Rural comprehensive cancer care: Qualitative analysis of current challenges and opportunities.

PURPOSE: While limited resources can make high-quality, comprehensive, coordinated cancer care provision challenging in rural settings, rural cancer patients often rely on local hospitals for care. To develop resources and strategies to support high-quality local cancer care, it is critical to understand the current experiences of rural cancer care physicians, including perceived strengths and challenges of providing cancer care in rural areas.  METHODS: Semi-structured interviews were conducted with 13 cancer providers associated with all 12 non-metropolitan/rural Iowa hospitals that diagnose or treat >100 cancer patients annually. Iterative thematic analysis was conducted to develop domains. FINDINGS: Participants identified geographic proximity and sense of community as strengths of local care. They described decision-making processes and challenges related to referring patients to larger centers for complex procedures, including a lack of dedicated navigators to facilitate and track transfers between institutions and occasional lack of respect from academic physicians. Participants reported a desire for strengthening collaborations with larger urban/academic cancer centers, including access to educational opportunities, shared resources and strategies to collect and monitor data on quality, and clinical trials. CONCLUSIONS: Rural cancer care providers are dedicated to providing high-quality care close to home for their patients and would welcome opportunities to increase collaboration with larger centers to improve coordination and comprehensiveness of care, collect and monitor data on quality of care, and access continuing education opportunities. Further research is needed to develop implementation approaches that will extend resources, services, and expertise to rural providers to facilitate high-quality cancer care for all cancer patients.

Breast cancer patients from the Midwest region of the United States have reduced levels of short-chain fatty acid-producing gut bacteria.

As geographical location can impact the gut microbiome, it is important to study region-specific microbiome signatures of various diseases. Therefore, we profiled the gut microbiome of breast cancer (BC) patients of the Midwestern region of the United States. The bacterial component of the gut microbiome was profiled utilizing 16S ribosomal RNA sequencing. Additionally, a gene pathway analysis was performed to assess the functional capabilities of the bacterial microbiome. Alpha diversity was not significantly different between BC and healthy controls (HC), however beta diversity revealed distinct clustering between the two groups at the species and genera level. Wilcoxon Rank Sum test revealed modulation of several gut bacteria in BC specifically reduced abundance of those linked with beneficial effects such as Faecalibacterium prausnitzii. Machine learning analysis confirmed the significance of several of the modulated bacteria found by the univariate analysis. The functional analysis showed a decreased abundance of SCFA (propionate) production in BC compared to HC. In conclusion, we observed gut dysbiosis in BC with the depletion of SCFA-producing gut bacteria suggesting their role in the pathobiology of breast cancer. Mechanistic understanding of gut bacterial dysbiosis in breast cancer could lead to refined prevention and treatment.

Optimization of Neoadjuvant Therapy for Early-Stage Triple-Negative and HER2 + Breast Cancer.

PURPOSE OF REVIEW: Neoadjuvant, or pre-operative, therapy for the treatment of early-stage breast cancer has several potential benefits, especially for patients with triple-negative or HER2 + subtypes. This review provides an overview of optimal practices for utilizing neoadjuvant therapy, guidelines for decision-making, and ongoing clinical trials that are expected to help refine therapy choices. RECENT FINDINGS: For triple-negative disease, the addition of the checkpoint inhibitor pembrolizumab to chemotherapy has shown remarkable efficacy, increasing response rates and survival. In the HER2 + setting, we are now able to safely avoid use of anthracyclines in most patients and refine adjuvant treatment choices based on response to neoadjuvant therapy. Results from recent clinical studies highlight advancements in systemic therapy and mark steps toward precision medicine, although reliable biomarkers of therapy response are still needed.

Hospital Rurality and Gene Expression Profiling for Early-Stage Breast Cancer among Iowa Residents (2010-2018).

Objective: Given the challenges rural cancer patients face in accessing cancer care as well as the slower diffusion and adoption of new medical technologies among rural providers, the aim of our study was to examine trends in gene expression profiling (GEP) testing and evaluate the association between hospital rurality and receipt of GEP testing. Methods: Data from the Iowa Cancer Registry (ICR) were used to identify women with newly diagnosed, histologically confirmed breast cancer from 2010 through 2018 who met eligibility criteria for GEP testing. Patients were allocated to the hospitals where their most definitive surgical treatment was received, and Rural-Urban Commuting Area codes were used to categorize hospitals into urban (N = 43), large rural (N = 16), and small rural (N = 48). Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression to evaluate the association between hospital rurality and GEP test use, adjusting for demographic and clinical characteristics. The association between test result and treatment received was assessed among patients who received Oncotype DX (ODX) testing. Results: Of 6,726 patients eligible for GEP test use, 46% (N = 3,069) underwent testing with 95% receiving ODX. While overall GEP testing rates increased over time from 42% between 2010 and 2012 to 51% between 2016 and 2018 (P trend < 0.0001), use continued to be the lowest among patients treated at hospitals in small rural areas. The odds of GEP testing remained significantly lower among patients treated at hospitals located in small rural areas (aOR 0.55; 95% CI 0.43-0.71), after adjusting for demographic and clinical characteristics. ODX recurrence scores were highly correlated with chemotherapy use across all strata of hospital rurality. Conclusions: GEP testing continues to be underutilized, especially among those treated at small rural hospitals. Targeted interventions aimed at increasing rates of GEP testing to ensure the appropriate use of adjuvant chemotherapy may improve health outcomes and lower treatment-related costs.

Analysis of the Understanding and Worry about Lymphedema of Patients with Breast Cancer.

BACKGROUND: Lymphedema is a potential lifelong sequela of breast cancer treatment. We sought to: (1) evaluate the worry and knowledge of patients about lymphedema, (2) quantify patients reporting lymphedema education and screening, and (3) determine willingness to participate in lymphedema screening and prevention programs. PATIENTS AND METHODS: A survey evaluating lymphedema-related knowledge and worry was sent to patients treated for stage 0-III breast cancer. Exclusion criteria included > 10 years since diagnosis, missing clinical staging, and those without axillary surgery. Responses were linked with clinicopathologic information. RESULTS: Of 141 patients meeting inclusion criteria, 89% of those without lymphedema were not at all or slightly worried about lymphedema. Higher levels of worry were associated with clinical stage II-III disease [odds ratio (OR) 2.63, p = 0.03], a history of axillary lymph node dissection (ALND) (OR 4.58, p < 0.01), and employment (OR 2.21, p = 0.05). A total of 102 (72%) patients recalled receiving lymphedema education. Lymphedema knowledge was limited, with < 25% of respondents answering > 50% of the risk factor questions correctly. Worry and knowledge were not significantly associated. Of patients without lymphedema, 36% were interested in learning more about lymphedema and 64% were willing to participate in or learn more about a screening program. Most (66%) felt that lymphedema information should be provided before and after cancer treatment. DISCUSSION: A majority of our breast cancer survivors had limited knowledge about lymphedema risk factors. While most patients were not worried about developing lymphedema, higher worry was seen in patients with a higher clinical stage at diagnosis, ALND, and employment. Our findings suggest potential targets and timing for patient-centered educational interventions.

Characterizing Early Changes in Quality of Life in Young Women With Breast Cancer.

Introduction: Younger age at diagnosis is a risk factor for poor health-related quality of life (HRQOL) in long-term breast cancer survivors. However, few studies have specifically addressed HRQOL in young adults with breast cancer (i.e., diagnosed prior to age 40), nor have early changes in HRQOL been fully characterized. Methods: Eligible female patients with breast cancer were identified through our local cancer center. To establish HRQOL, patients completed the Functional Assessment of Cancer Therapy-Breast (FACT-B) around diagnosis and 12 months later. Sociodemographic factors, genetic susceptibility to cancer, tumor- and treatment-related factors, and comorbidities (e.g., depression/anxiety) were abstracted from medical records and the local oncology registry. Mixed-effects models were used to identify changes in FACT-B scores during the first year of treatment and to determine whether any demographic/treatment-related factors modulated changes in scores. Results: Health-related quality of life in young patients with breast cancer was within normal limits at baseline, with a FACT-B overall well-being score of 108.5 (95% confidence limits [CI] = 103.7, 113.3). Participants reported slight improvements over a 12-month period: FACT-B overall well-being scores increased 6.6 points (95% CI = 2.1, 11.1, p < 0.01), functional well-being improved 3.0 points (95% CI = 2.0, 4.1, p < 0.01), emotional well-being improved 1.9 points (95% CI = 0.9, 2.8, p < 0.01), and physical well-being improved 1.5 points (95% CI = 0.2, 2.8, p = 0.03), on average. Participants with anxiety/depression at baseline reported greater improvements in FACT-B overall well-being (change: 12.9, 95% CI = 6.4, 9.5) and functional well-being (change: 5.2, 95% CI = 3.5, 6.9) than participants who did not have anxiety/depression at baseline (change in FACT-B overall well-being: 4.9, 95% CI = 0.2, 9.7; change in functional well-being: 2.3, 95% CI = 1.1, 3.4). Marital status, reconstructive surgery, and baseline clinical staging were also significantly associated with changes in aspects of HRQOL, although their impact on change was relatively minimal. Conclusion: Young women with breast cancer do not report HRQOL concerns during the first year of treatment. Improvements in HRQOL during the first year of treatment may be attributable to a sense of relief that the cancer is being treated, which, in the short run, may outweigh the negative late effects of treatment.

Breast Cancer Epidemiology and Contemporary Breast Cancer Care: A Review of the Literature and Clinical Applications.

Substantial progress has been made in contemporary breast cancer care, resulting in a consistently declining breast cancer mortality rate and an improvement in quality of life. Advancements include deescalation of therapy in low-risk populations and refining systemic therapy options. Research into molecular biomarkers continues to evolve and holds the promise of achieving the goal of precision medicine, while guidelines for supportive care and survivorship have been created to address the needs of an ever-increasing number of breast cancer survivors. A collaborative, multidisciplinary team approach is essential for patients and survivors to achieve optimal outcomes and enjoy productive high-quality lives. Gynecologists, in particular, play a key role in screening and survivorship care.

Directed movement toward, translocation along, penetration into and exit from vascular networks by breast cancer cells in 3D.

We developed a computer-assisted platform using laser scanning confocal microscopy to 3D reconstruct in real-time interactions between metastatic breast cancer cells and human umbilical vein endothelial cells (HUVECs). We demonstrate that MB-231 cancer cells migrate toward HUVEC networks, facilitated by filopodia, migrate along the network surfaces, penetrate into and migrate within the HUVEC networks, exit and continue migrating along network surfaces. The system is highly amenable to 3D reconstruction and computational analyses, and assessments of the effects of potential anti-metastasis monoclonal antibodies and other drugs. We demonstrate that an anti-RHAMM antibody blocks filopodium formation and all of the behaviors that we found take place between MB-231 cells and HUVEC networks.

Metastatic Presentations of Previously Treated Early-Stage Breast Cancer Patients and Association With Survival.

BACKGROUND: Breast cancer (BC) patients undergoing surveillance often fear recurrence. Given that routine imaging is not recommended, recognizing metastatic disease early requires a knowledge of recurrence patterns. The aim of this study was to analyze the most common presentations of metastatic disease. PATIENTS AND METHODS: A retrospective review was conducted of patients who were initially diagnosed with early-stage BC and who later developed metastatic disease. Data collected included method of metastatic disease diagnosis, types of symptoms at diagnosis, and survival. Chi-square tests as well as logistic and Cox regression models were used. RESULTS: Metastatic diagnoses were made from reported symptoms in 77.6% of patients, clinical examination in 3.2%, and 7.8% incidentally on imaging. Among those with symptoms, musculoskeletal pain was the most common (33.7%) and was more frequently noted at scheduled (48.9%) compared to acute-care visits (26.0%, P < .01). Receptor status was associated with nervous system symptoms at metastasis (P = .01), with higher odds of nervous system symptoms in triple-negative (odds ratio = 3.02) compared to estrogen receptor/progesterone receptor-positive, HER2- cases. On multivariable analysis, initial stage (P = .03), receptor status (P < .01), age (P < .01), and time to recurrence (P < .01) were significantly associated with 10-year survival after diagnosis of metastasis, whereas the presence of symptoms was not (P = .27). Providers of BC patients undergoing surveillance should modify their threshold of suspicion for recurrence depending on the characteristics of the initial diagnosis and the symptoms subsequently reported. CONCLUSION: In this retrospective study, patients who presented with symptoms did not have shorter survival compared to those who were diagnosed in other ways.

Dermatofibrosarcoma protuberans - the use of neoadjuvant imatinib for treatment of an uncommon breast malignancy: a case report.

BACKGROUND: Dermatofibrosarcoma protuberans is a rare soft tissue malignancy that, if left untreated, can be locally destructive and life-threatening. Dermatofibrosarcoma protuberans is uncommon in the breast, and the similarity of its morphologic features with other spindle cell malignancies can make correct identification difficult. Immunohistochemistry and molecular testing can aid in the correct diagnosis when there is diagnostic uncertainty. Imatinib, a selective tyrosine kinase inhibitor, has been used for adjuvant treatment of dermatofibrosarcoma protuberans following surgical resection. When used as a neoadjuvant treatment, imatinib offers the opportunity to decrease tumor size prior to surgery to lessen the chance for disfigurement. CASE PRESENTATION: We present the case of a Caucasian woman who was 46-year-old when she first noted a mass in her right breast in 2015; she was initially diagnosed as having metaplastic breast carcinoma. Mastectomy and systemic chemotherapy were planned; however, after review of pathology at a referral center, the diagnosis was changed to dermatofibrosarcoma protuberans. She was treated with 4 months of neoadjuvant imatinib with adequate tumor shrinkage to perform breast conservation. CONCLUSION: This patient's case stresses the importance of correctly diagnosing this rare breast tumor through the histopathologic appearance of dermatofibrosarcoma protuberans, molecular pathogenesis, and immunohistochemistry. These techniques can help differentiate dermatofibrosarcoma protuberans from metaplastic breast carcinoma and other spindle cell lesions of the breast. This is critical, as the treatment options for metaplastic breast carcinoma significantly differ from treatment options for dermatofibrosarcoma protuberans. This case describes the use of imatinib as a neoadjuvant option to reduce preoperative tumor size and improve surgical outcomes.

Beta blockade as adjunctive breast cancer therapy: A review.

Pre-clinical data has shown that beta adrenergic stimulation can affect the development and progression of many types of cancer. The use of beta blockers as an anti-neoplastic therapy has been studied in retrospective trials and observational trials, but no definitive conclusions about efficacy have been made. Within the realm of breast cancer, significant advances in therapy have led to improved survival outcomes, yet there is room for improvement. Beta adrenergic blockade may prove an effective adjunct to standard breast cancer therapy, with little associated toxicity. This article provides a review of the published literature on beta blockade as an adjunctive cancer therapy, with a focus on breast cancer.

Rapid and Sensitive Detection of Breast Cancer Cells in Patient Blood with Nuclease-Activated Probe Technology.

A challenge for circulating tumor cell (CTC)-based diagnostics is the development of simple and inexpensive methods that reliably detect the diverse cells that make up CTCs. CTC-derived nucleases are one category of proteins that could be exploited to meet this challenge. Advantages of nucleases as CTC biomarkers include: (1) their elevated expression in many cancer cells, including cells implicated in metastasis that have undergone epithelial-to-mesenchymal transition; and (2) their enzymatic activity, which can be exploited for signal amplification in detection methods. Here, we describe a diagnostic assay based on quenched fluorescent nucleic acid probes that detect breast cancer CTCs via their nuclease activity. This assay exhibited robust performance in distinguishing breast cancer patients from healthy controls, and it is rapid, inexpensive, and easy to implement in most clinical labs. Given its broad applicability, this technology has the potential to have a substantive impact on the diagnosis and treatment of many cancers.

Pembrolizumab Therapy Triggering an Exacerbation of Preexisting Autoimmune Disease: A Report of 2 Patient Cases.

Historically, metastatic melanoma was uniformly and rapidly lethal, and treatment options were limited. In recent years, however, checkpoint inhibitors have emerged as an accepted standard treatment for patients with advanced melanoma. In clinical trials, these agents have been largely well tolerated and have the potential to result in durable responses. Importantly though, one must recognize the unique side effect profile of these therapies, which can trigger or exacerbate underlying autoimmune disease. Whether this autoimmune activation is associated with a clinical response to therapy has been debated, and while not definitive, there is evidence in the literature of a possible association. The 2 cases presented describe this autoimmune phenomenon, along with a review of the existing literature on the relationship between response to immunotherapy and autoimmune side effects.

Effect of Body Mass Index- and Actual Weight-Based Neoadjuvant Chemotherapy Doses on Pathologic Complete Response in Operable Breast Cancer.

INTRODUCTION: The effect of body mass index (BMI) and chemotherapy dose reduction on pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) for locoregional breast cancer remains unclear. Contemporary studies have reported largely on trial populations and used dose-capping. PATIENTS AND METHODS: Patient registries at the University of Iowa were queried to identify patients with operable breast cancer who received NAC. Dose reductions were calculated for taxanes (T), anthracyclines (A) and non-A-T chemotherapy. Clinical-pathologic characteristics, chemotherapy dose reductions, and adverse events were compared between normal (BMI <25) and overweight/obese patients (BMI ≥25). Additionally, the synergistic effect of BMI and chemotherapy dose reduction on pCR was assessed. RESULTS: Of 171 eligible patients, 112 were overweight/obese. Chemotherapy dosing was capped in 2 patients; all others initiated full weight-based treatment. Overweight/obese patients required more frequent taxane (44.6% vs. 25.4%; P = .01) and any chemotherapy dose reductions (50.9% vs. 33.9%; P = .03). pCR was attained in 29.2% of patients. In a multivariable model, the interaction term for BMI as a continuous variable and any chemotherapy dose reduction was significant independent of the clinical stage and tumor receptor status (P = .04). For obese patients, any chemotherapy dose reduction was significantly associated with increased odds of not attaining pCR. CONCLUSION: During NAC, overweight/obese patients more often have chemotherapy dose reductions. Chemotherapy dose reduction in obese patients was a powerful predictor of not attaining pCR. This was not seen for normal or overweight patients. Opportunities might exist to improve pCR rates in this higher-risk group.

Frequency and Clinical Significance of Extramammary Findings on Breast Magnetic Resonance Imaging.

BACKGROUND: Use of breast magnetic resonance imaging (MRI) for screening and local staging of breast cancer has increased. With this, questions have emerged regarding the management and effect of extramammary findings (EMFs) reported on breast MRI. PATIENTS AND METHODS: Breast MRI studies performed between January 1, 2007 and December 31, 2012 at the University of Iowa were analyzed. Data were collected regarding number and location of EMFs, characteristics of the patients who had a breast MRI, and time to first treatment among the patients who had a breast MRI for stage I-III breast cancer. RESULTS: During the study period, 1305 breast MRIs were obtained in 772 women. An EMF was found in 140 studies (10.7%) and 113 women (14.6%). EMFs were more likely in MRIs of older patients (50 vs. 54 years, P = .004) and postmenopausal women (P = .001). Anatomically, most EMFs were seen in the liver (89 of 140) or bone (21 of 140). Eight women (0.6%) had an EMF on breast MRI that led to upstaging to stage IV breast cancer. For patients with stage I-III breast cancer, the finding of an EMF on breast MRI did not affect time to initial cancer treatment (13 vs. 14 days; P = .586). CONCLUSION: EMFs on breast MRI are seen with some frequency and occur more commonly in older, postmenopausal women. In our study, most EMFs were benign and did not affect patient outcome with regard to upstaging to stage IV disease or time to cancer treatment. A very small portion of studies revealed subclinical advanced breast cancer.