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.

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.

Histologic Transformation in an Untreated Waldenstrom's Macroglobulinemia After 14 Years: Case Report and Review of the Literature.

Waldenstrom's macroglobulinemia (WM) is an indolent B-cell non-Hodgkin lymphoma characterized by lymphoplasmacytic histology in the bone marrow with monoclonal IgM. Median survival can be in excess of 10 years. The 5-year cumulative incidence of death is low at about 10%. One-third of all-cause specific mortality is due to the lymphoma for which histologic transformation (HT) is rare. Here we present a case of a 60-year-old man with longstanding untreated WM, presenting with minimally symptomatic transformation to diffuse large B-cell lymphoma (DLBCL), with an accompanying review of the literature. Transformed WM, diagnosed greater than 5 years, has a reported survival period of 8 - 9 months. This case highlights that after a decade of continued stability in WM, not requiring treatment, an acute change in laboratory data with minimally progressive IgM levels, in the absence of B symptoms and clinical findings, may be the harbinger of transformation and at the time of diagnosis can have a rapidly deteriorating clinical course. In this case, the tripling of the lactate dehydrogenase (LDH) as the primary drastic change demonstrates the importance of the rapid increase in LDH as a singly reliable marker for HT. Late transformation has been borne out as a negative variable as the generally indolent course of WM is curtailed with the poor outcome in HT. Although MYD88 wildtype is a possible predictive factor for transformation, it is unclear if late transformation is clonally or non-clonally related and further molecular investigation is needed.

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.

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.

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.

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.

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.

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.

Long-Term Effect of a Nonrandomized Psychosocial Mindfulness-Based Intervention in Hispanic/Latina Breast Cancer Survivors.

Background: There is a paucity of research on the long-term impact of stress-reduction in Hispanic/Latina breast cancer (BC) survivors, a growing minority. In this article, we assess the long-term efficacy of an 8-week training program in mindfulness-based stress reduction (MBSR) on quality of life (QoL) in Hispanic BC survivors. Methods: Hispanic BC survivors, within the first 5 years of diagnosis, stages I to III BC, were recruited. Participants were enrolled in bilingual, 8-week intensive group training in MBSR and were asked to practice a- home, daily. They were also provided with audio recordings and a book on mindfulness practices. Patient-reported outcomes for QoL and distress were evaluated at baseline, and every 3 months, for 24 months. Results: Thirty-three self-identified Hispanic women with BC completed the MBSR program and were followed at 24 months. Statistically significant reduction was noted for the Generalized Anxiety Disorder measure (mean change -2.39, P=0.04); and Patient Health Questionnaire (mean change -2.27, P=0.04), at 24 months, compared with baseline. Improvement was noted in the Short-Form 36 Health-related QoL Mental Component Summary with an increase of 4.07 (95% confidence interval = 0.48-7.66, P=0.03). However, there was no significant change in the Physical Component Summary. Conclusions: Hispanic BC survivors who participated in an 8-week MBSR-based survivorship program reported persistent benefits with reduced anxiety, depression, and improved mental health QoL over 24 months of follow-up. Stress reduction programs are beneficial and can be implemented as part of a comprehensive survivorship care in BC patients.

Asteroid Hyalosis Simulating Vitreous Seeds in a Patient With Retinoblastoma.

A patient treated for retinoblastoma developed vitreous floaters 15 years later and was referred for recurrence with vitreous seeding. Clinical examination demonstrated a regressed scar and numerous calcified vitreous opacities with a "clear zone" on ultrasonography. The final diagnosis was asteroid hyalosis in an eye with regressed retinoblastoma. [J Pediatr Ophthalmol Strabismus. 2019;56:e41-e44.].

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF CONGENITAL SIMPLE HAMARTOMA OF THE RETINAL PIGMENT EPITHELIUM.

PURPOSE: To describe the optical coherence tomography angiography features of congenital simple hamartoma of the retinal pigment epithelium. METHODS: Case report. RESULTS: A 14-year-old boy was referred for an asymptomatic fundus tumor in the left eye. Visual acuity was 20/20 in the right eye and 20/40 in the left eye. The right fundus was normal. The left fundus disclosed a gray-white nodular retinal mass of 2-mm diameter in the juxtafoveal region, protruding into the vitreous cavity and causing radial retinal folds. The mass demonstrated echodensity without calcification on ultrasonography, hypoautofluorescence on short-wavelength autofluorescence, and mixed hyporeflective and hyperreflective areas on near-infrared reflectance imaging. By fluorescein angiography, the mass showed absolute hypofluorescence through the arteriovenous phase and diffuse late hyperfluorescence and staining. Optical coherence tomography revealed an optically dense lesion with abrupt posterior shadowing, whereas optical coherence tomography angiography showed an extensive haphazard intratumoral vascular network with fairly large-caliber (100-200 microns) vessels occupying full-thickness tumor, demonstrating more vascular details than visualized on fluorescein angiography. Serial segmental evaluation of the optical coherence tomography angiography en face images confirmed an intratumoral vascular network for full tumor depth down to retinal pigment epithelium, not related to projection artifact. Final diagnosis was congenital simple hamartoma of the retinal pigment epithelium. Considering the benign tumor, observation was recommended. CONCLUSION: Optical coherence tomography angiography of congenital simple hamartoma of the retinal pigment epithelium revealed an extensive intratumoral, haphazard, large-caliber vascular network, more evident than seen on fluorescein angiography. Optical coherence tomography angiography has added new insight into this rare tumor.