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Background: Triple-negative breast cancer (TNBC) accounts for a disproportionate amount of poor outcomes among breast cancers. A subset of TNBCs demonstrates an aggressive course with marked chemoresistance, rapid distant metastatic spread, and poor survival. The clinicopathologic and sociodemographic features associated with rapid relapse among TNBCs remain poorly understood. Primary Objective: To evaluate the relationship between clinicopathologic and sociodemographic features with rapid relapse in TNBC (rrTNBC). Methods: This large multi-institutional study analyzed a cohort of breast cancer patients diagnosed with TNBC who received treatment at one of ten academic centers that previously participated in a National Comprehensive Cancer Network (NCCN) outcomes database between 1998 and 2012. We defined rrTNBC as a distant metastatic recurrence event or death from any cause ≤24 months after diagnosis. We included patients with ≥2 years follow-up or had suffered a survival event within that timeframe. We excluded patients with de novo metastatic disease and those who did not receive chemotherapy. We randomly divided the total dataset into 70% training and 30% validation cohorts, balanced by the number of rrTNBC events. Covariates included study site, age at diagnosis, body mass index (BMI), race/ethnicity, education, median annual household income (2000 census tract), insurance type (Managed Care, Medicare, Medicaid, and Other), Charlson comorbidity index, tumor stage and grade at diagnosis, and adjuvant radiation treatment. Logistic regression was performed among the training dataset univariately for associations with rapid relapse vs. not. Features with a p-value Results: Among 41,839 patients with invasive breast cancer treated in these ten centers, 5256 had TNBC (12.6%), among whom 3016 had adequate follow-up to be included in the analysis. Bivariable analyses in the training cohort (n=2112) identified tumor stage at diagnosis, insurance type, age at diagnosis, BMI, race, and income to be associated with rrTNBC events (p15x increased risk of rapid relapse (adjusted OR [95% CI]: 16.5 [10.3, 26.4]; p Conclusion: Advanced tumor stage at diagnosis was the most influential predictor of rapid relapse among patients who had TNBC, while type of insurance remains an independent predictor in training and validation cohorts. Given the known association of sociodemographic disparities with tumor stage, further study of underlying causes and potential interventions to reduce rapid relapse of TNBC is warranted. Citation Format: Sarah Asad, Carlos H. Barcenas, Richard J. Bleicher, Adam L. Cohen, Sara H. Javid, Ellis G. Levine, Nancy U. Lin, Beverly Moy, Joyce Niland, Antonio C. Wolff, Michael J. Hassett, Daniel G. Stover. Factors associated with rapid relapse in triple negative breast cancer: A multi-institution study [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 P5-07-02.

Nipple-areola sparing mastectomy (NSM) may be offered to some women with breast cancer as an alternative to skin sparing (SSM) or total mastectomy (TM) with excellent cosmetic results and acceptable recurrence risk. The aim of this study is to determine the local/regional recurrence rate of NSM in comparison to SSM and TM at our institution and to determine the factors that may be associated with risk of recurrence. Women who underwent NSM (n=148), SSM (n=660) or TM (n=443) at City of Hope National Medical Center between May 2007 and December 2014 for Stage 0-III breast cancer were identified retrospectively. Exclusions were: women with inflammatory breast cancer and those who had mastectomy for recurrent breast cancer. Overall survival (OS) and disease free survival (DFS) were analyzed using Cox regression controlling for age, race/ethnicity, stage, histology, grade, hormone receptor and Her2 receptor status. There were total of 165 NSMs, 704 SSMs and 466 TMs performed for cancer, accounting for the patients with bilateral cancers. The median follow up time was 38, 58 and 55 months for NSM, SSM and TM, respectively. Median (range) age at diagnosis was 49 (23-74) for NSM, 51 (23-90) for SSM and 59 (26-92) for TM. In the NSM group, 76% of patients had invasive ductal cancer (IDC) and 15% had ductal carcinoma in-situ (DCIS); this was comparable to 73% and 13% in the SSM group and 78% and 9% in the TM group, respectively. The majority of patients who underwent NSM had Stage II disease (45%), which was similar to SSM (43%) and TM (44%). Only 3% of NSM patients had Stage III disease compared to 17% of SSM patients and 29% of TM patients. Most of the patients in all 3 surgical groups received adjuvant chemotherapy (NSM 59%; SSM 52%; TM 51%). Of patients who underwent NSM, 20% received neoadjuvant chemotherapy, compared with 29% of SSM patients and 35% of TM patients. The local/regional recurrence rate per breast was 12/165 (7.3%) for NSM, 23/704 (3.3%) for SSM and 11/466 (2.4%) for TM (n=11). Median time to recurrence was 20, 26 and 16 months for NSM, SSM and TM, respectively. Of the NSMs performed only 1 recurrence occurred at the nipple-areolar complex (0.6%), 9 recurrences were at the chest wall (5.5%) and 2 were at the axilla (1.2%). Eight recurrences after NSM had DCIS in addition to IDC at the time of initial diagnosis while 2 had pure DCIS, 1 had pure IDC and 1 had invasive lobular cancer. There were 8 recurrences with estrogen receptor (ER) and progesterone receptor (PR) positivity at the time of initial diagnosis, that converted to ER+, PR-. One third of recurrences after NSM had multifocal disease. There was no significant difference found in adjusted overall survival (p=0.49) and adjusted disease free survival (p=0.10) among NSM, SSM and TM patients. Even though there is higher rate of local/regional recurrence with NSM, there is no difference in overall and disease-free survival at our institution. Presence of DCIS may be an important factor for recurrence. From these data we conclude that NSM is an oncologically acceptable alternative to SSM and TM, with excellent cosmetic results. Citation Format: Bostanci Z, Wang X, Ottesen R, Nikowitz J, Jones VC, Springer L, Lai L, Taylor L, Vito CA, Paz IB, Niland J, Kruper L, Yim JH. Oncological safety of nipple-areola sparing mastectomy in comparison with skin sparing and total mastectomy: Results from a NCI-designated comprehensive cancer center [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-22-12.

Introduction: Population based studies (eg, Hershman et al. BCRT 2006 and Lohrisch et al. JCO 2006) showed poorer survival associated with long delays in adjuvant chemotherapy (CTX) initiation following definitive surgery (DS) for women with breast cancer (BC). Delays in CTX following diagnosis (DX) have not been evaluated. The ASCO/NCCN quality measures (QMs) recommend CTX Methods: 4,608 women with stage I-III HER2 negative breast cancer diagnosed between 2000 and 2006 at 8 NCCN centers were identified using the NCCN outcomes database. Patients with T3/4 disease or who received neoadjuvant therapy were excluded. The association between CTX timing and OS was evaluated using multivariate Cox models adjusted for CTX type, age, race, BMI, residential distance, insurance, SES, comorbidity, ER/PR, LVI, grade, T stage, and N stage. The impact of CTX timing was evaluated using a >90-day (d) DS-to-CTX threshold, based on poor outcomes observed in prior studies, and a >120d DX-to-CTX threshold, based on the ASCO/NCCN QMs. Results: Median follow-up was 7.2 years and OS at 7 years was 89%. Overall, 401 (8.7%) patients received CTX >120d after DX and 113 (2.4%) patients received CTX >90d after DS. The DX-to-CTX interval was more strongly correlated with the DX-to-DS (r = 0.74) interval than DS-to-CTX (r = 0.54) interval. A >90d DS-to-CTX interval was significantly associated with poorer survival (HR: 1.65, 95% CI 1.04–2.60, p = 0.03) in adjusted analyses. Shorter DS-to-CTX thresholds of >60d (n = 636, HR: 1.13, 95% CI: 0.89–1.43, p = 0.319) or >75d (n = 273, HR: 1.05, 95% CI 0.74–1.49, p = 0.76) were not associated with OS. The association between a >120d DX-to-CTX interval and OS was not statistically significant (HR: 1.32, 95% CI 0.99–1.76, p = 0.06). Patients who received CTX >135d (n = 231, HR 1.25, 95% CI: 0.87–1.81, p = 0.22) or >150d (n = 128, HR 1.15, 95% CI: 0.59–2.24, p = 0.69) after DX did not display an increased risk of death. Excluding pathological staging factors from the model had no effect on the results. In subgroup analyses stratified by ER/PR, LVI, grade, T stage or N stage, a >120d delay in CTX did not display significant associations with OS. Among ER/PR negative patients, the association between a >120d delay and OS was borderline non-significant after adjusting the p-value for multiple hypothesis testing using the false discovery rate method (HR: 1.80, 95% CI: 1.16–2.79, p = 0.09). Conclusion: Consistent with previous studies, CTX delays of >90 days following surgery were associated with poorer survival. OS was not significantly compromised in patients with DX-to-CTX intervals >120 days although this analysis may have limited power to detect small effects. More variation in the DX-to-CTX interval was attributed to pre-surgery time which may explain the differences observed between the DX-to-CTX and DS-to-CTX intervals. Among patients with ER/PR negative disease, a non-significant association between OS and a >120 day DX-to-CTX interval was observed that warrants further examination. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-13-05.

PURPOSE: Well-conducted cancer therapeutic clinical trials are essential for improving patient outcomes. Unfortunately, less than 5% of new cancer patients participate in clinical trials on average nationwide. Failure to recruit eligible patients represents a major impediment to the success of clinical trials. Barriers to patient accrual in cancer clinical trials must be identified and overcome to increase patient participation. MATERIALS AND METHODS: A retrospective analysis of 418 patients with a diagnosis of breast cancer seen at City of Hope Medical Center in 2009 was performed. Along with descriptive analysis of patient demographic data, logistic regression analyses were performed to evaluate predictors of enrollment. RESULTS: Of the 418 new breast cancer patients in 2009, we determined that 138 (33%) were eligible for available therapeutic clinical trials at City of Hope. At the initial visits, physicians did not consider clinical trials in 32% (44/138) of these patients. Of the 138 eligible patients, 58% (80/138) of patients participated in clinical trials. The remainder (58/138, 42%) either declined trial participation despite meeting eligibility criteria (14/58, 24%), or were not considered for clinical trials by their respective physician (44/58, 76%). By logistic regression analysis, patients with Stages II and III disease were significantly more likely to enroll in clinical trials compared to those with stage 0 or I (OR=2.89, 95% CI, 1.17−7.12, P = .02; OR=9.17, 95% Cl, 2.65−31.76, P=0.0005;, respectively). Age, preferred language, marital status, family history of breast cancer, and race were not found to be significant predictors of enrollment in therapeutic clinical trials. CONCLUSION: While enrollment of eligible breast cancer patients onto therapeutic clinical trials at City of Hope is high (58%), overall the proportion going onto clinical trials remains low (80/418, 19%), though higher than national averages. We found that the majority of patients did not enroll due to lack of availability of a suitable trial, ineligibility, or lack of offering of trial enrollment by the treating MD. Barriers to cancer clinical trial accrual should be prospectively identified and addressed in future studies, with the hope of leading to more vigorous enrollment. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-11-06.

Background: Previous research has suggested that young age at diagnosis is an independent risk factor for breast cancer recurrence and death in women with early stage breast cancer. However, young women are more likely to have aggressive subtypes of breast cancer. No prior studies have adequately controlled for tumor phenotype, including HER-2/neu (HER2) status, in particular. Recent evidence has suggested that the prognostic effect of young age varies by tumor subtype. Methods: We examined data from women with newly diagnosed Stage 1–3 breast cancer presenting to one of 8 NCCN centers between January 2000 and December 2007. Multivariate Cox proportional hazards models were used to assess the relationship between age and breast cancer specific survival, controlling for known prognostic factors and treatment. In addition, we conducted stratified analyses by estrogen receptor (ER) and HER2 status. Results: 19,633 women with Stage 1–3 breast cancer eligible for analysis including 2,177 (11%) who were age 40 years or younger at diagnosis. Younger women were more likely to be non-white or Hispanic, more educated, employed, and to have higher stage, high grade, ER-negative, progesterone receptor (PR) negative, and HER2−positive disease, and treated with chemotherapy and trastuzumab (all variables P< 0.0001 by Chi-Square test). 5-year survival among younger women was 94.1 (95% Confidence Interval [CI] 92.9−95.3) and 96.3 (95% CI 95.9−96.6) for older women. In a multivariate Cox proportional hazards model controlling for sociodemographic, disease, and treatment characteristics, women age < 40 or younger at diagnosis had increased mortality compared to older women (Hazard Ratio [HR] 1.26, 95% CI 1.02−1.56). In stratified analyses, age 40 or less was associated with increased mortality among women with ER-positive disease (HR 1.44, 95% CI 1.01−2.05), but was not among those with ER-negative disease (HR 1.15, 95% CI 0.85−1.55). Younger age was associated with a statistically significant increase in mortality among women with HER2−negative disease (HR 1.29, 95% CI 1.00−1.68), but this difference did not reach statistical significance among those with HER2−positive disease (HR 1.30, 95% CI 0.82−2.09). Conclusions: The effect of age on short-term survival of women with early breast cancer appears to vary by breast cancer subtype, particularly ER status. Further research to elucidate differences in breast cancer biology and efficacy of therapy within tumor types by age is warranted. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-08-05.