Genomic landscape of malignant phyllodes tumors reveals multiple targetable opportunities.

BACKGROUND: Malignant phyllodes tumors (MPT) are rare fibroepithelial breast cancers with no known effective systemic therapy; metastatic progression portends a dismal prognosis. We sought to describe the genomic landscape of MPTs through genomic profiling and immunotherapeutic biomarker analysis. MATERIALS AND METHODS: Cases of sequenced MPT were identified from a Clinical Laboratory Improvement Amendments-certified, College of American Pathologists-accredited laboratory (Foundation Medicine). All cases underwent genomic profiling using adaptor ligation-based, next-generation sequencing assay of 324 genes. Tumor agnostic immunotherapy biomarkers, microsatellite instability, tumor mutational burden (TMB), and programmed death-ligand 1 (PD-L1) expression were evaluated. Fisher's Exact Tests and analysis of variance were used to test for differences between groups and for continuous variables as appropriate. RESULTS: Of 135 MPT cases identified; 94 (69.6%) were localized/locally recurrent and 41 (30.4%) were metastatic. Median age was 54 years (range 14-86). The median TMB was 2.5 mut/Mb and 3 were TMB-high (≥10 mut/Mb). 21.4% were PD-L1+ via Dako 22C3 assay (CPS ≥1). Most commonly altered genes included TERT-promoter (69.7%), CDKN2A (45.9%), TP53 (37.8%), NF1 (35.6%), CDKN2B (33.3%), MED12 (28.9%), MTAP (27.7%), KMT2D (22.2%), PIK3CA (20.0%), PTEN (18.5%), and RB1 (18.5%). Several tumors harboring genomic alterations with US Food and Drug Administration-approved indications in other tumor types were found including NF1, PIK3CA, EGFR Exon 19/20 insertions, and BRAF V600E mutations. CONCLUSIONS: In the largest genomic evaluation of MPT to date, multiple clinically actionable mutations were found. Routine sequencing of metastatic MPT may provide additional information to guide treatment decisions and clinical trial enrollment.

Germline genetic mutations in a multi-center cohort of 248 phyllodes tumors.

PURPOSE: Germline genetic mutations in women with phyllodes tumors (PT) are understudied, although some describe associations of PT with various mutations. We sought to determine the prevalence of pathogenic/likely pathogenic (P/LP) variants in women with PT. METHODS: A 6-site multi-center study of women with a PT was initiated, then expanded nationally through an online "Phyllodes Support Group." All women underwent 84-gene panel testing. We defined eligibility for testing based on select NCCN (National Comprehensive Cancer Network) criteria (v1.2022). Logistic regression was used to estimate the association of covariates with the likelihood of a P/LP variant. RESULTS: 274 women were enrolled: 164 (59.9%) through multi-center recruitment and 110 (40.1%) via online recruitment. 248 women completed testing; overall 14.1% (N = 35) had a P/LP variant, and over half (N = 19) of these individuals had a mutation in genes associated with autosomal dominant (AD) cancer conditions. The most common AD genes with a P/LP variant included CHEK2, ATM, and RAD51D. A quarter of participants (23.8%) met NCCN criteria for testing, but we found no difference in prevalence of a P/LP variant based on eligibility (p = 0.54). After adjustment, the presence of P/LP variants was not associated with age, NCCN testing eligibility, or PT type (all p > 0.05). CONCLUSION: Our study demonstrates that 7.7% of women with PT harbor germline P/LP variants in genes associated with AD cancer conditions. Early identification of these variants has implications for screening, risk reduction, and/or treatment. National guidelines for women with PT do not currently address germline genetic testing, which could be considered.

Omission of Axillary Lymph Node Dissection in Patients with Residual Nodal Disease After Neoadjuvant Chemotherapy.

BACKGROUND: Axillary management after neoadjuvant chemotherapy (NAC) is evolving but axillary lymph node dissection (ALND) remains the standard of care for patients with residual nodal disease. The results of the Alliance A011202 trial evaluating the oncologic safety of ALND omission in this cohort are pending but we hypothesize that ALND omission is already increasing. METHODS: The National Cancer Database was queried to identify patients diagnosed with cT1-3N1M0 breast cancer who underwent NAC and had residual nodal disease (ypN1mi-2) from 2012 to 2021. Temporal trends in omission of completion ALND were assessed annually. Multivariable logistic and Cox regression models were used to identify factors associated with ALND omission and overall survival (OS), respectively. RESULTS: A total of 6101 patients were included; the majority presented with cT2 disease (57%), with 69% HER2+, 23% triple-negative, and 8% hormone receptor-positive/HER2-. Overall, 34% underwent sentinel lymph node biopsy (SLNB) alone. Rates of ALND were the lowest in the last 4 years of observation. After adjustment, treatment at community centers (vs. academic) and lower pathologic nodal burden were associated with omission of ALND. ALND omission was associated with a higher unadjusted OS (5-year OS: 86% SLNB alone vs. 84% ALND; log-rank p = 0.03), however this association was not maintained after adjustment. CONCLUSIONS: Despite the impending release of the Alliance A011202 results, omission of ALND in patients with residual nodal disease after NAC is increasing. This practice appears more prominent in community centers and in patients with a lower burden of residual nodal disease. No association with OS was noted.

Utility of Axillary Staging in Older Patients with HER2-Positive Breast Cancer.

BACKGROUND: The utility of sentinel lymph node biopsy (SLNB) in older patients remains controversial. Advancements in human epidermal growth factor receptor 2 (HER2)-directed therapy have revolutionized disease response rates and prognosis, supporting efforts to re-evaluate the utility of SLNB. We aimed to assess the differences in treatment and overall survival (OS) in older patients with HER2-positive breast cancer based on SLNB. METHODS: Using the National Cancer Database (2010-2020), patients ≥ 70 years of age diagnosed with cT1-2/cN0/M0, HER2-positive breast cancer were identified. Logistic regression assessed associations with SLNB, systemic therapy, and radiation. Cox proportional hazard models were used to identify factors associated with OS. Analyses were stratified by treatment sequence, i.e. upfront surgery or neoadjuvant therapy (NAT) followed by surgery. RESULTS: Of the 17,609 patients included, 94% underwent upfront surgery (n = 16,492) and the remaining underwent NAT (n = 1117). Those who underwent SLNB were more likely to receive adjuvant therapy, irrespective of nodal status {upfront surgery/systemic therapy (odds ratio [OR] 2.82, 95% confidence interval [CI] 2.17-3.67); upfront surgery/radiation (OR 3.97, 95% CI 3.03-5.21); NAT/radiation (OR 5.69, 95% CI 1.83-17.69)}. The breast pathologic complete response (pCR) rate was highest among the hormone receptor (HR)-negative/HER2-positive subtype (50.0%), of which none were found to be ypN+. Comorbidity burden was associated with significantly lower rates of adjuvant systemic therapy and worse OS. CONCLUSIONS: Patients who underwent SLNB, regardless of pN status, were more likely to receive adjuvant therapy. Nodal positivity is exceedingly rare for patients with a breast pCR following NAT, especially among the HR-negative/HER2-positive subtype. It is reasonable to consider omission of SLNB in select subgroups of older patients with HER2-positive breast cancer.

Triple-Negative Breast Cancer in Older Patients: Does SLNB Guide Therapy?

BACKGROUND: Older breast cancer patients represent a heterogeneous population. Studies demonstrate that sentinel lymph node biopsy (SLNB) omission may be appropriate in some clinical scenarios, yet patients with triple-negative breast cancer (TNBC) are often excluded from these studies. This study evaluated differences in treatment and survival for older patients with TNBC based on SLNB receipt and result. METHODS: Patients 70 years old or older with a diagnosis of cT1-2/cN0/M0 TNBC (2010-2019) who underwent surgery were selected from the National Cancer Database. Logistic regression estimated the association of SLNB with therapy, and Cox proportional hazards models estimated the association of SLNB with overall survival (OS) after adjustment for select factors. RESULTS: Of the 15,167 patients included in the study (median age, 77 years), 13.02% did not undergo SLNB, 5.14% had pN1 disease, 0.12% had pN2 disease, and 0.01% had pN3 disease. Most of the patients (83.9%) underwent surgery first, and 16.1% received neoadjuvant chemotherapy. Of those who underwent surgery first and SLNB, 6.2% had pN+ disease. Receipt of SLNB was associated with a higher likelihood of chemotherapy (odds ratio [OR] 1.85; 95% confidence interval [CI] 1.55-2.21), regardless of pN status. Compared with those who did not undergo a SLNB, a negative SLNB was significantly associated with lower mortality (hazard ratio [HR] 0.68; 95% CI 0.63-0.75), although there was no difference for a positive SLNB (HR 1.14; 95% CI 0.98-1.34). The patients receiving chemotherapy first showed no difference in survival based on SLNB receipt or result (p = 0.23). CONCLUSIONS: Most older patients with TNBC do not have nodal involvement and do not receive chemotherapy. The receipt and results of SLNB may be associated with outcomes for some who undergo surgery first, but not for those who receive neoadjuvant chemotherapy.

Rates of Pathologic Complete Response and Overall Survival in Patients with Inflammatory Breast Cancer: A National Cancer Database Study.

BACKGROUND: Patients with inflammatory breast cancer (IBC) have worse survival compared with stage III non-IBC matched cohorts; however, the prognostic significance of achieving pathologic complete response (pCR) in the setting of IBC is not well described. We evaluated overall survival (OS) between IBC patients and non-IBC patients who achieved pCR. METHODS: Adult females diagnosed in 2010-2018 with clinical prognostic stage III unilateral invasive breast cancer treated with neoadjuvant chemotherapy (NAC) followed by surgery were selected from the National Cancer Database. Unadjusted OS from surgery was estimated using the Kaplan-Meier method, and log-rank tests were used to compare groups. Cox proportional hazard models were used to estimate the association of study groups with OS after adjustment for available covariates. RESULTS: The study included 38,390 patients; n = 4600 (12.0%) IBC and n = 33,790 (88.0%) non-IBC. Overall pCR rates were lower for IBC compared with non-IBC (20.7% vs. 23.3%; p < 0.001). Among those achieving pCR, 5-year mortality was higher for IBC patients (16.4%, 95% confidence interval [CI] 13.9-19.1%) versus non-IBC patients (9.1%, 95% CI 8.4-9.8%; log-rank p < 0.001). Among all patients achieving pCR, IBC remained associated with worse OS compared with non-IBC (hazard ratio 1.48, 95% CI 1.19-1.85; p < 0.001). CONCLUSION: We found a lower pCR rate and worse OS in IBC patients compared with non-IBC stage III patients. Despite effective systemic therapies, achieving a pCR for IBC patients may not carry the same prognostic impact compared with non-IBC stage III patients.

Breast Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology.

Breast cancer is treated with a multidisciplinary approach involving surgical oncology, radiation oncology, and medical oncology. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer include recommendations for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget's disease, Phyllodes tumor, inflammatory breast cancer, and management of breast cancer during pregnancy. The content featured in this issue focuses on the recommendations for overall management of systemic therapy (preoperative and adjuvant) options for nonmetastatic breast cancer. For the full version of the NCCN Guidelines for Breast Cancer, visit NCCN.org.

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.

Neoadjuvant Chemotherapy and Endocrine Therapy for Older Patients with Estrogen Receptor Positive Breast Cancer: Comparison of Approaches.

BACKGROUND: Benefits of a pathologic complete response (pCR) following neoadjuvant therapy are well established, yet outcomes for older women are understudied. We sought to examine the pCR and overall survival (OS) rates of women with estrogen receptor (ER) positive breast cancer across age groups. METHODS: Women diagnosed with cT1-4, N0-3, M0, ER+/HER2- breast cancer (2010-2018) who underwent neoadjuvant chemotherapy (NACT) or neoadjuvant endocrine therapy (NET) followed by surgery were selected from the National Cancer Database and categorized by age. Differences were tested, and Cox proportional hazards models were used to estimate the association of response with OS after adjustment for covariates. RESULTS: In the 43,009-patient cohort, 84.8% received NACT and 15.2% received NET. Of those aged ≥ 70 (N = 5623), 51.0% received NACT, and 49.0% received NET. Compared with younger women receiving NACT, older women were less likely to have a breast or nodal pCR [no pCR by age: 85.1% (≥ 70 years) vs 82.2% (50-69 years) vs 77.7% (< 50 years), p < 0.001]. Rates of pCR were similarly low for all women receiving NET [no pCR by age: 95.6% (≥ 70 years) vs 95% (50-69 years) vs 96% (< 50 years), p = 0.06]. After adjustment, pCR after NACT was not associated with OS for older patients, but better survival outcomes were noted for older patients achieving pCR after NET. CONCLUSION: For women with ER+/HER2- breast cancer, pCR rates after NACT are lower in older women compared with younger women, and are equally low after NET for all women. However, pCR after NET is associated with improved OS among older women, unlike pCR after NACT.

NCCN Guidelines® Insights: Breast Cancer, Version 4.2023.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer address all aspects of management for breast cancer. The treatment landscape of metastatic breast cancer is evolving constantly. The therapeutic strategy takes into consideration tumor biology, biomarkers, and other clinical factors. Due to the growing number of treatment options, if one option fails, there is usually another line of therapy available, providing meaningful improvements in survival. This NCCN Guidelines Insights report focuses on recent updates specific to systemic therapy recommendations for patients with stage IV (M1) disease.

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.

A Novel Staging System for De Novo Metastatic Breast Cancer Refines Prognostic Estimates.

OBJECTIVE: We aim to identify prognostic groups within a de novo metastatic cohort, incorporating both anatomic and biologic factors. BACKGROUND: Staging for breast cancer now includes anatomic and biologic factors, although the guidelines for stage IV disease do not account for how these factors may influence outcomes. METHODS: Adults with de novo metastatic breast cancer were selected from the National Cancer DataBase (2010-2013). Recursive partitioning analysis was used to group patients with similar overall survival (OS) based on clinical T/N stage, tumor grade, ER, PR, HER2, number of metastatic sites, and presence of bone-only metastases. Categories were created by amalgamating homogeneous groups based on 3-year OS rates (stage IVA: >50%, stage IVB: 30%-50%, stage IVC: <30%). RESULTS: 16,187 patients were identified; median follow-up was 32 months. 65.2% had 1 site of distant metastasis, and 42.9% had bone-only metastases. Recursive partitioning analysis identified the number of metastatic sites (1 vs >1) as the first stratification point, and ER status as the second stratification point for both resulting groups. Additional divisions were made based on HER2 status, PR status, cT stage, tumor grade, and presence of bone-only metastases. After bootstrapping, significant differences in 3-year OS were noted between the 3 groups [stage IVB vs IVA: HR 1.58 (95% confidence interval 1.50-1.67), stage IVC vs IVA: HR 3.54 (95% confidence interval 3.33-3.77)]. CONCLUSIONS: Both anatomic and biologic factors yielded reliable and reproducible prognostic estimates among patients with metastatic disease. These findings support formal stratification of de novo stage IV breast cancer into 3 distinct prognosis groups.

Margin Management and Adjuvant Therapy for Phyllodes Tumors: Practice Patterns of the American Society of Breast Surgeons Members.

BACKGROUND: Phyllodes tumors (PTs) are rare breast neoplasms with variable clinical behavior by histologic type: benign, borderline, or malignant. Until recently, management guidelines recommended one approach for all subtypes. METHODS: A 21-question survey was sent to American Society of Breast Surgeon members to evaluate management patterns by subtype. Surgeon demographics, decisions regarding management of margins, re-excision, surveillance, and synoptic reporting were collected. Chi-square or analysis of variance (ANOVA) were used as appropriate, with significance set at p < 0.05. RESULTS: A total of 493 of 2969 surveys were completed for a response rate of 18.3%. Among the survey takers, 55% were fellowship trained, 72% were in practice > 10 years, and 82% performed > 100 breast cases per year. Although 25% of respondents enucleate a mass with clinical suspicion of a PT alone, this decreased to 18% if a preoperative core biopsy performed was suggestive of PT. For margin management, 47% do not re-excise positive margins for benign PTs, but 96% would for a borderline or malignant PTs (p < 0.001). Only 2% perform axillary staging for malignant PTs, and 90% refer borderline or malignant PTs for radiation. Two-year surveillance was performed by about half of respondents for benign PT. However, two-thirds of respondents would increase surveillance to 5 years for borderline or malignant PTs. Only 38% report a templated synoptic pathology report at their institution. CONCLUSION: PT management patterns are evolving but still variable when looking at initial margin intent, decision for re-excision, radiation referral, pathologic reporting, and surveillance. This suggests the need for more specific management guidelines by subtype given differences in clinical behavior.

The Influence of Body Mass Index on the Histopathology and Outcomes of Patients Diagnosed with Atypical Breast Lesions.

BACKGROUND: Multiple studies have demonstrated a link between obesity and breast cancer; however, the potential association between obesity and atypical high-risk breast lesions has not been well characterized. We sought to evaluate the characteristics and clinical outcomes of patients with breast atypia based on a woman's body mass index (BMI). METHODS: We retrospectively identified adult women diagnosed with atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), and/or lobular carcinoma in situ (LCIS) at a single institution from 2008 to 2017. BMI groups were defined as a BMI 18.5 to < 30 or BMI ≥ 30 (obese). Adjusted logistic regression was used to estimate the association of BMI group with the odds of (1) upstage to cancer after atypia on needle biopsy, and (2) subsequent diagnosis of breast cancer. RESULTS: Breast atypia was identified in 503 patients (most advanced atypia: 74.8% ADH, 4.6% ALH, 20.7% LCIS), and 41% of these patients were classified as obese. After adjustment, BMI group was not associated with upstage to breast cancer at surgical excision following needle biopsy (p = 0.16) or development of a subsequent breast cancer (p = 0.08). For those upstaged to breast cancer at the time of surgical excision, or those who developed a subsequent malignancy, tumor subtype, grade and stage were not associated with BMI group (p > 0.05). CONCLUSION: In a large cohort of patients diagnosed with atypical breast histology, the risk of upstaging and/or subsequent progression to a breast malignancy was not associated with BMI. Factors other than obesity may influence breast cancer risk.

Breast Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology.

The therapeutic options for patients with noninvasive or invasive breast cancer are complex and varied. These NCCN Clinical Practice Guidelines for Breast Cancer include recommendations for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget disease, phyllodes tumor, inflammatory breast cancer, and management of breast cancer during pregnancy. The content featured in this issue focuses on the recommendations for overall management of ductal carcinoma in situ and the workup and locoregional management of early stage invasive breast cancer. For the full version of the NCCN Guidelines for Breast Cancer, visit NCCN.org.

Malignant phyllodes tumor and primary breast sarcoma; distinct rare tumors of the breast.

BACKGROUND: Malignant phyllodes (MP) and primary breast sarcomas (PBS) are rare neoplasms with overlapping histopathologic features. We compared overall survival (OS) and estimated the association of surgery and therapies with OS. METHODS: We utilized the National Cancer Database (2004-2016). Patients without surgery, unknown surgery, or margins, or Stage IV disease were excluded. Kaplan-Meier curves and Cox proportional hazards models were used to estimate unadjusted and adjusted OS, respectively. RESULTS: A total of 3209 (59.5%) MP, and 2185 (40.5%) PBS were identified. Despite a larger median tumor size in MP (46 vs. 40 mm PBS, p < 0.001), lumpectomy rate was higher for MP (52.9% vs. 27.0% PBS, p < 0.001). Compared to MP, PBS patients more frequently received radiation (28.9% vs. 24%), and chemotherapy (28.1% vs. 4%), both p < 0.001. Unadjusted OS was lower for PBS (57% vs. 85% MP, log-rank p < 0.001). PBS (vs. MP) had persistently worse survival (hazard ratio [HR]: 1.98, 95% confidence interval [CI]: 1.69-2.31) after adjustment. Receipt of adjuvant therapies was not associated with OS (either neoplasm); however, lumpectomy was associated with improved OS (vs. mastectomy) for both PBS (HR: 0.59, 95% CI: 0.50-0.75) and MP (HR: 0.65, 95% CI: 0.53-0.81). Positive margins had no association with OS for MP (HR: 1.09, 95% CI: 0.75-1.60), but was associated with worse survival for PBS (HR: 2.35, 95% CI: 1.82-3.02). DISCUSSION: We found significant survival differences between MP and PBS, with PBS having a consistently worse OS. Our findings support surgery as the mainstay of treatment for both tumor types and suggest that lumpectomy may be a reasonable option for select patients without compromising outcomes.

Characterizing participants in the North Carolina Breast and Cervical Cancer Control Program: A retrospective review of 90,000 women.

BACKGROUND: The North Carolina Breast and Cervical Cancer Control Program (NC BCCCP) provides breast cancer screening services to underserved women to mitigate disparities in access to care. The authors sought to characterize this understudied population. METHODS: Women 21 years old or older who underwent their first breast cancer screen through NC BCCCP from 2008 to 2018 were included. Demographic factors associated with the timeline of care and odds of a breast cancer diagnosis were identified with negative binomial and logistic regression, respectively. RESULTS: Of the 88,893 women identified, 45.5% were non-Hispanic (NH) White, 30.9% were NH Black, 19.6% were Hispanic, 1.7% were American Indian, and 1.1% were Asian. Breast cancer was diagnosed in 2.5% of the women (n = 2255). Hispanic women were the least likely to be diagnosed with breast cancer (odds ratio vs NH White women, 0.40; 95% confidence interval [CI], 0.34-0.47). Among patients with breast pathology, the median time to diagnosis was 19 days (interquartile range [IQR], 10-33 days), and the time to treatment was 33 days (IQR, 19-54 days). After adjustments, a longer time to diagnosis was significantly associated with age (incidence rate ratio [IRR], 1.01; 95% CI, 1.01-1.02) and being NH Black (vs NH White; IRR, 1.17; 95% CI, 1.06-1.29). A longer time to treatment was significantly associated with age (IRR, 1.01; 95% CI, 1.01-1.01), being NH Black (vs NH White; IRR, 1.20; 95% CI, 1.10-1.31), and being Hispanic (vs NH White; IRR, 1.22; 95% CI, 1.05-1.41). CONCLUSIONS: NC BCCCP participants with breast cancer received treatment within approximately 1 month of presentation, and this finding aligns with quality care benchmarks. Nevertheless, racial/ethnic disparities in timeliness of care persist, and this suggests opportunities for improvement. LAY SUMMARY: This review of approximately 90,000 participants in a breast cancer screening program for uninsured and underinsured women highlights the importance of safety net programs in providing timely care to underserved patients. The authors found that the North Carolina Breast and Cervical Cancer Control Program met timeliness benchmarks from the Centers for Disease Control and Prevention across all racial/ethnic groups. However, non-Hispanic Black women experienced relative delays in the time to diagnosis, and both non-Hispanic Black women and Hispanic women experienced relative delays in the time to treatment. These findings demonstrate how racial/ethnic disparities in the timeliness of care can persist even within a program intended to reduce barriers to access.

Time to surgery among women treated with neoadjuvant systemic therapy and upfront surgery for breast cancer.

PURPOSE: Time to surgery (TTS) is a potentially modifiable factor associated with survival after breast cancer diagnosis and can serve as a proxy for quality of oncologic care coordination. We sought to determine whether factors associated with delays in TTS vary between patients who receive neoadjuvant systemic therapy (NST) vs upfront surgery and whether the impact of these delays on overall survival (OS) varies with treatment sequence. METHODS: Women ≥ 18 years old with Stage I-III breast cancer were identified in the National Cancer Database (2004-2014). Multivariate linear regression stratified by treatment sequence (upfront surgery vs NST [neoadjuvant chemotherapy {NAC}, neoadjuvant endocrine therapy {NAE}, or both {NACE}]) was used to identify factors associated with TTS. Cox proportional hazards models were used to estimate the effect of TTS on overall survival (OS). RESULTS: Of 693,469 patients, 14.8% (n = 102,326) received NST (NAC n = 85,143, NAE n = 10,004, NACE n = 7179). Non-White race/ethnicity, no or government-issued insurance, more extensive surgery (i.e., mastectomy and contralateral prophylactic mastectomy vs breast-conserving surgery), and post-mastectomy reconstruction were associated with significantly longer adjusted TTS for NAC and upfront-surgery recipients, but only upfront-surgery patients had progressively worse OS with increasing TTS (> 180 vs ≤ 30 days: HR = 1.31, all p < 0.001). CONCLUSIONS: Surgery extent, race/ethnicity, and insurance were associated with TTS across treatment groups, but longer TTS was only associated with worse OS in upfront-surgery patients. Our findings can help inform surgeon-patient communication, shared decision making, care coordination, and patients' expectations throughout both NST and in the perioperative period.

Contralateral Axillary Nodal Metastases: Stage IV Disease or a Manifestation of Progressive Locally Advanced Breast Cancer?

BACKGROUND: Contralateral axillary nodal metastases (CAM) is classified as stage IV disease, although many centers treat CAM with curative intent. We hypothesized that patients with CAM, treated with multimodality therapy, would have improved overall survival (OS) versus patients with distant metastatic disease (M1) and similar OS to those with locally advanced breast cancer (LABC). METHODS: Using the NCDB (2004-2016), we categorized adult patients with node-positive breast cancer into three study groups: LABC, CAM, and M1. Kaplan-Meier curves were used to visualize the unadjusted OS. Cox proportional hazards models were used to estimate the association of study group with OS. RESULTS: A total of 94,487 patients were identified: 122 with CAM, 12,325 with LABC, and 82,040 with M1 (median follow-up 63.6 months). LABC and CAM patients had similar histology and rates of chemotherapy and endocrine therapy receipt. However, the CAM group had significantly larger tumors, more estrogen-receptor expression, higher T-stage, and more mastectomies than the LABC group. Compared with M1 patients, CAM patients were more likely to have grade 3 and cT4 tumors. Patients with CAM and LABC had similar 5-year unadjusted OS and significantly improved OS vs M1 patients. After adjustment, LABC and CAM patients continued to have similar OS and better OS vs M1 patients. CONCLUSIONS: CAM patients who receive multi-modal therapy with curative intent may have OS more comparable to LABC patients than M1 patients. Out data support a reevaluation of whether CAM should remain classified as M1, as N3 may better reflect disease prognosis and treatment goals.

Mortality in Older Patients with Breast Cancer Undergoing Breast Surgery: How Low is "Low Risk"?

BACKGROUND: Breast surgery carries a low risk of postoperative mortality. For older patients with multiple comorbidities, even low-risk procedures can confer some increased perioperative risk. We sought to identify factors associated with postoperative mortality in breast cancer patients ≥70 years to create a nomogram for predicting risk of death within 90 days. METHODS: Patients diagnosed with nonmetastatic invasive breast cancer (2010-2016) were selected from the National Cancer Database. Unadjusted OS was estimated using the Kaplan-Meier method. Multivariate logistic regression was used to estimate the association of age and surgery with 90-day mortality and to build a predictive nomogram. RESULTS: Among surgical patients ≥70 years, unadjusted 90-day mortality increased with increasing age (70-74 = 0.4% vs. ≥85 = 1.6%), comorbidity score (0 = 0.5% vs. ≥3 = 2.7%), and disease stage (I = 0.4% vs. III = 2.7%; all p < 0.001). After adjustment, death within 90 days of surgery was associated with higher age (≥85 vs. 70-74: odds ratio [OR] 3.16, 95% confidence interval [CI] 2.74-3.65), comorbidity score (≥3 vs. 0: OR 4.79, 95% CI 3.89-5.89), and disease stage (III vs. I: OR 4.30, 95% CI 3.69-5.00). Based on these findings, seven variables (age, gender, comorbidity score, facility type, facility location, clinical stage, and surgery type) were selected to build a nomogram; estimates of risk of death within 90 days ranged from <1 to >30%. CONCLUSIONS: Breast operations remain relatively low-risk procedures for older patients with breast cancer, but select factors can be used to estimate the risk of postoperative mortality to guide surgical decision-making among older women.