A randomized controlled trial to assess the influence of a picture-based antiemetic medication calendar on medication-taking behavior in adults receiving chemotherapy.

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.

Genetic and clinical predictors of arthralgia during letrozole or anastrozole therapy in breast cancer patients.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Letrozole concentration is associated with CYP2A6 variation but not with arthralgia in patients with breast cancer.

PURPOSE: 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. METHODS: 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. RESULTS: 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 < 0.0001), and increased plasma letrozole levels were observed in patients with CYP2A6 reduced-function genotypes. Plasma levels of letrozole and CYP2A6 genotype were not significantly associated with a change in pain score from baseline. CONCLUSIONS: CYP2A6 genotype was a significant predictor of letrozole plasma levels, but was not associated with the development of arthralgia.

Patient- and family-centered care: a qualitative exploration of oncologist perspectives.

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.

Automated pain intervention for underserved minority women with breast cancer.

BACKGROUND: Minority patients with breast cancer are at risk for undertreatment of cancer-related pain. The authors evaluated the feasibility and efficacy of an automated pain intervention for improving pain and symptom management of underserved African American and Latina women with breast cancer. METHODS: Sixty low-income African American and Latina women with breast cancer and cancer-related pain were enrolled in a pilot study of an automated, telephone-based, interactive voice response (IVR) intervention. Women in the intervention group were called twice weekly by the IVR system and asked to rate the intensity of their pain and other symptoms. The patients' oncologists received e-mail alerts if the reported symptoms were moderate to severe. The patients also reported barriers to pain management and received education regarding any reported obstacles. RESULTS: The proportion of women in both groups reporting moderate to severe pain decreased during the study, but the decrease was significantly greater for the intervention group. The IVR intervention also was associated with improvements in other cancer-related symptoms, including sleep disturbance and drowsiness. Although patient adherence to the IVR call schedule was good, the oncologists who were treating the patients rated the intervention as only somewhat useful for improving symptom management. CONCLUSIONS: The IVR intervention reduced pain and symptom severity for underserved minority women with breast cancer. Additional research on technological approaches to symptom management is needed.

Effect of age and race on quality of life in young breast cancer survivors.

BACKGROUND: Given their early age at diagnosis, young breast cancer survivors (YBCSs) face issues that differ widely from their older counterparts. PATIENTS AND METHODS: We mailed a survey to 2209 patients who were ≤ 45 years at the time of breast cancer (BC) diagnosis. Each survey was composed of the Quality of Life in Adult Cancer Survivors instrument, Menopause Symptom Scale, and questions aimed at obtaining pertinent background information. RESULTS: One thousand ninety patients completed the survey. Mean age at time of diagnosis was 39.5 years; median years from diagnosis was 6.6 years. Distress related to vaginal dryness (P = .0002) and pain from intercourse (P = .0014) was significantly higher in patients who were < 5 years from diagnosis compared with those > 10 years from diagnosis. In the area of financial problems, black women had greater distress than did white women (P = .0010). Compared with white women, Hispanic women had worse family distress scores (P = .0028) and summary cancer-specific scores (P = .0076). Patients > 10 years from diagnosis had less sexual interest (P = .003) than did women who were closer to diagnosis. Women ≥ 40 years at diagnosis had significantly lower sexual interest (P = .0016) than did women < 40 years. Stage and neoadjuvant chemotherapy did not have a significant effect on quality of life (QOL). CONCLUSION: Even in comparison to stage and neoadjuvant chemotherapy, race, age at diagnosis, and time from diagnosis have significant long-term effects on QOL after treatment for BC.

Case control study of women treated with chemotherapy for breast cancer during pregnancy as compared with nonpregnant patients with breast cancer.

BACKGROUND: The purpose of this analysis was to compare disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS) between pregnant and nonpregnant patients with breast cancer. METHODS: From 1989 to 2009, 75 women were treated with chemotherapy during pregnancy. Each pregnant case was matched on age and cancer stage to two nonpregnant patients with breast cancer (controls). Fisher's exact test, the Kaplan-Meier method, and Cox proportional hazards regression models were used. RESULTS: Median follow-up time for patients who were alive at the end of follow-up (n = 159) was 4.20 years (range: 0.28-19.94 years). DFS at 5 years was 72% (95% confidence interval [CI]: 58.3%-82.1%) for pregnant patients and 57% (95% CI: 46.7%-65.8%) for controls (p = .0115). Five-year PFS was 70% (95% CI: 56.8%-80.3%) for pregnant patients and 59% (95% CI: 49.1%-67.5%) for controls (p = .0252). Five-year OS was 77% (95% CI: 63.9%-86.4%) for pregnant patients and 71% (95% CI: 61.1%-78.3%) for controls (p = .0461). Hazard ratio estimates favored improved survival for pregnant patients in univariate analyses and multivariate analyses, controlling for age, year of diagnosis, stage, and tumor grade. CONCLUSIONS: For patients who received chemotherapy during pregnancy, survival was comparable to-if not better than-that of nonpregnant women. Pregnant patients with breast cancer should receive appropriate local and systemic therapy for breast cancer.

Selective genomic copy number imbalances and probability of recurrence in early-stage breast cancer.

A number of studies of copy number imbalances (CNIs) in breast tumors support associations between individual CNIs and patient outcomes. However, no pattern or signature of CNIs has emerged for clinical use. We determined copy number (CN) gains and losses using high-density molecular inversion probe (MIP) arrays for 971 stage I/II breast tumors and applied a boosting strategy to fit hazards models for CN and recurrence, treating chromosomal segments in a dose-specific fashion (-1 [loss], 0 [no change] and +1 [gain]). The concordance index (C-Index) was used to compare prognostic accuracy between a training (n = 728) and test (n = 243) set and across models. Twelve novel prognostic CNIs were identified: losses at 1p12, 12q13.13, 13q12.3, 22q11, and Xp21, and gains at 2p11.1, 3q13.12, 10p11.21, 10q23.1, 11p15, 14q13.2-q13.3, and 17q21.33. In addition, seven CNIs previously implicated as prognostic markers were selected: losses at 8p22 and 16p11.2 and gains at 10p13, 11q13.5, 12p13, 20q13, and Xq28. For all breast cancers combined, the final full model including 19 CNIs, clinical covariates, and tumor marker-approximated subtypes (estrogen receptor [ER], progesterone receptor, ERBB2 amplification, and Ki67) significantly outperformed a model containing only clinical covariates and tumor subtypes (C-Index(full model), train[test]  =  0.72[0.71] ± 0.02 vs. C-Index(clinical + subtype model), train[test]  =  0.62[0.62] ± 0.02; p<10(-6)). In addition, the full model containing 19 CNIs significantly improved prognostication separately for ER-, HER2+, luminal B, and triple negative tumors over clinical variables alone. In summary, we show that a set of 19 CNIs discriminates risk of recurrence among early-stage breast tumors, independent of ER status. Further, our data suggest the presence of specific CNIs that promote and, in some cases, limit tumor spread.

Caregiver symptom burden: the risk of caring for an underserved patient with advanced cancer.

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.

Wound complications from surgery in pregnancy-associated breast cancer (PABC).

BACKGROUND: there are concerns that physiologic changes of the peripartum breast may result in complications in breast conservation therapy. We present the complications of breast conservation surgeries and mastectomies performed for pregnancy-associated breast cancer (PABC). MATERIALS AND METHODS: from April 1989 through April 2008, sixty-seven breast cancer patients underwent surgical management for PABC, defined as surgery during pregnancy or within one year postpartum. Records of women who had surgery were examined for post-operative wound complications of milk fistula, cellulitis, abscess, or hematoma. RESULTS: Forty-seven patients underwent mastectomy. Twenty were treated with conservative breast surgery. There were six complications, all treated in the outpatient setting. There were no documented milk fistulae. CONCLUSIONS: in our series, we had few postoperative complications and no milk fistulae for those patients undergoing surgery for PABC. When compared to those who had mastectomy for PABC, women who underwent breast conserving therapy did not appear to have increased frequency of surgical complications.

Effect of postmastectomy radiotherapy in patients <35 years old with stage II-III breast cancer treated with doxorubicin-based neoadjuvant chemotherapy and mastectomy.

PURPOSE: 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 patients <35 years old treated with doxorubicin-based neoadjuvant chemotherapy for Stage II-III breast cancer. PATIENTS AND METHODS: We retrospectively analyzed 107 consecutive breast cancer patients <35 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. RESULTS: 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). CONCLUSION: Among breast cancer patients <35 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.

Relationship between epidemiologic risk factors and breast cancer recurrence.

PURPOSE: Early-stage breast cancers are biologically heterogeneous and vary in clinical behavior, supporting the role of factors other than tumor size and lymph node involvement as outcome determinants. We evaluated the effect of epidemiologic breast cancer risk factors on recurrence in women with early-stage disease. PATIENTS AND METHODS: Medical records from 2,327 women with early-stage breast cancer, treated at the M.D. Anderson Cancer Center between 1985 and 2000, were used to derive information on epidemiologic, clinical, and histological factors. Cox proportional hazards models were used to estimate the hazard ratios of 5-year risk of breast cancer recurrence adjusted for treatment and stage. Statistical tests were two-sided. RESULTS: None of the breast cancer risk factors were associated with recurrence, adjusting for tumor characteristics and treatment. A significant interaction between hormone replacement therapy (HRT) use and tumor hormone receptor status on risk of recurrence (P = .0003) was observed. Among ever-users of HRT, recurrence risk was two-fold lower for estrogen receptor (ER)--positive and progesterone receptor (PR)--positive tumors compared with ER- and PR-negative tumors; whereas, among never-users of HRT, there was no statistically significant association between recurrence risk and receptor status. CONCLUSION: HRT users who develop receptor-positive early-stage disease have better outcomes than those who develop receptor-negative disease. Among never-users of HRT, the expected beneficial effect of ER- or PR-positive tumors on recurrence risk was absent. These data lend support to the notion that the biology of hormone receptor-positive disease in HRT users differs from that in nonusers.

Factors associated with advanced disease stage at diagnosis in a population-based study of patients with newly diagnosed breast cancer.

Breast cancer is diagnosed at a younger age and a more advanced stage in African-American women than in White women. The authors investigated the effects of several factors, including race, on stage of breast cancer in women aged 20-54 years living in Atlanta, Georgia, and diagnosed between 1990 and 1992. A total of 251 African-American and 580 White women were interviewed and their medical records reviewed. By use of polytomous logistic regression, factors possibly influencing stage and racial differences in stage were studied. In African-American women, the odds of stage III/IV breast cancer at diagnosis were almost four times the odds in White women (odds ratio = 3.79, 95% confidence interval: 2.45, 5.89) and approximately two and one-half times for stage IIA or stage IIB disease (odds ratio = 2.57, 95% confidence interval: 1.66, 3.99; odds ratio = 1.94, 95% confidence interval: 1.31, 2.86, respectively). These racial differences appeared to be largely explained by insurance status, poverty, history of mammography, method of tumor detection, and obesity. Interventions targeting these factors could potentially lower the stage at diagnosis for African-American breast cancer patients and, in doing so, improve their survival and other outcomes.

Management of breast cancer in pregnancy.

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.

African-American race is associated with a poorer overall survival rate for breast cancer patients treated with mastectomy and doxorubicin-based chemotherapy.

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.

Treatment of pregnant breast cancer patients and outcomes of children exposed to chemotherapy in utero.

BACKGROUND: As women in the US delay childbearing, it has been hypothesized that the incidence of breast cancer diagnosed during pregnancy will increase. There are very little prospective data on the treatment of pregnant women with breast cancer with chemotherapy and even less data on the outcomes of their children who were exposed to chemotherapy in utero. METHODS: Fifty-seven pregnant breast cancer patients were treated on a single-arm, multidisciplinary, institutional review board-approved protocol with FAC (5-fluorouracil, doxorubicin, cyclophosphamide) in the adjuvant (n = 32) or neoadjuvant (n = 25) setting. Parents/guardians were surveyed by mail or telephone regarding outcomes of children exposed to chemotherapy in utero. RESULTS: Of the 57 women, 40 are alive and disease-free, 3 have recurrent breast cancer, 12 died from breast cancer, 1 died from other causes, and 1 was lost to follow-up. Of the 25 patients who received neoadjuvant FAC, 6 had a pathologic complete response, whereas 4 had no tumor response to chemotherapy and eventually died from their disease. All women who delivered had live births. One child has Down syndrome and 2 have congenital anomalies (club foot; congenital bilateral ureteral reflux). The children are healthy and those in school are doing well, although 2 have special educational needs. CONCLUSIONS: Breast cancer can be treated with FAC chemotherapy during the second and third trimesters without significant short-term complications for the majority of children exposed to chemotherapy in utero. Longer follow-up of the children is needed to evaluate possible late side effects such as impaired cardiac function and fertility.