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Objective To determine prevalence and frequency of malignancy among bone lesions detected on breast MRI and to identify clinical and imaging features associated with bone metastases from breast cancer (BC), as bone lesions are suboptimally evaluated on breast imaging protocols and can present a diagnostic challenge. Methods This IRB-approved retrospective review of breast MRIs performed from June 2009 to June 2018 identified patients with bone lesions. Demographic, clinical, and MRI features were reviewed. Clinical outcome of bone lesions was determined based on pathology and/or additional diagnostic imaging. All benign lesions had ≥2 years of imaging follow-up. Statistics were computed using Fisher exact and Wilcoxon rank sum tests. Results Among all patients with breast MRI, 1.2% (340/29 461) had bone lesions. Of these, 224 were confirmed benign or metastatic BC by pathology or imaging follow-up, with 70.1% (157/224) benign and 29.9% (67/224) metastatic. Bone metastases were associated with BC history (P Conclusion Of clinically confirmed breast MRI–detected bone lesions, 30% were bone metastases; all were detected in patients with current or prior BC. Metastases were associated with advanced stage, invasive carcinoma, larger lesion size, multiplicity, low T1 signal, and non-spine location.

Vaccination-associated adenopathy is a frequent imaging finding after administration of COVID-19 vaccines that may lead to a diagnostic conundrum in patients with manifest or suspected cancer, in whom it may be indistinguishable from malignant nodal involvement. To help the medical community address this concern in the absence of studies and evidence-based guidelines, this paper offers recommendations developed by a multidisciplinary panel of experts from three of the leading tertiary care cancer centers in the United States. According to these recommendations, some routine imaging examinations, such as those for screening, should be scheduled before or at least 6 weeks after the final vaccination dose to allow for any reactive adenopathy to resolve. However, there should be no delay of other clinically indicated imaging (e.g., for acute symptoms, short-interval treatment monitoring, urgent treatment planning or complications) due to prior vaccination. The vaccine should be administered on the side contralateral to the primary or suspected cancer, and both doses should be administered in the same arm. Vaccination information (date(s) administered, injection site(s), laterality, and type of vaccine) should be included in every pre-imaging patient questionnaire, and this information should be made readily available to interpreting radiologists. Clear and effective communication between patients, radiologists, referring physician teams and the general public should be considered of the highest priority when managing adenopathy in the setting of COVID-19 vaccination. Summary COVID-19-vaccination–related adenopathy is a frequent imaging finding that may lead to a diagnostic conundrum in patients with manifest or suspected cancer, in whom it may be indistinguishable from malignant nodal involvement. This special report offers recommendations developed by a multidisciplinary panel of experts from three of the leading tertiary care cancer centers in the United States.

Background: The androgen-signaling pathway plays a role in breast cancer (BC) pathogenesis and emerging evidence suggests the androgen receptor (AR) is a therapeutic target. TBCRC011 established safety and efficacy of inhibiting AR with bicalutamide (B) in patients (pts) with androgen AR+/ER/PgR- metastatic BC (MBC). Treatment with B at 150 mg oral daily demonstrated a clinical benefit rate (CBR) of 19% in this population. The rationale for combining palbociclib (P) with AR blockade stems from prior work in ER+ MBC. P is an oral, selective inhibitor of CDK4/6 activity which significantly improved median progression-free survival (PFS) in combination with letrozole compared to letrozole monotherapy for the treatment of postmenopausal pts with ER+ MBC in the first-line setting. Consistent with preclinical data, P has been shown to reduce growth of AR+ ER/PgR- MDA-MB-453 breast cancer cells via reduced Rb phosphorylation. It has been shown that AR+ TNBC expresses a luminal profile and has intact Rb protein, the target of palbociclib activity. Therefore, we hypothesize that P will increase the efficacy of B in pts with metastatic AR+ TNBC. NCT02605486. Methods: Pts with AR+ (IHC ≥ 1%)/ER any/HER2(-) MBC on central review at MSK were eligible if met following criteria: ECOG ≤2, postmenopausal, no limit to prior regimens. Pts with ER+ BC must have had 1 prior endocrine therapy. Treatment: B orally daily and P orally daily 3 weeks on 1 week off. DLT period = 28 days. Pts are evaluated for toxicity every 2-4 weeks and for response every 8 weeks. Phase I standard 3+3 design with 3 dose escalations. The primary objective of the phase I portion of the study is to determine the recommended phase II dose of P in combination with B. Plasma for pharmacokinetics (PK) was collected throughout the study. Results: As of 5/11/17, 15 pts with AR+ MBC were enrolled to the phase I portion. Target accrual has been met for the phase I and has since closed. No DLTs were reported in any of the dose escalation cohorts. The maximum tolerated dose was determined to be B 150 mg daily and P 125 mg daily for 21 days in a 28 day cycle. Treatment has been well tolerated with no related Grade 4 or 5 adverse events (AEs). The most common grade 3 significant AEs were hematologic including neutropenia n =5, leukopenia n= 4, and lymphocytopenia n=3 and thought to be related to P. One Grade 4 hypercalcemia led to hospitalization and was deemed related to disease progression. Median time on study was 8 weeks (2-47 weeks). One patient from the phase I remains on study. PK analysis is ongoing and will be presented, including drug-drug interaction data. Conclusions: The combination of B+P has been well tolerated with no unexpected toxicity observed. Updated safety, response, and PK data will be presented. Enrollment on phase II is ongoing. Citation Format: Gucalp A, Edelweiss M, Patil S, Gounder MM, Feigin KN, Corben A, Arumov A, Traina TA. Phase I/II trial of palbociclib in combination with bicalutamide for the treatment of androgen receptor (AR)+ metastatic breast cancer (MBC) [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 P3-11-04.

This abstract was withdrawn by the authors.

1017 Background: Genome-wide transcriptional analysis has identified a unique subset of androgen receptor (AR) +, estrogen receptor (ER)/progesterone receptor (PR)- breast cancer (BC). The functional role of AR was confirmed initially in preclinical models demonstrating that androgen-driven growth could be abrogated by antiandrogen therapy. TBCRC011 established the safety and efficacy of inhibiting AR with bicalutamide (B) in patients (pts) with AR+/ER/PR- metastatic BC (MBC) with a median progression free survival (PFS) of 12 weeks (wks) (95% CI, 11–22 wks). In preclinical data, palbociclib (P) has been shown to reduce growth of AR+/ER/PR- MDA-MB-453 BC cells. It has been shown that AR+ triple negative BC (TNBC) expresses a luminal profile and has intact Rb protein, the target of P activity. We conducted this Phase I/II trial of the AR inhibitor B in combination with the CDK4/6 inhibitor P in pts with AR+/ER/PR/HER2- BC (NCT02605486) to test the hypothesis that androgen blockade, paired with CDK4/6 inhibition would have increased efficacy in pts with androgen-dependent BC. Methods: Postmenopausal pts with AR+ TN MBC defined as IHC ≥ 1% nuclear staining (DAKO, Clone AR441 (5/2016-11/2016) then Ventana AR SP107 (11/2016-6/2018), ECOG ≤2, measurable/non-measurable disease were eligible for enrollment. Any number of prior regimens was permitted. Pts received B 150 mg daily and P 125 mg daily 3 wks on 1 wk off. Pts were evaluated for toxicity every 2-4 wks and for response every 8-12 wks. Primary endpoint: 6 month (mo) PFS. Secondary endpoints: clinical benefit rate, toxicity, correlative studies to better characterize AR+ TNBC. A Simon 2-stage minimax design that discriminates between 6 mo PFS rates of 20% and 40% was used. If ≥ 11/33 pts were PF at 6 mo then B+P would warrant further study. Results: As of 1.1.20 33 pts were enrolled on study with median (med) age 67 (42-79), performance status 0 (0-1). Number of pts with visceral metastases: 20, measurable disease: 22. AR% 1-9: 3, 10-50: 6; 51-100: 24. Med prior lines for MBC: 3 (0-9). Best response: (31 evaluable pts): 11 pts PF at 6mo: 10 SD > 6mo, 1 PR. Med wks on study: 14 (2-101). Toxicity > 10% grade >3 related: Number of pts with leukopenia: 21, neutropenia: 21, lymphocytopenia: 6, thrombocytopenia: 3. One pt with febrile neutropenia. One death due to disease progression within 30 days off study. Conclusions: In this selected subset of pts with AR+ TN MBC, this study met its prespecified endpoint with 11 pts PF at 6 mo on B 150 mg + P 125 mg. B+P has been well tolerated with no unexpected toxicity observed. Clinical trial information: NCT02605486 .

Diagnostic radiologists are often the first to know of a patient’s medical diagnosis, disease progression, or response to treatment. Communicating this information to both the referring physician and often directly to the patient has become increasingly important as the role of radiologists in patient care has evolved. As technology advances, and the field of radiology extends beyond the interpretation of diagnostic imaging into that of intervention and treatment, timely and clear communication of imaging results, limitations of radiology examinations, and the risks associated with image-guided interventional and therapeutic procedures is a priority. Instituting structured reporting, reporting lexicons, and formal communication skills training for radiologists are a few measures that radiologists can take to improve communication in the field. Such efforts to improve communication in radiology are integral components to enhancing and expanding the role of radiologists in patient care.

Our group applied mathematical modeling to capecitabine dosing and predicted 7 days of treatment followed by 7 days of rest (7-7) would improve efficacy and minimize toxicity. The conventional schedule of capecitabine limits full dosing in combination with other agents due to toxicity. Lapatinib inhibits the tyrosine kinase of HER2 and has activity when added to conventionally scheduled capecitabine for the treatment of patients with trastuzumab-refractory, HER2-positive, metastatic breast cancer (MBC). We performed this study to evaluate the activity and tolerability of capecitabine 7-7 with lapatinib in patients with trastuzumab-refractory MBC. Eligible patients had measurable, HER2-positive, MBC that progressed following exposure to trastuzumab. Treatment consisted of capecitabine 2,000 mg orally twice daily, 7-7 and lapatinib 1,250 mg orally daily. The primary endpoint was response rate. Secondary endpoints included toxicity, progression-free survival, and stable disease ≥ 6 months. Twenty-three patients were treated on study. More than 60% had prior chemotherapy for MBC and all had prior trastuzumab. After a median of 23 weeks (range 2-96+), five patients had partial responses (23; 95 CI, 7-44%) and six (27; 95 CI, 10-48%) had stable disease ≥ 6 months. Median progression-free survival was 9.4 months. The most common treatment-related toxicities ≥ grade (gr) 2 were hand-foot syndrome (gr 2 43%; gr 3 4% gr 4 0%), diarrhea (gr 2 26%; gr 3/4 0%), elevated liver chemistries (gr 2 17%; gr 3/4 0%), and anemia (gr 2 13%; gr 3 4%; gr 4 4%). No grade ≥ 3 nausea, vomiting, or diarrhea events occurred. This study demonstrated feasibility and after meeting biostatistical requirements for continued accrual was terminated in anticipation of slow enrollment. Capecitabine 7-7 with lapatinib was well tolerated with minimal gastrointestinal toxicity. Antitumor activity was observed in patients with trastuzumab-refractory MBC.

Background Capecitabine (C) administered for 14 days followed by a 7 day rest (14—7) in combination with lapatinib (L) improved TTP in patients (pts) with HER2(+) metastatic breast cancer (MBC) that progressed following trastuzumab (T). Our mathematical modeling of C dosing predicted 7 days of therapy followed by 7 days of rest (7—7) to maximize efficacy and minimize drug-related toxicity. In xenograph models, C (7—7) was better tolerated than C (14—7) at higher doses and led to improved survival. We established the maximum tolerated dose of C (7—7) to be 2,000 mg twice daily and have studied C (7—7) in combination with targeted therapies. We now report the results of C (7—7) with L in pts with trastuzumab-refractory HER2(+) MBC. Methods Eligible pts had measurable, HER2(+) MBC with progression following T. HER2(+) is defined as 3+ on IHC or FISH-amplified. Pts had normal LVEF by MUGA, ECOG performance status (PS) ≥2, and 6 months, and progression free survival (PFS). Using a Simon optimal 2-stage design, with alpha 10% and power 90% to discriminate between RR 10% and 25%, 21 pts were planned for the 1st stage. If >2 pts responded, then 29 additional pts were to have been enrolled to 2nd stage. If >7/50 pts responded, C (7—7) with L would be considered worthy of further study. Results As of 6/14/10, 22 pts were enrolled on study with the following characteristics: median (med) age 55 years (42-72), med PS 0 (0-2), ER/PR(+) 12, HER2(+) 22, med LVEF 64% (51-70%). Sites of MBC include viscera 16, brain 3. Prior therapy includes 8 pts with adjuvant anthracycline and taxane exposure, 4 pts with adjuvant T, 18 pts with metastatic T, and a med of 1 CRx for MBC. After a med of 5 cycles (1-16), 18 patients are evaluable for response: 0 CR, 3 PR, 6 SD >6 months, 9 SD 10% of patients include: hand-foot syndrome (gr 3: 5%, gr2: 41%), diarrhea (gr 3: 0%, gr 2: 23%), elevated AST/ALT or bilirubin (gr 3: 0%, gr 2: 18%). There have been no declines in LVEF. Conclusion Due to slower than expected accrual and an anticipated randomized, phase III trial comparing C (7—7) with C (14—7), we closed this study to further accrual. However, our data suggests that C (7—7) with lapatinib is active, well-tolerated, feasible and associated with mild gastrointestinal toxicity in pts with trastuzumab-refractory, HER2(+) MBC. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-11-12.

Purpose This study was conducted to determine, in patients with advanced-stage breast cancer, the maximum tolerated dose (MTD) of capecitabine administered orally for 7 days followed by a 7-day rest (7/7), a schedule based on a mathematical method for the optimization of anticancer drug scheduling. Patients and Methods Eligible patients had measurable, metastatic breast cancer. There was no limit to number of prior treatments. A standard, three-patients-per-cohort dose-escalation scheme used flat-dose capecitabine beginning at 1,500 mg orally twice daily (bid) on a 7/7 schedule. Each cohort was monitored for 28 days before escalation to the next cohort to assess for delayed toxicity. Response was evaluated radiographically every 12 weeks; toxicity was assessed every 2 weeks. Results Twenty-one patients were treated on study. The most frequently reported treatment-related grade 2/3 adverse events were hand-foot syndrome (29%), leukopenia/neutropenia (24%), and fatigue (19%). Grade 3 toxicity was transient and easily managed. Three patients experienced grade 3 hand-foot syndrome; one of these patients had grade 3 diarrhea. There were no grade 4 events. The MTD of capecitabine 7/7 is 2,000 mg twice daily. Conclusion As predicted by mathematical modeling, capecitabine dosing for 7 days followed by a 7-day rest is well tolerated. Efficacy of this schedule is being determined in a phase II clinical trial in patients with advanced breast cancer.

This study was undertaken to examine the characteristics of cancers detected at the earliest possible point on MRI and to determine their significance.This institutional review board-approved Health Insurance Portability and Accountability Act-compliant retrospective study evaluated invasive breast cancers ≤1 cm histologically. MRI was performed within 6 months before diagnosis. Between 1 January 2005 and 31 December 2015, 163 cancers in 161 patients were evaluated. Breast Imaging-Reporting and Data System lesion characteristics were assessed by two radiologists independently. In cases of disagreement, arbitration by a third reader was performed.Cancers ≤1 cm became more obviously malignant as they enlarged with regard to shape (p = 0.021), margin (p = 0.0006), internal enhancement (p = 0.0158) and kinetics (p = 0.0001). Cancers ≤5 mm had benign characteristics of circumscribed margins in 71% (71/100), round/oval shape in 67% (67/100) and persistent enhancement in 41% (41/100). High TBenign characteristics are present in most invasive cancers ≤5 mm. Small cancers on MRI may need to demonstrate growth to determine need for biopsy. Advances in knowledge: MR lesion characteristics may not be helpful in determining whether small lesions on MR are benign or malignant. However, as 97% of cancers in our study showed interval change when a prior MR for comparison was available, new lesions or increasing size should lead to consideration of biopsy.

Address for correspondence: Ariela Noy, MD, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065 Clinical Pra ● Primary gastric diffuse large B cell lymphoma (DLBCL), a common form of extranodal lymphoma, is an aggressive B cell malignancy arising in the stomach. ● Modern treatment is conservative and systemic, involving a combination of chemotherapy and radiation. Primary surgical resection is no longer standard of care. Incidence of perforation is extremely rare.

We report the case of a 39-year-old asymptomatic woman who presented for screening mammography. Mammography revealed a round, partially circumscribed, partially indistinct, noncalcified 4.5 cm mass in upper outer right breast. This vaguely palpable mass appeared as a well-circumscribed, oval, hyperechoic, parallel, septated mass on sonography. Ultrasound-guided core biopsy led to the diagnosis of hibernoma. Few cases of hibernomas have been reported in the English literature, and their occurrence in the breast is particularly rare [Eur J Surg Oncol 26 (2000) 430; Am J Surg Pathol 25 (2001) 809]. To our knowledge, this is the first case of mammary hibernoma in which the ultrasonographic and mammographic features of this unusual entity are demonstrated.

To retrospectively evaluate the cost of clinical breast examination (CBE) and its contribution to screening mammography in the detection of breast cancer.The study received a waiver of authorization from the institutional review board, informed patient consent was not required, and the study was compliant with HIPAA regulations. The records of 60 027 consecutive asymptomatic patients who underwent screening mammography were retrospectively reviewed. CBE was performed on all patients by a nurse practitioner. Patients with positive CBE findings were required to convert from screening to diagnostic evaluation; the number of cancer diagnoses that resulted was determined. The reports, four-view mammograms, or both of patients requiring conversion to diagnostic evaluation were reviewed to determine those patients likely to undergo diagnostic imaging on the basis of screening mammographic findings alone. The cost of CBE was calculated and divided by the number of cancers detected solely with CBE to determine the cost of CBE per additional cancer detected.Four hundred seventy-four (age range, 32-95) of 60 027 asymptomatic patients had positive CBE findings which required conversion to diagnostic evaluation. Forty-six cancers in 44 patients were subsequently diagnosed; 32 would have been detected with mammography alone, whereas 14 were imperceptible at screening mammography. The cost of CBE was $122 598 per cancer detected solely with positive CBE findings.CBE performed by nurse practitioners led to the diagnosis of 14 cancers in 13 patients with mammographically occult tumors (0.02% of the screening population and approximately 3% of all cancers diagnosed at the facility during this study). The cost of detecting these additional cancers is estimated to be $122 598 per cancer.

We present the computed tomography (CT) and magnetic resonance (MR) imaging features of a gluteal hibernoma found incidentally at CT in an 80-year-old woman. Large, tortuous vessels were demonstrated within a high-T1-signal mass at MR imaging, a combination of findings in hibernomas that has been illustrated but not emphasized in the literature. Such a constellation of findings should strongly suggest the diagnosis of hibernoma (rather than well-differentiated liposarcoma or other soft tissue tumor).

Background: Our group and others have identified a subset of ER/PR(−) breast cancers characterized by expression of the androgen receptor (AR) and androgen-dependent growth (Doane 2006). We conducted a proof-of-concept multicenter phase II study to test the efficacy of the AR-antagonist, bicalutamide for the treatment of AR(+) ER/PR(−) MBC (NCT00468715). Results of the primary endpoint, clinical benefit rate (CBR), were presented at ASCO (Gucalp 2012). Data for the impact of bicalutamide on circulating hormone levels in women are limited. Elevations in serum testosterone (T) and estradiol (E) have been observed for men treated with bicalutamide. We hypothesized comparable patterns of change in circulating endocrine markers in response to bicalutamide for women with MBC. Methods: Patients (pts) with AR(+) (IHC ≥10%), ER/PR(−) (IHC Results: 26 patients with AR(+) ER/PR(−) MBC were treated on study. Evaluable number (n) of pts at baseline, C2 and EOS are 26, 26 and 19 respectively. Two pts remain on study. Menopausal status: pre=2, post=24. Baseline median total and free T and estradiol were consistent with expected norms, however a wide range was observed (Table). There were no significant differences observed for median free T, total T, E or SHBG between baseline and C2 or baseline and EOS. Changes in hormone levels could not be stratified by menopausal status or response to bicalutamide given small sample size. Given the wide range of baseline values, we examined the percent change for each endocrine biomarker from baseline to C2 and EOS. As shown in the Table, there was no difference in median percent change observed across time points for each biomarker. Conclusions: No discernible patterns of change in T, E or SHBG were observed in response to bicalutamide therapy when given to women for the treatment of AR(+), ER/PR(−) MBC. These circulating hormones require further evaluation for use as a pharmacodynamic marker. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-05-02.

1006 Background: Patients (pts) with ER-/PR- MBC do not benefit from endocrine treatment (tx). Doane et al (Oncogene 2006;25:3994) described a subset of ER-/PR- BC with a gene expression profile similar to ER+ BC but characterized by AR expression and AR-dependent growth in vitro. Hence, we conducted a multicenter phase II trial (NCT00468715) of the AR antagonist, bicalutamide (B) for pts with AR+ ER-/PR- MBC. Methods: Pts with ER-/PR- (IHC 6mo (SD). B would be considered worthy of further study if ≥4/28 pts have clinical benefit. Results: As of 12/21/11,436 pts consented for AR testing. 24 were ineligible, 12 await testing. 47/400 tested were AR+ (12%). 26 received tx with B (6 ineligible for tx, 15 are eligible for tx with B at progression (POD) if clinically appropriate and study slots remains). Two AR+ pts treated with B were ER+ and removed from study. Three have received tx 6mo 4, CR/PR 0, SD

TPS122 Background: Patients with ER-/PR- MBC do not benefit from endocrine therapy. Doane et al. described a subgroup of ER-/PR- breast cancers with a gene expression profile similar to ER+ tumors but characterized by AR expression (Oncogene 2006). Farmer et al. identified an AR+ER-, non-basal-like group of breast tumors in a separate data set and termed them molecular apocrine breast cancer (Oncogene 2005). In vitro studies with the MDA-MB-453 cell-line, which is representative of this subtype, demonstrated AR-dependent growth and supported AR inhibition as a potential therapeutic approach for these patients (Doane et al., Oncogene 2006). We are testing the efficacy of the AR antagonist, bicalutamide (B) for patients with AR+/ER-/PR- MBC in a multicenter Phase II trial. Clinical trial registry #: NCT00468715. Methods: Patients with ER-/PR- (immunohistochemistry (IHC)

BackgroundCapecitabine (C) administered for 14 days followed by a 7 day rest (14—7) in combination with lapatinib (L) improved TTP in patients with HER2(+) metastatic breast cancer (MBC) that progressed following trastuzumab (T). We applied mathematical methods to C dosing which predicted 7 days of treatment (Tx) followed by 7 days of rest (7—7) to be optimal. In animal models, C(7—7) was better tolerated than C(14—7) at higher doses and led to improved survival. A phase I study in patients (pts) with MBC concluded the MTD of C(7—7) is 2,000mg BID. To optimize the combination of C+L, we are testing C(7—7) + L.MethodsEligible pts have measurable, HER2(+) MBC with progression following trastuzumab. HER2(+)=3+ or FISH-amplified. Pts have normal LVEF by MUGA, ECOG performance status (PS) ≤2 and normal organ function. Prior therapy is limited to 6 months and PFS. Using a Simon optimal 2-stage design, with alpha 10% and power 90% to discriminate between RR 10% and 25%, 21 pts will be accrued to the 1st stage. If >2 patients respond, 29 additional pts will be enrolled. If >7/40 pts respond, then C(7—7) + L will be considered worthy of further study.ResultsAs of 5/28/09, 12 pts are enrolled; 6 are evaluable for response. Median (med) age 61 years (41-71), med ECOG PS 0 (0-2), ER/PR(+) 5, HER2(+) 12. Sites of MBC: Viscera 5, Brain 2. Med LVEF 64% (51-71%). Prior Tx: Adjuvant: CRx (7), hormone Tx (3), T (4); MBC: CRx (6), hormone Tx (4), T (8). After a med of 3 cycles (1-8), 6 pts are evaluable for response: CR 0, PR 1, SD>6mo 2, SD10% of pts includes: hand-foot syndrome (Gr 3: 8%, Gr 2: 17%) and diarrhea (Gr 2: 17%). There were no declines in LVEF.ConclusionCapecitabine (7—7) plus lapatinib appears well-tolerated and demonstrates activity in pts with HER2(+) MBC that has progressed following trastuzumab based therapy. Additional efficacy and safety data is expected prior to this meeting. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5113.

1131 Background: Capecitabine (C) is active in breast cancer and is usually dosed for 14 days (d) followed by a 7d rest (14 - 7). We described a mathematical method which predicts the optimal schedule for C to be 7d followed by a 7d rest (7 - 7) (Norton et al, Amer Assn Can Res. 2005). The MTD of C(7 - 7) is 2,000mg BID (Traina et al, J Clin Oncol. April 2008). Lapatinib (L) improves time to progression when added to C(14 - 7) in patients (pts) with HER-2-positive (+) metastatic breast cancer (MBC) that progressed after trastuzumab (T). To optimize this effective combination, we are testing C(7 - 7) + L in a phase II trial. Methods: Eligible pts have measurable, HER-2(+) MBC that has progressed after T. HER-2(+)=IHC 3+ or FISH>2. Pts have normal LVEF by MUGA, ECOG performance status (PS) 6 months, PFS. Using a Simon optimal 2-stage design, with alpha = 10%, power = 90% to discriminate between RR 10% and 25%, 21 pts will be accrued to the first stage. If >2 pts respond, 29 additional pts will be enrolled. If >7/ 40 pts respond, then C(7 - 7) + L will be considered worthy of further study. Results: As of January 5, 2008, 6 pts are enrolled and evaluable. Median (med) age 64 yrs (42–71), med ECOG PS 1 (0–1), ER/PR(+) 3, HER-2(+) 6, sites of MBC: bone (2), viscera (4), soft tissue (5). Med baseline LVEF 62% (51–68%). Prior tx: Adjuvant: CRx (5), hormone tx (3), T (3); MBC: CRx (2), hormone tx (1), T (3). After a med of 3 cycles (1–4), there were no grade 3, 4, or 5 events. Tx-related toxicity is: Gr 2 fatigue (1); Gr 1 AST (4), diarrhea (3), ALT (2), vomiting (1), hand-foot (1), fatigue (1). No withdrawls due to reduced LVEF. Two pts evaluable for response: PR = 1, SD [Table: see text]

Abstract #6121 Background Capecitabine (Xeloda®,C) has activity in breast cancer when dosed for 14 days (d) followed by a 7d rest (14 - 7). Using mathematical methods, we predict the optimal dosing schedule of C to be 7d followed by a 7d rest (7 - 7) (Norton et al, AACR 2005). Xenograft studies show this schedule improves tolerability and survival. The MTD of C(7 - 7) is higher than that for conventional dosing (Traina et al, JCO 2008). Bevacizumab (B), an anti-VEGF antibody, improves response when added to capecitabine in pts previously treated for metastatic disease (Miller et al, JCO) and improves PFS when added to taxanes in the 1st-line treatment of advanced disease (Miller et al, NEJM 2007; Miles ASCO 2008). B + conventionally-dosed capecitabine modestly increased TTP when used as 1st-line therapy (Sledge, ASCO 2007). This study tests C(7 - 7) with bevacizumab (B) in a Phase II trial. Methods Eligible patients (pts) have measurable, metastatic breast cancer (MBC), ECOG performance status (PS) ≤2 and normal organ function. Any number of prior chemotherapy (CRx) regimens is permitted. Pts with prior fluoropyrimidine or bevacizumab are excluded. Therapy (tx) consists of C (2,000mg BID, 7 - 7) and B (10mg/kg IV q2 weeks(wk)). Pts are evaluated for toxicity q2wk and for response q12wk. Cycle length: 4 wks. Primary endpoint: response rate (RR). Secondary endpoints: clinical benefit, TTP, PFS, toxicity. Using a mini-max, two-stage design, up to 40 patients will be enrolled. If >6/40 pts respond, then C(7 - 7) + B will be considered worthy of further study. If >11 pts experience Grade 3/4 capecitabine-related toxicity the trial will be stopped. Results Twenty-seven pts are enrolled. Median (med) age 57 yrs (29-71), med ECOG performance status 0 (0-2), ER/PR(+) 13, HER2(+) 1, sites of MBC: bone(13), liver/lung(13), soft tissue(12). Prior tx: Adjuvant: CRx (20), hormone tx (14); MBC: CRx (2), hormone tx (16). 27 pts are evaluable for toxicity. After a med of 6 (1-12) cycles: Twenty-three pts evaluable for response: PR=7 (confirmed=5), stable disease (SD) >6 mo =6, SD Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6121.

1101 Background: Capecitabine has activity in breast cancer and is usually dosed for 14 days (d) followed by a 7d rest (14 - 7). We described a mathematical method which predicts the optimal dosing...

1045 Background: We have previously described a mathematical method to optimize chemotherapy dose and schedule (Norton et al, AACR 2005). Capecitabine (C) has activity in breast cancer when conventionally dosed for 14 days (d) q3 weeks (14/7). However, the predicted optimal dosing schedule for C using our model is 7d followed by a 7d rest (biweekly, 7/7). We tested this hypothesis in a Phase I/II study described below. Methods: Eligible patients (pts) have measurable, metastatic breast cancer (MBC), ECOG performance status (PS) =2 and normal organ function. There is no limit to number of prior chemotherapy (CRx) regimens. Pts with prior fluoropyrimidine for MBC are excluded. HER2+ pts must not be candidates for trastuzumab. C is given in divided daily doses for 7d followed by a 7d rest. A standard “3+3” dose escalation scheme employs flat dosing which begins at 1,500mg BID and increases by 500mg/dose level. Primary endpoint is the maximum tolerated dose (MTD), defined as the highest dose for which the incidence of dose-limiting toxicity (DLT) is [Table: see text] No significant financial relationships to disclose.