Early Local Therapy for the Primary Site in De Novo Stage IV Breast Cancer: Results of a Randomized Clinical Trial (EA2108).

PURPOSE: Distant metastases are present in 6% or more of patients with newly diagnosed breast cancer. In this context, locoregional therapy for the intact primary tumor has been hypothesized to improve overall survival (OS), but clinical trials have reported conflicting results. METHODS: Women presenting with metastatic breast cancer and an intact primary tumor received systemic therapy for 4-8 months; if no disease progression occurred, they were randomly assigned to locoregional therapy for the primary site (surgery and radiotherapy per standards for nonmetastatic disease) or continuing sysmetic therapy. The primary end point was OS; locoregional control and quality of life were secondary end points. The trial design provided 85% power to detect a 19.3% absolute difference in the 3-year OS rate in randomly assigned patients. The stratified log-rank test and Cox proportional hazards model were used to compare OS between arms. Cumulative incidence of locoregional progression was compared using Gray's test. Quality-of-life assessment used standard instruments. RESULTS: Of 390 participants enrolled, 256 were randomly assigned: 131 to continued systemic therapy and 125 to early locoregional therapy. The 3-year OS was 67.9% without and 68.4% with early locoregional therapy (hazard ratio = 1.11; 90% CI, 0.82 to 1.52; P = .57). The median OS was 53.1 months (95% CI, 47.9 to not estimable) in the systemic therapy arm and 54.9 months (95% CI, 46.7 to not estimable) in the locoregional therapy arm. Locoregional progression was less frequent in those randomly assigned to locoregional therapy (3-year rate: 16.3% v 39.8%; P < .001). Quality-of-life measures were largely similar between arms. CONCLUSION: Early locoregional therapy for the primary site did not improve survival in patients presenting with metastatic breast cancer. Although it was associated with improved locoregional control, this had no overall impact on quality of life.

Impact of adjuvant endocrine therapy in older patients with comorbidities and estrogen receptor-positive, node-negative breast cancer-A National Cancer Database analysis.

BACKGROUND: Data are lacking about the benefit of adjuvant endocrine therapy (ET) in older patients with multiple comorbidities. The authors sought to determine the effect of ET on the survival of older patients who had multiple comorbidities and estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative, pathologic node-negative (pN0) breast cancer. METHODS: Women aged ≥70 years in the National Cancer Database (2010-2014) with Charlson/Deyo comorbidity scores of 2 or 3 who had pathologic tumor (pT1)-pT3/pN0, ER-positive/HER2-negative breast cancer were divided into 2 cohorts: adjuvant ET and no ET. Propensity scores were used to match patients based on age, comorbidity score, facility type, pT classification, chemotherapy, surgery, and radiation therapy. A Cox proportional hazards model was used to estimate the effect of ET on overall survival (OS). RESULTS: In the nonmatched cohort (n = 3716), 72.8% of patients received ET (n = 2705), and 27.2% did not (n = 1011). The patients who received ET were younger (mean age, 76 vs 79 years; P < .001) and had higher rates of breast conservation compared with those who did not receive ET (lumpectomy plus radiation: 43.4% vs 23.8%, respectively; P < .001). In the matched cohort (n = 1972), the median OS was higher in the ET group (79.2 vs 67.7 months; P < .0001). In the adjusted analysis, ET was associated with improved survival (hazard ratio, 0.70; 95% CI, 0.59-0.83). CONCLUSIONS: In older patients who have pN0, ER-positive/HER2-negative breast cancer with comorbidities, adjuvant ET was associated with improved OS, which may have been overestimated given the confounders inherent in observational studies. To optimize outcomes in these patients, current standard recommendations should be considered stage-for-stage based on life expectancy and the level of tolerance to treatment.

Outcomes after Treatment of Metaplastic Versus Other Breast Cancer Subtypes.

Purpose: Metaplastic breast cancer (BC) is an uncommon yet aggressive histologic subtype of BC. We sought to identify factors associated with its diagnosis and compare the management and outcomes of metaplastic BC with those of other BCs and triple negative invasive ductal carcinoma in particular given how often it has a triple negative phenotype. Patients and Methods: We identified women diagnosed with invasive BC in 2010-2014 in the National Cancer Data Base, and used univariate analysis to compare baseline patient and tumor characteristics by BC subtype. Overall survival (OS) was estimated with the Kaplan-Meier method, and multivariate Cox proportional hazards models were used to identify independent predictors of OS. Results: Of 247,355 cases, 2,084 (0.8%) were metaplastic BC, 55,998 (23%) triple negative BC, and 77% other BC. Relative to non-metaplastic BC, women with metaplastic BC were more likely to be older at diagnosis (median age, 62 vs. 59 years), have ≥1 comorbid conditions (22% vs. 18%), and be on Medicare (41% vs. 33%; P<0.001). Metaplastic BCs tended to be basal-like (77%), and relative to triple-negative or other BC, metaplastic BC was associated with higher clinical T status (cT3-4, 18% vs. 11%, 8%), no clinical nodal involvement (cN0, 86%, 77%, 80%), no lymphovascular invasion (72%, 65%, 62%), and high-grade tumors (71%, 77%, 35%) (P<0.001). Most metaplastic BCs were treated with mastectomy (58%), sentinel lymph node dissection (65%), chest wall or breast irradiation (74%), and chemotherapy (75%) as adjuvant therapy (60%). At a median follow-up time of 44.5 months, OS rates were lower for metaplastic BC than for triple-negative or other BC across all clinical stages at 5 years (stage I, 85%, 87%, 91%; II, 73%, 77%, 87%; III, 43%, 53%, 75%) and at 3 years (Stage IV, 15%, 22%, 64%; P<0.001). On multivariate analysis, increasing age, advanced clinical stage, lymphovascular invasion, axillary (vs. sentinel) node dissection, and no radiation or chemotherapy were associated with worse outcomes in metaplastic BC. Extent of surgery affected survival for triple-negative and other BC but not for metaplastic BC. Conclusion: Outcomes for metaplastic BC continue to be worse than those for other BC subtypes despite modern treatments. Optimizing systemic therapy options, which was a significant predictor of survival, should be a priority in managing metaplastic BC.

Lumpectomy Plus Hormone or Radiation Therapy Alone for Women Aged 70 Years or Older With Hormone Receptor-Positive Early Stage Breast Cancer in the Modern Era: An Analysis of the National Cancer Database.

PURPOSE: Deintensification of adjuvant therapy is being considered for older women with early-stage, biologically favorable breast cancer. Although radiation therapy (RT) can be omitted in some cases, toxicity from hormone therapy (HT) is not trivial, and adherence rates vary. We hypothesized that adjuvant RT alone would produce survival outcomes comparable to those with adjuvant HT alone among elderly patients treated with lumpectomy. METHODS AND MATERIALS: We searched the National Cancer Database (2010-2014) for healthy women (aged ≥70 years, Charlson/Deyo [CD] score 0-1) with T1N0 hormone-receptor-positive, HER-2-negative breast cancer treated with lumpectomy and adjuvant HT or RT. Propensity scores were used to match patients for analysis. RESULTS: We identified 2995 patients (median age, 78 years), most (81%) with a CD score of 0, clinical stage IA (77%), of whom 65% received HT alone and 35% received RT only after lumpectomy. On multivariate analysis of the matched cohort, older age (hazard ratio [HR] 1.10; 95% confidence interval [CI] 1.07-1.13; P < .001), CD score 1 (HR 1.92; 95% CI 1.37-2.70; P = .0002), and living in a metropolitan (vs urban) area (HR 3.09; 95% CI 1.43-6.67; P = .004) were associated with inferior overall survival (OS), whereas treatment with HT (vs RT) was not (HR 1.13; 95% CI 0.85-1.49; P = .406). At a median follow-up of 45 months, no difference was found in OS between HT versus RT cohorts (85% and 86%, respectively; P = .44). CONCLUSIONS: For healthy, older women with biologically favorable breast cancer treated with lumpectomy, adjuvant RT or HT is associated with equivalent 5-year OS rates. A randomized controlled trial is warranted to explore these adjuvant monotherapy options in elderly patients with hormone receptor-positive breast cancer.

Evolution in practice patterns of axillary management following mastectomy in patients with 1-2 positive sentinel nodes.

PURPOSE: The optimal management of breast cancer patients with a positive sentinel lymph node (SLN) who undergo mastectomy remains controversial. This study aimed to describe treatment patterns of patients with positive SLNs who undergo mastectomy using a large population-based database. METHODS: The NCDB was queried for cT1-2N0 breast cancer patients treated with mastectomy between 2006 and 2014 who had 1-2 positive SLNs. Patients receiving neoadjuvant chemotherapy were excluded. Axillary management included SLN dissection (SLND) alone, axillary lymph node dissection (ALND), post-mastectomy radiation (PMRT) alone, and ALND + PMRT. Trends of axillary management and patient characteristics were examined. RESULTS: Among 12,190 patients who met study criteria, the use of ALND dropped with a corresponding increase in other approaches. In 2006, 34% of patients had SLND alone, 47% ALND, 8% PMRT and 11% ALND + PMRT. By 2014, 37% had SLND, 23% ALND, 27% PMRT and 13% ALND + PMRT. Patients who underwent SLND alone were older (mean 60.6 years) with more comorbidities (Charlson-Deyo score > 2), smaller primary tumors (mean 2.1 cm), well-differentiated histology, hormone receptor-positive, HER2-negative tumors, without lymphovascular invasion (all P values < 0.01). Treatment with SLND alone was more likely if patients had only one positive SLN (P < 0.001) or micrometastatic disease (P < 0.001), and were treated at community centers compared with academic centers (P < 0.001). CONCLUSIONS: The management of breast cancer patients undergoing mastectomy with positive SLNs has evolved over time with decreased use of ALND and increased use of radiation. Some patient subsets are underrepresented in recent clinical trials, and therefore, future trials should focus on these patients.

A Pictorial Review of Sonography of Intramammary Lymph Nodes: When to Care and What to Do About It.

This pictorial essay reviews and illustrates benign and malignant features of intramammary lymph nodes on mammography, ultrasound, and magnetic resonance imaging, including a review of the clinical and the prognostic significance in patients with known breast cancer. This pictorial essay discusses management suggestions for intramammary lymph nodes in patients with breast cancer.

Prospective Comparison of Toxicity and Cosmetic Outcome After Accelerated Partial Breast Irradiation With Conformal External Beam Radiotherapy or Single-Entry Multilumen Intracavitary Brachytherapy.

PURPOSE: This study aimed to prospectively characterize toxicity and cosmesis after accelerated partial breast irradiation (APBI) with 3-dimensional conformal radiation therapy (CRT) or single-entry, multilumen, intracavitary brachytherapy. METHODS AND MATERIALS: A total of 281 patients with pTis, pT1N0, or pT2N0 (≤3.0 cm) breast cancer treated with segmental mastectomy were prospectively enrolled from December 2008 through August 2014. APBI was delivered using 3-dimensional CRT (n = 29) or with SAVI (n = 176), Contura (n = 56), or MammoSite (n = 20) brachytherapy catheters. Patients were evaluated at protocol-specified intervals, at which time the radiation oncologist scored cosmetic outcome, toxicities, and recurrence status using a standardized template. RESULTS: The median follow-up time is 41 months. Grade 1 seroma and fibrosis were more common with brachytherapy than with 3-dimensional CRT (50.4% vs 3.4% for seroma; P < .0001 and 66.3% vs 44.8% for fibrosis; P = .02), but grade 1 edema was more common with 3-dimensional CRT than with brachytherapy (17.2% vs 5.6%; P = .04). Grade 2 to 3 pain was more common with 3-dimensional CRT (17.2% vs 5.2%; P = .03). Actuarial 5-year rates of fair or poor radiation oncologist-reported cosmetic outcome were 9% for 3-dimensional CRT and 24% for brachytherapy (P = .13). Brachytherapy was significantly associated with inferior cosmesis on mixed model analysis (P = .003). Significant predictors of reduced risk of adverse cosmetic outcome after brachytherapy were D0.1cc (skin) ≤102%, minimum skin distance >5.1 mm, dose homogeneity index >0.54, and volume of nonconformance ≤0.89 cc. The 5-year ipsilateral breast recurrence was 4.3% for brachytherapy and 4.2% for 3-dimensional CRT APBI patients (P = .95). CONCLUSIONS: Brachytherapy APBI is associated with higher rates of grade 1 fibrosis and seroma than 3-dimensional CRT but lower rates of grade 1 edema and grade 2 to 3 pain than 3-dimensional CRT. Rates of radiation oncologist-reported fair or poor cosmetic outcomes are higher with brachytherapy. We identified dosimetric parameters that predict reduced risk of adverse cosmetic outcome after brachytherapy-based APBI. Ipsilateral breast recurrence was equivalent for brachytherapy and 3-dimensional CRT.

Reconstruction in the Metastatic Breast Cancer Patient: Results from the National Cancer Database.

PURPOSE: Modern treatments are prolonging life for metastatic breast cancer patients. Reconstruction in these patients is controversial. The purpose of this study was to characterize de novo metastatic breast cancer patients who undergo mastectomy and reconstruction and to report complication and survival rates. METHODS: We queried the National Cancer Database for de novo metastatic breast cancer patients, who underwent systemic therapy and mastectomy with reconstruction (R) or without reconstruction (NR) between 2004 and 2013. Patient-tumor characteristics, mortality, and readmissions were compared. Propensity score matched analysis was performed, and survival was calculated using the Kaplan-Meier method. RESULTS: A total of 8554 patients fulfilled study criteria (n = 980/11.5% R vs. n = 7574/88.5% NR). There was a significant increase in reconstruction rates by year: 5.2% in 2004, 14.3% in 2013 (p < 0.0001). Compared with the NR patients, R patients were younger (mean age 49 vs. 58 years, p < 0.0001), more hormone receptor-positive (76.1% vs. 70.5%, p = 0.0004), had lower grade disease (p = 0.0082), and fewer sites of metastases (85.7% had 1 metastasis; 14.3% had ≥ 2 R vs. 79% had 1; 21% had ≥ 2 NR, p = 0.0002). R patients received more hormonal and chemotherapy than NR but equally received radiation. Median overall survival of the total cohort was 45 months, and median overall survivals of R and NR groups by matched analysis were 56.7 and 55.3 months respectively (p = 0.86). Thirty-day mortality (0.2%-R, 0.3%-NR, p = 0.56) and readmissions (5.9%-R, 5.8%-NR, p = 0.81) were similar; 90-day mortality also was similar (1.1%-R vs. 1.6%-NR, p = 0.796). CONCLUSIONS: There is an increasing trend to reconstruct metastatic breast cancer patients with low complication rates, without survival compromise. Impact on quality of life warrants further assessment.

Safety and Efficacy of Panitumumab Plus Neoadjuvant Chemotherapy in Patients With Primary HER2-Negative Inflammatory Breast Cancer.

Importance: Combining conventional chemotherapy with targeted therapy has been proposed to improve the pathologic complete response (pCR) rate in patients with inflammatory breast cancer (IBC). Epidermal growth factor receptor (EGFR) expression is an independent predictor of low overall survival in patients with IBC. Objective: To evaluate the safety and efficacy of the anti-EGFR antibody panitumumab plus neoadjuvant chemotherapy in patients with primary human epidermal growth factor receptor 2 (HER2)-negative IBC. Design, Setting, and Participants: Women with primary HER2-negative IBC were enrolled from 2010 to 2015 and received panitumumab plus neoadjuvant chemotherapy. Median follow-up time was 19.3 months. Tumor tissues collected before and after the first dose of panitumumab were subjected to immunohistochemical staining and RNA sequencing analysis to identify biomarkers predictive of pCR. Intervention: Patients received 1 dose of panitumumab (2.5 mg/kg) followed by 4 cycles of panitumumab (2.5 mg/kg), nab-paclitaxel (100 mg/m2), and carboplatin weekly and then 4 cycles of fluorouracil (500 mg/m2), epirubicin (100 mg/m2), and cyclophosphamide (500 mg/m2) every 3 weeks. Main Outcomes and Measures: The primary end point was pCR rate; the secondary end point was safety. The exploratory objective was to identify biomarkers predictive of pCR. Results: Forty-seven patients were accrued; 7 were ineligible. The 40 enrolled women had a median age of 57 (range, 23-68) years; 29 (72%) were postmenopausal. Three patients did not complete therapy because of toxic effects (n = 2) or distant metastasis (n = 1). Nineteen patients had triple-negative and 21 had hormone receptor-positive IBC. The pCR and pCR rates were overall, 11 of 40 (28%; 95% CI, 15%-44%); triple-negative IBC, 8 of 19 (42%; 95% CI, 20%-66%); and hormone receptor-positive/HER2-negative IBC, 3 of 21 (14%; 95% CI, 3%-36%). During treatment with panitumumab, nab-paclitaxel, and carboplatin, 10 patients were hospitalized for treatment-related toxic effects, including 5 with neutropenia-related events. There were no treatment-related deaths. The most frequent nonhematologic adverse event was skin rash. Several potential predictors of pCR were identified, including pEGFR expression and COX-2 expression. Conclusions and Relevance: This combination of panitumumab and chemotherapy showed the highest pCR rate ever reported in triple-negative IBC. A randomized phase 2 study is ongoing to determine the role of panitumumab in patients with triple-negative IBC and to further validate predictive biomarkers. Trial Registration: ClinicalTrials.gov Identifier: NCT01036087.

Prospective Feasibility Trial of Sentinel Lymph Node Biopsy in the Setting of Inflammatory Breast Cancer.

BACKGROUND: Most inflammatory breast cancer (IBC) patients have axillary disease at presentation. Current standard is axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NACT). Advances in NACT have improved pathologic complete response (pCR) rates increasing interest in performing sentinel lymph node (SLN) biopsy (SLNB). Previous studies on SLNB for IBC patients did not assess nodal response with imaging or use dual tracer mapping. We sought to prospectively determine false negative rates of SLNB in IBC patients using dual tracer mapping, and to correlate pathology with preoperative axillary imaging. PATIENTS AND METHODS: Patients with IBC were prospectively enrolled. Patients underwent axillary staging with physical examination and axillary ultrasound before and after NACT. All patients underwent SLNB using blue dye and radioisotope, followed by ALND. RESULTS: Sixteen patients were prospectively enrolled. Clinical N stage was N0 in 1 patient, N1 in 8, and N3 in 7. SLN mapping was successful in only 4 patients (25%) with 12 (75%) not draining either tracer to a SLN. Three of the 4 (75%) who mapped had an axillary pCR. The patient who mapped but did not have an axillary pCR had a positive SLNB with additional axillary nodal disease identified on ALND. All patients who successfully mapped had presumed residual nodal disease on preoperative axillary ultrasound. CONCLUSION: SLNB was unsuccessful in most IBC patients. A small subset who have pCR might undergo successful SLNB, but preoperative axillary imaging failed to identify these patients. ALND should remain standard practice for IBC patients.

Randomized trial of Tibetan yoga in patients with breast cancer undergoing chemotherapy.

BACKGROUND: The current randomized trial examined the effects of a Tibetan yoga program (TYP) versus a stretching program (STP) and usual care (UC) on sleep and fatigue in women with breast cancer who were undergoing chemotherapy. METHODS: Women with stage (American Joint Committee on Cancer (AJCC) TNM) I to III breast cancer who were undergoing chemotherapy were randomized to TYP (74 women), STP (68 women), or UC (85 women). Participants in the TYP and STP groups participated in 4 sessions during chemotherapy, followed by 3 booster sessions over the subsequent 6 months, and were encouraged to practice at home. Self-report measures of sleep disturbances (Pittsburgh Sleep Quality Index), fatigue (Brief Fatigue Inventory), and actigraphy were collected at baseline; 1 week after treatment; and at 3, 6, and 12 months. RESULTS: There were no group differences noted in total sleep disturbances or fatigue levels over time. However, patients in the TYP group reported fewer daily disturbances 1 week after treatment compared with those in the STP (difference, -0.43; 95% confidence interval [95% CI], -0.82 to -0.04 [P = .03]) and UC (difference, -0.41; 95% CI, -0.77 to -0.05 [P = .02]) groups. Group differences at the other time points were maintained for TYP versus STP. Actigraphy data revealed greater minutes awake after sleep onset for patients in the STP group 1 week after treatment versus those in the TYP (difference, 15.36; 95% CI, 7.25-23.48 [P = .0003]) and UC (difference, 14.48; 95% CI, 7.09-21.87 [P = .0002]) groups. Patients in the TYP group who practiced at least 2 times a week during follow-up reported better Pittsburgh Sleep Quality Index and actigraphy outcomes at 3 months and 6 months after treatment compared with those who did not and better outcomes compared with those in the UC group. CONCLUSIONS: Participating in TYP during chemotherapy resulted in modest short-term benefits in sleep quality, with long-term benefits emerging over time for those who practiced TYP at least 2 times a week. Cancer 2018;124:36-45. © 2017 American Cancer Society.

Factors impacting the accuracy of intra-operative evaluation of sentinel lymph nodes in breast cancer.

Sentinel lymph node dissection (SLND) is a standard axillary staging technique in breast cancer and intraoperative sentinel lymph node (SLN) assessment is important for decision-making regarding additional treatment and reconstruction. This study was undertaken to investigate clinicopathologic factors impacting the accuracy of intraoperative SLN evaluation. Records of patients with clinically node-negative, invasive breast cancer who underwent SLND with frozen section intraoperative pathologic evaluation from 2004 to 2007 were reviewed. Intraoperative SLN assessment results were compared to final pathology. Patients with positive SLNs that were initially reported as negative during intraoperative assessment were considered false negative (FN) events. Primary tumor histology, grade, receptor status, size, lymphovascular invasion (LVI), multifocality, neoadjuvant chemotherapy or hormonal therapy, number of SLNs retrieved, and SLN metastasis size were evaluated. The study included 681 patients, of whom 262 (38%) received neoadjuvant therapy. There were 183 (27%) patients who had a positive SLN on final pathology, of whom 60 (33%) had FN events. On univariate analysis, lobular histology, favorable histology, absence of LVI and micrometastasis were associated with a higher FN rate. On multivariate analysis, favorable and lobular histology and micrometastasis were independent predictors of FN events whereas LVI and receipt of neoadjuvant therapy were not statistically significant predictors. The accuracy of intraoperative SLN evaluation for breast cancer is affected by primary tumor histology and size of the SLN metastasis. There was no significant association between neoadjuvant therapy and the FN rate by intraoperative assessment. This information may be helpful in counseling patients about their risk for a FN intraoperative SLN assessment and for planning for immediate breast reconstruction in patients undergoing mastectomy.

Use of regional nodal irradiation and its association with survival for women with high-risk, early stage breast cancer: A National Cancer Database analysis.

PURPOSE: The role of regional nodal irradiation (RNI) for patients with breast cancer remains controversial, particularly on the basis of nodal involvement. Using the National Cancer Database, we aimed to validate published data on whether expanding treatment fields from whole-breast irradiation (WBI) to encompass the regional nodes (WBI+RNI) affected overall survival (OS) for patients with node-positive (pN1-3) or high-risk node-negative (pN0) breast cancer treated with breast-conserving surgery and adjuvant chemotherapy. METHODS AND MATERIALS: Women diagnosed with invasive breast cancer between 2004 and 2012 who met the selection criteria for the National Cancer Institute of Canada MA.20 trial were identified and stratified by receipt of RNI. Propensity score matching was used to compare 1:1 matched pairs of patients. Five-year OS was estimated using the Kaplan-Meier method. We used multivariate logistic regression to predict receipt of WBI+RNI and a multivariable Cox model to examine associations between patients' demographic, tumor, and treatment characteristics and OS using double robust estimation. RESULTS: Of 23,567 patients, 6,920 (29%) received WBI+RNI and 16,647 (71%) WBI. Median follow-up was 56 months. Use of WBI+RNI increased from 25.2% in 2004 to 32.2% in 2012 (P < .001). Patients receiving WBI+RNI more often had negative hormone-receptor status, ≥5 cm tumors and >1 involved node, and were not privately insured. For all patients, the 5-year OS rates were 90.8% with WBI+RNI versus 92.6% with WBI (P < .001). In the matched cohort (n = 10,922), the corresponding 5-year OS rates were 92% and 91.9% (P = .45), respectively. On multivariate analysis, WBI+RNI did not affect OS in the matched cohort (hazard ratio, 1.02; 95% confidence interval, 0.89-1.17, P = .76), regardless of pathologic nodal status. CONCLUSIONS: In this large retrospective analysis, use of WBI+RNI did not affect 5-year OS rates for women with high-risk, early stage breast cancer undergoing breast-conserving surgery and adjuvant chemotherapy, regardless of nodal status, which confirms the findings of the MA.20 trial.

A phase 2 study of capecitabine and concomitant radiation in women with advanced breast cancer.

PURPOSE: To examine the response rate of gross chemo-refractory breast cancer treated with concurrent capecitabine (CAP) and radiation therapy in a prospective Phase II study. METHODS AND MATERIALS: Breast cancer patients with inoperable disease after chemotherapy, residual nodal disease after definitive surgical resection, unresectable chest wall or nodal recurrence after a prior mastectomy, or oligometastatic disease were eligible. Response by RECIST criteria was assessed after 45 Gy. Conversion to operable, locoregional control, and grade ≥3 toxicities were assessed. The first 9 patients received CAP 825 mg/m2 twice daily continuously. Because of toxicity, subsequent patients received CAP only on radiation days. Kaplan-Meier analysis was used to estimate overall survival (OS) and locoregional recurrence-free survival. RESULTS: From 2009 to 2012, 32 patients were accrued; 26 received protocol-specified treatment. Median follow-up was 12.9 months (interquartile range, 7.10-42.9 months). Nineteen patients (73%) had partial or complete response. Fourteen patients (53.9%) experienced grade 3 non-dermatitis toxicity (7 of 9 continuous dosing). Three of four inoperable patients converted to operable. One-year actuarial OS in the treated cohort was 54%. The trial was stopped early after interim analysis suggested futility independent of response. Treatment was deemed futile (ie, conversion to operable but M1 disease immediately postoperatively) in 9 of 10 patients with triple-negative (TN) versus 6 of 16 with non-TN disease (P=.014). Median OS and 1-year locoregional recurrence-free survival among non-TN versus TN patients was 22.8 versus 5.1 months, and 63% versus 20% (P=.007). CONCLUSIONS: Capecitabine can be safely administered on radiation days with careful clinical monitoring and was associated with encouraging response in this chemo-refractory cohort. However, patients with TN breast cancer had poor outcomes even when response was achieved. Further study in non-TN patients may be warranted.

4-1BB-Enhanced Expansion of CD8+ TIL from Triple-Negative Breast Cancer Unveils Mutation-Specific CD8+ T Cells.

Triple-negative breast cancer (TNBC) highly infiltrated with CD8+ tumor-infiltrating lymphocytes (TIL) has been associated with improved prognosis. This observation led us to hypothesize that CD8+ TIL could be utilized in autologous adoptive cell therapy for TNBC, although this concept has proven to be challenging, given the difficulty in expanding CD8+ TILs in solid cancers other than in melanoma. To overcome this obstacle, we used an agonistic antibody (urelumab) to a TNFR family member, 4-1BB/CD137, which is expressed by recently activated CD8+ T cells. This approach was first utilized in melanoma and, in this study, led to advantageous growth of TILs for the majority of TNBC tumors tested. The agonistic antibody was only added in the initial setting of the culture and yet favored the propagation of CD8+ TILs from TNBC tumors. These expanded CD8+ TILs were capable of cytotoxic functions and were successfully utilized to demonstrate the presence of immunogenic mutations in autologous TNBC tumor tissue without recognition of the wild-type counterpart. Our findings open the way for a successful adoptive immunotherapy for TNBC. Cancer Immunol Res; 5(6); 439-45. ©2017 AACR.

Using the National Cancer Data Base for quality evaluation to assess adherence to treatment guidelines for nonmetastatic inflammatory breast cancer.

BACKGROUND: Guidelines for the treatment of nonmetastatic inflammatory breast cancer (IBC) using trimodality therapy (TT) (chemotherapy, surgery, and radiotherapy) have remained largely unchanged since 2000. However, many patients with nonmetastatic IBC do not receive TT. It is unknown how patient-level (PL) and facility-level (FL) factors contribute to TT use. METHODS: Using the National Cancer Data Base, patients with nonmetastatic IBC who underwent locoregional treatment from 2003 through 2011 were identified. The authors correlated PL factors, including demographic and tumor characteristics, with TT use. An observed-to-expected ratio for the number of patients treated with TT was calculated for each hospital by adjusting for significant PL factors. Hierarchical mixed effects models were used to assess the percentage of variation in TT use attributable to PL and FL factors, respectively. RESULTS: Of the 542 hospitals examined, 55 (10.1%) and 24 (4.4%), respectively, were identified as significantly low and high outliers for TT use (P<.05). The percentage of the total variance in the use of TT attributable to the facility (11%) was nearly triple the variance attributable to the measured PL factors (3.4%). The nomogram generated from multivariate logistic regression of PL factors only allows a facility to assess TT use given their PL data. CONCLUSIONS: FL factors rather than PL factors appear to contribute disproportionately to the underuse of TT in patients with nonmetastatic IBC. To improve treatment guideline adherence for patients with nonmetastatic IBC, it is critical to identify the specific FL factors associated with TT underuse. More organized FL intervention is required to train physicians and to build multidisciplinary teams. Cancer 2017;123:2618-25. © 2017 American Cancer Society.

DCIS and axillary nodal evaluation: compliance with national guidelines.

BACKGROUND: The National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology (ASCO) provide guidelines regarding axillary nodal evaluation in ductal carcinoma in situ (DCIS), but data regarding national compliance with these guidelines remains incomplete. METHODS: We conducted a retrospective review of the National Cancer Data Base (NCDB) analyzing all surgical approaches to axillary evaluation in patients with DCIS. Logistic regression analysis was used to assess the multivariate relationship between patient demographics, clinical characteristics, and probability of axillary evaluation. RESULTS: We identified 88,083 patients diagnosed with DCIS between 1998 and 2011; 31,912 (37%) underwent total mastectomy (TM) and 55,349 (63%) had breast conserving therapy (BCT). Axillary evaluation increased from 44.4% in 1998 to 63.3% in 2011. In TM patients, axillary evaluation increased from 74.3% in 1998 to 93.4% in 2011. This correlated with an increase in sentinel lymph node biopsy (SLNB) from 24.3 to 77.1%, while ALND decreased from 50.0 to 16.3% (p <0.01). In BCT patients, evaluation increased from 20.1 to 43.9%; SLNB increased from 7.2 to 39.4% and ALND decreased from 12.9 to 4.5%. Factors associated with axillary nodal evaluation in BCT patients included practice type and facility location. Among TM patients, use of axillary lymph node dissection (ALND) for axillary staging was associated with earlier year of diagnosis, black race, and older age, as well as community practice setting and practice location in the Southern US. CONCLUSIONS: Compliance with national guidelines regarding axillary evaluation in DCIS remains varied. Practice type and location-based differences suggest opportunities for education regarding the appropriate use of axillary nodal evaluation in patients with DCIS.

A Comprehensive Lifestyle Randomized Clinical Trial: Design and Initial Patient Experience.

BACKGROUND: Although epidemiological research demonstrates that there is an association between lifestyle factors and risk of breast cancer recurrence, progression of disease, and mortality, no comprehensive lifestyle change clinical trials have been conducted to determine if changing multiple risk factors leads to changes in biobehavioral processes and clinical outcomes in women with breast cancer. This article describes the design, feasibility, adherence to the intervention and data collection, and patient experience of a comprehensive lifestyle change clinical trial (CompLife). METHODS: CompLife is a randomized, controlled trial of a multiple-behavior intervention focusing on diet, exercise, and mind-body practice along with behavioral counseling to support change. The initial exposure to the intervention takes place during the 4 to 6 weeks of radiotherapy (XRT) for women with stage III breast cancer and then across the subsequent 12 months. The intervention group will have 42 hours of in-person lifestyle counseling during XRT (7-10 hours a week) followed by up to 30 hours of counseling via video connection for the subsequent 12 months (weekly sessions for 6 months and then monthly for 6 months). The primary outcome is disease-free survival. Multiple secondary outcomes are being evaluated, including: (1) biological pathways; (2) overall survival; (3) patient-reported outcomes; (4) dietary patterns/fitness levels, anthropometrics, and body composition; and (5) economic outcomes. Qualitative data of the patient experience in the trial is collected from exit interviews, concluding remarks, direct email correspondences, and web postings from patients. RESULTS: Fifty-five patients have been recruited and randomized to the trial to date. Accrual of eligible patients is high (72%) and dropout rates extremely low (5%). Attendance to the in-person sessions is high (95% attending greater than 80% of sessions) as well as to the 30 hours of video counseling (88% attending more than 70% of sessions). Adherence to components of the behavior change intervention is high and compliance with the intensive amount of data collection is exceptional. Qualitative data collected from the participants reveals testimonials supporting the importance of the comprehensive nature of intervention, especially the mind-body/mindfulness component and social support, and meaningful lifestyle transformations. CONCLUSION: Conducting a comprehensive, multicomponent, lifestyle change clinical trial for women with breast was feasible and collection of biobehavioral outcomes successful. Adherence to behavior change was high and patient experience was overwhelmingly positive.

Outcomes of Sentinel Lymph Node-Positive Breast Cancer Patients Treated with Mastectomy Without Axillary Therapy.

PURPOSE: Early-stage breast cancer patients with minimal axillary disease identified by sentinel lymph node dissection (SLND) have low regional recurrence rates when treated with breast-conserving surgery and radiation therapy (XRT) and many avoid a completion axillary lymph node dissection (CLND). As the incidence of total mastectomy (TM) has increased, it has become important to characterize which TM patients with a positive SLN may not benefit from further axillary treatment. METHODS: An institutional database was utilized to identify patients treated with a TM for invasive breast cancer and who had a positive SLN from 1994 to 2010. Clinicopathologic factors were analyzed. Regional recurrence rate, recurrence-free survival (RFS), and overall survival (OS) were determined. RESULTS: A total of 525 patients with invasive breast cancer and a positive SLN were treated with TM, including 58 patients who did not have CLND or XRT and 12 patients who did not have CLND but did receive XRT. Median follow-up was 66 months. The incidence of regional recurrence was not significantly different for patients who received no further axillary treatment compared to those who underwent CLND without XRT or those treated with XRT without CLND (10 years rate: 3.8 vs. 1.6 and 0 % respectively). RFS and OS were not significantly different among patients who received no further axillary treatment compared to those who underwent CLND, XRT, or both. CONCLUSIONS: In select patients with early-stage breast cancer treated with mastectomy with a positive SLN, CLND may be avoided without adversely affecting recurrence or survival.