Critical updates in neuroendocrine tumors: Version 9 American Joint Committee on Cancer staging system for gastroenteropancreatic neuroendocrine tumors.

The American Joint Committee on Cancer (AJCC) staging system for all cancer sites, including gastroenteropancreatic neuroendocrine tumors (GEP-NETs), is meant to be dynamic, requiring periodic updates to optimize AJCC staging definitions. This entails the collaboration of experts charged with evaluating new evidence that supports changes to each staging system. GEP-NETs are the second most prevalent neoplasm of gastrointestinal origin after colorectal cancer. Since publication of the AJCC eighth edition, the World Health Organization has updated the classification and separates grade 3 GEP-NETs from poorly differentiated neuroendocrine carcinoma. In addition, because of major advancements in diagnostic and therapeutic technologies for GEP-NETs, AJCC version 9 advocates against the use of serum chromogranin A for the diagnosis and monitoring of GEP-NETs. Furthermore, AJCC version 9 recognizes the increasing role of endoscopy and endoscopic resection in the diagnosis and management of NETs, particularly in the stomach, duodenum, and colorectum. Finally, T1NXM0 has been added to stage I in these disease sites as well as in the appendix.

At the Intersection of Intersectionality: Race and Gender Diversity Among Surgical Faculty and Trainees.

OBJECTIVE: To compare the representation of intersectional (ie, racial/ethnic and gender) identities among surgical faculty versus medical students. BACKGROUND: Health disparities are pervasive in medicine, but diverse physicians may help the medical profession achieve health equity. METHODS: Data from the Association of American Medical Colleges for 140 programs (2011/2012-2019/2020) were analyzed for students and full-time surgical faculty. Underrepresented in medicine (URiM) was defined as Black/African American, American Indian/Alaskan Native, Hispanic/Latino/Spanish Origin, or Native Hawaiian/Other Pacific Islander. Non-White included URiM plus Asian, multiracial, and non-citizen permanent residents. Linear regression was used to estimate the association of year and proportions of URiM and non-White female and male faculty with proportions of URiM and non-White students. RESULTS: Medical students were comprised of more White (25.2% vs 14.4%), non-White (18.8% vs 6.6%), and URiM (9.6% vs 2.8%) women and concomitantly fewer men across all groups versus faculty (all P < 0.01). Although the proportion of White and non-White female faculty increased over time (both P ≤ 0.001), there was no significant change among non-White URiM female faculty, nor among non-White male faculty, regardless of whether they were URiM or not. Having more URiM male faculty was associated with having more non-White female students (estimate = +14.5% students/100% increase in faculty, 95% CI: 1.0% to 8.1%, P = 0.04), and this association was especially pronounced for URiM female students (estimate = +46.6% students/100% increase in faculty, 95% CI: 36.9% to 56.3%, P < 0.001). CONCLUSIONS: URiM faculty representation has not improved despite a positive association between having more URiM male faculty and having more diverse students.

Survival among patients with untreated metastatic breast cancer: "What if I do nothing?"

PURPOSE: We sought to assess survival outcomes of patients with de novo metastatic breast cancer (dnMBC) who did not receive treatment irrespective of the reason. METHODS: Adults with dnMBC were selected from the NCDB (2010-2016) and stratified based on receipt of treatment (treated = received at least one treatment and untreated = received no treatments). Overall survival (OS) was estimated using the Kaplan-Meier method, and groups were compared. Cox proportional hazards models were used to identify factors associated with OS. RESULTS: Of the 53,240 patients with dnMBC, 92.1% received at least one treatment (treated), and 7.9% had no documented treatments, irrespective of the reason (untreated). Untreated patients were more likely to be older (median 68 y vs 61 y, p < 0.001), have higher comorbidity scores (p < 0.001), have triple-negative disease (17.8% vs 12.6%), and a higher disease burden (≥ 2 metastatic sites: 38.2% untreated vs 29.2% treated, p < 0.001). The median unadjusted OS in the untreated subgroup was 2.5 mo versus 36.4 mo in the treated subgroup (p < 0.001). After adjustment, variables associated with a worse OS in the untreated cohort included older age, higher comorbidity scores, higher tumor grade, and triple-negative (vs HR + /HER2-) subtype (all p < 0.05), while the number of metastatic sites was not associated with survival. CONCLUSIONS: Patients with dnMBC who do not receive treatment are more likely to be older, present with comorbid conditions, and have clinically aggressive disease. Similar to those who do receive treatment, survival in an untreated population is associated with select patient and disease characteristics. However, the prognosis for untreated dnMBC is dismal.

Impact of HER2-low status for patients with early-stage breast cancer and non-pCR after neoadjuvant chemotherapy: a National Cancer Database Analysis.

PURPOSE: To investigate potential differences in pathological complete response (pCR) rates and overall survival (OS) between HER2-low and HER2-zero patients with early-stage hormone receptor (HR)-positive and triple-negative breast cancer (TNBC), in the neoadjuvant chemotherapy setting. METHODS: We identified early-stage invasive HER2-negative BC patients who received neoadjuvant chemotherapy diagnosed between 2010 and 2018 in the National Cancer Database. HER2-low was defined by immunohistochemistry (IHC) 1+ or 2+ with negative in situ hybridization, and HER2-zero by IHC0. All the methods were applied separately in the HR-positive and TNBC cohorts. Logistic regression was used to estimate the association of HER2 status with pCR (i.e. ypT0/Tis and ypN0). Kaplan-Meier method and Cox proportional hazards model were applied to estimate the association of HER2 status with OS. Inverse probability weighting and/or multivariable regression were applied to all analyses. RESULTS: For HR-positive patients, 70.9% (n = 17,934) were HER2-low, whereas 51.1% (n = 10,238) of TNBC patients were HER2-low. For both HR-positive and TNBC cohorts, HER2-low status was significantly associated with lower pCR rates [HR-positive: 5.0% vs. 6.7%; weighted odds ratio (OR) = 0.81 (95% CI: 0.72-0.91), p < 0.001; TNBC: 21.6% vs. 24.4%; weighted OR = 0.91 (95% CI: 0.85-0.98), p = 0.007] and improved OS [HR-positive: weighted hazard ratio = 0.85 (95% CI: 0.79-0.91), p < 0.001; TNBC: weighted hazard ratio = 0.91 (95% CI: 0.86-0.96), p < 0.001]. HER2-low status was associated with favorable OS among patients not achieving pCR [HR-positive: adjusted hazard ratio = 0.83 (95% CI: 0.77-0.89), p < 0.001; TNBC: adjusted hazard ratio = 0.88 (95% CI 0.83-0.94), p < 0.001], while no significant difference in OS was observed in patients who achieved pCR [HR-positive: adjusted hazard ratio = 1.00 (95% CI: 0.61-1.63), p > 0.99; TNBC: adjusted hazard ratio = 1.11 (95% CI: 0.85-1.45), p = 0.44]. CONCLUSION: In both early-stage HR-positive and TNBC patients, HER2-low status was associated with lower pCR rates. HER2-zero status might be considered an adverse prognostic factor for OS in patients not achieving pCR.

Patient Characteristics Impact Performance of AI Algorithm in Interpreting Negative Screening Digital Breast Tomosynthesis Studies.

Background Artificial intelligence (AI) is increasingly used to manage radiologists' workloads. The impact of patient characteristics on AI performance has not been well studied. Purpose To understand the impact of patient characteristics (race and ethnicity, age, and breast density) on the performance of an AI algorithm interpreting negative screening digital breast tomosynthesis (DBT) examinations. Materials and Methods This retrospective cohort study identified negative screening DBT examinations from an academic institution from January 1, 2016, to December 31, 2019. All examinations had 2 years of follow-up without a diagnosis of atypia or breast malignancy and were therefore considered true negatives. A subset of unique patients was randomly selected to provide a broad distribution of race and ethnicity. DBT studies in this final cohort were interpreted by a U.S. Food and Drug Administration-approved AI algorithm, which generated case scores (malignancy certainty) and risk scores (1-year subsequent malignancy risk) for each mammogram. Positive examinations were classified based on vendor-provided thresholds for both scores. Multivariable logistic regression was used to understand relationships between the scores and patient characteristics. Results A total of 4855 patients (median age, 54 years [IQR, 46-63 years]) were included: 27% (1316 of 4855) White, 26% (1261 of 4855) Black, 28% (1351 of 4855) Asian, and 19% (927 of 4855) Hispanic patients. False-positive case scores were significantly more likely in Black patients (odds ratio [OR] = 1.5 [95% CI: 1.2, 1.8]) and less likely in Asian patients (OR = 0.7 [95% CI: 0.5, 0.9]) compared with White patients, and more likely in older patients (71-80 years; OR = 1.9 [95% CI: 1.5, 2.5]) and less likely in younger patients (41-50 years; OR = 0.6 [95% CI: 0.5, 0.7]) compared with patients aged 51-60 years. False-positive risk scores were more likely in Black patients (OR = 1.5 [95% CI: 1.0, 2.0]), patients aged 61-70 years (OR = 3.5 [95% CI: 2.4, 5.1]), and patients with extremely dense breasts (OR = 2.8 [95% CI: 1.3, 5.8]) compared with White patients, patients aged 51-60 years, and patients with fatty density breasts, respectively. Conclusion Patient characteristics influenced the case and risk scores of a Food and Drug Administration-approved AI algorithm analyzing negative screening DBT examinations. © RSNA, 2024.

Demographics and Clinical Decision Making in Patients with Germline Moderate Penetrance Non-BRCA Mutations in Breast Cancer Related Genes.

BACKGROUND: Management of pathogenic variants in high penetrance genes related to breast cancer (BC), such as BRCA1 and BRCA2, are well established. However, moderate penetrance mutations are understudied. We aim to compare risk reduction decision-making patterns in patients with a moderate penetrance BC-related genetic mutations, without a prior BC diagnosis. PATIENTS AND METHODS: Female patients aged ≥ 18 years who tested positive for a BRCA1/2, high penetrance, or moderate penetrance mutation related to BC between 1996 and 2023 without a concurrent or prior BC diagnosis were retrospectively identified from a single academic center's database. Groups were stratified by mutation type: BRCA1/2 mutations (BRCA1, BRCA2), high penetrance mutations (HPM; CDH1, PALB2, PTEN, STK11, TP53), or moderate penetrance mutations (MPM; ATM, BARD1, CHEK2, NF1, RAD51C, RAD51D). Demographics and clinical outcomes were compared. RESULTS: A total of 528 patients met the inclusion criteria, with 66% (n = 350) having a BRCA1/2 mutation, 8% (n = 44) having HPM, and 25% (n = 134) having MPM; the median follow-up was 56.0 months. In our cohort, 20.9% of patients with BRCA mutations, 9.1% with HPM, and 7.5% with MPM chose to undergo risk-reducing mastectomies (RRM). Within the moderate penetrance cohort, patients who chose to undergo RRM were younger at the time of genetic testing (39.4 vs. 47.5 years, p = 0.03) and had a higher number of family members with BC (2 vs. 1, p = 0.05). CONCLUSIONS: Our findings provide insights into the demographic characteristics and family history of patients with moderate penetrance mutations and those who pursue risk-reducing surgery.

Guideline-Concordant Surgical Care for Lobular Versus Ductal Inflammatory Breast Cancer.

INTRODUCTION: Quality of surgical care is understudied for lobular inflammatory breast cancer (IBC), which is less common, more chemotherapy-resistant, and more mammographically occult than ductal IBC. We compared guideline-concordant surgery (modified radical mastectomy [MRM] without immediate reconstruction following chemotherapy) for lobular versus ductal IBC. METHODS:  Female individuals with cT4dM0 lobular and ductal IBC were identified in the National Cancer Database (NCDB) from 2010-2019. Modified radical mastectomy receipt was identified via codes for "modified radical mastectomy" or "mastectomy" and "≥10 lymph nodes removed" (proxy for axillary lymph node dissection). Descriptive statistics, chi-square tests, and t-tests were used. RESULTS: A total of 1456 lobular and 10,445 ductal IBC patients were identified; 599 (41.1%) with lobular and 4859 (46.5%) with ductal IBC underwent MRMs (p = 0.001). Patients with lobular IBC included a higher proportion of individuals with cN0 disease (20.5% lobular vs. 13.7% ductal) and no lymph nodes examined at surgery (31.2% vs. 24.5%) but were less likely to be node-negative at surgery (12.7% vs. 17.1%, all p < 0.001). Among those who had lymph nodes removed at surgery, patients with lobular IBC also had fewer lymph nodes excised versus patients with ductal IBC (median [interquartile range], 7 (0-15) vs. 9 (0-17), p = 0.001). CONCLUSIONS: Lobular IBC patients were more likely to present with node-negative disease and less likely to be node-negative at surgery, despite having fewer, and more frequently no, lymph nodes examined versus ductal IBC patients. Future studies should investigate whether these treatment disparities are because of surgical approach, pathologic assessment, and/or data quality as captured in the NCDB.

Utility of Axillary Staging in Older Patients with HER2-Positive Breast Cancer.

BACKGROUND: The utility of sentinel lymph node biopsy (SLNB) in older patients remains controversial. Advancements in human epidermal growth factor receptor 2 (HER2)-directed therapy have revolutionized disease response rates and prognosis, supporting efforts to re-evaluate the utility of SLNB. We aimed to assess the differences in treatment and overall survival (OS) in older patients with HER2-positive breast cancer based on SLNB. METHODS: Using the National Cancer Database (2010-2020), patients ≥ 70 years of age diagnosed with cT1-2/cN0/M0, HER2-positive breast cancer were identified. Logistic regression assessed associations with SLNB, systemic therapy, and radiation. Cox proportional hazard models were used to identify factors associated with OS. Analyses were stratified by treatment sequence, i.e. upfront surgery or neoadjuvant therapy (NAT) followed by surgery. RESULTS: Of the 17,609 patients included, 94% underwent upfront surgery (n = 16,492) and the remaining underwent NAT (n = 1117). Those who underwent SLNB were more likely to receive adjuvant therapy, irrespective of nodal status {upfront surgery/systemic therapy (odds ratio [OR] 2.82, 95% confidence interval [CI] 2.17-3.67); upfront surgery/radiation (OR 3.97, 95% CI 3.03-5.21); NAT/radiation (OR 5.69, 95% CI 1.83-17.69)}. The breast pathologic complete response (pCR) rate was highest among the hormone receptor (HR)-negative/HER2-positive subtype (50.0%), of which none were found to be ypN+. Comorbidity burden was associated with significantly lower rates of adjuvant systemic therapy and worse OS. CONCLUSIONS: Patients who underwent SLNB, regardless of pN status, were more likely to receive adjuvant therapy. Nodal positivity is exceedingly rare for patients with a breast pCR following NAT, especially among the HR-negative/HER2-positive subtype. It is reasonable to consider omission of SLNB in select subgroups of older patients with HER2-positive breast cancer.

Anatomy Versus Biology: What Guides Chemotherapy Decisions in Older Patients With Breast Cancer?

INTRODUCTION: With the increasing utilization of genomic assays, such as the Oncotype DX recurrence score (RS), the relevance of anatomic staging has been questioned for select older patients with breast cancer. We sought to evaluate differences in chemotherapy receipt and/or survival among older patients based on RS and sentinel lymph node biopsy (SLNB) receipt/result. METHODS: Patients aged ≥ 65 diagnosed with pT1-2/cN0/M0 hormone-receptor-positive (HR+)/HER2-breast cancer (2010-2019) were selected from the National Cancer Database. Logistic regression was used to identify factors associated with chemotherapy receipt. Cox proportional hazards models were used to estimate the association of RS/SLNB group with overall survival. A cost-benefit study was also performed. RESULTS: Of the 75,428 patients included, the majority had an intermediate RS (58.2% versus 27.9% low, 13.8% high) and were SLNB- (85.1% versus 11.6% SLNB+, 3.3% none). Chemotherapy was recommended for 13,442 patients (17.8%). After adjustment, chemotherapy receipt was more likely with higher RS and SLNB+. After adjustment, SLNB receipt/result was only associated with overall survival among those with an intermediate RS. However, returning to the OR for SLNB is not cost-effective. CONCLUSIONS: SLNB receipt/result was associated with survival for those with an intermediate RS, but not a low or high RS, suggesting that an SLNB may indeed be unnecessary for select older patients with breast cancer.

Implications of missing data on reported breast cancer mortality.

BACKGROUND: National cancer registries are valuable tools to analyze patterns of care and clinical outcomes; yet, missing data may impact the accuracy and generalizability of these data. We sought to evaluate the association between missing data and overall survival (OS). METHODS: Using the NCDB (National Cancer Database) and SEER (Surveillance, Epidemiology, End Results Program), we assessed data missingness among patients diagnosed with invasive breast cancer from 2010 to 2014. Key variables included demographic (age, race, ethnicity, insurance, education, income), tumor (grade, ER, PR, HER2, TNM stages), and treatment (surgery in both databases; chemotherapy and radiation in NCDB). OS was compared between those with and without missing data using Cox proportional hazards models. RESULTS: Overall, 775,996 patients in the NCDB and 263,016 in SEER were identified; missing at least 1 key variable occurred for 29% and 13%, respectively. Of those, the overwhelming majority (NCDB 80%; SEER 88%) were missing tumor variables. When compared to patients with complete data, missingness was associated with a greater risk of death: NCDB HR 1.23 (99% CI 1.21-1.25) and SEER HR 2.11 (99% CI 2.05-2.18). Patients with complete tumor data had higher unadjusted OS estimates than that of the entire sample: NCDB 82.7% vs 81.8% and SEER 83.5% vs 81.7% for 5-year OS. CONCLUSIONS: Missingness of select variables is not uncommon within large national cancer registries and is associated with a worse OS. Exclusion of patients with missing variables may introduce unintended bias into analyses and result in findings that underestimate breast cancer mortality.

Surveillance Imaging after Primary Diagnosis of Ductal Carcinoma in Situ.

Background Guidelines recommend annual surveillance imaging after diagnosis of ductal carcinoma in situ (DCIS). Guideline adherence has not been characterized in a contemporary cohort. Purpose To identify uptake and determinants of surveillance imaging in women who underwent treatment for DCIS. Materials and Methods A stratified random sample of women who underwent breast-conserving surgery for primary DCIS between 2008 and 2014 was retrospectively selected from 1330 facilities in the United States. Imaging examinations were recorded from date of diagnosis until first distant recurrence, death, loss to follow-up, or end of study (November 2018). Imaging after treatment was categorized into 10 12-month periods starting 6 months after diagnosis. Primary outcome was per-period receipt of asymptomatic surveillance imaging (mammography, MRI, or US). Secondary outcome was diagnosis of ipsilateral invasive breast cancer. Multivariable logistic regression with repeated measures and generalized estimating equations was used to model receipt of imaging. Rates of diagnosis with ipsilateral invasive breast cancer were compared between women who did and those who did not undergo imaging in the 6-18-month period after diagnosis using inverse probability-weighted Kaplan-Meier estimators. Results A total of 12 559 women (median age, 60 years; IQR, 52-69 years) were evaluated. Uptake of surveillance imaging was 75% in the first period and decreased over time (P < .001). Across the first 5 years after treatment, 52% of women participated in consistent annual surveillance. Surveillance was lower in Black (adjusted odds ratio [OR], 0.80; 95% CI: 0.74, 0.88; P < .001) and Hispanic (OR, 0.82; 95% CI: 0.72, 0.94; P = .004) women than in White women. Women who underwent surveillance in the first period had a higher 6-year rate of diagnosis of invasive cancer (1.6%; 95% CI: 1.3, 1.9) than those who did not (1.1%; 95% CI: 0.7, 1.4; difference: 0.5%; 95% CI: 0.1, 1.0; P = .03). Conclusion Half of women did not consistently adhere to imaging surveillance guidelines across the first 5 years after treatment, with racial disparities in adherence rates. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Rahbar and Dontchos in this issue.

Breast Cancer Risk Assessment and Screening Practices Reported Via an Online Survey.

BACKGROUND: Breast cancer screening guidelines differ between organizations, and significant variations in practice patterns exist. Previous evidence suggests that provider-level factors are the greatest contributors to risk assessment and screening practice variability. This study aimed to characterize provider factors associated with breast cancer risk assessment and screening practice patterns, and to assess perceived barriers to providing risk assessment. METHODS: An online survey was distributed to providers at a single academic institution and to providers publicly via social media (January to August 2022). Respondents in the United States who care for adult women at risk for the development of breast cancer were included. RESULTS: Most of the respondents in the 143 completed surveys were white/Caucasian (79%) females (90%) age 50 years or younger (79%), and whereas 97% discuss breast cancer screening with their patients, only 90% order screening mammograms. Risk factor assessment was common (93%), typically performed at the first visit (51%). Additional training in genetics or risk assessment was uncommon (17%), although the majority were interested but did not have the time or resources (55%). Although most (64%) did not perceive barriers to providing risk assessment or appropriate screening, the most common barriers were time (77%) and education (55%). Barriers were more common among family practice or obstetrics and gynecology (OB/GYN) providers and those who worked in an academic setting (all p < 0.05). CONCLUSIONS: Breast cancer risk assessment and screening practices are highly variable. Although time is the major barrier to providing risk assessment, providers also need education. Primary care organizations could partner with breast cancer-focused societies for additional resources.

Neoadjuvant Chemotherapy and Endocrine Therapy for Older Patients with Estrogen Receptor Positive Breast Cancer: Comparison of Approaches.

BACKGROUND: Benefits of a pathologic complete response (pCR) following neoadjuvant therapy are well established, yet outcomes for older women are understudied. We sought to examine the pCR and overall survival (OS) rates of women with estrogen receptor (ER) positive breast cancer across age groups. METHODS: Women diagnosed with cT1-4, N0-3, M0, ER+/HER2- breast cancer (2010-2018) who underwent neoadjuvant chemotherapy (NACT) or neoadjuvant endocrine therapy (NET) followed by surgery were selected from the National Cancer Database and categorized by age. Differences were tested, and Cox proportional hazards models were used to estimate the association of response with OS after adjustment for covariates. RESULTS: In the 43,009-patient cohort, 84.8% received NACT and 15.2% received NET. Of those aged ≥ 70 (N = 5623), 51.0% received NACT, and 49.0% received NET. Compared with younger women receiving NACT, older women were less likely to have a breast or nodal pCR [no pCR by age: 85.1% (≥ 70 years) vs 82.2% (50-69 years) vs 77.7% (< 50 years), p < 0.001]. Rates of pCR were similarly low for all women receiving NET [no pCR by age: 95.6% (≥ 70 years) vs 95% (50-69 years) vs 96% (< 50 years), p = 0.06]. After adjustment, pCR after NACT was not associated with OS for older patients, but better survival outcomes were noted for older patients achieving pCR after NET. CONCLUSION: For women with ER+/HER2- breast cancer, pCR rates after NACT are lower in older women compared with younger women, and are equally low after NET for all women. However, pCR after NET is associated with improved OS among older women, unlike pCR after NACT.

Racial-ethnic variations in phyllodes tumors among a multicenter United States cohort.

BACKGROUND AND OBJECTIVES: Previous studies have identified racial-ethnic differences in the diagnostic patterns and recurrence outcomes of women with phyllodes tumors (PT). However, these studies are generally limited in size and generalizability. We therefore sought to explore racial-ethnic differences in age, tumor size, subtype, and recurrence in a large US cohort of women with PT. METHODS: We performed an 11-institution retrospective review of women with PT from 2007 to 2017. Differences in age at diagnosis, tumor size and subtype, and recurrence-free survival according to race-ethnicity. RESULTS: Women of non-White race or Hispanic ethnicity were younger at the time of diagnosis with phyllodes tumor. Non-Hispanic Other women had a larger proportion of malignant PT. There were no differences in recurrence-free survival in our cohort. CONCLUSIONS: Differences in age, tumor size, and subtype were small. Therefore, the workup of young women with breast masses and the treatment of women with PT should not differ according to race-ethnicity. These conclusions are supported by our finding that there were no differences in recurrence-free survival.

Disease characteristics and mortality among Asian women with breast cancer.

BACKGROUND: Asian women with breast cancer are often studied in aggregate, belying significant intragroup diversity. The authors sought to examine differences in breast cancer characteristics and outcomes among Asian women. METHODS: Asian, non-Hispanic Black, Hispanic, and non-Hispanic White women aged 18 years and older who were diagnosed with breast cancer from 1990 to 2016 were identified in the Surveillance, Epidemiology, and End Results 18 database. Asian patients were subclassified as Chinese, Japanese, Korean, Filipino, Vietnamese, South Asian (Asian Indian or Pakistani), Southeast Asian (SEA, i.e., Cambodian, Laotian, Hmong, or Thai), or other Asian. Unadjusted overall survival (OS) and cancer-specific survival (CSS) were estimated using the Kaplan-Meier method. Cox proportional hazards models were used to estimate adjusted OS and CSS. RESULTS: In total, 910,415 women were included (Asian, n = 63,405; Black, n = 92,226; Hispanic, n = 84,451; White, n = 670,333). Asian women had higher rates of human epidermal growth factor receptor 2 (HER2)-positive disease compared with White women (18.7% vs 13.8%) and had the highest 10-year unadjusted OS and CSS among all racial/ethnic groups (all P < .001). SEA women had the highest rates of stage IV disease at presentation, whereas Japanese women had the lowest rates (5.9% vs 2.7%; P < .001). Japanese women had the highest 10-year unadjusted CSS (89.4%; 95% confidence interval, 88.7%-90.1%) of any distinct Asian group, whereas SEA women had the worst unadjusted CSS (78%; 95% confidence interval, 74.1%-81.3%; P < .001). After adjustment, SEA women had the worst OS of any Asian group and were the only Asian group without improved OS compared with White women (reference category; P = .08). CONCLUSIONS: Breast cancer characteristics and outcomes vary significantly among Asian women. Future research should consider disaggregation by country or region of origin to identify subgroups that are at risk for worse outcomes than aggregated data may suggest. LAY SUMMARY: Asian women with breast cancer are frequently studied as a single entity. However, Asian ethnic groups differ greatly by country of origin, genetic ancestry, disease frequency, socioeconomic status, patterns of immigration, as well as dietary and cultural practices. Women of different Asian ethnicities vary significantly with regard to cancer characteristics, such as mortality and tumor subtype. Future research should disaggregate these populations to better understand, treat, and counsel Asian patients with breast cancer.

A Novel Staging System for De Novo Metastatic Breast Cancer Refines Prognostic Estimates.

OBJECTIVE: We aim to identify prognostic groups within a de novo metastatic cohort, incorporating both anatomic and biologic factors. BACKGROUND: Staging for breast cancer now includes anatomic and biologic factors, although the guidelines for stage IV disease do not account for how these factors may influence outcomes. METHODS: Adults with de novo metastatic breast cancer were selected from the National Cancer DataBase (2010-2013). Recursive partitioning analysis was used to group patients with similar overall survival (OS) based on clinical T/N stage, tumor grade, ER, PR, HER2, number of metastatic sites, and presence of bone-only metastases. Categories were created by amalgamating homogeneous groups based on 3-year OS rates (stage IVA: >50%, stage IVB: 30%-50%, stage IVC: <30%). RESULTS: 16,187 patients were identified; median follow-up was 32 months. 65.2% had 1 site of distant metastasis, and 42.9% had bone-only metastases. Recursive partitioning analysis identified the number of metastatic sites (1 vs >1) as the first stratification point, and ER status as the second stratification point for both resulting groups. Additional divisions were made based on HER2 status, PR status, cT stage, tumor grade, and presence of bone-only metastases. After bootstrapping, significant differences in 3-year OS were noted between the 3 groups [stage IVB vs IVA: HR 1.58 (95% confidence interval 1.50-1.67), stage IVC vs IVA: HR 3.54 (95% confidence interval 3.33-3.77)]. CONCLUSIONS: Both anatomic and biologic factors yielded reliable and reproducible prognostic estimates among patients with metastatic disease. These findings support formal stratification of de novo stage IV breast cancer into 3 distinct prognosis groups.

The Influence of Body Mass Index on the Histopathology and Outcomes of Patients Diagnosed with Atypical Breast Lesions.

BACKGROUND: Multiple studies have demonstrated a link between obesity and breast cancer; however, the potential association between obesity and atypical high-risk breast lesions has not been well characterized. We sought to evaluate the characteristics and clinical outcomes of patients with breast atypia based on a woman's body mass index (BMI). METHODS: We retrospectively identified adult women diagnosed with atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), and/or lobular carcinoma in situ (LCIS) at a single institution from 2008 to 2017. BMI groups were defined as a BMI 18.5 to < 30 or BMI ≥ 30 (obese). Adjusted logistic regression was used to estimate the association of BMI group with the odds of (1) upstage to cancer after atypia on needle biopsy, and (2) subsequent diagnosis of breast cancer. RESULTS: Breast atypia was identified in 503 patients (most advanced atypia: 74.8% ADH, 4.6% ALH, 20.7% LCIS), and 41% of these patients were classified as obese. After adjustment, BMI group was not associated with upstage to breast cancer at surgical excision following needle biopsy (p = 0.16) or development of a subsequent breast cancer (p = 0.08). For those upstaged to breast cancer at the time of surgical excision, or those who developed a subsequent malignancy, tumor subtype, grade and stage were not associated with BMI group (p > 0.05). CONCLUSION: In a large cohort of patients diagnosed with atypical breast histology, the risk of upstaging and/or subsequent progression to a breast malignancy was not associated with BMI. Factors other than obesity may influence breast cancer risk.

Time course of human skeletal muscle nitrate and nitrite concentration changes following dietary nitrate ingestion.

Dietary nitrate (NO3-) ingestion can be beneficial for health and exercise performance. Recently, based on animal and limited human studies, a skeletal muscle NO3- reservoir has been suggested to be important in whole body nitric oxide (NO) homeostasis. The purpose of this study was to determine the time course of changes in human skeletal muscle NO3- concentration ([NO3-]) following the ingestion of dietary NO3-. Sixteen participants were allocated to either an experimental group (NIT: n = 11) which consumed a bolus of ∼1300 mg (12.8 mmol) potassium nitrate (KNO3), or a placebo group (PLA: n = 5) which consumed a bolus of potassium chloride (KCl). Biological samples (muscle (vastus lateralis), blood, saliva and urine) were collected shortly before NIT or PLA ingestion and at intervals over the course of the subsequent 24 h. At baseline, no differences were observed for muscle [NO3-] and [NO2-] between NIT and PLA (P > 0.05). In PLA, there were no changes in muscle [NO3-] or [NO2-] over time. In NIT, muscle [NO3-] was significantly elevated above baseline (54 ± 29 nmol/g) at 0.5 h, reached a peak at 3 h (181 ± 128 nmol/g), and was not different to baseline from 9 h onwards (P > 0.05). Muscle [NO2-] did not change significantly over time. Following ingestion of a bolus of dietary NO3-, skeletal muscle [NO3-] increases rapidly, reaches a peak at ∼3 h and subsequently declines towards baseline values. Following dietary NO3- ingestion, human m. vastus lateralis [NO3-] expressed a slightly delayed pharmacokinetic profile compared to plasma [NO3-].

Malignant phyllodes tumor and primary breast sarcoma; distinct rare tumors of the breast.

BACKGROUND: Malignant phyllodes (MP) and primary breast sarcomas (PBS) are rare neoplasms with overlapping histopathologic features. We compared overall survival (OS) and estimated the association of surgery and therapies with OS. METHODS: We utilized the National Cancer Database (2004-2016). Patients without surgery, unknown surgery, or margins, or Stage IV disease were excluded. Kaplan-Meier curves and Cox proportional hazards models were used to estimate unadjusted and adjusted OS, respectively. RESULTS: A total of 3209 (59.5%) MP, and 2185 (40.5%) PBS were identified. Despite a larger median tumor size in MP (46 vs. 40 mm PBS, p < 0.001), lumpectomy rate was higher for MP (52.9% vs. 27.0% PBS, p < 0.001). Compared to MP, PBS patients more frequently received radiation (28.9% vs. 24%), and chemotherapy (28.1% vs. 4%), both p < 0.001. Unadjusted OS was lower for PBS (57% vs. 85% MP, log-rank p < 0.001). PBS (vs. MP) had persistently worse survival (hazard ratio [HR]: 1.98, 95% confidence interval [CI]: 1.69-2.31) after adjustment. Receipt of adjuvant therapies was not associated with OS (either neoplasm); however, lumpectomy was associated with improved OS (vs. mastectomy) for both PBS (HR: 0.59, 95% CI: 0.50-0.75) and MP (HR: 0.65, 95% CI: 0.53-0.81). Positive margins had no association with OS for MP (HR: 1.09, 95% CI: 0.75-1.60), but was associated with worse survival for PBS (HR: 2.35, 95% CI: 1.82-3.02). DISCUSSION: We found significant survival differences between MP and PBS, with PBS having a consistently worse OS. Our findings support surgery as the mainstay of treatment for both tumor types and suggest that lumpectomy may be a reasonable option for select patients without compromising outcomes.

Examining the role of wide excision margins in pediatric melanoma: A National Cancer Database analysis.

BACKGROUND: Although adult guidelines are often applied to children, age-specific surgical margins have not been defined for pediatric melanoma. PROCEDURE: Patients <20 years of age with invasive, cutaneous melanoma were identified using the 2004-2016 National Cancer Database and categorized as undergoing wide (>1 cm) or narrow (≤1 cm) excision. Unadjusted overall survival (OS) was compared using the Kaplan-Meier method and log-rank test. Multivariable Cox proportional hazard models were used to estimate the effect of excision margin on OS after adjustment for available covariates. RESULTS: In total, 2081 patients met study criteria: 1338 (64.3%) patients underwent wide excision whereas 743 (35.7%) underwent narrow excision. Unadjusted OS was improved in the narrow-excision group (log-rank p = .01), which was consistent among patients with thicker (>1 mm) and thinner (≤1 mm) tumors. After adjustment for patient and tumor characteristics, we found no evidence of a difference in OS for patients who underwent narrow excision compared to patients who underwent wide excision (adjusted hazard ratio 0.57, 95% confidence interval 0.32-1.01, p = .053). There was no interaction between excision margin width and Breslow depth (p = .85), indicating that the effect of excision margin width on OS does not differ based on Breslow depth. CONCLUSIONS: In this analysis, wide excision (>1 cm) does not appear to be associated with improved survival in children with melanoma regardless of tumor characteristics. Although further studies are needed to define optimal excision margins in pediatric melanoma, this study suggests that more narrow margins (≤1 cm) may be acceptable.