Anatomy Versus Biology: What Guides Chemotherapy Decisions in Older Patients With Breast Cancer?

INTRODUCTION: With the increasing utilization of genomic assays, such as the Oncotype DX recurrence score (RS), the relevance of anatomic staging has been questioned for select older patients with breast cancer. We sought to evaluate differences in chemotherapy receipt and/or survival among older patients based on RS and sentinel lymph node biopsy (SLNB) receipt/result. METHODS: Patients aged ≥ 65 diagnosed with pT1-2/cN0/M0 hormone-receptor-positive (HR+)/HER2-breast cancer (2010-2019) were selected from the National Cancer Database. Logistic regression was used to identify factors associated with chemotherapy receipt. Cox proportional hazards models were used to estimate the association of RS/SLNB group with overall survival. A cost-benefit study was also performed. RESULTS: Of the 75,428 patients included, the majority had an intermediate RS (58.2% versus 27.9% low, 13.8% high) and were SLNB- (85.1% versus 11.6% SLNB+, 3.3% none). Chemotherapy was recommended for 13,442 patients (17.8%). After adjustment, chemotherapy receipt was more likely with higher RS and SLNB+. After adjustment, SLNB receipt/result was only associated with overall survival among those with an intermediate RS. However, returning to the OR for SLNB is not cost-effective. CONCLUSIONS: SLNB receipt/result was associated with survival for those with an intermediate RS, but not a low or high RS, suggesting that an SLNB may indeed be unnecessary for select older patients with breast cancer.

Racial/Ethnic Disparities in Pathologic Complete Response and Overall Survival in Patients With Triple-Negative Breast Cancer Treated With Neoadjuvant Chemotherapy.

PURPOSE: Black women have higher rates of death from triple-negative breast cancer (TNBC) than White women. We hypothesized that pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) and overall survival (OS) may vary by race/ethnicity in patients with TNBC. METHODS: We identified women 18 years and older with stage I-III TNBC who received NAC followed by surgery from the National Cancer Database (2010-2019). We excluded patients without race/ethnicity or pathology data. Primary outcomes were pCR rates and OS on the basis of race/ethnicity. RESULTS: Forty thousand eight hundred ninety women with TNBC met inclusion criteria (median age [IQR], 53 [44-61] years): 26,150 Non-Hispanic White (64%, NHW), 9,672 Non-Hispanic Black (23.7%, NHB), 3,267 Hispanic (8%), 1,368 Non-Hispanic Asian (3.3%, NHA), and 433 Non-Hispanic Other (1.1%, NHO) patients. Overall, 29.8% demonstrated pCR (NHW: 30.5%, NHB: 27%, Hispanic: 32.6%, NHA: 28.8%, NHO: 29.8%). Unadjusted OS was significantly higher for those with pCR compared with those with residual disease (5-year OS, 0.917 [95% CI, 0.911 to 0.923] v 0.667 [95% CI, 0.661 to 0.673], log-rank P < .001), and this association persisted after adjustment for demographic and tumor factors. The effect of achieving pCR on OS did not differ by race/ethnicity (interaction P = .10). However, NHB patients were less likely (odds ratio [OR], 0.89 [95% CI, 0.83 to 0.95], P = .001) and Hispanic patients were more likely (OR, 1.19 [95% CI, 1.08 to 1.31], P = .001) to achieve pCR than NHW patients. After adjustment for patient and disease factors, including achievement of pCR, Hispanic (hazard ratio [HR], 0.76 [95% CI, 0.69 to 0.85], P < .001) and NHA (HR, 0.64 [95% CI, 0.55 to 0.75], P < .001) race/ethnicity remained associated with OS. CONCLUSION: Odds of achieving pCR and OS in patients with TNBC appear to be associated with race/ethnicity. Additional research is necessary to understand how race/ethnicity is associated with rates of pCR and OS, whether related to socioeconomic factors or biologic variables, or both.

Axillary nodal disease burden is not associated with an elevated 21-gene recurrence score in post-menopausal women presenting with a clinically negative axilla.

BACKGROUND: The predictive and prognostic value of the recurrence score (RS) has emphasized the importance of tumor biology and has reduced the prognostic implications of limited nodal burden in post-menopausal women with HR+/HER2-invasive breast cancer (IBC). It is unclear whether routine axillary staging has a continued role in the management of small, clinically node negative (cN0) HR+/HER2- IBC. We sought to estimate the association of RS with pN stage. METHODS: Patients >50yo diagnosed with cN0, HR+/HER2- IBC (2015-2019) with an available RS were identified from the National Cancer Database. The clinicopathologic characteristics and rates of pN-stage (pN0, pN1, pN2/3) were compared for RS of ≤25 vs. >25. RESULTS: The median patient age was 64.1 (IQR 58-69) and the majority (75%) of tumors displayed ductal histology. Most (81.6%) were cT1 on presentation and pT1 (74.7%) on final pathology. There were 130,568 (86.2%) with a RS â€‹≤ â€‹25 and 20,879 (13.8%) with a RS â€‹> â€‹25. On final pathology, 128,995 (85.2%) were pN0 and 21,991 (14.5%) pN1. Of the pN1, 2699 (12.3%) yielded a RS â€‹> â€‹25. There were 461 (0.3%) patients with pN2-pN3 disease. Of those, 57 (12.4%) had RS â€‹> â€‹25. CONCLUSION: In our analysis, pN0 and pN1 tumors are biologically similar by gene expression assay in postmenopausal patients with similar proportions of high RS. These data support the notion that tumor biology examined via RS may have more prognostic and predictive value than metastatic dissemination to limited lymph nodes. These findings support the ongoing evaluation of routine axillary staging in postmenopausal patients with HR+/HER2- IBC.

Changes in Surgical Management of the Axilla Over 11 Years - Report on More Than 1500 Breast Cancer Patients Treated with Neoadjuvant Chemotherapy on the Prospective I-SPY2 Trial.

BACKGROUND: Axillary surgery after neoadjuvant chemotherapy (NAC) is becoming less extensive. We evaluated the evolution of axillary surgery after NAC on the multi-institutional I-SPY2 prospective trial. METHODS: We examined annual rates of sentinel lymph node (SLN) surgery with resection of clipped node, if present), axillary lymph node dissection (ALND), and SLN and ALND in patients enrolled in I-SPY2 from January 1, 2011 to December 31, 2021 by clinical N status at diagnosis and pathologic N status at surgery. Cochran-Armitage trend tests were calculated to evaluate patterns over time. RESULTS: Of 1578 patients, 973 patients (61.7%) had SLN-only, 136 (8.6%) had SLN and ALND, and 469 (29.7%) had ALND-only. In the cN0 group, ALND-only decreased from 20% in 2011 to 6.25% in 2021 (p = 0.0078) and SLN-only increased from 70.0% to 87.5% (p = 0.0020). This was even more striking in patients with clinically node-positive (cN+) disease at diagnosis, where ALND-only decreased from 70.7% to 29.4% (p < 0.0001) and SLN-only significantly increased from 14.6% to 56.5% (p < 0.0001). This change was significant across subtypes (HR-/HER2-, HR+/HER2-, and HER2+). Among pathologically node-positive (pN+) patients after NAC (n = 525) ALND-only decreased from 69.0% to 39.2% (p < 0.0001) and SLN-only increased from 6.9% to 39.2% (p < 0.0001). CONCLUSIONS: Use of ALND after NAC has significantly decreased over the past decade. This is most pronounced in cN+ disease at diagnosis with an increase in the use of SLN surgery after NAC. Additionally, in pN+ disease after NAC, there has been a decrease in use of completion ALND, a practice pattern change that precedes results from clinical trials.

Breast Conservation Surgery and Mastectomy Have Similar Locoregional Recurrence After Neoadjuvant Chemotherapy: Results From 1462 Patients on the Prospective, Randomized I-SPY2 Trial.

Neoadjuvant chemotherapy (NAC) increases rates of successful breast-conserving surgery (BCS) in patients with breast cancer. However, some studies suggest that BCS after NAC may confer an increased risk of locoregional recurrence (LRR). We assessed LRR rates and locoregional recurrence-free survival (LRFS) in patients enrolled on I-SPY2 (NCT01042379), a prospective NAC trial for patients with clinical stage II to III, molecularly high-risk breast cancer. Cox proportional hazards models were used to evaluate associations between surgical procedure (BCS vs mastectomy) and LRFS adjusted for age, tumor receptor subtype, clinical T category, clinical nodal status, and residual cancer burden (RCB). In 1462 patients, surgical procedure was not associated with LRR or LRFS on either univariate or multivariate analysis. The unadjusted incidence of LRR was 5.4% after BCS and 7.0% after mastectomy, at a median follow-up time of 3.5 years. The strongest predictor of LRR was RCB class, with each increasing RCB class having a significantly higher hazard ratio for LRR compared with RCB 0 on multivariate analysis. Triple-negative receptor subtype was also associated with an increased risk of LRR (hazard ratio: 2.91, 95% CI: 1.8-4.6, P < 0.0001), regardless of the type of operation. In this large multi-institutional prospective trial of patients completing NAC, we found no increased risk of LRR or differences in LRFS after BCS compared with mastectomy. Tumor receptor subtype and extent of residual disease after NAC were significantly associated with recurrence. These data demonstrate that BCS can be an excellent surgical option after NAC for appropriately selected patients.

Is the Face an Air Bag for the Brain and Torso?-The Potential Protective Effects of Severe Midface Fractures.

We investigated the patterns of injury associated with major midface trauma. Our hypothesis is that midface injuries are associated with a decrease in certain traumatic brain injuries as well as major torso injuries. The registry of our Level I trauma center was queried for all adult patients treated over 25 years from 1989 to 2013. Patients with midface fractures were identified based on the ICD-9 code. Associated injuries were defined based both on individual ICD-9 codes as well as the Barell Injury Matrix. Injury etiology was defined based on e-codes. Univariate analysis was performed using chi-squared test, Fisher's exact test, and Wilcoxon test. A total of 29,152 patients were identified. Excluding pediatric patients, those with exclusively penetrating trauma, and patients with incomplete data, 20,971 patients were included for subsequent analysis. Midface fractures were identified in 752 patients. Patients with Le Fort fractures were more likely to be male, have a higher Injury Severity Score, a lower arrival Glasgow Coma Scale, and more likely to require intensive care unit admission and mechanical ventilation, with a longer hospital length of stay. Patients with midface fractures had significantly fewer subdural hematomas, subarachnoid hemorrhages, spine fractures, and were less likely to have associated abdominal and pelvic injuries. Patients with midface fractures were more likely to require facial reconstruction procedures and craniotomy. Patients presenting with midface fractures after blunt trauma have a distinctly different pattern of injuries. One potential mechanism for this is a deceleration effect, where midface impact and resulting fractures dissipate some of the energy.