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PURPOSE Given the heterogeneity and improvement in outcomes for metastatic breast cancer (MBC), we developed a staging system that refines prognostic estimates for patients with metastatic cancer at the time of initial diagnosis, de novo MBC (dnMBC), on the basis of survival outcomes and disease-related variables. METHODS Patients with dnMBC (2010-2016) were selected from the National Cancer Database (NCDB). Recursive partitioning analysis (RPA) was used to group patients with similar overall survival (OS) on the basis of clinical T category, grade, estrogen receptor (ER), progesterone receptor, human epidermal growth factor receptor 2, histology, organ system site of metastases (bone-only, brain-only, visceral), and number of organ systems involved. Three-year OS rates were used to assign a final stage: IVA: >70%, IVB: 50%-70%, IVC: 25 to RESULTS At a median follow-up of 52.9 months, the median OS of the original cohort (N = 42,467) was 35.4 months (95% CI, 34.8 to 35.9). RPA stratified patients into 53 groups with 3-year OS rates ranging from 73.5% to 5.7%; these groups were amalgamated into four stage groups: 3-year OS, A = 73.2%, B = 61.9%, C = 40.1%, and D = 17% (log-rank P < .001). After bootstrapping, the survival outcomes for the four stages remained significantly different (log-rank P < .001). This staging system was then validated using SEER data (N = 20,469) and a separate cohort from the NCDB (N = 7,645) (both log-rank P < .001). CONCLUSION Our findings regarding the heterogeneity in outcomes for patients with dnMBC could guide future revisions of the current American Joint Committee on Cancer staging guidelines for patients with newly diagnosed stage IV disease. Our findings should be independently confirmed.

Introduction: Despite the recent overall improvement in survival for patients with breast cancer, racial disparities in outcomes persist. While studies have demonstrated that socioeconomic factors and access to treatment play a role, differences in tumor biology may also contribute. Black women are significantly more likely to develop triple negative breast cancer (TNBC), the deadliest of the breast cancer subtypes, with more TNBC patients progressing to incurable, metastatic disease than patients with any other breast cancer subtype. Studies have demonstrated that TNBC patients who achieve a pathologic complete response (pCR), defined as no residual invasive cancer in the breast or lymph nodes after neoadjuvant chemotherapy (NAC), have improved survival. We hypothesize that rates of pCR and overall survival (OS) in patients with TNBC may differ by race/ethnicity, which may account in part for the disparities in outcomes observed. Methods: Adult female patients with stage I-III TNBC diagnosed in 2010-2019 who received NAC followed by surgery were identified from the National Cancer Database (NCDB). Race/ethnicity was defined as Hispanic (H), Non-Hispanic White (NHW), Non-Hispanic Black (NHB), Non-Hispanic Asian (NHA), and Non-Hispanic Other (NHO). pCR was defined as no invasive cancer in either the breast or axilla (ypT0/is,N0) at surgery. Logistic regression was used to estimate the association of race/ethnicity with achievement of pCR after adjustment for covariates. Unadjusted OS was estimated using the Kaplan-Meier method, and the log-rank test was used to compare groups. Cox Proportional Hazards models were used to estimate the association of race/ethnicity and achievement of pCR with OS after adjustment for covariates. Additional interaction and subgroup analyses were also conducted. Results: Of the 40,890 patients identified, 29.8% (n=12,173) demonstrated pCR after NAC. The unadjusted 5-year OS rates for those who achieved pCR were significantly higher compared to patients with no pCR (0.917, 95% CI 0.911-0.923 vs 0.667, 95% CI 0.661-0.673, log-rank p< 0.001). Hispanic patients were more likely to achieve pCR (OR 1.19, 95% CI 1.08-1.31, p=0.001), and NHB patients were less likely to achieve pCR (OR 0.89, 95% CI 0.83-0.95, p=0.001) compared to NHW, even after adjustment. Unadjusted OS was also notably lower for NHB patients compared to every other race group (5-year OS rate: NHB 0.709 vs NHW 0.746 vs NHO 0.771 vs H 0.772 vs NHA 0.816, log-rank p< 0.001); however, this difference did not persist after adjustment for patient and disease factors, including achievement of pCR. Interval from diagnosis to start of chemotherapy (OR 0.95, 95% CI 0.94-0.96, p< 0.001) and duration after chemotherapy start to surgery (OR 1.02, 95% CI 1.02-1.03, p< 0.001) were associated with the odds of achieving pCR. Overall, the effect of achieving pCR on OS did not differ by race/ethnicity (interaction p=0.10). Discussion: Achieving pCR after NAC in patients with TNBC is associated with a significant improvement in OS. Yet, rates of pCR appear to differ based on race/ethnicity, with NHB patients demonstrating significantly lower rates of pCR than NHW patients, which may contribute to the disparities in survival outcomes observed. In addition to addressing socioeconomic factors and access to treatment, further research examining whether biological differences exist based on race that influence response of TNBC to current standard therapies is essential for improving survival outcomes for this disproportionately affected patient population. Citation Format: Hannah E. Woriax, Samantha M. Thomas, Jennifer K. Plichta, Laura H. Rosenberger, Astrid Botty van de bruele, Akiko Chiba, Gayle DiLalla, Carolyn Menendez, E Shelley Hwang, Maggie L. DiNome. The effect of race on pathologic complete response rates and overall survival in patients with triple negative breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-06-02.

Background: The predictive and prognostic value of the 21-gene recurrence score (RS) has emphasized the importance of tumor biology and minimized the credence of a limited (1-3 positive) nodal burden. The practice changing results of RxPonder demonstrated that post-menopausal women with 1-3 positive lymph nodes (pN1) and a RS of ≤25 did not necessarily benefit from adjuvant chemotherapy. Given that RS influences adjuvant therapy decision-making more significantly than nodal status, it is unclear whether axillary staging with sentinel lymph node biopsy (SLNB) has a continued role in the surgical care of post-menopausal patients otherwise presenting with early stage, clinically node negative (cN0) hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) invasive breast cancer. In this context, the de-escalation of axillary staging, especially in the presence of a low RS, is an area of active investigation. To help elucidate this further, we sought to estimate the association of RS with pathologic nodal stage. Methods: Using the 2004-2019 National Cancer Database (NCDB) Patient User File (2022 release), we evaluated the association of RS with the incidence of pN0, pN1 and pN2-3 disease. Only female patients diagnosed who were age 50 and older with HR+/HER2- invasive breast cancer were eligible, and only those presenting with cT1-T2N0 who underwent upfront surgery with a SLNB comprised our study population. Those with Oncotype DX testing performed with an available RS were included. Given the limitations within the dataset, age 50 and over was selected as a surrogate for post-menopausal status. Categorical variables were compared between RS groups (≤25 vs. >25) using chi-square tests and continuous variables were compared using t-tests. A logistic regression analysis was performed to estimate the association between RS (≤25 vs. >25) and nodal burden (pN2-3 vs pN0-1). Results: There were 151,447 patients with an invasive breast cancer diagnosis between 2015 and 2019 who met inclusion criteria. The average age at diagnosis was 64.1 (IQR 58-69) and almost 75% of tumors displayed ductal histology. There were 130,568 (86.2%) patients with a RS≤25 and 20,879 (13.8%) with a RS >25. On final pathology, 85.2% were pN0 and 14.8% were pN1-3. For those with a RS ≤25, 84.9% were pN0, 14.8% were pN1 and 0.3% were pN2-3. For those with a RS >25, 86.8% were pN0, 12.9% were pN1 and 0.3% were pN2-3. Overall, 14.5% demonstrated pN1 disease, of which 12.3% yielded a RS >25. Of the 461 patients with pN2-3 disease for whom RS was available, 12.4% (57 patients) had RS >25. After adjustment, RS >25 was associated with reduced incidence of pN2-3 compared to pN0-1 (OR=0.64, 95% CI 0.47-0.87, p=0.004). Conclusion: In this population of post-menopausal patients with cT1-T2N0, HR+/HER2- invasive breast cancer and an available RS, almost 86% displayed pN0 or pN1 disease in conjunction with a RS ≤25. Based on the current available literature, less than 5% of cT1-2N0 patients are thought to harbor >pN1 disease. These data add further support, suggesting that this patient population is unlikely to harbor a higher than limited nodal burden given a clinically negative axilla. Though less than 0.5% of the studied patient population demonstrated pN2-3 disease, an important caveat to make is that these patients would not have met criteria for RS, and it’s likely this low number reflects the absence of testing. Given that RS has not been validated for this higher nodal stage, we cannot make recommendations to omit axillary surgery in this cohort of patients. The data presented here provides further rationale for the two large prospective studies addressing whether SLNB could be eliminated in patients with otherwise small HR+/HER2- tumors which are currently ongoing. Table 1: Pathologic Nodal Staging Based on Recurrence Score Citation Format: Astrid Botty van den Bruele, Morgan Paul, Samantha M. Thomas, Sarah L. Sammons, Maggie L. DiNome, Jennifer K. Plichta, Akiko Chiba, Laura H. Rosenberger, E Shelley Hwang. Low 21-Gene Recurrence Score Is Not Associated with a High Axillary Nodal Burden in Post-Menopausal Women Presenting with a Clinically Negative Axilla [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-20.

Although breast reconstruction after bilateral mastectomies including a contralateral prophylactic mastectomy is known to have a higher overall complication profile, whether reconstructive complication rates differ between the therapeutic mastectomy and contralateral prophylactic mastectomy sides remains unclear.Women undergoing bilateral mastectomies with autologous or implant-based breast reconstruction for a unilateral breast cancer at a single institution were identified (2009 to 2019). Postoperative complications were stratified by laterality (therapeutic mastectomy versus contralateral prophylactic mastectomy). Paired data were analyzed to compare the risks of complications between prophylactic and therapeutic reconstruction sides in the same patient.A total of 130 patients (260 reconstructions) underwent bilateral autologous or implant-based reconstruction. Although most women underwent a simple mastectomy, a higher proportion of therapeutic mastectomies were modified radical mastectomies including axillary lymph node dissections compared to contralateral prophylactic mastectomies (15.4 percent versus 0 percent). Forty-four percent of women completed postmastectomy radiation therapy of the therapeutic side before definitive reconstruction. Overall, both therapeutic and prophylactic reconstructions had a similar incidence of reconstructive failure (p = 0.57), return to the operating room (p = 0.44), mastectomy skin flap necrosis (p = 0.32), seroma (p = 0.82), fat necrosis (p = 0.16), wound infection (p = 0.56), and cellulitis (p = 0.56). Nearly one-fifth of patients experienced complications limited to the prophylactic side [contralateral prophylactic mastectomy reconstruction complications, n = 26 (20.0 percent); therapeutic mastectomy reconstruction complications, n = 15 (11.5 percent)].Despite a history of local radiation therapy and more extensive oncologic surgery on the therapeutic side, there are no significant differences in the incidence of postsurgical complications on the therapeutic mastectomy and contralateral prophylactic mastectomy sides after bilateral reconstruction.Risk, II.

Genetic testing offers providers a potentially life saving tool for identifying and intervening in high-risk individuals. However, disparities in receipt of genetic testing have been consistently demonstrated and undoubtedly have significant implications for the populations not receiving the standard of care. If correctly used, there is the potential for genetic testing to play a role in decreasing health disparities among individuals of different races and ethnicities. However, if genetic testing continues to revolutionize cancer care while being disproportionately distributed, it also has the potential to widen the existing mortality gap between various racial and ethnic populations.

BACKGROUND: We sought to identify characteristics of metastatic breast cancer (MBC) patients who may benefit most from primary tumor resection. METHODS: Recursive partitioning analysis (RPA) was used to categorize non-surgical patients with de novo MBC in the NCDB (2010–2015) into 3 groups (I/II/III) based on 3-year overall survival (OS). After bootstrapping (BS), group-level profiles were applied, and the association of surgery with OS was estimated using Cox proportional hazards models. RESULTS: All patients benefitted from surgery (median OS, surgery vs no surgery): 72.7 vs 42.9 months, 47.3 vs 30.4 months, 23.8 vs 14.4 months (all p

PURPOSE To determine if physicians' self-reported knowledge, attitudes, and practices regarding genetic counseling and testing (GCT) vary by patients' race. METHODS We conducted a nationwide 49-item survey among breast oncology physicians in the United States. We queried respondents about their own demographics, clinical characteristics, knowledge, attitudes, practices, and perceived barriers in providing GCT to patients with breast cancer. RESULTS Our survey included responses from 277 physicians (females, 58.8%; medical oncologists, 75.1%; academic physicians, 61.7%; and Whites, 67.1%). Only 1.8% indicated that they were more likely to refer a White patient than refer an African American patient for GCT, and 66.9% believed that African American women with breast cancer have lower rates of GCT than White women. Regarding perceived barriers to GCT, 63.4% of respondents indicated that African American women face more barriers than White women do and 21% felt that African American women require more information and guidance during the GCT decision-making process than White women. Although 32% of respondents indicated that lack of trust was a barrier to GCT in all patients, 58.1% felt that this was a greater barrier for African American women ( P < .0001). Only 13.9% believed that noncompliance with GCT is a barrier for all patients, whereas 30.6% believed that African American women are more likely than White women to be noncompliant ( P < .0001). CONCLUSION We demonstrated that racial differences exist in oncology physicians' perceived barriers to GCT for patients with breast cancer. This nationwide survey will serve as a basis for understanding physicians' determinants of GCT for African American women and highlights the necessity of education and interventions to address bias among physicians. Awareness of such physician biases can enable further work to address inequities, ultimately leading to improved GCT equity for African American women with breast cancer.

Genetic testing plays an important role in assessing breast cancer risk and often the risk of other types of cancers. Accurate risk assessment and stratification represents a critical element of identifying who is best served by increased surveillance and consideration of other prevention or treatment options while also limiting overtreatment and unnecessary testing. The indications for testing will likely continue to expand, and ideally, more women with a genetic predisposition to breast cancer will be identified before they are diagnosed with breast cancer and thus have the option to consider effective screening and prevention management strategies.

PURPOSE Outcomes for patients with metastatic breast cancer (MBC) are continually improving as more effective treatments become available. Granular data sets of this unique population are lacking, and the standard method for data collection relies largely on chart review. Therefore, using electronic health records (EHR) collected at a tertiary hospital system, we developed and evaluated a computational phenotype designed to identify all patients with MBC, and we compared the effectiveness of this algorithm against the gold standard, clinical chart review. METHODS A cohort of patients with breast cancer were identified according to International Classification of Diseases codes, the institutional tumor registry, and SNOMED codes. Chart review was performed to determine whether distant metastases had occurred. We developed a computational phenotype, on the basis of SNOMED concept IDs, which was applied to the EHR to identify patients with MBC. Contingency tables were used to aggregate and compare results. RESULTS A total of 1,741 patients with breast cancer were identified using data from International Classification of Diseases codes, the tumor registry, and/or SNOMED concept identifiers. Chart review of all patients classified each patient as having MBC (n = 416; 23.9%) versus not (n = 1,325; 75.9%). The final computational phenotype successfully classified 1,646 patients (95% accuracy; 82% sensitivity; 99% specificity). CONCLUSION Hospital systems with robust EHRs and reliable mapping to SNOMED have the ability to use standard codes to derive computational phenotypes. These algorithms perform reasonably well and have the added ability to be run at disparate health care facilities. Better tooling to navigate the polyhierarchical structure of SNOMED ontology could yield better-performing computational phenotypes.

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.

BACKGROUND. Although metastatic breast cancer (MBC) remains incurable, advances in therapies have improved survival. Using a contemporary dataset of de novo MBC patients, we explore how overall (OS) and cancer-specific survival (CSS) changed over time. METHODS. All patients with de novo MBC from 1988 to 2016 were selected from Surveillance, Epidemiology, and End Results (SEER) 18. Unadjusted OS and CSS were estimated by Kaplan–Meier method and stratified by disease characteristics. Cox proportional hazards models determined factors associated with survival. RESULTS. 47,034 patients were included, with median OS of 25 months and CSS of 27 months. Survival steadily improved over time (1988: 1-year OS 62%, CSS 65%; 2015: 1-year OS 72%, CSS 74%). Patients with triple-negative breast cancer (TNBC) had the worst prognosis and were most likely to die from MBC [versus human epidermal growth factor receptor 2 (HER2)+ and hormone receptor (HR)+/HER2−]. Those with ≥ 4 sites of metastatic disease were also more likely to die from MBC with nearly identical OS and CSS (5-year OS 9%, CSS 9%), when compared with those with 1 site (5-year OS 31%, CSS 35%). After adjustment, improved CSS was associated with bone-only disease [hazard ratio (HR) 0.88, 95% confidence interval (CI) 0.83–0.94], while TNBC (versus HER2+: HR 3.12, 95% CI 2.89–3.36) and > 3 sites of metastatic disease (versus 1 site: HR 3.24, 95% CI 2.68–3.91) were associated with worse CSS (all p < 0.001). CONCLUSIONS. Accurate prognostic estimates are essential for patient care. As treatments for patients with MBC have expanded, OS and CSS have improved, and more patients, particularly with limited distant disease or favorable tumor subtypes, are also dying from non-MBC causes.

Patients undergoing evaluation for solid organ transplantation (SOT) often have a history of malignancy. Although the cancer has been treated in these patients, the benefits of transplantation need to be balanced against the risk of tumor recurrence, especially in the setting of immunosuppression. Prior guidelines of when to transplant patients with a prior treated malignancy do not take in to account current staging, disease biology, or advances in cancer treatments. To develop contemporary recommendations, the American Society of Transplantation held a consensus workshop to perform a comprehensive review of current literature regarding cancer therapies, cancer stage-specific prognosis, the kinetics of cancer recurrence, and the limited data on the effects of immunosuppression on cancer-specific outcomes. This document contains prognosis based on contemporary treatment and transplant recommendations for breast, colorectal, anal, urological, gynecological, and nonsmall cell lung cancers. This conference and consensus documents aim to provide recommendations to assist in the evaluation of patients for SOT given a history of a pretransplant malignancy.

Patients undergoing evaluation for solid organ transplantation (SOT) frequently have a history of malignancy. Only patients with treated cancer are considered for SOT but the benefits of transplantation need to be balanced against the risk of tumor recurrence, taking into consideration the potential effects of immunosuppression. Prior guidelines on timing to transplant in patients with a prior treated malignancy do not account for current staging, disease biology, or advances in cancer treatments. To update these recommendations, the American Society of Transplantation (AST) facilitated a consensus workshop to comprehensively review contemporary literature regarding cancer therapies, cancer stage specific prognosis, the kinetics of cancer recurrence, as well as the limited data on the effects of immunosuppression on cancer-specific outcomes. This document contains prognosis, treatment, and transplant recommendations for melanoma and hematological malignancies. Given the limited data regarding the risk of cancer recurrence in transplant recipients, the goal of the AST-sponsored conference and the consensus documents produced are to provide expert opinion recommendations that help in the evaluation of patients with a history of a pretransplant malignancy for transplant candidacy.

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

BACKGROUND: Elderly women with clinically node-positive (cN+) breast cancer (BC) often have comorbidities that limit life expectancy and complicate treatment. We sought to determine whether the number of lymph nodes (LNs) retrieved among older women with node-positive breast cancer was associated with overall survival (OS). METHODS: Using the National Cancer Database (2010–2015), women 70–90y with cN+ BC and ≥1 LN removed were categorized by treatment sequence: upfront surgery or neoadjuvant chemotherapy (NAC). Multivariable Cox proportional hazards models with restricted cubic splines characterized the functional association of LN retrieval with OS; threshold values of LN retrieval were estimated. Cox proportional hazards models were used to estimate the association of LN retrieval groups with OS. RESULTS: In the upfront surgery cohort, a non-linear association was identified between LNs retrieved and OS. In the NAC cohort, no association was identified. For the upfront surgery cohort, the optimal threshold value of LN retrieval was 21 LN (90% CI 18–23). Based on this estimate, LN retrieval groups were created: 23 LNs. After adjustment, retrieval of

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: 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.

We investigated whether tumor phenotype influences surgical decision-making, and how that may impact overall survival (OS) for early-stage breast cancer.Women aged 18-69 with cT0-2/cN0/cM0 breast cancer in the National Cancer Database (2010-2017) were included. A generalized logistic model was used to identify factors associated with surgery type. A Kaplan-Meier curve was used to visualize unadjusted OS, and the log-rank test was used to test for differences in OS between surgery types.Of 597,149 patients, 58% underwent lumpectomy with radiation (BCT), 25% unilateral mastectomy (UM), and 17% bilateral mastectomy (BM). After adjustment, HER2+ and triple-negative (TN) tumors were less likely to undergo UM than BCT, versus hormone receptor-positive tumors (OR = 0.881, 95% CI = 0.860-0.903; OR = 0.485, 95% CI = 0.470-0.501). UM and BM had worse 5-year OS versus BCT (UM: 0.926, vs BM: 0.952, vs BCT: 0.960).BCT is increasingly used to treat HER2+ and TN tumors. More extensive surgery is not associated with better survival outcomes, regardless of tumor phenotype.

Objective The majority of tumor sequencing currently performed on cancer patients does not include a matched normal control, and in cases where germline testing is performed, it is usually run independently of tumor testing. The rates of concordance between variants identified via germline and tumor testing in this context are poorly understood. We compared tumor and germline sequencing results in patients with breast, ovarian, pancreatic, and prostate cancer who were found to harbor alterations in genes associated with homologous recombination deficiency (HRD) and increased hereditary cancer risk. We then evaluated the potential for a computational somatic-germline-zygosity (SGZ) modeling algorithm to predict germline status based on tumor-only comprehensive genomic profiling (CGP) results. Methods A retrospective chart review was performed using an academic cancer center’s databases of somatic and germline sequencing tests, and concordance between tumor and germline results was assessed. SGZ modeling from tumor-only CGP was compared to germline results to assess this method’s accuracy in determining germline mutation status. Results A total of 115 patients with 146 total alterations were identified. Concordance rates between somatic and germline alterations ranged from 0% to 85.7% depending on the gene and variant classification. After correcting for differences in variant classification and filtering practices, SGZ modeling was found to have 97.2% sensitivity and 90.3% specificity for the prediction of somatic versus germline origin. Conclusions Mutations in HRD genes identified by tumor-only sequencing are frequently germline. Providers should be aware that technical differences related to assay design, variant filtering, and variant classification can contribute to discordance between tumor-only and germline sequencing test results. In addition, SGZ modeling had high predictive power to distinguish between mutations of somatic and germline origin without the need for a matched normal control, and could potentially be considered to inform clinical decision-making.

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.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.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).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.

Asian women with breast cancer are often studied in aggregate, belying significant intragroup diversity. The authors sought to examine differences in breast cancer characteristics and outcomes among Asian women.Asian, non-Hispanic Black, Hispanic, and non-Hispanic White women aged 18 years and older who were diagnosed with breast cancer from 1990 to 2016 were identified in the Surveillance, Epidemiology, and End Results 18 database. Asian patients were subclassified as Chinese, Japanese, Korean, Filipino, Vietnamese, South Asian (Asian Indian or Pakistani), Southeast Asian (SEA, i.e., Cambodian, Laotian, Hmong, or Thai), or other Asian. Unadjusted overall survival (OS) and cancer-specific survival (CSS) were estimated using the Kaplan-Meier method. Cox proportional hazards models were used to estimate adjusted OS and CSS.In total, 910,415 women were included (Asian, n = 63,405; Black, n = 92,226; Hispanic, n = 84,451; White, n = 670,333). Asian women had higher rates of human epidermal growth factor receptor 2 (HER2)-positive disease compared with White women (18.7% vs 13.8%) and had the highest 10-year unadjusted OS and CSS among all racial/ethnic groups (all P.001). SEA women had the highest rates of stage IV disease at presentation, whereas Japanese women had the lowest rates (5.9% vs 2.7%; P.001). Japanese women had the highest 10-year unadjusted CSS (89.4%; 95% confidence interval, 88.7%-90.1%) of any distinct Asian group, whereas SEA women had the worst unadjusted CSS (78%; 95% confidence interval, 74.1%-81.3%; P.001). After adjustment, SEA women had the worst OS of any Asian group and were the only Asian group without improved OS compared with White women (reference category; P = .08).Breast cancer characteristics and outcomes vary significantly among Asian women. Future research should consider disaggregation by country or region of origin to identify subgroups that are at risk for worse outcomes than aggregated data may suggest.Asian women with breast cancer are frequently studied as a single entity. However, Asian ethnic groups differ greatly by country of origin, genetic ancestry, disease frequency, socioeconomic status, patterns of immigration, as well as dietary and cultural practices. Women of different Asian ethnicities vary significantly with regard to cancer characteristics, such as mortality and tumor subtype. Future research should disaggregate these populations to better understand, treat, and counsel Asian patients with breast cancer.

Background: Guideline-concordant care (GCC) for DCIS includes surgery, radiation, and endocrine treatment. Active surveillance (AS) is a strategy under study for management of low risk DCIS. The PORTAL Study was designed to evaluate patient reported outcomes (PROs) after GCC for DCIS compared to women who received AS for DCIS combined with women with a history of other atypical lesions (atypical ductal hyperplasia (ADH), or atypical lobular hyperplasia/lobular carcinoma in situ (LN), as proxies for AS-managed DCIS. Methods: The PORTAL Study invited women age≥ 18, diagnosed with DCIS, ADH, or LN between 2012-2017 from 4 academic centers to complete a one-time, cross-sectional survey. Clinical, pathological, and treatment information was obtained from medical record review. The primary outcome was breast/chest wall pain assessed with the Breast Cancer Pain Questionnaire (BCPQ) including severity (10-point scale, ≥3=clinically relevant), a Pain Burden Index (PBI), which is a composite of severity, frequency, and location (breast, arm, side, axilla) and assessments of sensory disturbances, and impact of pain on emotional and physical functioning. Additional PROs included measures of generalized pain (Brief Pain Inventory), anxiety (STAI-Short Form), depression (CES-D), and QOL (Quality of Life in Adult Cancer Survivors). Pain, psychosocial, and QOL outcomes were compared between the GCC vs. AS groups using Wilcoxon Rank Sum and Chi-Square tests. Results: Of 1565 patients invited and sent a survey, 927 (59%) responded to the survey with evaluable pain outcome data. Median time from diagnosis was 3.8 years. Median age at survey completion was 58 (range: 26-94) years; 13% identified as non-White; 4% Hispanic. Among those with DCIS (n=554), 97% had GCC (62%, lumpectomy, 38%, mastectomy; 48%, radiation), representing 58% of participants vs 42% representing AS. The prevalence of clinically relevant pain was higher in the GCC vs. AS group (16.5% vs 9%, p=.0009). Median BCPQ-PBI, sensory disturbance, physical, and emotional impact scores were all higher (p BCPQ Scores, GCC vs. ASGCCASMean (range)Median (IQR)Mean (range)Median (IQR)p*PBI6.4 (0-80)0 (0-9)2.9 (0-64)0 (0-0) Citation Format: Shoshana M Rosenberg, Laura H Hendrix, Kristin L Schreiber, Alastair M Thompson, Isabelle Bedrosian, Kevin S Hughes, Thomas Lynch, Desiree Basila, Deborah E Collyar, Elizabeth S Frank, Sonja Darai, Conor Lanahan, Jeffrey R Marks, Jennifer K Plichta, Terry Hyslop, Ann H Partridge, E. Shelley Hwang. The Patient-reported Outcomes after Routine Treatment of Atypical Lesions (PORTAL) study: Pain, psychosocial wellbeing, and quality of life among women undergoing guideline concordant care for DCIS vs. active surveillance for in situ and atypical lesions [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-21-07.

Background: Meta-analyses have demonstrated that young women ≤40 (YW) derive the most benefit from chemotherapy (EBCTCG, Lancet. 1998). Oncotype DX was designed to determine the benefit of chemotherapy in women with ER+/HER2-, node-negative (LN-) breast cancer based on recurrence score (RS). TAILORx reported clinically meaningful benefits in freedom-from-distant recurrence in women Methods: Using the National Cancer Data Base (NCDB), we identified individuals age 25) RS. Age categories were classified as ≤40, 41-50, and >50. Chi-square tests or Fisher’s exact tests were used to compare categorical variables. Logistic regression was used to estimate the association of RS score and age group with adjuvant chemotherapy use, after adjustment for known covariates. Kaplan-Meier curves were used to visualize unadjusted overall survival (OS), and Cox proportional hazards models were used to estimate adjusted OS. Results: 120,051 women were identified, of whom 4,781 were ≤40 years, 24,846 were 41-50, and 90,424 were >50. By age group, 20% of YW had a high RS compared to 12% of women age 41-50 and 15% of women >50 (p50 to receive chemotherapy (p Conclusions: High RS is more common in YW (≤40) than those age 41-50 or >50, and is associated with worse OS. YW with an int or low RS are more likely to receive chemotherapy despite unclear benefit. Chemotherapy was omitted in over half of YW with RS of 16-25, highlighting the uncertainty in clinical practice which will remain until further studies inform optimal systemic treatment specific to YW. 1. Sparano, J.A., et al., Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for Breast Cancer. New England Journal of Medicine, 2019. 380(25): p. 2395-2405. Citation Format: Sarah Sammons, Yi Ren, Jeremy Force, Oluwadamilola M. Fayanju, Laura H. Rosenberger, Jennifer K. Plichta, Gretchen Kimmick, Kelly Westbrook, Susan Dent, Carey Anders, Samantha M. Thomas, Terry Hyslop, E. S. Hwang, P. K. Marcom, Rachel A. Greenup. Characterization of oncotype DX recurrence score and chemotherapy utilization patterns in young women (≤40) with early stage ER+/HER-, lymph node negative breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-10.

Pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) is associated with improved overall survival (OS) in patients with breast cancer, but it is unclear how post-NACT response influences radiation therapy administration in patients presenting with node-positive disease. We sought to determine whether nodal pCR is associated with likelihood of receiving nodal radiation and whether radiation therapy among patients experiencing nodal pCR is associated with improved OS.Clinical N1 (cN1) female breast cancer patients diagnosed during 2010 to 2015 who were ypN0 (ie, nodal pCR; n = 12,341) or ypN1 (ie, residual disease; n = 13,668) after NACT were identified in the National Cancer Database. Multivariate logistic regression was used to identify factors associated with receiving radiation therapy. Cox proportional hazards modeling was used to estimate the association between radiation therapy and adjusted OS.The study included 26,009 patients; 43.9% (n = 5423) of ypN0 and 55.3% (n = 7556) of ypN1 patients received nodal radiation. Rates of nodal radiation remained the same over time among ypN0 patients (trend test, P = .29) but increased among ypN1 patients from 49% in 2010 to 59% in 2015 (trend test, P.001). After adjusting for covariates, nodal pCR (vs no stage change) was associated with decreased likelihood of nodal radiation after mastectomy (∼20% decrease) and lumpectomy (∼30% decrease; both P.01). After mastectomy, nodal (vs no) radiation conferred no significant survival benefit in ypN0 patients, but it approached significance for ypN1 patients (hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.69-0.99, P = .04; overall P = .11). After lumpectomy, nodal radiation was associated with improved adjusted OS for ypN0 (HR, 0.38; 95% CI, 0.22-0.66) and ypN1 patients (HR, 0.44; 95% CI, 0.30-0.66; both P.001), but this improvement was not significantly greater than that associated with breast-only radiation.ypN0 patients were less likely to receive nodal radiation than ypN1 patients were, suggesting that selective omission already occurs and, in the context of limited survival data, could potentially be appropriate for select patients.

BACKGROUND: Given presumed differences in disease severity between young (≤ 45 years) and elderly (≥ 75 years) women with breast cancer, we sought to compare tumor histopathology, stage at presentation, patterns of care, and survival at the extremes of age. METHODS: Adults with stages 0–IV breast cancer in the National Cancer Database (2004–2015) were categorized by age (18–45 years, 46–74 years, ≥ 75 years) and compared. Kaplan–Meier curves were used to visualize unadjusted overall survival (OS). A Cox proportional-hazards model was used to estimate the effect of age group, including adjustment for tumor subtype [hormone receptor [HR]+/HER2−, HER2+, triple-negative (TN)]. RESULTS: Of the 1,201,252 patients identified, 13% were ≤ 45 years and 17.5% were ≥ 75 years. Women ≤ 45 years were more likely to have higher pT/N stages and grade 3 disease compared to older patients; however, rates of de novo cM1 disease were comparable (3.7% vs 3.5%). HER2+ and TN tumors were more common in those ≤ 45 years (HER2+ : 18.6% vs 9.2%; TN: 14.9% vs 8.2%), while HR+/HER2− tumors were more likely in women ≥ 75 years (69.3% vs 51.3%) (all p < 0.001). Younger patients were more likely to undergo mastectomy vs lumpectomy (56% vs 34%), and receive chemotherapy (65.8% vs 10.2%) and radiation (56.2% vs 39.5%). After adjustment, OS was worse in older patients (older HR 2.94, CI 2.86–3.03). CONCLUSIONS: High-risk tumor subtypes and comprehensive multimodal treatment remain significantly more common among younger women (≤ 45 years) with breast cancer, yet, elderly women are similarly diagnosed with incurable de novo metastatic disease. Tailored screening and treatment strategies are critical to prevent age-related disparities in breast cancer care.

PURPOSE: Inflammatory breast cancer (IBC) is an aggressive variant for which axillary lymph node dissection following neoadjuvant chemotherapy (NACT) remains standard of care. But with increasingly effective systemic therapy, it is unclear whether more limited axillary surgery may be appropriate in some IBC patients. We sought to examine whether extent of axillary lymph node (LN) surgery was associated with overall survival (OS) for IBC. METHODS: Female breast cancer patients with non-metastatic IBC (cT4d) diagnosed 2010–2014 were identified in the National Cancer Data Base. Cox proportional hazards modeling was used to estimate the association between extent of axillary surgery (≤9 vs ≥10 LNs removed) and OS after adjusting for covariates, including post-NACT nodal status (ypN0 vs ypN1–3) and radiotherapy receipt (yes/no). RESULTS: 3,471 patients were included: 597 (17.2%) had cN0 disease, 1,833 (52.8%) had cN1 disease, and 1,041 (30%) had cN2–3 disease. 49.9% of cN0 patients were confirmed to be ypN0 on post-NACT surgical pathology. Being ypN0 (vs ypN1–3) was associated with improved adjusted OS for all patients. Radiotherapy was associated with improved adjusted OS for cN1 and cN2–3 patients but not for cN0 patients. Regardless of ypN status, there was a trend towards improved adjusted OS with having ≥10 (vs ≤9) LNs removed for cN2–3 patients (HR 0.78, 95% CI 0.60–1.01, p=0.06) but not for cN0 patients (p=0.83). CONCLUSIONS: A majority of IBC patients in our study presented with node-positive disease, and for those presenting with cN2–3 disease, more extensive axillary surgery is potentially associated with improved survival. For cN0 patients, however, more extensive axillary surgery was not associated with a survival benefit, suggesting an opportunity for more personalized care.

Background We aim to determine clinical and pathological stage discordance rates and to evaluate factors associated with discordance. Methods Adults with clinical stages I-III breast cancer were identified from the National Cancer Data Base. Concordance was defined as cTN = pTN (discordance: cTN≠pTN). Multivariate logistic regression was used to identify factors associated with discordance. Results Comparing clinical and pathological stage, 23.1% were downstaged and 8.7% were upstaged. After adjustment, factors associated with downstaging (vs concordance) included grade 3 (OR 10.56, vs grade 1) and HER2-negative (OR 3.79). Factors associated with upstaging (vs concordance) were grade 3 (OR 10.56, vs grade 1), HER2-negative (OR 1.25), and lobular histology (OR 2.47, vs ductal). ER-negative status was associated with stage concordance (vs downstaged or upstaged, OR 0.52 and 0.87). Conclusions Among breast cancer patients, nearly one-third exhibit clinical-pathological stage discordance. This high likelihood of discordance is important to consider for counseling and treatment planning.

Neoadjuvant chemotherapy (NACT) is often recommended for patients with node-positive invasive lobular carcinoma (ILC) despite unclear benefit in this largely hormone receptor-positive (HR+) group. We sought to compare overall survival (OS) between patients with node-positive ILC who received neoadjuvant endocrine therapy (NET) and those who received NACT. Women with cT1–4c, cN1–3 HR+ ILC in the National Cancer Data Base (2004–2014) who underwent surgery following neoadjuvant therapy were identified. Kaplan–Meier curves and Cox proportional hazards modeling were used to estimate unadjusted and adjusted overall survival (OS), respectively. Of the 5942 patients in the cohort, 855 received NET and 5087 received NACT. NET recipients were older (70 vs. 54 years) and had more comorbidities (Charlson–Deyo score ≥ 1: 21.1% vs. 11.5%), lower cT classification (cT3–4: 44.2% vs. 51.0%), lower rates of mastectomy (72.5% vs. 82.2%), lower rates of pathologic complete response (0% vs. 2.5%), and lower rates of postlumpectomy (73.2% vs. 91.0%) and postmastectomy (60.0% vs. 80.8%) radiation versus NACT recipients (all p

Standard treatment for ductal carcinoma in situ (DCIS) is similar to that of invasive carcinoma. However, there is significant controversy regarding the true clinical implications of DCIS, and thus, the best management strategy. The aim of this review is to highlight relevant biology, diagnostic considerations, treatment options, and recent clinical trials. Outcomes are generally excellent with low recurrence rates and exceptional disease-specific survival. Outcomes can be predicted using various prognostic indicators and/or nomograms to guide treatment decisions. Ongoing clinical trials of active surveillance are based upon the argument that ipsilateral invasive recurrence is the most clinically meaningful endpoint. These trials seek to compare ipsilateral invasive cancer diagnoses between standard of care and close monitoring. Recent trials have revealed the marked heterogeneity in the biology of DCIS, offering an opportunity to de-escalate therapy for women at lowest risk for progression. DCIS also presents an ideal setting in which to test novel prevention agents. Future care of patients with DCIS will include biomarker-based risk assessment in order to better individualize treatment to biologic risk of invasive progression.

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 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.

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.

Breast reconstructive surgery has changed significantly over the past decade. The incidence of nipple-sparing procedures and prophylactic mastectomy has also increased significantly as women and their surgeons use shared decision-making strategies. The following case history of two sisters, one with breast cancer and one at elevated risk for breast cancer, highlights the current standard of care with newer gold-standard procedures for mastectomy and subsequent reconstruction. A comparison of types of mastectomies, steps in reconstruction, and reconstruction options are discussed.

PURPOSE: We sought to examine tumor subtype, stage at diagnosis, time to surgery (TTS), and overall survival (OS) among Hispanic patients of different races and among Hispanic and non-Hispanic (NH) women of the same race. METHODS: Women 18 years of age or older who had been diagnosed with stage 0-IV breast cancer and who had undergone lumpectomy or mastectomy were identified in the National Cancer Database (2004-2014). Tumor subtype and stage at diagnosis were compared by race/ethnicity. Multivariable linear regression and Cox proportional hazards modeling were used to estimate associations between race/ethnicity and adjusted TTS and OS, respectively. RESULTS: A total of 44,374 Hispanic (American Indian [AI]: 79 [0.2%]; Black: 1,011 [2.3%]; White: 41,126 [92.7%]; Other: 2,158 [4.9%]) and 858,634 NH women (AI: 2,319 [0.3%]; Black: 97,206 [11.3%]; White: 727,270 [84.7%]; Other: 31,839 [3.7%]) were included. Hispanic Black women had lower rates of triple-negative disease (16.2%) than did NH Black women (23.5%) but higher rates than did Hispanic White women (13.9%; P < .001). Hispanic White women had higher rates of node-positive disease (23.2%) versus NH White women (14.4%) but slightly lower rates than Hispanic (24.6%) and NH Black women (24.5%; P < .001). Hispanic White women had longer TTS versus NH White women regardless of treatment sequence (adjusted means: adjuvant chemotherapy, 42.71 v 38.60 days; neoadjuvant chemotherapy, 208.55 v 201.14 days; both P < .001), but there were no significant racial differences in TTS among Hispanic patients. After adjustment, Hispanic White women (hazard ratio, 0.77 [95% CI, 0.74 to 0.81]) and Black women (hazard ratio, 0.75 [95% CI, 0.58 to 0.96]) had improved OS versus NH White women (reference) and Black women (hazard ratio, 1.15 [95% CI, 1.12 to 1.18]; all P < .05). CONCLUSION: Hispanic women had improved OS versus NH women, but racial differences in tumor subtype and nodal stage among Hispanic women highlight the importance of disaggregating racial/ethnic data in breast cancer research.

BACKGROUND. In 2002, breast cancer patients with supraclavicular nodal metastases (cN3c) were downstaged from AJCC stage IV to IIIc, prompting management with locoregional treatment. We sought to estimate the impact of multimodal therapy on overall survival (OS) in a contemporary cohort of cN3c patients. METHODS. Women ≥ 18 years with cT1-T4c/cN3c invasive breast cancer who underwent systemic therapy were identified from the 2004–2016 National Cancer Database. We compared three patient cohorts: (a) cN3c + multimodal therapy (systemic therapy, surgery, and radiation); (b) cN3c + non-standard therapy; and, (c) cM1. Logistic regression identified factors associated with receipt of multimodal therapy and Kaplan–Meier was used to estimate unadjusted OS. The Cox proportional hazards model estimated effects of diagnosis and treatment on OS after adjustment. RESULTS. Overall, 1827 (3.7%) patients with cN3c disease and 46,919 (96.3%) cM1 patients were identified. Of cN3c patients, 74.5% (n = 1362) received multimodal therapy and 25.5% (n = 465) received non-standard therapy; receipt of multimodal therapy was associated with improved 5-year OS (multimodal: 59% vs. M1: 28% vs. non-standard: 28%, log-rank p < 0.001). Adjusting for covariates, non-standard therapy was associated with an increased risk of death compared with receipt of multimodal therapy (HR 2.20, 95% CI 1.71–2.83, p < 0.001). Private insurance was the only patient characteristic associated with a greater likelihood of receiving multimodal therapy (OR 2.81; 95% CI, 1.64–4.82; p < 0.001). CONCLUSION. Women with cN3c breast cancer who received multimodal therapy demonstrated improved overall survival when compared with patients undergoing non-standard therapy and those with metastatic (M1) disease. Although selection bias may contribute to worse overall survival among cN3c patients undergoing non-standard therapy, national guidelines should encourage locoregional treatment in carefully selected patients.