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Background: PARP inhibitors are currently approved for the treatment of germline BRCA1/2 mutant metastatic breast cancer (MBC), which accounts for 5-10% of breast cancer. We hypothesize that a PARP inhibitor may also have efficacy in somatic BRCA1/2 mutant MBC, expanding the potential clinical applicability of PARP inhibitors. We previously demonstrated that somatic BRCA1/2 mutations can be identified by both cell-free DNA and tumor tissue genotyping in a subset of patients with MBC who are not germline BRCA1/2 carriers. Furthermore, a PARP inhibitor was demonstrated to induce cell growth inhibition in a circulating tumor cell culture model generated from a patient with pathogenic somatic BRCA1 mutant MBC (Vidula, Dubash, CCR, 2020). In this trial, we are evaluating the efficacy of a PARP inhibitor in somatic BRCA1/2 mutant MBC. Trial Design: This phase II investigator-initiated clinical trial is enrolling 30 patients with somatic BRCA1/2 mutant MBC identified via cell-free DNA or tumor tissue genotyping. Patients are treated with talazoparib, a PARP inhibitor, until disease progression. At baseline and every 3 months, patients undergo CT chest, abdomen, and pelvis, and a bone scan for disease assessment. Patients undergo blood collection at baseline for the Cancer Risk B (CR-B) assay, a novel flow variant assay to assess double-strand break repair mutations in circulating blood cells (Syeda, 2017) and monthly blood collection for cell-free DNA analysis to evaluate changes in the genomic environment. Eligibility Criteria: Patients with MBC with a pathogenic somatic BRCA1/2 mutation identified by cell-free DNA or tumor tissue genotyping are eligible. Both patients with triple-negative breast cancer (≥ 1 prior chemotherapy) or hormone receptor positive/HER2- MBC (≥ 1 prior hormone therapy) are eligible. Patients should not be known germline BRCA1/2 carriers. There is no limit on prior therapies including receipt of a prior platinum (in the absence of disease progression on prior platinum). A prior PARP inhibitor is not allowed. Adequate performance status and organ function are needed. Specific Aims: Primary aim is progression-free survival (PFS) assessed by RECIST 1.1. Secondary aims include objective response rate and toxicity assessed by NCI CTCAE v 5.0. Exploratory aims include assessing impact of BRCA1/2 reversion mutations in cell-free DNA, studying serial changes in BRCA1/2 mutant allelic frequency in cell-free DNA, comparing pre- and post-treatment cell-free DNA results to identify changes in the genomic environment, assessing the CR-B assay positivity rate, and correlating these biomarker analyses with patient response. Statistical Methods: This study uses a two-stage design with 80% power to demonstrate that talazoparib is associated with “success” (PFS > 12 weeks) in 53% patients (4% alpha). Accrual: This study (NCT03990896) is open at Massachusetts General Hospital, MD Anderson, University of California San Francisco, and Emory, with pending activation at Northwestern, Cornell, and Vanderbilt. Five patients are enrolled as of 7/2022. Funding: This study is supported by a Pfizer ASPIRE award and Conquer Cancer Foundation of ASCO–Breast Cancer Research Foundation- Career Development Award. Contact information: Neelima Vidula, MD, Massachusetts General Hospital, nvidula@mgh.harvard.edu Citation Format: Neelima Vidula, Senthil Damodaran, Erica L. Blouch, Nora Horick, Nathan Royce Ruffle-Deignan, Manali Bhave, Ami N. Shah, Leticia Varella, Vandana Abramson, Joseph Sparano, Leif Ellisen, Ishraq Alim, Harry Ostrer, Hope Rugo, Aditya Bardia. Phase II study of talazoparib, a PARP inhibitor, in somatic BRCA1/2 mutant metastatic breast cancer identified by cell-free DNA or tumor tissue genotyping [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-11-01.

National comprehensive cancer network guidelines recommend delivery of adjuvant chemotherapy in node-negative triple-negative breast cancer (TNBC) if the tumor is 1 cm and consideration of adjuvant chemotherapy for T1b but not T1a disease. These recommendations are based upon sparse data on the role of adjuvant chemotherapy in T1a and T1b node-negative TNBC. Our objective was to clarify the benefits of chemotherapy for patients with T1N0 TNBC, stratified by tumor size.We performed a retrospective analysis of survival outcomes of TNBC patients at two academic institutions in the United States from 1999 to 2018. Primary tumor size, histology, and nodal status were based upon surgical pathology. The Kaplan-Meier plot and 5-year unadjusted survival probability were evaluated.Among 282 T1N0 TNBC cases, the status of adjuvant chemotherapy was known for 258. Mean follow-up was 5.3 years. Adjuvant chemotherapy was delivered to 30.5% of T1a, 64.7% T1b, and 83.9% T1c (p 0.0001). On multivariable analysis, factors associated with delivery of adjuvant chemotherapy were tumor size and grade 3 disease. Improved overall survival was associated with use of chemotherapy in patients with T1c disease (93.2% vs. 75.2% p = 0.008) but not T1a (100% vs. 100% p = 0.3778) or T1b (100% vs. 95.8% p = 0.2362) disease.Our data support current guidelines indicating benefit from adjuvant chemotherapy in node-negative TNBC associated with T1c tumors but excellent outcomes were observed in the cases of T1a and T1b disease, regardless of whether adjuvant chemotherapy was delivered.

PURPOSETo update key recommendations of the American Society of Clinical Oncology/College of American Pathologists estrogen (ER) and progesterone receptor (PgR) testing in breast cancer guideline.METHODSA multidisciplinary international Expert Panel was convened to update the clinical practice guideline recommendations informed by a systematic review of the medical literature.RECOMMENDATIONSThe Expert Panel continues to recommend ER testing of invasive breast cancers by validated immunohistochemistry as the standard for predicting which patients may benefit from endocrine therapy, and no other assays are recommended for this purpose. Breast cancer samples with 1% to 100% of tumor nuclei positive should be interpreted as ER positive. However, the Expert Panel acknowledges that there are limited data on endocrine therapy benefit for cancers with 1% to 10% of cells staining ER positive. Samples with these results should be reported using a new reporting category, ER Low Positive, with a recommended comment. A sample is considered ER negative if < 1% or 0% of tumor cell nuclei are immunoreactive. Additional strategies recommended to promote optimal performance, interpretation, and reporting of cases with an initial low to no ER staining result include establishing a laboratory-specific standard operating procedure describing additional steps used by the laboratory to confirm/adjudicate results. The status of controls should be reported for cases with 0% to 10% staining. Similar principles apply to PgR testing, which is used primarily for prognostic purposes in the setting of an ER-positive cancer. Testing of ductal carcinoma in situ (DCIS) for ER is recommended to determine potential benefit of endocrine therapies to reduce risk of future breast cancer, while testing DCIS for PgR is considered optional. Additional information can be found at www.asco.org/breast-cancer-guidelines .

Purpose.—To update key recommendations of the American Society of Clinical Oncology/College of American Pathologists estrogen receptor (ER) and progesterone receptor (PgR) testing in breast cancer guideline.Methods.—A multidisciplinary international Expert Panel was convened to update the clinical practice guideline recommendations informed by a systematic review of the medical literature.Recommendations.—The Expert Panel continues to recommend ER testing of invasive breast cancers by validated immunohistochemistry as the standard for predicting which patients may benefit from endocrine therapy, and no other assays are recommended for this purpose. Breast cancer samples with 1% to 100% of tumor nuclei positive should be interpreted as ER positive. However, the Expert Panel acknowledges that there are limited data on endocrine therapy benefit for cancers with 1% to 10% of cells staining ER positive. Samples with these results should be reported using a new reporting category, ER Low Positive, with a recommended comment. A sample is considered ER negative if < 1% or 0% of tumor cell nuclei are immunoreactive. Additional strategies recommended to promote optimal performance, interpretation, and reporting of cases with an initial low to no ER staining result include establishing a laboratory-specific standard operating procedure describing additional steps used by the laboratory to confirm/adjudicate results. The status of controls should be reported for cases with 0% to 10% staining. Similar principles apply to PgR testing, which is used primarily for prognostic purposes in the setting of an ER-positive cancer. Testing of ductal carcinoma in situ (DCIS) for ER is recommended to determine potential benefit of endocrine therapies to reduce risk of future breast cancer, while testing DCIS for PgR is considered optional. Additional information can be found at www.asco.org/breast-cancer-guidelines.

Purpose: National Comprehensive Cancer Network guidelines recommend delivery of adjuvant chemotherapy in node-negative triple negative breast cancer (TNBC) if the tumor is > 1 cm and consideration of adjuvant chemotherapy for T1b but not T1a disease. These recommendations are based upon sparse data regarding the role of adjuvant chemotherapy in T1a and T1b node-negative TNBC. Our objective was to clarify the benefits of chemotherapy for patients with T1N0 TNBC, stratified by tumor size.Methods: We performed a retrospective analysis of survival outcomes in an IRB-approved prospectively-maintained database of TNBC patients treated at two academic institutions in the United States from 1999-2018. Primary tumor size, histology, and nodal status were based upon definitive surgical pathology. Mean follow-up was 5.3 years.Results: 756 TNBC cases were analyzed; 258 T1N0 TNBC patients were identified. Adjuvant chemotherapy was delivered to 30.5% of T1a, 64.7% T1b, and 83.9% T1c (p < 0.0001). Factors associated with delivery of adjuvant chemotherapy were age, histology, high-grade disease, and postoperative adjuvant radiation therapy. At a mean follow-up of 5.3 years, increase in overall survival was associated with use of chemotherapy in patients with T1c disease (93.2% v. 75.2% p = 0.008) but not in those with T1a (100% v. 100% p = 0.3778) or T1b (100% v. 95.8% p = 0.2362) disease.Conclusion: Our data support current guidelines indicating benefit from adjuvant chemotherapy in node-negative TNBC associated with T1c tumors but excellent outcomes were observed in cases of T1a and T1b disease, regardless of whether adjuvant chemotherapy was delivered.

Real-world data are critical to demonstrate the reproducibility of evidence and external generalizability of randomized clinical trials. Palbociclib is an oral small-molecule inhibitor of cyclin-dependent kinases 4 and 6 that has been shown to improve progression-free survival (PFS) when combined with letrozole or fulvestrant in phase 3 clinical trials. We evaluated real-world outcomes in metastatic breast cancer patients who received palbociclib in combination with endocrine therapy in routine clinical practice. Records of patients with advanced hormone receptor (HR)-positive breast cancer treated with palbociclib at the Cleveland Clinic health system from February, 2015 to December, 2017 were retrospectively reviewed. The primary end point was PFS. In this cohort, 411 women were included. The median age and follow-up times were 53.5 years and 10.2 months, respectively. The median PFS for palbociclib plus letrozole was 15.1 months for patients treated in first line, 10.5 months in second line, and 4.2 months in third line and beyond. For patients who received fulvestrant plus palbociclib, the median PFS in first, second, and third line and beyond were 11.6, 12.3, and 6.4 months, respectively. The most common adverse events were hematologic, with grade 3–4 neutropenia occurring in 58% of patients. Thirty-one (8%) patients permanently discontinued palbociclib due to adverse events. Among patients with HR-positive advanced breast cancer, the estimated PFS in patients treated with fulvestrant and palbociclib was comparable to a previously reported phase 3 trial. However, the median PFS with letrozole and palbociclib was shorter than previously reported data from phase 2 and 3 trials. Palbociclib toxicity was very manageable, with a low drug discontinuation rate.

Background CDK4/6 inhibitors (CDK4/6i), in combination with aromatase inhibitors, are United States Food and Drug Administration-approved for the treatment of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (MBC). The effectiveness of continuing them beyond first disease progression (PD) is currently unknown. This retrospective study evaluated the impact of the continuation of CDK4/6i beyond first PD in HR+/HER2− MBC using real-world experience. Patients and Methods A single-institution retrospective review of patients with HR+ MBC who received CDK4/6is from 2015 to 2018 and where CDK4/6is were continued beyond first PD. The primary outcome was progression-free survival (PFS) after initial PD on CDK4/6i therapy. Results Thirty women with HR+/HER2− MBC met eligibility criteria. Patients were identified from a prospective database of patients at the Cleveland Clinic Foundation who were prescribed CDK4/6is. The median age and follow-up duration were 47.5 years and 27 months, respectively. Most patients received palbociclib (PA)/letrozole as initial therapy (67%), followed by PA/fulvestrant (23%), and PA/other aromatase inhibitor (20%), and abemaciclib with either fulvestrant or letrozole (6%). As of January 31, 2019, 25 (83.3%) patients were still alive, and 19 (63%) patients had progressed. The estimated median PFS for continued CDK4/6i use beyond the first PD was 11.8 months (95% confidence interval, 5.34-13.13 months). Conclusions Among a small cohort of patients with HR+ MBC in a non-clinical trial setting, continuation of CDK4/6i-endocrine treatment post initial PD was associated with a median PFS of about 12 months. Formal randomized clinical trials evaluating the continuation of CDK4/6is beyond the first PD are currently ongoing and will provide more answers to this important clinical question.

Bevacizumab is a monoclonal antibody directed against vascular endothelial growth factor (VEGF) that interferes with VEGF binding to its receptor on vascular endothelium. Bevacizumab has been approved for the treatment of various malignant tumors, and has been studied in combination with several cytotoxic agents in the treatment of breast cancer. In 2008, the US Food and Drug Administration granted accelerated approval for the use of bevacizumab in combination with weekly paclitaxel for first-line treatment of HER2-negative metastatic breast cancer. However, this approval was later reversed in 2010 because of concerns for safety and lack of improvement in overall survival in randomized clinical trials. In this review, we summarize relevant clinical studies conducted to investigate the role of bevacizumab in the management of breast cancer, both in the early stage and in the metastatic disease settings. We also provide commentary regarding the future of this agent in breast cancer treatment.

Purpose: Hospital transfers may affect clinical outcomes. Evaluation of admission by source of transfer, time of admission, and provider type may identify opportunities to improve inpatient outcomes. Methods: We reviewed charts of patients admitted to the solid tumor oncology service between July and December 2014 from the Cleveland Clinic Foundation (CCF) Main Campus emergency department (ED), CCF Regional EDs, outside hospital (OSH) ED, OSH inpatient services, and CCF outpatient clinics. Data collected included time of admission, mortality and severity risk scores, and provider type. Risk factors were assessed for clinical outcomes, including activations of the Adult Medical Emergency Team, intensive care unit transfers, in-hospital mortality, and length of stay (LOS). Results: Five hundred admissions were included. OSH inpatient transfers had significantly higher disease severity compared with all other origins of admission. OSH inpatient transfers demonstrated significantly longer LOS compared with all other origins of admission, and higher mortality rates compared with the outpatient direct admits and CCF Main Campus ED admits. After adjusting for disease severity and risk of mortality, OSH ED patients remained at higher risk for Adult Medical Emergency Team activation, OSH inpatient transfers had the longest LOS, and CCF Main Campus ED patients had the lowest risk of mortality. Time of admission and provider type were not associated with any of the outcomes. Conclusion: Oncology inpatients transferred from an outside health care facility are at higher risk for adverse outcomes. The magnitude of difference is lessened, but still significant, after adjustment for disease severity and risk of mortality.

e12538 Background: CDK inhibitors (CDKi), in combination with aromatase inhibitors (AI), are approved for the treatment of hormone receptor positive (HR+) Her2 negative metastatic breast cancer (MBC). The effectiveness of continuing CDKi beyond first disease progression is not known. This study evaluated real world evidence and assessed the impact of continuation of CDKi beyond first disease progression in combination with endocrine therapy. Methods: This is a retrospective, single institution review of HR+ MBC patients treated with CDKi from 2015-2018 who continued CDKi after initial progression. The primary outcome was progression-free survival (PFS) beyond first disease progression, as assessed by the clinician based on radiological and/or clinical criteria. Overall survival (OS) – defined as date of initial CDKi treatment to date of death or last follow up – was a secondary outcome. Results: 30 women with HR+/HER2- MBC, median age 47.5 years (range: 31 – 81), sequentially continued on CDKi beyond first progression were identified from a database of patients treated with Palbociclib. Median and average follow up times on CDKi were 27.18 and 24.53 months, respectively. Initial endocrine/CDKi regimen received included: palbociclib (PA)/letrozole (LTZ) [67%], PA/fulvestrant (FULV) [23%], and PA/other AI [10%]. Prescribed combinations beyond 1st progression were: PA/FULV [56.7%], PA/LTZ [16.7%], and PA/other AI [20%], abemaciclib plus LTZ or FULV [6%]. As of 1/31/2019, 25 patients (83.3%) were still alive, and 19 (63%) had undergone a second progression on CDKi. The estimated median PFS for the entire duration while on CDKi was 23.5 months (95% CI 12.8 – 27.8), of which 11.8 months (95% CI 5.34 – 13.13) was the median PFS beyond first progression. The estimated median OS was 45.4 months. Conclusions: Among a small cohort of HR+ MBC patients, in a non-clinical trial setting, continuation of palbociclib plus endocrine therapy beyond first progression was associated with a median PFS of approximately 11 months. Formal clinical evaluation of continuation of CDK inhibitor plus endocrine therapy beyond first progression is warranted.

The relationship between renal cell cancer (RCC) and hematologic malignancy (HM) in the same individual has been reported for more than 20 years, and is noted in SEER database studies. Family histories suggest a familial association as well. This study evaluates the occurrence of renal cell cancer and hematologic malignancies in individual patients and families, and the occurrence of age-of-onset anticipation among generations. Family history data from our familial patient registry, including more than 700 pedigrees of familial hematologic malignancies, and 700 patients with renal cell cancer, were reviewed. Twenty-six patients with a personal history of both RCC and HM are reported. Seventy four patients with RCC are noted to have 95 family members with HM. Consistent with past reports, there was male predominance among the patients with both diseases (71 %), and among the RCC patients’ relatives with HM (57 %). Also consistent was a predominance of lymphoid malignancies in those with both diseases (92 %) and in the HMs among family members of RCC patients (79 %). The majority (95 %) of HM relatives were first or second degree relatives of the patient with RCC. Thirty of 34 parent/child pairs demonstrated age of onset anticipation in which the child developed either disease at a younger age than the parent. The co-occurrence of RCC and HM in the same patient has been shown to be significantly greater than expected. Families also appear to have an increased association. The appearance of anticipation suggests that genetic factors may be significant in this association of RCC and HM.

Purpose: Metastasectomy is often incorporated in overall treatment in patients with metastatic renal cell carcinoma. While this approach was studied in the immunotherapy era, only a few cases have been described in the targeted therapy era. Thus, we evaluated the role of metastasectomy in patients with metastatic renal cell carcinoma who received prior targeted therapy.Materials and Methods: We retrospectively evaluated the records of patients who underwent consolidative metastasectomy after targeted therapy at 3 institutions from 2004 to 2009. All patients received at least 1 cycle of targeted therapy before surgical resection of all visible disease.Results: We identified 22 patients. Metastasectomy sites included the retroperitoneum in 12 patients, lung in 6, adrenal gland in 2, bowel in 2, and mediastinum, bone, brain and inferior venal caval thrombus in 1 each. A total of 6 postoperative complications were observed in 4 patients within 12 weeks after surgery, which resolved with appropriate management...

e13034Background: Palbociclib (PA), a CDK4/CDK6 inhibitor, has been shown in clinical trials to prolong progression free survival (PFS) in HR+/Her-2 negative MBC when combined with an aromatase inh...

6547Background: Due to complexity of disease and treatments, oncology patients (pts) have among the highest hospitalization rate. In our cancer institute, just 6% of all discharged pts accounted fo...

171 Background: Due to complexity of disease and treatments, oncology patients have among the highest hospitalization rate, especially towards End of Life (EOL). In our cancer institute, just 6% of all discharged patients accounted for >40% of unplanned readmissions, and continue to be highest risk of future admissions, ICU stay, ED visits, overuse of chemotherapy and under use of hospice care. We hypothesized that developing individualized care plans (ICP) for this high-utilization group will provide guidance in the complex care they require to reduce unnecessary and aggressive medical services. Methods: An Interdisciplinary Care Team (ICT) was created consisting of palliative medicine and oncology physicians, social workers, care coordinators, and nurses. On a bimonthly basis, patients with at least two unplanned hospital readmissions over the last 60 days were identified. ICPs were created using a team-based approach with parallel input from patient’s primary outpatient providers. Results: A total of 36 patients, 226 hospitalizations, and 163 ED visits were evaluated over a 6-month period, with an average number of hospitalizations of 1.08 per patient month (ppm). After implementation of ICP, hospitalizations decreased to 0.23 ppm, with an average length of stay decrease from 7.17 to 4.06 days per admission. Average ED visits decreased from 0.58 to 0.34 ppm, and the average number of unplanned readmissions decreased from 0.43 to 0.13 ppm. Of the 10 patients expired since creation of ICP, 8 utilized hospice care, while 2 patients died in an ICU. Average time to death from creation of ICP was 72 days among this cohort, while time to death from last exposure to chemotherapy was 58 days. Conclusions: Creation of individualized care plans for high-utilizing cancer patients decreased number of hospitalizations, ED visits, unplanned readmissions, and length of stay. A dedicated focus from a team of experts, beyond disease biology, on a unique patient situation may result in improved patient experience with decreased aggressiveness of care at EOL and overall resource utilization.

191 Background: We previously reported that inter-hospital transfer patients to our institution’s oncology service experienced higher mortality and increased length of stay (LOS) compared to other origins of admission. We sought to identify risk factors for adverse outcomes in this hospital transfer population. Methods: We reviewed all inter-hospital transfers from Jan-June 2016 to the Cleveland Clinic’s solid tumor oncology service. Patient characteristics, including age, albumin, and case severity indices (mortality and severity risk scores and AP-DRG), as well as encounter characteristics, including admitting provider (house staff or hospitalist), admission time (8AM-5PM or evening), admission day (weekday or weekend), and time between transfer acceptance and admission were recorded. Adverse events examined included activation of adult medical emergency team (AMET), ICU transfer, LOS, in-hospital mortality, and 30-day readmission. Associations of patient and encounter characteristics with adverse events were assessed using Wilcoxon and Fisher’s exact tests. Results: Fifty-three transfer admissions were identified. Patients had a median age of 67 years and 58.5% were male. House staff admitted the majority of patients (81.1%) and most occurred after hours (62.3%). Age, admission time and day, and type of admitting physician were not associated with adverse events. There was a significant association between higher AP-DRG and mortality/severity risk scores with ICU transfers, AMET activations, and mortality. Patients who experienced any adverse events on average had a lower mean albumin than those who did not (2.3 vs 3.0 g/dL p=0.006). LOS and readmission were not significantly associated with any patient or encounter characteristics. Conclusions: Burden of disease as measured by mortality/severity risk and AP-DRG as well as lower albumin levels are associated with adverse events in solid tumor inter-hospital transfer patients, while encounter characteristics do not predict for poorer outcomes. This population should be targeted for improvements in communication and handoffs at the time of transfer, as well as early involvement of palliative care providers.

e18217Background: Use of staging imaging (SI), including CT, PET and bone scans, is not routinely recommended in stage I-IIA breast cancer patients (ESBCP) in the absence of signs or symptoms of me...

e17091 Background: The RTOG and EORTC have reported benefit from adding chemotherapy to post-operative radiation therapy (PORT) in high-risk patients (pts) with squamous cell head and neck cancer, ...

449 Background: An increased incidence of both RCC and HM occurring in the same patients has been reported. Also, a relationship between adenocarcinoma and HM has been previously suggested. Moreover, detailed family history in our patients with RCC suggested an increased incidence of HM in their family members. The purpose of this study is to characterize the HM in relatives of patients with RCC. Methods: Data from 700 patients with RCC seen by us from 2004 to the present were retrospectively evaluated through chart review. The patient, family history and pathology characteristics were collected to determine the frequency of HM in first and second-degree relatives of patients with RCC. Pedigrees were then constructed and subtypes of HM were characterized. Results: A family history of HM was observed in 74 relatives involving 59 families. Of these, 50/74 cases of HM were in first-degree relatives and 19/74 were in second-degree relatives. The most common HMs were lymphoma and leukemia: 24 non-Hodgkin’s lymphoma, 8 Hodgkin’s lymphoma, 8 lymphoma not further specified (NOS), 11 chronic lymphocytic leukemia, 1 chronic myeloid leukemia, 1 acute myeloid leukemia, 5 acute leukemia NOS and 4 leukemia NOS. Other HM observed were multiple myeloma in 2 patients, Waldenström’s macroglobulinemia, myelodysplastic syndrome, and myelofibrosis. Additionally, 2 relatives had blood cancers that were NOS. Of the 59 patients with RCC, 40 had clear cell histology, 4 papillary, 3 chromophobe, 1 sarcomatoid, 1 transitional and in 10, RCC histology was not recorded. Conclusions: HM is observed in patients with RCC with increased frequency compared with the SEER database. We now observed an increased frequency of HM in relatives of patients with RCC. The majority of HMs observed were B-cell malignancies, as we previously reported for HMs that occur in patients with breast cancer or RCC. The etiology of this association remains unclear, but suggests a common etiopathogenesis for RCC and B-cell tumors. Genetic mutations, hereditary immunological defects, and environmental factors may be involved. A larger study with statistical evaluation for confirmation is required. We plan to collect serum and tissue samples from patients and relatives for future molecular studies.

Abstract 5086 Purpose of the study: We observed an increased frequency of hematologic malignancy (HM) in patients and family members of patients with renal cell cancer (RCC) and sought to characterize the association further in terms of frequency and characteristics of HM, and the importance of such an association. Methods: We performed a chart review of our data base of approximately 700 RCC patients seen by us from 2004 to the present in an effort to determine the frequency of HM in patients and in the families of patients diagnosed with RCC. Results: Of the 700 charts reviewed, both HM and RCC occurred in 19 individuals. [11 males and 8 females]. HM diagnosis included acute myeloid leukemia in 1 patient, Hodgkin's lymphoma (HL) in 4 pts, non-Hodgkin lymphoma (NHL) in 7 pts, (3 small cell and 4 large B-cell lymphoma), chronic lymphocytic leukemia (CLL) in 2 pts and hairy cell leukemia (HCL), monoclonal gammopathy of undetermined significance (MGUS) myelodysplasia (MDS) in one patient each. A family history of HM was found in 71 relatives involving 56 families of patients with RCC. Of these, 48/71 cases of HM were in first degree relatives and 18/71 were in second degree relatives. The most common HMs were lymphoma and leukemia: 24 NHL, 9 HL, 6 lymphoma not further specified (NOS), 11 CLL, 1 acute myeloid leukemia, 5 acute leukemia NOS and 6 leukemia NOS. Other HM observed once were multiple myeloma, Waldenström's macroglobulinemia, chronic myeloid leukemia, myelofibrosis and polycythemia vera. In addition, 2 family members had blood cancers that were NOS. Thus, of 77 patients/family members with known HM diagnosis 94% were B-cell malignancies. Clear cell histology was the most common subtype of RCC, and all subtypes of RCC occurred in the study population with expected frequency. RCC and HM occurred in the same patient in this study more frequently at 2. 7% than would be expected from a SEER database. In that database the observed to expected (O/E) ratio of NHL and RCC was 1. 86 to 2. 07% [Kunthur et al. Am J Hematol 2006; 81:271–80]. Conclusions: Increased incidence of B-cell malignancy has been reported in individuals with RCC [Dutcher et al. Proc Am Fed Clin Res, Eastern Division, April 2011]. Wiernik et al. [Cancer J 2000] reported a similar increase was noted between adenocarcinoma of the breast and B cell malignancies in same individual and mouse mammary tumor virus was proposed a potential causative agent. There is a preponderance of B-cell malignancy in both the individuals and in the families of the patients with RCC noted in this study. The etiology of this association between RCC and HM is unclear and suggests a common etiopathogenesis for RCC and B-cell tumors, or a familial immunologic defect that facilitates both malignancies. We plan to further explore the relationship of HM to RCC. Disclosures: No relevant conflicts of interest to declare.