Shelly S. Lo

Extended follow-up results from a prospective multi-center study of the impact of the 21-gene recurrence score assay on medical oncologist and patient adjuvant breast cancer treatment selection, satisfaction, and anxiety.

CTRC-AACR San Antonio Breast Cancer Symposium: 2008 Abstracts Abstract #3113 Background: The 21-gene Recurrence Score (RS) assay has been validated to quantify the risk of distant recurrence in tamoxifen treated patients (pts) in node negative, estrogen receptor positive breast cancer (BC) and predict magnitude of chemotherapy benefit. We previously showed that the RS impacted medical oncologists (MOs) and pts adjuvant treatment decision making, decreased situational anxiety and decisional conflict, and improved pt satisfaction regarding adjuvant treatment decisions. Herein, we present the 12 month post-RS data for MOs and pts. Material and Methods: MOs stated their treatment recommendation and confidence in it pre- and post-RS assay, and completed a 12 month questionnaire. Pts completed 4 questionnaires pre- and immediately post-RS, and 12 months later: 1) Patient Treatment Decision Making Questionnaire; 2) Decisional Conflict Scale (DCS); 3) State-Trait Anxiety Inventory; and 4) Functional Assessment of Cancer Therapy-Breast. Frequency distributions, means and standard deviations summarized data. Paired samples t-tests and repeated measures ANOVA assessed quality of life, decisional conflict and anxiety. Results: Accrual goal was met with 89 evaluable pts. 16/17 (94%) MOs and 67 pts (75%) completed the 12 month assessment. There were no breast cancer recurrences recorded at 12 months. The majority of MOs reported increase confidence in their treatment recommendation (n=15, 93.8%), felt the RS provided additional information (n=15, 93.8%), and influenced treatment recommendation (n=14, 87.6%). Results from the DCS immediately post-RS indicate reduced conflict over treatment ( p <.0001), greater pt satisfaction, and increased confidence with choice of adjuvant therapy ( p <.0001). Pts reported they were glad they took the test 12 months later (n=62, 92.5%), found results easy to understand (n=60, 89.6%), and the test influenced treatment decision (n=54, 80.6%). Sixty four (95.5%) were satisfied with their adjuvant decision. State anxiety decreased over the year (mean 38.9 to 34.0, p . = 007), the most significant decline occurred pre- to immediately post-RS. Quality of life remained constant. Conclusions: The RS assay has an immediate and enduring impact on MOs and pts adjuvant decision making. MOs and pts report continued confidence and satisfaction with the assay. Pts had a decrease in decisional conflict right after the test, situational anxiety declined over the next 12 months and quality of life remained stable. Investigator initiated trial supported by an unrestricted clinical trials grant from Genomic Health Inc. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3113.

Abstract PD10-02: Metabolic syndrome and recurrence within the 21-gene recurrence score assay risk categories in lymph node negative breast cancer

Background: The incidence of the metabolic syndrome (MS) has been increasing in the United States and elsewhere. The interaction of MS with breast cancer (BC) incidence, tumor biology and outcomes are under study. We hypothesized that the presence of MS would predict BC recurrence to a variable degree across the diverse BC biology as defined by the risk categories of the 21-gene recurrence score (RS) assay. Patients and Methods: We studied consecutive patients (pts) with newly diagnosed, estrogen receptor (ER) positive, lymph node (LN) negative BC treated in our institution between 2006–2011 who had a 21-gene RS assay done on their tumors. All pts were treated with standard systemic and local therapy. The electronic medical record was queried for key diagnoses including MS and its constituent parts. The WHO definition was used to categorize pts as having MS defined as diabetes mellitus (DM) or glucose intolerance, plus at least 2 of the following: hypertension (HTN), dyslipidemia (HL), central obesity and microalbuminemia. Tumor characteristics including Ki67 index, grade, tumor size, HER2/neu status; and pt characteristics including age, race, menopausal status, body mass index were recorded. The association of MS and the tumor and patient characteristics with the RS tertiles of low, intermediate and high risk was analyzed. Results: We identified 332 pts, median age 62 years, of whom 88 (27%) had MS. There was no significant association between the MS and any of the patient or tumor variables including the 21-gene RS assay, except for race (p = 0.004). Eleven of 21 (52%) African-American women had MS, 68 of 284 (24%) Caucasian women had MS, and 9 of 21 (43%) others including Hispanic and Asian women had MS. However, there was a significant association between recurrence and MS (p = 0.0002) independent of other factors. Of the 21 pts who recurred, 13 (61.9%) had MS. There was an association of recurrence and MS within RS tertiles. For pts with low risk scores, 7/44 (15.9%) with MS vs. 1/126 (0.79%) without MS had recurrence (p = 0.0003). For pts with intermediate risk scores, 5/30 (16.67%) with MS vs. 4/83 (4.82%) without MS had recurrence (p = 0.05). For patients with high risk scores, 1/9 (11.11%) with MS vs. 2/15 (13.33%) without MS had recurrence (p = 1). Conclusion: MS is an independent risk factor for BC recurrence among women with LN negative, ER positive BC treated with standard adjuvant therapy. There is a striking impact of MS on recurrence in pts with tumor biologies defined by low (and to a lesser degree) intermediate risk 21-gene RS assay scores. However, there is no difference in recurrence risk by MS among those pts with high RS. This implies that interventions directed at modifying MS in newly diagnosed pts with early BC may potentially favorably impact survival in those with specific tumor biologies as defined by multigene assays. Thus, long-term prospective studies should be conducted to further evaluate both the short and long term effects of MS on BC outcomes. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD10-02.

Cancer Survivorship Care: How Primary Care Providers Perceive Their Role.

Background: The majority of cancer survivors are breast cancer patients since about 80% live five years beyond diagnosis. It is projected that by 2020, demand for medical oncologists will exceed supply, in large part due to this increased number of cancer survivors. One proposed solution to address the disparity of resources is to enlist primary care physicians (PCP) in the care of cancer survivors. This pilot study aims to describe the perceptions of primary care physicians relative to cancer survivorship care.Materials and Methods: We conducted a prospective, cross sectional survey of PCPs including internists, family practitioners and gynecologists in the outpatient setting. The primary outcome measure was a 45 item measure of knowledge and perceived role of the PCP in the care of cancer survivors.Results: A total of 84 PCPs of 200 surveyed (42%) responded. Overall, 66 PCPs stated they are interested in participating in the care of cancer survivors (79%); however, only a minority of the PCPs commonly discuss the survivorship phase of the cancer control continuum (n=8, 10%). The majority of PCPs believe that the medical oncologist should remain active in the follow up care in association with the PCP (n=28, 36%) or as a single provider (n=17, 20%). Only 20 PCPs (25%) agreed or strongly agreed that survival outcomes are similar for PCPs and medical oncologists. Most PCPs felt that cancer survivors are more compliant with survivorship care recommendations when proposed by the medical oncologist versus PCP (n=42, 55%). The majority of PCPs felt that survivorship follow up care guidelines would be extremely helpful or very helpful (n=61, 81%), a treatment summary of care document would be extremely helpful or very helpful (n=60, 80%), and a treatment summary care plan would change current practice (n=67, 90%). PCPs treat co-morbidities such as diabetes mellitus, obesity and hypertension; however only a minority of PCPs are aware of the relationship between co-morbidities and cancer survivorship. A little over a third of the PCPs strongly agreed that co-morbidities impacted upon the incidence of cancer, incidence of cancer recurrence and overall cancer mortality; n=30, (39%), n=27 (35%), and n=41 (42%) respectively.Discussion: Although PCPs recognize the opportunity to favorably impact on cancer survivorship issues, there appears to be a level of uncertainty regarding their role. PCPs are receptive to participating in the care of cancer survivors provided that they are given the necessary educational resources to do so. Interventions need to be developed and validated to improve the role of the PCP cancer survivorship care. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1061.

Brief spiritual well-being screening is nonlinearly related to psychological distress in ambulatory cancer patients

Religious and spiritual (RS) beliefs and associated social supports can buffer against anxiety, depression, and other supportive oncology concerns. Patients with cancer who have adequate RS resources often fare better psychologically, physically, and socially. Inversely, among patients with cancer and other serious illnesses, some types of negative RS processes such as feeling abandoned or punished by God are linked to greater emotional distress and poorer quality of life. Existing evidence suggests 20% to 50% or more patients with cancer experience religious distress depending on the patient sample and the assessments administered. The combined evidence regarding prevalence and outcomes of religious concerns points to the need for effective screening. Such screening could identify patients experiencing RS concerns who should receive further assessment and spiritual care if indicated. Leading accrediting bodies now mandate psychosocial distress screening in cancer centers and spiritual concerns/well‐being are one facet of concerns included in common measures. However, there is limited evidence about the psychometric performance of these measures in ambulatory cancer settings. The present study was a preliminary test of the psychometric properties of a brief spiritual well‐being (SWB) screen used in routine clinical practice at an academic cancer center. One task of construct validation was to determine whether the SWB

Abstract P6-08-42: Association of metabolic syndrome, its components and multigene assays for recurrence risk

Background: There is an association of metabolic syndrome (MS) and its constituents (obesity; diabetes mellitus, DM; hypertension, HTN; hyperlipidemia, HL) with breast cancer (BC) causation and outcomes. Previously we showed an impact of obesity on tumor biology as defined by a multigene assay. Our objective was to study the association between MS, its components and tumor biology, as determined by the 70 gene signature (70-GS) and the 21-gene Recurrence Score (RS). Methods: Consecutive patients with newly diagnosed ER+, lymph node-negative BC from 2005-2012 were studied. A 70-GS was done for those pts with tumors that had either low or intermediate RS. Pearson’s Chi-square tests for univariate analyses and logistic regression for multivariate analysis were used. Results: Low or intermediate RS were found on tumors from 151 pts of which 133 had a 70-GS. The MS was present in 23/104 (22%) pts with intermediate RS and 21/46 (46%) pts with low RS (p=0.004). DM, HTN, and obesity were each inversely associated with 21-gene RS in univariate analyses (p=0.002, p=0.003, p=0.004 respectively, see Table). However, MS and its individual components were not significantly associated with the 70-GS. Upon adjustment for age and race, the association between MS and RS was not significant (OR=0.64; p=0.28); however, DM (OR=0.35; p=0.01), HTN (OR=0.44; p=0.05) and obesity (OR=0.35; p=0.01) remained significantly inversely associated with RS. Independent of age and race, patients with DM, HTN, or obesity were more likely to be in the low-risk 21-gene RS group. Conclusions and Implications: The association of MS and its components differs for the 70-GS and RS assays. There is significant association between MS (and DM, HTN, obesity) and RS, but no association with 70-GS. Patients with MS (and components) are more likely to have a biology (low RS) known to have less chemotherapy benefit. Given the reported impact of MS on BC incidence and outcomes along with the global increased MS incidence, the MS may have profound impact on BC biology and treatment outcomes in the coming years. It is also possible that multigene assays currently in use for prognosis and prediction may need refinement in the presence of MS and/or its components. Citation Format: Hanh P Mai, Stephanie Kliethermes, Shikha Jain, Shelly S Lo, Ellen R Gaynor, Kathy S Albain, Patricia Robinson. Association of metabolic syndrome, its components and multigene assays for recurrence risk [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 P6-08-42.

Abstract P6-06-50: Obesity and the influence on tumor biology as determined by the intermediate risk 21-gene recurrence scores (RS) and the 70-gene breast cancer recurrence signature (70-GS) assay

BACKGROUND Obesity is an apparent risk factor for postmenopausal breast cancer (BC), estrogen receptor (ER) positive BC, larger tumors, lymph node (LN) involvement, as well as recurrence of BC and BC death despite treatment. However, the specific mechanism of these increased risks remains unclear. Our prior work described the negative influence of metabolic syndrome on BC recurrence in patients assessed by a 21 gene recurrence score (RS) in the low risk and intermediate risk tertiles (Lakhani et al PSABCS 2012). The objective of this study was to analyze the interaction of obesity and BC biology in patients assessed by the 70 gene signature (70-GS) for BC recurrence and the 80 gene molecular subtyping. METHODS We studied consecutive patients with newly diagnosed ER positive, LN negative BC treated at Loyola University Medical Center between 2005 -2012 who had an intermediate RS. The 70-GS was done on these same paraffin-embedded tumor blocks for risk level and molecular subtype. Standard descriptive statistics are reported. Wilcoxon rank sum tests were performed for the comparison of BMI by groups defined by RS scores (≤24 vs ≥25) and the 70 gene signature assay (high risk vs low risk). In addition, Chi-squared test, or Fishers exact test as appropriate, was used to examine the association between BMI tertiles and the 70GS or molecular subtype. RESULTS From 102 patients with intermediate RS, the 70-GS was successful in 89 samples. The average age was 61 years (range 41-79). The median body mass index (BMI) was 29 (range 18-53). There was a significant association between BMI and RS (p = 0.0110): median BMI = 28 in patients with RS ≤24; median BMI 33 in patients with RS ≥25. There was a significant association between BMI and the 70-GS (p = 0.0116). Median BMI 27 in low risk group; median BMI 32 in high risk group. There was a significant association between the 70-GS and BMI (p = 0.0190). View this table: Association between the 70-GS and BMI There was a significant association between molecular subtype and BMI tertiles (p = 0.0803). View this table: Association between molecular subtype and BMI tertiles CONCLUSION There is a striking interaction of obesity and BC biology as defined by the RS and 70-GS assays. Our data suggest that BC in obese women may have more aggressive tumor biology and higher risk of recurrence than BC in those with a low BMI. Further molecular characterization of the BC from obese patients may elucidate the role obesity plays in BC development and progression, as well as provide rationale for targeted therapeutic trials. Clinical trials targeting known carcinogenic pathways related to obesity (such as metformin and statins) are ongoing. Several genes in the 70-GS are the same genes expressed in obese patients. Additional studies examining the prognostic and predictive value of the 70-GS need to be conducted for this patient population. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-06-50.

Prevalence of secondary causes of bone loss in patients with breast cancer initiating treatment on clinical trials with aromatase inhibitors or bisphosphonates.

e11019 Background: We previously demonstrated that treatable secondary causes of bone loss (SCBL) are prevalent in breast cancer survivors (Camacho, JCO 2008). SCBL may amplify bone loss caused by aromatase inhibitors (AIs) or compromise response to bisphosphonates (BPs). Goals of our study were to determine the frequency of screening for osteoporosis and SCBL in patients (pts) enrolling onto clinical trials involving AIs or BPs, and to determine the prevalence of SCBL in this population. Methods: A retrospective chart review of pts enrolled between 2003-2009 in clinical trials involving treatment with AIs (MA-27, NSABP B-35, SWOG 0226, SOFT, MAP-3) and BPs (SWOG 0307, SWOG 0702) was conducted at a single institution. Charts were reviewed for bone density assessment with dual energy x-ray absorptiometry (DXA scan), and for SCBL including 25OH-vitamin D (25 OHD), parathyroid hormone (PTH) panel, thyroid stimulating hormone (TSH), 24 hr urine for calcium and creatinine. The WHO criteria were used to categor...