Long-Term Patient-Reported Arm Symptoms in Breast Cancer Survivors.

BACKGROUND: Understanding long-term arm symptoms in breast cancer survivors is critical given excellent survival in the modern era. METHODS: This cross-sectional study included patients treated for stage 0-III breast cancer at our institution from 2002 to 2012. Patient-reported arm symptoms were collected from the EORTC QLQ-BR23 questionnaire. We used linear regression to evaluate adjusted associations between locoregional treatments and the continuous Arm Symptom (AS) score (0-100; higher score reflects more symptoms). RESULTS: A total of 1126 patients expressed interest in participating and 882 (78.3%) completed the questionnaire. Mean time since surgery was 10.5 years. There was a broad distribution of locoregional treatments, including axillary lymph node dissection (ALND) in 37.1% of patients, mastectomy with reconstruction in 36.5% of patients, and post-mastectomy radiation in 38.2% of patients. Overall, 64.3% (95% confidence interval [CI] 61.1-67.4%) of patients reported no arm symptoms, 17.0% (95% CI 14.7-19.6%) had one mild symptom, 9.4% (95% CI 7.7-11.5%) had two or more mild symptoms, and 9.3% (95% CI 7.6-11.4%) reported one or more severe symptoms. Adjusted AS scores were significantly higher with ALND versus sentinel node biopsy (ß 3.5, p = 0.01), and with autologous reconstruction versus all other breast/reconstructive surgery types (ß 4.5-5.5, all p < 0.05). There was a significant interaction between axillary and breast/reconstructive surgery, with the greatest effect of ALND in those with mastectomy with implant (ß 9.7) or autologous (ß 5.7) reconstruction. CONCLUSIONS: One in three patients reported arm symptoms at a mean of 10 years from treatment for breast cancer, although rates of severe symptoms were low (<10%). Attention is warranted to the arm morbidity related to both axillary and breast surgery during treatment counseling and survivorship.

Incorporating Patient-Reported Outcome Measures into Breast Surgical Oncology: Advancing Toward Value-Based Care.

Value in health care is defined as the health outcome achieved per unit of cost. For health care systems, improving value means achieving better outcomes at lower costs. Improving outcomes, including patient-reported outcomes (PROs), as well as more established metrics such as mortality and complication rates, ensures high-quality care. This is particularly true in breast cancer surgery, where survival and recurrence rates are comparable across different surgical approaches. Outcomes reflecting survivorship quality may therefore better inform decision making regarding surgical approaches. PROs can be assessed using validated instruments known as patient-reported outcome measures (PROMs). They are obtained directly from patients reflecting their health-related quality of life (HRQOL). Ongoing initiatives strive to define PROMs that accurately reflect HRQOL and demonstrate value, with the goal of establishing benchmarks for quality of care. Clinicians caring for patients with breast cancer are well positioned to be involved in defining meaningful measures of value-based breast cancer care. This article reviews value-based breast cancer care in the context of locoregional therapy, with attention paid to the work done by the International Consortium of Health Outcome Measures in which a "standard set" of value-based patient-centered outcomes for breast cancer for international use is defined. In addition, an overview is provided of relevant PROMs and previously reported scores. Recommendations and future challenges for implementation of routine collection of PROs are also discussed. IMPLICATIONS FOR PRACTICE: Opportunity exists to act as early adopters of the routine collection of longitudinal patient-reported outcome data for breast cancer, allowing transition of current care to value-based cancer care.

Breast conserving therapy and mastectomy revisited: Breast cancer-specific survival and the influence of prognostic factors in 129,692 patients.

This large population-based study compared breast-conserving surgery with radiation therapy (BCT) with mastectomy on (long-term) breast cancer-specific (BCSS) and overall survival (OS), and investigated the influence of several prognostic factors. Patients with primary T1-2N0-2M0 breast cancer, diagnosed between 1999 and 2012, were selected from the Netherlands Cancer Registry. We investigated the 1999-2005 (long-term outcome) and the 2006-2012 cohort (contemporary adjuvant systemic therapy). Cause of death was derived from the Statistics Netherlands (CBS). Multivariable analyses, per time cohort, were performed in T1-2N0-2, and separately in T1-2N0-1 and T1-2N2 stages. The T1-2N0-1 stages were further stratified for age, hormonal receptor and HER2 status, adjuvant systemic therapy and comorbidity. In total, 129,692 patients were included. In the 1999-2005 cohort, better BCSS and OS for BCT than mastectomy was seen in all subgroups, except in patients < 40 years with T1-2N0-1 stage. In the 2006-2012 cohort, superior BCSS and OS were found for T1-2N0-1, but not for T1-2N2. Subgroup analyses for T1-2N0-1 showed superior BCSS and OS for BCT in patients >50 years, not treated with chemotherapy and with comorbidity. Both treatments led to similar BCSS in patients <50 years, without comorbidity and those treated with chemotherapy. Although confounding by severity and residual confounding cannot be excluded, this study showed better long-term BCSS for BCT than mastectomy. Even with more contemporary diagnostics and therapies we identified several subgroups that may benefit from BCT. Our results support the hypothesis that BCT might be preferred in most breast cancer patients when both treatments are suitable.

Evaluation of cosmetic outcome following breast-conserving therapy in trials: panel versus digitalized analysis and the role of PROMs.

Cosmetic outcome is an important quality of life-related end point following breast-conserving therapy (BCT). To advise on a gold standard, we compare cosmetic outcome evaluated by panel and an objective evaluation (BCCT.core software). Second, patient-reported outcome measures (PROMs) are compared to cosmetic outcome evaluation by panel and BCCT.core. Sixty-eight breast cancer patients were included following BCT between 2007 and 2012. Two independent 6-member panels and two observers using the BCCT.core evaluated cosmetic outcome. First, reproducibility, repeatability, and relatedness of panel and BCCT.core were analyzed using the interclass correlation coefficient (ICC). Second, the association between panel/BCCT.core with PROMs (EORTC-QLQ-C30/BR23, EQ-5D-5L, and BREAST-Q) was analyzed with a linear regression and the goodness of fit by the R2 . Both panel and BCCT.core evaluations showed "excellent" intraobserver agreement (ICC 0.93 [95% CI: 0.83; 0.97] and 0.93 [95% CI: 0.84; 0.97]) for respectively panel 1 and BCCT.core 1 and "excellent" interobserver agreement (ICC 0.94 [95% CI: 0.90; 0.96] and 0.85 [95% CI: 0.77; 0.91]) respectively for panel and BCCT.core. Association between panel and BCCT.core varied, ICC 0.59-0.69. Only the PROM BREAST-Q showed a significant association with both panel evaluations and BCCT.core observers (panel 1 and BCCT.core 1; R2 of .157 [P = .002] and .178 [P = .001]). Both panel and BCCT.core showed comparable "excellent" intraobserver and interobserver agreement. For future trials evaluating cosmetic outcome following BCT, one of those can be chosen. Solely, the PROM BREAST-Q showed a significant association with panel and/or BCCT.core evaluation. To enable standardized cosmetic outcome evaluation and corresponding patient satisfaction in future trials, at least the BREAST-Q should be combined with a panel or BCCT.core evaluation.

Arm morbidity and financial difficulty in breast cancer survivors.

PURPOSE: Long-term upper extremity symptoms after breast cancer treatment may impact patient-reported financial difficulty. In this cross-sectional investigation, we hypothesized that severity of arm symptoms would be associated with greater financial difficulty. METHODS: Stage 0-III breast cancer patients treated at our institution from 2002 to 2012 were recruited for a 2018 survey study appraising disease-specific patient-centered outcomes using EORTC-QLQ-BR23 and EORTC-QLQ-C30 questionnaires. The association between Arm Symptom (AS) score and Financial Impact (FI) score was assessed, adjusting for clinically relevant variables. RESULTS: Of 1126 interested participants, 882 (78%) responded to surveys. Three hundred fourteen (36%) with incomplete responses were excluded. Median time from surgery was 9 years; 181 (32%) and 117 (21%) had mastectomy with or without reconstruction, 126 (22%) received postmastectomy radiation (PMRT), and 221 (39%) underwent axillary lymph node dissection. 76 (13%) reported some degree of financial difficulty; 10 (2%) the highest degree of difficulty. Of 217 (38%) patients experiencing arm symptoms, 60 (28%) had severe symptoms. Seven (70%) of those with highest degree of financial difficulty had severe arm symptoms. Younger age at surgery (p = .029), mastectomy with reconstruction (p = 0.003), Hispanic ethnicity (p < 0.001), PMRT (p = 0.027), recurrence (p < 0.001), and higher AS score (p < 0.001) were associated with greater financial difficulty. On multivariable analysis, AS score, younger age, Hispanic ethnicity, and recurrence remained associated with financial difficulty. CONCLUSION: In this study, younger age, Hispanic ethnicity, and arm morbidity were associated with increased risk for financial difficulty. Clarifying how treatment-related adverse events such as arm morbidity increase financial hardship may guide interventions to mitigate this burden.

Impact of surgical complications on patient reported outcomes (PROs) following nipple sparing mastectomy.

INTRODUCTION: Nipple sparing mastectomy (NSM) is oncologically safe and provides excellent cosmetic outcomes. Complications after surgery may impact patient reported outcomes (PROs). We assessed the impact of complications on PROs after NSM. METHODS: We enrolled 63 patients (pts) who met eligibility criteria for NSM from September 2011 until August 2014. PROs were administered before surgery and at 1 year. Clinical data were collected from the electronic health record. Analyses were performed in SPSS Statistics for Windows (version 21.0). Pts with and without complications were compared using a one-way ANOVA. DATA: Sixty-three women were enrolled with a median age of 46. Postoperative complications requiring surgical treatment were seen in 10 patients (15.9%). Two patients required nipple excision due to necrosis (3.1%). No statistically significant differences in BREAST-Q scores were seen between pts with and without complications. CONCLUSION: Experiencing a complication after initial NSM surgery is not associated with decrease in PROs.

Correction: MicroRNA expression in pre-treatment plasma of patients with benign breast diseases and breast cancer.

[This corrects the article DOI: 10.18632/oncotarget.25262.].

MicroRNA expression in pre-treatment plasma of patients with benign breast diseases and breast cancer.

BACKGROUND: MicroRNAs (miRs) are small RNA molecules, influencing messenger RNA (mRNA) expression and translation, and are readily detectable in blood. Some have been reported as potential breast cancer biomarkers. This study aimed to identify and validate miRs indicative of breast cancer. RESULTS: Based on the discovery and literature, 18 potentially informative miRs were quantified in the validation cohort. Irrespective of patient and tumour characteristics, hsa-miR-652-5p was significantly upregulated in the malignant compared to benign patients (1.26 fold, P = 0.005) and therefore validated as potential biomarker. In the validation cohort literature-based hsa-let-7b levels were higher in malignant patients as well (1.53 fold, P = 0.011). Two miRs differentiated benign wildtype from benign BRCA1 mutation carriers and an additional 8 miRs differentiated metastastic (n = 8) from non-metastatic (n = 41) cases in the validation cohort. METHODS: Pre-treatment plasma samples were collected of patients with benign breast disease and breast cancer and divided over a discovery (n = 31) and validation (n = 84) cohort. From the discovery cohort miRs differentially expressed between benign and malignant cases were identified using a 2,000-miR microarray. Literature-based miRs differentiating benign from malignant disease were added. Using RT-qPCR, their expression was investigated in a validation cohort consisting of pre-treatment benign, malignant and metastatic samples. Additionally, benign and malignant cases were compared to benign and malignant cases of BRCA1-mutation carriers. CONCLUSIONS: Plasma microRNA levels differed between patients with and without breast cancer, between benign disease from wildtype and BRCA1-mutation carriers and between breast cancer with and without metastases. Hsa-miR-652-5p was validated as a potential biomarker for breast cancer.