PURPOSE Differences in cellular levels of histone modifications have predicted clinical outcome in certain cancers. Here, we studied the prognostic and predictive value of three histone modifications in pancreatic adenocarcinoma. METHODS Tissue microarrays (TMAs) from two pancreatic adenocarcinoma cohorts were examined, including those from a 195-patient cohort from Radiation Therapy Oncology Group trial RTOG 9704, a multicenter, phase III, randomized treatment trial comparing adjuvant gemcitabine with fluorouracil and a 140-patient cohort of patients with stage I or II cancer from University of California, Los Angeles Medical Center. Immunohistochemistry was performed for histone H3 lysine 4 dimethylation (H3K4me2), histone H3 lysine 9 dimethylation (H3K9me2), and histone H3 lysine 18 acetylation (H3K18ac). Positive tumor cell staining for each histone modification was used to classify patients into low- and high-staining groups, which were related to clinicopathologic parameters and clinical outcome measures. Results Low cellular levels of H3K4me2, H3K9me2, or H3K18ac were each significant and independent predictors of poor survival in univariate and multivariate models, and combined low levels of H3K4me2 and/or H3K18ac were the most significant predictor of overall survival (hazard ratio, 2.93; 95% CI, 1.78 to 4.82) in the University of California, Los Angeles cohort. In subgroup analyses, histone levels were predictive of survival specifically for those patients with node-negative cancer or for those patients receiving adjuvant fluorouracil, but not gemcitabine, in RTOG 9704. CONCLUSION Cellular levels of histone modifications define previously unrecognized subsets of patients with pancreatic adenocarcinoma with distinct epigenetic phenotypes and clinical outcomes and represent prognostic and predictive biomarkers that could inform clinical decisions, including the use of fluorouracil chemotherapy.

Phyllodes tumors of the breast are rare fibroepithelial tumors that are characterized as benign, borderline, or malignant based on cellular characteristics such as stromal overgrowth and number of mitoses. Currently, there is a lack of consensus on risk factors and management of patients with phyllodes tumors, which has led to variation in treatment patterns as well as patient outcomes across many institutions. This study seeks to understand the clinicopathologic features, risk factors for local and metastatic recurrence, and clinical outcomes of patients with phyllodes tumors to better define optimal treatment patterns.

This report shows substantially higher FH documentation and appropriate genetic testing rates than prior reports. Many patients with indications for genetic testing may have only FH-based indications for testing, and this subset may account for the sizable proportion of patients with newly diagnosed BCa who have actionable mutations.

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Objective The potential influence of hypothyroidism on breast cancer remains incompletely understood. The objective of this study was to investigate the relationship between serum thyrotropin [thyroid-stimulating hormone (TSH)] concentration and markers of aggressive breast cancer biology, as defined by receptor expression profile, tumor grade, and American Joint Committee on Cancer (AJCC) stage characteristics. Methods This was a retrospective cohort study of patients from 2002–2014. All breast cancer patients who had complete receptor (estrogen receptor, ER; progesterone receptor, PR; and Her2/neu) and pre-diagnosis serum TSH data (n=437) were included. All patients had one of six receptor profiles: ER+ PR+ Her2/neu −, ER+ PR− Her2/neu−, ER+ PR+ Her2/neu+, ER+ PRHer2/ neu+, ER− PR− Her2/neu+, ER− PR− Her2/neu−. Log-transformed serum TSH concentrations were analyzed using multinomial and logistic regressions for a potential relationship with markers of breast cancer aggressiveness. Results Increasing serum TSH concentration was associated with a lower probability of having the receptor expression profile ER+ PR+ Her2/neu+ compared to patients with the ER+ PR+ Her2/neu− profile (OR=0.52, p=0.0045). No significant associations between other receptor expression profiles and serum TSH concentration were found. All time-weighted and unweighted median serum TSH concentrations were within normal limits. No significant associations between serum TSH concentration and tumor grade, overall AJCC stage, or tumor size (T), lymph node positivity (N), or presence of metastasis (M) were observed. Conclusions Serum TSH was not associated with markers of breast cancer aggressiveness in our cohort.

Background Mastectomy rates, both therapeutic and prophylactic, are on the rise in the United States. After recent implementation of a multidisciplinary breast clinic for newly diagnosed women at our institution, we sought to examine the impact of multidisciplinary care on surgical decision making. Materials/Methods Women with newly diagnosed breast cancer at our institution are referred to a multidisciplinary breast clinic where they are seen by a team of breast specialists (MDC) or to an individual practitioner (non-MDC) for initial consultation. We retrospectively analyzed rates of breast conserving surgery (BCS) and mastectomy among women with newly diagnosed breast cancer seen in either setting. For mastectomy cases, we designated the mastectomy as clinically indicated vs not clinically indicated based on National Comprehensive Cancer Network (NCCN) guidelines for breast conservation. T-test and chi-square were used to examine the comparability between MDC and non-MDC cohorts. Logistic regression was used to evaluate the overall prevalence of BCS among MDC and non-MDC cohorts. Stratification analysis was further conducted to examine BCS rates among women in each cohort receiving neoadjuvant chemotherapy vs up front surgery. Results A total of 341 consecutive patients were analyzed, including 202 MDC and 139 non-MDC patients seen in initial consultation between June 2012 and April 2014. The MDC and non-MDC cohorts were statistically equivalent in terms of age, tumor and nodal stage, histology, biomarker status, receipt of neoadjuvant chemotherapy, and proportion with genetic mutations. In the MDC cohort, 66% underwent BCS vs 42% in the non-MDC cohort (p<0.0001). Of those receiving neoadjuvant chemotherapy, 37% in the MDC cohort underwent BCS vs 12% in the non-MDC cohort (p=0.08). Of those proceeding to surgery without neoadjuvant therapy, 70% underwent BCS in the MDC cohort vs 46% in the non-MDC cohort (p<.0001). Among mastectomies performed in the MDC vs non-MDC cohorts, 77% and 41% respectively were clinically indicated (P<.0001). Rates of unnecessary contralateral prophylactic mastectomy were comparable in both groups, 39% (p=0.99). Conclusions Breast cancer patients seen in an MDC setting at the time of initial diagnosis are significantly more likely than women seen in a non-MDC setting to undergo breast conservation. We hypothesize that the MDC model of breast cancer care, via facilitation of more informed medical decision making, may be a viable strategy to curtail rising mastectomy rates in the United States. Citation Format: Caitlin L Gomez, Pin-Chieh Wang, Nicole A Dawson, Robyn L Dvorak, Nova Foster, Anne Hoyt, Sara A Hurvitz, Amy Kusske, Charles Y Tseng, Susan A McCloskey. Multidisciplinary breast cancer care is associated with a higher rate of breast conservation in comparison with non-multidisciplinary care [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 P1-16-02.

124 Background: After recent implementation of a multidisciplinary breast clinic (MDC) for newly diagnosed women at our institution, we sought to examine the impact of MDC on patient satisfaction, timeliness and guideline concordant care. Methods: Women with newly diagnosed breast cancer at our institution are referred to MDC where they are seen by a team of breast specialists for initial consultation. The MDC model is further facilitated by a patient navigator/coordinator who serves as a single point of contact across disciplines and through the continuum of care. We deployed patient satisfaction surveys querying helpfulness of the care coordinator and satisfaction with seeing breast cancer specialty physicians together in one visit. We further retrospectively analyzed timeliness of care and guideline concordant care since MDC implementation. Results: Patient satisfaction survey response rate was 42% (n=133).On a scale of 1 (very poor) – 5 (excellent), 93% of respondents rated helpfulness of care coordinator as excellent and seeing specialty physicians together in one visit as excellent. 99% of respondents rated these factors as either excellent (5) or good (4). Regarding timeliness, among 202 women with newly diagnosed, non-metastatic breast cancer seen in MDC between June 2012 and April 2014, mean time from neoadjuvant chemotherapy to surgery was 43.1 days (range 26-78 days), from surgery to adjuvant radiation was 39.2 days (range 22-79 days), from surgery to adjuvant chemotherapy was 40.6 days (range 19-89 days), and from adjuvant chemotherapy to radiation was 34.9 days (range 13-67 days). All timeliness metrics well exceeded established national standards of 60-90 days. Regarding guideline concordant care, 94% and 90% respectively received indicated radiation therapy and chemotherapy in accordance with National Comprehensive Cancer Network (NCCN) Guidelines. Those not receiving guideline concordant care either declined, were of advanced age, or had prohibitive co-morbidities. Conclusions: The MDC model, which emphasizes care coordination via a team approach and patient navigation, is associated with excellent patient satisfaction and timely, guideline concordant breast cancer care.

45 Background: Approximately 5% to 10% of women diagnosed with breast cancer have a genetic predisposition, which can affect management recommendations. The National Comprehensive Cancer Network (NCCN) has established guidelines for genetics referral and testing, however recent publications have indicated low rates of family history documentation and appropriate genetics referral. We sought to assess the impact of standardized family history documentation on rates of appropriate genetics referral in a multidisciplinary breast clinic (MDC) setting. Methods: In advance of MDC consultation, women with newly diagnosed breast cancer complete an intake questionnaire which includes documentation of Ashkenazi Jewish ancestry along with a thorough family history. We retrospectively analyzed family history documentation to inform eligibility for genetic testing and rates of appropriate genetics referral. Results: Between June 2012 and April 2014, 202 women with newly diagnosed, nonmetastatic breast cancer were seen in MDC. We noted 100% compliance with family history documentation. Per NCCN Guidelines, genetic testing was indicated in 52% (106 patients), of which 77% were appropriately referred to a genetic counselor for evaluation. All patients who met criteria based on personal history factors including age ≤ 45, triple-negative disease under age 60, or two or more breast primaries under age 50 were appropriately referred. Patients who were eligible but not referred ranged in age from 46 to 93 and were eligible for testing based on Ashkenzi Jewish ancestry (3 patients) or family history factors including a relative with ovarian cancer (3 patients), ≥2 relatives with breast cancer (5 patients), or a relative with breast cancer < age 50 (7 patients). Conclusions: Compared with recently published national averages, rates of appropriate family history documentation and genetic testing referrals are significantly higher in our MDC setting. However, this analysis has identified significant opportunity for improvement via identification of overlooked referral indications. Initiatives are underway to improve future compliance.