The Increasing Incidence of Young-Onset Colorectal Cancer: A Call to Action

In the United States, colorectal cancer (CRC) is the third most common and second most lethal cancer. More than one-tenth of CRC cases (11% of colon cancers and 18% of rectal cancers) have a young onset (ie, occurring in individuals younger than 50 years). The CRC incidence and mortality rates are decreasing among all age groups older than 50 years, yet increasing in younger individuals for whom screening use is limited and key symptoms may go unrecognized. Familial syndromes account for approximately 20% of young-onset CRCs, and the remainder are typically microsatellite stable cancers, which are more commonly diploid than similar tumors in older individuals. Young-onset CRCs are more likely to occur in the distal colon or rectum, be poorly differentiated, have mucinous and signet ring features, and present at advanced stages. Yet, stage-specific survival in patients with young-onset CRC is comparable to that of patients with later-onset cancer. Primary care physicians have an important opportunity to identify high-risk young individuals for screening and to promptly evaluate CRC symptoms. Risk modification, targeted screening, and prophylactic surgery may benefit individuals with a predisposing hereditary syndrome or condition (eg, inflammatory bowel disease) or a family history of CRC or advanced adenomatous polyps. When apparently average-risk young adults present with CRC-like symptoms (eg, unexplained persistent rectal bleeding, anemia, and abdominal pain), endoscopic work-ups can expedite diagnosis. Early screening in high-risk individuals and thorough diagnostic work-ups in symptomatic young adults may improve young-onset CRC trends.     

Approach to the Patient With Hematochezia

The evaluation of the patient with hematochezia can be complex because of the broad differential diagnosis and the number of management strategies available. In this article, a simplified approach to the history and physical examination is presented, with management illustrated in a case-oriented manner.     

Evaluation and Management of Patients With Heart Disease and Cancer: Cardio-Oncology

The care for patients with cancer has advanced greatly over the past decades. A combination of earlier cancer diagnosis and greater use of traditional and new systemic treatments has decreased cancer-related mortality. Effective cancer therapies, however, can result in short- and long-term comorbidities that can decrease the net clinical gain by affecting quality of life and survival. In particular, cardiovascular complications of cancer treatments can have a profound effect on the health of patients with cancer and are more common among those with recognized or unrecognized underlying cardiovascular diseases. A new discipline termed cardio-oncology has thus evolved to address the cardiovascular needs of patients with cancer and optimize their care in a multidisciplinary approach. This review provides a brief introduction and background on this emerging field and then focuses on its practical aspects including cardiovascular risk assessment and prevention before cancer treatment, cardiovascular surveillance and therapy during cancer treatment, and cardiovascular monitoring and management after cancer therapy. The content of this review is based on a literature search of PubMed between January 1, 1960, and February 1, 2014, using the search terms cancer, cardiomyopathy, cardiotoxicity, cardio-oncology, chemotherapy, heart failure, and radiation.     

A DPYD Variant (Y186C) Specific to Individuals of African Descent in a Patient With Life-Threatening 5-FU Toxic Effects: Potential for an Individualized Medicine Approach

5-Fluorouracil (5-FU) is commonly administered as a therapeutic agent for the treatment of various aggressive cancers. Severe toxic reactions to 5-FU have been associated with decreased levels of dihydropyrimidine dehydrogenase (DPD) enzyme activity. Manifestations of 5-FU toxicity typically include cytopenia, diarrhea, stomatitis, mucositis, neurotoxicity, and, in extreme cases, death. A variety of genetic variations in DPYD, the gene encoding DPD, are known to result in decreased DPD enzyme activity and to contribute to 5-FU toxic effects. Recently, it was reported that healthy African American individuals carrying the Y186C DPYD variant (rs115232898) had significantly reduced DPD enzyme activity compared with noncarriers of Y186C. Herein, we describe for the first time, to our knowledge, an African American patient with cancer with the Y186C variant who had severe toxic effects after administration of the standard dose of 5-FU chemotherapy. The patient lacked any additional toxic effect–associated variations in the DPYD gene or the thymidylate synthase (TYMS) promoter. This case suggests that Y186C may have contributed to 5-FU toxicity in this patient and supports the use of Y186C as a predictive marker for 5-FU toxic effects in individuals of African ancestry.     

Transcranial Magnetic Stimulation as an Antidepressant Alternative in a Patient With Brugada Syndrome and Recurrent Syncope

Brugada syndrome (BrS) is a common occult cause of sudden cardiac arrest in otherwise healthy-appearing adults. The pathognomonic electrocardiographic pattern may be unmasked only by certain medications, many of which are unknown. We report a case of a depressed but otherwise healthy man with an asymptomatic right bundle branch block on electrocardiography who experienced antidepressant-induced BrS and ultimately recovered with transcranial magnetic stimulation (TMS). After an initial trial of nortriptyline, the patient’s depressive symptoms improved; however, he experienced a syncopal event and was subsequently diagnosed as having BrS. Cross titration to bupropion, which had not previously been known to exacerbate BrS, was followed by another cardiac event. As a result, the patient was referred for TMS as a substitute for pharmacotherapy. After 31 TMS sessions over 8 weeks, the patient demonstrated significant improvement by subjective report and objective reduction in his Patient Health Questionnaire-9 scores from 10 (moderate) to 1 (minimal). Transcranial magnetic stimulation is a Food and Drug Administration–approved nonpharmacologic treatment for depression. Given the potential lethality of BrS with known and unknown psychopharmacologic agents, providers should consider TMS as first-line therapy in this patient population. Bupropion should be added to the list of agents known to exacerbate this disease.     

Pneumatosis Intestinalis With a Focus on Hyperbaric Oxygen Therapy

Pneumatosis intestinalis is a rare condition of air in the bowel wall. Pneumatosis intestinalis is most often secondary to another medical condition. The diagnosis is most often made radiologically with a computed tomography scan. The disease severity ranges from benign to life-threatening. Predictors of poor outcomes include pH less than 7.3, bicarbonate level of less than 20 mEq/L, lactate level of more than 2 mmol/L, amylase level of more than 200 U/L, and portal venous gas on imaging. Early recognition of life-threatening signs and symptoms is critical. Treatment options include bowel rest, antibiotics, surgery, and, more recently, the use of hyperbaric oxygen therapy. Hyperbaric oxygen therapy is extremely safe, with no reported complications in the literature when used for pneumatosis intestinalis. When surgery is not emergently needed, symptomatic pneumatosis intestinalis can be safely treated with hyperbaric oxygen with a high likelihood of success without any considerable adverse effects.     

My Treatment Approach to Management of the Pregnant Patient With Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is frequently diagnosed in women of childbearing age. Of paramount concern are questions about the effect of the disease on a woman's ability to conceive and carry the pregnancy safely to term, as well as the effect of the disease and its therapies on the health of the fetus. For health care providers, there is also the issue of medication dose adjustments and management of flares during pregnancy. Growing experience with IBD in pregnancy suggests that most women will have good outcomes; however, concerns and uncertainty remain for both the patient and the physician. This article outlines our approach to the treatment of these patients with respect to preconception counseling and management during pregnancy and the postpartum period.     

Racial Disparities in Survival for Patients With Clinically Localized Prostate Cancer Adjusted for Treatment Effects

ObjectiveTo examine whether racial disparities in survival exist among black, Hispanic, and Asian patients compared with white patients with clinically localized prostate cancer (CLPC) after adjustment for the effects of treatment.Patients and MethodsWe performed a retrospective cohort study of patients with CLPC diagnosed from January 1, 1995, through December 31, 2003, as documented in the Surveillance, Epidemiology, and End Results registry. Treatment-stratified, risk-adjusted Cox proportional hazards models were constructed.ResultsDuring the study period, CLPC was diagnosed in 294,160 patients. Of these patients, 123,850 (42.1%) underwent surgery and 101,627 (34.5%) underwent radiotherapy, whereas 68,683 (23.3%) received no treatment. Overall 5-year and 10-year survival rates for Asians (85.6% and 67.6%, respectively), Hispanics (85.9% and 69.0%, respectively), and whites (83.9% and 65.7%, respectively) were higher than for blacks (81.5% and 61.7%, respectively) (P<.001). Prostate cancer–specific survival also varied significantly by race (P<.001). A risk-adjusted model stratified by primary treatment modality revealed that blacks had worse overall survival than whites (hazard ratio, 1.37; 95% CI, 1.33-1.41; P<.001), whereas Asians had better survival compared with whites (hazard ratio, 0.79; 95% CI, 0.76-0.83; P<.001). After the effects of treatment were accounted for, Hispanics had similar overall survival compared with whites (hazard ratio, 0.97; 95% CI, 0.94-1.01; P=.10).ConclusionBlacks with CLPC have poorer survival than whites, whereas Asians have better survival, even after risk adjustment and stratification by treatment. These data may be relevant to US regions with large underserved populations that have limited access to health care.     

Prostate Cancer Ki-67 (MIB-1) Expression,Perineural Invasion,and Gleason Score as Biopsy-Based Predictors of Prostate Cancer Mortality: The Mayo Model

ObjectiveTo determine the role of cellular proliferation and other biopsy-based features in the prediction of prostate cancer mortality.Patients and MethodsBetween 1993 and 2012, our institution has performed quantitation of prostate cancer DNA ploidy and Ki-67 (MIB-1) on most prostate cancer needle biopsy specimens. The outcomes of 451 consecutive patients with biopsy-proven cancer treated by radical prostatectomy between January 24, 1995, and December 29, 1998, without neoadjuvant hormonal therapy were assessed. Clinical and biopsy information obtained before radical prostatectomy was placed in multivariate Cox proportional hazards regression models to predict local or systemic progression and cancer-specific death. Predictive ability was evaluated using a concordance index.ResultsWith a median follow-up of 12.9 years, 46 patients experienced local or systemic progression, and 18 patients died of prostate cancer. On multivariate analysis, the biopsy features of Ki-67 expression, perineural invasion, and Gleason score were associated with local or systemic progression. Ki-67 expression, perineural invasion, and Gleason score were associated with cancer-specific death with a concordance index of 0.892. After adjusting for perineural invasion and Gleason score, each 1% increase in Ki-67 expression was associated with a 12% increased risk of cancer-specific death (P<.001). Ki-67 expression alone was a strong predictor of cancer-specific outcomes and improved the predictive ability of currently used algorithms.ConclusionThis study documents that long-term prostate cancer outcomes are best estimated with a combination of Gleason score, perineural invasion, and Ki-67 expression. Given its low cost, rapid assessment, and strong predictive power, we believe that adding Ki-67 expression to perineural invasion and Gleason score at biopsy should be considered a standard by which all new biomarkers are compared before introducing them into clinical practice.     

Comparative Effectiveness of Telaprevir-Based Triple Therapy in Patients With Chronic Hepatitis C

ObjectiveTo examine the effectiveness and tolerability of triple therapy with pegylated interferon (p-IFN), ribavirin (RBV), and telaprevir in patients with chronic hepatitis C receiving treatment in an academic practice setting and in a more clinically diverse population compared with patients receiving treatment in phase 3 trials.Patients and MethodsA prospective database of all patients with viral hepatitis undergoing antiviral therapy from January 1, 2006, to July 1, 2012, was queried to identify treatment-naive and -experienced patients with chronic hepatitis C receiving dual and triple therapies. On-treatment response categories included rapid virologic response, extended rapid virologic response, early virologic response, and sustained virologic response. These patients were compared with matched controls, namely, patients who underwent dual therapy with p-IFN and RBV. Matching was performed for age, cirrhosis status, and prior treatment.ResultsThere were 55 patients who received triple therapy and met the eligibility criteria, consisting of treatment-naive (n=35) and -experienced patients (n=20: those with relapse, 9; those with nonresponse, 9; and those who terminated the treatment early, 2). Rapid virologic response was achieved in 41% of the patients, extended rapid virologic response in 41%, and early virologic response in 75%. Sustained virologic response was observed in 51% (18/35) of treatment-naive patients, 67% (6/9) of the patients with prior nonresponse, and 56% (5/9) of those with prior relapse. Corresponding results after dual therapy were 37% (23/62), 11% (2/18), and 27% (3/11), respectively. The mean decrease in the hemoglobin level at weeks 4, 8, and 24 of triple therapy was 2.8, 3.8, and 3.2 mg/dL compared with 2.4, 2.6, and 2.4 mg/dL with dual therapy (to convert mg/dL to mmol/L, multiply values by 0.0259).ConclusionTelaprevir-based triple therapy in clinical practice is considerably more effective than dual therapy with p-IFN and RBV despite the significant degree of anemia that complicated therapy, requiring RBV dose reduction and erythropoietin support.     

Over-the-Counter Enzyme Supplements: What a Clinician Needs to Know

Over-the-counter (OTC) enzyme use is increasing in frequency in the United States. The numerous health benefit claims by manufacturers are leading to a surge in enzyme use for various conditions and symptoms. Clinicians need to help patients navigate this complex realm and make informed decisions about the use of OTC enzymes. This review focuses on key concepts for health care providers to understand the current evidence, risks, and benefits of OTC enzymes.     

The Effect of Resistance Exercise on All-Cause Mortality in Cancer Survivors

ObjectiveTo examine the independent associations of leisure-time aerobic physical activity (PA) and resistance exercise (RE) on all-cause mortality in cancer survivors.Patients and MethodsPatients included 2863 male and female cancer survivors, aged 18 to 81 years, who received a preventive medical examination between April 8, 1987, and December 27, 2002, while enrolled in the Aerobics Center Longitudinal Study in Dallas, Texas. Physical activity and RE were assessed by self-report at the baseline medical examination. Cox proportional hazards regression analysis was performed to determine the independent associations of PA and RE with all-cause mortality in participants who had a history of cancer.ResultsPhysical activity in cancer survivors was not associated with a lower risk of all-cause mortality. In contrast, RE was associated with a 33% lower risk of all-cause mortality (95% CI, 0.45-0.99) after adjusting for potential confounders, including PA.ConclusionIndividuals who participated in RE during cancer survival had a lower risk for all-cause mortality. The present findings provide preliminary evidence for benefits of RE during cancer survival. Future randomized controlled trials examining RE and its effect on lean body mass, muscular strength, and all-cause mortality in cancer survivors are warranted.     

Comparison of the Quality of Patient Referrals From Physicians,Physician Assistants,and Nurse Practitioners

ObjectiveTo compare the quality of referrals of patients with complex medical problems from nurse practitioners (NPs), physician assistants (PAs), and physicians to general internists.Patients and MethodsWe conducted a retrospective comparison study involving regional referrals to an academic medical center from January 1, 2009, through December 31, 2010. All 160 patients referred by NPs and PAs combined and a random sample of 160 patients referred by physicians were studied. Five experienced physicians blinded to the source of referral used a 7-item instrument to assess the quality of referrals. Internal consistency, interrater reliability, and dimensionality of item scores were determined. Differences between item scores for patients referred by physicians and those for patients referred by NPs and PAs combined were analyzed by using multivariate ordinal logistical regression adjusted for patient age, sex, distance of the referral source from Mayo Clinic, and Charlson Index.ResultsFactor analysis revealed a 1-dimensional measure of the quality of patient referrals. Interrater reliability (intraclass correlation coefficient for individual items: range, 0.77-0.93; overall, 0.92) and internal consistency for items combined (Cronbach α=0.75) were excellent. Referrals from physicians were scored higher (percentage of agree/strongly agree responses) than were referrals from NPs and PAs for each of the following items: referral question clearly articulated (86.3% vs 76.0%; P=.0007), clinical information provided (72.6% vs 54.1%; P=.003), documented understanding of the patient's pathophysiology (51.0% vs 30.3%; P<.0001), appropriate evaluation performed locally (60.3% vs 39.0%; P<.0001), appropriate management performed locally (53.5% vs 24.1%; P<.0001), and confidence returning patient to referring health care professional (67.8% vs 41.4%; P<.0001). Referrals from physicians were also less likely to be evaluated as having been unnecessary (30.1% vs 56.2%; P<.0001).ConclusionThe quality of referrals to an academic medical center was higher for physicians than for NPs and PAs regarding the clarity of the referral question, understanding of pathophysiology, and adequate prereferral evaluation and documentation.     

Body Composition and Mortality in a Large Cohort With Preserved Ejection Fraction: Untangling the Obesity Paradox

ObjectiveTo evaluate the effects of body composition as a function of lean mass index (LMI) and body fat (BF) on the correlation between increasing body mass index (BMI; calculated as the weight in kilograms divided by the height in meters squared) and decreasing mortality, which is known as the obesity paradox.Patients and MethodsWe retrospectively assessed 47,866 patients with preserved left ventricular ejection fraction (≥50%). We calculated BF by using the Jackson-Pollock equation and LMI using (1 − BF) × BMI. The population was divided according to the sex-adjusted BMI classification, sex-adjusted LMI classification, and sex-adjusted BF tertiles. The population was analyzed by using multivariate analysis for total mortality over a mean follow-up duration of 3.1 years by using the National Death Index, adjusting for left ventricular ejection fraction, left ventricular mass index, age, sex, and relative wall thickness.ResultsIn the entire population, higher BMI was narrowly associated (hazard ratio [HR], 0.99; P<.001) with lower mortality. The higher LMI group was clearly protective (HR, 0.71; P<.001), whereas BF tertile was associated with lower mortality only if no adjustment was made for LMI (HR, 0.87; P<.001 without LMI; HR, 0.97; P=.23 with LMI). In the lean patients, low BMI was clearly associated with higher mortality (HR, 0.92; P<.001) and lower BF tertile was associated with lower mortality only if no adjustment was made for LMI (HR, 0.80; P<.001 without LMI; HR, 1.01; P=.83 with LMI). The underweight patients stratified by BF seemed to have an increased mortality (HR, 1.91; 95% CI, 1.56-2.34) that was independent of LMI. However, in obese patients, both BMI (HR, 1.03; P<.001) and BF (HR, 1.18; P=.003) were associated with higher mortality, even after adjusting for LMI, which remained protective (HR, 0.57; P<.001) independently of BF.ConclusionBody composition could explain the inverse J shape of the mortality curve noted with increasing BMI. Body fat seems to be protective in this cohort only if no adjustment was made for LMI, although being underweight stratified by BF seems to be an independent risk factor. Lean mass index seems to remain protective in obese patients even when BMI is not.     

Myocardial Infarction Risk Among Patients With Fractures Receiving Bisphosphonates

ObjectiveTo determine if bisphosphonates are associated with reduced risk of acute myocardial infarction (AMI).Patients and MethodsA cohort of 14,256 veterans 65 years or older with femoral or vertebral fractures was selected from national administrative databases operated by the US Department of Veterans Affairs and was derived from encounters at Veterans Affairs facilities between October 1, 1998, and September 30, 2006. The time to first AMI was assessed in relationship to bisphosphonate exposure as determined by records from the Pharmacy Benefits Management Database. Time to event analysis was performed using multivariate Cox proportional hazards regression. An adjusted survival analysis curve and a Kaplan-Meier survival curve were analyzed.ResultsAfter controlling for atherosclerotic cardiovascular disease risk factors and medications, bisphosphonate use was associated with an increased risk of incident AMI (hazard ratio, 1.38; 95% CI, 1.08-1.77; P=.01). The timing of AMI correlated closely with the timing of bisphosphonate therapy initiation.ConclusionOur observations in this study conflict with our hypothesis that bisphosphonates have antiatherogenic effects. These findings may alter the risk-benefit ratio of bisphosphonate use for treatment of osteoporosis, especially in elderly men. However, further analysis and confirmation of these findings by prospective clinical trials is required.     

Biomedical System Dynamics to Improve Anemia Control With Darbepoetin Alfa in Long-Term Hemodialysis Patients

ObjectiveTo determine the value of a biomedical system dynamics (BMSD) approach for optimization of anemia management in long-term hemodialysis patients because elevated hemoglobin levels and high doses of erythropoiesis-stimulating agents (ESAs) may negatively affect survival in this population.Patients and MethodsA model of erythropoiesis and its response to ESAs on the basis of a BMSD method (Mayo Clinic Anemia Management System [MCAMS]) was developed. Thereafter, an open-label, prospective, nonrandomized practice quality improvement project was performed with retrospective analysis in 8 community-based outpatient hemodialysis facilities. All prevalent hemodialysis patients seen from January 1, 2007, through December 31, 2010 (300-342 patients per month), were included with darbepoetin as the ESA. The primary outcome was the percentage of patients who attained the desired hemoglobin level. Secondary outcome measures included the percentage of patients with hemoglobin values above the desired range and mean dose of darbepoetin used.ResultsThe 3 treatment periods were (1) standard ESA protocol in 2007, (2) transition to the MCAMS (2008 to June 2009), and (3) stability period with the MCAMS used in all hemodialysis facilities (2009 to 2010). In the first 6 months of 2007, 69% of patients were in the desired range and 26% were above the range. In comparison, during the first 5 months of 2010, 83% were in and 6% were above the range (P<.001). The mean monthly darbepoetin dose per patient decreased from 304 μg in 2007 to 173 μg by the second half of 2009 (P<.001).ConclusionWith the introduction of the MCAMS, more patients had hemoglobin levels in the desired range and fewer patients exceeded the target range, with a concomitant 40% reduction in darbepoetin use.     

A Prospective Pilot Study of Predictors of Acute Stroke in Emergency Department Patients With Dizziness

ObjectiveTo prospectively examine undifferentiated emergency department (ED) patients with dizziness to identify clinical features associated with acute stroke.Patients and MethodsWe conducted a pilot study from November 1, 2009, through October 30, 2010, of adult patients with dizziness presenting to 3 urban academic EDs. Data collected included demographic characteristics, medical history, presenting symptoms, examination findings, clinician pretest probability of stroke, and neuroimaging results. Logistic regression was used to identify variables with a significant association with acute stroke (P<.05).ResultsDuring the study period, we enrolled 473 patients (mean ± SD age, 56.7±19.3 years; 60% female; and 71% white). We found 30 acute, serious diagnoses (6.3%), including 14 ischemic strokes, 2 subarachnoid hemorrhages, 7 mass lesions, 2 demyelinating lesions, 2 severe vertebral artery stenoses, 2 acute coronary syndromes, and 1 case of hydrocephalus and meningitis). We identified 6 clinical variables associated with stroke: age (odds ratio [OR], 1.04; 95% CI, 1.0-1.07), hyperlipidemia (OR, 3.62; 95% CI, 1.24-10.6), hypertension (OR, 4.91; 95% CI, 1.46-16.5), coronary artery disease (OR, 3.33; 95% CI, 1.06-10.5), abnormal tandem gait test result (OR, 3.13; 95% CI, 1.10-8.89), and high or moderate physician pretest probability for acute stroke (OR, 18.8; 95% CI, 4.72-74.5).ConclusionsMost ED patients with dizziness do not have a serious cause of their symptoms. Although the small number of outcomes precluded development of a multivariate model, we identified several individual high-risk variables associated with acute ischemic stroke. Further study will be needed to validate the findings of this pilot investigation.     

Bone Mass in Individuals With Chronic Spinal Cord Injury: Associations With Activity-Based Therapy,Neurologic and Functional Status,a Retrospective Study

ObjectiveTo describe the prevalence of osteoporosis and its association with functional electrical stimulation (FES) use in individuals with spinal cord injury (SCI)-related paralysis.DesignRetrospective cross-sectional evaluation.SettingClinic.ParticipantsConsecutive persons with SCI (N=364; 115 women, 249 men) aged between 18 and 80 years who underwent dual-energy x-ray absorptiometry (DXA) examinations.InterventionsNot applicable.Main Outcome MeasurePrevalence of osteoporosis defined as DXA T score ≤−2.5.ResultsThe prevalence of osteoporosis was 34.9% (n=127). Use of FES was associated with 31.2% prevalence of osteoporosis compared with 39.5% among persons not using FES. In multivariate adjusted logistic regression analysis, FES use was associated with 42% decreased odds of osteoporosis after adjusting for sex, age, body mass index, type and duration of injury, Lower Extremity Motor Scores, ambulation, previous bone fractures, and use of calcium, vitamin D, and anticonvulsant; (adjusted odds ratio [OR]=.58; 95% confidence interval [CI], .35–.99; P=.039). Duration of injury >1 year was associated with a 3-fold increase in odds of osteoporosis compared with individuals with injury <1 year; (adjusted OR=3.02; 95% CI, 1.60–5.68; P=.001).ConclusionsFES cycling ergometry may be associated with a decreased loss of bone mass after paralysis. Further prospective examination of the role of FES in preserving bone mass will improve our understanding of this association.     

Breast Density and Breast Cancer Risk: A Practical Review

New legislation in several states requiring breast density notification in all mammogram reports has increased awareness of breast density. Estimates indicate that up to 50% of women undergoing mammography will have high breast density; thus, with increased attention and high prevalence of increased breast density, it is crucial that primary care clinicians understand the implications of dense breasts and are able to provide appropriate counseling. This review provides an overview of breast density, specifically by defining breast density, exploring the association between breast density and breast cancer risk, both from masking and as an independent risk factor, and reviewing supplemental screening options as part of a larger framework for counseling patients with dense breasts.