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BackgroundThe American Joint Committee on Cancer (AJCC) 8th edition staging system for breast cancer has been validated in the upfront surgery setting, but has not been examined for its prognostic impact on patients undergoing neoadjuvant chemotherapy.MethodsThe National Cancer Data Base was used to identify patients with invasive unilateral breast cancer from 2010 to 2015 who underwent neoadjuvant chemotherapy. AJCC clinical stage classification was compared between the 7th and 8th editions. Receiver operating characteristic analysis of Kaplan–Meier overall survival (OS) was used to determine the predictive fit of the 7th and 8th edition staging in estimating OS.ResultsAJCC 7th and 8th clinical staging assignments were applied to 57,466 patients who underwent neoadjuvant chemotherapy for stage I–III breast cancer from 2010 to 2015. Overall, 37.5% of patients were downstaged and 27.8% were upstaged from the 7th to the 8th edition classification. Kaplan–Meier curves comparing 7th and 8th edition staging differed in OS rates, with a mean follow-up time of 41.5 months. AJCC 8th edition prognostic staging was a better predictor of OS than 7th edition anatomic staging for both clinical stage [area under the curve (AUC) 0.67 vs. 0.62, p < 0.01] and pathological stage (AUC 0.70 vs. 0.66, p < 0.01).ConclusionsSixty-five percent of patients have a shift in clinical stage in the AJCC 8th edition. AJCC 8th edition staging has better predictive value for OS than 7th edition staging. While validation of these findings with an independent dataset is needed, 8th edition staging will help improve prognostic modeling in patients undergoing neoadjuvant chemotherapy.

Purpose To evaluate weight change patterns over time following the diagnosis of breast cancer and to examine the association of post-diagnosis weight change and survival outcomes in Black and White patients. Methods The study included 2888 women diagnosed with non-metastatic breast cancer in 2000–2017 in Chicago. Longitudinal repeated measures of weight and height were collected, along with a questionnaire survey including questions on body size. Multilevel mixed-effects models were used to examine changes in body mass index (BMI). Delayed entry Cox proportional hazards models were used to investigate the impacts of changing slope of BMI on survival outcomes. Results At diagnosis, most patients were overweight or obese with a mean BMI of 27.5 kg/m 2 and 31.5 kg/m 2 for Blacks and Whites, respectively. Notably, about 45% of the patients had cachexia before death and substantial weight loss started about 30 months before death. In multivariable-adjusted analyses, compared to stable weight, BMI loss (> 0.5 kg/m 2 /year) showed greater than 2-fold increased risk in overall survival (hazard ratio [HR] = 2.60, 95% CI 1.88–3.59), breast cancer-specific survival (HR = 3.05, 95% CI 1.91–4.86), and disease-free survival (HR = 2.12, 95% CI 1.52–2.96). The associations were not modified by race, age at diagnosis, and pre-diagnostic weight. BMI gain (> 0.5 kg/m 2 /year) was also related to worse survival, but the effect was weak (HR = 1.60, 95% CI 1.10–2.33 for overall survival). Conclusion BMI loss is a strong predictor of worse breast cancer outcomes. Growing prevalence of obesity may hide diagnosis of cancer cachexia, which can occur in a large proportion of breast cancer patients long before death.

Background Malignant phyllodes tumors of the breast have traditionally been treated with surgical excision. Recently, the use of adjuvant radiotherapy has been advocated to reduce the risk of local recurrence; however, this recommendation is controversial in the absence of consistent outcome data. We hypothesize that there has been a trend toward increased utilization of adjuvant radiotherapy for malignant phyllodes tumors despite its uncertain effect on outcomes. Methods Using the National Cancer Data Base, predictors of radiotherapy utilization were examined for women with malignant phyllodes from 1998 to 2009. Kaplan–Meier and Cox regression models were generated to determine the effect of radiotherapy on local recurrence (LR), disease-free survival (DFS), and overall survival (OS). Results Of the 3,120 patients with malignant phyllodes, 57 % underwent breast conservation surgery and 42 % underwent mastectomy. Overall, 14.3 % of women received adjuvant radiotherapy. Utilization of radiotherapy doubled over the study period (9.5 % in 1998–1999 vs. 19.5 % in 2008–2009, p  < 0.001). Women were significantly more likely to receive radiotherapy if they were diagnosed later in the study, were age 50–59 years old, had tumors >10 cm, or had lymph nodes removed. For the 1,774 patients with available recurrence data, overall recurrence was 14.1 %, and LR was 5.9 %. In adjusted models, adjuvant radiotherapy reduced LR (aHR 0.43, 95 % CI 0.19–0.95) but did not impact DFS or OS after 53 months’ median follow-up. Conclusions Utilization of adjuvant radiotherapy for malignant phyllodes doubled from 1998 to 2009. Radiotherapy significantly reduced LR but had no effect on DFS or OS.

PurposeDifferences in tumor biology, genomic architecture, and health care delivery patterns contribute to the breast cancer mortality gap between White and Black patients in the US. Although this gap has been well documented in previous literature, it remains uncertain how large the actual effect size of race is for different survival outcomes and the four breast cancer subtypes.MethodsWe established a breast cancer patient cohort at the University of Chicago Comprehensive Cancer Center. We chose five major survival outcomes to study: overall survival, recurrence-free survival, breast-cancer-specific survival, time-to-recurrence and post-recurrence survival. Cox proportional hazards models were used to estimate the hazard ratios between Black and White patients, adjusting for selected patient, tumor, and treatment characteristics, and also stratified by the four breast cancer subtypes.ResultsThe study included 2795 stage I–III breast cancer patients (54% White and 38% Black). After adjusting for selected patient, tumor and treatment characteristics, Black patients still did worse than White patients in all five survival outcomes. The racial difference was highest within the HR−/HER2+ subgroup, in both overall survival (hazard ratio = 4.00, 95% CI 1.47–10.86) and recurrence-free survival (hazard ratio = 3.00, 95% CI 1.36–6.60), adjusting for age at diagnosis, cancer stage, and comorbidities. There was also a significant racial disparity within the HR+/HER2− group in both overall survival and recurrence-free survival.ConclusionsOur study confirmed that racial disparity existed between White and Black breast cancer patients in terms of both survival and recurrence, and found that this disparity was largest among HR−/HER2+ and HR+/HER2− patients.

PurposeThere are a paucity of data and a pressing need to evaluate response to neoadjuvant chemotherapy (NACT) and determine long-term outcomes in young Black women with early-stage breast cancer (EBC).MethodsWe analyzed data from 2196 Black and White women with EBC treated at the University of Chicago over the last 2 decades. Patients were divided into groups based on race and age at diagnosis: Black women ≤ 40 years, White women ≤ 40 years, Black women ≥ 55 years, and White women ≥ 55 years. Pathological complete response rate (pCR) was analyzed using logistic regression. Overall survival (OS) and disease-free survival (DFS) were analyzed using Cox proportional hazard and piecewise Cox models.ResultsYoung Black women had the highest risk of recurrence, which was 22% higher than young White women (p = 0.434) and 76% higher than older Black women (p = 0.008). These age/racial differences in recurrence rates were not statistically significant after adjusting for subtype, stage, and grade. In terms of OS, older Black women had the worst outcome. In the 397 women receiving NACT, 47.5% of young White women achieved pCR, compared to 26.8% of young Black women (p = 0.012).ConclusionsBlack women with EBC had significantly worse outcomes compared to White women in our cohort study. There is an urgent need to understand the disparities in outcomes between Black and White breast cancer patients, particularly in young women where the disparity in outcome is the greatest.

Background The effectiveness of postmastectomy radiotherapy (PMRT) in terms of survival for breast cancer patients with American Joint Committee on Cancer (AJCC) pT1–2 and one to three tumor positive lymph nodes is controversial, especially in this era of more effective systemic treatment. Methods Using data from the National Cancer Database (NCDB) and the Surveillance, Epidemiology, and End Results (SEER) program between 1998 and 2008, this study respectively identified 93,793 and 36,299 women with AJCC pT1-2pN1 breast cancer who underwent mastectomy. The association of PMRT use with overall and cause-specific survival was examined using multivariable Cox models in subgroups defined by tumor stage. Results In the NCDB cohort, 21.5 % of the patients ( n  = 20,236) received PMRT, and a very similar percentage (21.9 %, n  = 7939) received PMRT in the SEER cohort. In the NCDB cohort, PMRT was associated with a 14 % relative risk reduction in all-cause mortality among the patients with two positive lymph nodes and tumors 2–5 cm in size or three positive nodes [hazard ratio (HR), 0.86; 95 % confidence interval (CI), 0.81–0.91; p  < 0.0001], but PMRT had no beneficial effect for the patients with one positive node or two positive nodes and tumors 2 cm in size or smaller. Analysis of the SEER cohort confirmed this heterogeneous effect, showing PMRT to be associated with a 14 % relative risk reduction in breast cancer cause-specific mortality among the patients with two positive nodes and tumors 2–5 cm in size or three positive nodes (HR 0.86; 95 % CI 0.77–0.96; p  = 0.007) but not in the other subgroup. Conclusion The effectiveness of radiotherapy depends on the combination comprising the number of positive lymph nodes and tumor size, which may enable more precise patient selection for PMRT.

Background The purpose of this study was to determine if newly diagnosed breast cancer patients undergoing contralateral prophylactic mastectomy (CPM) experience more complications than patients undergoing unilateral mastectomy (UM). Methods A total of 600 patients underwent either UM or CPM between January 2009 and March 2012 for unilateral breast cancer. Operative complications were classified as minor (aspirations, infection requiring antibiotics, partial flap and nipple necrosis, minor bleeding, delayed wound healing) or major (hematoma or seroma requiring operation, infection requiring rehospitalization, blood product transfusion, total flap or nipple loss, implant removal), mixed (both minor and major complications), or multiple. Chi-square and multivariate logistic regressions were used for the analysis. Results Of the 600 patients, 391 (65 %) underwent UM and 209 (35 %) underwent CPM. Across all complication groups, there were significantly more complications in the CPM group versus the UM group (41.6 vs. 28.6 %, p  = 0.001). Major complications alone were significantly greater in the CPM versus the UM group (13.9 vs. 4.1 %, p  < 0.001). When adjusting for age, body mass index, smoking and diabetes history, AJCC stage, reconstruction, previous radiation therapy, and adjuvant therapy, CPM patients were 1.5 times more likely to have any complication (odds ratio [OR] 1.53; 95 % CI 1.04–2.25, p  = 0.029) and 2.7 times more likely to have a major complication compared with UM patients (OR 2.66; 95 % CI 1.37–5.19, p  = 0.004). Conclusions CPM patients have an increased risk of complications, especially major complications requiring rehospitalization or reoperation. These complications may influence patient and physician decisions to choose CPM.

BackgroundTwo-dimensional (2D) specimen radiography (SR) and tomosynthesis (DBT) for breast cancer yield data that lack high-depth resolution. A volumetric specimen imager (VSI) was developed to provide full-3D and thin-slice cross-sectional visualization at a 360° view angle. The purpose of this prospective trial was to compare VSI, 2D SR, and DBT interpretation of lumpectomy margin status with the final pathologic margin status of breast lumpectomy specimens.MethodsThe study enrolled 200 cases from two institutions. After standard imaging and interpretation was performed, the main lumpectomy specimen was imaged with the VSI device. Image interpretation was performed by three radiologists after surgery based on VSI, 2D SR, and DBT. A receiver operating characteristic (ROC) curve was created for each method. The area under the curve (AUC) was computed to characterize the performance of the imaging method interpreted by each user.ResultsFrom 200 lesions, 1200 margins were interpreted. The AUC values of VSI for the three radiologists were respectively 0.91, 0.90, and 0.94, showing relative improvement over the AUCs of 2D SR by 54%, 13%, and 40% and DBT by 32% and 11%, respectively. The VSI has sensitivity ranging from 91 to 94%, specificity ranging from 81 to 85%, a positive predictive value ranging from 25 to 30%, and a negative predicative value of 99%.ConclusionsThe ROC curves of the VSI were higher than those of the other specimen imaging methods. Full-3D specimen imaging can improve the correlation between the main lumpectomy specimen margin status and surgical pathology. The findings from this study suggest that using the VSI device for intraoperative margin assessment could further reduce the re-excision rates for women with malignant disease.