Treatment Options For Breast Cancer Research Articles

Improvement of treatment outcomes after implementation of comprehensive pharmaceutical care in breast cancer patients receiving everolimus and exemestane.

Combination therapy with everolimus and an aromatase inhibitor such as exemestane is an effective treatment option for advanced or recurrent breast cancer. However, the therapy is often limited because of the occurrence of severe adverse events (AEs), including oral mucositis, interstitial lung disease, diarrhea, and rash. Therefore, early management of AEs is extremely important to obtain maximum treatment outcome. We investigated here the effects of comprehensive pharmaceutical care for prevention of severe AEs on patient's quality-of-life (QOL) and continuation of therapy. QOL was assessed every month based on the five-level version of EuroQol-5-Dimension (EQ-5D-5L). AEs were graded according to the Common Terminology Criteria for Adverse Events (ver 4.0). Implementation of comprehensive pharmaceutical care remarkably reduced the incidence of severe oral mucositis as compared with those without such interventions. EQ-5D-5L health states were almost constant during 6 months after intervention, ranging from 0.850 to 0.889. Median time to treatment failure (TTF) was significantly longer after intervention than before [224.0 days, 95% confidence interval (CI): 117-331 days versus 34 days, 21-47 days, hazard ratio (HR): 0.027, 95% CI: 0.005 - 0.154, p<0.001]. These findings suggest that our comprehensive pharmaceutical care is highly effective for enhancing treatment outcome by maintaining patient's QOL.

The safety of palbociclib for the treatment of advanced breast cancer

ABSTRACTIntroduction: Despite improvements in the diagnosis and management of early stage breast cancer, about one third of the patients still progress to metastatic disease. Most of the patients with metastatic breast cancer have a hormone receptor positive and human epidermal growth factor receptor 2 negative subtype with a median survival of more than 3 years. For these patients, endocrine therapy with its favorable toxicity profile is the current standard of care. However, patients with metastatic breast cancer have an incurable disease. Therefore, not only efficacy but also quality of life are key when selecting a therapy regimen.Areas covered: This paper aims to discuss the efficacy and toxicity profile of the new endocrine-based therapy option palbociclib together with endocrine treatment.Expert opinion: The addition of targeted agents like palbociclib can overcome intrinsic or acquired resistance to endocrine therapy and substantially prolong progression free survival. The combination of palbociclib plus endocrine therapy is associated with a tolerable and well manageable toxicity profile as well as maintenance of quality of life. Thus, addition of palbociclib to endocrine therapy offers a new and important treatment option for hormone receptor positive metastatic breast cancer.

Evaluation of drug mechanism and efficacy of a novel anti-angiogenic agent, TTAC-0001, using multi-modality bioimaging in a mouse breast cancer orthotopic model.

PurposeTargeting of vascular endothelial growth factor receptors (VEGFRs) has potential anti-angiogenic effects because VEGFR-2 is the major signaling regulator of VEGF/VEGFR pathways. We aimed to elucidate the drug mechanism and anti-tumor efficacy of TTAC-0001, a novel, fully human anti-VEGFR-2/KDR monoclonal antibody, in mouse orthotopic breast cancer model using multi-modal bioimaging.Materials and methodsWe used orthotopic xenograft tumor model in which human breast cancer cells (MDA-MB-231) were injected into the right mammary fat pad of Balb/c nude mice. We investigated its biodistribution using serial fluorescence imaging after injecting fluorescent-labelled-drug and mode of action using Matrigel plug angiogenesis assays. The anti-tumor efficacy of drug was assessed using ultrasonography and bioluminescence imaging. Histopathologic analyses, including hematoxylin and eosin staining and immunohistochemistry with anti-CD31 and anti-Ki-67 antibodies, were performed. Each experiment had four groups: control, bevacizumab 10 mg/kg (BVZ-10 group), TTAC-0001 2 mg/kg (TTAC-2 group), and TTAC-0001 10 mg/kg (TTAC-10 group).ResultsThe TTAC-10 group showed good tumor targeting that lasted for at least 6 days and had a good anti-angiogenic effect with decreased hemoglobin content and fewer CD31-positive cells in the Matrigel plug. Compared with BVZ-10 and TTAC-2 groups, the TTAC-10 group showed the strongest anti-tumor efficacy, inhibiting tumor growth as detected by ultrasonography and bioluminescence imaging. The TTAC-10 group also showed the lowest viable tumor and micro-vessel areas and the lowest Ki-67 index in histopathologic analyses.ConclusionWe firstly demonstrated that TTAC-0001 effectively inhibited tumor growth and neovascularization in mouse orthotopic breast cancer model. It may provide a future treatment option for breast cancer.

Patient-reported outcomes of catheter-based accelerated partial breast brachytherapy and whole breast irradiation, a single institution experience.

Accelerated partial breast irradiation (APBI) and whole breast irradiation (WBI) are treatment options for early-stage breast cancer. The purpose of this study was to compare patient-reported-outcomes (PRO) between patients receiving multi-channel intra-cavitary brachytherapy APBI or WBI. Between 2012 and 2015, 131 patients with ductal carcinoma in situ (DCIS) or early stage invasive breast cancer were treated with adjuvant APBI (64) or WBI (67) and participated in a PRO questionnaire. The linear analog scale assessment (LASA), harvard breast cosmesis scale (HBCS), PRO-common terminology criteria for adverse events- PRO (PRO-CTCAE), and breast cancer treatment outcome scale (BCTOS) were used to assess quality of life (QoL), pain, fatigue, aesthetic and functional status, and breast cosmesis. Comparisons of PROs were performed using t-tests, Wilcoxon rank-sum, Chi square, Fisher exact test, and regression methods. Median follow-up from completion of radiotherapy and questionnaire completion was 13.3months. There was no significant difference in QoL, pain, or fatigue severity, as assessed by the LASA, between treatment groups (p>0.05). No factors were found to be predictive of overall QoL on regression analysis. BCTOS health-related QoL scores were similar between treatment groups (p=0.52).The majority of APBI and WBI patients reported excellent/good breast cosmesis, 88.5% versus 93.7% (p=0.37). Skin color change (p=0.011) and breast elevation (p=0.01) relative to baseline were more common in the group receiving WBI. APBI and WBI were both associated with favorable patient-reported outcomes in early follow-up. APBI resulted in a lesser degree of patient-reported skin color change and breast elevation relative to baseline.

Update on intraoperative radiotherapy: new challenges and issues.

Intraoperative radiotherapy (IORT) for breast cancer has challenged the standard external beam radiotherapy (EBRT) and has been shown to be non-inferior for treating early breast cancer in the past decade. Several technologies have been tested for IORT and various randomised controlled trials are still ongoing. Different methods of application of IORT have also been evaluated, from early breast cancer to tumour bed boost radiotherapy amongst high risk women. TARGIT-A and ELIOT trials have reported a low incidence of local recurrence and good survival in both arms. Moreover, mortality has been found to be lower amongst women who underwent partial breast radiotherapy compared to those treated with EBRT in a recent meta-analysis. Despite this, IORT has not been introduced in the current clinical practice as yet, and many clinicians do not mention this treatment option to patients awaiting breast cancer surgery. The scientific community does not unanimously support the effectiveness of IORT and still raises concerns about introducing IORT as a standard treatment option for breast cancer. Current evidence demonstrates that IORT is ready for roll-out; it is time to let well-selected and informed patients be offered this treatment option in the current clinical practice.

Panduratin A Inhibits Cell Proliferation by Inducing G0/G1 Phase Cell Cycle Arrest and Induces Apoptosis in Breast Cancer Cells.

Because of the unsatisfactory treatment options for breast cancer (BC), there is a need to develop novel therapeutic approaches for this malignancy. One such strategy is chemotherapy using non-toxic dietary substances and botanical products. Studies have shown that Panduratin A (PA) possesses many health benefits, including anti-inflammatory, anti-bacterial, anti-oxidant and anticancer activities. In the present study, we provide evidence that PA treatment of MCF-7 BC cells resulted in a time- and dose-dependent inhibition of cell growth with an IC50 of 15 μM and no to little effect on normal human MCF-10A breast cells. To define the mechanism of these anti-proliferative effects of PA, we determined its effect critical molecular events known to regulate the cell cycle and apoptotic machinery. Immunofluorescence and flow cytometric analysis of Annexin V-FITC staining provided evidence for the induction of apoptosis. PA treatment of BC cells resulted in increased activity/expression of mitochondrial cytochrome C, caspases 7, 8 and 9 with a significant increase in the Bax:Bcl-2 ratio, suggesting the involvement of a mitochondrial-dependent apoptotic pathway. Furthermore, cell cycle analysis using flow cytometry showed that PA treatment of cells resulted in G0/G1 arrest in a dose-dependent manner. Immunoblot analysis data revealed that, in MCF-7 cell lines, PA treatment resulted in the dose-dependent (i) induction of p21WAF1/Cip1 and p27Kip1, (ii) downregulation of Cyclin dependent kinase (CDK) 4 and (iii) decrease in cyclin D1. These findings suggest that PA may be an effective therapeutic agent against BC.

Women’s Knowledge of Breast Cancer: A Cross-Sectional Study

Background: There is a recognised need for a mass populationbased breast cancer screening programme in Bahrain. Better understanding of the level of knowledge and the different perceptions regarding breast cancer among women in Bahrain can potentially aid in the development of a culturally appropriate and efficient educational campaign. This study set out to explore the knowledge of women in Bahrain with regards to breast cancer risk factors, screening and treatment options. Methods: This study is a cross-sectional study including 300 participants from breast clinics in the primary health care centres in Bahrain. Questionnaires were completed via face to face interviews. Results: In terms of risk factor knowledge, 51.3% of respondents answered “yes” on whether family history is a risk to developing breast cancer. This was closely followed by 51% of participants answering “yes” with regards to BRCA genetic mutation being a risk factor. Mammogram was exceedingly the method rated as most effective for detecting BC; 13.7% gave it a rank of 1 (best). Physical examination came second in terms the percentage of respondents ranking it as the best. Furthermore, 91.0% of respondents believed that BC screening is safe. In addition, there was a statistically significant negative relationship between age of respondents and how safe screening was perceived. Education was a statistically significant positive predictor with regards to whether screening was thought to improve survival. Surgery was chosen by the majority as the most important treatment for cancer (43.7%). Conclusions: The findings of this study point to improved screening knowledge level but limited knowledge regarding risk factors and treatment. These areas can be targeted in future educational campaigns.

Breast cancer information on the internet: Type of websites, accuracy and readability of online resources

Background: Offering breast cancer patients treatment choice has become a priority as the involvement of patients in the decision-making process is associated with improved physical and psychological outcomes. The Internet is increasingly being used by patients to find health information. The aim of this project is to evaluate the quality of online resources on breast cancer treatment options.

Quality of online information on breast cancer treatment options

Offering breast cancer patients treatment choice has become a priority as the involvement of patients in the decision-making process is associated with improved physical and psychological outcomes. As the Internet is increasingly being used by patients as a source of medical information, it is important to evaluate the quality of information relating to breast cancer on the Internet. We analysed 200 websites returned by google.co.uk searching “breast cancer treatment options” in terms of their typology and treatment options described. These were related to standard measures of health information quality such as the JAMA score and the presence of quality certifications, as well as readability.We found that health portals were of higher quality whilst commercial and professional websites were of poorer quality in terms of JAMA criteria. Overall, readability was higher than previously reported for other conditions, and Google ranked websites with better readability higher. Most websites discussed surgical and medical treatments. Few websites, with a large proportion being of commercial typology, discussed complementary and alternative medicine. Google ranked professional websites low whilst websites from non-profit organizations were promoted in the ranking.

A Novel Delivery of Accelerated Partial Breast Irradiation Using Intraoperative Brachytherapy Device Placement and Completion of Breast Conservation Therapy Within 10 Days

Accelerated partial breast irradiation (APBI) is a treatment option for early stage breast cancer. To improve patient compliance with adjuvant radiotherapy and decrease the total time for completion of breast conservation therapy (BCT), we initiated intraoperative catheter placement and starting brachytherapy within 2 weekdays. From October 2012 to December 2016, 190 patients were prospectively evaluated and registered for intraoperative brachytherapy catheter placement. Inclusion criteria included age ≥ 50 years, estrogen receptor positive invasive carcinoma or ductal carcinoma in-situ, ≤ 2 cm on imaging, and negative surgical margins and sentinel lymph node (SLN) on intraoperative pathology. Target volume was defined as 1 cm of breast tissue beyond the cavity limited to exclude pectoralis, chest wall, and within 5 mm of skin surface. 3D planning was performed on CT images obtained on the weekday after surgery and treatment was initiated on the following weekday. The cumulative incidence of recurrence was estimated considering death as a competing risk. 170 patients (89%) had intraoperative catheter placement. 19 patients were registered but did not have catheter placed due to intraoperative findings (11 positive SLN, 5 extensive disease, 2 failed SLN mapping, 1 no residual disease). One patient had delayed positive SLN on permanent pathology and catheter was used to boost the cavity prior to converting to whole breast radiation. Prescription doses were 34 Gy in 10 BID (57%), 32 Gy in 8 BID (14%), and 21 Gy in 3 daily (29%) fractions. Median age was 67 and 9% were premenopausal. Median tumor size was 0.9 cm, 18% DCIS, and 6% grade 3. BCT was completed in a median of 9 days. Three patients received adjuvant chemotherapy and 64% had adjuvant endocrine therapy. Median follow up is 1.7 years (39% with at least 2 years), and 2-year local recurrence rate is 2%. Intraoperative pathology and brachytherapy catheter placement with initiation of APBI within 2 weekdays allows completion of BCT within 10 consecutive days in select patients with low short-term local recurrence rate. Long term follow up is planned for oncologic and cosmetic outcomes.

Catheter-Based Accelerated Partial Breast Brachytherapy Results in Excellent Patient-Reported Quality of Life

Accelerated partial breast irradiation (APBI) and whole breast radiotherapy (WBR) are treatment options for early stage breast cancer. The purpose of this study was to compare patient-reported-outcomes (PRO) between patients receiving APBI or WBR. 197 chronologically matched patients (pts) with low risk, early stage breast cancer were treated with either APBI or WBR between October 2012 and May 2015. The Linear Analog 10-point Scales (LASA), Breast Cancer Treatment Outcome Scale (BCTOS), and Harvard Breast Cosmesis Scale (HBCS) were used to assess overall quality of life (LASA), pain (LASA, BCTOS), fatigue (LASA), perceived aesthetic and functional status (BCTOS, LASA), and breast cosmesis (BCTOS, HBCS). Comparisons of PROs between treatment groups were performed using Fisher exact test, chi-square, Wilcoxon rank-sum, and regression methods. Survey compliance was 66% (64 APBI and 67 WBR pts). Median follow-up was 13.3 months, with a mean interval between the last fraction and survey completion of 15.4 v 14.2 months (p=0.58), for the APBI and WBR groups, respectively. The majority of respondents had grade 1-2 (86%), T1 (92%), and N0 (93%) in-situ or invasive ductal carcinoma. Pts treated with WBR were more likely to be younger (median 65 v 69 yrs, p=0.02), have T2 tumors (15% v 2%, p=0.01), and to receive chemotherapy (21% v 2%, p<0.001). In the WBR group, the median dose delivered was 42.56 Gy in 16 fractions, with 54% of pts receiving a lumpectomy cavity boost (median dose 10 Gy). In the APBI group, the median dose delivered was 34 Gy in 10 twice daily fractions utilizing an intraoperatively-placed high dose rate brachytherapy applicator. There was no difference in overall quality of life (8.5 v 8.9, p=0.14), pain (2.1 v 2.1, p=0.21) or fatigue (3.0 v 3.0, p=0.21) between the APBI and WBR groups, respectively. The mean overall BCTOS (31.6 v 34.3, p=0.52) was similar between groups, as was the BCTOS overall cosmetic status, and individual cosmetic measures including breast size, nipple appearance, breast shape, and breast heaviness (all p>0.05). Individual BCTOS functional measures, including arm heaviness, breast/arm swelling, arm/shoulder range of motion, and joint stiffness were similar between groups, all p>0.05. A higher proportion of pts receiving WBR reported breast elevation (slight: 33% v 16%, moderate: 25% v 8%, p=0.01). Skin color change relative to baseline was also more common in the WBR group (p=0.01), with a trend towards greater telangiectasia formation (p=0.053). For the APBI and WBR groups, most pts reported excellent (48% v 54%) or good (41 v 40%) cosmesis, with no difference between groups (p=0.37). APBI and WBR are associated with excellent and comparable 1-year PROs. In this sample, APBI resulted in a lesser degree of patient-reported breast elevation and skin color change relative to baseline.

MEK inhibitor, PD98059, promotes breast cancer cell migration by inducing β-catenin nuclear accumulation.

Abnormal activation of the RAF/MEK/ERK signaling pathway has been observed in breast cancer. Thus, a number of MEK inhibitors have been designed as one treatment option for breast cancer. Although some studies have found that these MEK inhibitors inhibit the growth of a variety of human cancer cells, some trials have shown that the use of MEK inhibitors as a treatment for breast cancer does not adequately improve survival for unknown reasons. In the present study, MEK inhibitor PD98059 was used to evaluate its anticancer effects on human breast cancer MCF-7 and MDA-MB-231 cells and to explore the possible mechanism of action. Our results revealed that MEK inhibitor PD98059 exhibited antiproliferative effects in a dose-and time-dependent manner in MCF-7 and MDA-MB-231 breast cancer cells. Conversely, incubation of MCF-7 and MDA-MB-231 cells with PD98059 promoted their migration. Further investigation disclosed that the enhanced ability of migration promoted by PD98059 was dependent on β-catenin nuclear translocation in the MCF-7 and MDA-MB‑231 cells. Subsequent experiments documented that activation of EGFR signaling induced by PD98059 increased the amount of β-catenin in the nucleus. Taken together, our findings may elucidate a possible mechanism explaining the ineffectiveness of MEK inhibitors in breast cancer treatment and improve our understanding of the role of MEK in cancer.

Predicting response to neoadjuvant chemotherapy in breast cancer

&lt;p&gt;A team of Malaysian researchers has found that neoadjuvant chemotherapy is a reasonable treatment option for localized (hormones negative and HER2 positive) breast cancer and further demonstrating its utility in downstaging primary breast tumor, according to a study published in the recent issue of the journal Advances in Modern Oncology Research (AMOR).&lt;/p&gt;

T-independent response mediated by oncolytic tanapoxvirus recombinants expressing interleukin-2 and monocyte chemoattractant protein-1 suppresses human triple negative breast tumors

Human triple negative breast cancer (TNBC) is an aggressive disease, associated with a high rate of recurrence and metastasis. Current therapeutics for TNBC are limited, highly toxic and show inconsistent efficacy due to a high degree of intra-tumoral and inter-tumoral heterogeneity. Oncolytic viruses (OVs) are an emerging treatment option for cancers. Several OVs are currently under investigation in preclinical and clinical settings. Here, we examine the oncolytic potential of two tanapoxvirus (TPV) recombinants expressing mouse monocyte chemoattractant protein (mMCP)-1 [also known as mCCL2] and mouse interleukin (mIL)-2, in human TNBC, in vitro and in vivo. Both wild-type (wt) TPV and TPV recombinants demonstrated efficient replicability in human TNBC cells and killed cancer cell efficiently in a dose-dependent manner in vitro. TPV/∆66R/mCCL2 and TPV/∆66R/mIL-2 expressing mCCL2 and mIL-2, respectively, suppressed the growth of MDA-MB-231 tumor xenografts in nude mice significantly, as compared to the mock-injected tumors. Histological analysis of tumors showed areas of viable tumor cells, necrotic foci and immune cell accumulation in virus-treated tumors. Moreover, TPV/∆66R/mIL-2-treated tumors showed a deep infiltration of mononuclear immune cells into the tumor capsule and focal cell death in tumors. In conclusion, TPV recombinants expressing mCCL2 and mIL-2 showed a significant therapeutic effect in MDA-MB-231 tumor xenografts, in nude mice through induction of potent antitumor immune responses. Considering the oncolytic potency of armed oncolytic TPV recombinants expressing mCCL2 and mIL-2 in an experimental nude mouse model, these viruses merit further investigation as alternative treatment options for human breast cancer.

Information needs and decision-making preferences of older women offered a choice between surgery and primary endocrine therapy for early breast cancer.

To establish older women's (≥75years) information preferences regarding 2 breast cancer treatment options: surgery plus adjuvant endocrine therapy versus primary endocrine therapy. To quantify women's preferences for the mode of information presentation and decision-making (DM) style. This was a UK multicentre survey of women, ≥75years, who had been offered a choice between PET and surgery at diagnosis of breast cancer. A questionnaire was developed including 2 validated scales of decision regret and DM preferences. Questionnaires were sent to 247 women, and 101 were returned (response rate 41%). The median age of participants was 82 (range 75 to 99), with 58 having had surgery and 37 having PET. Practical details about the impact, safety, and efficacy of treatment were of most interest to participants. Of least interest were cosmetic outcomes after surgery. Information provided verbally by doctors and nurses, supported by booklets, was preferred. There was little interest in technology-based sources of information. There was equal preference for a patient- or doctor-centred DM style and lower preference for a shared DM style. The majority (74%) experienced their preferred DM style. Levels of decision regret were low (15.73, scale 0-100). Women strongly preferred face to face information. Written formats were also helpful but not computer-based resources. Information that was found helpful to women in the DM process was identified. The study demonstrates many women achieved their preferred DM style, with a preference for involvement, and expressed low levels of decision regret.

Overcoming aromatase inhibitor resistance in breast cancer: possible mechanisms and clinical applications

Estrogen plays crucial roles in the progression of hormone-dependent breast cancers through activation of nuclear estrogen receptor α (ER). Estrogen is produced locally from circulating inactive steroids and adrenal androgens in postmenopausal women. However, conversion by aromatase is a rate-limiting step in intratumoral estrogen production in breast cancer. Aromatase inhibitors (AIs) inhibit the growth of hormone-dependent breast cancers by blocking the conversion of adrenal androgens to estrogen and by unmasking the inhibitory effect of androgens, acting via the androgen receptor (AR). AIs are thus a standard treatment option for postmenopausal hormone-dependent breast cancer. However, although initial use of AIs provides substantial clinical benefit, some breast cancer patients relapse because of the acquisition of AI resistance. A better understanding of the mechanisms of AI resistance may contribute to the development of new therapeutic strategies and aid in the search for new therapeutic targets and agents. We have investigated AI-resistance mechanisms and established six AI-resistant cell lines. Some of them exhibit estrogen depletion-resistance properties via constitutive ER-activation or ER-independent growth signaling. We examined how breast cancer cells can adapt to estrogen depletion and androgen superabundance. Estrogen and estrogenic androgen produced independently from aromatase contributed to cell proliferation in some of these cell lines, while another showed AR-dependent cell proliferation. Based on these findings, currently proposed AI-resistance mechanisms include an aromatase-independent estrogen-producing pathway, estrogen-independent ER function, and ER-independent growth signaling. This review summarizes several hypotheses of AI-resistance mechanisms and discusses how existing or novel therapeutic agents may be applied to treat AI-resistant breast cancers.

Abstract P5-15-13: Capecitabine in combination with bendamustine in pretreated women with HER2-negative metastatic breast cancer: Final PFS results of a phase II trial (AGMT MBC-6)

Abstract Background: Capecitabine is a well-established treatment option in HER2-negative advanced breast cancer (ABC) patients. Bendamustine is a generally well tolerated cytotoxic drug. Since bendamustine has already shown anticancer activity in ABC we evaluated the efficacy and tolerability of bendamustine in combination with capecitabine in pretreated patients with ABC. Here we present the final PFS results of this phase II trial. Patients and methods: MBC-6 is a non-randomized, multicenter, open-label, single-arm phase II study in patients with HER2-negative ABC (ClinicalTrials.gov: NCT01891227). All patients were pretreated with anthracyclines and/or taxans and had measurable disease according to RECIST 1.1. Patients received 1000 mg/m2 capecitabine twice daily on days 1 to 14 in combination with 80 mg/m2 bendamustine on day 1 and 8 of a 3-week cycle for a maximum of 6 cycles. Afterwards capecitabine was continued as monotherapy. The primary endpoint was overall response rate (ORR). Secondary endpoints were progression-free survival (PFS), clinical benefit rate (CBR), safety and quality of life. Results: From September 2013 to May 2015, 40 patients were recruited in eight Austrian centers. Median age was 60 years (range 29-77). Twenty-five percent of patients had triple-negative disease (TNBC) and 93% showed visceral involvement. Sixty-five percent had received prior chemotherapy in the (neo)adjuvant setting and 63% for ABC (43% one line, 15% two lines, 5% three lines). All patients with ER-positive disease had received prior endocrine therapy.At data cut-off on 06/08/16 overall 39 of 40 patients had discontinued treatment with a median PFS of 7.0 months (95% CI 4.6-9.5), 7.4 months in ER-positive and 4.0 months in triple negative disease (TNBC), respectively. Twelve patients (30%) experienced at least one drug related non-hematological AE ≥ grade 3 during combination treatment and further 6 patients (15%) during capecitabine maintenance. Three grade 4 hematological AEs (neutropenia) were observed. One patient died as a result of restrictive cardiomyopathy, where a relationship to capecitabine cannot be excluded, but seems unlikely. Conclusion: The combination of capecitabine and bendamustine shows promising efficacy and a moderate toxicity profile. Further evaluation of this drug combination is warranted.Background: Capecitabine is a well-established treatment option in HER2-negative advanced breast cancer (ABC) patients. Bendamustine is a generally well tolerated cytotoxic drug. Since bendamustine has already shown anticancer activity in ABC we evaluated the efficacy and tolerability of bendamustine in combination with capecitabine in pretreated patients with ABC. Here we present the final PFS results of this phase II trial. Patients and methods: MBC-6 is a non-randomized, multicenter, open-label, single-arm phase II study in patients with HER2-negative ABC (ClinicalTrials.gov: NCT01891227). All patients were pretreated with anthracyclines and/or taxans and had measurable disease according to RECIST 1.1. Patients received 1000 mg/m2 capecitabine twice daily on days 1 to 14 in combination with 80 mg/m2 bendamustine on day 1 and 8 of a 3-week cycle for a maximum of 6 cycles. Afterwards capecitabine was continued as monotherapy. The primary endpoint was overall response rate (ORR). Secondary endpoints were progression-free survival (PFS), clinical benefit rate (CBR), safety and quality of life. Results: From September 2013 to May 2015, 40 patients were recruited in eight Austrian centers. Median age was 60 years (range 29-77). Twenty-five percent of patients had triple-negative disease (TNBC) and 93% showed visceral involvement. Sixty-five percent had received prior chemotherapy in the (neo)adjuvant setting and 63% for ABC (43% one line, 15% two lines, 5% three lines). All patients with ER-positive disease had received prior endocrine therapy.At data cut-off on 06/08/16 overall 39 of 40 patients had discontinued treatment with a median PFS of 7.0 months (95% CI 4.6-9.5), 7.4 months in ER-positive and 4.0 months in triple negative disease (TNBC), respectively. Twelve patients (30%) experienced at least one drug related non-hematological AE ≥ grade 3 during combination treatment and further 6 patients (15%) during capecitabine maintenance. Three grade 4 hematological AEs (neutropenia) were observed. One patient died as a result of restrictive cardiomyopathy, where a relationship to capecitabine cannot be excluded, but seems unlikely. Conclusion: The combination of capecitabine and bendamustine shows promising efficacy and a moderate toxicity profile. Further evaluation of this drug combination is warranted. Citation Format: Rinnerthaler G, Gampenrieder SP, Voskova D, Petzer A, Hubalek M, Petru E, Hartmann B, Andel J, Balic M, Melchardt T, Ulmer H, Mlineritsch B, Greil R. Capecitabine in combination with bendamustine in pretreated women with HER2-negative metastatic breast cancer: Final PFS results of a phase II trial (AGMT MBC-6) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-15-13.

Abstract P4-17-06: First posts: A content analysis of an online breast cancer community user's initial postings

Abstract Introduction: Online breast cancer communities provide users with both information and emotional support. Members of these communities include both patients and caregivers. We aimed to characterize the differences in content between patients' and caregivers' first posts. Methods: 20189 posts were downloaded from a public online breast cancer community. Posts were sorted by user name and date to identify unique posters and coded for user demographics and content. Descriptive statistics (e.g. chi-square test) characterized differences between patients and caregivers in terms of topics and content. Results: Of the 1827 unique posters, 83% were identified as the patient (n=1277, 70%) and 13% were identified as a caregiver (n=230). 835 (69%) patients had been previously diagnosed with breast cancer. Chemotherapy was the most common topic among cancer patients. Patients tended to seek information about physical concerns more often than psychosocial concerns. In contrast, caregivers used the community significantly more often as a source of emotional support (p&amp;lt;.001), although they also sought information on how to best support patients. Breast Cancer Patients' Topics of ConversationTopicN(%)ExplanationExampleChemotherapy296 (36)Patients discussing the decision for chemotherapy, or their experiences with it.“I was allergic to some of the chemo meds”Radiation255 (31)Patients discussing the decision for radiation, or their experiences with it.“I wanted to answer your query about radiation…”Estrogen Modulating Therapy156 (19)Patients discussing the decision to take estrogen modulating medications (e.g. Tamoxifen) or their experiences with it.“I don't know if I'm going to take this with all the side effects I read.”Surgery55 (7)Patients discussing surgical options for breast cancer treatment (not reconstruction) or experiences with the procedures.“I don't want them to leave half of my breast with a chance for a new diagnosis”Reconstruction49 (6)Patients discussing reconstruction options or experiences with the procedures.“I recently had a TE recon and it went fine but a week later i developed an infection…” Thematic Content of Posts: Patients v. CaregiversDomainPatients n(%)Caregivers n(%)Chi-Square p-valueExplanationExampleDiscussing Physical Issues234 (29)25 (11)&amp;lt;.001Discussing physical symptoms as a result of cancer or treatment.“I was allergic to some of the chemo meds”Seeking Emotional Support113 (14)34 (15)&amp;lt;.001Poster discusses feeling upset, or directly asks for support.“Thanks for listening to my pity party...”Discussing Psychosocial Issues89 (11)21 (9).165Poster mentions psychological issues including depression or anxiety, or with social sequelae of cancer such as marital difficulties.“I also found help through the use of an antidepressant…I feel like a fog has lifted.” Conclusion: First post content varied depending on if the poster was a patient or a caregiver. Patients' first posts were often information-seeking about physical concerns, whereas caregivers tended to use the forum as a source of emotional support. By analyzing the frequency of topics and content of posts, clinicians may better understand the educational needs of patients and caregivers. Citation Format: Marmor RA, Ward EP, Epstein E, Reghunathan M, Schoenbrunner A, Unkart JT, Blair SL, Huh J. First posts: A content analysis of an online breast cancer community user's initial postings [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-17-06.

Abstract P1-10-19: Two-year follow-up results of a multi-center trial of intra-operative electronic brachytherapy during breast conservation surgery for early stage breast cancer

Abstract Objective To assess the safety and efficacy of single-fraction, intra-operative radiation therapy (IORT) delivered with the Xoft® Axxent® Electronic Brachytherapy System® (eBx®) immediately following surgical resection for treatment of early stage breast cancer. Methods This phase 4, open-label, single-arm, prospective, non-randomized trial is still enrolling participants and is currently being conducted at 26 hospitals in the USA (25) and Portugal (1). 878 participants with biopsy-proven ductal carcinoma in situ (DCIS) or invasive ductal carcinoma who met the inclusion criteria underwent lumpectomy followed by single-fraction IORT to the lumpectomy cavity. Briefly, a small, presterilized lead shield piece was placed on the chest wall to reduce the dose to the ribs, and then a balloon applicator, suitable to the surgical bed, was placed in the lumpectomy cavity and inflated with saline (30-75 cc); skin was temporarily closed over the balloon and ultrasound was used to confirm a balloon surface-to-skin distance ≥ 1.0 cm. The Xoft System was used to deliver the 20 Gy dose at the balloon applicator surface. The balloon was deflated, lead shield and balloon removed and the surgical site sutured. The prespecified primary outcome of this 10-year follow-up study is recurrence of ipsilateral breast tumor at 5 years. Prespecified secondary outcomes include 10-year recurrence and cosmesis (Harvard Scale). Trial Registry: ClinicalTrials.gov; Identifier: NCT01644669. Findings Of the 878 participants treated, 877 participants received the prescribed 20 Gy dose with a mean radiation treatment time of 594.5 seconds, whereas one participant received 14 Gy due to a source failure. 569 participants have reached 18-month (333), 2-year (199), and 3-year (37) follow-up. The mean age at enrollment was 65 years (range 41-90). 219 participants had DCIS and 658 had invasive ductal carcinoma. The DCIS nuclear grade was high (N=79), intermediate (N=100), or low (N=40). Invasive cancers were Grade 1 (N=282), 2 (N=282), or 3 (N=94). 664 participants had T1 lesions, 56 had T2 lesions, and 3 were unknown. The mean tumor size was 12.33 ± 10.5 mm. Cosmesis was excellent to good in 90% of participants who reached 2-year follow-up. To date, 155 reported adverse events were Grade 2 or higher. The most frequent side effects were breast pain, seroma, induration, and erythema. There were nine deaths, none of which were breast cancer related, four ipsilateral breast recurrences, and three new contralateral breast cancers. Conclusions Early results from this multi-center trial demonstrate that IORT using the Xoft Axxent eBx System at the time of breast conservation surgery continues to be a promising treatment option for early stage breast cancer. The short course of radiation therapy for select patients has excellent to good cosmetic results and a low rate of high-grade adverse events and recurrences. Funding Funded by Xoft, Inc., a subsidiary of iCAD, Inc. Acknowledgement Medical writing support from Dr. Theresa E. Singleton, Singleton Science, LLC. Citation Format: Syed AMN, Chang H, Schwartzberg BS, Bremmer AK, Boylan S, Lopez-Penalver C, Vito CA, Davis M, Dooley WC, Chakravarthy AB, Croomer C, Proulx GM, Golder SL, Ivanov O, Fernandez KL, Farha M, Gonzalez V, Wengler C, Bhatnagar A, Neuner G, Kopkash K, Rahman S, Corn C, Costa P, Ellenhorn J, Cox C. Two-year follow-up results of a multi-center trial of intra-operative electronic brachytherapy during breast conservation surgery for early stage breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-10-19.

Abstract OT1-04-05: A phase 2 randomized, double-blind, placebo-controlled trial of radium-223 dichloride with exemestane and everolimus in patients with HER2-negative, hormone receptor–positive breast cancer and bone metastases

Abstract Background: Treatment options for bone-dominant metastatic breast cancer (MBC) are limited. Radium-223, a first-in-class α emitter with a targeted antitumor effect on bone metastases (mets), was well tolerated and reduced bone biomarker levels in a phase 2 study in patients with bone-dominant MBC (Coleman et al. Breast Cancer Res Treat. 2014). In patients with HER2- estrogen receptor+ (ER+) bone-dominant MBC, everolimus + exemestane (EVE+EXE) improved progression-free survival (PFS) versus EXE alone. Radium-223 combined with EVE+EXE may improve outcomes in patients with HER2- ER+ bone-dominant MBC; this trial will evaluate efficacy and safety of radium-223 versus placebo in these patients (NCT02258451). Trial design: Patients are randomized to receive (1:1) radium-223 (50 kBq/kg [55 kBq/kg after National Institute of Standards and Technology update] IV) or placebo × 6 cycles q 4 wk + EXE (25 mg PO q d) + EVE (10 mg PO q d) plus best supportive care. EXE+EVE continues until disease progression or unacceptable toxicity. Stratification is by geographic region (EU/N America vs Asia), prior hormone therapy (1 vs ≥ 2), and presence of visceral disease (yes vs no). Eligibility criteria: Eligible patients are pre- or postmenopausal with HER2- ER+ MBC and have ≥ 2 bone mets or have soft tissue and/or visceral mets. Patients must have measurable disease per RECIST v1.1, ≥ 1 prior line of hormone therapy for MBC, and 1-2 prior skeletal-related events; be on bisphosphonates or denosumab; and have an ECOG score of 0-1. Patients must have had no past or current need for chemotherapy for MBC, no unresolved spinal cord compression, and no prior EVE treatment. Specific aims: The primary end point is symptomatic skeletal event–free survival (SSE-FS). Secondary end points are overall survival; times to opiate use, pain progression, and cytotoxic chemotherapy; radiologic PFS; and safety. Safety and efficacy are assessed every 4 weeks. Long-term safety is assessed until study termination. Statistical methods: Assuming a 1-sided α of 0.1, 90% power, ∼ 160 SSE-FS events will be required for the analysis. Efficacy will be analyzed by a stratified log-rank test. Safety analysis will be descriptive. Present and target accrual: Estimated enrollment is ∼ 311 patients. Currently, 74 patients are randomized. Contact Oana Petrenciuc, Bayer HealthCare Pharmaceuticals, oana.petrenciuc@bayer.com, for more information. Citation Format: Rugo HS, Drumea KC, Campone M, Barnadas A, Petrenciuc O, Zhang A, Li R, Coleman RE. A phase 2 randomized, double-blind, placebo-controlled trial of radium-223 dichloride with exemestane and everolimus in patients with HER2-negative, hormone receptor–positive breast cancer and bone metastases [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT1-04-05.