Nodal Surgery for Patients ≥ 70 Undergoing Mastectomy for DCIS? Choose Wisely.

BACKGROUND: Routine sentinel lymphadenectomy (SLNB) for early-stage HR+/HER2- breast cancer in women ≥70 is discouraged by Choosing Wisely, but whether SLNB can be routinely omitted in women ≥70 with DCIS undergoing mastectomy is unclear. This study aims to evaluate rates of axillary surgery and nodal positivity (pN+) in this population to determine the impact of axillary surgery on treatment decisions. METHODS: Females ≥70 with DCIS undergoing mastectomy were identified from the National Cancer Database (2012-2020). The rate of upstaging to invasive cancer (≥pT1) or pN+ was assessed. Subset analyses were conducted for ER+ patients. Adjuvant therapies were evaluated among ≥pT1 patients after stratifying by nodal status. RESULTS: Of 9,030 patients, 1,896 (21%) upstaged to ≥pT1. Axillary surgery was performed in 86% of patients, predominantly sentinel lymphadenectomy (SLNB, 65%). Post hoc application of Choosing Wisely criteria demonstrated that 93% of the entire cohort and 97% of ER+ DCIS patients could have avoided axillary surgery. Nodal positivity was 0.3% among those who didn't upstage, and 12% among those upstaging to ≥pT1, with <2% having pN2-3 disease, irrespective of receptor subtype. Node-positive patients had higher adjuvant therapy usage, but there was no recommendation for adjuvant chemotherapy or radiation for 71% and 66% of pN+ patients, respectively. CONCLUSIONS: Axillary surgery can be omitted for most patients ≥70 undergoing mastectomy for ER+ DCIS, aligning with recommendations for invasive cancer, and omission can be considered in those with ER- disease. Future guidelines incorporating preoperative imaging, as in the SOUND trial, may aid in identifying patients benefiting from axillary surgery.

What Proportion of BRCA-Associated Breast Cancer Is Human Epidermal Growth Factor 2-Low and Eligible for Additional Targeted Therapy?

INTRODUCTION: DESTINY B04 provided clinical meaning to a new classification of human epidermal growth factor 2 (HER2) expression in breast cancer: HER2-low. Patients with germline breast cancer type 1 gene pathogenic variants (gBRCA1) often develop triple negative breast cancer (TNBC), but the proportion who could be classified as HER2-low and qualify for an additional targeted therapy option is unknown. This study aims to characterize the proportion of gBRCA1 or germline breast cancer type 2 gene pathogenic variants patients for whom these novel targeted therapies may be an option. METHODS: We performed a retrospective chart review of patients with gBRCA1/2 treated at our institution for invasive breast cancer from 2000 to 2021. Synchronous or metachronous contralateral breast cancers were recorded separately. HER2 status was determined by immunohistochemistry and fluorescence in situ hybridization. We excluded patients without complete HER2 data. RESULTS: Among the 95 breast cancers identified in our cohort of 85 gBRCA1/2 patients, 41 (43%) were TNBC, 38 (40%) were hormone receptor positive (HR+)/HER2-negative, and 16 (17%) were HER2-positive based on standard conventions. We found that 82% of the HR+/HER2-cancers and 66% of TNBCs would be reclassified as HER2-low. After stratifying by BRCA gene status, 64% of cancers in patients with gBRCA1 and 58% of cancers in patients with germline breast cancer type 2 gene pathogenic variants were HER2-low. CONCLUSIONS: A significant portion of gBRCA1/2 patients who were previously diagnosed with TNBC or HR+/HER2- breast cancer would now be classified as HER2-low and could be considered for the use of trastuzumab deruxtecan in the metastatic setting. Outcome differences from therapy changes in this cohort should now be assessed.

Update on Hypermetabolism in Pediatric Burn Patients.

Despite advancements in pediatric burn care, the profound hypermetabolic response associated with severe burns remains a multifaceted challenge throughout the continuum of care. Understanding the various physiologic disturbances that constitute hypermetabolism is crucial for a thorough evaluation and for implementing appropriate surgical and nonsurgical interventions. In this article, we describe the pathophysiology and treatment of hypermetabolism in pediatric burn patients with a focus on reducing resting energy requirements, minimizing infection, and optimizing nutrition for patients undergoing frequent surgical intervention.

Lost in Translation: Multilingual Analysis of Online Breast Cancer Information.

INTRODUCTION: Patients use the internet to learn more about health conditions. Non-English-speaking patients may face additional challenges. The quality of online breast cancer information, the most common cancer in women, is uncertain. This study aims to examine the quality of online breast cancer information for English and non-English-speaking patients. METHODS: Three search engines were queried using the terms: "how to do a breast examination," "when do I need a mammogram," and "what are the treatment options for breast cancer" in English, Spanish, and Chinese. For each language, 60 unique websites were included and classified by type and information source. Two language-fluent reviewers evaluated website quality using the Journal of American Medical Association benchmark criteria (0-4) and the DISCERN tool (1-5), with higher scores representing higher quality. Scores were averaged for each language. Health On the Net code presence was noted. Inter-rater reliability between reviewers was assessed. RESULTS: English and Spanish websites most commonly originated from US sources (92% and 80%, respectively) compared to Chinese websites (33%, P < 0.001). The most common website type was hospital-affiliated for English (43%) and foundation/advocacy for Spanish and Chinese (43% and 45%, respectively). English websites had the highest and Chinese websites the lowest mean the Journal of American Medical Association (2.2 ± 1.4 versus 1.0 ± 0.8, P = 0.002) and DISCERN scores (3.5 ± 0.9 versus 2.3 ± 0.6, P < 0.001). Health On the Net code was present on 16 (8.9%) websites. Inter-rater reliability ranged from moderate to substantial agreement. CONCLUSIONS: The quality of online information on breast cancer across all three languages is poor. Information quality was poorest for Chinese websites. Improvements to enhance the reliability of breast cancer information across languages are needed.

Recent Advances in the Upfront Surgical Management of the Axilla in Patients with Breast Cancer.

Nodal status is an important prognostic indicator. Upfront axillary surgery for patients with breast cancer has historically been both diagnostic and therapeutic-serving to determine nodal status and inform adjuvant therapies, and to remove clinically significant disease. However, trials of de-escalation or omission of axillary surgery altogether consistently demonstrate noninferior oncologic outcomes in a wide variety of patient subsets. These strategies also reduce the morbidity associated with either sentinel lymphadenectomy or axillary lymph node dissection. Here we will briefly review landmark trials that have shaped upfront axillary surgery as well as recent advances, and discuss areas of ongoing investigation and future needs.

Liposomal Bupivacaine Use During Orthognathic Surgery in Cleft Lip and Palate Patients.

INTRODUCTION: Effective pain management is crucial in cleft lip and palate (CLP) patients undergoing orthognathic surgery for earlier recovery and decreased opioid reliance. Liposomal bupivacaine (Exparel) is a local anesthetic that provides extended postoperative analgesia in adult patients; however, research on its use in adolescents is limited. This study explores the efficacy of liposomal bupivacaine for postoperative pain management in adolescent CLP patients undergoing orthognathic surgery. METHODS: The authors performed a retrospective chart review at their institution between July 2020 and December 2022 to identify patients who underwent LeFort I or mandibular osteotomy. Two cohorts were compared: patients who received liposomal bupivacaine and patients who received standard pain medications alone. Outcome measures included intraoperative pain medications, length of stay, breakthrough opioid use, time to first oral intake, volume of oral intake, and opioids prescribed at discharge. RESULTS: This study included 22 patients who underwent orthognathic surgery. The liposomal bupivacaine group (n=10) demonstrated earlier and greater oral intake during hospitalization compared with controls (n=12). The most significant difference was observed in total breakthrough opioid use, with an average of 8.60 morphine milligram equivalents for liposomal bupivacaine patients compared with 35.1 morphine milligram equivalents for controls (P=0.037). CONCLUSIONS: This study provides the first analysis of liposomal bupivacaine use in adolescent CLP patients undergoing orthognathic surgery, demonstrating a significant reduction in postoperative opioid consumption compared with controls. These results may guide future studies of liposomal bupivacaine within CLP patients, potentially as a component of enhanced recovery after surgery guidelines, as well as in cost-analysis studies.

Should patients with hormone receptor-positive, HER2-negative breast cancer and one or two positive sentinel nodes undergo axillary dissection to determine candidacy for adjuvant abemaciclib?

BACKGROUND: The monarchE trial demonstrated improved outcomes with the use of adjuvant abemaciclib in patients with high-risk hormone receptor-positive, HER2-negative (HR+/HER2-) breast cancer defined as ≥4 positive lymph nodes (+LNs) or one to three +LNs with one or more additional high-risk features (HRFs). The proportion of patients with one or two positive sentinel lymph nodes (+SLNs) without HRFs who had ≥4 +LNs at the time of completion axillary lymph node dissection (cALND), and who therefore qualified for receipt of abemaciclib, was investigated. METHODS: Females with pathologically node-positive nonmetastatic HR+/HER2- breast cancer stratified by the number of +SLNs and +LNs and the presence of one or more HRFs were identified from the National Cancer Database (2018-2019). The proportion of patients meeting the criteria for abemaciclib both before and after ALND was assessed. RESULTS: Of the 22,048 patients identified, 1578 patients underwent upfront surgery, had one or two +SLNs without HRFs, and went on to cALND. Only 213 (13%) of these patients had ≥4 +LNs; thus, cALND performed solely to determine abemaciclib candidacy would have constituted surgical overtreatment in 1365 patients (87%). When stratified by the number of +SLNs, only 10% of those with one +SLN and 24% of those with two +SLNs had ≥4 +LNs after cALND, which meets the criteria for abemaciclib. CONCLUSIONS: Patients with one +SLN without HRFs are unlikely to have ≥4 +LNs and should not be subjected to the morbidity of ALND in order to inform candidacy for abemaciclib. An individualized multidisciplinary discussion should be undertaken about the risk:benefit ratio of ALND and abemaciclib for those with two +SLNs.

Use of a supervised machine learning model to predict Oncotype DX risk category in node-positive patients older than 50 years of age.

PURPOSE: The use of the Oncotype DX recurrence score (RS) to predict chemotherapy benefit in patients with hormone receptor-positive/HER2 negative (HR+/HER2-) breast cancer has recently expanded to include postmenopausal patients with N1 disease. RS availability is limited in resource-poor settings, however, prompting the development of statistical models that predict RS using clinicopathologic features. We sought to assess the performance of our supervised machine learning model in a cohort of patients > 50 years of age with N1 disease. METHODS: We identified patients > 50 years of age with pT1-2N1 HR+/HER2- breast cancer and applied the statistical model previously developed in a node-negative cohort, which uses age, pathologic tumor size, histology, progesterone receptor expression, lymphovascular invasion, and tumor grade to predict RS. We measured the model's ability to predict RS risk category (low: RS ≤ 25; high: RS > 25). RESULTS: Our cohort included 401 patients, 60.6% of whom had macrometastases, with a median of 1 positive node. The majority of patients had a low-risk observed RS (85.8%). For predicting RS category, the model had specificity of 97.3%, sensitivity of 31.8%, a negative predictive value of 87.9%, and a positive predictive value of 70.0%. CONCLUSION: Our model, developed in a cohort of node-negative patients, was highly specific for identifying cN1 patients > 50 years of age with a low RS who could safely avoid chemotherapy. The use of this model for identifying patients in whom genomic testing is unnecessary would help decrease the cost burden in resource-poor settings as reliance on RS for adjuvant treatment recommendations increases.

Are We Overtreating Patients With T1a HER2+ Breast Cancer? An Analysis of the National Cancer Database.

INTRODUCTION: The potential benefit of systemic therapy in patients with T1a HER2+ cancers is not well understood, and no consensus guidelines exist. We sought to investigate practice patterns of chemotherapy use in this population. METHODS: From the National Cancer Database (2013-2018), we identified female patients with HER2+ cancers staged as cT1aN0 or pT1aN0 and stratified by receipt of chemotherapy. Using univariate and multivariable analyses we assessed the clinicopathologic features associated with the receipt of chemotherapy. We also compared rates of overall survival (OS). RESULTS: Of 5176 women with cT1aN0 HER2+ cancers, 88 (2%) received neoadjuvant chemotherapy. Younger age and hormone-receptor (HR) negative tumors were factors independently associated with receipt of neoadjuvant chemotherapy (all P < .001). Of 11,688 women with pT1aN0 HER2+ cancers, 5,588 (48%) received adjuvant chemotherapy. Rates of use increased over the analysis period from 39% in 2013 to 53% in 2018 (P < .001). Factors independently associated with receipt of adjuvant chemotherapy included younger age, having a poorly differentiated tumor, exhibiting lymphovascular invasion, undergoing adjuvant radiation (all P < .001). There were no differences in OS when comparing those who did and did not receive chemotherapy in either group. CONCLUSIONS: The use of chemotherapy in patients with HER2+ T1a cancers is increasing over time and is, as expected, more common among patients with unfavorable clinicopathologic features. Since no prognostic algorithm currently exists, more prospective data is needed to understand which of these patients may derive benefit from systemic therapy and which may safely avoid the morbidity of chemotherapy.

Omission of Intraoperative Frozen Section May Reduce Axillary Overtreatment Among Clinically Node-Negative Patients Having Upfront Mastectomy.

BACKGROUND: The growing use of postmastectomy radiation/regional nodal irradiation (PMRT) has resulted in many women receiving both axillary dissection (ALND) and PMRT, increasing lymphedema rates. After developing standardized PMRT criteria, we adopted a policy of ALND omission among cN0 patients with 1-2 positive sentinel nodes (+SLNs) requiring PMRT. We evaluated how often overtreatment with ALND+PMRT was avoided with this approach. METHODS: A retrospective review of a prospectively maintained database was performed beginning 1 year before policy adoption. Intraoperative SLN evaluation was routine pre- and post-policy. ALND was performed for SLN macrometastasis pre-policy, and selectively performed post-policy for 1-2 +SLNs based on PMRT criteria. ALND+PMRT was required for ≥ 3 +SLNs. RESULTS: From March 1, 2018 to November 30, 2020, a total of 2207 cT1-3N0 patients had mastectomy and 231 had +SLNs; 109 (47%) were treated pre-policy and 122 (53%) post-policy. Most (81%) had 1-2 +SLNs. There was no change in rates of ALND+PMRT (64% pre-policy vs. 58% post-policy, p = 0.09), including in patients with 1-2 +SLNs (61% vs. 51%, p = 0.20). Post-policy, ALND was omitted in 9 (7%) patients recognized intraoperatively as PMRT candidates; avoidable ALND was performed in 40 (33%) patients not identified as PMRT candidates until receipt of final pathology. Overall, had intraoperative SLN evaluation been deferred, only 5.7% of patients would have required completion ALND: 2.2% (n = 49/2207) for ≥ 3 +SLNs and 3.5% (n = 77/2207) for 1-2 +SLNs without PMRT indication. CONCLUSIONS: Most patients could have avoided ALND+PMRT if decision making was deferred until final pathology was available. Selective intraoperative SLN evaluation in cN0 patients having upfront mastectomy may reduce avoidable overtreatment.

Neoadjuvant Chemotherapy for Breast Cancer In the Elderly: Are We Accomplishing Our Treatment Goals?

INTRODUCTION: Rates of downstaging and tolerability to NAC in women age ≥ 70 years with operable breast cancer have not been well studied. We sought to compare downstaging rates and NAC completion between women age 50-69 years and age ≥ 70 years. METHODS: Consecutively treated women age ≥ 50 years with cT1-3N0-1 breast cancer receiving NAC followed by surgery from November 2013 to April 2020 were studied. Rates of downstaging from breast-conserving surgery (BCS)-ineligible to BCS-eligible and avoidance of axillary dissection (ALND) in cN1 patients were compared between patients age 50-69 and ≥ 70 years. NAC regimens and rates of completion also were assessed. RESULTS: Overall, 651 women, age ≥ 50 years, with 668 cT1-3N0-1 breast cancers that were treated with NAC, were identified; 75 (11.1%) were age ≥ 70 years. Patients age ≥ 70 years were less likely to have lobular cancers (5% vs. 10%, p = 0.03), receive an anthracycline-based regimen (69% vs. 93%, p < 0.001), and complete their entire prescribed regimen (57% vs. 78%, p < 0.001). Of 312 BCS-ineligible patients eligible for downstaging, conversion rates to BCS-eligibility were similar between age groups (72% [≥ 70] vs. 74% [50-69], p > 0.9). Women age ≥ 70 years who converted to BCS-eligible post-NAC were more likely to undergo BCS than younger patients (93% vs. 74%, p = 0.04). Of 390 cN1 patients, 162 (42%) achieved a nodal pCR; ALND avoidance was similar between age groups (43% [≥ 70] vs. 42% [50-69], p > 0.9). CONCLUSIONS: While patients age ≥ 70 years received less anthracycline-based NAC and were less likely to complete their prescribed regimen, they experienced high rates of breast and axillary downstaging, similar to younger patients, suggesting that well-selected elderly patients can safely receive NAC with substantial clinical benefit.

The use of neoadjuvant therapy increases the rate of breast conservation in men with locally advanced breast cancer.

BACKGROUND: Male breast cancer (MBC) is often diagnosed at a later stage and with a more unfavorable tumor-to-breast ratio compared to women, prompting lower rates of breast conservation (BCT). We sought to assess the practice patterns of neoadjuvant therapy (NT) in MBC patients and the impact on BCT. METHODS: Men with nonmetastatic, invasive breast cancer were identified from the National Cancer Database. Patients were categorized as having small (cT1/2) or locally advanced (cT3/4) tumors and by whether they received NT (which included endocrine or chemotherapy). Univariate and multivariable analyses were performed to assess patterns of NT use and rates BCT. RESULTS: Of 15,151 male patients, 4.8% received NT and 21.6% underwent BCT. NT was more common among males with cT3/4 tumors than those with cT1/2 tumors (8.2 vs. 2.1%, P < .001). Overall, unadjusted rates of BCT were higher for patients receiving NT in the cT3/4 subgroup (19.0 vs. 12.5%, P < .001), a difference which persisted on multivariable analysis. For all patients analyzed, overall survival (OS) did not differ between males who underwent NT and those who did not (110 vs. 122 months, P = .67), but NT was associated with poorer OS in both univariate and multivariate analyses for patients with cT3/4 tumors (both P < .01). CONCLUSIONS: Men with invasive breast cancer have an expected low rate of BCT, but NT appears to reduce the use of mastectomy in patients with locally advanced cancers. More work is needed to understand the impacts of BCT on locoregional recurrence and disease-free and overall survival for MBC.

Racial and socioeconomic disparities in breast cancer diagnosis and mortality in Pennsylvania.

PURPOSE: Many studies have demonstrated disparities in breast cancer (BC) incidence and mortality among Black women. We hypothesized that in Pennsylvania (PA), a large economically diverse state, BC diagnosis and mortality would be similar among races when stratified by a municipality's median income. METHODS: We collected the frequencies of BC diagnosis and mortality for years 2011-2015 from the Pennsylvania Cancer Registry and demographics from the 2010 US Census. We analyzed BC diagnoses and mortalities after stratifying by median income, municipality size, and race with univariable and multivariable logistic regression models. RESULTS: In this cohort, of 5,353,875 women there were 54,038 BC diagnoses (1.01% diagnosis rate) and 9,828 BC mortalities (0.18% mortality rate). Unadjusted diagnosis rate was highest among white women (1.06%) but Black women had a higher age-adjusted diagnosis rate (1.06%) than white women (1.02%). Race, age and income were all significantly associated with BC diagnosis, but there were no differences in BC diagnosis between white and Black women across all levels of income in the multivariable model. BC mortality was highest in Black women, a difference which persisted when adjusted for age. Black women 35 years and older had a higher mortality rate in all income quartiles. CONCLUSION: We found that in PA, age, race and income are all associated with BC diagnosis and mortality with noteworthy disparities for Black women. Continued surveillance of differences in both breast cancer diagnosis and mortality, and targeted interventions related to education, screening and treatment may help to eliminate these socioeconomic and racial disparities.