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Background: Biosimilars for trastuzumab were introduced into the US market for the treatment of HER2-positive breast cancer in 2019, with the goal of providing the clinical benefit of the brand product at a lower price (increased value). Adoption of trastuzumab biosimilars may be affected by multiple factors, including physician confidence in biosimilar efficacy and efficacy across stages, practice reimbursement, payer medical policy/redirection. To look at the adoption of trastuzumab biosimilars in the US medical oncology community, we queried a database of submitted treatment plans for patients with breast cancer. Methods: Data from a pre-authorization platform used by multiple commercial insurance companies in the US (NantHealth Eviti) was analyzed. Cases were identified from approved treatment plans for patients with breast cancer by inclusion of brand trastuzumab or trastuzumab + hyaluronidase-oysk, or trastuzumab biosimilars. Results: As of July 1, 2020, 10,557 treatment plans trastuzumab-based therapy were submitted, 1740 (16.5%) of which used a trastuzumab biosimilar. Adoption of trastuzumab biosimilars increased over time, from 1.6% (27/1676) treatment plans in Q3-2109 to 43.3% (753/1736) in Q2-2020. No clear differences were observed between use in stage 0-IIIc disease (17.4%) vs stage IV/recurrent disease (14.5%). Using the July 1, 2020 CMS pricing for these drugs at normalized dose of 440 mg for trastuzumab/trastuzumab biosimilars or 600 mg of trastuzumab + hyaluronidase, the average cost/cycle/patient for brand therapy and biosimilar therapy is $4502 and $3618, respectfully, representing a savings of $1,374,620/cycle across the biosimilar-treated population. Additional analyses to be presented will include Q3 2020 utilization and patterns of utilization across payers with/without medical policy favoring biosimilars. Conclusions: Adoption of trastuzumab biosimilars in this commercial population has been rapid since their introduction. Use of these drugs provides a substantial opportunity for societal savings in the treatment of HER2-positive breast cancer. Citation Format: William A Flood, Tiffany Avery, Vlad Kozlovsky, Neil Margolis, Sandeep Reddy. Real world data on the adoption of trastuzumab biosimilars in the treatment of HER2-positive breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-63.

Background Cardiovascular health is of increasing concern to breast cancer survivors and their health care providers, as many survivors are more likely to die from cardiovascular disease than cancer. Implementing clinical decision support tools to address cardiovascular risk factor awareness in the oncology setting may enhance survivors’ attainment or maintenance of cardiovascular health. Objective We sought to evaluate survivors’ awareness of cardiovascular risk factors and examine the usability of a novel electronic health record enabled cardiovascular health tool from the perspective of both breast cancer survivors and oncology providers. Methods Breast cancer survivors (n=49) recruited from a survivorship clinic interacted with the cardiovascular health tool and completed pre and posttool assessments about cardiovascular health knowledge and perceptions of the tool. Oncologists, physician assistants, and nurse practitioners (n=20) who provide care to survivors also viewed the cardiovascular health tool and completed assessments of perceived usability and acceptability. Results Enrolled breast cancer survivors (84% White race, 4% Hispanic ethnicity) had been diagnosed 10.8 years ago (SD 6.0) with American Joint Committee on Cancer stage 0, I, or II (45/49, 92%). Prior to viewing the tool, 65% of survivors (32/49) reported not knowing their level for one or more cardiovascular health factors (range 0-4). On average, only 45% (range 0%-86%) of survivors’ known cardiovascular health factors were at an ideal level. More than 50% of survivors had ideal smoking status (45/48, 94%) or blood glucose level (29/45, 64%); meanwhile, less than 50% had ideal blood pressure (12/49, 24%), body mass index (12/49, 24%), cholesterol level (17/35, 49%), diet (7/49, 14%), and physical activity (10/49. 20%). More than 90% of survivors thought the tool was easy to understand (46/47, 98%), improved their understanding (43/47, 91%), and was helpful (45/47, 96%); overall, 94% (44/47 survivors) liked the tool. A majority of survivors (44/47, 94%) thought oncologists should discuss cardiovascular health during survivorship care. Most (12/20, 60%) oncology providers (female: 12/20, 60%; physicians: 14/20, 70%) had been practicing for more than 5 years. Most providers agreed the tool provided useful information (18/20, 90%), would help their effectiveness (18/20, 90%), was easy to use (20/20, 100%), and presented information in a useful format (19/20, 95%); and 85% of providers (17/20) reported they would use the tool most or all of the time when providing survivorship care. Conclusions These usability data demonstrate acceptability of a cardiovascular health clinical decision support tool in oncology practices. Oncology providers and breast cancer survivors would likely value the integration of such apps in survivorship care. By increasing awareness and communication regarding cardiovascular health, electronic health record–enabled tools may improve survivorship care delivery for breast cancer and ultimately patient outcomes.

Purpose To determine whether three-dimensional subharmonic aided pressure estimation (SHAPE) and subharmonic imaging can help predict the response of breast cancer to neoadjuvant chemotherapy. Materials and Methods In this HIPAA-compliant prospective study, 17 women (age range, 45-70 years) scheduled to undergo neoadjuvant therapy for breast cancer underwent ultrasonography (US) immediately before therapy and at completion of 10%, 60%, and 100% of chemotherapy. All patients provided written informed consent. At each examination, radiofrequency data were collected from SHAPE and subharmonic imaging during infusion of a US contrast agent. Maximum-frequency magnitude and mean intensity were calculated for SHAPE and subharmonic imaging. The signal differences in the tumor relative to the surrounding area were compared with the final treatment response by using the Student t test. Results Four patients left the study, and data from two patients were discarded because of technical problems. Eight patients completed the entire imaging protocol, and an additional three patients dropped out after the imaging session at completion of 10% of chemotherapy as a result of disease progression (these patients were counted as nonresponders). Patients' imaging outcomes consisted of six responders (tumor volume reduction90%) and five partial responders or nonresponders. The results at completion of 10% of therapy showed that the subharmonic signal increased more in the tumor than in the surrounding area for responders than in partial responders or nonresponders (mean ± standard deviation, 3.23 dB ± 1.41 vs -0.88 dB ± 1.46 [P = .001], respectively, for SHAPE and 1.32 dB ± 0.73 vs -0.82 dB ± 0.88 [P = .002], respectively, for subharmonic imaging). Moreover, three patients whose tumor measurements initially increased were correctly predicted to be responders with SHAPE and subharmonic imaging after completion of 10% of therapy. Conclusion SHAPE and subharmonic imaging have the potential to help predict response to neoadjuvant chemotherapy for breast cancer as early as completion of 10% of therapy, albeit on the basis of a small sample size.

Introduction: African Americans (AA) present more frequently with triple negative breast cancer (TN) and other aggressive breast cancer subtypes. Invasive lobular (ILC) breast cancer most commonly presents as estrogen receptor (ER)+, progesterone receptor (PR)+ and HER2-, though less frequently the more aggressive ER- or PR- luminal, TN or HER2+ subtypes occur. For women presenting with ILC 2010-2013, we report by race, differences in disease subtype, grade and stage at presentation and 2-year outcomes. Methods: We conducted a retrospective cohort analysis using Surveillance, Epidemiology and End Results Program. Women diagnosed with first primary malignant lobular breast cancer from 2010-2013 were included. Subtypes were categorized into four exclusive groups: ER+ and PR+ HER2-, ER+ or PR+ HER2-, TN and HER2+. Two-year survival was compared across race, and a multivariate cox model assessed overall survival. Results: ILC occurred less frequently in non-whites (Table 1). AA and other non-whites were younger at diagnosis than whites (p Conclusion: In this large, recent ILC cohort there were significant racial disparities in disease biology at presentation, with non-whites having more aggressive ILC subtypes, but only AAs having higher grade ILC. Short-term survival outcomes were inferior for AAs. Whether AAs presenting with advanced stage disease more frequently is due to biology or access to care is unknown. Further study of disease biology and healthcare delivery disparities could offer improved outcomes for AAs with ILC. Table 1: ILC Characteristics by Race WhiteAA Other non-white N13,5571,445 957 ILC - % diagnoses per race category9.67.2 5.8 Rate of ILC (per 100,000 women of that race)10.56.4 4.4 Median Age6461 60 %%OR*p%OR*pSubtype ER+ and PR+ HER2-80.978.30.850.01977.00.790.003ER+ or PR+ HER2-12.914.41.140.10615.31.220.036TN1.52.11.440.0642.11.400.158HER2+4.75.11.090.4735.61.210.186Stage I40.536.4 39.0 Table 2: Multivariate Cox Model for 2-year Survival HRp95% CIRace Whiteref AA1.320.0101.071.64Other non-white0.580.0080.380.87Subtype ER+ and PR+ HER2-ref ER+ or PR+ HER2-1.80 Citation Format: Thomas A, Altekruse S, Avery TP, Melin SA, Howard-McNatt MM, Schroeder MC. African Americans have more aggressive invasive lobular carcinoma subtypes and inferior early outcomes: SEER 2010-2013 [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-10-02.

The primary aim in the management of DCIS is the prevention of recurrence and contralateral tumor. Risk factors for DCIS recurrence and appropriate treatments are still widely debated. Adjuvant therapies after surgical resection reduce recurrences and contralateral disease, but these treatments have significant financial costs, side effects and there is a group of low-risk patients who would not gain additional benefit. The aim of our analysis was to identify clinical-pathological features and treatment modalities associated with recurrence in DCIS and microinvasive carcinoma. In the Thomas Jefferson University Cancer Registry of Philadelphia, we identified 865 patients with DCIS or micro-invasive carcinoma treated between 2003 and 2013. Associations between recurrence and demographic factors (age at diagnosis, ethnicity), biological features (ER, PR and HER2) and treatment modalities (surgery, radiotherapy and endocrine treatment) were assessed. Our single institution register-based study showed that distribution of age at diagnosis and biological features did not significantly differ among ethnic groups. Younger women and micro-invasive carcinoma patients were more likely to undergo mastectomy, while African Americans were more likely to take endocrine therapy and undergo radiotherapy. In our sample only ER/PR negative DCIS were associated with significantly higher recurrence rate. Moreover, we reported a high rate of HER2 positive recurrences, suggesting that expression of this oncogene may represent a potential biomarker for DCIS at high risk of recurrence. To better define the molecular profile of the subgroup at worse prognosis might help to identify biomarkers predictive of recurrence or second tumors, identifying patients candidates for more appropriate treatments.

African American breast cancer survivors (AABCS) have a lower survival rate across all disease stages (79 %) compared with White survivors (92 %) and often have more aggressive forms of breast cancer requiring multimodality treatment, so they could experience a larger burden of post-treatment quality of life (QOL) problems. This paper reports a comprehensive assessment of the number, severity, and domains of problems faced by AABCS within 5 years after treatment completion and identifies subgroups at risk for these problems. A population-based random sample was obtained from the Pennsylvania Cancer Registry of African American females over 18 years of age who completed primary treatment for breast cancer in the past 5 years. A mailed survey was used to document survivorship problems. Two hundred ninety-seven AABCS completed the survey. The median number of survivor problems reported was 15. Exploratory factor analysis of the problem scale revealed four domains: emotional problems, physical problems, lack of resources, and sexuality problems. Across problem domains, younger age, more comorbid conditions, and greater medical mistrust were risk factors for more severe problems. The results demonstrated that AABCS experienced significant problem burden in the early years after diagnosis and treatment. In addition to emotional and physical problem domains that were documented in previous research, two problem domains unique to AABCS included lack of resources and sexuality concerns. At risk groups should be targeted for intervention. The study results reported in this manuscript will inform future research to address problems of AABCS as they make the transition from cancer patient to cancer survivor.

Inflammatory breast carcinoma (IBC) is the most aggressive form of breast cancer. The hallmark of IBC is regional extension into dermal lymphatics as tumor emboli causing breast edema and erythema. Pathologic characteristics of IBC include high grade, negative hormone receptor status and overexpression of HER2 and E-cadherin. The latter is the most attractive therapeutic target in IBC. In preclinical studies the histone deacetylase inhibitor, romidepsin targeted E-cadherin, affecting tumor emboli and increasing taxane sensitivity. Rationale: In vitro studies show that histone deacetylase inhibitors (HDACi) with taxanes provide synergy to enhance cell death. HDACi alter expression of AIRH1, a regulator of autophagy, typically silenced in breast cancer. In vitro treatment with HDACi induces expression of AIRH1, resulting in enhanced cell death with taxanes. In vitro studies of IBC have demonstrated the utility of HDACi and romidepsin in IBC cell lines. SAHA and romidespin, HDACis, inhibited self-renewal of IBC tumor spheroids from IBC cell lines. This trial combines romidepsin with a taxane proven in metastatic breast cancer to explore whether the combination will be effective in IBC. Design: This is a phase I trial to assess the safety of romidepsin plus nab-paclitaxel in patients with recurrent or metastatic IBC. The maximum tolerated dose (MTD) of romidepsin + weekly nab-paclitaxel was determined to define the dose for the phase II trial. Secondary objectives included describing the adverse event profile and assessing the overall response rate (ORR) and Clinical Benefit Rate (CBR). This study employed a 3+3 design. DLTs included febrile neutropenia or non-hematologic grade 3 or 4 toxicities. Patients were treated with nab-paclitaxel 100 mg/m2 iv with romidepsin, 7 mg/m2 iv (1st cohort) and 10 mg/m2 iv (2nd cohort), on days 1, 8, 15 of a 28 day cycle. Results: Nine patients were treated. The median age was 52. Three patients were treated in the first cohort. Two patients showed progressive disease (PD). One patient has had stable disease (SD) over 10 cycles and continues treatment. DLT was not reached at 7 mg. Toxicities related to romidepsin included neutropenia, anemia and fatigue. Six patients were treated in the 2nd cohort. Grade 3 hypophosphatemia, a DLT, was reached. One patient had complete response (CR). One patient had SD; four patients had PD. Toxicities related to romidepsin were anemia, neutropenia, GI upset, edema, hyperglycemia, fatigue, hypophosphatemia, pruritis, dry mouth, and increased lab values. The overall response rate (ORR) was 33% (3/9). The table below shows results. CohortResponse# Prior TherapiesMetastatic Sites# Cycles on study1PD2pleura, nodes51PD0lung31SD2lung, nodes102PD2pleura, nodes, soft tissue42PD0liver, nodes, bone22CR2 chemotherapy, 2 endocrinebone, nodes72SD0nodes52PD0lung,liver, nodes22PD0liver, bone, nodes2 Conclusions: This phase I trial shows that romidepsin and nab-paclitaxel are well-tolerated in patients with advanced IBC. The MTD and recommended dose of romidepsin is 10 mg/m2 with nab-paclitaxel 100 mg/ m2 days 1, 8, 15 of a 28 day cycle. A phase II trial is planned in recurrent HER negative IBC patients. Citation Format: Avery TP, Jaslow R, Basu-Mallick A, Zibelli A, Fellin F, Cristofanilli M. A phase I study of romidepsin in combination with nab-paclitaxel in patients with metastatic HER-2 negative inflammatory breast cancer (IBC). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-13-18.

Inflammatory breast cancer (IBC) is the most aggressive type of breast cancer with survival rates far lower than other types of breast cancer. Patterns of development, invasion, and presentation are unique to IBC compared with other breast cancers. However, therapies targeted specifically to the treatment of IBC are lacking. Specific therapies, which address the unique features of IBC, are needed to improve prognosis for this type of breast cancer. The first step in developing improved treatments is to identify biomarkers and genes, which are preferentially expressed in IBC and to develop therapies targeted to these markers. In this paper, we discuss advances made in the studies of biomarkers and gene expression in IBC over the last 5 years. Some of the markers have proven to be prognostic or predictive of response to therapy. In some cases, therapies targeted for biomarkers are already used in the treatment of cancer and could be evaluated in IBC patients.

The use of erythropoiesis stimulating agents (ESAs) to treat anemia in breast cancer patients who are treated with chemotherapy is a matter of ongoing debate. Several recent randomized trials challenged conventional wisdom, which holds that ESAs are contraindicated for breast cancer patients undergoing curative treatment. We aimed to perform the first large national population-based study to analyze the association between ESA use and breast cancer patient outcomes. Cytotoxic chemotherapy-treated invasive breast cancer patients were identified from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Non-ESA users were sequentially 1:1 matched to 2,000 randomly sampled ESA users on demographics (age, diagnosis year, race, marital status, and socioeconomic status), tumor presentation (stage, grade, and status of hormone receptors), and treatments (surgery, radiation, and sub-types of chemotherapy) using a minimum distant strategy. Breast cancer-specific survival of ESA and matched non-ESA users was compared using Fine and Gray competing risk model. Compared to ESA users, non-ESA users exhibited dramatically different baseline characteristics such as less advanced tumor, and fewer co-morbidities. Non-ESA users had a significantly more favorable breast cancer-specific survival (subdistribution hazard ratio [sHR] = 0.75, p < 0.0001). This survival disparity was progressively diminished in the sequential matching of demographics (sHR = 0.74, p = 0.0004), presentation (sHR = 0.86, p = 0.06), and treatment (sHR = 0.89, p = 0.17) variables. Stratified analyses identified subgroups of patients whose breast cancer-specific survival were not different between ESA and non-ESA users. In the SEER-Medicare database, ESA usage does not seem to be associated with unfavorable breast cancer-specific survival in breast cancer patients receiving cytotoxic chemotherapy. The ESA-breast cancer prognosis association is complex and requires more intensive investigations.

The aim of this study was to evaluate the association of bone mineral density (BMD) at the time of diagnosis with clinical-pathologic findings in patients with operable postmenopausal breast cancer. One hundred and fifty-eight postmenopausal women who had a baseline lumbar and hip BMD measurement were included in the analysis. Patients were divided into two groups based on the median BMD. p ≤ 0.002 was considered to be statistically significant. Hormone replacement therapy (HRT) use longer than 5 years was associated with increased lumbar BMD compared with patients who used HRT less than 5 years (p = 0.002). Patients with higher BMD tended to have low grade disease, no lympho-vascular invasion, progesterone receptor-positive tumors, and low Ki-67 levels (p < 0.05). Higher baseline BMD in postmenopausal patients with breast cancer is associated with favorable prognostic features.

Triple-negative breast cancer (TNBC) is an aggressive disease subtype that has a poor prognosis. Extensive epidemiological evidence demonstrates clear socioeconomic and demographic associations with increased likelihood of TNBC in both poorer and minority populations. Thus, biological aggressiveness with few known therapeutic directions generates disparities in breast cancer outcomes for vulnerable populations. Emerging molecular evidence of potential targets in triple-negative subpopulations offers great potential for future clinical trial directions. However, trials must appropriately consider populations at risk for aggressive subtypes of disease in order to address this disparity most completely. New US FDA draft guidance documents provide both flexible outcomes for accelerated approvals as well as flexibility in design with adaptive trials. Careful planning with design, potential patient population and choices of molecular targets informed by biomarkers will be critical to address TNBC clinical care.

Neoadjuvant chemotherapy is standard of care for localized breast. The patient response to neoadjuvant chemotherapy correlates with survival and early response assessment is therefore beneficial. The purpose of this study was to determine if 4D subharmonic aided pressure estimation (SHAPE) can predict the response of breast cancer to neoadjuvant chemotherapy based on changes in interstitial fluid pressure and breast tumor vascularity. Seventeen patients scheduled for neoadjuvant therapy of a breast cancer underwent 4 ultrasound exams: prior to therapy, at 10%, 60%, and 100% completion of chemotherapy. Ultrasound exams were performed using a modified Logiq 9 scanner with a 4D10L probe (GE Healthcare, Milwaukee, WI, USA). Modified software enabled the collection of radiofrequency data from 4D pulse inversion subharmonic imaging (transmitting at 5.8 MHz and receiving at 2.9 MHz) before and during a continuous infusion of Definity (Lantheus Medical Imaging, N Billerica, MA, USA) at acoustic settings optimized for SHAPE. The ratios of maximum subharmonic magnitude acquired during infusion relative to unenhanced signals were calculated offline in the tumor and surrounding areas for all 4 exams. The difference between ratios in the tumor and the surrounding area were then compared to the final tumor treatment response. Four patients left the study and 2 patients' data were discarded. Patients' clinical outcomes consisted of 6 responders (tumor volume reduction > 90%) and 5 partial/non responders. The results from 10% completion of therapy showed the subharmonic signal increased more in the tumor than in the surrounding area for responders compared to partial/non responders (3.23 ± 1.41 dB vs. −0.88 ± 1.46 dB; p = 0.001). Moreover, 3 patients whose tumor size initially increased during therapy were correctly predicted by SHAPE to be responders. In conclusion, SHAPE has the potential to predict the neoadjuvant chemotherapy response of breast cancer as early as at 10% completion of the therapy; albeit based on a small sample size.

Background: To improve access to screening, the National Breast and Cervical Cancer Early Detection Program (NBCCEDP) was developed through the Centers for Disease Control and Prevention (CDC) to provide low-income, and uninsured underserved women access to timely breast and cervical cancer screening and diagnostic services. This population-based study investigates the demographics and diagnostic outcomes of women who underwent breast cancer screening through this program established at an urban university cancer center compared to data obtained from the national program database. Methods: The Kimmel Cancer Center at Jefferson (KCC) launched its screening program with resources from the CDC, the State of Pennsylvania, and the Susan G. Komen Foundation in 2008. The core of the program is staff lead by a Social Worker/Navigator who connects patients to education and screening services, institutional information and guidance, and follow-up to minimize barriers to access, lessen dropout, and ensure follow-through for timely diagnosis and treatment. Working with our Community-Based partner organizations, uninsured and underinsured women in Philadelphia are able to seamlessly travel from education and screening through to treatment and support. All KCC patients evaluated through this program from 2008–2011 were included and records of the NBCCDP database 2006–2010 for this study and analyses. Results: KCC has a substantially larger African American (54.44% vs. 13.8%), smaller Hispanic (8.59% vs. 27.6%), larger percentage of abnormal mammograms (25.96% vs. 14%), higher breast cancer diagnosed per mammogram (2.13 vs 1.0) and a much younger population than the national cohort. Fewer than 1% of KCC patients have been lost to follow-up. Conclusions: The KCC Breast and Cervical Screening and Treatment Program Services reaches a highly vulnerable and at-risk population, has a higher abnormal mammogram and breast cancer detection rate, and a higher continued participation rate than the national cohort. The Social/Worker/Navigator has a distinct role in providing follow-up for abnormal findings to minimize no-shows by providing creative problem-solving, support, counseling, finding resources to minimize barriers, and contributes significantly to the ease of operation and the continued participation of patients in the program. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-14-03.

e22083Background: Chemotherapy-induced peripheral neuropathy (CIPN) occurs in 40% of breast cancer patients receiving taxanes and may lead to early treatment discontinuation. Taxane microtubular hy...

129 Background: Cardiovascular health (CVH) is of increasing concern to cancer survivors and their healthcare providers, since survivors of many early-stage cancers are more likely to die of cardiovascular disease than cancer. Our team adapted an existing EHR-based CVH data visualization application designed for the primary care setting to be used in the community oncology setting. We evaluated the acceptability of the Automated Heart-Health Application (AH-HA) among oncology providers and cancer survivors. Methods: We queried oncologists, physician assistants, and nurse practitioners (n=20) who provide care to survivors regarding their perceived usability of AH-HA. Oncologists’ responses were assessed on a 7-point Likert scale from strongly disagree (1) to strongly agree (7); we categorized responses of 5-7 as “agreeing”. We additionally asked cancer survivors (N=48) for their opinions of AH-HA. Patients’ responses were assessed on a 5-point Likert scale from strongly disagree (1) to strongly agree (5); responses of 4 or 5 were categorized as “agreeing”. Results: The majority (60%) of oncology providers (60% female, 65% medical oncologists) had been practicing for more than 5 years. Breast cancer survivors comprised the majority of the survivor sample (98%). Usability data are presented below. 85% of providers reported they would use the tool most or all of the time when providing survivorship care. 94% of patients thought oncologists should discuss heart health during survivorship care; 69% would like to use AH-HA with their oncologist. Conclusions: These usability data demonstrate acceptability and feasibility of implementing the AH-HA application in oncology practices and suggest that oncology providers and survivors would value the integration of such applications in survivorship care. [Table: see text]

Background: Historically, breast cancer (BC) patients were offered cytotoxic or endocrine therapy based on factors such as tumor size, stage, and immunohistochemistry (IHC) markers for estrogen receptor (ER) and HER2-positivity. In 2010 the College of American Pathologists revised the breast cancer guidelines on endocrine therapy (ET) to include a lower threshold of ER positivity by immunohistochemistry, changing the definition from 10% to 1% [Hammond et al]. As a result, although a larger number of patients are offered ET, not all may benefit from this expanded definition of ER positivity if their disease is not truly estrogen driven. More recently, sensitive gene profiling assays, such as Blueprint®, can determine intrinsic molecular subtype which may be more sensitive in predicting which patients will benefit from ET. Additionally, Mammaprint® provides risk stratification which can aid in determining which patients could benefit from neoadjuvant therapy. Methods This is an observational analysis of 60 patients with stage I-IV BC. Tissue analysis for ER, PR and HER2 status were determined by IHC/FISH. mRNA expression profiles of 80 genes for Blueprint® (Agendia) analysis provided molecular subtyping: luminal, basal or her2. Moreover, Mammaprint® (Agendia) analysis of 70 genes subdivided patients into low risk or high risk providing further stratification for Luminal-type. Results By IHC staining, 48% of patients were ER+/HER2-, 10% were ER+/HER2+, 8.3% were ER-/HER2+, and the remaining patients (20%) were triple negative (TN) BC. By comparison, molecular profiling classified 21% as luminal A, 18% luminal B, 11.6% Her2 and 35% basal subtype. The 35 ER+ patients were heterogeneous by subtype: 13 were classified as molecular luminal A, 16 were luminal B, 4 were reclassified as HER2 and 2 were basal-like (one of whom had 40% ER positivity). Of the ER+ patients whose IHC quantitative staining was known, 29% with low positivity (less than 10%) were reclassified as basal subtype. Of the 5 patients who are ER+/HER2+, 2 were luminal B and 3 were of the HER2-subtype. Two patients who were TN were reclassified as luminal B, and an ER-/HER2+ was classified as a basal subtype. One patient with ER+/HER2- disease had evidence of both HER2 and luminal B subtype. Of the patients who received neo-adjuvant therapy, pCR was obtained in 33% of luminal, 60% of HER2 and 50% of basal-type patients. Conclusions BluePrint® and Mammaprint® Molecular profiling are useful diagnostic tools which further characterize tumors to predict risk of recurrence and response to treatment. About one third of ER+ patients with low positivity (less than 10%) were reclassified as basal subtype, suggesting that there is a proportion of patients who are exposed to the morbidity of hormonal therapy with little therapeutic benefit. Additionally, the test is predictive of pCR, with the highest rates in the basal and Her2 subtypes, thus enabling clinicians to predict and improve clinical outcomes through more personalized treatment decisions. Citation Format: Mikkilineni L, Austin LK, Limentani K, Jaslow RJ, Avery TP, Palazzo J, Cristofanilli M. Improving personalized management of primary breast cancer: Mammaprint® risk stratification and blueprint® molecular subtyping. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-05-07.

Background. Cancer Stem Cells (CSC) have the ability to self-renew and generate the full range of cells that make up a bulk tumor. Experimental models and retrospective clinical observations point to CSC as responsible for tumor recurrence and metastasis. An ideal CSC targeting agent should be a non toxic molecule that can be safely administered also in combination with chemotherapy to improve disease control. CXCR1, one of the receptors for CXCL8, has been identified on breast cancer CSC. Reparixin, an allosteric inhibitor of CXCR1, reduced CSC in breast cancer (BC) xenografts (Ginestier C et al., JCI 2010) both as single agent and in combination with taxane chemotherapy. Methods. Patients were female aged ≥ 18 years with HER-2 negative metastatic BC, non taxane-refractory, who had received up to 3 prior chemotherapy (CT) lines for advanced BC (not including neo/adjuvant CT), had measurable disease according to RECIST 1.1, ECOG PS of 0-1, adequate organ function, and no brain metastases. Patients received a 3-day run-in with reparixin oral tablets 3 times daily (tid) followed by paclitaxel 80 mg/m2 (days 1, 8, and 15 for 28-day cycle) + reparixin oral tablets tid for 21 days. Three dose levels of 3-6 subjects were explored: 400 mg, 800 mg and 1200 mg oral reparixin tid. The highest safe dose level was expanded twice to gain additional safety and activity data. Treatment continued until disease progression, unacceptable toxicity or withdrawal of consent. Primary endpoints were safety and tolerability, and pharmacokinetic (PK) profile of the combination treatment. Among secondary endpoints, assessment of disease response every 2 cycles for indication of efficacy and correlative evaluations on peripheral blood samples were conducted. First analysis (i.e., 60 days post last patient in, LPI) of the results from this trial was reported earlier (Schott AF et al., SABC 2014). Results. Herein we report data at 6 months post LPI. From 02/2012 to 04/2014, 33 patients entered the study (4 in cohort 1, 3 in cohort 2 and 26 in cohort 3). 30 patients were evaluable for safety. Neither grade 4 adverse events (AE) nor Serious AE related to reparixin were reported. 9/23 patients at the highest dose level reported Grade 3 AE among which granulocytopenia (3 patients) and peripheral neuropathy (2 patients) that are commonly seen with paclitaxel alone. Overall, 8 confirmed responses (2 CR, 6 PR) were observed among 26 patients who underwent at least 1 tumor assessment (every 8 weeks). Response duration (days) was 645+, 466+ (for CR) and 280+, 169, 141, 113, 113+, 47 (for PR). Two additional patients experienced SD > 6 months (318 and 288 days, respectively). Of responding patients, all but one was from cohort 3. Median TTP (days) in the safety population was 58, 67 and 170 in cohorts 1, 2 and 3, respectively. Conclusions. Combination treatment demonstrated good tolerability with low incidence and severity of adverse reactions. The recommended dose of reparixin for the combination was established at 1200 mg tid. A sizeable response rate and mTTP was recorded, with some interesting long term responders. A randomized phase II study of the combination versus single agent weekly paclitaxel in frontline treatment of patients with metastatic triple-negative BC is ongoing (NCT02370238). Citation Format: Anne F. Schott, Max S. Wicha, Raymond P. Perez, Giraldo Kato, Tiffany Avery, Massimo Cristofanilli, James M. Reuben, R. Katherine Alpaugh, Pier Adelchi Ruffini, Susan Mccanna, Lori J. Goldstein. A phase Ib study of the CXCR1/2 inhibitor Reparixin in combination with weekly paclitaxel in metastatic HER2 negative breast cancer - final analysis. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C22.

Background MBC is an incurable disease characterized by genomic abnormalities including somatic mutations, amplifications and gene rearrangements. It is believed that treatment resistance and disease progression is related to genomic instability making “molecular monitoring” and consequent therapeutic management a dynamic and potentially more effective approach. The detection of circulating DNA fragments with tumor-specific sequence alterations (ctDNA) found in the blood of patients is the ideal diagnostic tool for non-invasive molecular monitoring. Methods This is a retrospective evaluation of 75 patients with advanced or MBC who both completed primary therapy and were NED (stage 1-3), or failed standard therapies and had baseline plasma analyzed for ctDN before starting new therapy (stage 4). For patients with progression, selection criteria included: progression of disease after standard therapies, need to detect novel molecular abnormalities for possible therapeutic targeting, or confirmation of persistence of genomic abnormalities already demonstrated in tissue or blood analysis. Guardant360™(Guardant Health) involves ctDNA isolation from plasma using a Qiagen circulating nucleic acid kit, then a panel of 54 gene mutations associated with solid tumors as reported in the COSMIC database sequenced using single-molecule digital sequencing technology. Results Most of the patients have metastatic disease (95%), but four patients had stage III disease and are now NED after neo-adjuvant therapy and surgery. According to subtype, 41% ER+/HER2-, 17% ER+/HER2+, 11% ER-/HER2+, and 31% TNBC. ctDNA was detected in 84% (63) of all patients; however, only 20% of patients who are now NED had ctDNA detected. Of patients with detected mutations, 52% had an actionable mutation that was incorporated into treatment planning. The most common mutations were TP53 (65%), PIK3CA (38%), ALK (21%) and NOTCH1 (17%). One patient with ER+/HER2- disease had ctDNA drawn at progression demonstrating a PIK3CA mutation, started on clinical trial with Letrozole/Palbociclib with clinical response and no ctDNA detected on two serial draws. Another patient with ER+/HER2- disease with 11 alterations noted in her blood, including PIK3CA and ATM, was started on targeted therapy with Trastuzumab based on HER2+ CTCs with clinical response but upon progression, ctDNA showed a dramatic increase in the resistant ATM clone, increasing from 1.1% to 27.8%. Conclusions ctDNA can be detected in the majority of patients with MBC irrespective of disease subtype. Actionable mutations can be identified and used for selection of targeted therapies. Longitudinal monitoring can accurately predict treatment response but also detect the onset of new mutations likely related to resistant clones. The real-time molecular monitoring and therapeutic implications hold the promise to significantly change our approach to the management of MBC with survival benefit. Citation Format: Laura K. Austin, Rebecca Jaslow, Tiffany Avery, Paolo Fortina, Dragan Sebisanovic, LaiMun Siew, Aubrey Zapanta, AmirAli Talasaz, Massimo Cristofanilli. Clinical utility of circulating tumor DNA (ctDNA) in advanced and metastatic breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4928. doi:10.1158/1538-7445.AM2015-4928

Background MBC is an incurable disease with complex molecular features including somatic mutations that evolve in relation to genomic instability and selective treatment pressure. Patients with treatment-refractory MBC may benefit from tissue genomic evaluation using next-genomic sequencing (NGS). Furthermore, circulating DNA fragments with tumor-specific sequence alterations (ctDNA) found in the blood of patients with advanced disease offer the possibility of non-invasive molecular monitoring. ctDNA detects actionable mutations with the advantage of serial evaluation and allowing capture of inter- and intra-tumor heterogeneity. Methods This is a retrospective evaluation of 28 patients with MBC who failed standard therapies and had baseline plasma analyzed for ctDNA and tissue analysis (NGS) before starting new therapy. We were interested in the performance of the ctDNA test and the concordance rate of genomic alterations detected in the two tests. Selection criteria: progression of disease after standard therapies, need to detect novel molecular abnormalities for possible therapeutic targeting, or confirmation of persistence of genomic abnormalities already demonstrated in tissue or blood analysis. Guardant360™(Guardant Health) involves comprehensive sequencing of a panel of 54 gene associated with solid tumors using single-molecule digital sequencing technology. FoundationOne®(Foundation Medicine) performed the NGS on tissue evaluates the entire coding sequence of 315 cancer-related genes. Results All patients had biopsy-proved metastatic disease, and had ctDNA and NGS performed. 93% of patients had ctDNA alterations detected (with 0.1%-27.8% circulating tumor fraction), and 9 patients had serial ctDNA. Overall, for the patients we detected mutations in ctDNA and tissue, 89% of patients had a specific alteration on ctDNA that matched the NGS analysis. Among all mutations detected in tumors which are in overlapped genes, 71% of alterations were common (83% excluding gene amplifications). Interestingly, for patients who had both tests done within 8 weeks, 70% of had additional alterations in the ctDNA that were not found on NGS, such as ERBB2 mutations. Conclusions Genomic analysis using ctDNA and NGS detects genomic abnormalities in all patients with MBC with high concordance. However, each method was able to detect alterations that the other did not, suggesting the two methods can be complementary in detecting actionable mutations and expanding therapeutic options. Intriguingly, this occurred more frequently with the ctDNA, demonstrating its utility as an adjunct to tissue sampling which permits capture of the inter- and intra-tumor heterogeneity of the disease, and warrants further investigation prospectively. Citation Format: Laura K. Austin, Tiffany Avery, Rebecca Jaslow, Paolo Fortina, Dragan Sebisanovic, LaiMun Siew, Aubrey Zapanta, AmirAli Talasaz, Massimo Cristofanilli. Concordance of circulating tumor DNA (ctDNA) and next-generation sequencing (NGS) as molecular monitoring tools in metastatic breast cancer (MBC). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4918. doi:10.1158/1538-7445.AM2015-4918

Background Inflammatory Breast Cancer (IBC) is a clinicopathologic entity characterized by rapid progression and poor prognosis, even with the advent of targeted therapies and a multimodal approach. Gene expression profiles of IBC tumors vs. non-IBC demonstrated that HER2+ IBC have increased mTOR signaling compared to non-IBC (Iwamoto et al). mTOR activation is a mechanism for both HER-2 targeted and endocrine resistance. Combining the molecular diagnostics of next-generation sequencing (NGS) and reverse-phase protein microarray (RPMA) may identify additional therapeutic targets as well as mechanisms of resistance to targeted therapy. Methods This is an observational analysis of 12 IBC patients who had tissue biopsy after progression on standard therapies. All patients had tissue analysis by NGS and RPMA. NGS was performed by either FoundationOne™ or our in-house hot spot panel of 45 genes. RPMA was performed using TheraLink™ to identify expression of cancer-related phosphoproteins; it quantifies HER1, HER2, and HER3 receptor overexpression, and evaluates for phosphorylation of the receptor which indicates activation. Phosphorylation of HER downstream signaling pathways such as JAK2, AKT/mTOR and MEK1/2 are also detected. Subset of 7 patients had AR, MET, ALK and PDL1 expression evaluation. Results All patients had IBC and 75% had metastatic disease. 17% of patients were ER+/HER2-, 42% ER+/HER2+, 25% ER-/HER2+, and 17% TNBC. All HER2+ patients by IHC had activation of HER2 on RPMA, and 75% of those patients had confirmed ERBB2 amplification on NGS. 75% of patients had mTOR activation on RPMA, 78% of whom had a concomitant alteration in the PIK3CA pathway on NGS. 71% of the patients evaluated had ALK expression and 80% of those patients had concomitant mTOR activation. Also, both TNBCs had HER2 activation by RPMA. HER2 targeted therapy was continued on 2 patients after RPMA confirmed activation of HER2. 4 patients were initiated on combinations with an mTOR inhibitor, Everolimus (Afinitor®), and one of whom initially obtained a clinical response, upon progression had repeat RPMA demonstrating only persistent mild activation of mTOR with a decrease in downstream proteins. Another patient with TNBC IBC who underwent 3 lines of neoadjuvant therapy prior to surgery was found to have HER1, HER2, HER3 and mTOR activation; she was started on adjuvant lapatinib and capecitabine and remains with no recurrent disease. Conclusions Patients with IBC often have activation of members of the HER family and mTOR pathway indicating molecular targets and potential mechanisms of resistance in IBC. The concomitant use of NGS and RPMA is an intriguing approach to molecular diagnostics as they provide complimentary data on molecular pathways activation which expands therapeutic options, predicts treatment-sensitivity and selects more effective combinations. Citation Format: Laura K. Austin, Keithe Shensky, Juan Palazzo, Tiffany Avery, Rebecca Jaslow, Corrine Ramos, Nicholas Hoke, Emanuel Petricoin, Massimo Cristofanilli. Identifying molecular targets and mechanisms of treatment resistance in inflammatory breast cancer (IBC) using next-generation sequencing (NGS) and reverse-phase protein microarrays (RPMA). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4847. doi:10.1158/1538-7445.AM2015-4847

Inflammatory breast cancer (IBC) is an extremely aggressive form of locally advanced breast cancer that affects about 5% of breast cancer patients. The prognosis of IBC patients is remarkably poor, with a three-year survival rate of approximately 30% compared to 60% for patients with non-IBC breast cancers. These facts highlight the importance of accurate characterization, early detection, and timely treatment of IBC patients. Thus, it is important to develop novel and clinically applicable non-invasive biomarkers to characterize the unique presentation of IBC. In this study, we searched for somatic mutations in the circulating tumor DNAs (ctDNAs) that could be used to non-invasively characterize IBC patients and inform their clinical management. Using ctDNAs extracted from plasma of 10 pairs of IBC and non-IBC patients that were matched on major demographic and clinical variables, we conducted a high-depth target next-generation sequencing study that interrogated a comprehensive panel of 127 TCGA (The Cancer Genome Atlas)-reported cancer-related genes with >7000 uniquely designed and validated probes. Overall, we obtained >500x coverage in >80% of the interrogated regions, and >100x coverage in >97% of the regions. We found that C>T mutations predominated in well-reported mutated genes such as TP53, PIK3CA, EGFR, and CDH1. Compared to non-IBC patients, IBC patients appeared to have a higher percentage of mutations in PIK3CA but a lower percentage in TP53. Interestingly, about 78% of mutated genes that were only detected in IBC patients encode zinc finger-related proteins, a family of transcriptional factors that have been implicated in IBC development. In comparison, about 43% of genes that were detected only in non-IBC patients encode proteins important to cell division regulation. Furthermore, network-based stratification (NBS) analysis of the mutation profile revealed clusters of IBC relative to non-IBC samples, indicating the potential of mutation profiling in identifying molecularly distinct subtypes of IBC patients. Preliminary longitudinal analysis of ctDNAs from three patients with multiple plasma samples indicated that de novo mutations in important genes including PIK3CA, RB1, and KRAS appeared in patient blood after chemotherapy and/or targeted therapy treatments. Moreover, the emergence of some of these mutations was temporally correlated with the responses of patients to the treatments they received. Overall, this study provides novel evidence that ctDNA mutation status may help to non-invasively characterize IBC tumors, and might also serve as a novel non-invasive marker to monitor treatment efficacy and prognosis of breast cancer patients. Future studies with larger sample sizes are warranted to confirm our findings and identify additional clinically useful markers for the characterization and management of IBC and non-IBC patients. Citation Format: Hushan Yang, Xue Zhong, Qiang Wei, Zhaomei Mu, Zhong Ye, Yinzhi Lai, Huei-Wen Lin, Rebecca Jaslow, Tiffany Avery, Laura Austin, Zhaohui Sun, Shengrong Lin, Grace Zhao, Ling Fang Tang, Ronald E. Myers, Juan P. Palazzo, Laura Biederman, Bingshan Li, Massimo Cristofanilli. Comprehensive high-depth target sequencing in circulating tumor DNAs of patients with inflammatory and non-inflammation breast cancers. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2788. doi:10.1158/1538-7445.AM2015-2788

Background. Experimental models and retrospective clinical observations point to cancer stem cells (CSCs) as the culprits for tumor recurrence and metastasis. CSCs account for a small proportion of tumor cells, suggesting that their elimination through pharmacological targeting would not necessarily translate in any sizeable tumor regression. Thus, an ideal CSCs targeting agent should be a nontoxic molecule that can be safely administered in combination with chemotherapy to reduce tumor burden and improve disease control. CXCR1, one of the receptors for CXCL8, has been identified on breast cancer (BC) CSCs (Ginestier C et al., JCI 2010). Reparixin, an allosteric inhibitor of CXCR1 with a large safety database in non-cancer patients, effectively targeted CSC in BC xenografts (Ginestier C et al., JCI 2010). Methods. Patients were female aged > 18 years with HER-2 neg metastatic breast cancer (MBC), eligible for treatment with paclitaxel (not taxane-refractory), had received up to 3 prior CT lines for advanced BC (not including neo/adjuvant chemotherapy), had measurable disease according to RECIST 1.1, had ECOG PS of 0-1, had adequate organ function, and had no brain metastases. Patients received a 3-day run-in with reparixin oral tablets 3 times daily (tid) followed by paclitaxel 80 mg/m2/week (Days 1, 8, and 15 for 28-day cycle) + reparixin oral tablets tid for 21 days. Three dose levels of 3-6 subjects were explored: 400 mg, 800 mg and 1200 mg oral reparixin tid. A further 17 subjects were enrolled at the highest tolerated dose (total 20 patients). Safety was assessed following one cycle. Treatment continued until disease progression, unacceptable toxicity or withdrawal of consent. Primary endpoints were safety and tolerability, and pharmacokinetic (PK) profile of the combination treatment. Among secondary endpoints, assessment of disease response every 2 cycles for indication of efficacy and correlative evaluations on peripheral blood samples were conducted. Results. From 02/12 to 04/14, 33 patients entered the study. PK of reparixin at 400 mg tid, tmax = 0.5-1.5 hr, t1/2= 1.7 hr; at 800 mg tid, tmax = 0.5-3 hr, t1/2= 4.6 hr; at 1200 mg tid, tmax = 0.5-2 hr, t1/2 = 1.6 h. Co-administration of reparixin on days 1 and 8 had no effect on paclitaxel kinetics. Fifteen SAEs were recorded, none of which was related to Reparixin. Grade 3-4 adverse reactions were recorded in 30% (10/33) patients including haematological toxicity (5/10). Only one patient discontinued treatment for a reversible GI adverse reaction due to reparixin at the 1200 mg dose level. To date, 5 confirmed responses (2 CR, 3 PR) were recorded among 18 patients who underwent at least 1 tumor assessment (at 8 weeks). Response duration was 20m+ and 3m+(for CR) and 9m+, 6m+, 2m+ (for PR). Final data will be presented at the meeting. Conclusions. Combination treatment was safe and well tolerated at all dose levels without evidence of pharmacologic interactions and the recommended dose for subsequent studies is 1200 mg tid. Efficacy was demonstrated both in hormone receptor positive and triple receptor negative disease. A randomized phase II study of the combination versus single agent weekly paclitaxel in patients with MBC is warranted. Citation Format: Anne F Schott, Max S Wicha, Raymond P Perez, Giraldo Kato, Tiffany Avery, Massimo Cristofanilli, James M Reuben, R Katherine Alpaugh, Susan McCanna, Pier Adelchi Ruffini, Lori J Goldstein. A phase Ib study of the CXCR1/2 inhibitor reparixin in combination with weekly paclitaxel in metastatic HER2 negative breast cancer – First analysis [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 P6-03-01.

acid (C22:6!3, DHA), play multifunctional roles in human health and diseases. The traditional source of these fatty acids is fish. Since fish stocks are in global decline, new sources of omega-3 LC-PUFA have to be found. The aim of the present study was to find potential alternative sources of these fatty acids in the territory of The Republic of Kazakhstan. Twelve strains of filamentous fungi isolated from soil and water were screened for lipids and LCPUFA: Penicillium sp., Penicillium restrictum, Penicillium aculeatum, Penicillium anatolicum, Penicillium bilaiae, Penicillium commune, Penicillium raistrikii, Penicillium crustosum, Fusarium sp. (2 strains), Aspergillus sp. and Mucor circinelloides. These fungi were grown in Sabouraud medium for 10 days. Lipid contents of these strains ranged from 1.5% to 7.4% of dry weight. No LC-PUFA were found in P. commune, P. crustosum, Aspergillus sp., M. circinelloides, whereas other strains contained EPA ranging from 1.0% to 3.5% of the total fatty acids, P. restrictum accumulated the largest amount. The cultural conditions that can increase the production of EPA in P. restrictum (e.g. the addition of glucose, glycerin and zinc) are currently under investigation.

595 Background: Breast Cancer among young women is on the rise. It is estimated there will be up to 13,000 new cases this year in this age group. There are no screening guidelines in place for wome...

e11503 Background: The main goal in treating DCIS remains the prevention of ipsilateral recurrence and contralateral tumors. Known risk factors for recurrence include multifocal disease, tumor size, nuclear grade, presence of comedo necrosis, hormone receptor (HR) and HER-2 status and young age. Despite the similar distribution of molecular characteristics and treatments among ethnic groups, previous research reported that African Americans (AA) have worse outcomes. Methods: We identified 446 patients with DCIS (395) or microinvasive carcinoma (51), treated between 2008 and 2013, in the Thomas Jefferson University Tumor Registry. Associations between recurrence and demographic factors, histology, and treatment were assessed. Student’s t-test was used to compare age between recurrent and non-recurrent patients, Pearson’s Chi-squared test to test associations between recurrence variables with more than two categories, and Fisher’s Exact test for testing associations between recurrence and two-level categori...

e17517 Background: Developing countries contribute substantially to breast cancer mortality worldwide, as early-stage diagnosis and effective adjuvant therapies have decreased breast cancer-specifi...

e22027 Background: Circulating Tumor Cells (CTCs) are an independent prognostic indicator of progression free survival (PFS) and overall survival (OS) in metastatic breast cancer (MBC), and are use...

e11506 Background: Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer and is usually misdiagnosed or not recognized in clinical practice. Since the disease is relatively ...

TPS1135 Background: Inhibition of poly (ADP-ribose) polymerase (Parp) is a potential targeted therapy for triple-negative breast cancer (TNBC). Clinical trials of Parp inhibitors in metastatic TNBC have shown conflicting results. Issues regarding the use of Parp inhibitors in TNBC include choosing a selective Parp inhibitor and selecting an appropriate chemotherapy backbone. The current trial addresses these questions by combining a validated Parp inhbitor, ABT-888, with carboplatin and paclitaxel. Platinum agents have shown synergy with Parp inhibitors in preclinical models and efficacy in clinical trials. The combination of paclitaxel and carboplatin with Parp inhibitors has shown efficacy in phase I trials. Methods: This is a phase II, two-arm neoadjuvant trial of women with TNBC. Eighty patients will be enrolled. Randomization will follow a 1:1 allocation initially, then will follow a Bayesian adaptive allocation in which each prior response will be evaluated and patients assigned preferentially to the better responding arm. The primary endpoint is pathologic complete response (pCR). Secondary endpoints include correlation of pCR with biomarkers, imaging, and circulating tumor cells (CTCs). Treatment: Arm 1: Paclitaxel 80 mg/m2 + carboplatin AUC=2 (12 weekly cycles) + filgrastim followed by doxorubicin 60 mg/m2 + cyclophosphamide 600 mg/m2 (4 cycles every 3 weeks) + pegfilgrastim. Arm 2: ABT-888 (150mg PO bid) + paclitaxel 80 mg/ m2 + carboplatin AUC=2 (12 weekly cycles) + (filgrastim) followed by doxorubicin 60 mg/m2 + cyclophosphamide 600 mg/m2 (4 cycles every 3 weeks) + (pegfilgrastim). Eligibility: Women ≥ 18 years old with clinical stage IIB or stage IIIA, IIIB, or IIIC untreated TNBC (ER

Abstract 2017 Background: Multiple myeloma (MM) remains an incurable disease and is the most common hematologic malignancy among African-Americans. In the United States, MM and its precursor monoclonal gammopathy of undetermined significance (MGUS) are twice as common in African Americans (Hari et al 2010). Analysis of the Surveillance Epidemiology and End Results (SEER) database from 1969 to 2003 demonstrated African-Americans have twice the mortality from MM compared to Caucasians. However this may be a function of the considerable difference in incidence of MM between Caucasian and African-American populations. Retrospective data from Southwest Oncology Group showed comparable outcomes between groups before the advent of autologous stem cell transplantation (auto-HCT). Recently Hari et al. determined that African-American and Caucasians have similar outcomes after auto-HCT for MM. In the age of novel therapy, Waxman et al addressed racial disparity in population based query of SEER and found disease specific survival was greater for African-Americans than Caucasians; and over time, survival improvement was much less pronounced among African-Americans than Caucasians. Nevertheless transplant specific data is sparse in the contemporary era with novel treatment options. Methods: We performed a retrospective review of 196 African-American multiple myeloma patients (pts) and 806 Caucasian patients initially seen at the M.D. Anderson Cancer Center from 1/1/2002 to 12/31/2010 who underwent autologous transplantation after high dose chemotherapy. The year 2002 was used to incorporate patients who had been exposed to novel agents. Results: A total of 1002 patients were analyzed, 196 African American and 806 Caucasian pts with multiple myeloma who underwent an autologous transplant. Median age at diagnosis was 59 years for both cohorts. Initial response prior to transplant was fairly evenly matched between groups (TABLE 1) as well as final response after transplant. 25% of Caucasian pts and 21% of African-American pts achieved a very good partial response (VGPR) while 28% of Caucasian and 21% of African-American pts achieved a complete response (CR). For evaluable patients, the International Staging System (ISS) at diagnosis was determined. The percentage of stage I, II and III patients in the African-American group was 27%, 20% and 17% respectively. The percentage of stage I, II and III patients in the Caucasian group was 26%, 19% and 17% respectively. Importantly 133/806 of Caucasians and 33/196 of African Americans were diagnosed at ISS stage III (p value=0.91). There was no measurable difference in progression free survival (figure 1) or overall survival (figure 1figure 2) with a maximum follow-up of >100 months. Conclusion: In this retrospective single-center study we demonstrated no difference in progression free survival or overall survival between African-American and Caucasian patients with MM treated in the era of novel agents and autologous stem cell transplantation. These findings concur with previous studies showing no difference in response to treatment between racial groups. In light of older SEER data this may be an effect of novel agents, improved access of care for African Americans or a combination of both. Disclosures: No relevant conflicts of interest to declare.

1590 Background: Incidence of breast cancer is lower in African-American women than White women, but African-American women have worse survival and represent a greater proportion of young women. Ob...

Background: The incidence of breast cancer is lower among African-American women than White women; however, African-American women have worse survival, represent a greater proportion of young women with breast cancer, and tend to have more aggressive tumors at diagnosis. A number of social factors contribute to the disparities; however, biologic differences are being explored. Obesity is a risk factor that has a significant effect in breast cancer disparities. Two cytokines produced by adipose tissue, leptin and adiponectin, have been shown to be active in breast cancer cell lines in vitro and to correlate with breast cancer risk and tumor characteristics in epidemiologic studies. Leptin has mitogenic effects on breast cancer cells in vitro and increases with obesity. Adiponectin has inhibitory effects on cancer growth and decreases with obesity. Data from studies of cardiovascular disease and metabolic syndrome suggest that levels of adipocytokines may differ by race, adjusted for body mass index (BMI). We measured levels of leptin and adiponectin in African-American and White women with breast cancer to test our hypothesis that serum levels differ by race. We hypothesized that African-American women would have higher levels of leptin and lower levels of adiponectin, adjusted for BMI. We also correlated tumor characteristics, including grade, age, stage, ER/PR and Her-2/neu status with levels of these adipocytokines to test the hypothesis that more aggressive tumor features would correlate with higher levels of leptin and lower levels of adiponectin. Methods: We performed a retrospective case-case study of 68 African-American and 59 White breast cancer patients. Adiponectin and leptin levels were measured in serum samples by enzyme-linked immunosorbent assay (ELISA). Medical records were abstracted for BMI, age, stage, tumor grade, ER/PR, and Her-2 neu status. Differences in leptin and adiponectin levels between races were assessed using the Kruskal-Wallis test. Linear regression was used to detect differences in levels after adjusting for BMI. Results: Mean levels of leptin and adiponectin were significantly higher in African-American women, compared to White women. Mean leptin levels were 57.8 ng/ml and 30.1 ng/ml in African-American and White women, respectively (p Conclusions: Our findings suggest that adipocytokine levels may differ by race in women with breast cancer, adjusted for BMI. There may also be a positive correlation between adipocytokine levels and higher tumor grade in women with breast cancer. Our study population was small, and we will validate the results in a larger sample size. If the results are demonstrated in further studies, differences in adipocytokine levels may prove to be a biologic cause of some of the observed racial disparities in women with breast cancer. Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):B74.

Background Multiple myeloma (MM) accounts for approximately 10% of hematologic malignancies diagnosed annually in the United States. It is well documented that the African American population is disproportionately affected by MM in incidence and mortality. Survival data from the SEER database from 2001-2005 demonstrated higher mortality in African American patients compared to Caucasian patients. However, more recent retrospective reviews in the era of autologous stem cell transplantation (ASCT) did not support this finding. Thus the persistence of racial survival disparities in the era of ASCT and novel therapeutic agents is an evolving question. Patients and Methods We performed a retrospective review of 170 African American MM patients and 170 age-matched and gender-matched Caucasian patients initially seen at the M. D. Anderson Cancer Center from 1/1/2002 to 12/31/2008. Results Three hundred forty previously untreated patients were analyzed. Median age at diagnosis was 57 years for both groups. For evaluable patients, the International Staging System at diagnosis was determined. The percentage of stage I, II, and III patients in the African American group was 53%, 28%, and 19%, respectively. The percentage of stage I, II, and III patients in the Caucasian group was 40%, 30%, and 29%, respectively. These staging data were not significantly different between racial groups. In both groups, 89% of patients received a novel therapeutic agent (thalidomide, lenalidomide, or bortezomib) during their treatment course. We found a statistically significant difference in the percentage of African American and Caucasian patients who received high-dose chemotherapy and ASCT (65% and 76%, respectively; P = .04). There was no difference observed in the number of second transplantations performed in the two groups (19 in both groups). Response to therapy is detailed in Table 1 . There was no difference in overall response to any therapy of evaluable patients between the two groups. With a median follow-up time of 35 months, the median overall survival from diagnosis has not been reached in either group. Kaplan-Meir analysis shows that there is no difference in overall survival between African American and Caucasian patients (P = .1) Conclusion In this single-center, retrospective study of MM patients treated predominately with novel agents, with or without ASCT, no survival difference was observed between African American and Caucasian patients. To our knowledge, this is the largest number of African American myeloma patients analyzed for survival in a single-center study. Recognizing the potential disparities in healthcare access, this may not represent outcomes for all African American patients with myeloma. Since median overall survival has not been reached in this data, it is possible that survival differences will become apparent in the future, and further follow-up is needed. However, this review suggests that in the era of novel therapeutics and ASCT resulting in improved overall response rates, survival in African American patients may be equivalent to Caucasian patients. Further efforts are needed to enroll African American patients on clinical trials to validate this observation prospectively. Abstract 6 - Table 1 . Best Response to Any Therapy Race CR VGPR PR ORR African American 56/154 (36%) 15/154 (10%) 76/154 (49%) 147/154 (95%) Caucasian 57/162 (35%) 32/162 (20%) 64/162 (40%) 153/162 (94%)

Abstract 1395 Poster Board I-417 Background: Multiple myeloma accounts for approximately 10% of hematologic malignancies diagnosed annually in the U.S. It is well documented that the African-American population is disproportionately affected by multiple myeloma in incidence and mortality. Survival data from the SEER database from 2001-2005 demonstrated higher mortality in African-American patients compared to Caucasian patients. However, more recent retrospective reviews in the era of autologous stem cell transplant (ASCT) did not support this finding. Thus the persistence of racial survival disparities in the era of ASCT and novel therapeutics is an evolving question. Methods: We performed a retrospective review of 170 African-American multiple myeloma patients and 170 age and gender-matched Caucasian patients initially seen at the M.D. Anderson Cancer Center from 1/1/2002 to 12/31/2008. Results: Three hundred forty previously untreated patients were analyzed. Median age at diagnosis was 57 years for both groups. For evaluable patients, the International Staging System at diagnosis was determined. The percentage of stage I, II and III patients in the African-American group was 53%, 28% and 19% respectively. The percentage of stage I, II and III patients in the Caucasian group was 40%, 30% and 29% respectively. These staging data were not significantly different between racial groups. In both groups, 89% of patients received a novel therapeutic (thalidomide, lenalidomide or bortezomib) during their treatment course. We found a statistically significant difference in the percentage of African-American and Caucasian patients who received high dose chemotherapy and ASCT (65% and 76%, respectively, p=0.04). There was no difference observed in the number of second transplants performed in the two groups (19 in both groups). Response to therapy is detailed in Table 1. There was no difference in overall response to any therapy of evaluable patients between the two groups. With a median follow-up time of 35 months, the median overall survival from diagnosis has not been reached in either group. Kaplan-Meir analysis shows that there is no difference in overall survival between black and white patients (p =0.1) Conclusions: In this single-center, retrospective study of multiple myeloma patients treated predominately with novel agents, with or without ASCT, no survival difference was observed between African-American and Caucasian patients. To our knowledge, this is the largest number of African-American myeloma patients analyzed for survival in a single-center study. Recognizing the potential disparities in healthcare access, this may not represent outcomes for all African-American patients with myeloma. Since median overall survival has not been reached in this data, it is possible that survival differences will become apparent in the future, and further follow-up is needed. However, this review suggests that in the era of novel therapeutics and ASCT resulting in improved overall response rates, survival in African-American patients may be equivalent to Caucasian patients. Further efforts are needed to enroll African-American patients on clinical trials to validate this observation prospectively. Disclosures: No relevant conflicts of interest to declare.