bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P4-10-02: Transmembrane protein 33 (TMEM33) induces apoptosis via UPR signaling and autophagy in breast cancer cells
Authors: Clarke R , Hu R , Zhang X , Hilakivi-Clarke L , Kasid U
Published: March 2017

Breast cancer is the most common cancer diagnosed in women. Endoplasmic reticulum stress (EnR stress) and the related unfolded protein response (UPR) are activated in breast cancer cells and can promote cell survival and endocrine resistance. TMEM33 is a novel transmembrane protein that resides in the endoplasmic reticulum (EnR) and has been shown to activate the PERK and IRE1α branches of the UPR. However, the underlying mechanism of action of this EnR resident protein TMEM33 and the cellular functions that it regulates remain largely unknown. In this study, we show that overexpression of TMEM33 induces robust cell death in breast cancer cells. TMEM33 overexpression strongly activates UPR associated pro-death JNK-p53 signaling. We also observed a significant inhibition of the downstream survivin, which blocks cell death activation by binding to caspases and inhibiting their activation. We further show that the blockage of JNK activation with either an inhibitor or overexpression of survivin, protects cells against TMEM33 induced apoptosis. In addition, we show that TMEM33 overexpression induces autophagy in breast cancer cells. Inhibition of autophagy with using either the inhibitor chloroquine or knockdown of the Atg5 gene, further sensitizes breast cancer cells to the effects of TMEM33 overexpression. Cell death induced by TMEM33 is also decreased by overexpression of the autophagy gene Beclin 1. The findings in this study demonstrate that the novel EnR resident protein TMEM33 induces cell death by activating IRE1α-JNK-p53-survivin signaling in breast cancer cells. Concurrently, autophagy is also activated by TMEM33, and functions as a pro-survival mechanism. Cell fate reflects the balance between the pro-death and pro-survival activities as regulated by TMEM33.

Citation Format: Clarke R, Hu R, Zhang X, Hilakivi-Clarke L, Kasid U. Transmembrane protein 33 (TMEM33) induces apoptosis via UPR signaling and autophagy in breast cancer cells [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 P4-10-02.
Abstract P4-10-03: Pterostilbene enhances TRAIL-induced apoptosis in TRAIL-resistant triple negative breast cancer cells
Authors: Wu Y-C , Wang H-C , Chen C-J , Liu L-C , Way T-D
Published: March 2017

Triple-negative breast cancer (TNBC) is refractory to commonly used chemotherapeutic agents, as a result it leads to relatively poor prognosis. TNF-related apoptosis-inducing ligand (TRAIL) is currently in clinical trials as a treatment for cancer. Unfortunately, patients develop resistance to the TRAIL, therefore, agents that can sensitize cells to TRAIL are urgently needed. Pterostilbene (PTER), a natural dimethylated analog of resveratrol, is known to have diverse pharmacologic activities. In the present study, we investigated whether PTER affect TRAIL-induced apoptosis and its mechanism in TRAIL-resistant TNBC cells. First, our results indicated that PTER induced apoptosis in TNBC BT-20 cells. Next, we found that PTER enhanced TRAIL-induced apoptosis in TRAIL-resistant TNBC BT20 and MDA-MB-468 cells. We demonstrated that PTER induced both death receptor (DR)-5, DR4 and decreased decoy receptor (DcR)-2 expression. PTER also decreased the expression of anti-apoptotic proteins survivin, Bcl-xL and c-FLIPS/L, but had minimal effect on the expression of Bcl-2. PTER caused the cleavage of bid protein and enhanced the expression of pro-apoptotic Bax. Moreover, we found that PTER induced DR4 and DR5 expression through the reactive oxygen species (ROS) –mediated activation of extracellular signal-regulated kinase 1/2 (ERK 1/2) and p38 mitogen activated protein kinase (p38 MAPK). Overall, our results show that PTER can potentiate TRAIL-induced apoptosis through the ROS–mediated activation of ERK 1/2 and p38 MAPK leading to DR4 and DR5 induction and down-regulation of anti-apoptotic proteins.

Citation Format: Wu Y-C, Wang H-C, Chen C-J, Liu L-C, Way T-D. Pterostilbene enhances TRAIL-induced apoptosis in TRAIL-resistant triple negative breast cancer cells [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 P4-10-03.
Abstract P4-13-01: Prospective association between breast cancer risk and an individual dietary index based on the British Food Standards Agency nutrient profiling system
Authors: Deschasaux M , Julia C , Zelek L , Kesse-Guyot E , Gourlet V , Lécuyer L , Méjean C , Ducrot P , Peneau S , Latino-Martel P , Fézeu L , Fassier P , Hercberg S , Touvier M
Published: March 2017

Background: The Food Standards Agency Nutrient Profiling System (FSA-NPS) constitutes the basis for the Five-Colour Nutrition Label suggested in France to be put on the front-of-pack of food products. At the individual level, a dietary index (FSA-NPS DI) has been derived and validated and corresponds to a weighted mean of all FSA-NPS scores of foods usually consumed by the individual, reflecting the nutritional quality of his/her diet. Our aim was to investigate the association between the FSA-NPS DI and breast cancer risk in a large cohort.

Methods: This prospective study included 46,864 women aged over 35y from the NutriNet-Santé cohort (2009-2015) who completed at least three 24h dietary records during the first 2y of follow-up (median follow-up: 4.0y). 555 incident breast cancers were diagnosed. FSA-NPS DI was computed for each subject using the following nutrient content for 100g of each foods and beverages consumed: energy, total sugar, saturated fatty acid, sodium, fruits and vegetables (%), fibres and proteins. Higher values of the FSA-NPS DI correspond to a lower nutritional quality of the diet. Associations were characterized by multivariate Cox proportional hazards models.

Results: The FSA-NPS DI was directly associated with breast cancer risk (HR1-point increment=1.06 (1.02-1.11), P-trend=0.005; HRQ5vs.Q1=1.52 (1.11-2.08), P-trend=0.002). These associations were similar after the exclusion of cases diagnosed during the first year of follow-up.

Conclusions: In this prospective study, a higher FSA-NPS individual score was associated with an increased breast cancer risk. These results suggested that unhealthy food choices may be associated with a 52% increase in breast cancer risk (FSA-NPS DI ≥7.7 (Q5) vs. <4.1 (Q1)), supporting the public health relevance of developing front-of-pack nutrition labels based on this score.

Citation Format: Deschasaux M, Julia C, Zelek L, Kesse-Guyot E, Gourlet V, Lécuyer L, Méjean C, Ducrot P, Peneau S, Latino-Martel P, Fézeu L, Fassier P, Hercberg S, Touvier M. Prospective association between breast cancer risk and an individual dietary index based on the British Food Standards Agency nutrient profiling system [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 P4-13-01.
Abstract P4-20-04: Young women with breast cancer in Mexico: A report of the pilot phase of the “Mujer Joven y Fuerte” prospective cohort
Authors: Villareal-Garza CM , Platas A , Castro-Sánchez A , Miaja M , Bargalló-Rocha E , Martinez-Cannon BA , Vega Y , Fonseca A , Ramos-Elias P , Márquez-Perez CJ , Bukowski A , Goss P , St. Louis J , Chapman J-A , Partridge A , Meneses A , Mohar A
Published: March 2017

Background: Despite high rates of breast cancer in young women from low-and-middle-income countries (LMICs), their needs and concerns are not systematically studied or addressed. Understanding the characteristics of young women with breast cancer (YWBC) and the issues they face is of great relevance to the medical community, in order to tailor clinical interventions and supportive care for this unique and understudied patient population. The Mexican cohort “Mujer Joven y Fuerte” (Young and Strong Woman) has the goal of comprehensively characterizing and assessing the needs of YWBC in Mexico using patient- and physician-based surveys. Methods: A prospective cohort of newly diagnosed YWBC was established in November 2014 at two Mexican cancer centers in Mexico City and Monterrey. Eligible women answer web-based surveys on relevant topics including physical activity, genetics, psychosocial needs, and fertility. Clinicians complete pre-specified surveys using the US NIH BOLD Task Force common data elements registering clinical/pathologic characteristics and outcomes. Patients are evaluated at diagnosis, after 6 months, and annually for 5 years. Sub-studies assessing changes in cognition, sexual function and satisfaction, quality of life and depression/anxiety are being conducted, and biologic samples are stored for future research. Results: 96 YWBC with median age at diagnosis of 34 (21-41 y) were accrued to our pilot phase. 26% were single and 25% childless. 43% had higher education and 28% were employed. 90% presented with a self-detected mass. Clinical stage at diagnosis was distributed as follows: stage 0: 2%; I: 15%; IIA: 13%; IIB: 17%; III: 47%, and stage IV: 6%. The most frequent molecular subtype was HR+/HER2- (47%), followed by HER2+ (26%) and triple negative (21%). First follow-up results will be available shortly. Conclusions: To our knowledge, this represents the first prospective cohort of YWBC in Latin America. We are expanding this project to other centers in the region. Our findings will help develop culturally tailored interventions aimed at improving the psychosocial and medical outcomes of this vulnerable patient population.

Citation Format: Villareal-Garza CM, Platas A, Castro-Sánchez A, Miaja M, Bargalló-Rocha E, Martinez-Cannon BA, Vega Y, Fonseca A, Ramos-Elias P, Márquez-Perez CJ, Bukowski A, Goss P, St. Louis J, Chapman J-A, Partridge A, Meneses A, Mohar A. Young women with breast cancer in Mexico: A report of the pilot phase of the “Mujer Joven y Fuerte” prospective cohort [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 P4-20-04.
Abstract P5-02-02: Combined use of elastography and color doppler ultrasound for the evaluation of breast masses detected at screening ultrasound in women with dense breasts
Authors: Lee SH , Chang JM , Cho N , Yi A , Choi SH , Kook SH , Youk JH , Son EJ , Chung J , Cha ES , Koo HR , Park JS , Chu AJ , Ko KH , Choi HY , Ryu EB , Han W , Moon WK
Published: March 2017

This abstract was withdrawn by the authors.
Abstract P5-03-04: To excise or not?: Scoring system for predicting malignancy in patients diagnosed with intraductal papilloma at ultrasound-guided core needle biopsy
Authors: Ahn Sk , Moon H-G , Han W , Noh D-Y , Ko E
Published: March 2017

Background: The management of benign intraductal papillomas on core biopsy is controversial. The aim of this study was to determine factors that predict under-evaluation of atypical lesion or malignancy in patients diagnosed with benign papilloma at ultrasound-guided core needle biopsy (CNB), and to develop a prediction algorithm for scoring the possibility of a diagnosis upgrade to atypical lesion or malignancy based on clinical, radiological and pathological factors.

Methods: The study enrolled patients diagnosed with benign papilloma at ultrasound-guided CNB who subsequently underwent surgical excision of the lesion. Multivariate analysis was used to identify relevant clinical, radiological and pathological factors that may predict malignancy.

Results: A total of 520 CNBs led to a diagnosis of benign papilloma (including benign and atypical papillary lesion), of which 452 CNBs were benign papilloma without atypia. Of the 250 lesions in 234 women were underwent subsequent surgical excision, 44 (17.6%) were diagnosed with atypia or malignancy. Multivariate analysis revealed that bloody nipple discharge, size on imaging ≥15 mm, BIRADS≥4b, peripheral location, and a palpable lesion were independent predictors of atypical lesion or malignancy. A scoring system was developed based on logistic regression models and beta coefficients for each variable. The area under the ROC curve was 0.830 (95% CI: 0.665-0.996), and the negative predictive value was 100% for a score ≤4.

Conclusions: A scoring system to predict malignancy in patients diagnosed with benign papilloma at CNB was developed based on five factors: bloody nipple discharge, size on imaging ≥15 mm, BIRADS≥4b, peripheral location, and a palpable lesion. This system was able to identify a subset of patients with lesions likely to be benign, indicating that imaging follow-up rather than surgical excision may be appropriate.

Citation Format: Ahn Sk, Moon H-G, Han W, Noh D-Y, Ko E. To excise or not?: Scoring system for predicting malignancy in patients diagnosed with intraductal papilloma at ultrasound-guided core needle biopsy [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 P5-03-04.
Abstract P5-03-05: Development of a panel of serum-based protein biomarkers for the non-invasive detection of breast cancer in BI-RADS category 4 patients
Authors: Chapman KB , Copeland K , Kidd J , Qiu L , Sheibani N , Tam O , Friedman L , Korn R , Fiorica J , Lourenco A , Suthers S , Hesterberg L
Published: March 2017

Background: Current breast cancer screening guidelines call for annual mammography for asymptomatic women age 45 to 54 and once every two years for women age 55 and older. Women with suspicious screening mammograms are recommended for a diagnostic mammogram and may also undergo MRI or ultrasound. Ultimately, suspicious findings unresolved by imaging typically result in the recommendation of a breast biopsy. Approximately 10% of suspicious diagnostic mammograms are recommended for breast biopsies and 67% to 95% of these biopsies yield negative results. With the goal of reducing the number of patients with benign pathology undergoing invasive biopsies, we conducted a screen for serum protein biomarkers and identified a novel panel for the non-invasive detection of breast cancer.

Methods: Serum samples were collected at two sites from women with suspicious diagnostic mammogram findings (primarily BI-RADS category 4) undergoing biopsy for the evaluation of a potential malignancy. Serum samples from 100-patients (50 benign pathology and 50 malignant pathology) were evaluated on the SOMAscan Assay 1.3k, which measures levels of 1,310 different protein analytes. Statistical screening methodologies, such as individual t-tests with control for false discovery, were used to identify markers with the potential to distinguish benign from malignant pathology. The candidate markers were further studied and combined using generalized linear modeling to develop three potential diagnostic models. K-fold cross validation was used to guard against over fitting of the models.

Results: A 15-marker model resulted in an AUC of 0.92 with a sensitivity of 90% and specificity of 76%. Two 6-marker models (with 4 markers in common) each resulted in AUC of 0.85, yielding a sensitivity of 90% with a specificity of 56% or 64%.

Conclusions: This study reveals a novel panel of serum protein biomarkers that may allow for the non-invasive and sensitive detection of breast cancer in BI-RADS category 4 patients. A multicenter study is underway to further refine and validate this panel in a larger set of prospectively collected patient samples.

Citation Format: Chapman KB, Copeland K, Kidd J, Qiu L, Sheibani N, Tam O, Friedman L, Korn R, Fiorica J, Lourenco A, Suthers S, Hesterberg L. Development of a panel of serum-based protein biomarkers for the non-invasive detection of breast cancer in BI-RADS category 4 patients [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 P5-03-05.
Abstract P5-04-03: Palbociclib synergizes with autophagy inhibitors to induce senescence in breast cancer
Authors: Keyomarsi K , Vijayaraghavan S , Karakas C , Doostan I , Chen X , Bui T , Hunt KK , Tripahty D
Published: March 2017

This abstract was withdrawn by the authors.
Abstract P5-04-04: Activation of ERβ in triple negative breast cancer results in cell cycle arrest
Authors: Reese JM , Bruinsma ES , Monroe DG , Goetz MP , Hawse JR
Published: March 2017

Background: Triple negative breast cancer (TNBC), which comprises approximately 20% of breast cancer diagnoses, lacks estrogen receptor alpha, progesterone receptor and Her-2 expression. However, we have identified that 30% of TNBC patients express estrogen receptor beta (ERβ), a nuclear hormone receptor and potential therapeutic target. Here we examine the effects of ERβ in triple negative breast cancer cell lines.

Methods: Cell lines that stably express ERβ were used to perform microarray analyses following five days of estrogen treatment. Ingenuity pathway analysis was conducted on differentially expressed genes to determine alterations in biological pathways. The effects of ERβ on cell cycle progression and apoptosis was determined. Cell cycle-related expression changes were confirmed with RT-qPCR and western blotting. The impact of siRNA mediated gene silencing of CDK1 on TNBC cell proliferation was assessed as was the ability of ERβ to elicit anti-proliferative effects in the setting of CDK1 knockdown.

Results: We have shown that estrogen or ERβ-specific agonist treatment causes decreased proliferation of ERβ+ TNBC cells. This inhibitory effect is not due to programmed cell death but rather a G1/S phase cell cycle arrest as indicated by flow cytometry experiments. Microarray data and ingenuity pathway analysis revealed a number of down regulated genes involved in cell-cycle progression. Specifically, estrogen treatment of ERβ positive TNBC cells was shown to result in suppression of cyclin-dependent kinase 1 (CDK1) and Cyclin B, effects that were confirmed following ERβ-specific agonist treatment at both the mRNA and protein levels via RT-qPCR and western blotting, respectively. Knockdown of CDK1 in ERβ+ TNBC cells using siRNA resulted in decreased proliferation and diminished the anti-proliferative effects observed following estrogen or ERβ-specific agonist treatment.

Conclusions: Our data demonstrate that estrogen and ERβ-specific agonists cause cell cycle arrest in ERβ positive TNBC. These effects are due to ERβ-mediated suppression of multiple genes involved in cell cycle progression including CDK1 and Cyclin B. Following knockdown of CDK1, estrogen or ERβ-specific agonist treatment displayed minimal impact on cell proliferation. Therefore, ERβ's effects on proliferation may primarily be mediated by blockade of CDK1 and Cyclin B. Regardless of ERβ, our data suggest that inhibition of CDK1 activity may have therapeutic benefit in a subset of TNBC patients, an area of study that has yet to be explored.

Citation Format: Reese JM, Bruinsma ES, Monroe DG, Goetz MP, Hawse JR. Activation of ERβ in triple negative breast cancer results in cell cycle arrest [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 P5-04-04.
Abstract P5-05-05: The role and regulation mechanism of HOXB5 in human breaset cancer cells
Authors: Kim JM , Lee J-Y , Kim MH
Published: March 2017

HOX genes are transcription factors that play important roles in body patterning and cell fate specification during normal development. Among of these, HOXB5, is involved in a variety of developmental processes, particularly during the enteric nervous system (ENS) development, and thus, abnormalities in HOXB5 function during embryo stages lead to Hirschsprung's disease. Importantly, many HOX genes, including HOXB5, are expressed not only during embryogenesis but also in adults and are dysregulated in various cancers. In a previous study, we found aberrant overexpression of HOXB5 in breast cancer tissues and cell lines and demonstrated that HOXB5 is important in the regulation of cell proliferation in breast cancer cells. Also, HOXB5 induces invasive potential through epithelial-mesenchymal transition (EMT). The relationship between HOXB5 and phenotypic changes in MCF7 breast cancer cells has been studied, however, HOXB5 functions as a transcription factor and its involvement in signaling pathways remain unclear. In this study, we selected putative downstream target genes of HOXB5, such as interleukin (IL)-6, Snail2 and epidermal growth factor receptor (EGFR) by PCR array analysis. These genes have been reported to be involved in cacner progression, which is characterised by increased growth speed and invasiveness of the tumor cells. Here, we discovered that HOXB5 transcriptionally upregulates the promoter activity of these genes. Chromatin immunoprecipitation (ChIP) analysis to confirm direct binding of HOXB5 to the promoter region is now ongoing. Since we found that HOXB5 induces EGFR protein expression and SRC phosphorylation, we will further investigate signaling pathway components to understand the underlying molecular mechanisms of HOXB5 action in breast cancer.

Citation Format: Kim JM, Lee J-Y, Kim MH. The role and regulation mechanism of HOXB5 in human breaset cancer cells [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 P5-05-05.
Abstract P5-06-08: BRCA1 promoter hypermethylation, but not BRCA1 expression, is associated with basal-like features and good prognosis in triple negative breast cancer
Authors: Jacot W , Simony-Lafontaine J , Mollevi C , Boissierre F , Lopez-Crapez E , Chartron E , Lamy P-J , Guiu S
Published: March 2017

Purpose: BRCA1 gene mutation is closely associated with familial hereditary breast cancer. Decreased expression of BRCA1 could be detected in certain types of sporadic breast cancer without BRCA1 mutations. Aberrant hypermethylation of DNA promoter CpG islands is one of the mechanisms by which tumor suppressor gene expression and function could be lost. We investigated BRCA1 methylation status and BRCA1 immunohistochemistry (IHC) expression and their clinic-pathological significance in triple negative breast cancers (TNBC).

Patients and methods: We analyzed BRCA1 promoter hypermethylation using a methylation specific PCR assay and BRCA1 IHC expression using the MS110 monoclonal antibody and Garg and Meisel scoring classification. Their clinicopathological and prognostic implications were analyzed in a TMA of TNBC samples from European patients.

Results: To date, 123 TNBC have been analyzed. 25 tumors (20%) presented a BRCA1 promoter hypermethylation. BRCA1 IHC expression was retained, equivocal and lost in 73 (59%), 17 (14%) and 33 (27%) cases respectively. No significant correlation was found between promoter hypermethylation and protein expression (p=0.28). A significant association was found between promoter hypermethylation and basal staining (CK5/6 and/or EGFR IHC staining), while using either a 10% or 1% cut-off for basal definition (p= 0.04 and 0.03, respectively). No significant association was found between BRCA1 expression and a basal phenotype. With a median follow-up of 6.3 years (range [0.01 – 11.8]), 35 relapses and deaths occurred (71.2% 5-years RFS and 77.8 5-years OS). RFS was significantly associated with T and N stage, and a trend was seen for a better prognosis of BRCA1 promoter hypermethylated tumors (5-years RFS: 84% vs. 68%, p=0.07). OS was significantly associated with T and N stage, and adjuvant chemotherapy.

Conclusion: BRCA1 promoter hypermethylation is associated with basal-like features and seems to be associated with a better prognosis in TNBC. BRCA1 IHC expression is not a good surrogate marker for evaluation of the methylation status of the tumors, and did not appear associated with prognosis in our series. The data will be updated for the meeting in term of number of analyzed tumors in order to strengthen the statistical analysis.

Citation Format: Jacot W, Simony-Lafontaine J, Mollevi C, Boissierre F, Lopez-Crapez E, Chartron E, Lamy P-J, Guiu S. BRCA1 promoter hypermethylation, but not BRCA1 expression, is associated with basal-like features and good prognosis in triple negative 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 P5-06-08.
Abstract P5-07-08: The role of inducible nitric oxide synthase in the stemness of triple negative breast cancer
Authors: Mehibel M , Simoes BM , Telfer B , Williams KJ , Stratford IJ
Published: March 2017

This abstract was not presented at the symposium.
Abstract P5-07-12: RAD51AP1 is a novel prognostic marker and therapeutic target for breast cancer
Authors: Thangaraju M , Kolhe RB , Pathania R
Published: March 2017

Background: Ionizing radiation is one of the most effective therapeutic strategies for the treatment of breast cancer and is considered as a more appropriate therapy for patients with high-risk of recurrence. Despite substantial benefits are achievable with this treatment, especially for ductal carcinoma and early invasive cancer, the critical barrier in using this treatment strategy is that tumor cells develop radioresistance, which in turn progress into advanced invasive cancer. Breast cancer stem cells (BCSCs), a subpopulation of cells within the tumor with a characteristic feature of self-renewal, play a critical role radioresistance and treatment failure. BCSCs exhibit increased DNA repair activity by increasing RAD51AP1 for their prolonged survival and to evade from the radiation therapy. We explored the expression profile of RAD51AP1 in BCSCs, human normal and various subtypes of breast tumor tissues and cell lines and response to chemo- and radiation- therapy.

Methods: Gene expression (RNA and protein) profile was assessed using semi-quantitative and real-time PCR (qPCR) and western blot analyses. RAD51AP1 expression and its prognostic value in large cohort of human samples were analyzed by TCGA, GOBO, and Kaplan-Meier plotter integrative bioinformatics interface analyses. Breast cancer stem cell (BCSC) status was analyzed by FACS using CD24 and CD49f cell surface marker. Cell death was analyzed by propidium iodide (PI) stained cell cycle analysis.

Results: We found that tumor propagating CD49f+CD24+ cells activate RAD51AP1 more promptly than non-tumorigenic CD49f-CD24- cells and confer chemo- and radiation- therapy resistance. RAD51AP1 inactivation facilitates chemo- and radiation- therapy response by depleting CD49f+CD24+ cells with significant activation of apoptotic cell death signaling. RAD51AP1 expression was significantly higher in BC, especially in the basal triple-negative and HER2-positive BC subtype, than in normal mammary tissue. Further, RAD51AP1 expression is highest in grade III histological tumor types and negatively associated to overall disease-free survival. RAD51AP1 levels across different BC cell lines showed that triple-negative breast cancer (TNBC) cell lines expressed highest level of this gene than other sub types.

Conclusion:Overall, our findings provide evidence that BCSCs utilize DNA repair signaling for their self-renewal and RAD51AP1 play a critical role in BCSC self-renewal and maintenance. Further, RAD51AP1 expression profile can be used as a prognostic marker to monitor disease progression and chemotherapy response.

Citation Format: Thangaraju M, Kolhe RB, Pathania R. RAD51AP1 is a novel prognostic marker and therapeutic target for 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 P5-07-12.
Abstract P5-07-13: Identification of a cancer stem sell-specific function for the histone deacetylases, HDAC1 and HDAC7, in breast and ovarian cancer
Authors: Ince TA , Witt AE , Lee C-W , Lee TI , Azzam DJ , Wang B , Caslini C , Petrocca F , Grosso J , Jones M , Cohick EA , Gropper AB , Wahlestedt C , Richardson AL , Shiekhattar R , Young RA
Published: March 2017

This abstract was withdrawn by the authors.
Abstract P5-08-07: The long-term prognosis of breast cancers patients diagnosed ≤40 years in the absence of adjuvant systemic therapy
Authors: Dackus GMHE , Ter Hoeve ND , Opdam M , Vreuls W , Koop EA , Varga Z , Willems SM , Van Deurzen CHM , Groen EJ , Cordoba-Iturriagagoitia A , Bart J , Mooyaart AL , Van den Tweel JG , Zolota V , Wesseling J , Sapino A , Chmielik E , Ryska A , Broeks A , Stathonikos N , Jozwiak K , Hauptmann M , Sonke GS , Van der Wall E , Siesling S , Van Diest PJ , Linn SC
Published: March 2017

This abstract was withdrawn by the authors.
Abstract P5-09-03: Associations between breast cancer subtypes and mutations in cancer predisposition genes identified by clinical genetic testing of breast cancer patients
Authors: Couch FJ , Lilyquist J , Na J , Hu C , Polley EC , Shimelis H , Akinhanmi M , McFarland R , LaDuca H , Goldgar DE , Dolinsky JS
Published: March 2017

Clinical genetic testing of individuals with a personal or family history of breast and ovarian cancer using panels for BRCA1/2 and other candidate cancer predisposition genes has become routine clinical practice. Several of the genes on hereditary cancer testing panels have been strongly associated with specific subtypes of breast cancer. In particular, individuals with germline mutations in BRCA1 predominantly develop estrogen receptor (ER)-negative and triple negative (TN) (estrogen receptor negative, progesterone receptor negative, HER2 negative) breast tumors. In contrast, CHEK2 and ATM mutations have been associated with ER-positive breast cancer. In this study, associations between mutations in panel genes and breast cancer subtypes were evaluated. A cohort of 60,000 breast cancer patients tested for germline cancer predisposing mutations using hereditary cancer gene panels was utilized. Information on personal and family cancer history, age of diagnosis, tumor pathology, and ethnicity of patients was obtained from test requisition forms or by follow up with ordering health care providers. Mutations in each gene were combined into four histological subtypes (triple negative; HER2 positive; ER-positive,HER2-positive; and ER-positive,HER2 negative). Associations for each subtype were estimated by case-control analyses comparing the frequencies of pathogenic mutations in each subtype with frequencies from non-TCGA controls from the Exome Aggregation Consortium (ExAC) database. In addition, case-case analyses were conducted to assess enrichment of gene mutations in specific breast cancer subtypes. Among the observed associations between genes and breast cancer subtypes, mutations in CHEK2 and ATM were highly enriched in luminal breast cancers and BARD1 was specifically associated with TN breast cancer. Refining the spectrum of pathological correlates with mutations in hereditary breast cancer genes will aid gene specific cancer risk management, and may accelerate the development of novel gene-specific therapeutic interventions.

Citation Format: Couch FJ, Lilyquist J, Na J, Hu C, Polley EC, Shimelis H, Akinhanmi M, McFarland R, LaDuca H, Goldgar DE, Dolinsky JS. Associations between breast cancer subtypes and mutations in cancer predisposition genes identified by clinical genetic testing of breast cancer patients [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 P5-09-03.
Abstract P5-09-04: Assessment of breast cancer risk among atomic-bomb survivors based on ATM polymorphisms, radiation dose, and age at exposure
Authors: Hayashi T , Yoshida K , Ohishi W , Kyoizumi S , Kusunoki Y , Nakachi K
Published: March 2017

RERF's epidemiological study on atomic bomb survivors has found increased incidence of several types of cancers with increased radiation dose. A great deal of inter-individual variation in susceptibility to radiation-associated breast cancer could not be explained solely by radiation dose, suggesting the possibility of partial involvement of DNA repair capacity. Of 11 known single nucleotide polymorphisms (SNPs) of the DNA repair gene ATM, we selected a particular SNP (located in the 5' untranslated region and therefore thought to be associated with ATM gene expression) and examined the association with radiation-associated breast cancer in the context of an RERF A-bomb survivor cohort study. A follow-up survey of 3,040 female members of the RERF Immunogenome Study Cohort during 1981-2009 identified a total of 108 breast cancer cases. ATM genotypes (ATM-G/G, -G/A, and -A/A) were determined by the TaqMan assay method for all cohort members. Relative risks (RRs) of breast cancer were estimated for radiation dose, the ATM genotypes, and the combined categories of dose levels and genotypes. As a result, RR of breast cancer significantly increased with increased radiation dose (RR = 1.46/Gy, 95% CI: 1.19-1.80). A-bomb survivors with ATM-G/G homozygote revealed a significantly-increased RR of breast cancer (RR = 1.74, 95%CI: 1.18-2.56), using as a reference the risk of those with ATM-A/A homozygotes combined with ATM-G/A heterozygotes. When dividing the subjects into two groups by age at exposure (under 20 years of age and over 20), RR of breast cancer significantly increased with radiation dose in the group aged less than 20 years at exposure (RR = 1.65/Gy, 95% CI: 1.29-2.11), but no significant increase in RR by genotype was observed. In the group aged over 20 years at exposure, there was no significant increase in RR of breast cancer by dose, but RR of breast cancer significantly increased among ATM-G/G homozygotes, using as a reference the risk of ATM-A/A homozygotes combined with ATM-G/A heterozygotes (RR = 2.28, 95%CI: 1.28-4.06). In all analyses, no interaction between RR of breast cancer and combinations of radiation dose and genotype was detected. These findings suggested that the ATM genotypes and radiation dose might affect the risk of breast cancer among A-bomb survivors and that the significance of such impact might differ by age at exposure.

Citation Format: Hayashi T, Yoshida K, Ohishi W, Kyoizumi S, Kusunoki Y, Nakachi K. Assessment of breast cancer risk among atomic-bomb survivors based on ATM polymorphisms, radiation dose, and age at exposure [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 P5-09-04.
Abstract P5-10-01: Adherence to healthy lifestyle behaviors in a predominantly Hispanic population of women undergoing screening mammography
Authors: Ali-Shaw T , Ueng WA , Trivedi MS , Yi H , David RR , Vanegas A , Vargas JM , Sandoval R , Wood J , Kukafka R , Crew KD
Published: March 2017

This abstract was not presented at the symposium.
Abstract P5-11-16: Do patients and nurses outside clinical trial prefer subcutaneous trastuzumab over conventional intravenous infusion? Instituto Oncologico Nacional experience
Authors: Castillo-Fernandez O , Cabreja A , Arauz E , Bellido D , Lim M , Lopez R , Montano L
Published: March 2017

Background In the PrefHer study, subcutaneous administration of trastuzumab was preferred over intravenous administration (iv). In 2014 our hospital approved subcutaneous (sc) trastuzumab for use in patients with early or metastatic Her 2 positive breast cancer. The aim of this study was to evaluate patients (pts) and nurses´s preferences in our institution.

Methods Patients with Her2 postive breast cancer and nurses who had received or administered both sc and iv trastuzumab were interviewed to evaluate their preference. Preference for sc was compared with a linear chi squared test.

Results 55 pts were interviewed. Median age was 53 years (30-83). 30 patients in adjuvant/neoad setting and 25 pts in the palliative setting. 41 pts (74.5%) preferred sc 95% CI (63-86) , 3 pts (5.5%) preferred iv 95% CI (-0.5-11.5) and 11 pts (20%) did not have preference 95% CI (9.4-20%) p< 0.0001. 72% of pts considered that sc trastuzumab was more convenient (p<0.0001). 11 nurses experienced with both iv and sc trastuzumab administration answered the questionnaire. Median age 41 years (30-55). 10/11 nurses preferred sc administration, 1/10 indicated no preference. All nurses considered that sc was the most convenient administration method for the patients and is highly recommended. The main reason for patients and nurses preference was that sc administration saved time.

Conclusion Patients and nurses prefer s.c over iv trastuzumab. Our results are consistent with PrefHer study. Incorporation of sc trastuzumab could improve quality of care in patients with Breast Cancer Her 2 positive.

Citation Format: Castillo-Fernandez O, Cabreja A, Arauz E, Bellido D, Lim M, Lopez R, Montano L. Do patients and nurses outside clinical trial prefer subcutaneous trastuzumab over conventional intravenous infusion? Instituto Oncologico Nacional experience [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 P5-11-16.
Abstract P5-11-17: Body image in women with breast cancer using a scalp cooling system to reduce chemotherapy induced alopecia
Authors: Cigler T , Melin SA , Klein P , Hurvitz SA , Melisko M , Moore A , Park GD , Bageman E , Ver Hoeve ES , Rugo HS
Published: March 2017

Background: Most women consider hair to be an important part of body image. Alopecia is an emotionally traumatic side effect for breast cancer patients undergoing adjuvant chemotherapy. The DigniCap™ Scalp Cooling System is the first scalp cooling system cleared by the US Food and Drug Administration to reduce the likelihood of chemotherapy induced alopecia.

Methods: Quality of Life (QOL) data were collected as part of a prospective clinical trial evaluating the clinical performance of scalp cooling in women with early stage BC receiving adjuvant chemotherapy.

The study's primary endpoint was hair loss as evaluated by patient self-assessment. Treatment success was defined as ≤ 50% hair loss. QOL was evaluated by the EORTC-QLQ-BR23 (BR23) administered at baseline, last chemotherapy cycle, and one month later. For BR23, 4 response categories were collapsed to 2 categories (Not at all/A little bit and Quite a bit/Very much) for analysis. QOL was compared between those with success vs. failure of scalp cooling.

Results: 101 patients were evaluable for the primary endpoint: Success was seen in 67 (66.3%) pts. QOL at study entry was comparable between pts with scalp cooling success or failure for each item in the BR23 questionnaire. Results reported as percentages of patients in each group who answered either quite a bit or very much to body image-related questions on the BR23 questionnaire are displayed in Table 1.

BR23 results (% quite a bit/very much) one month after chemotherapyBR23 ItemsTreatment Success % (95% CI)Treatment Failure % (95% CI)Felt physically less attractive18.5% (9.0%, 27.9%)52.2% (31.8%, 72.6%)Felt less feminine15.4% (6.6%, 24.2%)29.1% (19.2%, 59.1%)Found it difficult to see themselves naked13.8% (5.5%, 22.2%)21.7% (4.9%, 38.6%)Felt dissatisfied with their body12.3% (4.3%, 20.3%)26.1% (8.1%, 44.0%)

Conclusions: Women with breast cancer using scalp cooling during chemotherapy who had hair preservation experienced improved quality of life, according to self-assessment of body image, compared to women who had significant hair loss.

Citation Format: Cigler T, Melin SA, Klein P, Hurvitz SA, Melisko M, Moore A, Park GD, Bageman E, Ver Hoeve ES, Rugo HS. Body image in women with breast cancer using a scalp cooling system to reduce chemotherapy induced alopecia [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 P5-11-17.
Abstract P5-13-09: Development and implementation of a patient-centered, nurse practitioner-led survivorship intervention for breast cancer
Authors: Post KE , Moy B , Furlani CM , Smith BL , Strand EA , Taghian AG , Jeffrey P
Published: March 2017

This abstract was withdrawn by the authors.
Abstract P5-13-12: Symptom burden, unmet need for assistance, and psychosocial adaptation among longer term breast cancer survivors
Authors: Palmer SC , Blauch AN , Pucci DA , Jacobs LA
Published: March 2017

Introduction:

Advances have improved survival among breast cancer (BC) patients and 89% can expect >5 year survival. The price for this survival, however, may be physical and psychosocial symptoms that persist many years into the survivorship trajectory. Unmet needs for symptom management and the relationships between unmet needs, symptom burden, and psychosocial adaptation remain unclear. We examined these relationships among longer term BC survivors.

Method:

Eligibility included non-metastatic BC survivors diagnosed > 3 years prior and attendance at a survivorship-focused appointment. Nineteen common symptoms of disease and treatment were evaluated and participants reported unmet need for assistance for each symptom they experienced. Psychosocial adaptation was assessed through the Hospital Anxiety and Depression Scale (HADS).

Results:

103 primarily white (72%), middle aged (M=62.7 yrs) BC survivors were recruited. Participants were, on average, 11.4 yrs from diagnosis and most (78.2%) reported Stage I or II BC. Participants reported an average of 9.2 symptoms, most commonly fatigue (67%), joint pain (66%), weight gain (60%), decreased sexual drive (55%), and insomnia (52%). Participants reported an average of 2.8 unmet needs for assistance with symptoms, most commonly joint pain (29%), fatigue (25%), weight gain (23%), and difficulty with memory (21%). Overall levels of depressive (M=2.45) and anxiety (M=4.89) symptoms were low, and elevated depressive and anxiety symptoms were reported by 3% and 18% of the sample, respectively. Number of symptoms and anxiety were unrelated to any demographic, disease or treatment variables. Depressive symptoms and unmet needs were related younger age (p < .05) and depressive symptoms were further related to not having received radiotherapy (p < .05). Number of symptoms experienced and unmet needs were moderately related to both depressive (all r > 0.49, p < .001) and anxiety symptoms (all r > 0.31, p < .01).

Conclusion:

Among long term BC survivors symptoms are common, while unmet need and symptoms of anxiety and depression are more modest. However, both symptoms and unmet need are associated with symptoms of depression and anxiety and represent a potentially missed opportunity for improving outcomes among BC survivors.

Citation Format: Palmer SC, Blauch AN, Pucci DA, Jacobs LA. Symptom burden, unmet need for assistance, and psychosocial adaptation among longer term breast cancer survivors [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 P5-13-12.
Abstract P5-13-15: Longitudinal patterns of postdiagnosis weight changes according to adjuvant systemic treatments in Korean breast cancer survivors
Authors: Lee JW , Min Y , Chung IY , Son BH , Ahn SH
Published: March 2017

This abstract was withdrawn by the authors.
Abstract P5-13-16: Arthralgia-associated aging perceptions predict adherence to aromatase inhibitors among women with breast cancer
Authors: Mao JJ , Chambless DL , Chen J , Bao T , Brier MJ
Published: March 2017

Background:Aromatase inhibitors (AIs) are associated with reduced risk of breast cancer recurrence, yet many women discontinue their treatment prematurely, often due to arthralgia. Empirically, breast cancer survivors who experience AI-associated arthralgia often report that they have aged quickly over a short period of time. Objective: We aimed to determine whether survivors with a heightened sense of aging due to arthralgia were more likely to non-adhere to their AI regimen. Methods: We conducted a prospective cohort study in an urban academic cancer center among post-menopausal women with hormone receptor positive breast cancer who were within the first two years of their aromatase inhibitor therapy. Perceptions of aging due to arthralgia were measured by the previously validated Penn Arthralgia Aging Scale. Non-adherence was defined as interrupting treatment or discontinuing the AI before the prescribed treatment length was over. Trained raters abstracted adherence data from medical charts. We performed Cox proportional hazards regression to evaluate the relationship between perceptions of aging due to arthralgia and time to non-adherence while adjusting for potential confounders. Results: Among 509 participants, most were White (81.2%) and had at least some college education (77.9%). The majority had been prescribed anastrozole (88.0%), followed by letrozole (9.0%), and exemestane (3.0%). During the follow up period, 144 (28.3%) did not adhere to the AIs as originally prescribed. In univariate analysis, women with a heightened sense of aging due to arthralgia were at more than twice the risk of non-adherence compared to women with low levels of aging perceptions (Hazard Ratio [HR], 2.20; 95% CI, 1.50 – 3.21; p < 0.001). After adjusting for arthralgia pain severity, depression, and AI type, aging perceptions remained a statistically significant predictor of adherence (HR, 1.71; 95% CI, 1.10-2.67; p = 0.02). Depression status also uniquely predicted non-adherence risk (HR, 1.63; 95% CI, 1.03 – 2.59; p = 0.04). Arthralgia pain severity, which predicted adherence in univariate analysis, was not a significant predictor in the final model (HR, 1.21; 95% CI, 0.84 – 1.75; p = .30). Conclusions: Breast cancer survivors on AIs who have a heightened sense of aging due to arthralgia are at greater risk of non-adhering to their AI regimen. Interventions are needed to help survivors reduce arthralgia and develop adaptive appraisals of their AI experience to achieve optimal adherence.

Citation Format: Mao JJ, Chambless DL, Chen J, Bao T, Brier MJ. Arthralgia-associated aging perceptions predict adherence to aromatase inhibitors among women with 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 P5-13-16.