B Cell Function in the Tumor Microenvironment.

The tumor microenvironment (TME) is a heterogeneous, complex organization composed of tumor, stroma, and endothelial cells that is characterized by cross talk between tumor and innate and adaptive immune cells. Over the last decade, it has become increasingly clear that the immune cells in the TME play a critical role in controlling or promoting tumor growth. The function of T lymphocytes in this process has been well characterized. On the other hand, the function of B lymphocytes is less clear, although recent data from our group and others have strongly indicated a critical role for B cells in antitumor immunity. There are, however, a multitude of populations of B cells found within the TME, ranging from naive B cells all the way to terminally differentiated plasma cells and memory B cells. Here, we characterize the role of B cells in the TME in both animal models and patients, with an emphasis on dissecting how B cell heterogeneity contributes to the immune response to cancer.

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.

Impact of Neoadjuvant Chemoimmunotherapy on Surgical Outcomes and Time to Radiation in Triple-Negative Breast Cancer.

BACKGROUND: We examined the association between immunotherapy-containing and standard chemotherapy regimens with treatment delays and postoperative complications in stage II-III triple-negative breast cancer. The effect of immune-related adverse events (irAEs) was compared. PATIENTS AND METHODS: We compared 139 women treated with neoadjuvant pembrolizumab plus chemotherapy (KEYNOTE-522 regimen) from August 2021 to September 2022 with 287 consecutive patients who received neoadjuvant chemotherapy alone prior to July 2021 and underwent surgery. Baseline characteristics, time to treatments, and surgical complications were compared using two-sample non-parametric tests. Linear regression evaluated association of irAEs with time to surgery and radiation. Logistic regression identified factors associated with surgical complications. RESULTS: Age, body mass index, race, American Society of Anesthesiologists (ASA) class, and mastectomy rates were similar among cohorts. No clinically relevant difference in time from end of neoadjuvant treatment to surgery was observed [KEYNOTE-522: median 32 (IQR 27, 43) days; non-KEYNOTE-522: median 31 (IQR 26, 37) days; P = 0.048]. Time to radiation did not differ (P = 0.7). A total of 26 patients (9%; non-KEYNOTE-522) versus 11 (8%; KEYNOTE-522) experienced postoperative complications (P = 0.6). In the KEYNOTE-522 cohort, 59 (43%) of 137 patients experienced 82 irAEs; 40 (68%) required treatment. Older age (P = 0.018) and ASA class 4 (P = 0.007) were associated with delays to surgery after adjusting for clinical factors. Experiencing ≥ 1 irAE was associated with delay to radiation (P = 0.029). IrAEs were not associated with surgical complications (P = 0.4). CONCLUSIONS: We observed no clinically meaningful difference between times to surgery/adjuvant radiation or postoperative complications and type of preoperative chemotherapy. IrAEs were associated with delay to adjuvant radiation but not with postoperative complications or delay to surgery.

Can We Forgo Sentinel Lymph Node Biopsy in Women Aged ≥ 50 Years with Early-Stage Hormone-Receptor-Positive HER2-Negative Special Histologic Subtype Breast Cancer?

BACKGROUND: Breast cancer has significant biologic heterogeneity, which influences treatment decisions. We hypothesized that in postmenopausal women (≥ 50 years) with clinical T1-2, N0, hormone receptor positive (HR+), HER2 negative (HER2-) breast cancer of special histology (mucinous, tubular, cribriform, papillary), information from sentinel lymph node biopsy (SLNB) may not change adjuvant therapy recommendations. PATIENTS AND METHODS: We constructed a cohort from the National Cancer Database of women aged ≥ 18 years with cT1-2 N0 HR+ HER2- invasive breast cancer. We calculated the frequency of nodal positivity by histology. We measured the frequency of N2/N3 disease, the distribution of Oncotype DX 21-gene assay recurrence score (ODX RS) across special histology by nodal status, and frequency of chemotherapy use by ODX RS and pathologic N stage. RESULTS: In women with cN0 HR+/HER2- special histologic subtype breast cancer, the likelihood of pathologic nodal positivity is less than 5%, and 99.7% of patients had N0 or N1 disease. Among women aged ≥ 50 years with HR+/HER2- special histologic subtype breast cancer, there was low prevalence of high ODX RS > 25 in both N0 and N1 patients (7% overall). Receipt of chemotherapy correlated with Oncotype DX scores as anticipated, with the lowest use in women with a low/intermediate RS (from 2 to 6% for N0 and 6-24% for N1) and the highest use in women with high risk Oncotype scores (from 74 to 92%). CONCLUSIONS: Our study suggests that SLNB could potentially be omitted in select postmenopausal women with cT1-2 N0 HR+/HER2- special histologic subtype breast cancer when ODX RS is available.

Analysis of Specimen Mammography with Artificial Intelligence to Predict Margin Status.

BACKGROUND: Intraoperative specimen mammography is a valuable tool in breast cancer surgery, providing immediate assessment of margins for a resected tumor. However, the accuracy of specimen mammography in detecting microscopic margin positivity is low. We sought to develop an artificial intelligence model to predict the pathologic margin status of resected breast tumors using specimen mammography. METHODS: A dataset of specimen mammography images matched with pathologic margin status was collected from our institution from 2017 to 2020. The dataset was randomly split into training, validation, and test sets. Specimen mammography models pretrained on radiologic images were developed and compared with models pretrained on nonmedical images. Model performance was assessed using sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC). RESULTS: The dataset included 821 images, and 53% had positive margins. For three out of four model architectures tested, models pretrained on radiologic images outperformed nonmedical models. The highest performing model, InceptionV3, showed sensitivity of 84%, specificity of 42%, and AUROC of 0.71. Model performance was better among patients with invasive cancers, less dense breasts, and non-white race. CONCLUSIONS: This study developed and internally validated artificial intelligence models that predict pathologic margins status for partial mastectomy from specimen mammograms. The models' accuracy compares favorably with published literature on surgeon and radiologist interpretation of specimen mammography. With further development, these models could more precisely guide the extent of resection, potentially improving cosmesis and reducing reoperations.

A Review of Immune Checkpoint Blockade for the General Surgeon.

The immune system is a complex and interconnected system that has evolved to protect its host from foreign pathogens. CD8+ T cells are a type of immune cell that can be directly lethal to tumor cells. However, their tumor killing capabilities can be inhibited by checkpoint molecules. During the last decade, the development of medications that block these checkpoint molecules has revolutionized treatment for some cancer types and indications for use continue to grow. As usage of immunotherapy increases, toxicities and adverse events unique to immunotherapy are becoming more prevalent. Here, we review the commonly targeted inhibitory molecules along with their food and drug administration-approved indications in various cancer therapeutic regimens, immunotherapy-related toxicities, and how this may impact surgical planning.

Cost-effectiveness of Choosing Wisely guidelines for axillary observation in women older than age 70 years with hormone receptor-positive, clinically node-negative, operable breast tumors.

BACKGROUND: The Society for Surgical Oncology's Choosing Wisely guidelines recommend against sentinel lymph node biopsy (SLNB) in favor of observation in this population. Recent analyses reveal that this has not been widely adopted. The purpose of this cost-effectiveness analysis is to compare the costs and benefits associated with observation or SLNB in women >70 years old with hormone receptor-positive, clinically node-negative, operable breast cancer. METHODS: A decision tree with Markov modeling was created to compare treatment strategies using long-term follow-up data from clinical trials in this population. Costs were estimated from published literature and publicly available databases. Breast cancer-specific health-state utilities were derived from the literature and expert opinion. One-way, 2-way, and probabilistic sensitivity analyses were conducted. A structural sensitivity analysis was performed to assess the effect of functional status and anxiety from nonevaluation of the axilla on cost-effectiveness. Costs and benefits, measured in life-years (LYs) and quality-adjusted life-years (QALYs), were tabulated across 10, 15, and 20 years and compared using incremental cost-effectiveness ratios (ICERs). RESULTS: SLNB is not cost-effective from the payer or societal perspectives with ICERs of $138,374/LY and $131,900/LY, respectively. When QALYs were considered, SLNB provided fewer QALYs (SLNB, 10.33 QALYs; observation, 10.53 QALYs) at a higher cost (SLNB, $15,845; observation, $4020). Structural sensitivity analysis revealed that SLNB was cost-effective in certain patients with significant anxiety related to axillary observation (ICER, $39,417/QALY). CONCLUSIONS: Routine SLNB in this population is not cost-effective. The cost-effectiveness of SLNB, however, is dependent on individual patient factors, including functional status as well as patient preference.

Prevalence of Pathologic N2/N3 Disease in Postmenopausal Women with Clinical N0 ER+/HER2- Breast Cancer.

BACKGROUND: The RxPONDER trial demonstrated that the 21-gene recurrence score can be used to guide adjuvant systemic therapy decisions in postmenopausal women with pN1 ER+/HER2- breast cancer. As such, a sentinel lymph node biopsy (SLNB) may not provide systemic treatment-altering information for many patients, and omission of SLNB in patients with low probability of pN2/N3 disease could be considered. METHODS: Postmenopausal women (aged ≥ 50 years) diagnosed with cN0cM0, ER+/HER- breast cancer from 2013 to 2017 were identified in the National Cancer Database. The primary outcome was the prevalence of pN2/N3 disease. RESULTS: Of 325,692 postmenopausal women with cN0 ER+/HER2- breast cancer, 7106 (2.2%) were pN2/N3. In total, 81.7% had cT1 tumors, 16.8% T2, 1.3% T3, and 0.2% T4. In patients with T1 tumors, the prevalence of pN2/N3 disease was 1.2% compared with 17.2% in patients with T3/T4 tumors. In multivariable models, cT stage was the strongest predictor of pN2/N3 disease (adjusted odds ratio [aOR] 14.9 [12.1-18.4]). Lobular histology (aOR 2.4 [2.3-2.6]), higher grade (aOR 2.9 [2.6-3.1]), and young age (aOR 1.5 [1.3-1.7]) were also associated with increased prevalence of pN2/N3. We created a model using histology, grade, and T stage that stratifies patients with low prevalence of pN2/3 disease (< 1%) and those at high risk (> 20%). CONCLUSIONS: In postmenopausal women with cN0 ER+/HER2- breast cancer, the prevalence of pN2/N3 disease is low, indicating a potential opportunity to use the results of RxPONDER to extend criteria to omit SLNB. Prospective study is needed to determine safety, including risk of nodal recurrence, of omission of SLNB in carefully selected patients.

Sociodemographic and Clinical Predictors of Neoadjuvant Chemotherapy in cT1-T2/N0 HER2-Amplified Breast Cancer.

BACKGROUND: The optimal treatment strategy for small node-negative human epidermal growth factor receptor 2-positive (HER2+) breast cancer remains controversial. Neoadjuvant chemotherapy may risk overtreatment, whereas surgery first fails to identify patients with residual disease in need of escalated adjuvant systemic therapy. We investigated patient characteristics associated with receipt of neoadjuvant chemotherapy. METHODS: Adult women with cT1-T2/N0, HER2+ breast cancer between 2013 and 2017 in the National Cancer Database who underwent surgery within 8 months of diagnosis were included. Patients were classified as receiving neoadjuvant chemotherapy versus a surgery-first approach. We assessed the sociodemographic and clinical predictors of neoadjuvant chemotherapy versus surgery first and associations between neoadjuvant chemotherapy and breast cancer treatments using multivariable regression models. RESULTS: We identified 56,784 women, of whom 12,758 (22%) received neoadjuvant chemotherapy, 29,139 (53%) received adjuvant chemotherapy, 12,907 (24%) received no chemotherapy, and 1980 were missing chemotherapy information. After adjustment, cT2 stage was the strongest predictor of neoadjuvant chemotherapy compared with surgery first. Younger age and later diagnosis year were positively associated with receipt of neoadjuvant chemotherapy. In contrast, hormone receptor positivity, Black race, rural county, and government-funded or no health insurance were inversely associated with neoadjuvant chemotherapy. In multivariable analyses, patients who received neoadjuvant chemotherapy were more likely to have a mastectomy (vs. lumpectomy) and sentinel lymph node biopsy or no nodal surgery (vs. axillary lymph node dissection). Patients who received neoadjuvant chemotherapy were more likely to receive multi-agent (vs. single-agent) chemotherapy than those who received adjuvant chemotherapy. CONCLUSIONS: Substantial differences in the utilization of neoadjuvant chemotherapy exist in women with HER2+ breast cancer, which reflect both clinical parameters and disparities. Optimal treatment strategies should be implemented equitably across sociodemographic groups.

Five decades of progress in surgical oncology: Breast.

Surgery remains the single most effective treatment for breast cancer but coincident with a deeper understanding of tumor biology and advances in multidisciplinary care (encompassing breast imaging, systemic adjuvant therapy, radiotherapy, and genomics) continues to de-escalate, supported by strong level I data. We have moved from mastectomy to breast conservation, and from routine axillary dissection to sentinel lymph node biopsy to selective omission of axillary node staging altogether. We have further de-escalated through consensus over margin width in breast conservation, through improvements in neoadjuvant therapy, and by demonstrating no benefit for upfront surgery in patients with stage IV disease. For patients with ipsilateral breast tumor recurrence, reconservation surgery and reirradiation are promising. Cell cycle and immune checkpoint inhibitors, when added to conventional systemic therapy, have now moved beyond stage IV disease to phase III trials in the adjuvant and neoadjuvant settings, promising even further de-escalation of surgery. Finally, with genomic profiling we are moving away from the primacy of axillary node status for prognostication and into a new era allowing prediction of response to therapy.

Suboptimal therapy following breast conserving surgery in triple-negative and HER2-positive breast cancer patients.

PURPOSE: To assess potential disparities in guideline-concordant care delivery among women with early-stage triple-negative and HER2-positive breast cancer treated with breast conserving therapy. METHODS: Women ≥ 40 years old diagnosed with pT2N0M0 triple-negative or HER2-positive breast cancer treated with primary surgery and axillary staging between 2012 and 2017 were identified using the National Cancer Database (NCDB). The primary outcome was receipt of adjuvant systemic therapy and radiation concordant with current guidelines. Multivariable log-binomial regression was used to assess the prevalence of optimal therapy use across patient and cancer characteristics. Kaplan-Meier curves were used to assess 5-year overall survival. Multivariable Cox proportional hazards regression was used to compare the impact of optimal therapy on 5-year mortality. RESULTS: 11,785 women were included with 7,843 receiving optimal therapy. Receipt of optimal therapy decreased with age even after adjusting for comorbidities and cancer characteristics; other sociodemographic factors were not associated with differences in receipt of optimal therapy. Among patients who did not receive adjuvant systemic therapy, most were not offered the treatment (49%) or refused (40%). Overall 5-year survival was higher among women who received optimal therapy (89% [95% CI 88.0-89.3] vs. 66% [95% CI 62.9-68.5]). Patients who received suboptimal therapy were over twice as likely to die within 5 years of their diagnosis (adjusted HR 2.44, 95% CI 2.12-2.82). CONCLUSION: Age is the primary determinant of the likelihood of a woman to receive optimal adjuvant therapies in high-risk early-stage breast cancer. Patients who did not receive optimal therapy had significantly diminished survival.

Surgical Axillary Staging Before Neoadjuvant Chemotherapy: Who Gets It and Why We Should Avoid It.

BACKGROUND: Surgical axillary staging demonstrating positive nodal disease before neoadjuvant chemotherapy (NAC) necessitates axillary lymph node dissection (ALND) post-NAC. Despite evidence supporting post-NAC surgical staging, we hypothesized that there is persistent use of pre-NAC staging and that it is associated with aggressive clinicopathologic features and a higher rate of subsequent ALND. PATIENTS AND METHODS: Stage I-III breast cancer patients who underwent lymph node staging surgery and received NAC between 2013 and 2017 in the National Cancer Database were included. Sequence of staging surgery and chemotherapy administration was determined. Multivariable regression was used to assess characteristics associated with pre-NAC staging. Rate of ALND was compared between those who had pre- and post-NAC surgical axillary staging. RESULTS: In total, 120,538 met inclusion; 68% received NAC first and 32% had pre-NAC staging. Pre-NAC staging surgery was associated with younger age (age < 30 versus 40-49 years, HR 1.1) and decreased with older age (ages 70-79/80+ versus 40-49 years, HR 0.86 and 0.73). Advancing clinical T stage, lobular subtype, higher grade, and HR+/HER2- subtype were also associated with pre-NAC surgical staging. Women who underwent pre-NAC surgical staging were more likely to undergo ALND. CONCLUSIONS: Over 30% of women underwent surgical axillary staging prior to NAC, resulting in higher rates of ALND in this cohort. While certain features suggestive of aggressive behavior (grade and T stage) were associated with pre-NAC surgical axillary staging, women with more aggressive tumor subtypes (triple negative/HER2+) were less likely to undergo pre-NAC surgical axillary staging. Pre-NAC surgical axillary staging should be performed only in rare circumstances to avoid unnecessary ALND.

The Prognostic Value of Axillary Staging Following Neoadjuvant Chemotherapy in Inflammatory Breast Cancer.

BACKGROUND: Inflammatory breast cancer (IBC) has historically been characterized by high rates of recurrence and poor survival; however, there have been significant improvements in systemic therapy. We sought to investigate modern treatment of IBC and define the yield and prognostic significance of axillary lymph nodes after neoadjuvant chemotherapy (NAC). METHODS: Women with clinical stage T4d, N0-N3, M0 IBC from 2012 to 2016 in the National Cancer Database were included. Kaplan-Meier survival curves and Cox regression were used to assess mortality by receptor subtype and nodal status. RESULTS: We identified 5265 patients; 37% hormone receptor (HR) +/HER2 - , 19% HR +/HER2 + , 18% HR -/HER2 + , and 26% triple-negative, and 5-year overall survival was 51.6%. Only 34% were treated according to guidelines with NAC, modified radical mastectomy, and adjuvant radiation. Pathologically positive lymph nodes (ypN +) after NAC varied by subtype and clinical nodal status (cN) ranging from 82% in cN + HR +/HER2 - patients to 19% in cN0 HR -/HER2 + patients. ypN + strongly correlated with survival in all subtypes with the most pronounced impact in HR +/HER2 + patients, with 90% 5-year overall survival in ypN0 versus 66% for ypN + (HR 4.29, 95% CI 1.58-11.70, p = 0.03). CONCLUSIONS: Five-year survival in M0 IBC is 51.6%. Positive nodes after NAC varied by subtype and clinical N status but is sufficiently high and provided meaningful prognostication in all subtypes to support continued routine pathologic assessment. Future study is warranted to identify reliable, less morbid, methods of staging the axilla in IBC patients appropriate for deescalation of axillary surgery.

Nodal positivity decreases with age in women with early-stage, hormone receptor-positive breast cancer.

BACKGROUND: Despite data demonstrating the safety of omitting axillary surgery in older women with early-stage breast cancer, the incidence of axillary surgery remains high. It was hypothesized that the prevalence of nodal positivity would decrease with advancing age. METHODS: The National Cancer Data Base was used to construct a cohort of adult women with early-stage, clinically node-negative, estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative breast cancer treated between 2013 and 2015. Multivariable logistic regression was used to assess the relationship between age and nodal positivity, and this was stratified by the axillary surgery category. Modified Poisson regression was used to estimate the proportion of women receiving adjuvant therapy according to age and nodal status. RESULTS: The incidence of axillary surgery among women aged 70 and older (n = 51,917) remained high nationwide (86%). There was a significant decrease in nodal positivity with advancing age in women with early-stage, ER+, clinically node-negative breast cancer from the youngest cohort up to patients aged 70 to 89 years, and this was independent of histologic subtype (ductal vs lobular), race, comorbidities, and socioeconomic factors. Overall, less than 10% of women aged 70 or older who underwent surgery had node-positive disease, regardless of axillary surgery type, and almost 95% of node-positive patients aged 70 or older were at pathological stage N1mi or N1. CONCLUSIONS: Axillary surgery may be safely omitted for many older women with ER+, clinically node-negative, early-stage breast cancer. Nodal positivity declines with advancing age, and this suggests varied biology in older patients versus younger patients.

Trends in Surgical Axillary Management in Early Stage Breast Cancer in Elderly Women: Continued Over-Treatment.

INTRODUCTION: In the past two decades, three prospective randomized trials demonstrated that elderly women with early stage hormone positive breast cancer had equivalent disease-specific mortality regardless of axillary surgery. In 2016, the Choosing Wisely campaign encouraged patients and providers to reconsider the role of axillary surgery in this population. We sought to identify factors that contribute to adopting non-operative management of the axilla in these patients. MATERIALS AND METHODS: We performed a retrospective analysis of women ≥ 70 years old with cT1/T2, hormone positive invasive ductal carcinoma who underwent partial or total mastectomy, with/without axillary surgery, and did not receive adjuvant chemotherapy from the National Cancer Database from 2004 to 2015. We used multivariable log-binomial regression to model the risk of undergoing axillary surgery across region, care setting, and Charlson-Deyo scores, and analyzed temporal trends using Poisson regression. From 2004 to 2015, 87,342 of 99,940 women who met inclusion criteria (83%) had axillary surgery. Over time, axillary surgery increased from 78% to 88% (p < 0.001). This rise was consistent across region (p = 0.81) and care setting (p = 0.09), but flattened as age increased (p < 0.001). Omitting axillary surgery was more likely in patients treated in New England (RR 0.88, 95% CI 0.86, 0.89) and patients ≥ 85 (RR 0.66, 95% CI 0.65, 0.67). CONCLUSIONS: Axillary surgery continues to be the preferred option of axillary management in elderly women with early stage, clinically node negative, hormone-positive, invasive breast cancer despite no survival benefit. Identifying factors to improve patient selection and dissemination of current recommendations can improve adoption of current evidence on axillary surgery in the elderly.

Microscopic Extracapsular Extension in Sentinel Lymph Nodes Does Not Mandate Axillary Dissection in Z0011-Eligible Patients.

BACKGROUND: In the ACOSOG (American College of Surgeons Oncology Group) Z0011 trial and the AMAROS (After Mapping of the Axilla: Radiotherapy or Surgery?) trial, matted nodes with gross extracapsular extension (ECE), a risk factor for locoregional recurrence, were an indication for axillary lymph node dissection (ALND), but the effect of microscopic ECE (mECE) in the sentinel lymph nodes (SLNs) on recurrence was not examined. METHODS: Between 2010 and 2017, 811 patients with cT1-2N0 breast cancer and SLN metastasis were prospectively managed according to Z0011 criteria, with ALND for those with more than two positive SLNs or gross ECE. Management of mECE was not specified. In this study, we compare outcomes of patients with one to two positive SLNs with and without mECE, treated with SLN biopsy alone (n = 685). RESULTS: Median patient age was 58 years, and median tumor size was 1.7 cm. mECE was identified in 210 (31%) patients. Patients with mECE were older, had larger tumors, and were more likely to be hormone receptor positive and HER2 negative, have two positive SLNs, and receive nodal radiation. At a median follow-up of 41 months, no isolated axillary failures were observed. There were 11 nodal recurrences; two supraclavicular ± axillary, four synchronous with breast, and five with distant failure. The five-year rate of any nodal recurrence was 1.6% and did not differ by mECE (2.3% vs. 1.3%; p = 0.84). No differences were observed in local (p = 0.08) or distant (p = 0.31) recurrence rates by mECE status. CONCLUSIONS: In Z0011-eligible patients, nodal recurrence rates in patients with mECE are low after treatment with SLN biopsy alone, even in the absence of routine nodal radiation. The presence of mECE should not be considered a routine indication for ALND.

Disparities of Management of the Axilla in Women With Clinically Node Negative Breast Cancer.

BACKGROUND: In women with clinically node-negative breast cancer, sentinel lymph node biopsy is the first step in axillary staging. A randomized trial published in 2013 concluded that patients with sentinel lymph node micrometastases (N1mi) do not benefit from axillary lymph node dissection (ALND). We hypothesized that disparities exist in management of the axilla in node-negative patients. METHODS: We included women aged >40 years with nonmetastatic, clinically node-negative breast cancer from 2014 to 2016 in the National Cancer Database. Women treated neoadjuvantly, with large tumors (cT4), or no tumor (cT0) were excluded. Multivariable logistic regression identified patient and facility characteristics associated with undergoing ALND as first axillary surgery and completion ALND in the setting of N1mi disease. RESULTS: Of 273,951 patients, 22,898 (8%) underwent ALND first. These patients were more likely to be Hispanic (OR: 1.21, 95% CI: 1.10, 1.32), have Medicare (OR: 1.13, 95% CI: 1.03, 1.24), be uninsured (OR: 1.28, 95% CI: 1.08, 1.53), have lower educational attainment (OR: 1.24, 95% CI: 1.17, 1.32), be treated at a community hospital (OR: 1.62, 95% CI: 1.52, 1.74), or reside in the South (OR: 1.19, 95% CI: 1.12, 1.26). In the sentinel lymph node biopsy first group, 8,882 (4%) were classified as N1mi and 1,872 (21%) underwent subsequent ALND. These patients were more likely to be Hispanic (OR: 1.70, 95% CI: 1.19, 2.42) and have the lowest income (OR: 1.62, 95% CI: 1.15, 2.27). CONCLUSION: Disparities persist in implementation of evidence-based management of the axilla in women with clinically node-negative breast cancer.

Impact of Age on Locoregional and Distant Recurrence After Mastectomy for Ductal Carcinoma In Situ With or Without Microinvasion.

BACKGROUND: Locoregional recurrence (LRR) after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) is increased in young women. We examined the impact of age on LRR and distant disease after mastectomy for DCIS ± microinvasion. METHODS: We identified consecutive patients with DCIS ± microinvasion treated with mastectomy from 1995 to 2017. LRR was defined as recurrence at the ipsilateral chest wall or regional nodes. RESULTS: Overall, 3121 cases were identified, of which 421 (13.5%) had DCIS + microinvasion. Median age was 49 years and median follow-up was 6.4 years; 821 were followed for 10 or more years. Thirty-four LRRs were observed: 33 (97%) were invasive, and 23 (68%) were in the chest wall alone. Cumulative 10-year LRR incidence was 1.4%. Age < 50 years, high grade, and DCIS + microinvasion were associated with LRR (p ≤ 0.001); however, margin status was not (p = 0.14). Adjusting for grade and DCIS + microinvasion, age < 50 years (hazard ratio [HR] 14.7, 95% confidence interval [CI] 3.5-61.5; p < 0.001) was associated with LRR. Compared with women ≥ 50 years of age, women age < 40 years had the highest risk (HR 27.0, 95% CI 6.0-121), and women age 40-49 years had intermediate risk (HR 11.8, 95% CI 2.8-50.5). The cumulative 10-year LRR incidence was 4.2% for women < 40 years of age, 2.0% for women 40-49 years of age, and 0.2% for women ≥ 50 years of age. Women age < 40 years had a 10-year distant disease rate of 1.6% versus women age 40-49 years (0.7%) and women age ≥ 50 years (0.7%) (log-rank p = 0.051). Grade, DCIS + microinvasion, and margins were unassociated with distant disease. CONCLUSIONS: LRR after mastectomy for DCIS ± microinvasion is uncommon, but is more frequent among women < 50 years of age, particularly in those < 40 years of age. The 10-year LRR rate in this youngest group remains low at 4.2%. Young age is an independent risk factor for LRR after BCS or mastectomy.

Radiation Therapy After Breast-Conserving Surgery in Women 70 Years of Age and Older: How Wisely Do We Choose?

BACKGROUND: Despite data from randomized trials supporting omission of radiation therapy (RT) for women ≥ 70 years of age with T1, estrogen receptor-positive (ER+) tumors undergoing breast-conserving therapy (BCT), RT usage remains high. We reviewed our institutional experience to determine if risk factors for local recurrence or comorbidities influenced use. METHODS: Women ≥ 70 years of age with T1, ER+, human epidermal growth factor receptor 2-negative (HER2-) tumors undergoing BCT in 2010-2012 were identified from a prospectively maintained database. Ten-year estimated mortality was calculated using the Suemoto index. The associations of clinicopathological features and mortality risk on receipt of RT were examined. RESULTS: Overall, 323 patients with 327 cancers were identified. Median age was 75 years, median tumor size was 1 cm, and all were clinically node negative; 53.7% of patients received RT. RT usage decreased with age (73.6%, age 70-74 years; 49.5%, age 75-79 years; 33.3%, age 80-84 years; 10.7%, ≥ 85 years; p < 0.001). Within age groups, estimated mortality did not impact RT usage. On multivariable analysis, only younger age and larger tumor size were associated with RT use. Recurrence-free survival was 98% versus 93% with and without RT, respectively (p = 0.011). Those who received adjuvant radiation also had improved overall survival (92% vs. 89%), although this effect did not reach statistical significance (p = 0.051). CONCLUSION: Neither the factors associated with risk of local recurrence nor the estimated risk of death in 10 years were associated with use of adjuvant radiation in a large cohort of women ≥ 70 years of age with small ER+ breast cancers treated with breast-conserving surgery.