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PURPOSE The ATEMPT trial was designed to determine if treatment with trastuzumab emtansine (T-DM1) caused less toxicity than paclitaxel plus trastuzumab (TH) and yielded clinically acceptable invasive disease-free survival (iDFS) among patients with stage I human epidermal growth factor receptor 2–positive (HER2+) breast cancer (BC). METHODS Patients with stage I centrally confirmed HER2+ BC were randomly assigned 3:1 to T-DM1 or TH and received T-DM1 3.6 mg/kg IV every 3 weeks for 17 cycles or T 80 mg/m 2 IV with H once every week × 12 weeks (4 mg/kg load →2 mg/kg), followed by H × 39 weeks (6 mg/kg once every 3 weeks). The co-primary objectives were to compare the incidence of clinically relevant toxicities (CRTs) in patients treated with T-DM1 versus TH and to evaluate iDFS in patients receiving T-DM1. RESULTS The analysis population includes all 497 patients who initiated protocol therapy (383 T-DM1 and 114 TH). CRTs were experienced by 46% of patients on T-DM1 and 47% of patients on TH ( P = .83). The 3-year iDFS for T-DM1 was 97.8% (95% CI, 96.3 to 99.3), which rejected the null hypothesis ( P < .0001). Serially collected patient-reported outcomes indicated that patients treated with T-DM1 had less neuropathy and alopecia and better work productivity compared with patients on TH. CONCLUSION Among patients with stage I HER2+ BC, one year of adjuvant T-DM1 was associated with excellent 3-year iDFS, but was not associated with fewer CRT compared with TH.

Abstract Background and Aims Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder characterized by hepatic oxalate overproduction. Excess oxalate is excreted by the kidneys, leading to recurrent kidney stones, nephrocalcinosis, and progressive kidney disease. Patients with PH1 generally experience a slow decline in kidney function over time that can be punctuated by abrupt worsening precipitated by infection, obstructing stones, or dehydration. Approximately half of patients with PH1 progress to kidney failure by early adulthood, and nearly all by 60 years of age. Lumasiran is an RNAi therapeutic indicated for the treatment of PH1 in all age groups. In clinical trials, treatment with lumasiran resulted in substantial reductions in urinary and plasma oxalate in pediatric and adult patients, with an acceptable safety profile. This analysis evaluates the change in kidney function of patients with PH1 with an eGFR of ≥30 mL/min/1.73m2 enrolled in clinical trials of lumasiran. Method We analyzed kidney function from 75 patients with PH1, age ≥12 months old, eGFR ≥30 mL/min/1.73m2, enrolled in 3 clinical trials of lumasiran (Phase 2 open-label extension, and Phase 3 ILLUMINATE-A and ILLUMINATE-B). In these trials, eGFR was calculated with the Modification of Diet in Renal Disease (MDRD) Study equation in adults or the bedside Schwartz equation in children. The effect of lumasiran on eGFR was assessed by baseline eGFR subgroup: ≥90, &lt;90, 60 to &lt;90, 45 to &lt;60, and 30 to &lt;45 mL/min/1.73m2. Results Of 75 patients available for analysis, 46 were treated with lumasiran from the start of the study through the Month 12 visit. eGFR remained stable in all eGFR subgroups. Patients with eGFR ≥90 mL/min/1.73m2 at baseline (N=16) demonstrated fluctuations in mean values by timepoint, with a mean change (95% CI) from baseline of -1 (-8, 6) mL/min/1.73m2 at Month 12. In patients with eGFR &lt;90 mL/min/1.73m2 (N=30), no change in mean eGFR from baseline was observed at Month 12; the mean change (95% CI) was 0 (-3, 3). When evaluating subgroups with impaired kidney function, variations in the mean change were observed at Month 12 due to small sample sizes. For patients with eGFR 60 to &lt;90 mL/min/1.73m2 (N=22), the mean change (95% CI) was -2 (-5, 1). For patients with eGFR 45 to &lt;60 mL/min/1.73m2 (N=5), the mean change (95% CI) was 3 (-8, 14). For patients with eGFR 30 to &lt;45 mL/min/1.73m2 (N=3), the mean change (95% CI) was 9 (7, 11). Conclusion Patients with PH1 had stable kidney function over time with lumasiran treatment, regardless of kidney function at baseline. Given the progressive kidney function decline that is characteristic of PH1, the eGFR stability observed during 12 months of treatment with lumasiran is encouraging. Kidney function will continue to be monitored for the duration of the lumasiran clinical trials.

Accurate pathologic evaluation is essential for proper diagnosis and treatment of patients with cancer. ASCO and the College of American Pathologists have successfully collaborated over the last 15 years to improve collaboration between clinical oncologists and pathologists and to standardize pathologic assay techniques. Cancer is an increasingly recognized societal burden in low- and middle-income countries. In 2015, ASCO and the College of American Pathologists implemented an initiative to identify countries that could benefit from peer insights by jointly convening an international workshop among members of both organizations and pathologists and clinical oncologists from Haiti, Honduras, Vietnam, and Uganda. Honduras was chosen as a pilot site, and representatives of ASCO, the College of American Pathologists, and the Honduras pathology and clinical oncology communities have identified areas in which collaboration might be productive. Multiple barriers, including high poverty levels, poor cancer awareness educational programs, lack of human resources, and delayed diagnosis and treatment, have resulted in a higher cancer mortality rate in Honduras compared with high/moderate-income countries and are shared by other low-income countries. ASCO and the College of American Pathologists member faculty supported a symposium led by Honduras colleagues for interested Honduran pathologists and oncologists. The Honduran communities are now working to establish national resource-appropriate guidelines for both pathology and clinical oncology. Taken together, these efforts indicate that barriers to meet the needs of the clinical oncologists in a low-income country such as Honduras are challenging but not insurmountable.

Introduction: Spontaneous coronary artery dissection (SCAD) is an uncommon but increasingly recognized cause of acute coronary syndrome and sudden cardiac death. We aim to review the occurrence of atrial fibrillation and atrial flutter in the Mayo Clinic SCAD Registry (MCSR) to gain insight into the association of SCAD and atrial arrhythmias. Methods: Atrial arrhythmias were queried amongst patients in the MCSR using diagnostic codes and text contained in both a large data repository known as the Advanced Cohort Explorer as well as a clinical database maintained by nurse abstractors for patients in the MCSR. All positive were manually verified using available medical records. Univariable logistic regression analysis was performed using JMP to investigate associations with classic cardiovascular risk factors. Results: A total of 1,215 patients from the Mayo SCAD registry were included. Six patients had a pre SCAD atrial arrhythmia, 19 had an atrial arrhythmia during a SCAD event, and 11 had a post SCAD atrial arrhythmia. Univariable analysis did not reveal significant associations with diabetes, hypertension, hyperlipidemia, or smoking. Conclusion: Atrial arrhythmias were not uncommonly seen in patients at the time of or after SCAD, especially after cardiac arrest or coronary artery bypass grafting. No significant associations with traditional cardiovascular risk factors were observed. Further investigation into the mechanism of atrial arrhythmia development as well as its management in the setting of SCAD is warranted.

Introduction: Spontaneous coronary artery dissection (SCAD) is an important cause of myocardial infarction in otherwise healthy and most times presumably fit young women. In the absence of evidence for benefit or harm, exercise prescription (EXP) after SCAD remains arbitrary. We assessed EXP patterns among participants in a large multinational SCAD registry. Methods: Participants with SCAD as confirmed by coronary angiography completed surveys detailing exercise (EX) habits prior to SCAD (initial survey), and EXP from their provider on initial and subsequent visits after SCAD (follow-up survey). Demographic and clinical characteristics were collected by electronic health record review by trained nurse abstractors. EXP was categorized according to EX components that include: type, intensity, frequency, time/session, and external conditions. Results: Among 950 participants, mean ± age was 46.8 ± 9.5 years, 96% were women and 77% reported attending ≥1 Cardiopulmonary Rehabilitation session. Prior to SCAD, 49% were aerobically exercising ≥ 3times per week, and only 32% performed strength-building EX regularly. Initial and subsequent post-SCAD visit details in 299/950 participants showed that most (93%) patients received some form of EX (Figure 1-A) counseling, namely: EXP, unspecific advice or were discouraged from any EX (Figure 1-B) . Limits regarding EX type and intensity were the most common advice received among EXP group (Figure 1-C) . Conclusions: Insights from our study show that only 40% of patients were achieving current exercise recommendations for adults prior to SCAD (vs 53% adult U.S population; CDC, 2018) which suggests that SCAD patients may not be as active as previously described. Most patients receive some form of EX counseling after SCAD; however, a structured EXP is needed to avoid overly cautious approaches that could lead to uncertainty, deconditioning, impaired quality of life, or increase risks associated with a sedentary lifestyle.

Introduction: Spontaneous coronary artery dissection (SCAD) is a rare but life threatening cause of acute coronary syndrome and a common etiology of pregnancy-associated myocardial infarction (PAMI). Hypothesis: We aimed to examine the clinical presentation, treatment, and outcomes of the largest pregnancy associated-SCAD (P-SCAD) patient cohort to date. Methods: A total of 128 women enrolled in the Mayo Clinic SCAD Registry between 2010-2020 who were pregnant or up to 1 year postpartum at time of P-SCAD were identified. We subdivided P-SCAD in an “early” group with <12 weeks of delivery and a “late” group presenting between >12 weeks -12 months following delivery. Results: Among the 128 women with P-SCAD, 7(5%) occurred during pregnancy (2/7 first trimester, 5/7 third trimester). Of the 121 women with postpartum P-SCAD, 88/121(72%) occurred <12 weeks of delivery and 33/121(27%) at 12 weeks to 1 year postpartum. The mean age of P-SCAD was 35.3 +/- 4 years (26-48). The most common symptom on presentation was chest pain 118/128(92%); 62/128(48%) presented with ST elevation MI and 58/128(45%) presented with non-ST elevation MI. Multivessel involvement occurred in 40/128(31%), left anterior descending artery (LAD) in 88/128(69%), and left main (LM) in 28/128(22%) of all P-SCAD. Percutaneous coronary intervention (PCI) was performed in 52/128(41%) with a success rate of 81%. Coronary artery bypass grafting was performed in 24/128(19%) of which 6/24 patients had an unsuccessful PCI, 14/24 had proximal or multivessel SCAD, and 4/24 had persistent or extension of initial SCAD. Of those treated conservatively 52/128(40%), 11/52(21%) had LM and LAD. Among all the P-SCAD patients, 84/128 (66%) were screened for an underlying arteriopathy, of whom 44 (52 %) were diagnosed with fibromuscular dysplasia. At a median follow up of 3 years (IQR 1 to 6), 12/128 (9%) of all P-SCAD survivors had a recurrent SCAD event and 7/12 (58%) were within 1 year postpartum. There were no deaths. Conclusions: P-SCAD most commonly presents with ST-elevation MI and multivessel involvement within the initial 12 weeks postpartum. Clinicians need to be familiar with this etiology of PAMI to avoid delay in diagnosis and appropriate management.

Purpose Parental leave for new parents is essential as they adjust to the physical and psychological changes that accompany childbirth and caring for a newborn. This study sought to determine the current state of parental leave policies for medical students at medical schools in the United States. Method From November to December 2019, 2 researchers independently reviewed the websites of 199 U.S. MD-granting and DO-granting medical schools (including in U.S. territories). Online student handbooks and school webpages were searched for the following keywords: “pregnant” OR “pregnancy” OR “maternity” OR “parent” OR “family” OR “child” OR “birth.” Data were analyzed using descriptive statistics. Fisher’s exact tests evaluated differences in proportion by group. Results Of 199 schools, 65 (32.66%) had parental leave policies available online or in the handbook: 39 of 155 (25.16%) MD-granting and 26 of 44 (59.09%) DO-granting schools. Of those policies, 59 (90.77%) were included in the student handbook. Most policies (28, 43.08%) were included as an option within the school’s general leave of absence policy. Both parents were included in 38 (58.46%) policies; 23 (35.38%) policies mentioned only mothers; and 4 (6.15%) were unknown. An option to maintain original graduation date was offered in 21 (32.1%) schools’ policies. Three schools (4.62%) included adoption as qualifying for parental leave. When comparing MD and DO programs, DO programs were statistically more likely to have a parental leave policy: 39 (25.16%) vs 26 (59.09%); P < .001. Conclusions Balancing medical school with pregnancy and childbirth necessitates administrative support to address the inherent scheduling challenges. Currently, many schools lack parental leave policies for medical students that are easily accessible, are separate from formal leaves of absence, allow for at least 12 weeks, and are tailored to the student academic year to ensure on-time completion of medical education.

Abstract Background Incidence of early-onset (younger than 50 years of age) colorectal cancer (CRC) is increasing in many countries. Thus, elucidating the role of traditional CRC risk factors in early-onset CRC is a high priority. We sought to determine whether risk factors associated with late-onset CRC were also linked to early-onset CRC and whether association patterns differed by anatomic subsite. Methods Using data pooled from 13 population-based studies, we studied 3767 CRC cases and 4049 controls aged younger than 50 years and 23 437 CRC cases and 35 311 controls aged 50 years and older. Using multivariable and multinomial logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) to assess the association between risk factors and early-onset CRC and by anatomic subsite. Results Early-onset CRC was associated with not regularly using nonsteroidal anti-inflammatory drugs (OR = 1.43, 95% CI = 1.21 to 1.68), greater red meat intake (OR = 1.10, 95% CI = 1.04 to 1.16), lower educational attainment (OR = 1.10, 95% CI = 1.04 to 1.16), alcohol abstinence (OR = 1.23, 95% CI = 1.08 to 1.39), and heavier alcohol use (OR = 1.25, 95% CI = 1.04 to 1.50). No factors exhibited a greater excess in early-onset compared with late-onset CRC. Evaluating risks by anatomic subsite, we found that lower total fiber intake was linked more strongly to rectal (OR = 1.30, 95% CI = 1.14 to 1.48) than colon cancer (OR = 1.14, 95% CI = 1.02 to 1.27; P = .04). Conclusion In this large study, we identified several nongenetic risk factors associated with early-onset CRC, providing a basis for targeted identification of those most at risk, which is imperative in mitigating the rising burden of this disease.

Abstract It was not known whether the polygenic risk scores (PRSs) that predict colorectal cancer could predict colorectal cancer for people with inherited pathogenic variants in DNA mismatch repair genes—people with Lynch syndrome. We tested a PRS comprising 107 established single-nucleotide polymorphisms associated with colorectal cancer in European populations for 826 European-descent carriers of pathogenic variants in DNA mismatch repair genes (293 MLH1, 314 MSH2, 126 MSH6, 71 PMS2, and 22 EPCAM) from the Colon Cancer Family Registry, of whom 504 had colorectal cancer. There was no evidence of an association between the PRS and colorectal cancer risk, irrespective of which DNA mismatch repair gene was mutated, or sex (all 2-sided P &gt; .05). The hazard ratio per standard deviation of the PRS for colorectal cancer was 0.97 (95% confidence interval = 0.88 to 1.06; 2-sided P = .51). Whereas PRSs are predictive of colorectal cancer in the general population, they do not predict Lynch syndrome colorectal cancer.