Omission of axillary lymph node dissection for breast cancer patients with three or more positive sentinel lymph nodes.

PURPOSE: The ACOSOG Z0011 (Z11) trial assessed the benefit of axillary dissection (ALND) for breast cancer patients with sentinel lymph node (SLN) metastases; however, Z11 excluded patients with ≥ 3 positive SLNs. We analyzed trends in ALND omission in patients with ≥ 3 positive SLNs. METHODS: Women with ≥ 3 positive SLNs who underwent breast-conserving surgery (BCS) or mastectomy between 2018 and 2020 in the National Cancer Database were included using SLN codes initiated in 2018. Patients with stage IV disease, recurrent breast cancer, and who underwent neoadjuvant chemotherapy were excluded. A multivariable logistic regression model was utilized to determine the proportion who received ALND and factors associated with ALND omission. A subgroup analysis was performed among patients who met the remainder of the Z11 inclusion criteria (BCS, T1/T2 breast cancer). RESULTS: We identified 3654 patients with ≥ 3 positive SLNs. ALND was omitted in 37% of patients, and omission significantly increased from 2018 to 2020 (29% vs. 41%, p < 0.0001). Older age, lower grade tumors, no radiation, non-academic facility, BCS, more SLNs examined and fewer positive SLNs were significantly associated with ALND omission. 942 patients with ≥ 3 positive SLNs met the remainder of the Z11 inclusion criteria. ALND was omitted in 49% of these patients, and omission increased from 2018 to 2020 (44% vs. 49%, p = 0.22). CONCLUSION: Approximately one-third of patients with ≥ 3 positive SLNs do not undergo ALND; omission of ALND increased from 2018 to 2020. Studies assessing oncologic outcomes of patients with ≥ 3 positive SLNs who do and do not receive ALND are required.

International Center-Level Variation in Utilization of Completion Lymph Node Dissection and Adjuvant Systemic Therapy for Sentinel Lymph Node-Positive Melanoma at Major Referral Centers.

OBJECTIVE: The aim of this study was to determine overall trends and center-level variation in utilization of completion lymph node dissection (CLND) and adjuvant systemic therapy for sentinel lymph node (SLN)-positive melanoma. SUMMARY BACKGROUND DATA: Based on recent clinical trials, management options for SLN-positive melanoma now include effective adjuvant systemic therapy and nodal observation instead of CLND. It is unknown how these findings have shaped practice or how these contemporaneous developments have influenced their respective utilization. METHODS: We performed an international cohort study at 21 melanoma referral centers in Australia, Europe, and the United States that treated adults with SLN-positive melanoma and negative distant staging from July 2017 to June 2019. We used generalized linear and multinomial logistic regression models with random intercepts for each center to assess center-level variation in CLND and adjuvant systemic treatment, adjusting for patient and disease-specific characteristics. RESULTS: Among 1109 patients, performance of CLND decreased from 28% to 8% and adjuvant systemic therapy use increased from 29 to 60%. For both CLND and adjuvant systemic treatment, the most influential factors were nodal tumor size, stage, and location of treating center. There was notable variation among treating centers in management of stage IIIA patients and use of CLND with adjuvant systemic therapy versus nodal observation alone for similar risk patients. CONCLUSIONS: There has been an overall decline in CLND and simultaneous adoption of adjuvant systemic therapy for patients with SLN-positive melanoma though wide variation in practice remains. Accounting for differences in patient mix, location of care contributed significantly to the observed variation.

Readability Analysis of Online Breast Cancer Surgery Patient Education Materials from National Cancer Institute-Designated Cancer Centers Compared with Top Internet Search Results.

BACKGROUND: The National Institutes of Health (NIH) recommends patient education materials reflect the average reading grade level of the US population. Due to the importance of shared decision-making in breast cancer surgery, this study evaluates the reading level of patient education materials from National Cancer Institute-designated cancer centers (NCI-DCC) compared with top Internet search results. METHODS: Online materials from NCI-DCC and top Internet search results on breast cancer, staging, surgical options, and pre- and postoperative expectations were analyzed using three validated readability algorithms: Simplified Measure of Gobbledygook Readability Formula, Coleman-Liau index, and Flesch-Kincaid grade level. Mean readability was compared across source groups and information subcategories using an unpaired t-test with statistical significance set at p < 0.05. Mean readability was compared using a one-way analysis of variance. RESULTS: Mean readability scores from NCI-DCC and Internet groups ranged from a 9th-12th grade level, significantly above the NIH recommended reading level of 6th-7th grade. There was no significant difference between reading levels from the two sources. The discrepancy between actual and recommended reading level was most pronounced for "surgical options" at a 10th-12th grade level from both sources. CONCLUSIONS: Patient education materials on breast cancer from both NCI-DCC and top Internet search results were written several reading grade levels higher than the NIH recommendation. Materials should be revised to enhance patient comprehension of breast cancer surgical treatment and guide patients in this important decision-making process to ultimately improve health outcomes.

Dual JAK2/Aurora kinase A inhibition prevents human skin graft rejection by allo-inactivation and ILC2-mediated tissue repair.

Prevention of allograft rejection often requires lifelong immune suppression, risking broad impairment of host immunity. Nonselective inhibition of host T cell function increases recipient risk of opportunistic infections and secondary malignancies. Here we demonstrate that AJI-100, a dual inhibitor of JAK2 and Aurora kinase A, ameliorates skin graft rejection by human T cells and provides durable allo-inactivation. AJI-100 significantly reduces the frequency of skin-homing CLA+ donor T cells, limiting allograft invasion and tissue destruction by T effectors. AJI-100 also suppresses pathogenic Th1 and Th17 cells in the spleen yet spares beneficial regulatory T cells. We show dual JAK2/Aurora kinase A blockade enhances human type 2 innate lymphoid cell (ILC2) responses, which are capable of tissue repair. ILC2 differentiation mediated by GATA3 requires STAT5 phosphorylation (pSTAT5) but is opposed by STAT3. Further, we demonstrate that Aurora kinase A activation correlates with low pSTAT5 in ILC2s. Importantly, AJI-100 maintains pSTAT5 levels in ILC2s by blocking Aurora kinase A and reduces interference by STAT3. Therefore, combined JAK2/Aurora kinase A inhibition is an innovative strategy to merge immune suppression with tissue repair after transplantation.

The 70-gene signature test as a prognostic and predictive biomarker in patients with invasive lobular breast cancer.

PURPOSE: Genomic expression assays provide prognostic information and guide adjuvant chemotherapy decisions for patients with estrogen receptor (ER)-positive breast cancer. Few studies have evaluated the utility of such assays for invasive lobular carcinoma (ILC). The objective of this study is to evaluate the 70-gene signature test (ST) as a prognostic and predictive tool for ILC using a national cancer database. METHODS: We identified patients diagnosed with stage I-III ER-positive ILC from 2004 to 2016 using the National Cancer Database. All patients underwent 70-gene ST testing. We used the Kaplan-Meier method and Cox proportional hazard analyses to determine overall survival based on genomic risk classification. We also determined the benefit of adjuvant chemotherapy for patients with high-genomic risk ILC based on 70-gene ST testing. RESULTS: We identified 2610 patients with ILC who underwent 70-gene ST testing; 280 (11%) were classified as high genomic risk. Five-year overall survival rates were significantly worse for patients classified as high risk (83%) as compared with those classified as low risk (94%, p < 0.05). In Cox models, high genomic risk was independently associated with a significantly increased hazard of death. In our Cox models of patients who were high genomic risk, adjuvant chemotherapy was not significantly associated with improved overall survival. CONCLUSION: In this large database study, we found that the genomic risk category determined by the 70-gene ST was significantly associated with survival outcomes for patients with ILC. However, the 70-gene ST failed to predict the benefit of adjuvant chemotherapy for patients with high genomic risk.

Active surveillance of patients who have sentinel node positive melanoma: An international, multi-institution evaluation of adoption and early outcomes after the Multicenter Selective Lymphadenectomy Trial II (MSLT-2).

BACKGROUND: For patients with sentinel lymph node (SLN)-positive cutaneous melanoma, the Second Multicenter Selective Lymphadenectomy trial demonstrated equivalent disease-specific survival (DSS) with active surveillance using nodal ultrasound versus completion lymph node dissection (CLND). Adoption and outcomes of active surveillance in clinical practice and in adjuvant therapy recipients are unknown. METHODS: In a retrospective cohort of SLN-positive adults treated at 21 institutions in Australia, Europe, and the United States from June 2017 to November 2019, the authors evaluated the impact of active surveillance and adjuvant therapy on all-site recurrence-free survival (RFS), isolated nodal RFS, distant metastasis-free survival (DMFS), and DSS using Kaplan-Meier curves and Cox proportional hazard models. RESULTS: Among 6347 SLN biopsies, 1154 (18%) were positive and had initial negative distant staging. In total, 965 patients (84%) received active surveillance, 189 (16%) underwent CLND. Four hundred thirty-nine patients received adjuvant therapy (surveillance, 38%; CLND, 39%), with the majority (83%) receiving anti-PD-1 immunotherapy. After a median follow-up of 11 months, 220 patients developed recurrent disease (surveillance, 19%; CLND, 22%), and 24 died of melanoma (surveillance, 2%; CLND, 4%). Sixty-eight patients had an isolated nodal recurrence (surveillance, 6%; CLND, 4%). In patients who received adjuvant treatment without undergoing prior CLND, all isolated nodal recurrences were resectable. On risk-adjusted multivariable analyses, CLND was associated with improved isolated nodal RFS (hazard ratio [HR], 0.36; 95% CI, 0.15-0.88), but not all-site RFS (HR, 0.68; 95% CI, 0.45-1.02). Adjuvant therapy improved all-site RFS (HR, 0.52; 95% CI, 0.47-0.57). DSS and DMFS did not differ by nodal management or adjuvant treatment. CONCLUSIONS: Active surveillance has been adopted for most SLN-positive patients. At initial assessment, real-world outcomes align with randomized trial findings, including in adjuvant therapy recipients. LAY SUMMARY: For patients with melanoma of the skin and microscopic spread to lymph nodes, monitoring with ultrasound is an alternative to surgically removing the remaining lymph nodes. The authors studied adoption and real-world outcomes of ultrasound monitoring in over 1000 patients treated at 21 centers worldwide, finding that most patients now have ultrasounds instead of surgery. Although slightly more patients have cancer return in the lymph nodes with this strategy, typically, it can be removed with delayed surgery. Compared with up-front surgery, ultrasound monitoring results in the same overall risk of melanoma coming back at any location or of dying from melanoma.

The New Normal? Patient Satisfaction and Usability of Telemedicine in Breast Cancer Care.

BACKGROUND: Telemedicine was adopted to minimize exposure risks for patients and staff during the coronavirus disease 2019 pandemic. This study measured patient satisfaction and telemedicine usability in breast cancer care. METHODS: Adult breast cancer patients who had a telemedicine visit at a single academic institution (with surgical, radiation, or medical oncology) from 15 June 2020 to 4 September 2020 were surveyed anonymously. Patient and cancer characteristics were collected, and patient satisfaction and telemedicine usability were assessed using a modified Telehealth Usability Questionnaire with a 7-point Likert scale. Associations of satisfaction and usability with patient characteristics were analyzed using Wilcoxon rank-sum and Kruskal-Wallis tests. RESULTS: Of 203 patients who agreed to be contacted, 78 responded, yielding a response rate of 38%. The median age of the respondents was 63 years (range 25-83 years). The majority lived in an urban area (61%), were white (92%), and saw a medical oncologist (62%). The median patient satisfaction score was 5.5 (interquartile range [IQR] 4.25-6.25). The median telemedicine usability score was 5.6 (IQR 4.4-6.2). A strong positive correlation was seen between satisfaction and usability, with a Spearman correlation coefficient (ρ) of 0.80 (p < 0.001). Satisfaction and usability scores did not vary significantly according to patient age, race, location of residence, insurance status, previous visit commute time, oncology specialty seen, prior telemedicine visits, or whether patients were actively receiving cancer treatment. CONCLUSIONS: Breast cancer patients were satisfied with telemedicine and found it usable. Patient satisfaction and telemedicine usability should not limit the use of telemedicine in future post-pandemic breast cancer care.

Surgeon decision-making for management of positive sentinel lymph nodes in the post-Multicenter Selective Lymphadenectomy Trial II era: A survey study.

BACKGROUND AND OBJECTIVES: Completion lymph node dissection (CLND) did not improve melanoma-specific survival for patients with sentinel lymph node (SLN)-positive melanoma in the second Multicenter Selective Lymphadenectomy Trial (MSLT-II). We assessed surgeons' awareness of MSLT-II and its impact on CLND recommendations. METHODS: An anonymous online cross-sectional survey of the Society of Surgical Oncology membership evaluated surgeon thresholds in offering CLND using patient scenarios and clinicopathologic characteristics ranking. RESULTS: Of the 2881 e-mails delivered, 146 surgeons (5.1%) completed all seven scenarios. Most (129 of 131, 98%) were aware of MSLT-II and 125 (95%) found it practice-changing. Specifically, 52% (65 of 125) always, 40% usually, 6% rarely, and 3% never offered CLND before MSLT-II. Meanwhile, 4% always, 9% usually, 78% rarely, and 8% never offer CLND now, after MSLT-II (p < .0001). The most important clinicopathologic factors in determining CLND recommendations were extracapsular extension, number of positive SLN, and SLN tumor deposit size, while primary tumor mitotic index and nodal basin location were the least important. Surgical oncology fellowship training, melanoma patient volume, and academic center practice also influenced CLND recommendations. CONCLUSIONS: Most surgeon respondents are aware of MSLT-II, but its application in practice varies according to several clinicopathologic and surgeon factors.

Intraoperative inking is superior to suture marking for specimen orientation in breast cancer.

Margin status is an important indicator of residual disease after breast-conserving surgery (BCS). Intraoperatively, surgeons orient specimens to aid assessment of margins and guide re-excision of positive margins. We performed a retrospective review of BCS cases from 2013 to 2017 to compare the two specimen orientation methods: suture marking and intraoperative inking. Patients with ductal carcinoma in situ, T1/T2 invasive cancer treated with BCS were included. Rates of positive margins and residual disease at re-excision were evaluated. 189 patients underwent BCS; 83 had suture marking, 103 had intraoperative inking and 3 had un-oriented specimens. The incidence of positive margins was 29% (24 patients) in the suture marked group and 20% (21 patients) in the intraoperative inked group (P = .18). Among the 45 patients with positive margins, 60% of tumors were stage T1, 76% were node negative, 36% were palpable with median tumor size of 1.5 cm. Residual disease was identified on re-excision in 21% of the suture marked specimens and 57% of intraoperative inked specimens (P = .028). The incidence of residual cancer at re-excision for positive margins was higher for intraoperatively inked versus suture marked specimens. This finding suggests that intraoperative inking is more effective at guiding re-excision of positive margins.

Trends in lobular carcinoma in situ management: endocrine therapy use in California and New Jersey.

PURPOSE: The diagnosis of lobular carcinoma in situ (LCIS) is a strong risk factor for breast cancer. Endocrine therapy (ET) for LCIS has been shown to decrease breast cancer risk substantially. The purpose of this study was to evaluate the trends of ET use for LCIS in two large geographic locations. PATIENTS AND METHODS: We identified women, ages 18 through 75, with a microscopic diagnosis of LCIS in California (CA) and New Jersey (NJ) from 2004 to 2014. We evaluated trends in unadjusted ET rates during the study period and used logistic regression to evaluate the relationship between patient, tumor, and treatment characteristics, and ET use. RESULTS: We identified 3,129 patients in CA and 2,965 patients in NJ. The overall use of ET during the study period was 14%. For the combined sample, women in NJ were significantly less likely to utilize ET then their counterparts in CA (OR 0.77, CI 0.66-0.90, NJ vs. CA). In addition, patients in the later year period (OR 1.27, CI 1.01-1.59, 2012-2014 vs. 2004-2005) and women who received an excisional biopsy (OR 2.35, CI 1.74-3.17), were more likely to utilize ET. Uninsured women were less likely to receive ET (OR 0.61, CI 0.44-0.84, non-insured vs. insured status). CONCLUSIONS: We observed that an increasing proportion of women are using ET for LCIS management, but geographical differences exist. Health insurance status played an important role in the underutilization of ET. Further research is needed to assess patient outcomes given the variations in management of LCIS.

Tumor grade and progesterone receptor status predict 21-gene recurrence score in early stage invasive breast carcinoma.

PURPOSE: The 21-gene recurrence score (RS) assay is increasingly utilized to predict the risk of recurrence in early stage estrogen receptor (ER)-positive breast cancer. We hypothesize that tumor grade and progesterone receptor (PR) status predict RS categorization. METHODS: We identified women between the ages of 18 and 74 years with stage I or II, ER-positive, invasive carcinoma of the breast from the Surveillance Epidemiology End-Results database from 2010 to 2013. Multivariable logistic regression was performed to determine factors associated with high-risk RS. RESULTS: We identified 42,530 patients that met inclusion criteria. Multivariable logistic regression demonstrated that grade I tumors [OR (odds ratio) 0.33, 95% CI (confidence interval) 0.31-0.37] and PR positive (PR+) status (OR 0.16, 95% CI 0.15-0.17) were significantly less likely to be associated with high-risk RS. Of patients with grade I PR+ tumors, 1% was in the high-risk group by the traditional cutoffs and 4% was in the high-risk group by the TAILORx cutoffs. The percentage of patients with high-risk RS remained low for grade I PR+ tumors regardless of age, race, tumor size, and lymph node status. CONCLUSIONS: We found that grade I PR+ tumors are associated a < 5% probability of having high-risk RS regardless of other patient demographic or pathologic factors. This suggests that the histologic factors of grade and PR status should be taken into consideration before ordering the 21-gene recurrence score assay.

Relative effectiveness of adjuvant chemotherapy for invasive lobular compared with invasive ductal carcinoma of the breast.

BACKGROUND: Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) have distinct clinical, pathologic, and genomic characteristics. The objective of the current study was to compare the relative impact of adjuvant chemotherapy on the survival of patients with ILC versus those with IDC. METHODS: Women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 1 (HER2) -negative, stage I/II IDC and ILC who received endocrine therapy were identified from the 2000 to 2014 California Cancer Registry. Patient, tumor, and treatment characteristics were collected. Ten-year overall survival (OS) was estimated using the Kaplan-Meier method and Cox proportional-hazards modeling. RESULTS: In total, 32,997 women with IDC and 4638 with ILC were identified. The receipt of chemotherapy significantly decreased during the study for both subtypes. For patients with IDC, the 10-year OS rate was 95% among those who received endocrine therapy alone versus 93% (P < .01) among those who received endocrine therapy plus chemotherapy. For patients with ILC, the 10-year OS rate was 94% among those who received endocrine therapy alone versus 92% (P < .01) among those who received endocrine therapy plus chemotherapy. After adjusting for patient and treatment factors, adjuvant chemotherapy was significantly associated with a decreased 10-year hazard of death for patients with IDC (hazard ratio, 0.83; 95% confidence interval, 0.74-0.92). In contrast, adjuvant chemotherapy was not independently associated with the adjusted 10-year hazard of death for patients with ILC (hazard ratio, 1.14; 95% confidence interval, 0.90-1.46). CONCLUSIONS: Adjuvant chemotherapy was not associated with improved OS for patients with ER-positive, HER2-negative, stage I/II ILC. Avoidance of ineffective chemotherapy will markedly reduce the adverse effects and economic burden of breast cancer treatment for a large proportion of patients with breast cancer. Cancer 2017;123:3015-21. © 2017 American Cancer Society.

Impact of the 21-gene recurrence score on outcome in patients with invasive lobular carcinoma of the breast.

PURPOSE: Invasive lobular carcinoma (ILC) of the breast has unique clinicopathologic characteristics, compared to invasive ductal carcinoma. The role of the 21-gene Recurrence Score (RS) has not been clearly defined for ILC. We sought to determine the prognostic value of RS and the impact of adjuvant chemotherapy on long-term survival in patients with ILC. METHODS: Utilizing the Surveillance, Epidemiology and End Results database from 2004 to 2013, we identified records of women aged 18-74 years, diagnosed with estrogen receptor (ER)-positive ILC (stage I to III) with RS available. We categorized patients into risk groups based on the traditional RS cutoffs and into those of the Trial Assigning Individualized Options for Treatment (TAILORx). Five-year breast cancer-specific survival (BCSS) was analyzed using the Kaplan-Meier method and Cox proportional hazards models. RESULTS: Of the 7316 women included, 21% were in the low-risk; 71%, intermediate-risk; and 8%, high-risk groups as per TAILORx RS cutoffs. The 5-year BCSS was 99% in the low-risk, 99% in the intermediate-risk, and 96% in the high-risk groups. A high-risk RS as per TAILORx cutoff was independently associated with increased mortality (hazard ratio [HR] of death 2.37, 95% confidence interval [CI] 1.14-4.95) when compared to a low-risk RS. In both the high-risk and intermediate-risk groups, adjuvant chemotherapy was not significantly associated with the HR of death (high-risk, HR 1.14, 95% CI 0.55-2.38; intermediate-risk, HR 1.08, 95% CI 0.62-1.87). CONCLUSION: For patients with ER-positive ILC, 8% were in the high-risk and 72% were in the intermediate-risk groups as per the TAILORx RS cutoffs. In the high-risk group, the RS predicted a lower 5-year BCSS. Adjuvant chemotherapy did not seem to confer a survival benefit for either the intermediate- or the high-risk cohorts.

Survival Rates for Patients with Resected Gastric Adenocarcinoma Finally have Increased in the United States.

BACKGROUND: In the United States, the overall survival rates for gastric adenocarcinoma have remained low, with surgical resection as the only therapy for many patients. Given the advances in multimodality treatment and the development of guidelines recommending adequate lymph node evaluation, the authors determined whether overall survival rates for patients with gastric adenocarcinoma have increased in the United States. METHODS: The study used the Surveillance Epidemiology and End Results (SEER) database to examine overall survival for patients with the diagnosis of gastric adenocarcinoma between 1988 and 2013. The study cohort was divided into five periods: 1988-1992, 1993-1997, 1998-2002, 2003-2007, and 2008-2013. Kaplan-Meier methods and Cox proportional hazards modeling were used to determine the effect that year of diagnosis had on overall survival. RESULTS: The diagnosis was determined for 13,470 patients between 1988 and 2013. The use of radiation therapy and the proportion of patients who had at least 15 lymph nodes evaluated significantly increased during the study period. Unadjusted Kaplan-Meier estimates demonstrated significantly better survival rates for the patients with a diagnosis of gastric cancer in the later periods (2003-2007 and 2008-2013) than for those in the three earlier periods. In our Cox proportional hazards model, recent period was associated with a significantly lower hazard of 5-year mortality. CONCLUSION: This analysis demonstrated for the first time that gastric cancer survival rates have significantly improved in the United States during the past 2 decades. This observation likely reflects improved adherence to cancer treatment guidelines, including adequate lymph node evaluation and delivery of adjuvant treatment more consistently.