Soluble urokinase plasminogen activator receptor and cardiotoxicity in doxorubicin-treated breast cancer patients: a prospective exploratory study.

BACKGROUND: Soluble urokinase plasminogen activator receptor is an inflammatory biomarker that may prognosticate cardiovascular outcomes. We sought to determine the associations between soluble urokinase plasminogen activator receptor and established markers of cardiotoxicity in breast cancer patients receiving doxorubicin. METHODS: We conducted a prospective cohort study of women with newly diagnosed breast cancer receiving standard-dose doxorubicin (240 mg/m2) at Rush University Medical Center and Rush Oak Park Hospital (Chicago, IL) between January 2017 and May 2019. Left ventricular ejection fraction, global longitudinal strain, and cardiac biomarkers (N-terminal prohormone B-type natriuretic peptide, troponin-I, and high-sensitivity C-reactive protein) were measured at baseline and at intervals up to 12-month follow-up after end of treatment. The associations between soluble urokinase plasminogen activator receptor and these endpoints were evaluated using multivariable mixed effects linear regression. RESULTS: Our study included 37 women (mean age 47.0 ± 9.3 years, 60% white) with a median baseline soluble urokinase plasminogen activator receptor level of 2.83 ng/dL. No participant developed cardiomyopathy based on serial echocardiography by one-year follow-up. The median percent change in left ventricular strain was -4.3% at 6-month follow-up and absolute changes in cardiac biomarkers were clinically insignificant. There were no significant associations between soluble urokinase plasminogen activator receptor and these markers of cardiotoxicity (all p > 0.05). CONCLUSIONS: In this breast cancer cohort, doxorubicin treatment was associated with a very low risk for cardiotoxicity. Across this narrow range of clinical endpoints, soluble urokinase plasminogen activator receptor was not associated with markers of subclinical cardiotoxicity. Further studies are needed to clarify the prognostic utility of soluble urokinase plasminogen activator receptor in doxorubicin-associated cardiomyopathy and should include a larger cohort of leukemia and lymphoma patients who receive higher doses of doxorubicin.

Managing hyperglycemia and rash associated with alpelisib: expert consensus recommendations using the Delphi technique.

Hyperglycemia and rash are expected but challenging adverse events of phosphatidylinositol-3-kinase inhibition (such as with alpelisib). Two modified Delphi panels were conducted to provide consensus recommendations for managing hyperglycemia and rash in patients taking alpelisib. Experts rated the appropriateness of interventions on a 1-to-9 scale; median scores and dispersion were used to classify the levels of agreement. Per the hyperglycemia panel, it is appropriate to start alpelisib in patients with HbA1c 6.5% (diabetes) to <8%, or at highest risk for developing hyperglycemia, if they have a pre-treatment endocrinology consult. Recommend prophylactic metformin in patients with baseline HbA1c 5.7% to 6.4%. Metformin is the preferred first-line anti-hyperglycemic agent. Per the rash panel, initiate prophylactic nonsedating H1 antihistamines in patients starting alpelisib. Nonsedating H1 antihistamines and topical steroids are the preferred initial management for rash. In addition to clinical trial evidence, these recommendations will help address gaps encountered in clinical practice.

Factors Mediating Racial/Ethnic Disparities in Delayed Treatment of Breast Cancer.

BACKGROUND: Despite improvements, disparities in breast cancer care have led to an inequitable distribution of treatment delays and worse outcomes among patients with breast cancer. This study aimed to quantify the contribution of mediators that may explain racial/ethnic disparities in breast cancer treatment delays. PATIENTS AND METHODS: We conducted a retrospective analysis of patients from the National Cancer Database with stage I-III breast cancer who underwent surgical resection. Mediation analyses estimated the extent to which racial/ethnic disparities in the distribution of patient characteristics account for racial/ethnic disparities in delayed treatment. RESULTS: Of the 1,349,715 patients with breast cancer included, 10%, 5%, and 4% were Black, Hispanic, and other non-white race/ethnicity, respectively. Multivariable models showed that patients in these racial/ethnic groups had 73%, 81%, and 24% increased odds of having a treatment delay relative to white patients. Mediation analyses suggested that 15%, 19%, and 15% of the treatment delays among Black, Hispanic, and other non-white race/ethnicity patients, respectively, are explained by disparities in education, comorbidities, insurance, and facility type. Therefore, if these mediators had been distributed equally among all races/ethnicities, a reduction of 15-19% in the delayed treatment disparities experienced by minority patients would have been observed. Academic facility type was the factor that could yield the largest reduction in time to treatment disparities, contributing to 8-13% of racial/ethnic disparities. CONCLUSIONS: Patients with breast cancer who identified as Black, Hispanic, and other non-white races/ethnicities are exposed to longer treatment delays relative to white patients. Efforts to equalize mediators could remove substantial portions of racial/ethnic disparities in delayed treatment.

A Case of Hepatopulmonary Syndrome as a Complication of Metastatic Breast Cancer to the Liver.

Many patients with metastatic breast cancer develop liver metastases. A rare complication of this is hepatopulmonary syndrome (HPS), which is associated with exertional dyspnea and intrapulmonary shunting. We present a patient who presented with HPS as a consequence of liver metastases and subsequently treated with chemotherapy leading to resolution of her symptoms.

Concordance of breast cancer biomarker testing in core needle biopsy and surgical specimens: A single institution experience.

BACKGROUND: Accurate diagnostic biomarker testing is crucial to treatment decisions in breast cancer. Biomarker testing is performed on core needle biopsies (CNB) and is often repeated in the surgical specimen (SS) after resection. As differences between CNB and SS testing may alter treatment decisions, we evaluated concordance between CNB and SS as well as associated changes in treatment and clinical outcomes. METHODS: We performed a retrospective analysis of breast cancer patients at our institution between January 2010 and May 2020. Concordance between CNB and SS was assessed for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Survival in patients, including recurrence, metastatic recurrence, and death, were assessed using chi-squared likelihood ratio. RESULTS: In total, 961 patients met eligibility criteria. Concordance, minor discordance, total concordance (concordance plus minor discordance), and major discordance between CNB and SS were reported for ER (87.7%, 9.2%, 90.8%, and 2.9%), PR (58.1%, 29.1%, 87.2%, and 12.8%), and HER2 IHC (52.5%, 20.9%, 73.4%, 26.6%), respectively. HER2 FISH concordance and major discordance were 58.5% and 1.2%, respectively. Of major discordance, ER (48.2%, p < 0.001) and HER2 FISH (50.0%) led to more management changes than HER2 IHC (2.4%, p = 0.04) and PR (1.6%, p = 0.10). Patients with ER major discordance had increased risk of death (6.7% concordance vs. 22.2% major discordance, p = 0.004). CONCLUSION: Overall, retesting ER and HER2 was more clinically beneficial than retesting PR. To aid decision-making and minimize healthcare costs, we propose patient-centered guidelines on retesting biomarker profiles.

Myosteatosis at diagnosis is adversely associated with 2-year survival in women with estrogen receptor-negative metastatic breast cancer.

PURPOSE: To examine the relationship between skeletal muscle (SM) and cancer-specific outcomes for women with estrogen receptor-negative (ER-) metastatic breast cancer (MBC). METHODS: For this retrospective cohort, females (≥ 18 years) with histologically confirmed ER- MBC and computerized tomography (CT) imaging were screened. Demographic, anthropometric, and clinical data were collected uniformly from the electronic medical record. CT images inclusive of the third lumbar region (L3) at diagnosis, 6 and 12 months, were used to classify sarcopenia (≤ 41 cm2/m2) and myosteatosis (< 41 or 33 Hounsfield Units, adjusted for body mass index (BMI)) and to evaluate changes in SM and total adipose tissue (TAT) over time. Kaplan-Meier curves, Cox Proportional Hazards (PH), and restricted mean survival time (RMST) estimates were generated to examine the relationship between sarcopenia and myosteatosis and time to tumor progression (TTP), treatment toxicity and 2-year survival, adjusting for covariates. RESULTS: Participants were 58.0 (15.0) years of age, ethnically diverse (55% non-Hispanic white, 31% Black, 11% Hispanic), post-menopausal (73%, n = 111), and classified as overweight (BMI 29.4 (7.6)). At diagnosis, 40% (n = 61) were sarcopenic, 49% had myosteatosis, and 28% (n = 42) had both. While Cox PH modeling and RMST analysis reveal no significant relationship between sarcopenia at diagnosis and 2-year survival (RMST difference - 1.6 (1.4) months, HR 1.35 (0.88-2.08)), these analyses support a significant, adverse association between myosteatosis at diagnosis and 2-year survival (RMST difference - 2.4 (1.5) months, HR 1.72 (1.09-2.72)). Incident sarcopenia was 11% (n = 5/45) and 2.5% (n = 1/40), respectively, while incident myosteatosis was 19% (n = 8/42) and 15% (n = 5/34) at 6 and 12 months, respectively. TTP and treatment toxicities did not appear to be related to diagnostic SM or body composition changes over time. CONCLUSION: Targeted interventions initiated within the first year of diagnosis to preserve or improve SM quality seem warranted for women with ER-MBC.

100 Disruptive Publications in Breast Cancer Research.

BACKGROUND: Breast cancer has a rich history of research over the past 75 years. Many studies have had disruptive influences on the field itself. Our study employs a new, validated measurement to determine the most disruptive publications within the field of breast cancer. MATERIALS AND METHODS: PubMed® database was queried for articles between 1954-2014 related to breast cancer with in 21 different journals deemed important to the field. Articles were then scored for disruption and citation count. The top 100 most disruptive and cited publications were compiled and analyzed. RESULTS: Disruption score was a distinct measurement from citation count and had low level of correlation. Disruptive publications tended to skew older with the median year of publication in 1977. The score identified a variety of study designs and publication types within multiple journals. CONCLUSIONS: Measurement of the disruptive quality of a publication is a new way to describe academic impact of a publication and is distinct from citation count. Used in conjunction with citation count in may give a more descriptive bibliometric assessment of the literature. Further exploration within the field of oncology is warranted.
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Treating Positive Axillary Disease in Elderly Breast Cancer Patients: The Impact of Age on Radiation Therapy.

INTRODUCTION: Breast cancer is the second most common cause of cancer death in females, and 30% of these patients are over the age of 70 years. Studies have shown deviation from the standard treatment paradigms in the elderly, especially in regard to radiation treatment. METHODS: We performed a retrospective chart review on 118 patients over the age of 70 years diagnosed with breast cancer and pathologically proven axillary disease over an 8-year period at an urban academic hospital to examine which patient factors influenced radiotherapy. RESULTS: Increasing patient age was associated with a decrease in the probability of receiving radiotherapy, while HER2-negative patients were more likely to receive radiation. Neither race, number of coexisting medical conditions, or insurance status showed any influence on radiation treatment. CONCLUSION: Patient age has a significant influence if elderly patients with axillary disease receive radiotherapy. Further investigation and validation are needed to understand why chronological age rather than biological age influences treatment modalities.

Gestational breast cancer: current challenges in staging and treatment of breast cancer.

Gestational breast cancer (GBC) is the most common form of invasive cancer in pregnancy and has unique challenges in both staging and treatment given the dual goal of appropriate cancer management and minimising the risk of fetal toxicity. A 38-year-old woman with no significant medical history and 21 weeks pregnant presented with a palpable right breast mass. She was diagnosed with human epidermal growth factor receptor 2-positive infiltrating ductal carcinoma with advanced disease. The patient underwent treatment; however, unfortunately, she passed away after developing devastating distant disease recurrence.We highlight both the challenges and current guidelines for management of GBC. Our goal is to discuss the current limitations of GBC management and the necessity of further investigation for safe novel imaging and treatment modalities for pregnant women. It is crucial to increase awareness across multiple subspecialities, as a multidisciplinary team is necessary for proper treatment of GBC.

Paired tumor sequencing and germline testing in breast cancer management: An experience of a single academic center.

BACKGROUND: Genetic testing for cancer predisposition is recommended to women with breast cancer who meet the criteria for such testing. After the FDA approvals of the poly ADP ribose polymerase (PARP) inhibitors, olaparib and talazoparib, for treatment of metastatic breast cancer, carrying germline mutations in BRCA1 and BRCA2 genes, the genetic testing result has become critical in their care. With the recent FDA approval of alpelisib for the treatment of PIK3CA-mutated hormone-receptor positive metastatic breast cancer, tumor molecular profiling to identify somatic mutations and potential molecularly targeted agents is increasingly utilized in the treatment of advanced breast cancer. AIM: Combining germline and somatic sequencing (paired testing) offers an advantage over a single technique approach. Our study evaluates the role of paired testing on the management of breast cancer patients. METHODS AND RESULTS: Forty-three breast cancer patients treated at Rush University Medical Center underwent paired germline and somatic variant testing in 2015 to 2017. A retrospective chart review was conducted with the analysis of demographic, clinical, and genomic data. Three actionable germline variants were found in the CHEK2 (2) and ATM (1) genes. 95% of tumors had somatic mutations. Seventy-seven percent of tumors had genomic alterations targetable with agents approved for breast cancer and 88% had molecular targets for agents approved for other cancers. Clinical examples of such use are described and potential future directions of tumor and paired testing are discussed. CONCLUSIONS: Germline variants were present in a relatively small patient group not routinely tested for inherited alterations. Potentially targetable somatic alterations were identified in the majority of breast cancers. Paired testing is a feasible and efficient approach that delivers valuable information for the care of breast cancer patients and eliminates serial testing.

Safety and Efficacy of Palbociclib and Radiation Therapy in Patients With Metastatic Breast Cancer: Initial Results of a Novel Combination.

PURPOSE: Palbociclib is a selective cyclin-dependent kinase 4/6 inhibitor approved for metastatic ER+/HER2- breast cancer. Preclinical evidence suggests a possible synergistic effect of palbociclib when combined with radiation therapy (RT); however, the toxicity of this pairing is unknown. We report preliminary results on the use of this combination. METHODS AND MATERIALS: Records of patients treated with palbociclib at our institution from 2015 to 2018 were retrospectively reviewed. Patients who received RT for symptomatic metastases concurrently or within 14 days of palbociclib were included. Local treatment effect was assessed by clinical examination and subsequent computed tomography/magnetic resonance imaging. Toxicity was graded based on Common Terminology Criteria for Adverse Events version 5.0. RESULTS: A total of 16 women received palliative RT in close temporal proximity to palbociclib administration. Four patients received palbociclib before RT (25.0%), 5 concurrently (31.3%), and 7 after RT (43.8%). The median interval from closest palbociclib use to RT was 5 days (range, 0-14). The following sites were irradiated in decreasing order of frequency: bone (11 axial skeleton [9 vertebra and 2 other]; 4 pelvis; 3 extremity), brain (4: 3 whole brain RT and 1 stereotactic radiosurgery), and mediastinum (1). The median and mean follow-up time is 14.7 and 17.6 months (range, 1.7-38.2). Pain relief was achieved in all patients. No radiographic local failure was noted in the 13 patients with evaluable follow-up imaging. Leukopenia, neutropenia, and thrombocytopenia were seen in 4 (25.0%), 5 (31.3%), and 1 (6.3%) patient before RT. After RT, 5 (31.3%), 1 (6.3%), and 3 (18.8%) patients were leukopenic, neutropenic, and thrombocytopenic, respectively. All but 2 (grade 2) hematologic toxicities were grade 1. No acute or late grade 2+ cutaneous, neurologic, or gastrointestinal toxicities were noted. Toxicity results did not differ based on disease site, palbociclib-RT temporal association, or irradiated site. CONCLUSIONS: The use of RT in patients receiving palbociclib resulted in minimal grade 2 and no grade 3+ toxicities. This preliminary work suggests that symptomatic patients receiving palbociclib may be safely irradiated.

Are Providers and Patients Following Hormonal Therapy Guidelines for Patients Over the Age of 70? The Influence of CALGB 9343.

BACKGROUND: The Cancer and Leukemia Group B (CALGB) 9343 clinical trial proved that omission of radiotherapy (RT) in patients 70 and older with T1cN0M0, estrogen receptor-positive tumors who undergo breast conservation therapy (BCT) and receive 5 years of endocrine therapy (ET) had no change in overall survival, distant disease-free survival, or breast preservation. We examined our institution's practice with this patient subset. PATIENTS AND METHODS: A single-institution retrospective chart review was performed on patients 70 years and older with T1N0M0, estrogen receptor-positive tumors, and who underwent BCT between April 2010 and October 2015. RESULTS: A total of 123 patients met inclusion criteria: 46% received RT and 73% received ET. The ET group had a mean age of 76.2 years, whereas the non-ET group had a mean age of 80.2 years (P = .00006). Race did not influence if patients received ET (P = .4). In patients who received ET, mean age at time of diagnosis for those that completed 5 years of therapy was 75.5 years, whereas those who stopped therapy early had a mean age of 77.6 years (P = .053). In patients who received ET but stopped early, reasons for cessation included side-effect profile (67%), death (22%), and noncompliance (11%). Of the 27% of patients that did not receive ET, 62% were not offered therapy, 24% refused, and 14% were lost to postoperative follow-up. CONCLUSION: Increasing age showed significant association to not receive ET. Contraindication to ET and provider's assessment of minimal benefit are the most common reasons why patients are not prescribed ET. If patients are non-compliant with ET, RT should be reconsidered.

Cardiovascular disease in cancer survivors.

Certain cancer therapies, including radiation therapy and some types of chemotherapies, are associated with increased risk of cardiovascular disease (CVD) and events. Some of these effects such as those presented by anthracyclines, radiation therapy, cisplatin, as well as those presented by hormone therapy for breast cancer-usually taken for many years for some breast and prostate cancers-are long-lasting and associated with cardiovascular events risk more than 20 years after cancer treatment. Cardiovascular testing, diagnostic assessment of suspected cardiovascular symptomatology, as well as laboratory tests for CVD risk factors are imperative. The early recognition and treatment of CVD processes that arise in survivorship years is pivotal, with specific attention to some CVD processes with specific suggested treatment modalities. Preventive measures include adequate screening, the use of medications such as ACE inhibitors/angiotensin receptor blockers and/or beta blockers, statin therapy and aspirin in persons who warrant these medications, as well as therapeutic lifestyle modifications such as exercise/physical activity, weight loss and appropriate diet for a healthy lifestyle. Periodic follow-up with a good primary care physician who understands the risks associated with cancer therapy is important, and referral to onco-cardiology for further management of cardiovascular risk in these survivors is based on a patient's cardiovascular risk level and the type, amount and duration of cancer therapies received during the patient's lifetime.

Four Synchronous Primary Malignancies of the Breast, Lung, Colon and Esophagus.

The literature contains few reports of patients with four more or more synchronous primary malignancies. We report the case of a 74-year-old woman who presented with synchronous primary malignant neoplasms of the breast (metaplastic carcinoma), lung (squamous cell carcinoma), esophagus (adenocarcinoma), and colon (adenocarcinoma). She was treated with multimodality therapy and demonstrated a favorable response at early follow-up. To our knowledge, this combination of synchronous primary malignancies has not been previously reported. The management of patients with multiple synchronous primary malignancies introduces a number of unique challenges which necessitate highly individualized treatment plans that may not strictly adhere to standard practices in the setting of a single malignancy.

Exploring Diet, Physical Activity, and Quality of Life in Females with Metastatic Breast Cancer: A Pilot Study to Support Future Intervention.

BACKGROUND: Historically, women with metastatic breast cancer are excluded from lifestyle interventions under the assumptions that diet and physical activity will have little impact on their disease trajectory. However, recent treatment advances have led to significant increases in survivorship that pose challenges to this assumption. OBJECTIVE: The objectives of this study were to measure dietary intake, physical functioning, and quality of life in a subset of women with metastatic breast cancer, and to inform future interventions in this growing population. DESIGN: Demographics, clinical characteristics, dietary intake, physical functioning, and quality of life were examined cross-sectionally using validated methodologies. PARTICIPANTS/SETTING: Twenty-five women with metastatic breast cancer were recruited during a 4-month period (June 2014 to September 2014) from two university hospitals in the Midwest that serve an ethnically diverse patient population. Women completed questionnaires and 24-hour dietary recalls (1 weekday, 1 weekend). MAIN OUTCOME: Lifestyle habits were analyzed. STATISTICAL ANALYSES: Means (±standard deviations) and frequencies were tallied and t tests were conducted. RESULTS: On average, participants were 58.8 (±12.8) years of age, predominantly minority, had been living with metastatic breast cancer for a mean of 36.9 (±29.3) months, and exhibited significant nutrition-impact symptomology (eg, pain, dry mouth, fatigue). Bone and lung were the most common sites of metastases. Compared to a larger, normative sample of women with metastatic breast cancer, study participants displayed similar physical (P=0.61) and functional well-being scores (P=0.76), but higher social (P=0.10) and emotional well-being scores (P<0.01). The analyses of lifestyle factors showed that the majority of women were overweight or obese (n=14), not routine exercisers (n=15), and had dietary patterns high in fat and low in fiber. CONCLUSIONS: This study supports that many women with metastatic breast cancer are in need of carefully tailored, evidence-based lifestyle strategies that address symptom burden, including weight management. The implications of diet and physical activity on quality of life in this population remain unexplored.

Assessing the quality of race/ethnicity, tumor, and breast cancer treatment information in a non-SEER state registry.

INTRODUCTION: The quality of population-based cancer registries are largely defined by the completeness, accuracy, and timeliness of incident cases and demographics reported. However, both Surveillance, Epidemiology, and End Results (SEER) cancer registries and non-SEER population-based state cancer registries have been regularly used to examine treatment patterns. While the quality of treatment data in SEER cancer registries has often been examined and improved, the quality of such data in non-SEER state registries has rarely been assessed. METHODS: We used self-reported (SR) and medical record (MR) abstracted data from a population-based breast cancer study for comparison with information contained in the Illinois State Cancer Registry (registry). Using either MR or SR as the gold standard, we estimated concordance, kappa, and sensitivity for the presence or absence of surgery and initiation of chemotherapy, radiation and hormone therapy, as well as tumor characteristics, race/ethnicity and insurance status. RESULTS: The accuracy of most of the data elements examined was generally high. For instance, there was almost perfect agreement between SR race/ethnicity and registry documentation (k = 0.92). MR and registry data on tumor stage, grade, ER/PR status, and node status had substantial agreement (k = 0.78-0.88). In regard to treatment information, surgery was rarely underdocumented in registry data, while radiation and chemotherapy were modestly underdocumented (8 percent-16 percent). On the other hand, per SR or MR, the registry generally failed to document hormonal treatment in a large proportion of cases (0.38 and 0.52, respectively). Health insurance information in the registry was also not well documented. There was only moderate agreement (k = 0.41) between SR and registry health insurance status, with uninsured patients being the least likely to be documented as such in the registry (sensitivity = 0.37 vs 0.96 and 0.63 for public and private insurance status, respectively). DISCUSSION: While some registry data elements are quite reliable, others warrant concern and must be interpreted with great caution. Understanding the strengths and limitations of a population-based non-SEER state cancer registry data can be useful to researchers who use these data sources to examine population cancer patterns or carry out cancer studies.

Assessing racial/ethnic disparities in chemotherapy treatment among breast cancer patients in context of changing treatment guidelines.

Conflicting study results with regards to racial/ethnic disparities in chemotherapy use among breast cancer patients may be due to the different sample populations, treatment data sources, and treatment eligibility definitions used. This study examined chemotherapy disparity in the context of changing treatment guidelines and explored factors that may help explain treatment differences observed. The data come from a population-based study that included interview and medical record data (including state cancer registry) from non-Hispanic (nH) White, nH Black, and Hispanic breast cancer patients diagnosed in 2005-2008. Logistic regression using model-based standardization was used to estimate age-adjusted risk differences and multivariate analysis was conducted to identify explanatory factors of the differences. Per the 2005/2006 National Comprehensive Cancer Network (NCCN) guidelines, minority patients appeared more likely than nH White patients to receive a chemotherapy recommendation (0.87 vs 0.75, p = 0.003). When eligibility was determined per the 2007 guidelines, there was no disparity because under these guidelines, nH White patients were more likely than minority patients to have tumors that no longer required chemotherapy. There was evidence that chemotherapy advances for breast cancer patients are implemented in the clinical setting well ahead of NCCN guidelines. Finally, among eligible patients, chemotherapy recommendation was very high and virtually always accepted and received, with no disparities found at these points of clinical care. The findings suggest that an evaluation of guideline-adherent chemotherapy treatment patterns must carefully consider the definition of treatment eligibility, given ongoing changes in treatment guidelines and early uptake of new diagnostic tools and treatments.