Cytogenetic Alterations and Correlation with Age and Gender in Patients of Multiple Myeloma: A Study from a Tertiary Care Center in Eastern India.

Karuna JhaBackground Multiple myeloma is a cytogenetically heterogeneous, evolving, and incurable disease. Differences in prevalence of myeloma already exist in Indian subcontinent as compared with Western world countries. This study attempts to investigate differences in incidence of cytogenetic abnormalities (CA) in Eastern Indian patients and study differences in incidence with respect to age and gender. Materials and Methods Interphase fluorescence in situ hybridization (FISH) was applied on purified plasma cells of 280 newly diagnosed myeloma cases using specific probes. Statistical Analysis Data was analyzed using SPSS software version 25. Results Note that 51.07% patients were FISH positive. Del13q was the most common CA. Significant association of del 13q with t(4;14), del 17p, and gain of 1q was seen. The frequencies of FISH positive and negative groups differed in the different age groups; higher number of cases in 41 to 50 years group in FISH positive group ( p < 0.05) and lower number of cases in FISH positive group in 61 to 70 years ( p < 0.05) as compared with FISH negative group. Del 17p had higher number of cases in age group 41 to 50 years and 51 to 60 years as compared with other age groups. Incidence of t(11;14) was in 5th to 7th decade while del 13q and t(4;14) had the widest range of age at presentation. Gender disparities were seen in high-risk cytogenetics like del 17p and 1q gain. Conclusion The differences in incidence rate of CAs per se in myeloma cases diagnosed in Indian subcontinent and the differences in incidence with respect to age and gender warrant further multicentric studies.

Worldwide survey on implantation of and outcomes for conduction system pacing with His bundle and left bundle branch area pacing leads.

BACKGROUND: Adoption and outcomes for conduction system pacing (CSP), which includes His bundle pacing (HBP) or left bundle branch area pacing (LBBAP), in real-world settings are incompletely understood. We sought to describe real-world adoption of CSP lead implantation and subsequent outcomes. METHODS: We performed an online cross-sectional survey on the implantation and outcomes associated with CSP, between November 15, 2020, and February 15, 2021. We described survey responses and reported HBP and LBBAP outcomes for bradycardia pacing and cardiac resynchronization CRT indications, separately. RESULTS: The analysis cohort included 140 institutions, located on 5 continents, who contributed data to the worldwide survey on CSP. Of these, 127 institutions (90.7%) reported experience implanting CSP leads. CSP and overall device implantation volumes were reported by 84 institutions. In 2019, the median proportion of device implants with CSP, HBP, and/or LBBAP leads attempted were 4.4% (interquartile range [IQR], 1.9-12.5%; range, 0.4-100%), 3.3% (IQR, 1.3-7.1%; range, 0.2-87.0%), and 2.5% (IQR, 0.5-24.0%; range, 0.1-55.6%), respectively. For bradycardia pacing indications, HBP leads, as compared to LBBAP leads, had higher reported implant threshold (median [IQR]: 1.5 V [1.3-2.0 V] vs 0.8 V [0.6-1.0 V], p = 0.0008) and lower ventricular sensing (median [IQR]: 4.0 mV [3.0-5.0 mV] vs. 10.0 mV [7.0-12.0 mV], p < 0.0001). CONCLUSION: In conclusion, CSP lead implantation has been broadly adopted but has yet to become the default approach at most surveyed institutions. As the indications and data for CSP continue to evolve, strategies to educate and promote CSP lead implantation at institutions without CSP lead implantation experience would be necessary.

COVID-19 and Cardiac Arrhythmias: a Contemporary Review.

Purpose of Review: A significant proportion of patients infected by the severe acute respiratory syndrome-coronavirus (SARS-CoV2) (COVID-19) also have disorders affecting the cardiac rhythm. In this review, we provide an in-depth review of the pathophysiological mechanisms underlying the associated arrhythmic complications of COVID-19 infection and provide pragmatic, evidence-based recommendations for the clinical management of these conditions. Recent Findings: Arrhythmic manifestations of COVID-19 include atrial arrhythmias such as atrial fibrillation or atrial flutter, sinus node dysfunction, atrioventricular conduction abnormalities, ventricular tachyarrhythmias, sudden cardiac arrest, and cardiovascular dysautonomias including the so-called long COVID syndrome. Various pathophysiological mechanisms have been implicated, such as direct viral invasion, hypoxemia, local and systemic inflammation, changes in ion channel physiology, immune activation, and autonomic dysregulation. The development of atrial or ventricular arrhythmias in hospitalized COVID-19 patients has been shown to portend a higher risk of in-hospital death. Summary: Arrhythmic complications from acute COVID-19 infection are commonly encountered in clinical practice, and COVID-19 patients with cardiac complications tend to have worse clinical outcomes than those without. Management of these arrhythmias should be based on published evidence-based guidelines, with special consideration of the acuity of COVID-19 infection, concomitant use of antimicrobial and anti-inflammatory drugs, and the transient nature of some rhythm disorders. Some manifestations, such as the long COVID syndrome, may lead to residual symptoms several months after acute infection. As the pandemic evolves with the discovery of new SARS-CoV2 variants, development and use of newer anti-viral and immuno-modulator drugs, and the increasing adoption of vaccination, clinicians must remain vigilant for other arrhythmic manifestations that may occur in association with this novel but potentially deadly disease.

Virtual Transformation and the Use of Social Media: Cardiac Electrophysiology Education in the Post-COVID-19 Era.

PURPOSE OF REVIEW: The COVID-19 pandemic has significantly impacted the delivery of education for all specialties, including cardiac electrophysiology. This review will provide an overview of the COVID-19 spurred digital transformation of electrophysiology education for practicing clinicians and trainees in electrophysiology and cover the use of social media in these educational efforts. RECENT FINDINGS: Major international, national, and local meetings and electrophysiology fellowship-specific educational sessions have transitioned rapidly to virtual and distanced learning, enhanced by social media. This has allowed for participation in educational activities by electrophysiologists on a wider, more global scale. Social media has also allowed rapid dissemination of new advances, techniques, and research findings in real time and to a global audience, but caution must be exercised as pitfalls also exist. SUMMARY: The digital and social media transformation of cardiac electrophysiology education has arrived and revolutionized the way education is delivered and consumed. Continued hybrid in-person and virtual modalities will provide electrophysiologists the flexibility to choose the best option to suit their individual needs and preferences for continuing education.

Analysis of blood stream infections, antibiograms and clinical outcomes in haematological patients with febrile neutropenia: data from a tertiary care haematology institute in India.

Timely administration of appropriate empirical antibiotics in febrile neutropenia is crucial for favourable patient outcomes. There are guidelines in place recommending such antibiotics. However, regional variations and local epidemiological data must be evaluated to tailor the antibiotics for best possible and rational use. In this study, we audited the clinical and microbiological data of febrile neutropenic episodes occurring at a tertiary care haematology institution. Three hundred and ninety-three febrile neutropenic episodes occurring in 123 patients over a 1-year period were analysed for microbial profile, sensitivity and resistance patterns, and finally clinical outcomes. Gram-negative bacilli (GNB) blood stream infections (46.9%) were more prevalent as compared to gram-positive infections (41.9%). Overall mortality due to complicated neutropenic sepsis was 19.5% (24/123 patients). Increased resistance to carbapenems, beta-lactam beta-lactamase inhibitor combinations, aminoglycosides, fluoroquinolones, and cephalosporins were observed. Cefepime and tigecycline resistance were seen in 20% and 15% GNB isolates, respectively. Chest was the most frequent focus of infection, and acute myeloid leukaemia (AML) was the most common underlying disorder which correlated with the likelihood of death (p < 0.01). Multidrug-resistant GNB (esp. Klebsiella sp.) are still most worrisome isolates in neutropenic patients. Single-agent cefepime or piperacillin-tazobactam/tigecycline combination may be considered empirical agents. Chest infections and AML were independent predictors of poor clinical outcome in neutropenic patients. Regular audit of infections and antibiotic susceptibility data is needed to improve clinical outcomes in patients with febrile neutropenia.

COVID-19 and cardiac arrhythmias: a global perspective on arrhythmia characteristics and management strategies.

BACKGROUND: Cardiovascular and arrhythmic events have been reported in hospitalized COVID-19 patients. However, arrhythmia manifestations and treatment strategies used in these patients have not been well-described. We sought to better understand the cardiac arrhythmic manifestations and treatment strategies in hospitalized COVID-19 patients through a worldwide cross-sectional survey. METHODS: The Heart Rhythm Society (HRS) sent an online survey (via SurveyMonkey) to electrophysiology (EP) professionals (physicians, scientists, and allied professionals) across the globe. The survey was active from March 27 to April 13, 2020. RESULTS: A total of 1197 respondents completed the survey with 50% of respondents from outside the USA, representing 76 countries and 6 continents. Of respondents, 905 (76%) reported having COVID-19-positive patients in their hospital. Atrial fibrillation was the most commonly reported tachyarrhythmia whereas severe sinus bradycardia and complete heart block were the most common bradyarrhythmias. Ventricular tachycardia/ventricular fibrillation arrest and pulseless electrical activity were reported by 4.8% and 5.6% of respondents, respectively. There were 140 of 631 (22.2%) respondents who reported using anticoagulation therapy in all COVID-19-positive patients who did not otherwise have an indication. One hundred fifty-five of 498 (31%) reported regular use of hydroxychloroquine/chloroquine (HCQ) + azithromycin (AZM); concomitant use of AZM was more common in the USA. Sixty of 489 respondents (12.3%) reported having to discontinue therapy with HCQ + AZM due to significant QTc prolongation and 20 (4.1%) reported cases of Torsade de Pointes in patients on HCQ/chloroquine and AZM. Amiodarone was the most common antiarrhythmic drug used for ventricular arrhythmia management. CONCLUSIONS: In this global survey of > 1100 EP professionals regarding hospitalized COVID-19 patients, a variety of arrhythmic manifestations were observed, ranging from benign to potentially life-threatening. Observed adverse events related to use of HCQ + AZM included prolonged QTc requiring drug discontinuation as well as Torsade de Pointes. Large prospective studies to better define arrhythmic manifestations as well as the safety of treatment strategies in COVID-19 patients are warranted.

The Presence of Cyclooxygenase 2, Tumor-Associated Macrophages, and Collagen Alignment as Prognostic Markers for Invasive Breast Carcinoma Patients.

Inflammation, and the organization of collagen in the breast tumor microenvironment, is an important mediator of breast tumor progression. However, a direct link between markers of inflammation, collagen organization, and patient outcome has yet to be established. A tumor microarray of 371 invasive breast carcinoma biopsy specimens was analyzed for expression of inflammatory markers, including cyclooxygenase 2 (COX-2), macrophages, and several collagen features in the tumor nest (TN) or the tumor-associated stroma (TS). The tumor microarray cohort included females, aged 18 to 80 years, with a median follow-up of 8.4 years. High expression of COX-2 (TN), CD68 (TS), and CD163 (TN and TS) predicted worse patient overall survival (OS). This notion was strengthened by the finding from the multivariate analysis that high numbers of CD163+ macrophages in the TS is an independent prognostic factor. Overall collagen deposition was associated with high stromal expression of COX-2 and CD163; however, total collagen deposition was not a predictor for OS. Conversely, local collagen density, alignment and perpendicular alignment to the tumor boundary (tumor-associated collagen signature-3) were predictors of OS. These results suggest that in invasive carcinoma, the localization of inflammatory cells and aligned collagen orientation predict poor patient survival. Additional clinical studies may help validate whether therapy with selective COX-2 inhibitors alters expression of CD68 and CD163 inflammatory markers.

Endovascular Versus Open Revascularization for Peripheral Arterial Disease.

OBJECTIVE: The aim of this study was to determine whether endovascular or open revascularization provides an advantageous approach to symptomatic peripheral arterial disease (PAD) over the longer term. SUMMARY OF BACKGROUND DATA: The optimal revascularization strategy for symptomatic lower extremity PAD is not established. METHODS: We evaluated amputation-free survival, overall survival, and relative rate of subsequent vascular intervention after endovascular or open lower extremity revascularization for propensity-score matched cohorts of Medicare beneficiaries with PAD from 2006 through 2009. RESULTS: Among 14,685 eligible patients, 5928 endovascular and 5928 open revascularization patients were included in matched analysis. Patients undergoing endovascular repair had improved amputation-free survival compared with open repair at 30 days (7.4 vs 8.9%, P = 0.002). This benefit persisted over the long term: At 4 years, 49% of endovascular patients had died or received major amputation compared with 54% of open patients (P < 0.001). An endovascular procedure was associated with a risk-adjusted 16% decreased risk of amputation or death compared with open over the study period (hazard ratio: 0.84; 95% confidence interval, 0.79-0.89; P < 0.001). The amputation-free survival benefit associated with an endovascular revascularization was more pronounced in patients with congestive heart failure or ischemic heart disease than in those without (P = 0.021 for interaction term). The rate of subsequent intervention at 30 days was 7.4% greater for the endovascular vs the open revascularization cohort. At 4 years, this difference remained stable at 8.6%. CONCLUSIONS: Using population-based data, we demonstrate that an endovascular approach is associated with improved amputation-free survival over the long term with only a modest relative increased risk of subsequent intervention.

Factors influencing sialocele or salivary fistula formation postparotidectomy.

BACKGROUND: Does the extent of parotidectomy or other patient or tumor characteristics influence the rate of sialocele/salivary fistula formation? METHODS: All patients who underwent parotidectomy at the University of Wisconsin from 1994 to 2013 were considered. Patients who developed a sialocele/salivary fistula were identified. Extent of dissection, age, sex, body mass index (BMI), volume of specimen, and rate of malignancy were examined. RESULTS: Seventy of 771 patients (9.1%) developed a sialocele/salivary fistula. Sixty-seven fistulae (96%) developed within 1 month and all resolved by 6 months. Age, sex, pathology, and BMI were not increased in the sialocele group. Inferior and middle superficial parotidectomy had a significantly higher rate of sialocele than other extents of dissection. Volume of tissue removed was not significantly different between dissection groups. CONCLUSION: Sialocele/salivary fistula is common postparotidectomy and is more likely with inferior and middle superficial parotidectomy. © 2016 Wiley Periodicals, Inc. Head Neck 39: 387-391, 2017.

Novel Implantable Cardioverter-defibrillator Lead Placement in a Patient with a Prosthetic Tricuspid Valve.

As the placement of transvenous leads across a prosthetic tricuspid valve is preferentially avoided, one must consider alternative solutions to provide necessary pacing and/or defibrillator therapy. Here, we present a case of novel placement of an implantable cardioverter-defibrillator (ICD) lead in the right atrium, in order to provide safe ICD therapy in a patient with a prosthetic tricuspid valve.

The impact of perioperative ß blocker use on patient outcomes after primary cytoreductive surgery in high-grade epithelial ovarian carcinoma.

OBJECTIVE: To quantify the impact of perioperative ß blocker use on survival after primary cytoreductive surgery for epithelial ovarian cancer. METHODS: We conducted a multi-center retrospective study of all women who underwent primary cytoreductive surgery for ovarian cancer (2000-2010). One institution had routinely used perioperative ß blockers for patients "at risk" for coronary events. The other institution did not routinely use perioperative ß blockers. Demographic, operative, and follow up data were collected. Cox proportional hazards models were used to assess the effect of ß blockers on progression-free interval (PFI) as well as overall survival (OS). RESULTS: Out of 185 eligible patients, 70 received ß blockers and 115 underwent cytoreductive surgery without perioperative ß blockers. Both groups were similar in demographics. A history of hypertension was present more often in the ß blocker group compared to the group that did not receive ß blockers (22% and 6%, p=0.002). PFI in ß blocker group was greater at 18.2 vs. 15.8months (p=0.66). The OS in the ß blocker group was significantly higher at 44.2 vs. 39.3months (p=0.01). In multivariate analysis, perioperative ß blocker use was associated with significant improvement in OS (HR 0.68 (0.46-0.99); p=0.046). CONCLUSION: Our study showed an association between perioperative ß blocker use and longer overall survival in patients undergoing primary ovarian cancer cytoreductive surgery. A prospective randomized clinical trial in this population would further validate these results.

Combined Right Ventricular Outflow Tract Epicardial and Endocardial Late Potential Ablation for Treatment of Brugada Storm: A Case Report and Review of the Literature.

A 34-year-old man with Brugada syndrome (BrS) presented with electrical storm, manifested as multiple appropriate shocks from his implantable cardioverter-defibrillator over a period of 7 hours. He had not tolerated prior treatment with quinidine, and had self-discontinued cilostazol citing persistent palpitations. After stabilization with intravenous isoproterenol, an electrophysiology study was performed but no spontaneous or induced ventricular ectopic beats were identified. A three-dimensional (3D) endocardial electro-anatomic map of the right ventricular outflow tract (RVOT), pulmonic valve, and pulmonary artery, as well as a 3D epicardial map of the RVOT, were created. Low voltage, complex, fractionated electrograms and late potentials were targeted for irrigated radiofrequency ablation both endocardially and epicardially. Post-procedure, he was maintained on cilostazol (referring clinician preference), and has had no further ventricular tachyarrhythmia episodes over the past forty-one months. We propose that this novel ablation strategy may be useful for acute management of selected patients with BrS.

Patterns of Facial Fractures and Protective Device Use in Motor Vehicle Collisions From 2007 to 2012.

IMPORTANCE: Facial fractures after motor vehicle collisions are a significant source of facial trauma in patients seen at trauma centers. With recent changes in use of seat belts and advances in airbag technology, new patterns in the incidence of facial fractures after motor vehicle collisions have yet to be quantified. OBJECTIVES: To evaluate the incidence of facial fractures and assess the influence of protective device use in motor vehicle collisions in patients treated at trauma centers in the United States. DESIGN, SETTING, AND PARTICIPANTS: Using a data set from the National Trauma Data Bank, we retrospectively assessed facial fractures in motor vehicle collisions occurring from 2007 through 2012, reported by level I, II, III, and IV trauma centers. Data analysis was performed from March 13 to September 22, 2015. MAIN OUTCOMES AND MEASURES: We characterized the data set by subsite of facial injury using International Classification of Diseases, Ninth Revision codes including mandible, midface, and nasal fractures. We assessed the influence of variables such as age, sex, race/ethnicity, crash occupant (driver or passenger), use of protective device, and presence or suspicion of alcohol use. RESULTS: A total of 518 106 patients required assessment at a trauma center after a motor vehicle collision, with 56 422 (10.9%) experiencing at least 1 facial fracture. Nasal fracture was the most common facial fracture (5.6%), followed by midface (3.8%), other (3.2%), orbital (2.6%), mandible (2.2%), and panfacial fractures (0.8%). Of the subset sustaining at least 1 facial fracture, 5.8% had airbag protection only, 26.9% used a seat belt only, and 9.3% used both protective devices, while 57.6% used no protective device. Compared with no protective device, the use of an airbag alone significantly reduced the likelihood of facial fracture after a motor vehicle collision (odds ratio, 0.82; 95% CI, 0.79-0.86); use of a seat belt alone had a greater effect (odds ratio, 0.57; 95% CI, 0.56-0.58) and use of both devices provided the greatest odds reduction (odds ratio, 0.47; 95% CI, 0.45-0.48). Younger age, male sex, and alcohol use significantly increased the likelihood of facial fracture. CONCLUSIONS AND RELEVANCE: For patients who presented to US trauma centers after motor vehicle collisions between 2007 and 2012, airbags, seat belts, and the combination of the 2 devices incrementally reduced the likelihood of facial fractures. LEVEL OF EVIDENCE: 3.

Targeting Estrogen Receptor Beta in a Phase 2 Study of High-Dose Estradiol in Metastatic Triple-Negative Breast Cancer: A Wisconsin Oncology Network Study.

BACKGROUND: Estrogen receptor beta (ERß) is expressed by 50% to 80% of triple-negative breast cancers (TNBC). Agonism of ERß has antiproliferative effects in TNBC cells expressing ERß. This phase 2 study evaluated single-agent high-dose estradiol in patients with advanced TNBC. PATIENTS AND METHODS: Adult women with measurable advanced TNBC were treated with estradiol 10 mg oral 3 times daily provided continuously for 28-day cycles. A Simon optimal 2-stage design was used. The primary end point was objective response (OR). Secondary end points included progression-free survival (PFS), clinical benefit (CB), and safety. OR, CB, and PFS by ERß status were also examined. RESULTS: Seventeen evaluable women were enrolled. Median age was 58 years (range, 34-90 years); the median number of prior systemic therapies was 2 (range, 0-6). One patient had a confirmed partial response (OR rate, 5.9%) and remained on the study for > 24 weeks. Three patients had stable disease, with one lasting more than 16 weeks. ERß expression was detected in 77% (13 patients). The CB rate at 16 weeks was 15% (2 of 13) in ERß-positive patients and 0% (0 of 4) in ERß-negative patients (P = 1). PFS was poor (median, 1.9 months) and not statistically significantly different between ERß-positive versus -negative patients. No new adverse events from estradiol were identified. The study closed after the first stage as a result of limited responses in these unselected patients. CONCLUSION: In unselected TNBC, high-dose estradiol has limited efficacy. However, further evaluation of ERß selective agonists in TNBC selected by ERß expression may be warranted.

Increased tumor response to neoadjuvant therapy among rectal cancer patients taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers.

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are commonly used antihypertensive medications that have been reported to affect aberrant angiogenesis and the dysregulated inflammatory response. Because of such mechanisms, it was hypothesized that these medications might affect the tumor response to neoadjuvant radiation in patients with rectal cancer. METHODS: One hundred fifteen patients who were treated with neoadjuvant radiation at the University of Wisconsin (UW) between 1999 and 2012 were identified. Univariate analyses were performed with anonymized patient data. In a second independent data set, 186 patients with rectal cancer who were treated with neoadjuvant radiation at the Queen's Medical Center of the University of Hawaii (UH) between 1995 and 2010 were identified. These data were independently analyzed as before. Multivariate analyses were performed with aggregate data. RESULTS: Among patients taking ACEIs/ARBs in the UW data set, a significant 3-fold increase in the rate of pathologic complete response (pCR) to neoadjuvant therapy (52% vs 17%, P = .001) was observed. This finding was confirmed in the UH data set, in which a significant 2-fold-increased pCR rate (24% vs 12%, P = .03) was observed. Identified patient and treatment characteristics were otherwise balanced between patients taking and not taking ACEIs/ARBs. No significant effect was observed on pCR rates with other medications, including statins, metformin, and aspirin. Multivariate analyses of aggregate data identified ACEI/ARB use as a strong predictor of pCR (odds ratio, 4.02; 95% confidence interval, 2.06-7.82; P < .001). CONCLUSIONS: The incidental use of ACEIs/ARBs among patients with rectal cancer is associated with a significantly increased rate of pCR after neoadjuvant treatment. Cancer 2016;122:2487-95. © 2016 American Cancer Society.

COX-2 modulates mammary tumor progression in response to collagen density.

BACKGROUND: High breast density is linked to an increased risk of breast cancer, and correlates with changes in collagen. In a mouse model of mammary carcinoma in the context of increased collagen deposition, the MMTV-PyMT/Col1a1 (tm1jae) , there is accelerated mammary tumor formation and progression. Previous gene expression analysis suggests that increased collagen density elevates expression of PTGS2 (prostaglandin-endoperoxide synthase 2), the gene for cyclooxygenase-2 (COX-2). METHODS: To understand the role of COX-2 in tumor progression within a collagen-dense microenvironment, we treated MMTV-PyMT or MMTV-PyMT/Col1a1 (tm1jae) tumors prior to and after tumor formation. Animals received treatment with celecoxib, a specific COX-2 inhibitor, or placebo. Mammary tumors were examined for COX-2, inflammatory and stromal cell components, and collagen deposition through immunohistochemical analysis, immunofluorescence, multiplex cytokine ELISA and tissue imaging techniques. RESULTS: PyMT/Col1a1 (tm1jae) tumors were larger, more proliferative, and expressed higher levels of COX-2 and PGE2 than PyMT tumors in wild type (WT) mice. Treatment with celecoxib significantly decreased the induced tumor size and metastasis of the PyMT/Col1a1 tumors, such that their size was not different from the smaller PyMT tumors. Celecoxib had minimal effect on the PyMT tumors. Celecoxib decreased expression levels of COX-2, PGE2, and Ki-67. Several cytokines were over-expressed in PyMT/Col1a1 compared to PyMT, and celecoxib treatment prevented their over-expression. Furthermore, macrophage and neutrophil recruitment were enhanced in PyMT/Col1a1 tumors, and this effect was inhibited by celecoxib. Notably, COX-2 inhibition reduced overall collagen deposition. Finally, when celecoxib was used prior to tumor formation, PyMT/Col1a1 tumors were fewer and smaller than in untreated animals. CONCLUSION: These findings suggest that COX-2 has a direct role in modulating tumor progression in tumors arising within collagen-dense microenvironments, and suggest that COX-2 may be an effective therapeutic target for women with dense breast tissue and early-stage breast cancer.