Search

Female patients with breast cancer frequently develop arthralgia when treated with aromatase inhibitors (AI). Although the mechanism of AI-induced arthralgia is unknown, potential biomarkers have been identified. The purpose of this study was to investigate the clinical and genetic predictors of AI-induced arthralgia in a prospective cohort of patients with estrogen receptor-positive breast cancer. One hundred and ninety-six patients were enrolled at initiation of AI therapy with either letrozole or anastrozole. Patients completed two validated self-report questionnaires assessing pain, stiffness, and physical function at baseline, and repeated the questionnaires at two and at six months after the initiation of treatment with an AI. Germline DNA of all patients was genotyped for seven single-nucleotide polymorphisms (SNPs) previously identified by genetic screens and genome-wide association studies as associated with AI-induced arthralgia. More than 50% of the study group experienced arthralgia symptoms. Genetic analysis revealed that four SNPs, in CYP19A1 (rs4775936) and ESR1 (rs9322336, rs2234693, rs9340799), were associated with the development of arthralgia (adjusted P = 0.016, 0.018, 0.017, 0.047). High body mass index (BMI) was also associated with the development of arthralgia symptoms (adjusted P = 0.001). Patients prescribed letrozole were significantly more likely to develop arthralgia than patients on anastrozole (P = 0.018), and also more likely to discontinue AI therapy due to arthralgia. The CYP19A1 (rs4775936) SNP was significantly associated with discontinuation of therapy due to intolerable arthralgia. Our results suggested that BMI and AI drug (letrozole versus anastrozole) were clinical predictors of arthralgia, while genetic variants rs4775936, rs9322336, rs2234693, and rs9340799 were genetic predictors of AI-induced arthralgia. Significantly, rs4775936 was also a predictor of discontinuation of therapy.

Background: Tamoxifen is widely used in patients with hormone sensitive breast cancer in the adjuvant setting to decrease risk of recurrence and metastasis. 5-10 years of tamoxifen has demonstrated a near 50% reduction in recurrence risk. Despite marked interpatient variation in the metabolism of tamoxifen to its active metabolite endoxifen, all patients are prescribed 20 mg daily dose of tamoxifen. Current evidence suggests that patients are at risk for suboptimal benefit if measured endoxifen concentration is below 5.9 ng/ml (~15nM). However, there have been conflicting data on the clinical utility of CYP2D6 genotype testing, and measuring endoxifen plasma concentration as a predictor of breast cancer recurrence. The goal of this prospective study was to determine the impact of endoxifen levels and CYP2D6 genetic variations to clinical outcome among patients with early breast cancer. Methods: Since 2010, as part of Personalized Medicine Program in Oncology, our team has been prospectively enrolling patients on tamoxifen therapy. To date 950 patients have been enrolled and preliminary analysis has been completed in 429. After initial CYP2D6 genotype testing, plasma concentration of tamoxifen and its metabolites were quantified using liquid chromatography-tandem mass spectrometry during each clinic visit. Baseline characteristic are outlined in table 1. Primary outcome assessed was invasive disease-free survival (IDFS) defined as time since start of tamoxifen therapy till an event of interest such as loco-regional recurrence, distant metastasis, new contralateral primary breast cancer, death due to breast cancer and other causes. Patients were censored at their last encounter at our institution (London Health Sciences Centre). Results: IDFS data for 426 patients were obtained. Outcome was stratified by CYP2D6 phenotypes (ultra-rapid, extensive, intermediate and poor metabolizers) and endoxifen levels (>5.9ng/ml or vs< 5.9 ng/ml showed a clear trend towards lower IDFS (hazard ratio = 2.4, (95%CI,1.26-4.77) P=0.0002) among those with endoxifen < 5.9 ng/ml. We note this preliminary data analysis was unadjusted and will undergo further in-depth statistical analysis. Conclusion: Preliminary finding suggests endoxifen concentration, but not CYP2D6 phenotype, may be a predictor of risk for suboptimal benefit during tamoxifen therapy. Detailed statistical analysis is planned for the full cohort, including adjustment for covariates including tumor stage, menopausal status, drug interactions, and use of aromatase inhibitors. To our knowledge, this is the first study of its type to prospectively collect multiple plasma samples for tamoxifen and endoxifen level in real-world patients during tamoxifen therapy, with sufficient sample size and follow-up period for primary clinical outcome. Table 1: Baseline Characteristics of PatientsCharacteristicsCYP2D6-Phenotypes, n=429 (%)Endoxifen concentration, n=429 (%)UM/EMIMPM>5.9ng/ml(~15nm) Citation Format: Veera Durga Sravanthi Panuganty, Denise Keller, Wendy A Teft, John Gordon Lenehan, Kylea Raijann Potvin, Jawaid Younus, Theodorus Anthony Vandenberg, Diane Mary Logan, Karin Hahn, Muriel Brackstone, Phillip Stanley Blanchette, Francisco Perera, Yun-Hee Choi, Richard Brian Kim. Clinical outcomes in early breast cancer patients on adjuvant tamoxifen: Impact of CYP2D6 genotype and observed endoxifen concentrations [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-12-05.

Objective A prospective open-label randomized controlled trial to assess the role of a picture-based medication calendar on adherence to antiemetic regimens for adult patients receiving chemotherapy and assess the effect on other medication taking behaviors as well as patient satisfaction with the tool. Methods Participants were randomly assigned 1:1 to routine care with or without calendar. Results Adherence, stratified by education (university or postgraduate, p = 0.09; grade school, high school or college p = 0.32), was non-significantly different between study arms. At least 70% of intervention arm participants moderately or completely agreed that the calendar helped with medication taking behaviors. There was no statistical difference between study arms for perceived regimen complexity ( p = 0.16). Medication Use and Self Efficacy score (adjusted for age) used to assess perceived self-efficacy with medication taking behaviors were not statistically significant between study arms ( p = 0.09). Conclusion The picture-based medication calendar did not statistically affect adherence to scheduled antiemetics among outpatients receiving chemotherapy for solid organ tumor origins. However, participants indicated that the calendar was effective for keeping track of medications, had an easy-to-understand layout, and provided help around when and how to take medications related to the oncology regimen.

The aromatase inhibitor (AI) letrozole is a first-line drug in the adjuvant treatment of breast cancer in postmenopausal women. Adherence to AI therapy, including letrozole, remains problematic due to the development of debilitating AI-induced arthralgia. Letrozole is metabolized in the liver by CYP2A6. It remains unknown if plasma letrozole levels or CYP2A6 genetic variation is associated with the development of arthralgia. We enrolled 126 female breast cancer patients initiated on letrozole therapy and prospectively collected blood samples at baseline and two follow-up time points to determine letrozole plasma concentrations and CYP2A6 genotype. At each visit, participants completed two validated questionnaires to assess the severity of arthralgia symptoms. More than half (55%) of patients experienced a significant increase in their arthralgia symptoms after initiation of treatment. The clinical variables of body mass index (P = 0.0003) and age (P = 0.0430) were negatively and positively associated with plasma letrozole concentrations, respectively. CYP2A6 genotype was significantly associated with letrozole levels (P

Purpose: Increasingly, patient- and family-centered care (PFCC) is recognized as a valuable component of healthcare reform with rich opportunities for improvement within oncology. Shifting toward PFCC requires physician buy-in; however, research examining their perspectives on PFCC is lacking. We sought to explore oncologists’ perspectives on PFCC to identify factors that influence their ability to practice PFCC. Methods: We conducted semi-structured interviews with 18 oncologists (8 radiation, 4 medical, 4 surgical, 2 hematologist-oncologists) at a single Canadian academic cancer institution. Interview data were analyzed using thematic analysis and principles drawn from grounded theory. Subsequently, focus groups consisting of the interviewed participants were facilitated to confirm and elaborate on our findings. Constant comparisons were used to identify recurring themes. Results: Three dominant themes emerged. First, physicians displayed cautious engagement in their approach to PFCC. Collectively, participants understood the general principles of PFCC. However, there was a limited understanding of the value, implications, and motivation for improving PFCC which may create reluctance with physician buy-in. Second, both individual and system barriers to practicing PFCC were identified. A lack of physician acknowledgement and engagement and competing responsibilities emerged as provider-level challenges. System barriers included impaired clinic workflow, physical infrastructure constraints, and delays in access to care. Third, physicians were able to identify existing and potential PFCC behaviors that were feasible within existing system constraints. Conclusions: Advancing PFCC will require continued physician education regarding the value of PFCC, acknowledgement and preservation of effective patient- and family-centered strategies, and creative solutions to address the system constraints to delivering PFCC.

Breast cancer is the number one cause of cancer deaths among Hispanic women in the United States, and in Mexico, it recently became the primary cause of cancer deaths. This malignnancy represents a poorly understood and understudied disease in Hispanic women. The ELLA Binational Breast Cancer Study was established in 2006 as a multi-center study to assess patterns of breast tumor markers, clinical characteristics, and their risk factors in women of Mexican descent. We describe the design and implementation of the ELLA Study and provide a risk factor comparison between women in the U.S. and those in Mexico based on a sample of 765 patients (364 in the U.S. and 401 in Mexico). Compared to women in Mexico, U.S. women had significantly (p < 0.05) lower parity (3.2 vs. 3.9 mean live births) and breastfeeding rates (57.5% vs. 80.5%), higher use of oral contraceptives (60.7% vs. 50.1%) and hormone replacement therapy (23.3% vs. 7.6%), and higher family history of breast cancer (15.7% vs. 9.0%). Results show that differences in breast cancer risk factor patterns exist between Mexico and U.S. women. We provide lessons learned from the conduct of our study. Binational studies are an important step in understanding disease patterns and etiology for women in both countries.

Postmastectomy radiotherapy (PMRT) improves locoregional control (LRC) in patients with high-risk features after mastectomy. Young age continues to evolve as a potentially important risk factor. The objective of this study was to assess the benefits of PMRT in patients35 years old treated with doxorubicin-based neoadjuvant chemotherapy for Stage II-III breast cancer.We retrospectively analyzed 107 consecutive breast cancer patients35 years old with Stage IIA-IIIC disease treated at our institution with doxorubicin-based neoadjuvant chemotherapy and mastectomy, with or without PMRT. The treatment groups were compared in terms of LRC and overall survival.Despite more advanced disease stages, the patients who received PMRT (n = 80) had greater rates of LRC (5-year rate, 88% vs. 63%, p = 0.001) and better overall survival (5-year rate, 67% vs. 48%, p = 0.03) than patients who did not receive PMRT (n = 27).Among breast cancer patients35 years old at diagnosis, the use of PMRT after doxorubicin-based neoadjuvant chemotherapy and mastectomy led to a statistically greater rate of LRC and overall survival compared with patients without PMRT. The benefit seen for PMRT in young patients provides valuable data to better tailor adjuvant, age-specific treatment decisions after mastectomy.

The concurrent diagnosis of breast cancer and pregnancy remains a challenging clinical situation. Ethical concerns regarding maternal and fetal well-being and potential risks and harms of treatment influence the clinical decision process. Ethical considerations of treatment initiation have emphasized the role of autonomy for the patient and the concept of beneficence and non-maleficence for patient and fetus. Limited prospective data are available to assist the physician and patient in making an informed decision. Recent data on diagnosis, evaluation, and management of pregnant patients with breast cancer have informed the development of international recommendations and guidelines for management of breast cancer during pregnancy. This article reviews the epidemiology, clinical presentation, diagnosis, therapy, and outcomes of breast cancer occurring concomitantly with pregnancy.

e18014Background: There is a growing recognition that patient- and family-centered care (PFCC) is a vital part of healthcare reform with rich opportunities for improvement within oncology. A shift ...

Feathers of selected bird species are used as pollution integrating biomonitors in areas of the German Environmental Specimen Bank. Lead, cadmium and mercury are analysed by Zeeman Solid Sampling AAS in feather vanes of selected bird species with different ecologies. In feather vanes there are quite different distribution patterns of lead and cadmium on the one hand and mercury on the other: lead and cadmium show strong gradients with respect to feather parts with high exposure to atmospheric influences. In contrast to this, mercury is distributed homogeneously. These different distribution patterns of lead and cadmium in feather vanes, in contrast to mercury, show that there are quite different incorporation paths. Cadmium and lead are deposited exogenously and indicate atmospheric pollution. Mercury in feathers is caused endogenously by food and physiology. Most of the mercury analysed in bird's feathers is in the ecotoxic methylated form and the contents in feathers depend on bioaccumulation in food chains. Feathers are suitable indicators for monitoring heavy metal pollution and give us information about incorporation paths and ecotoxic effects.

BACKGROUND: The growing diversity of the population of the United States and the high burden of cancer-related symptoms reflect the need for caregiver research within underserved groups. In this longitudinal study, the authors assessed changes in symptom severity in caregivers and underserved minority patients diagnosed with advanced solid tumors who were being treated at public hospitals. METHODS: A total of 85 matched patient-caregiver dyads completed the M. D. Anderson Symptom Inventory 3 times during 20 weeks of chemotherapy. At each time point, symptom severity and interference with daily activities were assessed. Group-based trajectory modeling was used to classify caregivers into high-symptom or low-symptom burden groups. RESULTS: Sadness and distress were more prevalent among caregivers (P = .005). Symptom burden remained stable among caregivers in the high-symptom group (40%), whereas the low-symptom group (60%) demonstrated a statistically significant decrease over time. Multivariate analysis found being a family-member caregiver (adjusted odds ratio [ADJ-OR], 4.1; 95% confidence interval [95% CI], 1.4-11.6) and caring for a highly symptomatic patient (ADJ-OR, 8.0; 95% CI, 1.5-41.4), rather than race, ethnicity, or sociodemographic characteristics, were significant predictors of the caregiver's membership in the high-symptom burden group. CONCLUSIONS: Approximately 40% of the caregivers in the current study were found to be at an increased risk for moderate to severe sadness and distress, which remained severe throughout the patient's treatment course at public hospitals. To the authors' knowledge, this study marks the first time that the concept of symptom burden has been used to measure caregiver burden, and the first time that symptom burden has been measured and documented in dyads of caregivers and underserved minority patients. Cancer 2011. © 2010 American Cancer Society.

The relatively high concentrations of lead and cadmium in feather vanes and the morphological structure of the feather makes it possible to use Zeeman Solid Sampling AAS as an ideal method for analysing microsamples of defined parts of the feather vane. In different feathers of different bird species there is an increase of lead and cadmium concentrations in more exposed parts of the feather vane. These results also confirm that the lead and cadmium burden of feathers predominantly depends on the exogenous deposition of heavy metals from the atmosphere on the surface of bird's feathers.

111 Background: Patient and family-centered care (PFCC) represents an evolution from traditional models of provider-focused and patient-focused care that places a strong emphasis on optimal patient communication, patient autonomy, and shared decision-making within care teams. A shift towards PFCC requires participation across all provider groups. Despite the importance of physician buy-in, research examining physicians’ perspectives on PFCC is lacking. We sought to explore oncologists’ familiarity with the principles of PFCC and perceived barriers to implementing principles of PFCC. Methods: In this qualitative exploratory study, we conducted semi-structured interviews with 18 oncologists (8 radiation, 4 medical, 4 surgical, 2 hematologist-oncologists) at a single Canadian academic cancer institution. Interview data were analyzed using coding principles drawn from grounded theory. Constant comparisons were used to identify recurring themes. Results: We identified 3 dominant themes related to physicians’ interpretations of PFCC: 1) Physicians expressed a limited understanding of the formal principles of PFCC, 2) Physicians identified patient autonomy as essential to PFCC and 3) Disparities between patient and physician objectives exist and result in compromises that may affect the quality of PFCC delivered. Oncologists perceived that spending more time with patients improved PFCC, but also recognized that it would leave less time for other necessary activities. Participants also identified a number of ‘system’ barriers to PFCC, including limited staff and clinical space, excessive case load, a lack of physician support and input into operational decisions, and funding constraints. Many felt that PFCC was challenged by inefficiencies in the system of care delivery, and that progress might lie in reorganization to more clearly match health care staff’s roles and responsibilities to their credentials and skills. Conclusions: Advancing PFCC in our institution will require continued education of physicians regarding the principles of PFCC, acknowledgement and preservation of the PFCC behaviors already in practice and creative solutions to address the system issues that may hamper their abilities to enact PFCC.

BACKGROUND. African-American (AA) race has been associated with a worse outcome in breast cancer. It is unclear whether this is due to biological factors, socioeconomic factors, or both. METHODS. The records from 2 independent cohorts of breast cancer patients treated on institutional protocols with mastectomy and adjuvant (n = 1456) or neoadjuvant (n = 684) doxorubicin-based chemotherapy were retrospectively reviewed. RESULTS. The adjuvant (Adj) chemotherapy cohort included 1142 Caucasian (CA), 186 Hispanic (HI), and 128 (AA) patients. The neoadjuvant (Neo) chemotherapy protocols included 448 CA, 114 HI, and 122 AA patients. In both groups, AA patients had later-stage tumors (Adj P = .017; Neo P = .051), a higher rate of estrogen receptor (ER)-negative disease (Adj P = .054; Neo P = .039), and a worse 10-year actuarial overall survival rate than CA or HI patients (Adj, 52%, 62%, and 62%, respectively, P = .009; Neo, 40%, 50%, and 56%, respectively, P = .015). In multivariate analyses, AA race remained independently associated with a poorer overall survival rate in both cohorts (Adj, hazard ratio = 1.39, P = .018; Neo, hazard ratio = 1.37, P = .02). CONCLUSIONS. The data suggest that AA race is associated with less favorable biological tumor features, such as an increased likelihood of ER-negative disease, than those found in CA and HI patients. Such differences in tumor biology, as well as previously described socioeconomic factors, likely contribute to the lower rate of survival in the AA breast cancer population. Cancer 2006. © 2006 American Cancer Society.

Mit standardisierten Habicht-Mauserfedern last sich die Schwermetallbelastung von Landschaftsausschnitten reprasentativ erfassen, wie der Vergleich mit auf physikalisch-technischem Weg ermittelten Depositionsraten aus dem gleichen Untersuchungsgebiet bestatigt. Zwischen den Cadmium-, Blei- und Kupfergehalten in standardisierten Habicht-Mauserfedern und den gemessenen Depositionsraten dieser Elemente besteht eine signifikante Korrelation. Die einzelnen Handschwingen zeigten unterschiedlich hohe Cadmium-, Blei- und Kupfergehalte, abhangig von ihrer Stellung im Flugel. Auch Federfahnen wiesen eine charakteristische Cadmium- und Bleiverteilung auf. Die exogene Auflagerung von Schwermetallen aus der Atmosphare auf/in die Federfahnen wird diskutiert.