be useful in future efforts to tailor treatments and target interventions for male BC. Funding: Breast Cancer Research Foundation, Dutch Pink Ribbon Foundation, Swedish BRO, and EBCC Council. Citation Format: Schroder C, Cardoso F, Dijkstra N, van Leeuwen-Stok E, Linderholm B, Morgenstern D, Van Poznak C, Wolff AC, Poncet C, Gomez HL, Aalders K, Bjelic-Radisic V, Werutsky G, Tryfonidis K, Coens C, Giordano SH, Ruddy KJ. Quality of life (QoL) in male breast cancer (BC): Prospective study of the EORTC10085/TBCRC029/BIG2-07/NABCG International male BC program [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-23-02.

1513PRISK FACTORS FOR HYPOCALCEMIA IN PATIENTS WITH CANCER RECEIVING DENOSUMAB

ABSTRACT Aim: The potent RANK ligand inhibitor denosumab (Dmab) can cause hypocalcemia (hypoCa). Patients (pts) with inadequate intake of Ca and vitamin D are at increased risk for hypoCa. Additional baseline risk factors for hypoCa in pts with metastatic bone disease (MBD) were evaluated to aid clinical risk assessment for this adverse event. Methods: A post hoc analysis used data from three identically designed, randomized, blinded phase 3 trials comparing monthly dosing of 4 mg zoledronic acid (ZA) to 120 mg Dmab in pts with MBD to identify lab events of grade≥2 hypoCa (CTCAE: Results: The overall incidence of lab grade≥2 hypoCa events in those treated with Dmab was equal to or greater than in those treated with ZA and occurred in 12.4% of Dmab-treated pts. Baseline pt characteristics with the greatest incidence of hypoCa include: male gender (15.4%), prostate cancer (20.5%), small cell lung cancer (18.0%), and CrCl 30 – 2 bone mets and those with higher BSAP or uNTx levels (Table). Osseous lesion type did not significantly increase the risk of developing hypoCa (P ≥ 0.23). Baseline Factor Hazard Ratio 95% CI P-value > 2 bone mets 1.329 (1.044, 1.692) 0.021 BSAP>median (20.77 mg/L) 2.078 (1.579, 2.734) BSAP>median vs≤median > 2 bone mets 4.236 (2.117, 8.479) ≤ 2 bone mets 1.773 (1.312, 2.395) Interaction of baseline BSAP and # of bone mets 0.021 uNTX>50 nmol/mmol 1.316 (1.031, 1.680) 0.027 Interaction of baseline uNTX and # of bone mets 0.21 Conclusions: The risk of hypoCa after Dmab for MBD is associated with the # of bone mets and elevated bone turnover markers, especially high BSAP with>2 mets. BSAP may indicate the potential for deposition of Ca in undermineralized matrix. Pts with high bone turnover may be more susceptible to hypoCa when osteoclasts are rapidly inhibited, particularly when Ca and vitamin D intake is insufficient. Disclosure: J. Body: Consultant for and received research funding from Amgen; received honoraria from Amgen and Novartis; H.G. Bone: Consultant for and received honoraria from Amgen and Novartis; C. van Poznak: Received research funding from Amgen and Novartis; R.H. De Boer: Consultant for and received honoraria from Novartis; received research funding and other remuneration from Amgen and Novartis; A. Stopeck: Consultant for Amgen; honoraria from Amgen and GlaxoSmithKline; research funding from Amgen and Novartis; K. Fizazi: Consultant for Amgen and Novartis; honoraria from Amgen; D.H. Henry: Consultant for and received research funding and honoraria from Amgen, Ortho Biotech, and Watson; T. Ibrahim: Consultant for Amgen; A. Lipton: Honoraria and research funding from Amgen; F. Saad: Consultant for and received research funding and honoraria from Amgen and Novartis; N.D. Shore: Consultant for Amgen, Astellas, Bayer, Dendreon, Janssen, and Medivation; T. Takano: Consultant for and received honoraria from Daiichi-Sankyo; H. Wang: Employee of and owns stock or stock options in Amgen; O.L. Bracco: Employee of and owns stock or stock options in Amgen; A. Balakumaran: Employee of and owns stock or stock options in Amgen; P.J. Kostenuik: Employee of and owns stock or stock options in Amgen. All other authors have declared no conflicts of interest.

Abstract P1-04-01: Significance of circulating tumor cells in metastatic triple negative breast cancer: Results of an open label, randomized, phase II trial of nanoparticle albumin-bound paclitaxel with or without the anti-death receptor 5 tigatuzumab (TBCRC 019)

Background: Circulating Tumor cells (CTCs) are prognostic at baseline and first follow-up in patients with metastatic breast cancer (MBC). Using the most commonly used assay (CellSearch®), we have previously reported the ability to detect apoptotic vs. non-apoptotic CTCs in patients with MBC. However, there has been concern regarding the performance of the CellSearch® assay in patients with triple negative (TN) MBC. We hypothesized that CellSearch® is an effective assay in patients with TN MBC, and that CTC-apoptosis might further separate prognosis. Therefore, we studied CTCs in patients with TN MBC who participated in a prospective randomized phase II trial testing for activity of tigatuzumab (TIG) in combination with nanoparticle albumin-bound paclitaxel (nab-PAC) conducted by the Translational Breast Cancer Research Consortium (overall results reported by Forero A., et al, ASCO 2013). Methods: Whole blood (WB) was drawn into a CellSave tube at baseline, day 15, and day 29 and CTC counts were determined using the CXC CellSearch® kit. Apoptosis was characterized by staining with a monoclonal antibody that detects a neo-epitope on fragmented cytokeratin (M-30) and independently by visual inspection (nucleic condensation and/or fragmentation, as well as granular cytokeratin). Association between levels of CTCs and CTC-apoptosis with the overall response rate (ORR) and progression free survival (PFS) at baseline, day 15, and day 29 was assessed using logistic regression, Kaplan Meier curves, and Cox proportional hazards modeling. Results: Of the 60 patients entered into the trial, 52 were evaluable for CTCs. Of these, 19/52 (36.5%), 14/52 (26.9%), and 13/49 (26.5%) had elevated CTCs (≥5CTC/7.5 ml WB) at baseline, day 15, and day 29, respectively. Patients with elevated CTCs at each time point had worse PFS than patients with low or no CTCs. Hazard rates (HR) at baseline, day 15, and day 29 were 2.38 (95% CI: 1.27-4.45, p = 0.007), 2.87 (95% CI: 1.46-5.66, p = 0.002), and 3.40 (95% CI: 1.68-6.89, p = 0.001), respectively. The odds of overall response for those who had elevated CTCs compared to those who did not at baseline, day 15, and day 29, were 0.25 (95% CI: 0.073-0.81, p = 0.024), 0.18 (95% CI: 0.04-0.67, p = 0.014), and 0.06 (95% CI: 0.01-0.28, p = 0.001), respectively. There was no apparent prognostic effect comparing the degree of CTC-apoptosis vs. non-apoptosis. Conclusions: Similar to observations in other intrinsic subgroups, CTCs were detected in a large fraction of TN MBC patients at baseline using CellSearch® assay, and reductions in CTC levels reflected response. In these homogenously prospectively enrolled TN MBC patients, regardless of treatment, CTCs are prognostic at baseline, day 15, and day 29. It does not appear that analysis of CTC-apoptosis is prognostic. Supported by Susan G. Komen for the Cure, Veridex, LLC, Fashion Footwear Charitable Foundation of New York/QVC Presents Shoes on Sale™ (DFH), Associazione Sandro Pitigliani and by a studentship from FIRC (CP), Triple Negative Breast Cancer Foundation, The AVON Foundation, and The Breast Cancer Research Foundation. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-04-01.