BACKGROUND/AIM:The 21-gene assay recurrence score (RS) can guide the use of chemotherapy for the management of patients with pN0- 1 [1-3 positive lymph nodes (LNs)] breast cancer. However, practice patterns based on this assay, as well as associated outcomes, have not been evaluated for patients with pN2 (4-9 positive LNs) disease. PATIENTS AND METHODS:The National Cancer Database (NCDB) was queried for patients with newly-diagnosed, non-metastatic, hormone receptor-positive, Her2-negative, pN2 breast cancer who underwent adjuvant endocrine therapy and had a known RS. Kaplan-Meier analysis was used to evaluate overall survival (OS); Cox proportional hazards modeling determined variables associated with OS. RESULTS:Of 1,658 patients, 1,109 (67%) received chemotherapy and 549 (33%) did not. Chemotherapy was administered to 54% of patients with a low-risk recurrence score (RS), 67% with intermediate-risk RS, and 75% with high-risk RS. Chemotherapy was associated with improved 5-year OS in low-risk RS (95.5% vs. 87.4%), intermediate-risk RS (91.9% vs. 83.5%), and high-risk RS (81.3% vs. 50.2%) (p≤0.001 for all). On Cox multivariable analysis, chemotherapy and the RS risk group significantly associated with OS (p<0.05 for both). Qualitatively, patients over 70 years of age appeared to benefit comparatively less from chemotherapy. CONCLUSION:Despite the underutilization of chemotherapy for hormone receptor-positive, Her2-negative, pN2 patients, it was associated with improved OS for all 21-gene panel risk groups. These results support the existing standard of chemotherapy for this population, although omission could be considered in patients over 70 years of age.

Abstract Background: High risk HER2-positive early breast cancer (EBC) patients are traditionally treated with neoadjuvant chemotherapy in combination with HER2-directed therapy. De-escalation approaches are being studied as benefits of chemotherapy in the HER2-enriched subset of EBC, but they have been inconclusive thus far. Preclinical studies suggest synergistic effect of immune checkpoint blockade (ICB) and HER2-directed therapy. This study hypothesizes that biologically directed HER-2 targeted therapy with Trastuzumab (T) and Pertuzumab (P) together with ICB (Durvalumab, D) will obviate the need of chemotherapy in HER2-enriched EBC patients. Methods: In this single arm, open-label phase II study, previously untreated, stage I-III, ER/PR negative, HER2-enriched breast cancer (BluePrint®, Agendia) patients were treated with D (1120mg IV, q3w), T (8mg/kg IV loading dose, 6 mg/kg IV q3w), and P (840 mg IV loading dose, 420 mg IV q3w) for 6 cycles. Response was assessed at end of 6 cycles with breast MRI and possible biopsy if residual disease was present. Responders (MRI and/or biopsy negative for residual cancer) proceeded to surgery, while patients with biopsy-proven residual disease were offered salvage standard chemotherapy (TCHP) before surgery. Primary end-point was pathological response rate defined as residual cancer burden (RCB)-0 and RCB-1. Patients who achieved RCB 0/1 received adjuvant DTP for 1 year. Results: A total of 51 patients were screened; 39 patients have been enrolled and received at least one cycle of treatment. Of these, 35 patients are evaluable for pathologic response, and 2 patients are still receiving treatment. One patient died of unrelated myocardial infarction, and one patient was lost to follow-up. The median age was 55 years (range 29-85). Thirty-one (79.5%) patients were white; 4 (10.3%) African American, and 4 (10.3%) Asian. Twenty-nine (74.3%) patients had >=T2 tumors; 21 (53.8%) patients had N1/N2/N3 disease. Six patients (15.3%) had biopsy-proven residual disease after DTP therapy, and they received salvage standard neoadjuvant TCHP chemotherapy. The combination was well tolerated; 5 (18.8%) patients had G3-4 adverse events. Twenty-seven of thirty-five patients (77.1%) had pathologic RCB 0/1 (RCB0, 20/35; RCB1 7/35), of whom only 3 patients had received salvage chemotherapy. Correlative studies, including tumor-infiltrating lymphocytes, immune-related gene signatures and PD-L1 expression are underway. Conclusions: Chemotherapy-free neoadjuvant regimen with DTP in HER2-enriched EBC showed high pathologic response rates comparable to that with chemotherapy. This DTP regimen may provide an effective, relatively non-toxic, and biologically driven alternative to standard of care chemotherapy in this HER2-enriched subset of EBC. Citation Format: Jian Guan, Kai Sun, Dharamvir Jain, Sunil Mathur, Hanh Mai, Polly Niravath, Jenny Chang. Chemotherapy-free neoadjuvant regimen with durvalumab, trastuzumab and pertuzumab (DTP) in HER2-enriched early breast cancer: A prospective, open-label phase II trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT029.

Abstract Background: Racial disparity outcomes in HER2-positive breast cancer have been previously described but the literature is limited. We examined data from our cancer center registry to investigate racial disparity in HER2-positive breast cancer. Method: We retrospectively queried patients diagnosed with HER2-positive breast cancer from Houston Methodist Cancer Center registry from 2016 to 2022. Patients’ demographics, cancer staging, treatment and outcomes including recurrence and survival were recorded and analyzed. We used the distressed communities index (DCI), a composite metric of multiple socioeconomic factors based on the patient’s zip code at diagnosis, as a surrogate of socioeconomic status. Multivariable logistic regression and Cox proportional hazards analysis were used. A p value <0.05 is considered statistically significant. Results: From 2016 to 2022, 992 patients were retrieved. 58.4% (579/992) patients were White, 17.3% (172/992) black, 16.2% (161/992) Hispanic and 8.1% (80/992) Asian. Although Black and Hispanic patients lived in more distressed communities, Black and Asian patients were diagnosed with more advanced disease. There were no statistically significant differences in neoadjuvant treatment received and pathologic complete response (pCR) rate among racial groups (table 1). Patients with higher stages are more likely to receive neoadjuvant treatment (OR: 5.49 [CI: 3.61-8.49] and 5.59 [CI: 3.15-10.2] for Stage 2 and 3 respectively). ER-HER2+ subtype was the only predictor of achieving pCR (OR: 0.47, CI: 0.29-0.79). Younger age, receiving neoadjuvant treatment and earlier stages were associated with improved all-cause mortality. There were no differences in receiving neoadjuvant treatment between racial groups, DCI; race and DCI are not associated with pCR or all-cause mortality. Conclusion: Our retrospective study from a single institution revealed no significant racial disparities in the treatment and outcome of HER2-positive breast cancers. Table 1. Characteristics of HER2-positive breast cancer in different racial groups Variables Asian, N = 80 Black, N = 172 Spanish, N = 161 White, N = 579 p-value Age (at diagnosis), mean (SD) 54 (13) 54 (12) 53 (13) 57 (13) <0.001 Distressed communities index, mean (SD) 28 (28) 49 (31) 49 (31) 35 (29) <0.001 HER2 subtype 0.7 ER-HER2+ 33/80 (41%) 64/169 (38%) 55/161 (34%) 204/576 (35%) ER+HER2+ 47/80 (59%) 105/169 (62%) 106/161 (66%) 372/576 (65%) Cancer stage 0.010 0 4/80 (5.0%) 4/172 (2.3%) 8/161 (5.0%) 31/579 (5.4%) 1 34/80 (43%) 51/172 (30%) 52/161 (32%) 227/579 (39%) 2 14/80 (18%) 44/172 (26%) 49/161 (30%) 172/579 (30%) 3 12/80 (15%) 30/172 (17%) 23/161 (14%) 52/579 (9.0%) 4 13/80 (16%) 30/172 (17%) 16/161 (9.9%) 63/579 (11%) Unknown 3/80 (3.8%) 13/172 (7.6%) 13/161 (8.1%) 34/579 (5.9%) Received neoadjuvant 0.074 No 31/66 (47%) 68/136 (50%) 54/134 (40%) 263/497 (53%) Yes 35/66 (53%) 68/136 (50%) 80/134 (60%) 234/497 (47%) Complete pathological response 0.9 No 17/35 (49%) 34/70 (49%) 40/75 (53%) 111/230 (48%) Yes 18/35 (51%) 36/70 (51%) 35/75 (47%) 119/230 (52%) Mortality (all cause) 0.052 Alive 76/80 (95%) 150/172 (87%) 147/161 (91%) 540/579 (93%) Dead 4/80 (5.0%) 22/172 (13%) 14/161 (8.7%) 39/579 (6.7%) Citation Format: Alan Hodges, Cornelius Rosenbaum, Claudia Santana, Polly A. Niravath, Hanh Mai, Dharamvir Jain, Jenny C. Chang, Jiaqiong Xu, Kai Sun. Racial disparity in HER2-positive breast cancer: A single cancer center registry review [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6113.

Abstract Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a very common dose-limiting side effect of many cancer treatments. However, the optimal treatment for CIPN remains unclear. Electroacupuncture (EA) is a non-pharmacologic treatment that combines traditional acupuncture with electrical stimulation. EA is being examined for CIPN and has shown modest benefits. Design: This is a pilot, single-center, prospective, single-arm, non-blinded study. All subjects had residual grade ≥2 CIPN after having received curative intent chemotherapy for stage I-III breast cancer, completed at least 3 months prior to study enrollment. Patients received 10 sessions of electro-acupuncture, administered by a licensed professional, over the course of 7 weeks. A sub-group of patients also had baseline and post-treatment skin punch biopsies to assess intra-epithelial nerve density (IEND). The primary objective was to determine the feasibility of completing a 10-treatment EA program in this patient population. Feasibility was defined as ≥15 subjects completing ≥8 EA treatments. Secondary endpoints included neuropathic pain, as assessed by the Brief Pain Inventory-Short Form (BPI-SF), and change in the quality of life, as assessed by the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-NTX) subscale. Results: Twenty eligible female subjects were included in the study, with a median age of 66.5 years (range 45-81 years old). All patients received taxane chemotherapy, with 15 (75%) patients receiving weekly paclitaxel, 4 (8%) patients receiving Taxotere every 3 weeks, and 1 (2%) patient received weekly abraxane. The duration between chemotherapy completion and EA treatment initiation ranged between 4-92 months, with a median of 29 months. Eight (40%) patients were taking gabapentin, 2 (10%) on duloxetine, 1 (5%) pregabalin, and 3 (15%) on NSAIDS before and during the study. The study met its primary endpoint of feasibility, with 18 of 20 (90%) patients completing 8 or more EA sessions. Pain level, as assessed by the worst pain score on BPI-SF, improved significantly from a mean of 6.3 to 3.7, 2 weeks after completion of EA treatments (p = .0058). FACT/GOG-NTX quality of life measurement, “I am bothered by side effects of my treatment” also significantly improved from a mean score of 2.1 to 0.8 (p = .0177). There were no major adverse events (AEs) related to EA. Nine mild AEs were noted among 6 (30%) patients; localized skin biopsy site infections: G1=3, G2=3, nonlocalized cellulitis G3=1, Fatigue G1-2 =2. The localized skin biopsy site infections led to the discontinuation of further skin biopsy procedures. [We will also present data on the IEND for the nine patients who have paired before and after skin punch biopsies – this will be available at the time of the conference.] Conclusion: Electroacupuncture is a feasible treatment for CIPN. Furthermore, this pilot study did show a benefit for perceived pain and quality of life. Further studies will need to be conducted in regards to longevity of response. As larger studies in the future confirm the benefit of acupuncture, insurance payors are more likely to cover this important service. Citation Format: Nikitha Vobugari, John Paul Liang, Loni Savage, Dharamvir Jain, Kai Sun, Hanh Mai, Jenny Chang, Monica Desai, Tejal Patel, Polly Niravath. A Single-Arm Pilot Study of the Feasibility and Efficacy of Electro-Acupuncture in Subjects with Chemotherapy-Induced Peripheral Neuropathy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-12-09.

Living guidelines are developed for selected topic areas with rapidly evolving evidence that drives frequent change in recommended clinical practice. Living guidelines are updated on a regular schedule by a standing expert panel that systematically reviews the health literature on a continuous basis, as described in the ASCO Guidelines Methodology Manual. ASCO Living Guidelines follow the ASCO Conflict of Interest Policy Implementation for Clinical Practice Guidelines. Living Guidelines and updates are not intended to substitute for independent professional judgment of the treating provider and do not account for individual variation among patients. See appendix for disclaimers and other important information (Appendix 1 and Appendix 2). Updates are published regularly and can be found at https://ascopubs.org/nsclc-non-da-living-guideline.

Living guidelines are developed for selected topic areas with rapidly evolving evidence that drives frequent change in recommended clinical practice. Living guidelines are updated on a regular schedule by a standing expert panel that systematically reviews the health literature on a continuous basis, as described in the ASCO Guidelines Methodology Manual. ASCO Living Guidelines follow the ASCO Conflict of Interest Policy Implementation for Clinical Practice Guidelines. Living Guidelines and updates are not intended to substitute for independent professional judgment of the treating provider and do not account for individual variation among patients. See Appendix 1 (online only) for disclaimers and other important information. Updates are published regularly and can be found at https://ascopubs.org/nsclc-non-da-living-guideline.

PURPOSE:To provide evidence-based recommendations updating the 2020 ASCO and Ontario Health (Cancer Care Ontario) guideline on systemic therapy for patients with stage IV non-small-cell lung cancer without driver alterations. METHODS:ASCO updated recommendations on the basis of an ongoing systematic review of randomized clinical trials from 2018 to 2021. RESULTS:This guideline update reflects changes in evidence since the previous update. Five randomized clinical trials provide the evidence base. Outcomes of interest include efficacy and safety. RECOMMENDATIONS:In addition to 2020 options for patients with high programmed death ligand-1 (PD-L1) expression (tumor proportion score [TPS] ≥ 50%), nonsquamous cell carcinoma (non-SCC), and performance status (PS) 0-1, clinicians may offer single-agent atezolizumab. With high PD-L1 expression (TPS ≥ 50%), non-SCC, and PS 0-1, clinicians may offer nivolumab and ipilumumab alone or nivolumab and ipilimumab plus chemotherapy. With negative (0%) and low positive PD-L1 expression (TPS 1%-49%), non-SCC, and PS 0-1, clinicians may offer nivolumab and ipilimumab alone or nivolumab and ipilimumab plus chemotherapy. With high PD-L1 expression, SCC, and PS 0-1, clinicians may offer single-agent atezolizumab. With high PD-L1 expression, squamous cell carcinoma (SCC), and PS 0-1, clinicians may offer nivolumab and ipilimumab alone or in combination with two cycles of platinum-based chemotherapy. With negative and low positive PD-L1 expression, SCC, and PS 0-1, clinicians may offer nivolumab and ipilimumab alone or in combination with two cycles of platinum-based chemotherapy. With non-SCC who received an immune checkpoint inhibitor and chemotherapy as first-line therapy, clinicians may offer second-line paclitaxel plus bevacizumab. With non-SCC, who received chemotherapy with or without bevacizumab and immune checkpoint inhibitor therapy, clinicians should offer the options of third-line single-agent pemetrexed, docetaxel, or paclitaxel plus bevacizumab.Additional information is available at www.asco.org/thoracic-cancer-guidelines.

1079 Background: Pembrolizumab, stereotactic body radiotherapy (SBRT), and viral vector-based gene therapy such as adenovirus-mediated expression of herpes simplex virus thymidine kinase (ADV/HSV-tk) plus ganciclovir have each shown antitumor immune activity. The combination of those modalities may represent a window of opportunity to enhance pembrolizumab efficacy in mTNBC patients. Methods: In this single-arm, open-label phase II trial, mTNBC patients were treated with in situ oncolytic ADV/HSV-tk (5 x 1011 vp) intratumoral injection, followed by SBRT to the injected tumor site, then pembrolizumab until progression or intolerable toxicity. Response was assessed in non-irradiated metastatic sites. The primary end point was clinical benefit rate (CR, PR and SD per RECIST version1.1). Secondary endpoints included duration on treatment (DoT) and safety. Immune correlative analysis with peripheral blood CYTOF (D1 baseline, D7 and D38), and tissue imaging mass cytometry (IMC) with 35 cell surface markers was performed on paired biopsies (D1 baseline and D17). Results: 28 mTNBC patients were enrolled; 18 (64.3%) had PD-L1 negative tumors. Median age was 54 years (range 34-78). Median prior lines of chemotherapy were 2 (range 0-6), with 8 (28.6%) having received >3. 3 (10.7%) had brain metastases. Clinical benefit was seen in 6 (21.43%) patients; 2 CR (7.1%),1 PR (3.57%) and 3 SD (10.7%). Patients who had clinical benefits had durable responses, with median DoT of 383 days (range 195-1195). One patient who had CR, but discontinued pembrolizumab due to Grade 3 pneumonitis, has remained disease free without any systemic therapy for 39 months. The combination was well tolerated; 9 (32.1%) patients had Grade 3- 4 AEs. Pre- and post-therapy CYTOF analysis showed significant association between immune biomarkers with clinical responses (AUC 0.75, Cohen’s Kappa 0.364). Tumor PDL1 was independently associated with response (AUC 0.70, Cohen’s Kappa 0.347); AUC for PDL1 together with immune biomarkers is 0.85. Conclusions: ADV/HSV-tk gene therapy followed by radiation therapy and then pembrolizumab is a well-tolerated promising treatment in heavily pretreated mTNBC patients. Early detection of increased effector and effector memory CD8 T cells and nonclassical monocytes correlates with response and non-response respectively. Clinical trial information: NCT03295916 .[Table: see text]

PURPOSE The aim of this work is to provide evidence-based recommendations updating the 2017 ASCO guideline on systemic therapy for patients with stage IV non–small-cell lung cancer (NSCLC) without driver alterations. A guideline update for patients with stage IV NSCLC with driver alterations will be published separately. METHODS The American Society of Clinical Oncology and Ontario Health (Cancer Care Ontario) NSCLC Expert Panel made updated recommendations based on a systematic review of randomized controlled trials from December 2015 to 2019. RESULTS This guideline update reflects changes in evidence since the previous guideline update. Five randomized controlled trials provide the evidence base. Additional literature suggested by the Expert Panel is discussed. RECOMMENDATIONS Recommendations apply to patients without driver alterations in epidermal growth factor receptor or ALK. For patients with high programmed death ligand 1 (PD-L1) expression (tumor proportion score [TPS] ≥ 50%) and non–squamous cell carcinoma (non-SCC), the Expert Panel recommends single-agent pembrolizumab. Additional treatment options include pembrolizumab/carboplatin/pemetrexed, atezolizumab/carboplatin/paclitaxel/bevacizumab, or atezolizumab/carboplatin/nab-paclitaxel. For most patients with non-SCC and either negative (0%) or low positive (1% to 49%) PD-L1, the Expert Panel recommends pembrolizumab/carboplatin/pemetrexed. Additional options are atezolizumab/carboplatin/nab-paclitaxel, atezolizumab/carboplatin/paclitaxel/bevacizumab, platinum-based two-drug combination chemotherapy, or non–platinum-based two-drug therapy. Single-agent pembrolizumab is an option for low positive PD-L1. For patients with high PD-L1 expression (TPS ≥ 50%) and SCC, the Expert Panel recommends single-agent pembrolizumab. An additional treatment option is pembrolizumab/carboplatin/(paclitaxel or nab-paclitaxel). For most patients with SCC and either negative (0%) or low positive PD-L1 (TPS 1% to 49%), the Expert Panel recommends pembrolizumab/carboplatin/(paclitaxel or nab-paclitaxel) or chemotherapy. Single-agent pembrolizumab is an option in select cases of low positive PD-L1. Recommendations are conditional on the basis of histology, PD-L1 status, and/or the presence or absence of contraindications. Additional information is available at www.asco.org/lung-cancer-guidelines .

Purpose: The utility of post-mastectomy radiotherapy (PMRT) in women with a nodal complete response (CRn) to neoadjuvant chemotherapy (NAC) is unknown. The NSABP B-51 trial is evaluating this question, but has not reported results thus far. Therefore, we sought to answer this question with the National Cancer Database. Methods: The National Cancer Database was queried for women with cT1-4N1-3M0 breast cancer who had undergone NAC and were ypN0 upon mastectomy. Statistics included multivariable logistic regres-sion, Kaplan-Meier overall survival (OS) analysis, Cox proportional hazards modeling, and construction of forest plots. Results: Of 14,690 women, 10,092 (69%) underwent adjuvant PMRT and 4598 (31%) did not. The median follow-up was 55.6 months. In all patients, the 10-year OS was 76.3% for PMRT and 78.6% without (p = 0.412). There were no notable effects of PMRT on OS based on age or the axillary management (num-ber of nodes removed). Specifically, in the NSABP B-51 population of cT1-3 cN1 patients, the 10-year OS was 82.6% for PMRT and 80.0% without (p = 0.250). PMRT benefitted women with increasing cT stage (i.e. cT3-4), increasing ypT stages (with the exception of ypT4 potentially owing to small sample sizes), and cN3 cases (p < 0.05 for all). Conclusions: In the absence of published results from NSABP B-51, this assessment of over 14,000 women from a contemporary US database revealed that PMRT may be most useful for a "moderately-high" risk group - women with more advanced primary and/or nodal disease at diagnosis, yet with tumor biology favorable enough that the disease does not progress or remain stable after NAC. The OS findings notwith-standing, this study cannot exclude potential differences between groups in recurrence-free survival, which is the primary endpoint of NSABP B-51, While the results of the NSABP B-51 will confirm optimal management for patients with limited nodal disease having a CRn following NAC, the present results sug-gest PMRT should remain the standard of care for more advanced disease than NSABP B-51 eligibility criteria. (c) 2021 Elsevier B.V. All rights reserved. Radiotherapy and Oncology 162 (2021) 52-59

This pilot study evaluated adherence to anti-estrogen therapy in women with hormone receptor-positive breast cancer utilizing bubble packaging.

Advanced age is a risk factor for cancer and is attributed to dysregulation of the immune system. Historically, treatment of advanced cancer has primarily involved systemic chemotherapy that is associated with high treatment related toxicity especially in older adults. Immune checkpoint inhibitors (ICIs) provide an exciting treatment option for older adults in terms of efficacy and safety as compared to systemic chemotherapy. Given the pace of approval of ICIs for multiple cancers, there is an increase in both the use of ICIs and the associated immune-related adverse events. In this article, we address how to approach immunotherapy related toxicities in older adults given the availability of limited data.

Objectives: To compare the outcomes and toxicity of high-dose cisplatin (HDC) versus weekly cisplatin (WC) definitive chemoradiotherapy (CRT) for patients with human papillomavirus (HPV) related oropharyngeal squamous cell carcinoma (SCCOPx).Methods: All patients with p16 positive SCCOPx treated with definitive CRT with cisplatin between 2010 and 2014 at a single institution were retrospectively reviewed. CTCAE v 4.03 toxicity criteria were used. The Kaplan-Meier method was used to estimate event-free survival (EFS) and the overall survival (OS).Results: Of the 55 patients included, 22 were patients treated with HDC at dose of 100 mg/m(2) on days 1 and 22; and the remaining 33 patients were treated with WC at 40 mg/m(2). Both cohorts received a median total dose of cisplatin of 200 mg/m(2). At median follow-up of 31 months, there was one local failure and no distant failures in the HDC cohort. In the WC group, there were 6 total failures (2 local, 4 distant). Estimated 2-year EFS was better in HDC cohort as compared to WC (96% vs. 75%; p = 0.04). There was no significant difference in 2-year OS (95% vs. 94%; p = 0.40). Weight loss, gastric tube dependence at six months, acute renal injury and grade 3 or 4 hematological toxicity were all similar between both groups.Conclusions: HPV-related SCCOPx treated with definitive CRT with either HDC or WC had similar toxicity profile. HDC had better EFS when compared with WC and this seems to be driven by increased distant failure rates, although the OS was similar. (C) 2017 Elsevier Ltd. All rights reserved.

Purpose: To report early outcome analysis of a prospective institutional phase 2 trial of weekly hypofractionated breast irradiation (WHBI) for patients undergoing breast-conserving surgery (BCS).Methods and Materials: Patients who underwent BCS for American Joint Committee on Cancer stage 0, I, or II breast cancer with negative surgical margins received whole-breast radiation therapy to 30 or 28.5 Gy in 5 weekly fractions with or without an additional boost. The eligibility criteria were the same as for NSABP (National Surgical Adjuvant Breast and Bowel Project) B39/RTOG (Radiation Therapy Oncology Group) 0413, and there were no restrictions on age, breast size, tumor grade, receptor status, or the use of cytotoxic chemotherapy for otherwise eligible patients. The primary endpoint was ipsilateral breast tumor recurrence. Patients were also evaluated for acute toxicity (Common Terminology Criteria for Adverse Events version 3.0), cosmesis (Harvard Scale), development of distant metastatic disease, and overall survival.Results: Between January 2011 and October 2015, 158 eligible patients underwent WHBI immediately following BCS. The median age was 60 years (range, 30-84 years), and the median follow-up period was 3 years. Ipsilateral breast tumor recurrence developed in a total of 2 patients (1.3%), 1 in conjunction with widespread metastatic disease. Distant metastatic disease developed in 4 patients (2.5%), and the 3-year disease-free survival and overall survival rates were 97.5% and 96.2%, respectively. The most common grade 1 or 2 acute toxicities were breast pain, radiation dermatitis, and fatigue. There were 2 grade 3 events (1.3%): pain requiring narcotic analgesics (1) and post-treatment infection requiring hospitalization (1). The rate of excellent or good cosmesis versus fair or poor cosmesis was 82.3% versus 17.7%. The rate of significant cosmetic change from baseline to last follow-up (dropping from excellent or good to fair or poor) was 11.6%.Conclusions: Early outcomes after WHBI are favorable and parallel those seen with daily hypofractionated whole-breast irradiation. With broader entry criteria than all previous reports of WHBI, this study will facilitate comparison to the results of NSABP B39/RTOG 0413. With continued follow-up, future reports will assess cosmetic stability and disease-specific outcomes. (C) 2017 Elsevier Inc. All rights reserved.

Aging poses an unique opportunity to study cancer biology and treatment in older adults. Breast cancer is often studied in young women; however, much investigation remains to be done on breast cancer in our expanding elderly population. Diagnostic and management strategies applicable to younger patients cannot be empirically used to manage older breast cancer patients. Lack of evidence-based data continues to be the major impediment toward delivery of personalized cancer care to elderly breast cancer patients. This article reviews the relevant literature on management of curable breast cancer in the elderly, the role of geriatric assessment, complex treatment decision making within the context of patient's expected life expectancy, comorbidities, physical function, socioeconomic status, barriers to health care delivery, goals of treatment, and therapy-related side effects. Continuing efforts for enrolling elderly breast cancer patients in contemporary clinical trials, and thus improving age-appropriate care, are emphasized.

The Human Epidermal growth factor Receptor 2 (HER2) is a potent mediator of cellular growth and proliferation. It plays an important role in cardiac development and maintaining the physiologic function of an adult heart. Amplification of the HER2 gene, and the corresponding overexpression of the HER2 receptor, occurs in roughly 20% of breast tumors and is associated with a poor outcome. Molecular targeting of the HER2 receptor with the humanized monoclonal antibody, Trastuzumab has improved disease-free and overall survival in patients with both metastatic and early HER2-positive breast cancer. Although trastuzumab is devoid of the classical toxicities associated with chemotherapy, one of the major concerns noted is the occurrence of symptomatic and asymptomatic cardiotoxicity (decline in left-ventricular-ejection-fraction (LVEF). Additionally, newer HER2 therapies such as Lapatinib, Pertuzumab and Ado-trastuzumab (TDM1) are either approved or are being evaluated in clinical trials for cancer therapy. Targeted therapies against HER2 have led to revolutionary strides in breast cancer research and treatment. With the concern of cardiotoxicity caused by these agents, new treatment strategies for preventing cardiac side effects need to be developed. In this review, we discuss the proposed mechanisms of HER 2 antagonist-induced cardiotoxicity and the ways to prevent it.

Tumor-associated macrophages (TAM) with an alternatively activated phenotype have been linked to tumor-elicited inflammation, immunosuppression, and resistance to chemotherapies in cancer, thus representing an attractive target for an effective cancer immunotherapy. In this study, we demonstrate that particulate yeast-derived β-glucan, a natural polysaccharide compound, converts polarized alternatively activated macrophages or immunosuppressive TAM into a classically activated phenotype with potent immunostimulating activity. This process is associated with macrophage metabolic reprograming with enhanced glycolysis, Krebs cycle, and glutamine utilization. In addition, particulate β-glucan converts immunosuppressive TAM via the C-type lectin receptor dectin-1-induced spleen tyrosine kinase-Card9-Erk pathway. Further in vivo studies show that oral particulate β-glucan treatment significantly delays tumor growth, which is associated with in vivo TAM phenotype conversion and enhanced effector T cell activation. Mice injected with particulate β-glucan-treated TAM mixed with tumor cells have significantly reduced tumor burden with less blood vascular vessels compared with those with TAM plus tumor cell injection. In addition, macrophage depletion significantly reduced the therapeutic efficacy of particulate β-glucan in tumor-bearing mice. These findings have established a new paradigm for macrophage polarization and immunosuppressive TAM conversion and shed light on the action mode of β-glucan treatment in cancer.

After the pathogenesis of thyroid carcinomas was better understood and the role of molecular alterations in RET, BRAF and RET/PTC rearrangement was revealed, several trials using multikinase inhibitors were developed during the last decade for the treatment of recurrent radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC), achieving a remarkable success. Sorafenib became the first drug approved for this indication in more than two decades after a significant improvement in the progression-free survival was demonstrated. Lenvatinib (E-7080), an orally active inhibitor of multiple receptor tyrosine kinases including vascular endothelial growth factor receptors (VEGFR) 1, 2 and 3, proto-oncogene tyrosine-protein kinase receptor Ret and mast/stem cell growth factor receptor Kit, yielded highly promising early clinical data, even when given after progression on first-line therapy. The phase III SELECT trial recently demonstrated the impressive clinical activity of the drug in RAI-refractory thyroid cancer, leading to the drug's approval by the regulatory agencies and potentially making lenvatinib the most effective drug available to date for the treatment of the disease.

Patients with locally advanced, neglected, recurrent, or metastatic inoperable breast cancer, or a combination of these conditions, may live for an extended period as a result of effective systemic therapy. Durable local control is needed to control symptomatic tumors. Twenty patients received concurrent chemoradiotherapy (CRT), with an overall response rate of 100%, 2-year local relapse-free survival of 73%, and acceptable toxicity.Background: This study aimed to assess the efficacy and safety of chemoradiotherapy (CRT) for locally recurrent or advanced inoperable breast cancer. Patients and Methods: Twenty patients treated between 2009 and 2013 were reviewed from a prospectively collected database. All patients had symptomatic recurrent or advanced breast cancer and had been deemed not to be ideal operative candidates. Treatment consisted of external beam radiotherapy to the primary tumor in the breast or regional lymph nodes, or both, concurrent with either capecitabine, paclitaxel, or cisplatin/etoposide chemotherapy. The grade of acute and late toxicity was evaluated, as was response to treatment, overall survival (OS), and local relapse-free survival (LRFS). Results: Of the 20 patients, 9 (45%) presented with primary disease and 11 (55%) had recurrent disease. A total of 11 (55%) patients had evidence of metastatic disease. The overall clinical response rate was 100%, with a clinical complete response (CR) observed in 65% of patients and a clinical partial response (PR) observed in 35% of patients. At a median follow up of 25.3 months, 2-year LRFS was 73% and 2-year OS was 80%. Local control was significantly better in patients with an initial diagnosis (hazard ratio [HR], 0.139; 95% confidence interval [CI], 0.014-0.935) and in those who had not had previous in-field radiation (HR, 0.011; 95% CI, 0.005-0.512). The only grade > 3 toxicity was acute dermatologic events (30%) and late dermatologic (15%) events. Conclusion: Concurrent CRT with capecitabine, paclitaxel, or cisplatin/etoposide for recurrent or advanced inoperable breast cancer is well tolerated with impressive clinical response rates and durable local control.

A planned interim analysis of an institutional Phase II trial of once-weekly radiation therapy for patients undergoing breast-conserving surgery (BCS). Patients who underwent BCS for AJCC Stage 0, I or II breast cancer with negative surgical margins were eligible to receive whole-breast radiation therapy to a dose of 30 Gy in 5 weekly fractions of 6 Gy with or without an additional boost. There were no restrictions on age, breast size or the use of cytotoxic chemotherapy for otherwise eligible patients. Patients were evaluated at baseline, 6 and 12 months with digital photography, physician assessment of cosmesis (Harvard Scale) and self-assessment (BCTOS). Patient-specific and disease factors, systemic therapies, dosimetric criteria, and considerations regarding surgeon experience and technique were all considered in the analysis of cosmesis. Between January 2011 and January 2013, 82 eligible patients underwent WHBI immediately following BCS (82.7%) or at the conclusion of adjuvant cytotoxic chemotherapy (17.3%). The median age was 60 years (range: 30-80y) and the median follow-up was 33.1 months and all patients had at least 1 year follow-up. The rate of Excellent/Good vs. Fair/Poor cosmesis at 12 months was 77.3% vs. 22.7%. The rate of significant cosmetic change from baseline was 14.7%. The only factor predictive of significant cosmetic change was smoking status (OR: 6.94; p = 0.016). The median BCTOS score increased only slightly from baseline (31) to one year (32), with patient-reported breast size differences worsening but complaints of pain improving over the study period. Cosmetic outcome after WHBI compares well with reports of daily hypofractionated whole-breast irradiation. Further follow-up with continued accrual is needed to assess cosmetic stability and disease-specific outcomes.