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Purpose BRCA1/2 pathogenic variant (PV) mutations confer radiation sensitivity preclinically, but there are limited data regarding breast cancer outcomes after radiation therapy (RT) among patients with documented BRCA1/2 PV mutations versus no PV mutations. Methods and Materials This retrospective cohort study included women with clinical stage I-III breast cancer who received definitive surgery and RT and underwent BRCA1/2 genetic evaluation at the The University of Texas MD Anderson Cancer Center. Rates of locoregional recurrence (LRR), disease-specific death (DSD), toxicities, and second cancers were compared by BRCA1/2 PV status. Results Of the 2213 women who underwent BRCA1/2 testing, 63% self-reported their race as White, 13.6% as Black/African American, 17.6% as Hispanic, and 5.8% as Asian/American Indian/Alaska Native; 124 had BRCA1 and 100 had BRCA2 mutations; and 1394 (63%) received regional nodal RT. The median follow-up time for all patients was 7.4 years (95% confidence interval [CI], 7.1-7.7 years). No differences were found between the groups with and without BRCA1/2 PV mutations in 10-year cumulative incidences of LRR (with mutations: 11.6% [95% CI, 7.0%-17.6%]; without mutations: 6.6% [95% CI, 5.3%-8.0%]; P = .466) and DSD (with mutations: 12.3% [95% CI, 8.0%-17.7%]; without mutations: 13.8% [95% CI, 12.0%-15.8%]; P = .716). On multivariable analysis, BRCA1/2 status was not associated with LRR or DSD, but Black/African American patients (P = .036) and Asians/American Indians/Alaska Native patients (P = .002) were at higher risk of LRR compared with White patients, and Black/African American patients were at higher risk of DSD versus White patients (P = .004). No in-field, nonbreast second cancers were observed in the BRCA1/2 PV group. Rates of acute and late grade ≥3 radiation-related toxicity in the BCRA1/2 PV group were 5.4% (n = 12) and 0.4% (n = 1), respectively. Conclusions Oncologic outcomes in a diverse cohort of patients with breast cancer who had a germline BRCA1/2 PV mutation and were treated with RT were similar to those of patients with no mutation, supporting the use of RT according to standard indications in patients with a germline BRCA1/2 PV mutation.

PURPOSE: There are limited prospective data on predictors of patient-reported outcomes (PROs) after whole-breast irradiation (WBI) plus a boost. We sought to characterize longitudinal PROs and cosmesis in a randomized trial comparing conventionally fractionated (CF) versus hypofractionated (HF) WBI. METHODS AND MATERIALS: From 2011 to 2014, women aged ≥40 years with Tis-T2 N0-N1a M0 breast cancer who underwent a lumpectomy with negative margins were randomized to CF-WBI (50 Gray [Gy]/25 fractions plus boost) versus HF-WBI (42.56 Gy/16 fractions plus boost). At baseline (pre-radiation), at 6 months, and yearly thereafter through 5 years, PROs included the Breast Cancer Treatment Outcome Scale (BCTOS), Functional Assessment of Cancer Therapy−Breast (FACTB), and Body Image Scale; cosmesis was reported by the treating physician using Radiation Therapy Oncology Group cosmesis values. Multivariable mixed-effects growth curve models evaluated associations of the treatment arm and patient factors with outcomes and tested for relevant interactions with the treatment arm. RESULTS: A total of 287 patients were randomized, completing a total of 14,801 PRO assessments. The median age was 60 years, 37% of patients had a bra cup size ≥D, 44% were obese, and 30% received chemotherapy. Through 5 years, there were no significant differences in PROs or cosmesis by treatment arm. A bra cup size ≥D was associated with worse BCTOS cosmesis (P < .001), BCTOS pain (P = .001), FACT-B Trial Outcome Index (P = .03), FACT-B Emotional Well-being (P = .03), and Body Image Scale (P = .003) scores. Physician-rated cosmesis was worse in patients who were overweight (P = .02) or obese (P < .001). No patient subsets experienced better PROs or cosmesis with CF-WBI. CONCLUSIONS: Both CF-WBI and HF-WBI confer similar longitudinal PROs and physician-rated cosmesis through 5 years of follow-up, with no relevant subsets that fared better with CF-WBI. This evidence supports broad adoption of hypofractionation with boost, including in patients receiving chemotherapy and in a population with a high prevalence of obesity. The associations of large breast size and obesity with adverse outcomes across multiple domains highlight the opportunity to engage at-risk patients in lifestyle intervention strategies, as well as to consider alternative radiation treatment regimens.

Purpose Mild breast cancer-related lymphedema (BCRL) is clinically diagnosed as a 5%–10% increase in arm volume, typically measured no earlier than 3–6 months after locoregional treatment. Early BCRL treatment is associated with better outcomes, yet amid increasing evidence that lymphedema exists in a latent form, treatment is typically delayed until arm swelling is obvious. In this study, we investigated whether near-infrared fluorescence lymphatic imaging (NIRF-LI) surveillance could characterize early onset of peripheral lymphatic dysfunction as a predictor of BCRL. Methods In a prospective, longitudinal cohort/observational study (NCT02949726), subjects with locally advanced breast cancer who received axillary lymph node dissection and regional nodal radiotherapy (RT) were followed serially, between 2016 and 2021, before surgery, 4–8 weeks after surgery, and 6, 12, and 18 months after RT. Arm volume was measured by perometry, and lymphatic (dys) function was assessed by NIRF-LI. Results By 18 months after RT, 30 of 42 study subjects (71%) developed mild–moderate BCRL (i.e., ≥ 5% arm swelling relative to baseline), all manifested by “dermal backflow” of lymph into lymphatic capillaries or interstitial spaces. Dermal backflow had an 83% positive predictive value and 86% negative predictive value for BCRL, with a sensitivity of 97%, specificity of 50%, accuracy of 83%, positive likelihood ratio of 1.93, negative likelihood ratio of 0.07, and odds ratio of 29.00. Dermal backflow appeared on average 8.3 months, but up to 23 months, before the onset of mild BCRL. Conclusion BCRL can be predicted by dermal backflow, which often appears months before arm swelling, enabling early treatment before the onset of edema and irreversible tissue changes.

Purpose Multigene panel testing has increased the detection of germline mutations in patients with breast cancer. The implications of using radiation therapy (RT) to treat patients with pathogenic variant (PV) mutations are not well understood and have been studied mostly in women with only BRCA1 or BRCA2 PVs. We analyzed oncologic outcomes and toxicity after adjuvant RT in a contemporary, diverse cohort of patients with breast cancer who underwent genetic panel testing. Methods and Materials We retrospectively reviewed the records of 286 women with clinical stage I-III breast cancer diagnosed from 1995 to 2017 who underwent surgery, breast or chest wall RT with or without regional nodal irradiation, multigene panel testing, and evaluation at a large cancer center's genetic screening program. We evaluated rates of overall survival, locoregional recurrence, disease-specific death, and radiation-related toxicities in 3 groups: BRCA1/2 PV carriers, non-BRCA1/2 PV carriers, and patients without PV mutations. Results PVs were detected in 25.2% of the cohort (12.6% BRCA1/2 and 12.6% non-BRCA1/2). The most commonly detected non-BRCA1/2 mutated genes were ATM, CHEK2, PALB2, CDH1, TP53, and PTEN. The median follow-up time for the entire cohort was 4.4 years (95% confidence interval, 3.8-4.9 years). No differences were found in overall survival, locoregional recurrence, or disease-specific death between groups (P > .1 for all). Acute and late toxicities were comparable across groups. Conclusion Oncologic and toxicity outcomes after RT in women with PV germline mutations detected by multigene pane testing are similar to those in patients without detectable mutations, supporting the use of adjuvant RT as a standard of care when indicated.

Male breast cancer treatment regimens are often extrapolated from female-based studies because of a paucity of literature analyzing male breast cancer. Using ClinicalTrials.gov, we analyzed breast cancer randomized clinical trials (RCTs) to determine which factors were associated with male-gender inclusion. Of 131 breast cancer RCTs identified, male patients represented 0.087% of the total study population, which is significantly less than the proportion of male patients with breast cancer in the U.S. (0.95%; p < .001). Twenty-seven trials included male patients (20.6%). Lower rates of male inclusion were seen in trials that randomized or mandated hormone therapy as part of the trial protocol compared with trials that did not randomize or mandate endocrine therapy (2.5% vs. 28.6% male inclusion; p < .001). It is imperative for breast cancer clinical trials to include men when allowable in order to improve generalizability and treatment decisions in male patients with breast cancer.

Purpose Optimal treatment of patients diagnosed with de novo metastatic breast cancer limited to the mediastinum or sternum has never been delineated. Herein, we sought to determine the efficacy of multimodality treatment, including metastasis-directed radiation therapy, in curing patients with this presentation. Methods and Materials This is a single-institution retrospective cohort study of patients with de novo metastatic breast cancer treated from 2005 to 2014, with a 50-month median follow-up for the primary cohort. The primary patient cohort had metastasis limited to the mediastinum/sternum treated with curative intent (n = 35). We also included a cohort of patients with stage IIIC disease treated with curative intent (n = 244). Additional groups included a mediastinal/sternal palliative cohort (treatment did not include metastasis-directed radiation therapy; n = 14) and all other patients with de novo stage IV disease (palliative cohort; n = 1185). The primary study outcomes included locoregional recurrence-free survival (LRRFS), recurrence-free survival (RFS), and overall survival (OS), which were calculated using the Kaplan-Meier method. Cox multivariable models compared survival outcomes across treatment cohorts adjusted for molecular subtype, age, and race. Results For the mediastinal/sternal curative-intent cohort, 5-year LRRFS was 85%, RFS was 52%, and OS was 63%. After adjustment, there was no statistically significant difference in LRRFS (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.13-1.13; P = .08), RFS (HR, 0.87; 95% CI 0.50-1.49; P = .61), or OS (HR, 0.79; 95% CI 0.44-1.43; P = .44) between the stage IIIC cohort and the mediastinal/sternal curative-intent cohort (referent). In contrast, RFS was worse for the mediastinal/sternal palliative cohort (HR, 2.29; 95% CI 1.05-5.00; P = .04). OS was worst for the de novo stage IV palliative cohort (HR, 2.61; 95% CI 1.50-4.53; P Conclusions For select patients presenting with breast cancer metastatic to the sternum and/or mediastinum, curative-intent treatment with chemotherapy, surgery, and radiation yields outcomes similar to those of stage IIIC disease and superior to de novo stage IV breast cancer treated with palliative intent.

Purpose The adoption of hypofractionated whole-breast irradiation (HF-WBI) remains low, in part because of concerns regarding its safety when used with a tumor bed boost or in patients who have received chemotherapy or have large breast size. To address this, we conducted a randomized, multicenter trial to compare conventionally fractionated whole-breast irradiation (CF-WBI; 50 Gy/25 fx + 10 to 14 Gy/5 to 7 fx) with HF-WBI (42.56 Gy/16 fx + 10 to 12.5 Gy/4 to 5 fx). Patients and Methods From 2011 to 2014, 287 women with stage 0 to II breast cancer were randomly assigned to CF-WBI or HF-WBI, stratified by chemotherapy, margin status, cosmesis, and breast size. The trial was designed to test the hypothesis that HF-WBI is not inferior to CF-WBI with regard to the proportion of patients with adverse cosmetic outcome 3 years after radiation, assessed using the Breast Cancer Treatment Outcomes Scale. Secondary outcomes included photographically assessed cosmesis scored by a three-physician panel and local recurrence-free survival. Analyses were intention to treat. Results A total of 286 patients received the protocol-specified radiation dose, 30% received chemotherapy, and 36.9% had large breast size. Baseline characteristics were well balanced. Median follow-up was 4.1 years. Three-year adverse cosmetic outcome was 5.4% lower with HF-WBI ( Pnoninferiority = .002; absolute risks were 8.2% [n = 8] with HF-WBI v 13.6% [n = 15] with CF-WBI). For those treated with chemotherapy, adverse cosmetic outcome was higher by 4.1% (90% upper confidence limit, 15.0%) with HF-WBI than with CF-WBI; for large breast size, adverse cosmetic outcome was 18.6% lower (90% upper confidence limit, −8.0%) with HF-WBI. Poor or fair photographically assessed cosmesis was noted in 28.8% of CF-WBI patients and 35.4% of HF-WBI patients ( P = .31). Three-year local recurrence-free survival was 99% with both HF-WBI and CF-WBI ( P = .37). Conclusion Three years after WBI followed by a tumor bed boost, outcomes with hypofractionation and conventional fractionation are similar. Tumor bed boost, chemotherapy, and larger breast size do not seem to be strong contraindications to HF-WBI.

Patients with breast cancer and ipsilateral supraclavicular (SCV) node involvement at the time of diagnosis (TNM cN3c) have historically had poor outcomes. Radiation therapy (RT) has an important role because SCV nodes are not routinely surgically dissected. However, optimal locoregional management, contemporary outcomes, and prognostic factors are not well defined.We reviewed the data of patients with cN3c breast cancer treated at our institution between 2014 and 2019 with curative intent, including neoadjuvant chemotherapy, surgery, and adjuvant RT. All patients received comprehensive regional RT, including to the SCV nodes. Institutional guidelines recommend a 10-Gy or 16-Gy boost to resolved and unresolved N3 nodes, respectively. Overall survival (OS), recurrence-free survival (RFS), locoregional recurrence-free survival (LRRFS), and supraclavicular recurrence-free survival (SCRFS) were analyzed.Data from 173 consecutive patients were analyzed with a median follow-up time of 2.8 years. The median age was 54 years, 76 patients (44%) were estrogen receptor positive/human epidermal growth factor receptor 2 negative, 100 patients (58%) had T3/4 disease, and 10 patients (6%) underwent a neck dissection. In addition, 156 patients (90%) received a cumulative SCV dose of ≥60 Gy. The 5-year OS, SCRFS, LRRFS, and RFS rates were 73%, 95%, 86%, and 50%, respectively. The 5-year OS rate for a cumulative SCV dose of ≥60 Gy versus60 Gy was 75% versus 39% (P = .04). In the multivariable analysis, a cumulative SCV dose of ≥60 Gy, extranodal extension, receptor status, and Eastern Cooperative Oncology Group performance status were associated with OS. The 5-year SCRFS rates with and without neck dissection were 100% versus 95% (P = .57). Among patients with a postchemotherapy SCV node size of ≥1 cm without neck dissection, the 5-year SCRFS rate was 83%.In one of the largest series of patients with cN3c breast cancer, multimodality therapy using adjuvant RT with a SCV boost resulted in a 5-year LRRFS rate of 86%. There is a limited role for neck dissection as the 5-year SCRFS rate was 95% overall and 83% for residual SCV disease ≥1 cm after chemotherapy with RT alone. A cumulative SCV dose of ≥60 Gy was associated with improved OS, but not SCRFS, LRRFS, or RFS. A SCV boost should be considered in these patients as treatment was well-tolerated. Despite advances in systemic therapy, nearly half of patients developed distant metastases, highlighting the need for close observation after treatment.

Purpose To perform a planned interim analysis of acute (within 12 months) and late (after 12 months) toxicities and cosmetic outcomes after proton accelerated partial breast irradiation (APBI). Methods and Materials A total of 100 patients with pTis or pT1-2 N0 (≤3cm) breast cancer status after segmental mastectomy were enrolled in a single-arm phase 2 study from 2010 to 2019. The clinically determined postlumpectomy target volume, including tumor bed surgical clips and operative-cavity soft-tissue changes seen on imaging plus a radial clinical expansion, was irradiated with passively scattered proton APBI (34 Gy in 10 fractions delivered twice daily with a minimum 6-hour interfraction interval). Patients were evaluated at protocol-specific time intervals for recurrence, physician reports of cosmetic outcomes and toxicities, and patient reports of cosmetic outcomes and satisfaction with the treatment or experience. Results Median follow-up was 24 months (interquartile range [IQR], 12-43 months). Local control and overall survival were 100% at 12 and 24 months. There were no acute or late toxicities of grade 3 or higher; no patients experienced fat necrosis, fibrosis, infection, or breast shrinkage. Excellent or good cosmesis at 12 months was reported by 91% of patients and 94% of physicians; at the most recent follow-up, these were 94% and 87%, respectively. The most commonly reported late cosmetic effect was telangiectasis (17%). The total patient satisfaction rate for treatment and results at 12 and 24 months was 96% and 100%, respectively. Patients’ mean time away from work was 5 days (IQR, 2-5 days), and the median out-of-pocket cost was $700 (IQR, $100-$1600). The mean left-sided heart dose was 2 cGy (range, 0.2-75 cGy), and the mean ipsilateral lung dose was 19 cGy (range, 0.2-164 cGy). Conclusions Proton APBI is a maturing treatment option with high local control, favorable intermediate-term cosmesis, high treatment satisfaction, low treatment burden, and exceptional heart and lung sparing.

Purpose Physical examination and diagnostic imaging are often less precise in determining the extent of disease in invasive lobular carcinoma (ILC) relative to nonlobular histologies. Anecdotally, surgical axillary evaluation frequently reveals positive lymph nodes in clinically N0 patients with ILC; however, few studies quantify the likelihood of finding unsuspected disease at the time of surgery. In this study, we evaluate whether the presence of lobular histology increases the incidence of surgical upstaging to pathologic stage IIIA or greater in patients with a clinically node-negative axilla and positive sentinel lymph node (SLN) biopsy. Methods and materials We examined patients from our institution between 1997 and 2009 treated specifically with mastectomy, SLN biopsy, and completion axillary lymph node dissection due to a positive SLN. For analysis, patients were grouped according to the presence of any lobular component on surgical pathology. The number of total positive lymph nodes, cancer stage, age, final tumor size, and ER/PR/HER2 status were assessed based on tumor histology. Results We evaluated 345 previously untreated women with clinical T0-T2 and N0 disease at the time of surgery. A total of 110 patients (32%) had a component of ILC on surgical pathology. In addition, 295 patients (85.5%) had ER + breast carcinoma, 243 (70.4%) had PR + disease, 56 (16.2%) were HER2 + , and 28 (8.1%) were triple negative. At the time of surgery, women with lobular disease were observed to have a greater number of positive lymph nodes (2.79 vs 2.26; P = .009) and were more frequently upstaged to at least pathologic stage IIIA compared with nonlobular patients (30.9% vs 17.4%; P = .007). Conclusions In this cohort, patients with a component of lobular carcinoma were more often surgically upstaged to pathologic stage IIIA or higher, which is a classical indication for postmastectomy radiation therapy. Our findings suggest that ILC is often more extensive than it appears clinically and has significant implications for management of patients with lobular carcinoma after the discovery of a positive SLN.

Background: Adoption of HF-WBI remains low due in part to concerns regarding its safety when used with a tumor bed boost or in patients who have received chemotherapy or have large breast size. To address this, we conducted a randomized, multicenter trial to compare CF-WBI (50Gy/25fx+10-14Gy/5-7fx) to HF-WBI (42.56Gy/16fx+10-12.5Gy/4-5fx). Methods: From 2011 and 2014, 287 women with stage 0-II breast cancer, age ≥40 years, were randomized to CF-WBI or HF-WBI, stratified by chemotherapy and breast size. The primary outcome was the proportion of patients with adverse Breast Cancer Treatment Outcomes Scale (BCTOS) cosmetic score three years post-WBI, defined as a score of ≥2.5 (a score of 1 indicates no difference between the treated breast and contralateral breast, 2-slight difference, 3-moderate difference, 4-large difference). Secondary patient-reported outcomes included BCTOS functional status, BCTOS breast pain, Body Image Scale (BIS), and the FACT-B Trial Outcome Index (TOI). Additional secondary outcomes included photographically-assessed cosmesis scored by a 3-physician panel blinded to randomization arm using the RTOG scale, physician-assessed CTCAEv4.0, overall survival (OS), local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS). Chi-square, Fisher's exact, Wilcoxon's rank sum, logistic regression, and log-rank tests evaluated differences by treatment arm; survival was measured using the Kaplan-Meier method. All analyses were intention-to-treat. Results: Of 287 patients enrolled, 286 received the protocol-specified radiation dose. Thirty percent received chemotherapy (73% anthracycline, 92% taxane, 22% trastuzumab), 37% had large breast size (D cup or larger), and 44% were obese (BMI≥30). All baseline characteristics were well-balanced by treatment arm (P>0.05). Median follow-up is 4.1 years. For the primary outcome, adverse BCTOS cosmetic score at 3 years was noted in 13.6% (n=15/110) of CF-WBI and 8.2% (n=8/97) of HF-WBI patients (P=0.22). There were trends for lower risk of adverse BCTOS cosmetic score with HF-WBI, compared to CF-WBI, among patients who did not receive chemotherapy (OR=0.25, 95%CI 0.06-1.03; Pinteraction=0.07) or with large breast size (OR=0.26, 95%CI 0.07-0.98; Pinteraction=0.08). There were no patient subgroups where risk of adverse BCTOS cosmetic outcome was significantly higher with HF-WBI compared to CF-WBI. For secondary outcomes, there was no difference by treatment arm for BCTOS functional status (P=0.83), BCTOS breast pain (P=0.69), BIS (P=0.45), or FACT-B TOI (P=0.79). Poor-fair cosmetic outcome at 3 years assessed by the 3-physician panel was noted in 28.8% of CF-WBI patients and 35.4% of HF-WBI patients (P=0.31). In total, 19% CF-WBI patients and 20% of HF-WBI patients had a grade 2-3 toxicity at the three-year evaluation, with no difference by treatment arm (P=0.84). Five-year OS, LRFS, and DMFS were 99%, 98%, and 99%, respectively, with no difference by treatment arm (P=0.68, 0.37, 0.62). Conclusions: Three years after WBI followed by a tumor bed boost, outcomes with HF and CF are similar. Tumor bed boost, modern chemotherapy, and large breast size do not appear to be clinically meaningful contraindications to HF-WBI. Citation Format: Shaitelman SF, Lei X, Thompson A, Schlembach P, Arzu I, Bloom ES, Buchholz DJ, Chronowski GM, Dvorak T, Grade EJ, Hoffman KE, Kelly P, Perkins GH, Reed V, Shah S, Stauder MC, Strom EA, Tereffe W, Woodward WA, Baumann D, Amaya D, Guerra W, Morrison M, Hortobagyi G, Hunt KK, Buchholz TA, Smith BD. Three-year outcomes with hypofractionated (HF) versus conventionally fractionated (CF) whole breast irradiation (WBI) [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 P2-11-02.

Purpose/Objective(s): To prospectively compare late toxicity after accelerated partial breast irradiation (APBI) with 3D-conformal external beam radiotherapy (3D-CRT) or single-entry multi-lumen intracavitary brachytherapy. Patients/Methods: Two hundred eighty-one patients with pTis or pT2N0 (≤3.0 cm) breast cancer treated with segmental mastectomy were prospectively enrolled on a multi-institution observational protocol from 12/2008 – 8/2014. Patients were enrolled and treated at primary, satellite, and affiliated academic institutions. APBI was delivered using 3D-CRT or with a Contura®, MammoSite®, or SAVI® brachytherapy catheter. 3D-CRT patients were treated to 34.0 Gy (7%) or 38.5 Gy (93%) at 3.4-3.85 Gy/fx BID and brachytherapy patients were treated to 34.0 Gy at 3.4 Gy/fx BID. Per protocol, patients were clinically evaluated at 2, 6, 12, 18, and 24 months and then annually. At each clinical evaluation the radiation oncologist scored cosmetic outcome (excellent/good/fair/poor according to the Harvard Cosmesis Scale), toxicity (seroma/infection/fat necrosis/pain/telangiectasia/radiation dermatitis/hyperpigmentation/hypopigmentation/fibrosis/induration/edema/other according to CTCAE v3.0) and recurrence status. Results: The median age was 61 years. Of 281 patients, 211 (75%) had invasive breast cancer and 70 (25%) had in situ disease. Among patients with invasive disease, 90% were HR+/HER2-, and among patients with in situ disease, 83% were HR+. APBI was delivered with 3D-CRT in 29 (10%) patients and with single-entry multi-lumen intracavitary brachytherapy in 252 (90%) patients. Among the brachytherapy patients, APBI was delivered with the SAVI®, Contura®, and MammoSite® devices in 176 (70%), 56 (22%), and 20 (8%) patients, respectively. With a median follow-up of 49 months, rates of Grade 1 (G1) and Grade 2-3 (G2-3) toxicity are: 3D-CRTBrachytherapy G1G2-3G1G2-3G1G2-3 N (%)N (%)N (%)N (%) Fibrosis13 (46%)1 (4%)176 (72%)6 (2%)p=0.008p=0.54Fat Necrosis0 (0%)0 (0%)0 (0%)4 (2%)p=1.00p=1.00Telangiectasia6 (21%)1 (4%)44 (18%)5 (2%)p=0.61p=0.48Seroma2 (7%)1 (4%)135 (55%)12 (5%)p Mean skin dose of the maximally-irradiated 0.1 cc (D0.1cc) of skin was significantly higher in patients who developed telangiectasia (103.4% ± 16.1% compared to 96.5% ± 18.6% of prescription dose, p=0.007) and fibrosis (100.1% ± 15.5% compared to 92.8% ± 23.0% of prescription dose, p=0.02). Crude rates of fair or poor cosmetic outcome at 2-4 and 4-6 years were 6.9% and 14.8%, respectively, for 3D-CRT and 14.8% and 21.3%, respectively, for brachytherapy (p>0.05 at both timepoints). Five-year recurrence-free survival was 96.3% with 3D-CRT and 96.1% for brachytherapy (p>0.05). Conclusion: APBI with single-entry multi-lumen intracavitary brachytherapy is associated with increased rates of grade 1 fibrosis and seroma than APBI with 3D-CRT. Higher mean skin D0.1cc is associated with increased risk of telangiectasia and fibrosis. Despite increased low-grade fibrosis, there is no significant difference in radiation oncologist-reported fair or poor cosmetic outcome out to six years, or rate of five-year ipsilateral breast recurrence. Citation Format: Stecklein SR, Babiera GV, Bedrosian I, Shaitelman SF, Ballo MT, Tereffe W, Arzu IY, Perkins GH, Strom EA, Reed VK, Dvorak T, Smith BD, Woodward WA, Hoffman KE, Schlembach PJ, Chronowski GM, Shah SJ, Kirsner SM, Nelson CL, Guerra W, Dibaj SS, Bloom ES. Prospective comparison of late toxicity and cosmetic outcome after accelerated partial breast irradiation with conformal external beam radiotherapy or single-entry multi-lumen intracavitary brachytherapy [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 P2-11-12.

Purpose/Objective(s) Breast cancer patients with clinical N3c (cN3c) disease at diagnosis have poor outcomes relative to other breast cancer patients. Radiotherapy (RT) has an important role in the management of these patients as the supraclavicular (SCV) nodes are not routinely surgically dissected. However, outcomes and prognostic factors in the era of modern neoadjuvant chemotherapy (NAC) are not well-described. Materials/Methods We reviewed breast cancer patients with non-metastatic cN3c disease treated at our institution from 2014-2019 with curative intent NAC, surgery, and adjuvant RT. All patients received nodal RT including the SCV, infraclavicular, and internal mammary nodes. Institutional guidelines recommend a 10 Gy boost to clinically resolved N3 nodal basins and 16 Gy to unresolved N3 nodes. Variables including initial and boost dose, pathologic response, and type of nodal dissection were collected. Local (LC) and regional control (RC), freedom from distant metastases (FFDM), and overall survival (OS) were analyzed with the Kaplan Meier method. A saturated multivariable Cox proportional hazards model of OS with backward elimination identified clinical variables associated with OS at P Results A total of 176 consecutive patients were analyzed. The median follow-up time was 2.83 years. The median age was 54 years, 76 (43%) were ER+/HER2-, 20 (11%) ER+/HER2+, 26 (15%) ER-/HER2+, and 54 (31%) ER-/HER2-. 102 (57%) had T3/4 disease, 41 (23%) underwent lumpectomy, 142 (81%) had pathologic confirmation of N3c, and 10 (6%) had a neck dissection. The median initial radiation dose was 50 Gy (range, 44-56.25), SCV boost 10 Gy (range, 6-16), and 156 (89%) received cumulative SCV dose ≥60 Gy. The 3-year OS, FFDM, RC, and LC were 79%, 64%, 93%, and 96%, respectively. For cumulative SCV dose of ≥60 Gy vs. Conclusion In a large, modern cohort of non-metastatic cN3c breast cancer patients treated with multimodality therapy, cumulative SCV dose ≥60 Gy was found to be associated with improved OS. Although optimal radiation dosing cannot be established from this data, a SCV radiation boost should be considered in cN3c patients treated with curative intent respecting normal tissue constraints.

Background We conducted a prospective phase II study to examine the response rate of gross chemo-refractory breast cancer treated with concurrent capecitabine (CAP) and radiotherapy (RT). Methods 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 45Gy. Conversion to operable (CTO), locoregional control, and grade>3 toxicities were assessed. The first nine patients received CAP 825 mg/m 2 BID continuously. Due to toxicity, subsequent patients received CAP only on radiation days. Kaplan-Meier analysis was used to estimate overall survival (OS) and locoregional recurrence-free survival (LRFS). Results From 2009-2012, 32 patients were accrued; 26 received protocol-specified treatment. Median follow-up was 12.9 months (interquartile range 7.1–42.9). Nineteen patients (73%) had partial or complete response. Fourteen patients (53.9%) experienced grade 3 non-dermatitis toxicity (7/9 continuous dosing). Three/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 (i.e., CTO but M1 disease immediately post-op) in 9/10 patients with triple-negative (TN) versus 6/16 with non-TN disease (p=0.014). Median OS and 1-yr LRFS among non-TN vs. TN patients was 22.8 vs. 5.1 months, and 63% vs. 20% (p=0.007). 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.

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.

Research in the area of cultural response pattern on questionnaires in the oncological setting and direct cross-cultural comparisons are lacking. This study examined response pattern in the reporting of depressive symptoms in Chinese and US women with breast cancer. We hypothesized that Chinese women are less likely to endorse positive affect items compared to their US counterparts. Additionally, we explored cultural differences in the association between positive affect and QOL. Secondary analyses of baseline assessments of two mind-body intervention studies for women with breast cancer undergoing radiotherapy in the USA (N = 62) and China (N = 97) are presented. All participants completed measures of depressive symptoms (CES-D) and cancer-specific QOL (FACT-B). We examined cultural differences on positive and negative affect items on the CES-D. Controlling for demographic factors, ANCOVA revealed a significant cultural difference in positive (F = 7.99, p = 0.005) but not negative affect (p = 0.82) with Chinese women reporting lower positive affect compared to US women (Chinese = 6.97 vs. US = 8.31). There was also a significant cultural difference (F = 3.94, p = 0.03) in the association between positive affect and QOL so that lower positive affect was more strongly associated with worse emotional well-being in Chinese (beta = 0.57, p

Hypothesis. This study examines moderators and mediators of a yoga intervention targeting quality-of-life (QOL) outcomes in women with breast cancer receiving radiotherapy. Methods. Women undergoing 6 weeks of radiotherapy were randomized to a yoga (YG; n = 53) or stretching (ST; n = 56) intervention or a waitlist control group (WL; n = 54). Depressive symptoms and sleep disturbances were measured at baseline. Mediator (posttraumatic stress symptoms, benefit finding, and cortisol slope) and outcome (36-item Short Form [SF]-36 mental and physical component scales [MCS and PCS]) variables were assessed at baseline, end-of-treatment, and 1-, 3-, and 6-months posttreatment. Results. Baseline depressive symptoms ( P = .03) and sleep disturbances ( P < .01) moderated the Group × Time effect on MCS, but not PCS. Women with high baseline depressive symptoms in YG reported marginally higher 3-month MCS than their counterparts in WL ( P = .11). Women with high baseline sleep disturbances in YG reported higher 3-months MCS than their counterparts in WL ( P < .01) and higher 6-month MCS than their counterparts in ST ( P = .01). YG led to greater benefit finding than ST and WL across the follow-up ( P = .01). Three-month benefit finding partially mediated the effect of YG on 6-month PCS. Posttraumatic stress symptoms and cortisol slope did not mediate treatment effect on QOL. Conclusion. Yoga may provide the greatest mental-health–related QOL benefits for those experiencing pre-radiotherapy sleep disturbance and depressive symptoms. Yoga may improve physical-health–related QOL by increasing ability to find benefit in the cancer experience.

It has been speculated that cancer survivors in Asia may have lower quality of life (QOL) compared with their Western counterparts. However, no studies have made international comparisons in QOL using a comprehensive measure. This study aimed to compare Chinese breast cancer survivors’ QOL with US counterparts and examine if demographic and medical factors were associated with QOL across groups. The sample consisted of 159 breast cancer patients (97 Chinese and 62 American) who completed the Functional Assessment for Cancer Therapy Breast Cancer (FACT-B) scale before the start of radiotherapy in Shanghai, China and Houston, USA. Higher income was associated with higher QOL total scores in both Chinese and American cancer patients, but QOL was not significantly associated with other factors including age, education, disease stage, mastectomy, and chemotherapy. Consistent with hypotheses, compared to their US counterparts, Chinese breast cancer survivors reported lower QOL and all four subdimensions including functional well-being (FWB), physical well-being (PWB), emotional well-being (EWB), and social well-being (SWB); they also reported more breast cancer-specific concerns (BCS). Differences were also clinically significant for Functional Assessment for Cancer Therapy General (FACT-G) scale total scores and the FWB subscale. After controlling for demographic and medical covariates, these differences remained except for the SWB and BCS. Furthermore, Chinese breast cancer survivors receiving chemotherapy reported significantly lower FACT-G scores than those who did not, but this difference did not emerge among US breast cancer survivors. Chinese breast cancer survivors reported poorer QOL on multiple domains compared to US women. Findings indicate that better strategies are needed to help improve the QOL of Chinese breast cancer survivors, especially those who underwent chemotherapy.

An integrated approach to skin sparing mastectomy with tissue expander placement followed by radiotherapy and delayed reconstruction was initiated in our institution in 2002. The purpose of this study was to assess the surgical outcomes of this strategy. Between September 2002 and August 2013, a total of 384 reconstructions had a tissue expander placed at the time of mastectomy and subsequently underwent radiotherapy. Rates and causes of tissue expander explantation before, during, and after radiotherapy, as well as tumor specific outcomes and reconstruction approaches, were collected. Median follow-up after diagnosis was 5.6 (range 1.3–13.4) years. In the study cohort, 364 patients (94.8%) had stage II–III breast cancer, and 7 patients (1.8%) had locally recurrent disease. The 5-year rates of actuarial locoregional control, disease-free survival, and overall survival were 99.2, 86.1, and 92.4%, respectively. The intended delayed-immediate reconstruction was subsequently completed in 325 of 384 mastectomies (84.6% of the study cohort). Of the remaining 59 tissue expanders, 1 was explanted before radiotherapy, 1 during radiotherapy, and 7 patients (1.8%) were lost to follow-up. Fifty patients (13.0%) required tissue expander explantation after radiation and before their planned final reconstruction, primarily due to cellulitis. Nonetheless, the cumulative rate of completed reconstructions was 89.6%. The median time from placement of the tissue expander until reconstruction was 12 (interquartile range 9–15) months. Tissue expander placement at skin-sparing mastectomy in patients who require radiotherapy appears to be a viable strategy for combining reconstruction and radiotherapy.

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.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/mFrom 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).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.

Purpose To develop a new approach for interobserver variability analysis. Methods and Materials Eight radiation oncologists specializing in breast cancer radiation therapy delineated a patient's left breast “from scratch” and from a template that was generated using deformable image registration. Three of the radiation oncologists had previously received training in Radiation Therapy Oncology Group consensus contouring for breast cancer atlas. The simultaneous truth and performance level estimation algorithm was applied to the 8 contours delineated “from scratch” to produce a group consensus contour. Individual Jaccard scores were fitted to a beta distribution model. We also applied this analysis to 2 or more patients, which were contoured by 9 breast radiation oncologists from 8 institutions. Results The beta distribution model had a mean of 86.2%, standard deviation (SD) of ±5.9%, a skewness of −0.7, and excess kurtosis of 0.55, exemplifying broad interobserver variability. The 3 RTOG-trained physicians had higher agreement scores than average, indicating that their contours were close to the group consensus contour. One physician had high sensitivity but lower specificity than the others, which implies that this physician tended to contour a structure larger than those of the others. Two other physicians had low sensitivity but specificity similar to the others, which implies that they tended to contour a structure smaller than the others. With this information, they could adjust their contouring practice to be more consistent with others if desired. When contouring from the template, the beta distribution model had a mean of 92.3%, SD ± 3.4%, skewness of −0.79, and excess kurtosis of 0.83, which indicated a much better consistency among individual contours. Similar results were obtained for the analysis of 2 additional patients. Conclusions The proposed statistical approach was able to measure interobserver variability quantitatively and to identify individuals who tended to contour differently from the others. The information could be useful as feedback to improve contouring consistency.

Purpose Previous research incorporating yoga (YG) into radiotherapy (XRT) for women with breast cancer finds improved quality of life (QOL). However, shortcomings in this research limit the findings. Patients and Methods Patients with stages 0 to III breast cancer were recruited before starting XRT and were randomly assigned to YG (n = 53) or stretching (ST; n = 56) three times a week for 6 weeks during XRT or waitlist (WL; n = 54) control. Self-report measures of QOL (Medical Outcomes Study 36-item short-form survey; primary outcomes), fatigue, depression, and sleep quality, and five saliva samples per day for 3 consecutive days were collected at baseline, end of treatment, and 1, 3, and 6 months later. Results The YG group had significantly greater increases in physical component scale scores compared with the WL group at 1 and 3 months after XRT (P = .01 and P = .01). At 1, 3, and 6 months, the YG group had greater increases in physical functioning compared with both ST and WL groups (P < .05), with ST and WL differences at only 3 months (P < .02). The group differences were similar for general health reports. By the end of XRT, the YG and ST groups also had a reduction in fatigue (P < .05). There were no group differences for mental health and sleep quality. Cortisol slope was steepest for the YG group compared with the ST and WL groups at the end (P = .023 and P = .008) and 1 month after XRT (P = .05 and P = .04). Conclusion YG improved QOL and physiological changes associated with XRT beyond the benefits of simple ST exercises, and these benefits appear to have long-term durability.

Purpose One interpretation of the American College of Surgeons Oncology Group Z0011 trial is that whole breast radiation therapy, known to treat a portion of the low axilla when delivered in the supine position, can treat residual microscopic disease in patients with involved axillary nodes that were not removed by axillary dissection. The purpose of this study was to quantify radiation dose delivered to the axilla for patients treated in the prone position. Methods and Materials We analyzed treatment plans from 40 consecutive patients who received radiation targeting the intact breast with tangent fields in the prone position. Axillary levels were contoured using Radiation Therapy Oncology Group (RTOG) definitions and radiation dose- volume calculations were made for axillary levels, heart, and lungs. We generated revised plans for 10 patients by modifying the tangent beams to increase axillary dose and compared original with modified plans. Results The median proportion of the axilla covered by 90% of the prescription dose was 13% of level I (range, 0%-61%), 0% of level II (range, 0%-6%), and 0% of level III (range, 0%-0%). More of the level I axilla was covered in obese compared with nonobese patients (P = .013). Level I coverage did not differ significantly by laterality (P = .740) or tumor location (P = .527). Modification of the treatment plans significantly increased level I coverage (P = .005) with all modified plans delivering 90% of the prescription dose to at least 96% of the level I axilla. The modified plans had increased lung (P = .005) and heart (P = .028) dose, which were within acceptable RTOG normal tissue constraints. Conclusions Most patients treated with standard whole breast tangential radiation in the prone position receive subtherapeutic dose to the level I and II axilla. Patients treated in the prone position who require therapeutic radiation dose to the low axilla need treatment field modification; this is feasible for many patients using tangent fields.

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.

Background:Circulating tumor cells (CTCs) are an independent predictor of survival in patients with breast cancer. In addition, mesenchymal (EMT-CTC) and stem-like (Stem-CTC) CTCs contribute to disease progression. The objective of the overall study is to determine whether a comprehensive lifestyle intervention program started prior to radiotherapy can modulate changes in CTC subsets that are correlated with disease recurrence and progression. For these analyses we examined the association between medical and treatment-related factors and CTCs. Patients and Methods: Seventy-eight patients with stage II/III breast cancer were recruited and randomized to either the intervention group or a standard care group. The intervention group (n=42) had in-person lifestyle counseling across the 4-6 weeks of radiotherapy (XRT) followed by video counseling for the subsequent 12 months. The standard care group (n=36) was provided patient-education materials for cancer prevention including information on diet, exercise, and stress management, without counseling. Blood samples were collected prior to initiation of XRT, end of XRT, and at 3-month intervals thereafter for up to 5 years. CTC subsets were detected by AdnaTest EMT2 kit (Qiagen, Venlo, Netherlands). Samples were considered positive for CTCs if any one of breast (EPCAM, MUC1, and HER2), EMT (TWIST1), or stem cell-related (ALDH1, AKT2, and PI3Kalpha) genes were detected by PCR above the manufacturer's suggested threshold. Results: The median age of patients was 49 years (range 26-82 years). Thirty-four patients were overweight (BMI 24.4-30) and 44 patients were obese (BMI >30). Forty-five patients were HR+Her2-, 12 patients were HR+Her2+, 5 patients were HR-Her2+, and 16 patients were TNBC. Sixteen patients were stage IIA or IIB, 34 patients were stage IIIA or IIIB, 27 patients were stage IIIC, and 1 was stage IV. Sixty-seven of 78 patients received neoadjuvant chemotherapy (NACT); 13 patients achieved a complete pathological response (pCR). The median follow-up was 21.6 months. CTC data of both intervention and standard groups were similar at baseline. Presence of CTCs at baseline or follow-up time points was not correlated to HR/Her2 status, stage, obesity, or pCR, but was significantly correlated with receiving NACT. Patients without NACT had significantly higher CTCs than patients who underwent NACT (Fisher Exact Test p=0.010). Furthermore, CTCs by the detection of any gene 3 months after completing XRT was associated with shorter PFS (log-rank p=0.016) and OS (p=0.03). Conclusions:This is an interim analysis of the prognostic potential of CTCs detected by AdnaTest EMT2 kit in non-metastatic breast cancer. We observed a lower proportion of patients with CTCs following neoadjuvant chemotherapy. However, the relative small sample size and short follow-up time preclude drawing conclusions to the efficacy of using CTCs as surrogate measures for lifestyle interventions, although the presence of CTCs in peripheral blood of patients 3 months after radiation therapy can be a promising indicator of disease relapse and overall survival. Citation Format: Gao H, Cohen EN, Yang P, Austin TA, Haddad R, Wu Q, Basen-Engquist KM, Ochoa JM, Arun BK, Perkins GH, Tin S, Vallone VS, Mallaiah SG, West CB, Thompson AS, Chaoul A, Cohen L, Reuben JM. Circulating tumor cell subset analysis to assess lifestyle interventions for breast cancer patients after neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-01-15.

Background: Capecitabine is an established radiosensitizer in rectal and other cancers. We conducted a prospective single arm phase II study to examine the response rate of gross chemo-refractory breast cancer treated with concurrent capecitabine and radiotherapy. Methods: Patients who had inoperable or marginally operable gross disease in the breast and/or lymph node(s) after chemotherapy or gross disease on the chest wall or in the regional lymphatics after mastectomy were eligible. Patients 1-9 received capecitabine 825 mg/m2 BID daily beginning on the first day of radiotherapy. Excess grade 3 toxicity (%) was observed; the protocol was amended and subsequent patients received drug only on radiation treatment days. Radiation dose was at the discretion of the treating physician (50Gy-72 Gy, with no more than 2.5 Gy/fraction). Response was assessed by a single physician using paired radiation planning CTs (pretreatment and on-treatment after 45 Gy). Clinical correlation to all other available imaging was also made. Kaplan-Meier curves were used to estimate overall survival (OS) and local recurrence-free survival (LRFS). Circulating tumor cells (CTCs) in blood were examined in consenting patients. Results: The trial was stopped early after an unplanned interim analysis prompted by slow accrual suggested futility independent of response. From 2009-2012, 32 patients were accrued; 26 completed protocol specific treatment (17 post-mastectomy radiation with gross nodes, 4 pre-op, 5 aggressive palliation) and are included in this analysis. Median follow up was 7.3 months (interquartile range 6.7 – 17.4). Nineteen patients (73%) had a partial or complete response. Fourteen patients (53.9%) experienced at least one grade 3 non-dermatitis toxicity including 7/9 treated with continuous dosing. Four inoperable patients were treated with pre-op radiation therapy and 3 converted to operable. None achieved a pCR or near pCR. One-year actuarial OS was 52%. There was no difference in OS comparing among PMRT vs. preoperative or palliative RT (P = 0.90). One-year actuarial local recurrence free survival among PMRT patients was 38%. Ten patients had triple negative (TN) receptor status. There was no difference in radiation response by receptor status (P = 0.56); however, treatment was deemed subjectively futile (i.e., converted to operable but death secondary to new widespread M1 disease immediately post-op) in 9 of the 10 patients with TN disease versus 6 of the 16 patients with non-TN disease (P = 0.014). Median OS and 1-yr actuarial OS, among non-TN vs. TN patients were not reached vs. 6.1 months and 77% vs. 10% (P < 0.001), respectively. Eight/fifteen patients tested were positive for CTCs. CTCs did not correlate to receptor status, futility of RT or OS. Conclusions: Capecitabine can be safely administered as a daily concurrent chemoradiation regimen with weekend holidays. However, in this small, prospective and selected cohort, concurrent chemoradiation with capecitabine was futile among patients with TN breast cancer. Alternative strategies are urgently needed in TN patients. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-14-08.

The treatment of locoregionally recurrent breast cancer in patients who have previously undergone radiation therapy is challenging. Special techniques are often required that both eradicate the disease and minimize the risks of retreatment. We report the case of a patient with an early-stage left breast cancer who developed inflammatory-type recurrence requiring re-irradiation of the chest wall using bolus electron conformal therapy with image-guided treatment delivery. The patient was a 51-year-old woman who had undergone lumpectomy, axillary lymph node dissection, and adjuvant whole-breast radiation therapy for a stage I left breast cancer in June 1998. In March 2009, she presented at our institution with biopsy-proven recurrent inflammatory carcinoma and was aggressively treated with multi-agent chemotherapy followed by mastectomy that left a positive surgical margin. Given the patient's prior irradiation and irregular chest wall anatomy, bolus electron conformal therapy was used to treat her chest wall and draining lymphatics while sparing the underlying soft tissue. The patient still had no evidence of disease 21 months after treatment. Our results indicate that bolus electron conformal therapy is an accessible, effective radiation treatment approach for recurrent breast cancer in patients with irregular chest wall anatomy as a result of surgery. This approach may complement standard techniques used to reduce locoregional recurrence in the postmastectomy setting.

Purpose Many patients with left-sided breast cancer receive adjuvant radiotherapy during deep-inspiration breath hold (DIBH) to minimize radiation exposure to the heart. We measured the displacement of the left anterior descending artery (LAD) and heart owing to cardiac motion during DIBH, relative to the standard tangential fields for left breast cancer radiotherapy. Methods and Materials A total of 20 patients who had undergone computed tomography-based coronary angiography with retrospective electrocardiographic gating were randomly selected for the present study. The patients underwent scanning during DIBH to control the influence of respiration on cardiac motion. Standard medial and lateral tangential fields were placed, and the LADs were contoured on the systolic- and diastolic-phase computed tomography data sets by the clinicians. Displacement of the LAD during cardiac contractions was calculated in three directions: toward the posterior edge of the treatment fields, left–right, and anteroposterior. Displacement of the entire heart was measured on the maximal and minimal intensity projection computed tomography images. Results The mean displacement of the LAD from cardiac contraction without the influence of respiration for 20 patients was 2.3 mm (range, 0.7–3.8) toward the posterior edge of the treatment fields, 2.6 mm (range, 1.0–6.8) in the left–right direction, and 2.3 mm (range, 0.6–6.5) in the anteroposterior direction. At least 30% of the LAD volume was displaced >5 mm in any direction in 2 patients (10%), and 5 mm in 10 patients (50%). The extent of displacement of the heart periphery during cardiac motion was negligible near the treatment fields. Conclusions Displacement of the heart periphery near the treatment fields was negligible during DIBH; however, displacement of the LAD from cardiac contraction varied substantially between and within patients. We recommend maintaining ≥5 mm of distance between the LAD and the field edge for patients undergoing breast cancer radiotherapy during DIBH.

Purpose: Optimal treatment of patients diagnosed with de novo metastatic breast cancer limited to the mediastinum or sternum has never been delineated. Herein the authors sought to determine the efficacy of multimodality treatment, including metastasis-directed radiotherapy (RT), in curing patients with this presentation.

The purpose of this study was to determine local-regional recurrence (LRR) risk according to whether postmastectomy radiation therapy (PMRT) was used to treat breast cancer patients with clinical T3N0 disease who received neoadjuvant chemotherapy (NAC) and mastectomy.Clinicopathology data from 162 patients with clinical T3N0 breast cancer who received NAC and underwent mastectomy were retrospectively reviewed. A total of 119 patients received PMRT, and 43 patients did not. The median number of axillary lymph nodes (LNs) dissected was 15. Actuarial rates were calculated using the Kaplan-Meier method and compared using the log-rank test.At a median follow-up of 75 months, 15 of 162 patients developed LRR. For all patients, the 5-year LRR rate was 9% (95% confidence interval [CI], 4%-14%). The 5-year LRR rate for those who received PMRT was 4% (95% CI, 1%-9%) vs. 24% (95% CI, 10%-39%) for those who did not receive PMRT (p0.001). A significantly higher proportion of irradiated patients had pathology involved LNs and were ≤40 years old. Among patients who had pathology involved LNs, the LRR rate was lower in those who received PMRT (p0.001). A similar trend was observed for those who did not have pathology involved LN disease. Among nonirradiated patients, the appearance of pathologic LN disease after NAC was the only clinicopathologic factor examined that significantly correlated with the risk of LRR.Breast cancer patients with clinical T3N0 disease treated with NAC and mastectomy but without PMRT had a significant risk of LRR, even when there was no pathologic evidence of LN involvement present after NAC. PMRT was effective in reducing the LRR rate. We suggest PMRT should be considered for patients with clinical T3N0 disease.

A previous randomized trial (CALGB 9344/Intergroup 0148) compared four cycles of adjuvant doxorubicin/cyclophosphamide (AC) to four cycles of AC plus four cycles of paclitaxel (AC + T) and demonstrated that the addition of paclitaxel improved locoregional control (LRC) in patients with node-positive breast cancer. However, it could not be determined whether it was the paclitaxel or the increased duration of chemotherapy that led to this improvement. The present study aimed to analyze whether the addition of paclitaxel to a doxorubicin-based regimen improves LRC in a cohort of patients who all received eight total cycles of chemotherapy. Five hundred eleven women with operable breast cancer were randomized on a single-institution prospective trial to receive 5-fluorouracil, doxorubicin, cyclophosphamide (FAC) × 8 cycles (n = 252) or FAC × 4 cycles plus paclitaxel × 4 cycles (TFAC) (n = 259). Rates of LRC and overall survival (OS) were analyzed. Median follow-up was 124 months (range 5-167 months). The 10-year LRC rate was 92.6 versus 93.1% in the FAC versus TFAC arms, respectively (P = 0.26). The LRC between treatment arms did not differ when analyzed by locoregional treatment group: breast conservation therapy (BCT), mastectomy alone (M), and mastectomy + radiation (M + RT). The 10-year LRC rates were 95.1% (FAC) versus 91.2% (TFAC) after BCT (P = 0.98), 89.5% (FAC) versus 93.4% (TFAC) after M (P = 0.24), and 94.7% (FAC) versus 96.5% (TFAC) after M + RT (P = 0.59). Additionally, there was no difference in OS between the treatment arms, with 10-year OS rates of 78.4% (FAC) versus 81.7% (TFAC) (P = 0.93). The addition of paclitaxel to a doxorubicin-based regimen had no impact on LRC, regardless of the type of local therapy received. Historically inferior LRC with AC chemotherapy alone versus AC + T may have been due to an inadequate duration of systemic therapy and not due to the absence of paclitaxel.

Background: Aggressive treatment of isolated breast cancer metastasis to either bone or lung has been reported to achieve long term survival. For the first time, we analyzed outcomes for patients (pts) with isolated metastasis to the contralateral (contra) supraclavicular (SCV) and/or axillary nodal basins. Material and Methods: Pts treated with definitive or palliative radiation to the contra nodal basin(s) at M.D. Anderson were analyzed from the period of 2005-2010. They were divided into two groups: pts initially diagnosed with contra SCV and/or axilla as the only site of metastasis (designated Primary), and pts with recurrence in the contra SCV and/or axilla, without other distant metastasis (designated Recurrent). Results: Of 34 potential pts with contra lymph node metastasis, 13 had isolated disease and were analyzed. In the Primary group (N=8, T4d N1- 3c M1), median survival was 25 mos, and 2-yr actuarial overall survivalwas 62.5%. All received neoadjuvant anthracycline and/or taxane-based chemotherapy followed by ipsilateral (ipsi) modified radical mastectomy and ipsi axillary lymph node dissection (ALND). The contra lymphatics were treated with ALND followed by radiation (N=5, 56-60 Gy) or with radiation alone (N=3, 45-66 Gy). Radiation fields included ipsi chest wall as well as ipsi and involved contra lymphatics. The contra chest wall or breast was radiated in 3 of the 8 pts. Two pts had estrogen receptor (ER) positive disease, and all had Her2-neu negative disease. Both ER+ pts are alive with no evidence of disease (NED; 1 had contra ALND; survival 25 and 51 mos). All 6 ER-pts died with disease (WD; 4 had contra ALND; survival 10 to 32 mos). One pt had an in-field recurrence in the contra nodal basin (51 Gy post ALND). No contra chest wall/breast recurrences were seen. All ER-pts developed additional distant metastasis, most within 4 mos of starting adjuvant radiation. Regarding the Recurrent group (N=5), median survival was 25 mos after recurrence. Two ER+ pts received initial anti-estrogen therapy; all ER-pts initially received a taxane-based chemotherapy. The contra chest wall or breast was radiated in addition to the involved contra lymphatics in 3 of the 5 pts. Two pts had adjuvant radiation treatment with definitive intent to the contra lymphatics after ALND (50-50.4 Gy), with 1 alive/NED (66 mos from recurrence, no radiation to the contra breast) and 1 dead/WD (25 mos from recurrence). Radiation intent was palliation in 3 pts (none received ALND) with 1 alive/WD (60 Gy, 64 mos from recurrence) and 2 dead/WD (53.8 and 45 Gy, 6 and 18 mos from recurrence, respectively). In-field recurrence in the contra nodal basin occurred in 1 pt (50.4 Gy). Pts who died had progressive disease or additional distant metastasis within 3 mos of starting radiation. Discussion: In this uncommon clinical scenario, locoregional control of the contra lymphatics was achieved with radiation alone or with surgery followed by radiation for a select group of pts; control was achieved without radiating the contra chest wall/breast. Only ER+ pts were rendered NED. Most ER-pts quickly developed other distant metastasis, highlighting the need for more effective systemic therapy. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-11-15.

BACKGROUND: Single-institution data suggest that treatment with radiation and axillary lymph node dissection (ALND) may be an appropriate alternative to mastectomy for T0N+ breast cancer. Population-based multi-institutional data supporting this approach are lacking. METHODS: The cause-specific survival (CSS) and overall survival (OS) of women with T0N+M0 ductal, lobular, or mixed breast cancer in the Surveillance, Epidemiology, and End Results database from 1983 to 2006 were analyzed. Groups were defined as: 1) no ALND, mastectomy, or RT (observation); 2) ALND only; 3) mastectomy plus ALND with or without postmastectomy radiation (Mast); and 4) breast-conserving therapy (BCT) with ALND and radiation (BCT). RESULTS: In total, 750 of 770,030 patients with breast cancer had T0N+M0 disease (incidence, 0.10%), and 596 of those patients underwent ALND (79.5%). Patients who underwent Mast or BCT (n = 470) had a 10-year OS rate of 64.9% compared with 58.5% for patients who underwent ALND only (n = 126; P = .02) and 47.5% for patients who underwent observation only (n = 94; P = .04). The 10-year CSS rate was 75.7% for patients who underwent BCT versus 73.9% for patients who underwent Mast (P = .55). In multivariate analysis of CSS for patients who underwent Mast or BCT, the following factors were correlated with an unfavorable outcome: positive estrogen receptor status (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.24-0.96; P = .04), ≥10 positive lymph nodes (HR, 5.7; 95%CI, 2.4-13.4; P ≤ .01), and

To determine the rate of locoregional recurrence (LRR) associated with modern tri-modality therapy.We retrospectively reviewed data from 291 consecutive PMRT patients treated from 1999 to 2001. These patients were compared to an historical group of 313 patients treated from 1979 to 1988 who had fluoroscopic simulation and contour-generated 2D planning. 1999-2001 spans the adoption of CT simulators for breast radiation therapy and a comparison was made between patients simulated before and after the implementation of CT simulation. Five-year actuarial rates for LRR, distal metastasis (DM), and overall survival (OS) between the pre and post CT simulation cohorts were compared as well.Compared to a 2D planned historic control, the combined contemporary patients had improved outcomes at 5years for all endpoints studied; LRR 3.0% vs. 11.5%, DM 29.2% vs. 39.2%, and OS 79.2% vs. 70.6% (p=0.0004, 0.0052, 0.0012, respectively). Significant factors in a multivariate analysis for LRR were: advanced T-stage (RR=2.14, CI=1.11-4.11, p=0.023), and percent positive nodes (RR=1.01, CI=1.00-1.02, p=0.012). The comparison of the pre and post CT-simulated PMRT patients (1999-2001) found no significant difference in any endpoint.The rate of locoregional control for PMRT patients treated with modern radiotherapy is outstanding and has improved significantly compared to historical controls.

BACKGROUND: there are concerns that physiologic changes of the peripartum breast may result in complications in breast conservation therapy. We present the complications of breast conservation surgeries and mastectomies performed for pregnancy-associated breast cancer (PABC). MATERIALS AND METHODS: from April 1989 through April 2008, sixty-seven breast cancer patients underwent surgical management for PABC, defined as surgery during pregnancy or within one year postpartum. Records of women who had surgery were examined for post-operative wound complications of milk fistula, cellulitis, abscess, or hematoma. RESULTS: Forty-seven patients underwent mastectomy. Twenty were treated with conservative breast surgery. There were six complications, all treated in the outpatient setting. There were no documented milk fistulae. CONCLUSIONS: in our series, we had few postoperative complications and no milk fistulae for those patients undergoing surgery for PABC. When compared to those who had mastectomy for PABC, women who underwent breast conserving therapy did not appear to have increased frequency of surgical complications.

To describe and evaluate the modified lateral decubitus boost, a breast irradiation technique. Patients are repositioned and resimulated for electron boost to minimize the necessary depth for the electron beam and optimize target volume coverage.A total of 2,606 patients were treated with post-lumpectomy radiation at our institution between January 1, 2000, and February 1, 2008. Of these, 231 patients underwent resimulation in the lateral decubitus position with electron boost. Distance from skin to the maximal depth of target volume was measured in both the original and boost plans. Age, body mass index (BMI), boost electron energy, and skin reaction were evaluated.Resimulation in the lateral decubitus position reduced the distance from skin to maximal target volume depth in all patients. Average depth reduction by repositioning was 2.12 cm, allowing for an average electron energy reduction of approximately 7 MeV. Mean skin entrance dose was reduced from about 90% to about 85% (p0.001). Only 14 patients (6%) experienced moist desquamation in the boost field at the end of treatment. Average BMI of these patients was 30.4 (range, 17.8-50.7). BMI greater than 30 was associated with more depth reduction by repositioning and increased risk of moist desquamation.The lateral decubitus position allows for a decrease in the distance from the skin to the target volume depth, improving electron coverage of the tumor bed while reducing skin entrance dose. This is a well-tolerated regimen for a patient population with a high BMI or deep tumor location.

PurposeThis study estimated the economic burden of breast cancer–related lymphedema (BCRL) among working-age women, the incidence of lymphedema, and associated risk factors.MethodsWe used claims data to study an incident cohort of breast cancer patients for the 2 years after the initiation of cancer treatment. A logistic regression model was used to ascertain factors associated with lymphedema. We compared the medical costs and rate of infections likely associated with lymphedema between a woman with BCRL and a matched control. We performed nonparametric bootstrapping to compare the unadjusted cost differences and estimated the adjusted cost differences in regression analysis.ResultsApproximately 10% of the 1,877 patients had claims indicating treatment of lymphedema. Predictors included treatment with full axillary node dissection (odds ratio [OR] = 6.3, P < .001) and chemotherapy (OR = 1.6, P = .01). A geographic variation was observed; women who resided in the West were more likely to have lymphedema claims than those in the Northeast (OR = 2.05, P = .01). The matched cohort analysis demonstrated that the BCRL group had significantly higher medical costs ($14,877 to $23,167) and was twice as likely to have lymphangitis or cellulitis (OR = 2.02, P = .009). Outpatient care, especially mental health services, diagnostic imaging, and visits with moderate or high complexity, accounted for the majority of the difference.ConclusionAlthough the use of claims data may underestimate the true incidence of lymphedema, women with BCRL had a greater risk of infections and incurred higher medical costs. The substantial costs documented here suggest that further efforts should be made to elucidate reduction and prevention strategies for BCRL.

Purpose To compare interobserver variations in delineating the whole breast for treatment planning using two contouring methods. Methods and Materials Autosegmented contours were generated by a deformable image registration-based breast segmentation method (DEF-SEG) by mapping the whole breast clinical target volume (CTVwb) from a template case to a new patient case. Eight breast radiation oncologists modified the autosegmented contours as necessary to achieve a clinically appropriate CTVwb and then recontoured the same case from scratch for comparison. The times to complete each approach, as well as the interobserver variations, were analyzed. The template case was also mapped to 10 breast cancer patients with a body mass index of 19.1–35.9 kg/m2. The three-dimensional surface-to-surface distances and volume overlapping analyses were computed to quantify contour variations. Results The median time to edit the DEF-SEG–generated CTVwb was 12.9 min (range, 3.4–35.9) compared with 18.6 min (range, 8.9–45.2) to contour the CTVwb from scratch (30% faster, p = 0.028). The mean surface-to-surface distance was noticeably reduced from 1.6 mm among the contours generated from scratch to 1.0 mm using the DEF-SEG method (p = 0.047). The deformed contours in 10 patients achieved 94% volume overlap before correction and required editing of 5% (range, 1–10%) of the contoured volume. Conclusion Significant interobserver variations suggested a lack of consensus regarding the CTVwb, even among breast cancer specialists. Using the DEF-SEG method produced more consistent results and required less time. The DEF-SEG method can be successfully applied to patients with different body mass indexes.

Purpose Young women with breast cancer have higher locoregional recurrence (LRR) rates than older patients. The goal of this study is to determine the impact of locoregional treatment strategy, breast-conserving therapy (BCT), mastectomy alone (M), or mastectomy with adjuvant radiation (MXRT), on LRR for patients 35 years or younger. Methods and Materials Data for 668 breast cancers in 652 young patients with breast cancer were retrospectively reviewed; 197 patients were treated with BCT, 237 with M, and 234 with MXRT. Results Median follow-up for all living patients was 114 months. In the entire cohort, 10-year actuarial LRR rates varied by locoregional treatment: 19.8% for BCT, 24.1% for M, and 15.1% for MXRT ( p = 0.05). In patients with Stage II disease, 10-year actuarial LRR rates by locoregional treatment strategy were 17.7% for BCT, 22.8% for M, and 5.7% for MXRT ( p = 0.02). On multivariate analysis, M (hazard ratio, 4.45) and Grade III disease (hazard ratio, 2.24) predicted for increased LRR. In patients with Stage I disease, there was no difference in LRR rates based on locoregional treatment (18.0% for BCT, 19.8% for M; p = 0.56), but chemotherapy use had a statistically significant LRR benefit (13.5% for chemotherapy, 27.9% for none; p = 0.04). Conclusions Young women have high rates of LRR after breast cancer treatment. For patients with Stage II disease, the best locoregional control rates were achieved with MXRT. For patients with Stage I disease, similar outcomes were achieved with BCT and mastectomy; however, chemotherapy provided a significant benefit to either approach.

Purpose To determine the differences in dosimetric coverage of the Level III axillary node target as a function of the superior tangential/supraclavicular match line in breast cancer patients undergoing with tangential breast and supraclavicular fossa radiotherapy. Methods and Materials The data from 20 consecutive breast cancer patients who were treated with breast conservation surgery and Level I and II axillary dissection followed by radiotherapy to the undissected Level III axilla/supraclavicular fossa were retrospectively analyzed. The nodal volumes were delineated from the computed tomography simulation data set. Three composite treatment plans were generated for each patient according to the placement of the match line. Results Coverage of the contoured Level III/axillary apex varied significantly with respect to the ipsilateral clavicular head, depending on the placement of the superior tangential/supraclavicular match line. The mean volume of the Level III/axillary apex covered by the 90% isodose line (45 Gy) was 100% for caudal placement of the match line, significantly greater than the 92% for intermediate placement (bisecting the clavicular head; p = 0.001) and the 68% for cranial placement with respect to the clavicular head ( p Conclusion Placement of the superior tangential/supraclavicular match line caudal to the clavicular head results in statistically improved dosimetric coverage of the Level III axilla/axillary apex in breast cancer patients undergoing tangential/supraclavicular radiotherapy.

Aims: Ductal carcinoma in situ (DCIS) associated with invasive mucinous carcinoma (IMC) has not been well characterized. The aim was to characterize mucinous DCIS (mDCIS) of the breast and to describe, to our knowledge for the first time, neovascularization in mucin. Methods and results: The pathology reports and slides were reviewed from 44 patients treated between 2003 and 2006 at The University of Texas M. D. Anderson Cancer Center, whose diagnosis fulfilled the criteria of IMC or DCIS with mucin production. The patients, all female, had a mean age of 62 years. DCIS was present in 93% of cases and the predominant histological types were solid, cribriform and micropapillary. The DCIS was grade 1 in 12 of 41 cases (29.3%), grade 2 in 25 of 41 cases (61%) and grade 3 in four of 41 cases (9.8%). Mucin was seen in the lumen of the ducts involved by DCIS in 88% of cases, mucin and vessels in 63.4% of cases and neither mucin nor vessels in 12.2%. The DCIS was vascular endothelial growth factor-positive, platelet-derived growth factor receptor-beta-positive and CDX-2-negative (100%). Occasional luminal cells within the DCIS were immunopositive for CD68. Conclusions: A significant number of mDCIS showed neovascularization in intraluminal mucin. When identified on core needle biopsy, the presence of vascularized mucin should not be used alone to discriminate between invasive and in situ carcinoma. A hypothesis proposed for the source of recruitment of vessels in the mucin is that mucin can promote neovascularization and that tumour cells invade not into the adjacent fibroconnective tissue, but rather into the mucinous, richly vascularized stroma that they have induced. Alternatively, it is possible that both cells and their secretory product invade together. To our knowledge, this is the first study to characterize neovascularization within the mucinous component of DCIS associated with and without IMC.

The aims of this study were to determine outcomes for patients with inflammatory breast cancer (IBC) treated with multimodality therapy, to identify factors associated with locoregional recurrence, and to determine which patients may benefit from radiation dose escalation.We retrospectively reviewed 256 consecutive patients with nonmetastatic IBC treated at our institution between 1977 and 2004.The 192 patients who were able to complete the planned course of chemotherapy, mastectomy, and postmastectomy radiation had significantly better outcomes than the 64 patients who did not. The respective 5-year outcome rates were: locoregional control (84% vs. 51%), distant metastasis-free survival (47% vs. 20%), and overall survival (51% vs. 24%) (p0.0001 for all comparisons). Univariate factors significantly associated with locoregional control in the patients who completed plan treatment were response to neoadjuvant chemotherapy, surgical margin status, number of involved lymph nodes, and use of taxanes. Increasing the total chest-wall dose of postmastectomy radiation from 60 Gy to 66 Gy significantly improved locoregional control for patients who experienced less than a partial response to chemotherapy, patients with positive, close, or unknown margins, and patients45 years of age.Patients with IBC who are able to complete treatment with chemotherapy, mastectomy, and postmastectomy radiation have a high probability of locoregional control. Escalation of postmastectomy radiation dose to 66 Gy appears to benefit patients with disease that responds poorly to chemotherapy, those with positive, close, or unknown margin status, and those45 years of age.

For patients with Stage II breast cancer with one to three positive lymph nodes, controversy exists about whether radiation as a component of treatment provides a survival benefit.We analyzed data from patients with Stage II breast cancer with one to three positive lymph nodes diagnosed from 1988-2002 in the Surveillance, Epidemiology, and End Results registry and compared the outcome of 12,693 patients treated with breast-conservation therapy with radiation (BCT + XRT) with the 18,902 patients treated with mastectomy without radiation (MRM w/o XRT).Patients treated with BCT + XRT were younger, were more likely to be treated in recent years of the study period, more commonly had T1 primary tumors, and had fewer involved nodes compared with those treated with MRM w/o XRT (p0.001 for all differences). The 15-year breast cancer-specific survival rate for the BCT + XRT group was 80% vs. 72% for the MRM w/o XRT group (p0.001). Cox regression analysis showed that MRM w/o XRT was associated with a hazard ratio for breast cancer death of 1.19 (p0.001) and for overall death of 1.25 (p0.001). The survival benefit in the BCT + XRT group was not limited to subgroups with high-risk disease features.Radiation use was independently associated with improved survival for patients with Stage II breast cancer with one to three positive lymph nodes. Because multivariate analyses of retrospective data cannot account for all potential biases, these data require confirmation in randomized clinical trials.