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.

How Often Does Retrieval of a Clipped Lymph Node Change Adjuvant Therapy Recommendations? A Prospective, Consecutive, Patient Cohort Study.

BACKGROUND: Prior studies examining sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NAC) for cN1 patients have demonstrated that 20% of biopsied, clipped lymph nodes (cLNs) are nonsentinel lymph nodes (non-SLNs). Our goal was to determine how often the cLN was a non-SLN among both cN0 and cN1 patients and how often cLN pathology impacted management. METHODS: Overall, 238 patients treated with NAC and surgery January 2019 to June 2020 were prospectively examined. Patients underwent routine axillary ultrasound, biopsy of suspicious nodes, and clip placement. Radioactive iodine-125 seed localization of the cLN was performed in cN1 patients only. Isolated tumor cells (ITCs) were considered node positive (ypN+) for both cN0 and cN1 cohorts. Chart review was performed to determine if cLNs were non-SLN and their ypN status. RESULTS: Of 118 cN0 patients, 115 of 118 (97%) underwent successful SLNB, 33 of whom had a cLN present; 21 of 33 (64%) cLNs were non-SLNs. Overall, 9 of 118 (8%) were ypN+; no cLN was ypN+ without additional +SLNs. Of 120 cN1 patients, 104 of 120 (87%) converted to cN0, 98 of 104 (94%) of which had attempted SLNB, and 95 of 98 (97%) successfully mapped. The cLN was a non-SLN in 18 of 95 (19%). Overall, 58 of 104 (56%) cN1 patients were ypN+. One patient had a positive cLN in the absence of +SLNs. This patient underwent axillary lymph node dissection (ALND); adjuvant treatment recommendations were unchanged. CONCLUSIONS: The cLN was a non-SLN in 19% of cN1 patients. cLN pathology did not impact adjuvant therapy recommendations, calling into question the utility of routinely clipping biopsied lymph nodes.

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.

Germline Genetic Mutations in a Multi-center Contemporary Cohort of 550 Phyllodes Tumors: An Opportunity for Expanded Multi-gene Panel Testing.

BACKGROUND: A paucity of data exists regarding inherited mutations associated with phyllodes tumors (PT); however, some are reported (TP53, BRCA1, and RB1). A PT diagnosis does not meet NCCN criteria for testing, including within Li-Fraumeni Syndrome (TP53). We sought to determine the prevalence of mutations associated with PT. METHODS: We performed an 11-institution review of contemporary (2007-2017) PT practice. We recorded multigenerational family history and personal history of genetic testing. We identified patients meeting NCCN criteria for genetic evaluation. Logistic regression estimated the association of select covariates with likelihood of undergoing genetic testing. RESULTS: Of 550 PT patients, 59.8% (n = 329) had a close family history of cancer, and 34.0% (n = 112) had ≥ 3 family members affected. Only 6.2% (n = 34) underwent genetic testing, 38.2% (n = 13) of whom had only BRCA1/BRCA2 tested. Of 34 patients tested, 8.8% had a deleterious mutation (1 BRCA1, 2 TP53), and 5.9% had a BRCA2 VUS. Of women who had TP53 testing (N = 21), 9.5% had a mutation. Selection for testing was not associated with age (odds ratio [OR] 1.01, p = 0.55) or PT size (p = 0.12) but was associated with grade (malignant vs. benign: OR 9.17, 95% CI 3.97-21.18) and meeting NCCN criteria (OR 3.43, 95% confidence interval 1.70-6.94). Notably, an additional 86 (15.6%) patients met NCCN criteria but had no genetic testing. CONCLUSIONS: Very few women with PT undergo germline testing; however, in those selected for testing, a deleterious mutation was identified in ~ 10%. Multigene testing of a PT cohort would present an opportunity to discover the true incidence of germline mutations in PT patients.

Bilateral mastectomy operations and the role for the cosurgeon technique: A Nationwide analysis of surgical practice patterns.

Traditionally, bilateral mastectomy (BM) operations are performed by a single surgeon but a two-attending co-surgeon technique (CST) has been described. A questionnaire was sent to members of the American Society of Breast Surgeons to assess national BM practices and analyze utilization and perceived benefits of the CST. Among surgeons responding, most continue to use the single-surgeon approach for BMs; however, 14.1% utilize the CST and up to 31% are interested in future CST use. Time savings, mentorship, cost savings, and opportunity to learn new techniques were identified as perceived CST advantages.

Impact of Residual Nodal Disease Burden on Technical Outcomes of Sentinel Lymph Node Biopsy for Node-Positive (cN1) Breast Cancer Patients Treated with Neoadjuvant Chemotherapy.

BACKGROUND: Recent trials have demonstrated the feasibility of sentinel lymph node biopsy (SLNB) for cN1 breast cancer patients after neoadjuvant chemotherapy (NAC). This study evaluated the technical outcomes of SLNB by residual nodal disease volume. METHODS: From a prospective database, cT1-3 cN1 patients receiving NAC and surgery from 2016 to 2017 were identified. Performance measures of post-NAC physical exam and imaging-based axillary assessment were compared. For the patients who converted to cN0 and underwent SLNB, adequate mapping (defined as ≥ 3 SLN) and the false-negative rate (FNR) of intraoperative SLN evaluation were assessed by residual nodal disease volume (ypN1-3 vs ypN0[i+]/ypN1mi vs ypN0). RESULTS: Of 156 cT1-3 cN1 patients, 96 converted to cN0 and underwent SLNB. Adequate mapping was achieved for 64 patients (66.7%) and was not associated with nodal volume (p = 0.12). The FNR of the intraoperative SLN evaluation was 37.8%, and smaller nodal volume was associated with FNR (p < 0.01). Of 36 patients (37.5%) who achieved an axillary pathologic complete response, 24 (66.7%) had three or more negative SLNs and were safely spared axillary lymph node dissection (ALND). The positive predictive values of physical exam versus imaging-based post-NAC nodal assessment were respectively 88% and 69.8%. CONCLUSIONS: This study showed SLNB to be an effective tool for minimizing axillary surgery in cN1 patients treated with NAC. However, important technical limitations exist, such as inability to identify three SLNs in more than two-thirds of patients and high-false negative rates for intraoperative SLN evaluation, particularly for patients with small residual nodal volumes. Preoperative counseling should include realistic assessment of the potential need for ALND in this population.

Bilateral mastectomies: can a co-surgeon technique offer improvements over the single-surgeon method?

PURPOSE: Bilateral mastectomy (BM) is traditionally performed using a single-surgeon (SS) technique (SST); a co-surgeon (CS) technique (CST), where each attending surgeon concurrently performs a unilateral mastectomy, offers an alternative approach. We sought to compare the CST and SST for BM with respect to operative times and complications. METHODS: Patients undergoing BM without reconstruction at our institution between 2005 and 2015 were identified using operative caselogs and stratified into CS- and SS-cohorts. Operative time (OT; incision to closure) was calculated. Patient age, cancer presence/stage, hormone receptor/BRCA status, breast weight, axillary procedure, and 30-day complications were extracted. Differences in OT, complications, and demographics between cohorts were assessed with t tests and Chi-square tests. A multivariate linear regression model was fit to identify factors independently associated with OT. RESULTS: Overall, 109 BM cases were identified (CS, n = 58 [53.2%]; SS, n = 51 [46.8%]). Average duration was significantly shorter for the CST by 33 min (21.6% reduction; CS: 120 min vs. SS: 153 min, p < 0.001), with no difference in complication rates (p = 0.65). Demographic characteristics did not differ between cohorts except for total breast weight (TBW) (CS: 1878 g vs. SS: 1452 g, p < 0.05). Adjusting for TBW, CST resulted in a 27.8% reduction in OT (44-min savings, p < 0.001) compared to SST. CONCLUSIONS: The CST significantly reduces OT for BM procedures compared to the SST without increasing complication rates. While time-savings was < 50% and may not be ideal for every patient, the CST offers an alternative BM approach potentially best-suited for large TBW patients and those undergoing axillary procedures.

Multidisciplinary Management of the Axilla in Patients with cT1-T2 N0 Breast Cancer Undergoing Primary Mastectomy: Results from a Prospective Single-Institution Series.

BACKGROUND: The after mapping of the axilla: radiotherapy or surgery (AMAROS) trial concluded that for patients with cT1-2 N0 breast cancer and one or two positive sentinel lymph nodes (SLNs), axillary radiotherapy (AxRT) provides equivalent locoregional control and a lower incidence of lymphedema compared with axillary lymph node dissection (ALND). The study prospectively assessed how often ALND could be replaced by AxRT in a consecutive cohort of patients undergoing mastectomy for cT1-2 N0 breast cancer. METHODS: In November 2015, our multidisciplinary group agreed to omit routine intraoperative SLN evaluation for cT1-2 N0 patients undergoing upfront mastectomy and potentially eligible for postmastectomy radiation therapy (PMRT), including those 60 years of age or younger and those older than 60 years with high-risk features. Patients with one or two positive SLNs on final pathology were reviewed to determine whether PMRT including the full axilla was an appropriate alternative to ALND. RESULTS: From November 2015 to December 2016, 154 patients met the study criteria, and 114 (74%) formed the final study cohort. Intraoperative SLN evaluation was omitted for 76 patients (67%). Of these patients, 20 (26%) had one or two positive SLNs, and 14 of these patients received PMRT + AxRT as an alternative to ALND. Three patients returned for ALND, and three patients were observed. On univariate analysis, tumor size, LVI, number of positive lymph nodes, and receipt of chemotherapy were associated with receipt of PMRT. CONCLUSIONS: For the majority of patients with one or two positive SLNs, ALND was avoided in favor of PMRT + AxRT. With appropriate multidisciplinary strategies, intraoperative evaluation of the SLN and immediate ALND can be avoided for patients meeting the AMAROS criteria and eligible for PMRT.

Does "Two is Better Than One" Apply to Surgeons? Comparing Single-Surgeon Versus Co-surgeon Bilateral Mastectomies.

BACKGROUND: Bilateral mastectomies (BM) are traditionally performed by single surgeons (SS); a co-surgeon (CS) technique, where each surgeon concurrently performs a unilateral mastectomy, offers an alternative approach. We examined differences in general surgery time (GST), overall surgery time (OST), and patient complications for BM performed by CS and SS. METHODS: Patients undergoing BM with tissue expander reconstruction (BMTR) between January 2010 and May 2014 at our center were identified through operative case logs. GST (incision to end of BM procedure), reconstruction duration (RST) (plastic surgery start to end of reconstruction) and OST (OST = GST + RST) was calculated. Patient age, presence/stage of cancer, breast weight, axillary procedure performed, and 30-day postoperative complications were extracted from medical records. Differences in GST and OST between CS and SS cases were assessed with a t test. A multivariate linear regression was fit to identify factors associated with GST. RESULTS: A total of 116 BMTR cases were performed [CS, n = 67 (57.8 %); SS, n = 49 (42.2 %)]. Demographic characteristics did not differ between groups. GST and OST were significantly shorter for CS cases, 75.8 versus 116.8 min, p < .0001, and 255.2 versus 278.3 min, p = .005, respectively. Presence of a CS significantly reduces BMTR time (ß = -38.82, p < .0001). Breast weight (ß = 0.0093, p = .03) and axillary dissection (ß = 28.69, p = .0003) also impacted GST. CONCLUSIONS: The CS approach to BMTR reduced both GST and OST; however, the degree of time savings (35.1 and 8.3 %, respectively) was less than hypothesized. A larger study is warranted to better characterize time, cost, and outcomes of the CS-approach for BM.

Contemporary Multi-Institutional Cohort of 550 Cases of Phyllodes Tumors (2007-2017) Demonstrates a Need for More Individualized Margin Guidelines.

PURPOSE: Phyllodes tumors (PTs) are rare breast neoplasms, which have little granular data on margins. Current guidelines recommend ≥ 1 cm margins; however, recent data suggest narrower margins are sufficient, and for benign PT, a negative margin may not be necessary. METHODS: We performed an 11-institution contemporary (2007-2017) review of PT practices. Demographics, surgical, and histopathologic data were captured. Logistic regression was used to estimate the association of select covariates with local recurrence (LR). RESULTS: Of 550 PT patients, the majority underwent excisional biopsy (55.3%, n = 302/546) or lumpectomy (wide excision) (38.5%, n = 210/546). Median tumor size was 30 mm, 68.9% (n = 379) were benign, 19.6% (n = 108) borderline, and 10.5% (n = 58) malignant. Surgical margins were positive in 42% (n = 231) and negative in 57.3% (n = 311). A second operation was performed in 38.0% (n = 209) of the total cohort, including 51 patients with an initial negative margin (82.4% with < 2 mm), and 157 with an initial positive margin, with residual disease only found in six (2.9%). Notably, 32.0% (n = 74) of those with an initial positive margin did not undergo a second operation, among whom only 2.7% (n = 2) recurred. Recurrence occurred in 3.3% (n = 18) of the total cohort (n = 15 LR, n = 3 distant), at median follow-up of 36.7 months. LR (all PT grades) was not reduced with wider negative margin width (≥ 2 mm v < 2 mm: odds ratio [OR] = 0.39; 95% CI, 0.07 to 2.10; P = .27) or final margin status (positive v negative: OR = 0.96; 95% CI, 0.26 to 3.52; P = .96). CONCLUSION: In current practice, many patients are managed outside of current guidelines. For the entire cohort, a wider margin width was not associated with a reduced risk of LR. We do not recommend re-excision of a negative margin for benign PT, regardless of margin width, as a progressively wider surgical margin is unlikely to reduce LR.