Should breast surgery be considered for patients with de novo metastatic inflammatory breast cancer?

INTRODUCTION: We aimed to identify factors predicting surgery for de novo stage IV inflammatory breast cancer (IBC) and determine the association of surgery with overall survival (OS). METHODS: Female patients with unilateral AJCC clinical stage IV IBC treated 2010-2018 in the NCDB were identified. Logistic regression and multivariable proportional Cox hazards regressions determined factors associated with treatment and OS. RESULTS: Of 1049 patients, 29.1% underwent breast surgery (BS) and 70.9% had no surgery (NS). Increasing age and more recent treatment year were significantly associated with NS. 2-Year OS was superior in BS patients (71% vs 38% NS). Single-site and bone-only metastasis had no association with treatment type or OS. CONCLUSION: Contrary to guidelines, 1/3 of de novo stage IV IBC patients underwent BS, and had an independent OS benefit irrespective of extent or site of metastasis. Further research is needed to determine which patients with stage IV IBC should undergo BS.

Using MammaPrint on core needle biopsy to guide the need for axillary staging during breast surgery.

BACKGROUND: At present, the only opportunity to omit axillary staging is with Choosing Wisely criteria for women ages >70 y with cT1 2N0 estrogen receptor-positive/human epidermal growth factor receptor 2-negative breast cancer. However, many women are diagnosed when pathologic node status-negative, raising the question of additional opportunities to omit sentinel lymph node biopsy. We sought to investigate the association between MammaPrint, a genomic test that estimates estrogen receptor-positive breast cancer recurrence risk, and pathologic node status, with the aim that low-risk MammaPrint could be considered for omission of sentinel lymph node biopsy if associated with pathologic node status-negative. METHODS: A single-institution database was queried for all women with cT1 2N0 estrogen receptor-positive/human epidermal growth factor receptor 2-negative invasive breast cancer with breast surgery as their first treatment and MammaPrint performed from 2020 to 2021. Patient and tumor factors, including MammaPrint score, were compared with axillary node status for correlation. RESULTS: A total of 668 women met inclusion criteria, with a median age of 66 y. MammaPrint was low-risk luminal A in 481 (72%) and high-risk luminal B in 187 (28%). At the time of breast surgery, 588 (88%) had sentinel lymph node biopsy, 27 (4%) had axillary lymph node dissection, and 53 (7.9%) had no axillary staging. Most women in both the pathologic node status-negative and pathologic node status-positive cohorts had low-risk MammaPrint (355 [73.3%] pathologic node status-negative vs 91 [69.5%] pathologic node status-positive), and women with low-risk MammaPrint did not have a significantly lower risk of pathologic node status-positive (P = .377). CONCLUSION: Low-risk MammaPrint does not predict lower risk of pathologic node status-positive breast cancer. Based on our results, genomic testing does not appear to provide additional personalization for the ability to omit sentinel lymph node biopsy for patients outside of the Choosing Wisely guidelines.

Validation of the PREDICT Prognostication Tool in US Patients With Breast Cancer.

BACKGROUND: PREDICT is an online prognostication tool derived from breast cancer registry information on approximately 6,000 women treated in the United Kingdom that estimates the postsurgical treatment benefit of surgery alone, chemotherapy, trastuzumab, endocrine therapy, and/or adjuvant bisphosphonates in early-stage breast cancer. Our aim was to validate the PREDICT algorithm in predicting 5- and 10-year overall survival (OS) probabilities using real-world outcomes among US patients with breast cancer. METHODS: A retrospective study was performed including women diagnosed with unilateral breast cancer in 2004 through 2012. Women with primary unilateral invasive breast cancer were included. Patients with bilateral or metastatic breast cancer, no breast surgery, or missing critical clinical information were excluded. Prognostic scores from PREDICT were calculated and external validity was approached by assessing statistical discrimination through area under time-dependent receiver-operator curves (AUC) and comparing the predicted survival to the observed OS in relevant subgroups. RESULTS: We included 708,652 women, with a median age of 58 years. Most patients were White (85.4%), non-Hispanic (88.4%), and diagnosed with estrogen receptor-positive breast cancer (79.6%). Approximately 50% of patients received adjuvant chemotherapy, 67% received adjuvant endocrine therapy, 60% underwent a partial mastectomy, and 59% had 1 to 5 axillary sentinel nodes removed. Median follow-up time was 97.7 months. The population's 5- and 10-year OS were 89.7% and 78.7%, respectively. Estimated 5- and 10-year median survival with PREDICT were 88.3% and 73.8%, and an AUC of 0.77 and 0.76, respectively. PREDICT performed most poorly in patients with high Charlson-Deyo comorbidity scores (2-3), where PREDICT overestimated OS. Sensitivity analysis by year of diagnosis and HER2 status showed similar results. CONCLUSIONS: In this prognostic study utilizing the National Cancer Database, the PREDICT tool accurately predicted 5- and 10-year OS in a contemporary and diverse population of US patients with nonmetastatic breast cancer.

Summary: Appropriate Use Criteria for Lymphoscintigraphy in Sentinel Node Mapping and Lymphedema/Lipedema.

Expert representatives from 11 professional societies, as part of an autonomous work group, researched and developed appropriate use criteria (AUC) for lymphoscintigraphy in sentinel lymph node mapping and lymphedema. The complete findings and discussions of the work group, including example clinical scenarios, were published on October 8, 2022, and are available at https://www.snmmi.org/ClinicalPractice/content.aspx?ItemNumber=42021 The complete AUC document includes clinical scenarios for scintigraphy in patients with breast, cutaneous, and other cancers, as well as for mapping lymphatic flow in lymphedema. Pediatric considerations are addressed. These AUC are intended to assist health care practitioners considering lymphoscintigraphy. Presented here is a brief overview of the AUC, including the rationale and methodology behind development of the document. For detailed findings of the work group, the reader should refer to the complete AUC document online.

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.

Trends in surgery and survival for T1-T2 male breast cancer: A study from the National Cancer Database.

BACKGROUND: Despite evidence that early-stage male breast cancer (MBC) can be treated the same as in females, we hypothesized that men undergo more extensive surgery. METHODS: Patients with clinical T1-2 breast cancer were identified in the National Cancer Database 2004-2016. Trends in surgery type and overall survival were compared between sexes. RESULTS: Of 9,782 males and 1,078,105 females, most were cN0 with AJCC stage I/II disease. Unilateral mastectomy was most common in men (67.1% vs. 24.1%, p < 0.001) and partial mastectomy in women (64.7% vs. 26.4%, p < 0.001), with no significant change over time. Over 1/3 of men received ALND in 2016. While overall survival was superior in females (HR 0.83, 95% CI 0.73-0.94, p = 0.003), partial mastectomy was associated with a 42% reduction in mortality risk for males (HR 0.58, 95% CI 0.4-0.8, p = 0.003). CONCLUSIONS: De-escalation of surgery could be considered for MBC to improve survival and align with current standards of care.

Modeling the COVID Pandemic: Do Delays in Surgery Justify Using Stereotactic Radiation to Treat Low-Risk Early Stage Non-Small Cell Lung Cancer?

INTRODUCTION: It was suggested that stereotactic radiation (SBRT) is an "alternative if no surgical capacity is available" for non-small cell lung cancer (NSCLC) care during the COVID-19 pandemic. The purpose of this study was to compare the oncologic outcomes of delayed surgical resection and early SBRT among operable patients with early stage lung cancer. METHODS: The National Cancer Database was queried for patients with cT1aN0M0 NSCLC who underwent surgery or SBRT (2010-2016) with no comorbidity. Patients with any comorbidities or age >80 were excluded. The outcome of interest was overall survival. Delays in surgical care were modeled using different times from diagnosis to surgery. A 1:1 propensity match was performed and survival was analyzed using multivariable Cox regression. RESULTS: Of 6720 healthy cT1aN0M0 NSCLC patients, 6008 (89.4%) received surgery and 712 (10.6%) received SBRT. Among surgery patients, time to surgery >30 d was associated with inferior survival (HR > 1.4, P ≤ 0.013) compared with patients receiving surgery ≤14 d. Relative to SBRT, surgery demonstrated superior survival at all time points evaluated: 0-30 d, 31-60 d, 61-90 d, and >90 d (all P < 0.001). Among a propensity-matched cohort of 256 pairs of patients, delayed surgery (>90 d) remained association with better overall survival relative to early SBRT (5-year survival 76.9% versus 32.3%, HR = 0.266, P < 0.001). CONCLUSIONS: Although longer time to surgery is associated with inferior survival among surgery patients, delayed surgery is superior to early SBRT. Surgical resection should remain the standard of care to treat operable early stage lung cancer despite delays imposed by the COVID-19 pandemic.

Detection of SARS-CoV-2 RNA in wastewater and comparison to COVID-19 cases in two sewersheds, North Carolina, USA.

Wastewater surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be useful for monitoring population-wide coronavirus disease 2019 (COVID-19) infections, especially given asymptomatic infections and limitations in diagnostic testing. We aimed to detect SARS-CoV-2 RNA in wastewater and compare viral concentrations to COVID-19 case numbers in the respective counties and sewersheds. Influent 24-hour composite wastewater samples were collected from July to December 2020 from two municipal wastewater treatment plants serving different population sizes in Orange and Chatham Counties in North Carolina. After a concentration step via HA filtration, SARS-CoV-2 RNA was detected and quantified by reverse transcription droplet digital polymerase chain reaction (RT-ddPCR) and quantitative PCR (RT-qPCR), targeting the N1 and N2 nucleocapsid genes. SARS-CoV-2 RNA was detected by RT-ddPCR in 100 % (24/24) and 79 % (19/24) of influent wastewater samples from the larger and smaller plants, respectively. In comparison, viral RNA was detected by RT-qPCR in 41.7 % (10/24) and 8.3 % (2/24) of samples from the larger and smaller plants, respectively. Positivity rates and method agreement further increased for the RT-qPCR assay when samples with positive signals below the limit of detection were counted as positive. The wastewater data from the larger plant generally correlated (⍴ ~0.5, p < 0.05) with, and even anticipated, the trends in reported COVID-19 cases, with a notable spike in measured viral RNA preceding a spike in cases when students returned to a college campus in the Orange County sewershed. Correlations were generally higher when using estimates of sewershed-level case data rather than county-level data. This work supports use of wastewater surveillance for tracking COVID-19 disease trends, especially in identifying spikes in cases. Wastewater-based epidemiology can be a valuable resource for tracking disease trends, allocating resources, and evaluating policy in the fight against current and future pandemics.

Age disparities in triple-negative breast cancer treatment and outcomes: An NCDB analysis.

BACKGROUND: Race, access to care, and molecular features result in outcome disparities in triple-negative breast cancer (TNBC). We sought to determine the role of age in TNBC disparity by hypothesizing that younger patients receive more comprehensive treatment, resulting in survival differences. METHODS: The National Cancer Database was used to identify women with unilateral TNBC treated from 2005 through 2017. Patients were stratified by age (≤40, 41-70, >70); demographics, clinical characteristics, and treatment factors were compared. Logistic regression determined factors associated with treatment received. Survival outcomes were analyzed using a stratified log-rank test. RESULTS: Of the 168,715 patients, 16,287 (9.6%) were ≤40 years. Patients ≤40 were significantly more likely to present at higher clinical stage (P < .001) and receive neoadjuvant chemotherapy (NAC, P < .001). Bilateral mastectomy was the most common surgery for patients ≤40 (37%), whereas partial mastectomy was most often used in patients 41 to 70 years old (48%) and those >70 (49%) (P < .001). Patients ≤40 years were significantly more likely to undergo both NAC and mastectomy than those >40 (odds ratio 1.5, both P < .05) despite a greater in-breast tumor response in the youngest patients. Patients treated with mastectomy and axillary lymph node dissection had inferior survival outcomes compared to those treated with partial mastectomy and sentinel lymph node biopsy across all 3 age groups (P < .001). CONCLUSION: The clinical characteristics of TNBC differ significantly at the extremes of age, likely driving treatment decisions. Although patients ≤40 present with a more advanced disease and appropriately receive NAC, they also undergo more extensive surgery that does not yield a survival benefit. Further research is needed to determine if age disparity is due to oncologic factors or patient and provider preferences.

Guideline-Consistent Treatment for Inflammatory Breast Cancer Provides Associated Survival Benefit Independent of Age.

BACKGROUND: Guideline-consistent treatment (GCT) for inflammatory breast cancer (IBC) includes neoadjuvant chemotherapy (NAC), modified radical mastectomy (MRM), and radiation. We hypothesized that younger patients more frequently receive GCT, resulting in survival differences. METHODS: Using the National Cancer Database (2004-2018), female patients with unilateral IBC (by histology code and clinical stage T4d) were stratified by age (< 50, 50-65, > 65 years). Factors associated with NAC, MRM, radiation, and "GCT" (defined as all three treatments) were identified using multivariable logistic regression. Multivariable Cox proportional hazards regression identified predictors of overall survival. RESULTS: Of 3278 IBC patients, 30% were younger than 50 years, 44% were 50-65 years of age, and 26% were older than 65 years. The youngest group comprised the greatest proportion of non-White patients ([35%] vs. [29%] age 50-65 years and [23%] age > 65 years, p < 0.001) and was most often treated at academic facilities ([33%] vs. [28%] age 50-65 years; and [23%] age > 65, p < 0.001). Patients older than 65 years received NAC, MRM, and radiation less frequently, and only 35% underwent GCT (vs. [57%] age 50-65 years and [52%] age < 50 years; p < 0.001). On multivariable logistic regression, age older than 65 years independently predicted omission of NAC (odds ratio [OR], 0.36), MRM (OR, 0.56), and radiation (OR, 0.56) (all p < 0.001), and patients older than 65 years also were less likely to undergo GCT than patients 50-65 years of age (OR, 0.65; p = 0.001). GCT was associated with superior overall survival in all three age groups ([hazard ratio {HR}, 0.61] age < 50 years, [HR, 0.62] age 50-65 years, [HR, 0.53] age > 65 years; all p < 0.001). CONCLUSION: Advanced age alone should not limit receipt of GCT for IBC. Multimodal care should be performed for IBC patients of all ages to improve oncologic outcomes for this aggressive breast cancer subtype.

Minimally Invasive Mastectomy Could Achieve Non-inferior Oncological Outcome in Appropriately Selected Patients: Propensity Matched Analysis of the National Cancer Database.

BACKGROUND: Minimally invasive mastectomy (MIM) was emerged as an approach to decrease morbidity and increase patient satisfaction through improved cosmetic results; however, there is a paucity of data regarding the long-term oncologic outcomes of these minimally invasive approaches. METHODS: Patients who underwent mastectomy procedures were identified in the National Cancer Database (2010-2016). Patients were categorized as MIM or open mastectomy. A 1:1 propensity match was performed to balance the bias on reconstruction, nipple sparing, lymph node procedures, and other confounding factors between the cohorts. Short- and long-term outcomes were compared. RESULTS: A total of 328 811 patients met the criteria: 327 643 (99.6%) received open mastectomy and 1168 (.4%) received MIM. Propensity match identified 384 "pairs" of MIM and open mastectomy patients. Among them, MIM was associated with shorter length of stay (LOS) (mean 1.3 vs. 1.06 days, P = .003). No differences were observed in the rates of positive margins, unplanned readmissions, or 90-day mortality between the 2 operative approaches. Overall survival (OS) was equivalent between MIM and open mastectomy patients. Cox proportional hazard regression showed no effect of the procedure performed on OS. DISCUSSION: MIM is associated with shorter LOS, and it is non-inferior to open mastectomy in terms of other short-term outcomes and long-term oncologic survival outcomes. These data suggest that MIM may be considered in appropriately selected breast cancer patients as an additional approach to the community.

Adjuvant trastuzumab with or without chemotherapy in stage 1 pT1N0 HER2+ breast cancer: a National Cancer Database analysis.

PURPOSE: Approximately 20% of all breast cancers (BC) are HER2 amplified. In the APT trial, weekly paclitaxel/trastuzumab in node negative HER2+ BC with tumors < 3 cm was associated with a 7-year invasive disease-free survival of 93%. However, this was in the context of a non-randomized trial, and for pT1N0 HER2+ BC it remains unclear whether HER2 monotherapy would provide similar clinical outcomes to chemo-HER2 therapy. We hypothesized that adjuvant chemo-HER2 therapy would be associated with a modestly improved overall survival compared to HER2 monotherapy in patients with tumors < 2 cm. METHODS: In the National Cancer Database (2004-2017), patients with a primary diagnosis of pT1N0M0 HER2+ BC, were separated into two groups: (i) HER2 monotherapy, i.e., trastuzumab, and (ii) chemo-HER2 therapy. A 3:1 propensity match was performed to balance patient selection bias between the two different cohorts. Long-term overall survival (OS) was compared between both groups. RESULTS: A total of 23,281 patients met the criteria. 22,268 (96.7%) received chemo-HER2 therapy and 1013 (4.4%) received HER2 monotherapy. Propensity match identified 1995 patients who received chemo-HER2 therapy, and 666 who received HER2 monotherapy. After matching, adjuvant chemo-HER2 therapy was associated with a modest survival advantage over HER2 monotherapy (5-year OS 94.1% vs. 90.6%, P = 0.041). CONCLUSIONS: Even though there is a modest OS advantage favoring adjuvant chemo-HER2 therapy in patients with pT1N0 HER2+ BC, HER2 monotherapy was associated with 5-year OS > 90%. Therefore, in select patients who have contraindications for cytotoxic chemotherapy, or decline adjuvant chemotherapy altogether, adjuvant trastuzumab monotherapy appears to be a reasonable alternative.

Neoadjuvant Endocrine Therapy as an Alternative to Neoadjuvant Chemotherapy Among Hormone Receptor-Positive Breast Cancer Patients: Pathologic and Surgical Outcomes.

BACKGROUND: Neoadjuvant chemotherapy (NCT) is considered more effective in downstaging hormone receptor-positive (HR+) breast cancer than neoadjuvant endocrine therapy (NET), particularly in node-positive disease. This study compared breast and axillary response and survival after NCT and NET in HR+ breast cancer. METHODS: Based on American College of Surgeons Oncology Group (ACOSOG) Z1031 criteria, women age 50 years or older with cT2-4 HR+ breast cancer who underwent NET or NCT and surgery were identified in the National Cancer Database 2010-2016. Chi-square and logistic regression analysis determined differences between the NCT and NET groups and therapy response, including downstaging and pathologic complete response (pCR, ypT0/is and ypN0). RESULTS: Of 19,829 patients, 14,025 (70.7%) received NCT and 5804 (29.3%) received NET. The NET patients were older (mean age, 68.9 vs. 60.3; P < 0.001) and had greater comorbidity (1+ Charlson-Deyo score, 21% vs. 16%; P < 0.001). Therapy achieved T downstaging (any) for 58% of the patients with NCT versus 40.5% of the patients with NET, and in-breast pCR was achieved for 9.3% of the NCT versus 1.3% of the NET patients (P < 0.001). Approximately half of the mastectomy procedures could have been potentially avoided for the patients with in-breast pCR (53.6% of the NCT and 43.8% of the NET patients). For the cN+ patients, N downstaging (any) was 29% for the NCT patients versus 18.3% for the NET patients (P < 0.001), and nodal pCR was achieved for 20.3% of the NCT versus 13.5% of the NET patients (P < 0.001). Among those with nodal pCR, axillary lymph node dissection (ALND) still was performed for 56% of the patients after NCT and 45% of the patients after NET. CONCLUSIONS: Although the response rates after NCT were higher, NET achieved both T and N downstaging and pCR. Neoadjuvant endocrine therapy can be used to de-escalate surgery for patients who cannot tolerate NCT or when chemotherapy may not be effective based on genomic testing.

Behavioral Implications of the Complete Absence of Guests on a Zoo-Housed Gorilla Troop.

Research conducted on the effects that zoo visitors have on primate behavior has yielded inconsistent patterns. This study aims to contribute to the growing body of literature regarding visitor effects on zoo-housed primate's activity budgets, with the purpose of quantifying the behavioral variability under two conditions: guest presence and guest absence. Due to the COVID-19 pandemic, many zoos were closed to the public for varying lengths of time. The Buffalo Zoo was closed to guests for an 18-week period including the summer of 2020, which allowed us to effectively control for zoo guest presence. This case report compares data on the zoo's gorilla troop from the same time period in 2019. We found inconsistent results, similar to prior studies conducted with zoo-housed gorilla troops. Most gorillas were observed foraging less and exhibiting more inactivity in 2020, whereas the adult male silverback showed the opposite pattern. Abnormal or undesirable behaviors were performed less frequently when guests were absent however, these differences were not significant. We encourage others to compare behavior patterns during the pandemic shutdown to add to our knowledge base of visitor effects. We suggest that researchers do not try and generalize their individual and troop results to the entire population of gorillas in managed care, as both intrinsic and extrinsic factors contribute to individual differences in behavioral response.

Limited Reporting of Histopathologic Details in a Multi-Institutional Academic Cohort of Phyllodes Tumors: Time for Standardization.

BACKGROUND: Phyllodes tumors are rare fibroepithelial neoplasms that are classified by tiered histopathologic features. While there are protocols for the reporting of cancer specimens, no standardized reporting protocol exists for phyllodes. METHODS: We performed an 11-institution contemporary review of phyllodes tumors. Granular histopathologic details were recorded, including the features specifically considered for phyllodes grade classification. RESULTS: Of 550 patients, median tumor size was 3.0 cm, 68.9% (n = 379) of tumors were benign, 19.6% (n = 108) were borderline, and 10.5% (n = 58) were malignant. All cases reported the final tumor size and grade classification. Complete pathologic reporting of all histopathologic features was present in 15.3% (n = 84) of cases, while an additional 35.6% (n = 196) were missing only one or two features in the report. Individual details regarding the degree of stromal cellularity was not reported in 53.5% (n = 294) of cases, degree of stromal atypia in 58.0% (n = 319) of cases, presence of stromal overgrowth in 56.2% (n = 309) of cases, stromal cell mitoses in 37.5% (n = 206) of cases, and tumor border in 54.2% (n = 298) of cases. The final margin status (negative vs. positive) was omitted in only 0.9% of cases, and the final negative margin width was specifically reported in 73.8% of cases. Reporting of details was similar across all sites. CONCLUSION: In this academic cohort of phyllodes tumors, one or more histopathologic features were frequently omitted from the pathology report. While all features were considered by the pathologist for grading, this limited reporting reflects a lack of reporting consensus. We recommend that standardized reporting in the form of a synoptic-style cancer protocol be implemented for phyllodes tumors, similar to other rare tumors.