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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

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.

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.

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.

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

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. 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.

Background The clinical behavior of breast cancer varies by racial and ethnic makeup (REM), but the impact of REM on the clinical outcomes of breast atypia remains understudied. We examined the impact of REM on risk of underlying or subsequent carcinoma following a diagnosis of breast atypia. Methods In this retrospective, single-institution chart review, adult women diagnosed with breast atypia (atypical ductal hyperplasia, atypical lobular hyperplasia, or lobular carcinoma in situ) were stratified by REM. Regression modeling was used to estimate risk of underlying or subsequent carcinoma. Results We identified 539 patients with breast atypia, including 15 Hispanic (2.8%), 127 non-Hispanic black (23.6%), and 397 non-Hispanic white women (73.7%). Diagnoses included 75.1% atypical ductal hyperplasia (n = 405), 4.6% atypical lobular hyperplasia (n = 25), and 20.2% lobular carcinoma in situ (n = 109). Rates for each type of atypia did not vary by REM (P = 0.33). Of those with atypia on needle biopsy, the rate of underlying carcinoma at excision was 17.3%. After adjustment, REM was not associated with greater risk for carcinoma at excision (P = 0.41). Of those with atypia alone on surgical excision, the rate of a subsequent carcinoma diagnosis was 15.4% (median follow-up 49 mo). REM was not associated with a long-term risk for carcinoma (P = 0.37) or differences in time to subsequent carcinoma (log-rank P = 0.52). Chemoprevention uptake rates were low (10.6%), especially among Hispanic (0%) and non-Hispanic black (3.8%) patients (P = 0.01). Conclusions Among patients with atypia, REM does not appear to influence type of histologic atypia, risk for carcinoma, or clinical outcome, despite differences in chemoprevention rates.

BACKGROUND. Men represent a small proportion of breast cancer diagnoses, and they are often excluded from clinical trials. Current treatments are largely extrapolated from evidence in women. We compare practice patterns between men and women with breast cancer following the publication of several landmark clinical trials in surgery. PATIENTS AND METHODS. Patients with invasive breast cancer (2004–2015) from the National Cancer Data Base were identified; subcohorts were created based on eligibility for NSABP-B06, CALGB 9343, and ACOSOG Z0011. Practice patterns were stratified by gender and compared. Cox proportional hazards regression analyses were utilized to estimate the association between OS and gender. RESULTS. Of the 1,664,746 patients identified, 99% were women and 1% were men. Among NSABP-B06 eligible men, mastectomy rates did not change (consistently ~ 80%), and their adjusted OS was minimally worse compared with women (HR 1.19, 95% CI 1.11–1.28). Following publication of CALGB 9343, omission of radiation after lumpectomy was less likely in men and lagged behind that of women, despite similar OS (male HR 0.92, 95% CI 0.59–1.44). Application of ACOSOG Z0011 findings resulted in deescalation of axillary surgery for men and women with comparable OS (male HR 0.69, 95% CI 0.33–1.45). CONCLUSIONS. Uptake of clinical trial results for men with breast cancer often mirrors that for women, despite exclusion from these studies. Furthermore, when study findings were applied to eligible patients, men and women demonstrated similar survival. Observational studies can help inform the potential application of study findings to this unique population and improve patient enrollment in clinical trials.

To determine whether the association between overall survival (OS) and response to neoadjuvant chemotherapy (NACT) in breast cancer patients varies with tumor subtype and anatomic extent of pathologic complete response (pCR).pCR after NACT predicts improved OS in breast cancer, but it is unclear whether pCR limited to the breast or axilla is also associated with OS.Women with cT1-3/cN0-1 breast cancer diagnosed in 2010 to 2014 who underwent surgery following NACT were identified in the NCDB and divided into 4 subtypes based on reported hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status. Kaplan-Meier curves and Cox proportional hazards models were used to estimate OS. Multivariate logistic regression was used to identify factors associated with post-NACT response, defined as upstage (yp stageclinical stage); no change (clinical stage = yp stage); overall (breast+axilla, ypT0N0), breast-only (ypT0N1/N1mic), or node-only (ypT1-3N0) pCR.Of 33,162 identified patients, 20,265 experienced overall pCR (n = 6370, 19.2%), breast-only pCR (n = 494, 1.5%), node-only pCR (n = 1133, 3.4%), no stage change (n = 9641, 29.1%), or upstage (n = 2627, 7.9%). Compared with no stage change, breast-only pCR was associated with improved OS in triple-negative disease [hazard ratio = 0.58, 95% confidence interval (95% CI) = 0.37-0.89], and node-only pCR was associated with improved OS in both triple-negative (hazard ratio = 0.55,95% CI = 0.39-0.76) and HR+/HER2- disease (hazard ratio = 0.54, 95% CI = 0.33-0.89). For patients achieving overall (breast+axilla) pCR, unadjusted 5-year OS was 0.94 (95% CI = 0.93-0.95), with no difference between patients who were cN0 (hazard ratio = 0.95, 95% CI = 0.93-0.96) or cN1 (hazard ratio = 0.94, 95% CI = 0.92-0.96) at diagnosis.In node-positive patients, pCR limited to either the breast or axilla predicts survival for select receptor subtypes. In patients achieving pCR in both the breast and axilla, survival is driven by response to NACT rather than presenting cN stage.

Recent studies suggest that surgical lymph node (LN) evaluation may be omitted in select elderly breast cancer patients as it may not influence adjuvant therapy decisions. To evaluate differences in adjuvant therapy receipt and overall survival (OS), we compared clinically node-negative (cN0) elderly patients who did and did not undergo axillary surgery. Patients aged ≥70 years in the National Cancer Database (2004–2014) with cT1-3, cN0 breast cancer were divided into two cohorts—those with surgical LN evaluation (one or more nodes removed) and those without (no nodes removed). Propensity scores were used to match patients based on age, year of diagnosis, tumor grade, cT stage, estrogen receptor status, and Charlson–Deyo comorbidity score. A Cox proportional hazards model was used to estimate the effect of LN surgery on OS. Overall, 133,778 patients were matched, of whom 102,247 patients (76.4%) underwent nodal surgery. Patients undergoing nodal surgery were more likely to receive chemotherapy (pN1-3: 22.2%; pN0: 5.8%; cN0-no nodal surgery: 2.8%; p

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

Metaplastic breast cancer (MBC) is characterized by chemoresistance and hematogenous spread. We sought to identify factors associated with improved MBC outcomes and increased likelihood of MBC diagnosis. Women ≥ 18 years of age with stage I–III MBC and non-MBC diagnosed between 2010 and 2014 were identified in the National Cancer Data Base. Kaplan–Meier and multivariate Cox proportional hazards models were used to estimate associations with overall survival (OS). Multivariate logistic regression identified factors associated with MBC diagnosis. Overall, 2451 MBC and 568,057 non-MBC patients were included; 70.3% of MBC vs. 11.3% of non-MBC patients were triple negative (p

Breast cancer staging concisely summarizes disease status, creating a framework for assessing and relaying prognostic information. The fundamental concepts and components of breast cancer staging are reviewed. The AJCC Cancer Staging Manual, which includes traditional anatomic factors, now includes additional tumor characteristics: tumor grade, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor 2 status, and (when available) multigene panel testing from the primary tumor. With these updates, staging provides the most reliable system for accurately predicting patient outcome. When the AJCC 8th edition guidelines are adopted, they will more closely reflect tumor biology.

Background Nipple-sparing mastectomy (NSM) has gained popularity for breast cancer treatment and prevention. There are limited data about long-term oncologic safety of this procedure. Study Design We reviewed oncologic outcomes of consecutive therapeutic NSM at a single institution. Nipple-sparing mastectomy was offered to patients with no radiologic or clinical evidence of nipple involvement. Results There were 2,182 NSM performed from 2007 to 2016. Long-term outcomes were assessed in the 311 NSM performed in 2007 to 2012 for Stages 0 to 3 breast cancer; 240 (77%) NSM were for invasive cancer and 71 (23%) were for ductal carcinoma in situ. At 51 months median follow-up, 17 patients developed a recurrence of their cancer. Estimated disease-free survival was 95.7% at 3 years and 92.3% at 5 years. There were 11 (3.7%) locoregional recurrences and 8 (2.7%) distant recurrences; 2 patients had simultaneous locoregional and distant recurrences. There were 2 breast cancer-related deaths in patients with isolated distant recurrences. No patient in the entire 2,182 NSM cohort has had a recurrence in the retained nipple-areola complex. Conclusions Rates of locoregional and distant recurrence are acceptably low after nipple-sparing mastectomy in patients with breast cancer. No patient in our series has had a recurrence involving the retained nipple areola complex.

BACKGROUND: Surgeons face the unique challenge of being responsible for both clinical encounters and surgical outcomes. We aim to explore how patient evaluations of surgeons may be influenced by patient and provider factors. METHODS: Patient responses from the 2016 CGCAHPS survey at a single institution were identified. A Poisson regression model was used to identify patient/provider factors associated with ratings. RESULTS: 11,007 surveys of 134 surgeons were included. After adjustment, higher overall surgeon ratings were associated with older patient age (p

BACKGROUND AND OBJECTIVES We sought to evaluate the impact of chemotherapy sequence on survival by comparing node-positive invasive lobular carcinoma (ILC) patients who received neoadjuvant (NACT) and adjuvant (ACT) chemotherapy. METHODS cT1-4c, cN1-3 ILC patients in the National Cancer Data Base (2004-2013) who underwent surgery and chemotherapy were divided into NACT and ACT cohorts. Kaplan-Meier curves and Cox proportional hazards modeling were used to estimate unadjusted and adjusted overall survival (OS), respectively. RESULTS Five thousand five hundred fifty-one (35.6%) of 15 573 ILC patients treated with chemotherapy received NACT. NACT patients had similar rates of pT3/4 disease (26.6% vs 26.2%), nodal involvement (median 3 vs 4), and number of lymph nodes examined (median 13 vs 14) but higher rates of mastectomy (81.8% vs 74.5%, P

BACKGROUND. Ductal carcinoma in situ (DCIS) with microinvasion (DCISM) can be challenging in balancing the risks of overtreatment versus undertreatment. We compared DCISM, pure DCIS, and small volume (T1a) invasive ductal carcinoma (IDC) as related to histopathology, treatment patterns, and survival outcomes. METHODS. Women ages 18–90 years who underwent breast surgery for DCIS, DCISM, or T1a IDC were selected from the SEER Database (2004–2015). Multi-variate logistic regression and Cox proportional hazards models were used to estimate the association of diagnosis with treatment and survival, respectively. RESULTS. A total of 134,569 women were identified: 3.2% DCISM, 70.9% DCIS, and 25.9% with T1a IDC. Compared with invasive disease, DCISM was less likely to be ER? or PR? and more likely to be HER2?. After adjustment, DCIS and invasive patients were less likely to undergo mastectomy than DCISM patients (DCIS: OR 0.53, 95% CI 0.49–0.56; invasive: OR 0.86, CI 0.81–0.92). For those undergoing lumpectomy, the likelihood of receiving radiation was similar for DCISM and invasive patients but lower for DCIS patients (OR 0.57, CI 0.52–0.63). After adjustment, breast-cancer-specific survival was significantly different between DCISM and the other two groups (DCIS: HR 0.59, CI 0.43–0.8; invasive: HR 1.43, CI 1.04–1.96). However, overall survival was not significantly different between DCISM and invasive disease, whereas patients with DCIS had improved OS (HR 0.83, CI 0.75–0.93). CONCLUSIONS. Although DCISM is a distinct entity, current treatment patterns and prognosis are comparable to those with small volume IDC. These findings may help providers counsel patients and determine appropriate treatment plans.

Burn injury increases the risk of morbidity and mortality by promoting severe hemodynamic shock and risk for local or systemic infection. Graft failure due to poor wound healing or infection remains a significant problem for burn subjects. The mechanisms by which local burn injury compromises the epithelial antimicrobial barrier function in the burn margin, containing the elements necessary for healing of the burn site, and in distal unburned skin, which serves as potential donor tissue, are largely unknown. The objective of this study was to establish defects in epidermal barrier function in human donor skin and burn margin, in order to identify potential mechanisms that may lead to graft failure and/or impaired burn wound healing. In the present study, we established that epidermal lipids and respective lipid synthesis enzymes were significantly reduced in both donor skin and burn margin. We further identified diverse changes in the gene expression and protein production of several candidate skin antimicrobial peptides (AMPs) in both donor skin and burn margin. These results also parallel changes in cutaneous AMP activity against common burn wound pathogens, aberrant production of epidermal proteases known to regulate barrier permeability and AMP activity, and greater production of pro-inflammatory cytokines known to be induced by AMPs. These findings suggest that impaired epidermal lipid and AMP regulation could contribute to graft failure and infectious complications in subjects with burn or other traumatic injury.

Young age at breast cancer diagnosis has been associated with increased risk of recurrence and mortality. We reevaluated this assumption in a large, modern cohort of women diagnosed with breast cancer at age ≤40 years. We identified women with breast cancer at age ≤40 years at a single institution from 1996–2008. We assessed locoregional recurrence (LRR), distant recurrence, disease-free survival (DFS), and overall survival (OS), and correlated patient and tumor characteristics with outcomes. We identified 584 women aged ≤40 years with breast cancer. Median age was 37 years, and median follow-up was 124 months; 61.5 % were stages 0–I and 38.5 % were stages II–III. Overall, 57.4 % had lumpectomies and 42.5 % mastectomies. DFS was 93 % at 5 years and 84.5 % at 10 years. OS was 93 % at 5 years and 86.5 % at 10 years. On multivariate analysis, worse DFS was associated with positive nodes (p = 0.002); worse OS was associated with larger tumor size (p = 0.042). When stratified by lumpectomy versus mastectomy, there were no significant differences in survival or recurrence. For lumpectomy patients, DFS was 96 % at 5 years and 88 % at 10 years; OS was 96 % at 5 years and 89 % at 10 years. For mastectomy patients, DFS was 89.5 % at 5 years and 79 % at 10 years; OS was 90 % at 5 years and 83 % at 10 years. Lumpectomy LRR rates were 1 % at 5 years and 4 % at 10 years. Mastectomy LRR rates were 3.5 % at 5 years and 8.7 % at 10 years. Outcomes for women with breast cancer at age ≤40 years have improved. Lumpectomy recurrence rates are low, suggesting that lumpectomy is oncologically safe for young breast cancer patients.

The American Society of Breast Surgeons (ASBrS) sought to provide educational guidelines for breast surgeons on how to incorporate genetic information and genomics into their practice. A comprehensive nonsystematic review was performed of selected peer-reviewed literature. The Genetics Working Group of the ASBrS convened to develop guideline recommendations. Clinical and educational guidelines were prepared to outline the essential knowledge for breast surgeons to perform germline genetic testing and to incorporate the findings into their practice, which have been approved by the ASBrS Board of Directors. Thousands of women in the USA would potentially benefit from genetic testing for BRCA1, BRCA2, and other breast cancer genes that markedly increase their risk of developing breast cancer. As genetic testing is now becoming more widely available, women should be made aware of these tests and consider testing. Breast surgeons are well positioned to help facilitate this process. The areas where surgeons need to be knowledgeable include: (1) identification of patients for initial breast cancer-related genetic testing, (2) identification of patients who tested negative in the past but now need updated testing, (3) initial cancer genetic testing, (4) retesting of patients who need their genetic testing updated, (5) cancer genetic test interpretation, posttest counseling and management, (6) management of variants of uncertain significance, (7) cascade genetic testing, (8) interpretation of genetic tests other than clinical cancer panels and the counseling and management required, and (9) interpretation of somatic genetic tests and the counseling and management required.

Although several prognostic variables and risk factors for breast cancer are age-related, the association between age and risk of cancer with breast atypia is controversial. This study aimed to compare the type of breast atypia and risk of underlying or subsequent breast cancer by age.Adult women with breast atypia (atypical ductal hyperplasia, atypical lobular hyperplasia, and lobular carcinoma in situ) at a single institution from 2008 to 2017 were stratified by age at initial diagnosis:50 y, 50-70 y, and70 y. Regression modeling was used to estimate the association of age with risk of underlying carcinoma or subsequent cancer diagnosis.A total of 530 patients with atypia were identified: 31.1% 50 y (n = 165), 58.1% 50-70 y (n = 308), and 10.8% 70 y (n = 57). The proportion of women with atypical ductal hyperplasia steadily increased with age, compared with atypical lobular proliferations (P = 0.04). Of those with atypia on needle biopsy, the overall rate of underlying carcinoma was 17.5%. After adjustment, older age was associated with a greater risk of underlying carcinoma (odds ratio: 1.028, 95% confidence interval: 1.003-1.053; P = 0.03). Of those confirmed to have atypia on surgical excision, the overall rate of a subsequent cancer diagnosis was 15.7%. Age was not associated with a long-term risk for breast cancer (P = 0.48) or the time to a subsequent diagnosis of carcinoma (log-rank P = 0.41).Although atypia diagnosed on needle biopsy may be sufficient to warrant surgical excision, older women may be at a greater risk for an underlying carcinoma, albeit the long-term risk for malignancy associated with atypia does not appear to be affected by age.

OBJECTIVE:: We assessed the changes that have resulted from the latest breast cancer staging guidelines and the potential impact on prognosis. BACKGROUND: Contemporary data suggest that combining anatomic staging and tumor biology yields a predictive synergy for determining breast cancer prognosis. This forms the basis for the American Joint Committee on Cancer’s (AJCC) Staging Manual, 8th edition. We assessed the changes that have resulted from the new staging guidelines and the potential impact on prognosis. METHODS: Women with stages I to III breast cancer from 2010 to 2014 in the National Cancer Data Base were pathologically staged according to the 7th and 8th editions of the AJCC Staging Manual. Patient characteristics and restaging outcomes were summarized. Unadjusted overall survival (OS) was estimated, and differences were assessed. Cox proportional-hazards models were utilized to estimate the adjusted association of stage with OS. RESULTS: After restaging the 493,854 women identified, 6.8% were upstaged and 29.7% were downstaged. The stage changes varied by tumor histology, receptor status, tumor grade, and Oncotype DX scores (all P < 0.0001). Applying the 8th edition criteria yielded an incremental reduction in survival for each increase in stage, which was not consistently seen in the 7th edition. In a subgroup analysis based on hormone receptor (HR) status, those with stages II and III, and HR− disease had a worse OS than those with HR+ disease. CONCLUSIONS: Applying the 8th edition staging criteria resulted in a stage change for >35% of patients diagnosed with invasive breast cancer and refined OS estimates. Overall, the transition to the 8th edition is expected to better drive clinical care, treatment recommendations, and future research.

Although surgical management of the axilla for breast cancer continues to evolve, axillary lymphadenectomy remains the standard of care for women with advanced nodal disease. We sought to evaluate national patterns of care in axillary surgery, and its association with overall survival (OS) among women with N2–3 invasive breast cancer. Women (18–90 years) with clinical N2–3 invasive breast cancer who underwent axillary surgery were identified from the National Cancer Data Base (NCDB) from 2004 to 2013. Axillary surgery was categorized as sentinel lymph node biopsy (SLNB, 1–5 nodes) or axillary lymph node dissection (ALND, ≥ 10 nodes). Patient and treatment characteristics, trends over time, and overall survival (OS) were compared by surgical treatment. Overall, 22,156 patients were identified. At diagnosis, 68.5% had cN2 and 31.5% had cN3 disease. Treatment included: lumpectomy (27%), mastectomy (73%), adjuvant chemotherapy (53.4%), neoadjuvant chemotherapy (NAC) (39.7%), radiation (74%), and endocrine therapy (54.4%). In total, 9.9% (n = 2190) underwent SLNB and 90.1% (n = 19,966) underwent ALND. Receipt of SLNB was associated with private insurance, grade 3 disease, invasive ductal cancer, NAC, and lumpectomy (all p

Introduction: With a reported incidence of 2-12% in breast biopsy specimens, the appropriate management of atypical ductal hyperplasia (ADH) remains in evolution. At present, the optimal screening guidelines for patients with high-risk breast lesions such as ADH remain unclear. Current practices often parallel the surveillance of cancer patients and include a 6 month interval mammogram prior to resuming annual screening, which may result in unnecessary procedures and financial costs. This interval mammogram is typically a diagnostic study, which is an additional cost to the patient and healthcare system. The purpose of this study was to identify interval pathology following initial surgical resection and review associated costs. Methods: Following institutional review board approval, the pathology database from a single institution was queried for patients who underwent surgical excision for ‘atypical ductal hyperplasia’ from 2008 to 2013. Those who did not have follow-up data available were excluded. Subsequent clinical care was reviewed, including interval imaging and need for additional intervention. Based on a review of hospital charges from 2013, the average charge for a unilateral diagnostic mammogram (out-patient, digital) was $382. Results: There were 55 patients who underwent an excisional biopsy that were diagnosed with ADH and had subsequent follow-up. The median age was 57 years (range 38-82 years), and the median breast cancer risk assessment score was 2.3% at 5 years (range 0.5-17.9%) and 12.5% lifetime risk (range 2.2-37.6%). Pathology included concurrent lobular carcinoma in situ (n=1), atypical lobular hyperplasia (n=3), flat epithelial atypia (n=14), and papillary lesions (n=19). In addition to a routine clinical breast exam, a short-term follow-up diagnostic (ipsilateral) mammogram was performed in 35 patients. Of the 35 interval mammograms obtained, 31 yielded benign findings on initial imaging, while 4 patients required additional imaging that ultimately resulted in benign findings. The overall hospital charges for the 35 short interval mammograms alone during this 6 year period were roughly $13,370. For the patients that resumed annual surveillance, 3 had abnormal mammograms requiring additional imaging, and no malignancies were identified in this subset of patients. To date, the median physician follow-up is 3 years, and 52 patients have undergone at least one mammogram since their initial imaging; all subsequent findings have been benign for all patients. When extrapolated to national data, cost savings to the healthcare system from eliminating short interval mammograms would exceed $12 million annually without compromising clinical outcomes. Conclusions: Based on our findings, a 6 month follow-up mammogram is not recommended and incurs unnecessary costs to the patient and healthcare system. In the post-surgical breast, imaging may be misleading and result in additional procedures and significant charges that ultimately do not affect clinical outcomes. Although a clinical exam is still recommended at 6 months following surgical excision for a diagnosis of ADH, patients should forego short interval (6 month) imaging and resume annual mammogram surveillance. Citation Format: Jennifer K Plichta, Adrienne N Cobb, Gerard J Abood, Constantine Godellas, Claudia B Perez. Post-operative imaging after atypical ductal hyperplasia excision: The findings and costs [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-10-04.

Introduction. While the incidence of pancreatic cystic lesions has steadily increased, we sought to evaluate the changes in their surgical management. Methods. Patients with pancreatic cystic lesions who underwent surgical resection from 2003 to 2013 were identified. Clinicopathologic factors were analyzed and compared to a similar cohort from 1992 to 2002. Results. There were 134 patients with pancreatic cystic lesions who underwent surgical resection from 2003 to 2013, compared to 73 from 1992 to 2002. The most common preoperative imaging was a CT scan, although 66% underwent EUS and 63% underwent biopsy. Pathology included 18 serous, 47 mucinous, 11 pseudopapillary, and 58 intraductal papillary mucinous neoplasms (IPMN). In comparing cohorts, there were significantly fewer serous lesions and more IPMN. Postoperative complication rates were similar, and perioperative mortality rates were comparable. Conclusion. There has been a dramatic change in surgically treated pancreatic cystic tumors over the past two decades. Our data suggests that the incorporation of new imaging and diagnostic tests has led to greater detection of cystic tumors and a decreased rate of potentially unnecessary resections. Therefore, all patients with cystic pancreatic lesions should undergo a focused CT-pancreas, and an EUS biopsy should be considered, in order to best select those that would benefit from surgical resection.

Background The adequacy of breast-conserving surgery (BCS) for invasive or in situ disease is largely determined by the final surgical margins. Although margin status is associated with various clinicopathologic features, the influence of resident involvement remains controversial. Methods Patients who underwent BCS for malignancy from 2009 to 2012 were identified. The effects of various clinicopathologic characteristics and resident involvement were evaluated. Results Of the 502 cases performed, a resident assisted with most surgeries (95%). The overall rate of positive margins was 30%, which was not associated with resident involvement. Interns assisting from July to September had significantly lower rates of positive margins. Margins were more likely to be positive following any given resident's first 3 cases on their breast rotation than throughout the remainder of their rotation. Conclusion Although resident level alone does not influence the adequacy of BCS, experience gained over time does appear to be associated with lower rates of positive margins.

OBJECTIVE: We evaluated patterns of surgical care and their association with overall survival among a contemporary cohort of women with stage IV breast cancer. BACKGROUND: Surgical resection of the primary tumor remains controversial among women with stage IV breast cancer. METHODS: Women diagnosed with clinical stage IV breast cancer from 2003 to 2012 were identified from the American College of Surgeons National Cancer Database. Those with intact primary tumors who were alive 12 months after diagnosis were categorized by treatment sequence: (1) surgery before systemic therapy, (2) systemic therapy before surgery, and (3) systemic therapy alone. Multivariate logistic regression was used to estimate the association of treatment sequence with surgery type. Overall survival was estimated using multivariate Cox proportional hazards models. RESULTS: Among 24,015 women, 56.2% (13,505) underwent systemic therapy alone and 43.8% (10,510) underwent surgical resection. Rates of surgery decreased slightly over time (43.1% in 2003 to 41.9% in 2011). Treatment with systemic therapy before surgery was associated with larger tumor size (median 4.5 vs 3.1 cm, P < 0.001) and receipt of mastectomy (81.4% vs 52.2%, P < 0.001) when compared to those who underwent surgery first. Receipt of surgery, whether before or after systemic therapy (Hazard Ratio, 0.68; 95% confidence interval, 0.62–0.73; Hazard Ratio, 0.56; 95% confidence interval, 0.52–0.61; P < 0.001), was independently associated with improved adjusted overall survival when compared to systemic therapy alone. CONCLUSIONS: Surgical resection of the primary tumor occurs in almost half of women with stage IV breast cancer alive 1 year after diagnosis, and is increasingly occurring after systemic therapy. Coordinated multidisciplinary care remains highly relevant in the setting of metastatic breast cancer, where surgical decisions should be made on an individual basis and may affect survival in select women.

The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial established the safety of omitting axillary lymph node dissection (ALND) for early-stage breast cancer patients with limited nodal disease undergoing lumpectomy. We examined the extent of axillary surgery among women eligible for Z0011 based on patient age and tumor subtype. Patients with cT1–2, cN0 breast cancers and one or two positive nodes diagnosed from 2009 to 2014 and treated with lumpectomy were identified in the National Cancer Data Base. Sentinel lymph node biopsy (SLNB) was defined as the removal of 1–5 nodes and ALND as the removal of 10 nodes or more. Tumor subtype was categorized as luminal, human epidermal growth factor 2-positive (HER2+), or triple-negative. Logistic regression was used to estimate the odds of receiving SLNB alone versus ALND. The inclusion criteria were met by 28,631 patients (21,029 SLNB-alone and 7602 ALND patients). Patients 70 years of age or older were more likely to undergo SLNB alone than ALND (27.0% vs 20.1%; p

The appropriate management of breast cancer risk in BRCA mutation carriers following ovarian cancer diagnosis remains unclear. We sought to determine the survival benefit and cost effectiveness of risk-reducing mastectomy (RRM) among women with BRCA1/2 mutations following stage II–IV ovarian cancer. We constructed a decision model from a third-party payer perspective to compare annual screening with magnetic resonance imaging (MRI) and mammography to annual screening followed by RRM with reconstruction following ovarian cancer diagnosis. Survival, overall costs, and cost effectiveness were determined by decade at diagnosis using 2015 US dollars. All inputs were obtained from the literature and public databases. Monte Carlo probabilistic sensitivity analysis was performed with a $100,000 willingness-to-pay threshold. The incremental cost-effectiveness ratio (ICER) per year of life saved (YLS) for RRM increased with age and BRCA2 mutation status, with greater survival benefit demonstrated in younger patients with BRCA1 mutations. RRM delayed 5 years in 40-year-old BRCA1 mutation carriers was associated with 5 months of life gained (ICER $72,739/YLS), and in 60-year-old BRCA2 mutation carriers was associated with 0.8 months of life gained (ICER $334,906/YLS). In all scenarios, $/YLS and mastectomies per breast cancer prevented were lowest with RRM performed 5–10 years after ovarian cancer diagnosis. For most BRCA1/2 mutation carriers following ovarian cancer diagnosis, RRM performed within 5 years is not cost effective when compared with breast cancer screening. Imaging surveillance should be advocated during the first several years after ovarian cancer diagnosis, after which point the benefits of RRM can be considered based on patient age and BRCA mutation status.