Paula Rosenblatt

CYFRA 21-1 as a Prognostic and Predictive Marker in Advanced Non–Small-Cell Lung Cancer in a Prospective Trial: CALGB 150304

Background: Cytokeratin 19 and its soluble fragment CYFRA have been studied as markers that may be associated with response to therapy and survival in non–small-cell lung cancer (NSCLC). As a prospective correlative study of Cancer and Leukemia Group B 30203, a randomized phase II trial of carboplatin/gemcitabine with eicosanoid modulators (celecoxib, zileuton, or both) in advanced NSCLC, serum CYFRA levels were obtained before and during treatment. Methods: Serum CYFRA levels were measured at baseline and after the first cycle of treatment using an electrochemoluminescent assay. Paired specimens were available from 88 patients. The logarithms of the initial concentration and of the difference in concentrations were analyzed for association with overall survival (OS) and failure-free survival (FFS). Results: Lower baseline CYFRA levels were associated with both longer OS and FFS (p < 0.0001 and p = 0.0003). In addition, larger reductions in CYFRA levels correlated with longer OS and FFS (p = 0.0255 and p = 0.0068). Conclusion: CYFRA and change in CYFRA were found to be reliable markers for response to chemotherapy for NSCLC; however, a precise threshold to mark response has yet to be determined.

Patient-reported Adherence to Adjuvant Aromatase Inhibitor Therapy Using the Morisky Medication Adherence Scale: An Evaluation of Predictors.

Objectives: Endocrine therapy is part of standard adjuvant therapy for patients with hormone receptor-positive breast cancer and has been shown to improve recurrence-free and overall survival. However, adherence to endocrine therapy is suboptimal and is difficult to measure. In this study we evaluate the feasibility of using the Morisky Medication Adherence Scale (MMAS) to assess patient adherence to aromatase inhibitor (AI) therapy. Methods: Patients with stage 1 to 3, hormone receptor-positive breast cancer receiving adjuvant AI therapy were prospectively enrolled on an Institutional Review Board approved protocol. The MMAS questionnaire was administered to each patient and adherence was measured. Information on duration of AI therapy, patient and tumor characteristics, and treatment was collected. A multivariable logit model approach was utilized to evaluate potential barriers to adherence. Results: Between 2011 and 2014, 100 patients were enrolled. The distribution of adherence levels was 13% low, 37% medium, and 50% high. High adherence was reported more frequently in white women (58%), patients with stage 2 and 3 disease (54%), and patients who did not receive chemotherapy (62%). Multivariable analysis demonstrated that higher adherence was more likely in white women compared with African American women (estimated odds ratio=2.8). Conclusions: Using the MMAS, only 50% of women with stage 1 to 3 breast cancer reported high adherence to AI therapy, consistent with other reports showing suboptimal adherence to adjuvant endocrine therapy. The MMAS allows for the rapid assessment of adherence to oral adjuvant endocrine therapy and is valuable in a busy clinical setting.

Effect of reduction mammoplasty on acute radiation side effects and use of lumpectomy cavity boosts

PURPOSE Reduction mammoplasty (RM) during breast-conserving surgery is popular among women with large-volume breasts because it reduces redundant breast folds and may decrease skin-related morbidity from radiation therapy. However, RM may obscure the lumpectomy cavity (LC) and pose challenges to administering an LC boost, potentially affecting local control. We investigated the impact of RM on acute side effects and use of LC boosts. METHODS AND MATERIALS The records of 645 consecutive women treated with whole-breast irradiation at an urban university and 2 community practices between January 2012 and December 2014 were reviewed on an institutional review board-approved study. The primary endpoint was grade ≥3 radiation dermatitis; the secondary endpoint was use of LC boost. Student 2-sample t tests, Pearson χ2 tests, Fisher exact tests, and univariate and multivariable logistic regression analyses were performed. RESULTS Forty-three (7%) RMs were performed in 650 treated breasts. No significant differences in grade 3 toxicities were identified among RM and non-RM patients. LC boost was delivered to 474 breasts. Fewer (16/43) RM patients received LC boosts compared with non-RM patients (458/607), P = .0001. RM patients were more likely to have neoadjuvant chemotherapy, stage III or multifocal disease, higher body mass index, larger planning treatment volumes, and conventional fractionation (P < .05). CONCLUSIONS RM was associated with decreased use of LC boost without significant differences in acute toxicities. Further investigation to delineate LCs in patients undergoing RM or identify alternative strategies for delivering LC dose is needed.

Abstract 3277: The influence of cancer on working poor and working non-poor cancer survivors’ work productivity, employment and quality of life

Employment issues are cited as one of the most common unmet psychosocial needs of cancer survivors; specifically, patients indicate they want more information on how to navigate working during their illness, the return to work process and how to manage the immediate and long-term effects on job productivity. Yet, most oncology care providers feel limited in their ability to address this topic with patients, citing minimal guidance, limited access to resources they feel clients need to achieve work-related goals, and concerns regarding their knowledge of how cancer may impact work. Likewise, supervisors of employees diagnosed with cancer are ill-prepared to manage the needs of cancer survivors beyond the standard referral to human resources. One limitation of the existing research on cancer and employment is that most studies have only examined these issues among higher income and more educated cancer survivors. The employment experiences of low-wage and less educated cancer survivors have been understudied. This is a significant gap in the research on cancer survivorship and work given the massive growth of low-wage jobs in the US since the 2008 Great Recession. The employment circumstances are significantly different for workers in low-wage jobs than they are for other workers. Thus, the effects of cancer on the work productivity of working poor and working non-poor may vary and consequently may have different effects on long-term employment and quality of life for cancer survivors. This study addresses this gap in the cancer survivorship literature by examining whether there is variation in the effects of cancer on the work productivity of working poor and working non-poor cancer survivors and its radiating effects on employment and the quality of life of cancer survivors. Using data from the Medical Expenditure Panel Survey (MEPS) and the MEPS Cancer Survivorship Supplement, this secondary data analysis will study cancer survivors who were employed at the time of their cancer diagnosis, comparing the effects of cancer on work productivity among working poor and working non-poor respondents and determining whether differences in work productivity influence long-term employment and quality of life. Preliminary results indicate that a higher percentage of working poor cancer survivors were less productive at work due to cancer and reported lower current employment rates and quality of life indicators in comparison to working non-poor survivors. Study results could help oncology medical teams, supervisors, and human resources professionals assist working cancer survivors during this transition period in their lives. Note: This abstract was not presented at the meeting. Citation Format: Helen Nichols, Kathleen Tracy, Paula Rosenblatt, Robin Vanderpool, Jennifer Swanberg. The influence of cancer on working poor and working non-poor cancer survivors’ work productivity, employment and quality of life [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3277. doi:10.1158/1538-7445.AM2017-3277

Abstract C81: A systematic review of breast cancer screening strategies for African American women

BACKGROUND: Breast cancer mortality is higher among African American women (AAW) in comparison to any other racial/ethnic group. This disparity is reflective of multiple factors including health care access, biological factors and participation in screening mammography. Currently there is a scarcity of literature on evidence-based interventional strategies to increase AAW9s participation in screening mammography. Our study aims to: 1) Identify the literature from 2009-2015 on interventional strategies to increase the participation of AAW ≥40 years old in screening mammography and 2) Summarize the evidence from this literature including any impact of these interventions on breast cancer outcomes. METHODS: We conducted a systematic review of published and grey literature on breast cancer screening interventions from 2009-2015. The literature search was conducted in PubMed, Embase (Elsevier), CINAHL (Ebsco), PsycINFO (Ebsco) and the Cochrane Central Register of Controlled Trials (Wiley). Grey literature was searched for using ClinicalTrials.gov, National Cancer Institute9s clinical trials database and ProQuest Dissertations and Theses database. Queries utilized a combination of keywords and database-specific terminology derived from pre-determined eligibility criteria. The four reviewers were divided into two teams to balance expertise in public health, primary care, cancer disparities, breast oncology and breast cancer basic science research. The review protocol was developed with guidance from PRISMA standards. Methodological quality of the studies will be determined by examination of study design, theoretical framework and quality of data reporting. RESULTS: Our literature search yielded a total of 1,83O studies. After removal of duplicates, 1,274 studies were screened for inclusion. Twenty studies met all criteria and were designated for abstraction and data analysis. Nineteen studies presented original data from a US based intervention and had a population which included AAW ≥ 40 years old. Study designs included: randomized control trials, quasi-experimental, pre/post study, non-randomized with controls, cohort and case-control studies. The common interventional strategies employed were reminder systems; trained volunteers; media campaigns; telephone and DVD coaching; and patient navigation/case management. Reported outcome measures included: demographics, pre- and post-intervention mammography participation, and intervention retention rates. Study limitations stemmed from limited sample size, lack of generalizability, absence of theoretical framework, attrition rate and utilization of self-reported data. CONCLUSION: Despite knowledge of disparities in breast cancer mortality for AAW and the impact of screening mammography on breast cancer mortality, there is a paucity of evidence on interventional strategies to increase the participation of AAW in screening mammography. The limited evidence available suggests that interventional strategies that incorporate mass media communication, family and social support networks, and nurse navigation increased the number of AAW who participate in screening mammography. Citation Format: Shana O. Ntiri, Laundette P. Jones, Gonca Kocoglu, Emilie Ludeman, Paula Y. Rosenblatt. A systematic review of breast cancer screening strategies for African American women. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr C81.

What is the impact of reduction mammoplasty for women undergoing breast-conserving surgery for breast cancer?

49 Background: Reduction mammoplasty (RM) at time of breast conserving surgery (BCS) is an increasingly popular procedure that reduces redundant breast folds and skin toxicity from whole breast irradiation (WBI). However, the tissue manipulation may obscure the lumpectomy cavity (LC) and hinder the ability to deliver a radiation boost to the LC, potentially impacting local control. We studied the impact of RM on acute radiation side effects and the use of LC boost. METHODS From Jan 2012 to Dec 2014, 652 consecutive women with DCIS or Stage I-III invasive cancer were treated with curative intent BCS and WBI at an urban university and 2 community practices. We reviewed the charts on an IRB-approved study with the primary endpoint of ≥ grade 3 radiation dermatitis scored via the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Secondary endpoint was the use of LC boost. Tested variables included age, race, body mass index, menopausal status, multi-focal disease, stage, tumor grade, receptor status, chemotherapy administered, specimen volume, 3D or intensity modulated radiation, fractionation, nodal irradiation, and planning treatment volume (PTV). Students t-tests and Pearsons chi-square tests were utilized. RESULTS Forty-three (7%) of 652 patients underwent RM. Larger volumes of tissue were removed from the RM patients (median 366.5 g v 35.3 g, P= 0.0001). No grade 4 toxicities and few (2-3%) grade 3 toxicities were seen, P= 1.00. Narcotic use was similar (4-5%), P= 0.70. A LC boost was used in 476 (73%) patients; RM significantly decreased the use of a boost [16/43 (37%) v 460/609 (76%)], P= 0.0001. RM patients were more likely to have neoadjuvant chemotherapy, stage III or multi-focal disease, higher BMI, nodal irradiation, and conventional fractionation (P< 0.05). Subgroup analysis of the patients with available PTVs (67%) revealed similar volumes (P= 0.16). CONCLUSIONS RM was associated with a decrease in the use of LC boost without significant differences in acute toxicities; however, the result is not surprising given that PTVs were similar. Further investigation is needed to better delineate LCs in patients undergoing RM to increase the use of LC boosts.

Abstract P1-08-05: An association between obesity and more aggressive breast cancer subtype

Background: Obesity has become epidemic in the United States with over one third of the adult population being obese. The incidence of obesity is even higher among African American population with slightly more than half of the population being obese. Elevated body mass index (BMI) has been associated with an increased risk of breast cancer in postmenopausal women. This is believed to be due to higher levels of estrogens, inflammation, and insulin. Given that adipose tissue is the major source of estrogen production via the aromatization of androgens into estrogens in postmenopausal women, there is a concern that obese women may have inadequate estrogen suppression with a fixed dose of aromatase inhibitors (AIs). Multiple recent retrospective analyses of large phase III adjuvant endocrine therapy trials demonstrated that obese patients had worse outcome when treated with AIs. However, it remains unclear whether there is also a difference in the tumor subtype among normal weight, overweight, and obese patients. Method: A retrospective review of breast cancer cases diagnosed from July 2008 and August 2011 was performed. Patient characteristics, BMI, and pathologic findings were collected. An immunohistochemistry (IHC)-based molecular subtypes was assigned based on St. Gallen criteria: Luminal A (ER/PR+, HER2- and Ki67 ≤ 14%), Luminal B (ER/PR+, HER2+ or Ki67 > 14% or grade 3), HER2 enriched (ER/PR-, HER2+), and Triple negative breast cancer (TNBC; ER/PR-, HER2-). Using the WHO classification, normal weight was defined as BMI Result: 143 patients were included in the analysis. The median age was 55 years. The majorities of our patients were African American (63%) and presented with early stage disease (stage I 29%, stage II 45%, stage III 22%, and stage IV 5%). IHC-based molecular subtypes were luminal A 20%, luminal B 48%, HER2 enriched 7%, and TNBC 25%. 21% were normal weight, 30% overweight and 49% obese. As shown in the table below, comparing between normal weight, overweight, and obese patients, there is a possible association between tumor subtype and BMI status (p = 0.03). The majority of TNBC patients (94.4%) were overweight or obese. Specifically, there is significantly more aggressive luminal B subtype compared to luminal A (52.86% vs. 15.71%) among obese patients (p = 0.017). We further evaluated the effect of obesity and tumor growth in xenograft model of MCF7Ca. Comparing between obese mice fed with high fat vs. lean mice fed with chow diet, there is a significant increase in tumor growth among obese mice (p = 0.04) which corresponds to the high proliferation index measured by Ki67 seen in patients with luminal B subtype. Conclusion: Our study suggests that obesity may provide a microenvironment that support and accelerate tumor growth, particularly in luminal breast cancer subtypes. Furthermore, the poor outcome seen in obese patients may also be in part due to more aggressive tumor subtype. Citation Format: Saranya Chumsri, Paula Rosenblatt, Candace Mainor, Gauri Sabnis, Olga Goloubeva, Angela H Brodie. An association between obesity and more aggressive breast cancer subtype [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 P1-08-05.

Presentation and pathology of breast cancer in patients with HIV.

39 Background: With the use of highly active antiretroviral therapy, it is postulated the prevalence of breast cancer will increase in the HIV infected population. Few studies have evaluated the presentation and pathological features of breast cancer in this population. METHODS Charts of approximately 5,000 HIV patients seen between 2000-2011 at the University of Maryland were reviewed to identify those diagnosed with breast cancer. Demographics, HIV data, cancer clinical presentation, family history, and pathologic findings were collected. Pathologic findings included receptor status (estrogen [ER], progesterone [PR], and human epidermal growth factor 2 [HER2]), grade, stage, lymphovascular invasion (LVI), multifocality/multicentricity (MF/MC), and presence of carcinoma in-situ. RESULTS Twenty cases of concomitant HIV and breast cancer were identified. At diagnosis of cancer, the median age, CD4 count, and duration of HIV infection were 48 years, 437 cells/mm3, and 6 years, respectively. 47% had a family history of breast or ovarian cancer. 79% self-palpated a mass. Pathologic findings included 18 invasive ductal carcinoma, 1 invasive lobular carcinoma, and 1 ductal carcinoma in-situ. 70% were ER-positive, 50% were PR-positive, and 47% were HER2-positive. 21% were Grade 1, 21% were Grade 2, and 57% were Grade 3. 21% luminal A (ER/PR+, HER2- and Ki67 ≤14%), 52% luminal B (ER/PR+, HER2+ or Ki67>14% or grade 3), 5% HER2 enriched (ER/PR-, HER2+), and 21% triple-negative/basal (ER/PR-, HER2-). 5% were stage 0, 40% were Stage I, 30% were Stage II, 25% were Stage III, and none were Stage IV. LVI was present in 36%, MF/MC was present in 35%, and carcinoma in-situ was present in 82%. CONCLUSIONS Compared to historical data of non-HIV infected individuals, our population presented at a younger age with a strong family history and a greater number of self-palpated breast masses. HIV-infected patients with breast cancer presented with more HER2 positivity, higher grade, less favorable luminal B subtype, and more MF/MC disease. Despite aggressive pathology, most patients still presented with a relatively early stage. Annual screening mammogram at earlier ages should be considered in HIV-infected patients, particularly in patients with positive family history.