Can Genomic Testing Help Refine Choosing Wisely the Omission of Axillary Staging in cN0 Breast Cancer?

INTRODUCTION: Choosing Wisely (CW) recommends women age ≥70 y with cT1-2cN0 ER+/HER2-invasive breast cancer (BC) should forgo routine axillary staging with sentinel lymph node biopsy (SLN) at the time of breast surgery. Despite this longstanding recommendation, acceptance of SLN omission has not been widely adopted. Genomic assays, such as MammaPrint (MP), may supplement the decision to apply CW. We hypothesized that having MP on BC core needle biopsy (CNB) meeting CW could provide additional information to aid in decision-making about the need for axillary staging with SLN. METHODS: A retrospective single-institution review was conducted for women with BC meeting CW criteria, who also had MP performed on CNB from 2020 to 2021. Categorical characteristics were compared using the chi-square test. Continuous variables were compared using the Mann-Whitney U-test. RESULTS: MP was available on CNB for 238 BC meeting CW criteria: 70% low risk and 30% high risk. Axillary staging was performed in 195 (82%). Eighty-one percent were pathologically node-negative and 19% were pathologically node-positive. The MP score did not correlate with pathologic nodal stage (P = 0.52). The rate of high nodal burden (pN2) was extremely low (n = 1, 0.5%). The only significant correlation with pathological node positivity was older age (P = 0.03). Appropriately, high-risk MP was strongly associated with increased recurrence risk (n = 4, P = 0.008). CONCLUSIONS: Having MP on CNB does not provide clinically meaningful information about the pN stage and does not further refine which BC patients within CW could benefit from escalation to SLN or delineate a group more likely to be pathologically node-negative.

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.

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.

Long-term central venous catheters: size and location do matter.

BACKGROUND: Right or left side of placement for subclavian vein catheterization for placement of long-term central catheters and size of the catheters has not been analyzed completely. METHODS: The records of 502 consecutive long-term central venous catheters placed in patients while in the operating room over a 1-year period were reviewed and 230 subclavian vein tunneled catheters were analyzed. Technical difficulties in placing the catheters were defined as arterial puncture, guidewire malposition, catheter malposition, need to switch site of access, sheath difficulty, and inability to place the catheter. RESULTS: Three complications were identified (1%) and technical difficulties occurred in 15% of the patients. More difficulty was associated with the insertion of larger triple-lumen catheters than smaller single-lumen catheters (31% vs. 11%, respectively; P < .009). Right subclavian placement was associated with a 24.4% technical difficulty rate versus a 10.4% technical difficulty rate for left subclavian placement (P < .005). CONCLUSIONS: This study supports placing the smallest catheter necessary via the left subclavian vein.

Touch preparations for the intraoperative evaluation of sentinel lymph nodes after neoadjuvant therapy have high false-negative rates in patients with breast cancer.

CONTEXT: The use of a touch preparation for intraoperative sentinel lymph node diagnosis has become a preferred method of many pathologists because of its reported high sensitivity and rapid turnaround time. However, after neoadjuvant chemotherapy many lymph nodes have significant treatment-related changes that may affect the diagnostic accuracy of the intraoperative evaluation. OBJECTIVE: To determine the accuracy of touch preparation for the intraoperative diagnosis of metastatic breast carcinoma in the neoadjuvant setting. DESIGN: We reviewed retrospectively the results of intraoperative evaluations for 148 different sentinel lymph nodes from 63 patients who had undergone neoadjuvant chemotherapy for invasive breast cancer at our institution. The intraoperative touch preparation results were compared with the final pathology reports in conjunction with relevant clinical data. RESULTS: Use of touch preparation for the evaluation of sentinel lymph nodes intraoperatively after neoadjuvant therapy was associated with a low sensitivity of 38.6% (95% confidence interval [CI], 24.4-54.5) but high specificity of 100% (95% CI, 96.5-100). There was no difference in sensitivity rates between cytopathologists and noncytopathologists in this cohort (P = .40). Patients with invasive lobular carcinoma and those who had a clinically positive axilla before the initiation of neoadjuvant therapy were the most likely to have a false-negative result at surgery. CONCLUSIONS: Intraoperative touch preparations should not be used alone for the evaluation of sentinel lymph nodes in the setting of neoadjuvant therapy for breast cancer because of low overall sensitivity.

Radiation therapy in addition to gross total resection of retroperitoneal sarcoma results in prolonged survival: results from a single institutional study.

Purpose. Typical treatment of retroperitoneal sarcomas (RPSs) is surgery with or without radiation therapy for localized disease. With surgery alone, local failure rates are as high as 90%; this led to radiation therapy playing an important role in the treatment of RPSs. Methods. Thirty-one patients with retroperitoneal sarcoma treated with gross total resection and radiation therapy make up this retrospective analysis. Nineteen were treated preoperatively and 12 postoperatively (median dose, 59.4 Gy)-sixteen also received intraoperative radiation therapy (IORT) (median dose, 11 Gy). Patients were followed with stringent regimens, including frequent CT scans of the chest, abdomen, and pelvis. Results. With a median follow-up of 19 months (range 1-66 months), the 2-year overall survival (OS) rate is 70% (median, 52 months). The 2-year locoregional control (LRC) rate is 77% (median, 61.6 months). The 2-year distant disease free survival (DDFS) rate is 70% (median not reached). There were no differences in radiation-related acute and late toxicities among patients treated pre- versus postoperatively, whether with or without IORT. Conclusions. Compared to surgery alone, neoadjuvant or adjuvant radiation therapy offers patients with RPS an excellent chance for long-term LRC, DDS, and OS. The integration of modern treatment planning for external beam radiation therapy and IORT allows for higher doses to be delivered with acceptable toxicities.

Phase II study of dose-dense sequential doxorubicin and docetaxel for patients with advanced operable and inoperable breast cancer.

Rapid sequential delivery of doxorubicin 75 mg/m2 q 2 weeksx3 cycles followed by docetaxel 100 mg/m2 q 2 weeksx3 cycles, with filgrastim support was evaluated in patients with inoperable and large operable breast cancers who were not initially candidates for breast conservation therapy. Postoperative CMF chemotherapy and/or radiation were administered based on surgical findings. Median age of the 39 enrolled patients was 47 (range 27-59), stage IIA (6 patients), IIB (14 patients), IIIA (10 patients), IIIB (9 patients), and 23 patients (59%) had clinical nodal involvement. The average bidimensional tumor size before treatment was 30 cm2. Clinical responses included 13 (33%) complete responses, 23 (59%) partial responses, 1 stable disease, and 2 progressive disease, for an overall response rate of 92%. Clinical response rate was 11/13(85%) in HER2/neu positive patients compared to 25/26 (96%) in tumors that did not express HER2/neu. Twenty patients (51%) underwent breast conservation surgery. Pathologic tumor response at the time of definitive surgery included 4 pathologic CR (pCR, 10%), 4 microscopic invasion (pINV), and 14 (36%) pathologically negative axillary nodes. pCR was not observed in any HER2/neu positive patients. 5/39 patients were unable to complete all cycles of docetaxel and 8 patients required dose reduction of docetaxel due to development of grade 3-4 mucositis and hand-foot syndrome. This observation prompted a protocol change requiring 3 weeks between doxorubicin and docetaxel. Primary chemotherapy with dose-dense doxorubicin and docetaxel given sequentially is well tolerated and allows a high rate of breast sparing in patients with large breast cancers.