Survival benefit of a combined surgical approach in patients with metastatic breast cancer.

BACKGROUND: We previously reported survival benefit of surgery in patients with stage IV breast cancer (BC); prospective trials yielded inconclusive results. METHODS: We sampled the National Cancer Database (2004-2016) for de novo stage IV BC patients undergoing both primary site resection and metastasectomy. A multivariate Cox-regression survival model investigated the overall survival (OS) of this surgical approach as compared to lumpectomy/mastectomy alone, metastasectomy alone, or no surgery. The Kaplan-Meier method was used to demonstrate the utility of surgery when metastasis were confined to 1 site stratifying by tissue type. RESULTS: A total of n = 55,125 patients were included. As compared to lumpectomy/mastectomy alone (43 months), lumpectomy/mastectomy + metastasectomy exhibited the best OS (50 months, p = 0.012), metastasectomy alone showed slightly worse OS (30 months, p < 0.0001), and no surgery had the worst OS (21 months, p < 0.0001). In metastasis confined to 1 site, superior OS with combined lumpectomy/mastectomy and metastasectomy versus lumpectomy/mastectomy alone was observed with liver (72.8 vs. 48.1 months, p < 0.001) or lung (49.2 vs. 36.8 months, p < 0.001) metastasis but not bone (52.2 vs. 49.9 months, p < 0.001) or brain (16.2 vs. 15.5 months, p < 0.001). CONCLUSION: Patients with metastatic BC undergoing primary site resection and metastasectomy exhibited optimal OS, particularly when metastasis involved only the liver or lung.

Medial calcar bone resorption after anatomic total shoulder arthroplasty: does it affect outcomes?

BACKGROUND: The incidence of medial calcar resorption has been shown to be common after uncemented total shoulder arthroplasty (TSA). With etiologies including stress shielding, debris-induced osteolysis, and infection, the clinical impact of medial calcar resorption has not been specifically examined. The purpose of this study was to determine whether resorption is associated with inferior outcomes or higher rates of radiographic loosening in TSA patients. METHODS: We conducted a retrospective review of TSA patients with minimum 2-year clinical follow-up. Patient-reported and functional outcome measures were recorded preoperatively and postoperatively. Postoperative radiographs were evaluated for glenoid and humeral component loosening. A new calcar resorption grading system was introduced to quantify the degree of resorption and assess the progression. RESULTS: A total of 171 patients met the inclusion criteria, with average clinical and radiographic follow-up periods of 50 and 46 months, respectively. Calcar resorption was identified in 110 patients (64.3%). No significant overall differences were observed between the patients with and without calcar resorption. Subgroup analysis showed that patients with grade 3 resorption had a higher incidence of glenoid radiolucencies (50%, P = .001) and patients with a progression from grade 1 to grade 3 had higher incidences of glenoid (50%, P = .003) and humeral (9%, P = .039) radiolucencies. CONCLUSION: Medial calcar resorption following TSA with a standard-length press-fit humeral component is common. Overall, no differences in patient-reported outcome measures or radiographic loosening were found compared with patients without calcar resorption. However, grade 3 calcar resorption and more dramatic progression of resorption should raise the suspicion of prosthetic loosening.

A Targeted Approach to Ligament Balancing Using Kinetic Sensors.

BACKGROUND: Currently, soft-tissue imbalance contributes to several of the foremost reasons for revision following primary TKA, including instability, stiffness, and aseptic loosening. In order to decrease the incidence of soft-tissue imbalance, intraoperative sensors were developed to provide real-time, quantitative load data within the knee. This study examines the intraoperative data of a group of multicenter patients to determine how targeted ligament releases affect intra-articular loading, and to understand which types of releases are necessary to achieve quantified ligament balance. METHODS: A group of 129 patients received sensor-assisted TKA, as part of a multicenter study. Medial and lateral loading data were collected pre-release, during any sequential releases, and post-release. All data were collected at 10°, 45°, and 90° during range of motion testing. Ligament release type, release technique type, and resultant loading were collected. RESULTS: Loading across the joint decreased, overall, and became more symmetrical after releases were performed. On average, between 2 and 3 corrections were made (up to 8) in order to achieve ligament balance. The ligament release type and subsequent quantified change in loading were in agreement with historical, qualified sources. CONCLUSION: Objective data from sensor output may assist surgeons in decreasing loading variability and, thereby, decreasing ligament imbalance and its associated complications.

A new method for defining balance: promising short-term clinical outcomes of sensor-guided TKA.

Recently, technological advances have made it possible to quantify pounds of pressure across the bearing surface during TKA. This multicenter evaluation, using intraoperative sensors, was performed for two reasons: 1) to define "balance" 2) to determine if patients with balanced knees exhibit improved short-term clinical outcomes. Outcomes scores were compared between "balanced" and "unbalanced" patients. At 6-months, the balanced cohort scored 172.4 and 14.5 in KSS and WOMAC, respectively; the unbalanced cohort scored 145.3 and 23.8 in KSS and WOMAC (P < 0.001). Out of all confounding variables, balanced joints were the most significant contributing factor to improved postoperative outcomes (P < 0.001). Odds ratios demonstrate that balanced joints are 2.5, 1.3, and 1.8 times more likely to achieve meaningful improvement in KSS, WOMAC, and activity level, respectively.

Are morbidly obese patients undergoing total hip arthroplasty at an increased risk for component malpositioning?

Acetabular cup positioning is a critical factor in determining adverse clinical outcomes in THA. This evaluation was performed to determine if morbid obesity (BMI ≥35kg/m(2)) is a contributing risk factor to cup malpositioning. Two groups of patients were obtained from a local arthroplasty registry and match-controlled for gender, age, and diagnosis (n=211 morbidly obese; n=211 normal). Intraoperative data and postoperative AP pelvis and cross-table lateral radiographs were obtained for each patient. The Martell Hip Analysis Suite was used to calculate cup positioning (successful positioning defined as 30°-45° of abduction, and 5°-25° of anteversion), as well as varus-valgus alignment of the femoral stem. There was a significant correlation between morbid obesity with respect to underanteversion; using multivariate analysis, there was a trend toward a combined underanteversion/overabduction of the acetabular cup. Of all variables considered, high BMI was the most significant risk factor leading to malpositioning.

Geographical Disparities and Factors Associated With the Decision to Decline Chemotherapy in Breast Cancer.

PURPOSE: Social determinants of health have been linked to treatment-related disparities in breast cancer. We analyzed data from a large national registry to explore factors related to accepting or declining recommended chemotherapy and whether patients' decisions vary geographically across the United States. METHODS: We used the National Cancer Database to study treatment decision making in patients with advanced breast cancer (American Joint Committee on Cancer clinical stage III-IV) between 2004 and 2017. We focused the analysis on patients who were recommended chemotherapy by their physicians but who declined this treatment. Multivariate logistic regression analysis was performed. RESULTS: A total of N = 215,284 patients with stage III and IV breast cancers were included. Patients in the New England region were more likely to refuse chemotherapy compared with the rest, with patients in the East South Central regions (AL, KY, MS, and TN) and West South Central (AR, LA, OK, and TX) noted to be least likely to refuse chemotherapy. Factors related to a higher rate of refusal by patients included older age > 70 years; hormone receptor-positive tumors; and having higher comorbidity. Patients identified as Hispanic, those who are privately insured, and patients at academic institutions were less likely to decline chemotherapy. CONCLUSION: This analysis identified a significant difference in rates of refusal of recommended chemotherapy by geographical location, insurance status, and treatment facility after adjusting for known social determinants of health. Further understanding of the factors affecting treatment decisions would be important to improve the efficacy of care delivery in patients with cancer and reduce reversible causes of disparity.

Factors Associated With the Decision to Decline Chemotherapy in Patients With Early-stage, ER+/HER2- Breast Cancer and High-risk Scoring on Genomic Assays.

INTRODUCTION: The rate of refusal of chemotherapy ranges from 3% to 19%, but varies widely by patient profile and treatment setting. Using a large national registry, we explore factors significantly associated with the decision to decline chemotherapy in patients with early-stage, HR+/HER2- breast cancer (BC) despite high risk scoring on multigene sequencing analysis for OncotypeDX (ODX) or MammaPrint (MP), in which the survival benefit of chemotherapy is clear. PATIENTS AND METHODS: Patients with HR+/HER2- BC and high risk scoring on ODX (score >26) or MP were selected from the National Cancer Database (2004-2017). Only those who refused to get chemotherapy despite their physician's recommendations were included. Univariate frequency and proportion statistics were used to describe the patient cohort. Bivariate Chi-square analysis evaluated the association between refusal of recommended chemotherapy and sociodemographic characteristics. Significant variables (P < .05) were included in a multivariable logistic regression model. RESULTS: N = 43,533 patients were included (88.7% ODX, 11.3% MP). A total of n = 4415 (10.1%) patients declined chemotherapy despite recommendation by the patient's primary oncologist. Age >70 (OR: 3.46, 95% CI: 2.96-4.04, P < .001), black race (OR: 1.20, 95% CI: 1.07-1.36, P = .01), non-private insurance, lobular carcinoma histology (OR: 1.21, 95% CI: 1.09-1.35, P < .001), and tumor grade of I significantly predicted chemotherapy decline. CONCLUSION: Identifying and addressing many of the factors that contribute to under-treatment in minorities is to be key to reducing cancer disparity and improving equity in cancer care and outcome.

Effect of immunotherapy on overall survival in limited-stage small cell lung carcinoma: a national cancer database analysis.

BACKGROUND: While immune-based therapies have been approved for extensive-stage small cell lung cancer, there is limited data on the efficacy of immunotherapy in patients with limited-stage disease. METHODS: We used the National Cancer Database to first evaluate factors associated with the inclusion of immunotherapy as part of the initial therapeutic course in patients diagnosed with limited-stage small cell lung cancer (LS-SCLC). Consequently, we evaluated the impact of this immunotherapy on 2-year and 5-year overall survival (OS). We did this by performing 1:1 matching for controls that did not receive immunotherapy, and comparing survival between cohorts using the Kaplan-Meier method. RESULTS: A total of 98 patients with LS-SCLC received immunotherapy as part of their initial therapeutic regimen. Age and facility type were the only significant predictors of the use of immunotherapy. There was no statistically significant difference between matched case-control cohorts in median OS (p = 0.985), 2-year OS (p = 0.747), and 5-year OS (p = 0.934). CONCLUSION: In this study using a large national database, we found that the inclusion of immunotherapy as part of the initial systemic therapy regimen was not significantly associated with improved OS in a cohort of LS-SCLC patients.

Effect of Surgery at Primary and Metastatic Sites in Patients With Stage IV Breast Cancer.

BACKGROUND: There is no clear evidence of a survival benefit of resection of the primary tumor, or distant site resection (metastasectomy) in patients with stage IV breast cancer. PATIENTS AND METHODS: This retrospective analysis of stage IV breast cancer using the National Cancer Database. To evaluate variables associated with surgery at the primary site, we used univariate analyses followed by multivariate logistic regression. Consequently, we evaluated the impact of lumpectomy, mastectomy or metastasectomy on survival by conducting multivariate Cox regression survival analyses on the following groups: all stage IV patients; a subset of those with only one metastatic site; and another subset with metastasis to multiple distant sites. RESULTS: A total of 54,871 stage IV breast cancer patients were included in this analysis. Variables associated with the use of surgery at the primary were: age, race, Charlson/Deyo score, insurance and facility type, involved breast quadrant, receptor status, N stage, extent of metastasis, and year of diagnosis. Survival analysis showed that both lumpectomy (median overall survival [OS], 45 months) and mastectomy (median OS, 44 months) were associated with better OS compared to no surgery (median OS, 22 months). The statistical effect was larger in the subgroup with metastasis to one site, but still significant in the subgroup with multiple metastatic sites. Distant site resection also yielded a survival benefit. CONCLUSION: In patients with metastasis to only one site, metastasectomy was associated with better OS when that site was the liver, lung, or brain.

Clinical and Demographic Factors, Treatment Patterns, and Overall Survival Associated With Rare Triple-Negative Breast Carcinomas in the US.

Importance: Triple-negative breast cancers are known collectively to demonstrate a more aggressive clinical course and earlier recurrence than cancers of other histological subtypes. However, the literature on rare triple-negative breast cancers and the association of histological type with survival and risk of metastasis is sparse. Objective: To present the clinical and demographic characteristics, treatment patterns, and overall survival (OS) for histologically rare (<10% of breast cancers) triple-negative breast cancer types: medullary carcinoma, adenoid cystic carcinoma, and metaplastic breast carcinoma. Design, Setting, and Participants: This cohort study was performed in the US using data reported by the National Cancer Database between 2010 and 2016. Confirmed cases of medullary carcinoma, adenoid cystic carcinoma, and metaplastic breast cancer were analyzed. Univariable analyses and multivariable Cox regression models were performed. Data analysis was performed from April to May 2020. Main Outcomes and Measures: The primary outcome was 5-year OS. Secondary outcomes included site of metastasis, effect of immunohistochemistry, management, and 2-year mortality. Results: A total of 8479 patients with breast cancer (mean [SD] age; 62.6 [14.3] years; 8435 women [99.48%]) were analyzed. Metaplastic carcinoma was the most commonly diagnosed histological type in this cohort, with 6867 patients (81%), followed by 1357 (16%) with adenoid cystic carcinoma and only 255 (3%) with medullary carcinoma. Medullary carcinoma presented earlier in life, at a median (interquartile range) age of 53 (45-62) years, compared with 62 (53-72) years for patients with adenoid cystic carcinoma and 63 (52-74) years for patients with metaplastic carcinoma. The proportion of tumors with triple-negative immunohistochemistry varied by histological type for medullary carcinoma (57 patients [22.4%]), adenoid cystic carcinoma (653 patients [48.1%]), and metaplastic carcinoma (3637 patients [53.0%]). Patients with adenoid cystic carcinoma were less likely to receive radiotherapy (711 patients [52.4%]) and chemotherapy (175 patients [12.9%]) compared with patients with medullary carcinoma (radiotherapy, 156 patients [61.2%]; chemotherapy, 190 patients [74.5%]) and metaplastic carcinoma (radiotherapy, 3416 patients [49.7%]; chemotherapy, 4709 patients [68.6%]). The 5-year OS rate was superior for patients with medullary (91.7%) and adenoid cystic carcinoma (88.4%) compared with patients with metaplastic carcinoma (63.1%). The 5-year mortality rate for adenoid cystic carcinoma was 8.33% vs 36.91% for metaplastic carcinoma. Conclusions and Relevance: Nationally, over the course of 7 years, medullary carcinoma was most common and metaplastic carcinoma had the worst 5-year OS among the rare histological breast cancer subtypes analyzed. Factors associated with a poor prognosis for metaplastic carcinoma included advanced stage, lung metastasis, older age, and not receiving chemotherapy or radiation therapy. Future research focusing on rare subtypes of breast cancer is desirable and could inform the optimal management of these relatively understudied carcinomas.

Newly-identified Pathways Relating Vitamin D to Carcinogenesis: A Review.

BACKGROUND: The epidemiological relationship between vitamin D levels and cancer has been thoroughly investigated. Published data from large studies appear to corroborate a significant relationship between higher serum vitamin D concentrations and improved survival. Mechanistic reviews on commonly-studied cancers - including breast cancer, colon cancer and melanoma - focus predominantly on data from older studies. In outlining avenues for future research, we believe there is utility in summarizing novel findings introduced to the literature. MATERIALS AND METHODS: In this narrative review, we used MEDLINE, PUBMED and Cochrane databases to identify mechanistic studies published from January 1, 2015 onwards exploring this topic. RESULTS: Twenty-five mechanistic studies were included in this review. It was found that vitamin D plays a critical role in both direct (i.e. tumor gene expression, proliferation, invasiveness, sensitivity to chemotherapy etc.) and indirect (i.e. effects on the tumor microenvironment and immunomodulation) tumor suppression mechanisms. CONCLUSION: These newly-identified pathways warrant further research, with the hopes that we may understand how and when vitamin D supplementation can be integrated into precision medicine therapeutics for cancers of the breast, colon and skin. Cancer care providers should consider recommendations to screen for vitamin D deficiency in this population.

Male Breast Cancer: A Comparative Analysis from the National Cancer Database.

PURPOSE: Breast cancer (BC) in males accounts for <0.5% of all male cancer diagnoses and ~1% of all BCs in the United States. We sought to describe clinicopathologic characteristics among male and female BC patients and differences in overall survival (OS) through the National Cancer Database over 13 years (2004-2016). MATERIALS AND METHODS: Secondary to the 1:99 ratio of male to female BC cases, we randomly selected female cases for equal comparison to males cases by diagnosis year. Chi-square and t-tests compared demographic and tumor characteristics. OS was examined using Kaplan-Meier survival analysis. RESULTS: Among the ~2.7 million BC patients, 9 per 1,000 BCs were in males, the rate remained similar over time. The mean (SD) age was 64.9±13.0 years for males and 60.7±13.6 years for females. Most of the male BC cases were white (non-Hispanic) (n=19,015 [80.2%]), clinical stage I (n=7,353 [32.1%]) or stage II disease (n=7,923 [34.6%]), and tumors were moderate or poorly differentiated (84.5%). Males exhibited more comorbidities, presented with a larger proportion of disease, and decreased OS (p<0.005) than females. Male OS was >10% lower at 5-years and nearly 20% lower at 10-years for males. More males had primary BC tumors under the nipple; the 10-year OS rate for this site was 48.8%. CONCLUSIONS: This study reports clinicopathologic characteristics of a large cohort of male BC. Males present at older age, with a greater comorbidity index, at later stages of disease. Increased education regarding the continued risks of male breast cancer may be warranted.

Metastasectomy versus radiation of secondary sites in stage IV breast cancer: Analysis from a national cancer registry.

PURPOSE: Locoregional therapy at primary or secondary sites in breast cancer may be associated with improved survival as compared to systemic therapy alone. We explored the sociodemographic and clinicopathologic factors associated with the use of radiation versus surgical resection of metastatic sites (metastasectomy) in patients with de novo stage IV breast cancer, followed by the associated overall survival. METHODS: We sampled the National Cancer Database for patients with de novo stage IV breast cancer, (2010-2017) and described cohort's characteristics using univariate analyses. We identified 5 subgroups based on malignant site involvement: 1. Bone only, 2. Brain only, 3. Liver only, 4. Lung only, and 5. Metastasis involving >1 site. Kaplan-Meier modeling with log-rank testing and multivariate Cox Regression analysis were used to explore differences in overall survival between those that received radiation at secondary sites and those that underwent metastasectomy. RESULTS: N = 22,749patients were included in this analysis. Radiation (81.2%) was used more commonly than metastasectomy (28.8%). Metastasectomy was associated with better median overall survival across all 5 cohorts (p < .001), with the survival benefit being the most pronounced with lung only (OS: 56.9 months; HR 0.8, 95% CI 0.7-0.9, p = .032), or liver only (OS: 41.6 months; HR: 0.9; 95% CI: 0.7-1.1, p < .001) metastasis. CONCLUSION: Metastasectomy in patients with de novo stage IV breast cancer may be associated with improved overall survival as compared to radiation of secondary lesions, particularly in those with only liver or lung involvement. Prospective randomized controlled trials investigating surgical resection of metastatic sites in patients with breast cancer are warranted.

Prognostic and Predictive Value of Circulating and Disseminated Tumor Cells in Breast Cancer: A National Cancer Database (NCDB) Analysis.

IMPORTANCE: Our understanding of the utility of circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) as clinical biomarkers continues to evolve. OBJECTIVE: This study evaluated (1) clinicopathologic factors associated with the presence of CTCs or DTCs, (2) the prognostic value of CTCs or DTCs by disease stage, 3), the value of these biomarkers in predicting the benefit of chemotherapy. DESIGN: This is a retrospective analysis of patients with breast cancer (BC) diagnosed between 2004 and 2016 using the National Cancer Database (NCDB). To evaluate variables associated with the presence of CTCs or DTCs at the univariate level, we used chi-squared and Wilcoxon rank-sum tests. Multivariate logistic regression models were then constructed using significant variables. Consequently, we included CTC or DTC status (i.e. positive or negative) in multivariate, stage-by-stage Cox regression analyses for overall survival (OS). After stratifying by receptor status and staging, we used the Kaplan-Meier method to explore chemotherapy efficacy in CTC- or DTC-positive vs. CTC- or DTC-negative subsets. RESULTS: Factors significantly associated with CTCs were race, progesterone receptor status, HER2 status, histology and AJCC N- and M-staging. Factors associated with DTCs were race, HER2 status, histology and AJCC N-staging. CTCs were associated with poor OS in late-stage (III and IV) but not early-stage (0-II) BC. DTCs were not significantly associated with OS in either context. In hormone receptor (HR)-positive disease, chemotherapy was associated with better OS when CTC status was positive, both in early-stage and late-stage disease. In a subset of patients without CTCs, however, chemotherapy conferred no survival benefit. DTC status was not a significant predictor of chemotherapy efficacy in early or late-stage, HR+ disease. CONCLUSIONS: This study suggests that CTC-status is a significant prognostic factor at later stages of BC; yet it can also help guide management of early-stage disease as it appears predictive for chemotherapy benefit.

Breast Cancer in the United States: A Cross-Sectional Overview.

INTRODUCTION: Breast cancer remains the most commonly diagnosed malignancy in women. It encompasses considerable heterogeneity in pathology, patient clinical characteristics, and outcome. This study describes factors associated with overall survival (OS) of breast cancer in an updated national database. METHODS: We conducted a retrospective analysis of patients with breast cancer diagnosed between 2004 and 2016 based on the National Cancer Database. Categorical variables were summarized using frequencies/percentages, whereas continuous variables were summarized using the median/interquartile range (IQR). OS was explored using the Kaplan-Meier method. RESULTS: Data from n = 2,671,549 patients were analyzed. The median age at diagnosis was 61 years (range 18-90). 75% were non-Hispanic (NH) White; 11% were NH-Black; 4.7% were Hispanic-White; 0.1% were Hispanic-Black; and 3.4% were Asian. Most cases (73%) presented with ductal carcinoma histology; while 15% with lobular carcinoma. Rarer subtypes included epithelial-myoepithelial, fibroepithelial, metaplastic, and mesenchymal tumors. OS was associated with molecular subtype, histologic subtype, and AJCC clinical staging. Survival also correlated with race: a cohort including Asians and Pacific Islanders had the best survival, while Black patients had the worst. Finally, facility type also impacted outcome: patients at academic centers had the best survival, while those at community cancer programs had the worst. CONCLUSION: This large database provides a recent and comprehensive overview of breast cancer over 12 years. Molecular subtype, histologic subtype, stage, race, and facility type were correlated with OS. In addition to the educational perspective of this overview, significant factors impacting the outcome identified here should be considered in future cancer research on disparities.

Pseudofungi in an Immunocompromised Patient with Breast Cancer and COVID-19.

Herein, we present a case of a male patient with breast cancer and a recent history of COVID-19 pneumonia, diagnosed with pseudofungi on pathological examination of lymph nodes after mastectomy. Pseudofungi are septate hyphae-like structures that morphologically mimic fungal elements despite the absence of true mycosis and thus predispose to overtreatment if not properly identified. We report a review of similar cases involving this diagnostic mimicker in the literature.

A Multimodal Approach to Evaluate for Cardiac Metastasis in a Case of Non-Small Cell Lung Cancer.

Malignancies have demonstrated the ability to metastasize to cardiac tissue. However, an optimal diagnostic algorithm for cardiac tumors has not yet been established, due at least in part to the scarcity of symptomatic cases. Several case reports describe how the usage of 18F-labeled fluorodeoxyglucose positron emission tomography (18F-FDG PET) incidentally revealed cardiac neoplasia. This modality, which indicates uptake sites of the radioisotope 18F-FDG, allows for whole-body imaging and is often used for preoperative determination of malignant metastasis or for assessing response to therapy over time. However, findings of false positivity are often reported due to increased FDG avidity caused by a range of other, nonmetastatic processes, most notably inflammation and infection. In this case report, an 84-year-old male with stage IV non-small cell lung cancer presented a clinical course, echocardiogram, and 18F-FDG PET-CT findings that were suggestive of endocardial metastasis. Nine months into therapy, after extensive consultation, the patient finally consented to a more complete workup using cardiac MRI (CMRI), which showed no evidence of cardiac metastasis. This case report supports the utility of CMRI as a means of further interpreting intracardiac, localized FDG uptake foci in PET-CT findings, in order to avoid false positivity and further refine proposed cardiac differential diagnoses in cancer patients.

Endocrine Therapy Plus Anti-HER2 Therapy as Adjuvant Systemic Therapy for Luminal HER2-Positive Breast Cancer: An Analysis of the National Cancer Database.

BACKGROUND: Guidelines regarding the usage of adjuvant systemic therapy in patients with small human epidermal growth factor receptor 2 (HER2)-positive and estrogen receptor/progesterone receptor-positive (luminal HER2 positive) tumors are nonspecific. Outcomes of chemotherapy followed by endocrine therapy (ET), with or without anti-HER2 therapy, vs ET alone (no chemotherapy) have not been widely studied in this disease subtype. We sought to examine the usage and outcomes of adjuvant systemic therapy (ET vs chemotherapy with or without trastuzumab) in stage I luminal HER2-positive breast cancer (BC), based on the large National Cancer Database. METHODS: We conducted a retrospective analysis of patients with luminal HER2-positive stage I BC, diagnosed between 2010 and 2015, in the United States, using univariable and multivariable logistic regression analyses. The Kaplan-Meier method estimated overall survival (OS). RESULTS: A total of 37 777 patients were included in the analysis; of these, n = 32 594 (86%) received adjuvant ET and n = 5183 (14%) received chemotherapy. Around 40% of all patients received anti-HER2 therapy (trastuzumab). Patients who received trastuzumab had a better 5-year OS (93.4% vs 92.0%, P = .0002) compared with those who did not. Patients who received anti-HER2 therapy plus ET had the best OS rate at 5 years (93.5%, confidence interval [CI]: 89.2%-98%, P < .0001) compared with those receiving anti-HER2 therapy plus chemotherapy (92.7%, CI: 89.4%-96.1%, P < .0001). CONCLUSIONS: Most patients in the United States, with stage I luminal HER2 positive BC, received ET, not chemotherapy but most of them do not receive anti-HER2 therapy resulting in inferior outcome. Future trials exploring the de-escalation of systemic adjuvant therapy for early-stage luminal HER2-positive BC to ET plus anti-HER2 therapy would be desirable.

Liver failure due to relapsed myeloma and hepatic iron overload.

Multiple myeloma is a hematologic malignancy that classically manifests with hypercalcaemia, renal insufficiency, anaemia and lytic bone lesions. Liver dysfunction in multiple myeloma is a lesser known complication that occurs through biliary obstruction, liver infiltration by plasma cells, amyloid/light chain deposition or due to liver injury from medications. Although transfusion-related hepatic iron overload-leading to significant liver disease-is a recognised complication in certain hematologic malignancies, little is known about transfusional iron overload in patients with multiple myeloma. We present a case of a 49-year-old female with relapsed/refractory multiple myeloma who presented with rapid onset liver failure, due to both iron deposition and malignant plasma cell infiltration of the liver as a terminal event. A review of the literature on hepatic complications in multiple myeloma patients is presented.

Checkpoint inhibitor-induced myocarditis and myasthenia gravis in a recurrent/metastatic thymic carcinoma patient: a case report.

BACKGROUND: Pembrolizumab, an immune checkpoint inhibitor (ICI), is an IgG4 antibody that blocks interaction between programmed cell death protein 1 and programmed death-ligand 1. Myocarditis, an immune-related adverse event, has been reported in thymic epithelial tumours. Pembrolizumab has also been associated with development/exacerbation of myasthenia gravis (MG). CASE SUMMARY: A 70-year-old woman with metastatic thymic cancer presented to the hospital with shortness of breath, 21 days after initiation of pembrolizumab. She was diagnosed with ICI-related myocarditis and was subsequently intubated due to respiratory failure. A dual-chamber pacemaker was placed due to complete heart block with asystole. Her troponin levels were elevated, an electrocardiogram was suspicious for myocardial infarction, but coronary angiogram revealed normal coronary arteries and endomyocardial biopsy confirmed the presence of myocarditis. Treatment was started with high-dose intravenous methylprednisolone and cardiovascular status improved. However, the patient was unable to be weaned from mechanical ventilation and tested positive for acetylcholine receptor binding/blocking antibodies due to de novo MG. After 50 days of hospitalization, she was discharged home in stable condition. A computed tomography scan was performed 6 weeks after pembrolizumab; results showed significant decrease/resolution of all measurable sites of metastatic disease in the lungs. DISCUSSION: This is the first reported case of a patient developing single-agent pembrolizumab-induced myocarditis concomitant with new-onset MG after treatment for advanced thymic malignancy. Additional studies are needed to explore the association between myocarditis, MG, and ICI therapy.