bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract OT3-02-01: RIBANNA — Real-world evidence of ribociclib plus aromatase inhibitor, or endocrine monotherapy, or chemotherapy as first-line therapy for postmenopausal women with HR+, HER2– advanced breast cancer (aBC)
Authors: Wöckel A , Fasching PA , Guderian G , Heim J , Jackisch C , Lück H-J , Lüftner D , Marmé F , Reimer T , Decker T
Published: May 2019

Background: In the pivotal phase 3 MONALEESA-2 trial, ribociclib, a highly selective oral CDK4/6 inhibitor in combination with letrozole significantly prolonged progression-free survival (PFS) compared to letrozole alone. In the year 2017, based on the results of MONALEESA-2, ribociclib in combination with an aromatase inhibitor (AI) was approved for the treatment of HR+, HER2– aBC in postmenopausal women with no prior therapy for their advanced disease (first-line treatment). Beyond phase 3 trials, further data for ribociclib are now becoming available from the phase 3b trials, RIBECCA and COMPLEEMENT-1, involving approximately 500 and 3000 patients with aBC, respectively. However, real-world evidence for the effectiveness, safety, and tolerability of ribociclib + AI in the routine clinical practice is needed to further support the use of this combination in the first-line therapy.

Methods: RIBANNA is a non-interventional study, which started in October 2017 and plans to enroll 3020 patients across ˜400 sites in Germany. Postmenopausal women diagnosed with aBC will be enrolled into 3 cohorts (cohort 1: ribociclib + AI; cohort 2: endocrine monotherapy; and cohort 3: chemotherapy). Across all cohorts, patients will be treated in accordance with the respective German-prescribing guidelines. Data related to efficacy (with PFS as the primary efficacy criterion), safety, tolerability, duration of therapy, and impact on quality of life (QoL) will be collected. QoL will be assessed using the validated patient questionnaires. This study was especially designed to analyze the patient data from sequential lines of therapy in all three cohorts over a period of up to 7 years. For this purpose, RIBANNA will collect the data on each line of treatment and the reason for changing treatment in all 3 cohorts. The same accounts for QoL, which will also be assessed periodically, regardless of disease progression and initiation of subsequent therapies.

RIBANNA is the first study to provide the real-world evidence regarding treatment of HR+, HER2− aBC with the CDK4/6 inhibitor, ribociclib. This study includes 3 treatment cohorts (ribociclib + AI, endocrine monotherapy, and chemotherapy) with subsequent treatment algorithms and assessment of QoL over the entire study period.

Citation Format: Wöckel A, Fasching PA, Guderian G, Heim J, Jackisch C, Lück H-J, Lüftner D, Marmé F, Reimer T, Decker T. RIBANNA — Real-world evidence of ribociclib plus aromatase inhibitor, or endocrine monotherapy, or chemotherapy as first-line therapy for postmenopausal women with HR+, HER2– advanced breast cancer (aBC) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT3-02-01.
Abstract OT3-05-01: A randomized double-blind phase III clinical trial of neoadjuvant chemotherapy (NAC) with atezolizumab or placebo in patients (pts) with triple negative breast cancer (TNBC) followed by adjuvant atezolizumab or placebo: NSABP B-59/GBG 96-GeparDouze
Authors: Geyer CE , Loibl S , Rastogi P , Seiler S , Costantino JP , Nekljudova VN , Cortazar P , Lucas PC , Denkert C , Mamounas EP , Jackisch C , Wolmark N
Published: May 2019

Background:

TNBC is associated with higher percentages of pathological complete response (pCR) to neoadjuvant chemotherapy (NAC), and women with a pCR have a favorable prognosis. However, Liedtke (2008) and Loibl (2017) found that women with residual disease have a substantially higher risk of recurrence than women with other subtypes of breast cancer. Additionally, Adams (2017) and Schmid (2017) found that therapeutic blockade of PD-L1 binding by atezolizumab has resulted in relevant anti-tumor efficacy.

Methods:

Design

This is a phase III, double blind, placebo-control trial evaluating neoadjuvant atezolizumab with NAC followed by adjuvant atezolizumab in TNBC. Pts are stratified by region (North America; Europe), tumor size (1.1-3.0cm; >3.0cm), AC/EC schedule (q2w; q3w), and nodal status (positive; negative), then randomized 1:1 to receive atezolizumab/placebo 1200 mg IV every 3 wks concurrently with both sequential regimens of weekly paclitaxel 80 mg/m2 IV for 12 doses with every 3-wk carboplatin AUC of 5 IV for 4 doses followed by AC/EC every 2-3 wks (per investigator discretion) for 4 cycles. Following surgery, pts resume atezolizumab/placebo 1200 mg IV every 3 wks as adjuvant therapy for 6 months. Radiotherapy based on local standards is co-administered with atezolizumab/placebo.

Eligibility criteria

Centrally-confirmed ER-neg, PR-neg, HER2-neg invasive breast cancer by ASCO/CAP guidelines. Primary tumor must be stage T2 or T3 if cN0 or cN1 with negative biopsy or T1c, T2, or T3 if cN1 with positive biopsy or cN2 or cN3. LVEF >55% and no significant cardiac history.

Statistical methods

Co-primary endpoints are event-free survival (EFS) and pCR breast/nodes. Secondary endpoints include pCR breast, overall survival, distant disease-free survival, safety and toxicity. Trial is an academic collaboration between NSABP and GBG with support from Genentech/Roche.

NCT03281954

Support: Genentech/Roche

Citation Format: Geyer, Jr. CE, Loibl S, Rastogi P, Seiler S, Costantino JP, Nekljudova VN, Cortazar P, Lucas PC, Denkert C, Mamounas EP, Jackisch C, Wolmark N. A randomized double-blind phase III clinical trial of neoadjuvant chemotherapy (NAC) with atezolizumab or placebo in patients (pts) with triple negative breast cancer (TNBC) followed by adjuvant atezolizumab or placebo: NSABP B-59/GBG 96-GeparDouze [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT3-05-01.
Abstract P1-03-09: The breast cancer care continuum in Tanzania: From accessing care for breast concerns to cancer diagnosis and treatment
Authors: Rositch AF , Chao CA , Masalu N , Visvanathan K
Published: May 2019

Background: Tanzania, like many low to middle income countries, has developed their first ever national guidelines focusing on early diagnosis of breast cancer to combat the high fatality rates. Thus, one component of the “Time to A.C.T.” study sought to provide critical information on women presenting to a health facility who might need clinical breast examination per the new guidelines and ultimately how many of these women were diagnosed and treated for breast cancer.

Methods: In this retrospective cohort study, data were abstracted from 777 medical charts from three health facilities spanning the health system hierarchy (district n=103, regional n=64, and zonal n=610 hospitals) in Mwanza, Tanzania. Charts were identified from the departments of oncology, surgery, gynecology, obstetrics and emergency medicine, and focused on women aged 30 and older who were seeking or receiving care related to any “breast concern” from January 2015 to April 2018.

Results: The median age of women seeking care for breast concerns was 43 years (IQR: 34-54). Women most commonly presented with complaints of swelling (43%), a palpable lump (27%), or pain (24%) of the breast or nipple. Ultimately, 26% of these care-seeking women were diagnosed with breast cancer (including DCIS=2, invasive ductal or lobular cancer=121, and metastatic cancer =15), of whom 73% were pathologically confirmed. Treatment data were available for only 79 women with breast cancer: 24 had surgery only, 33 had chemotherapy only, 21 had surgery and chemotherapy, and 1 woman had surgery, chemotherapy and radiation.

Conclusions: This study increases our understanding of the health services needs associated with Tanzania's commitment to down stage breast cancer through early detection and treatment. Almost a third of women who presented with a breast concern were diagnosed with breast cancer. Although this likely reflects the fact the majority of medical charts were identified at a zonal hospital that has the most capacity for cancer diagnosis and treatment, it also highlights the importance of getting women into care, proper referrals and ultimately diagnosis and treatment. This information on who seeks care, why, and where will help appropriately allocate and scale up capacity for breast cancer care.

Citation Format: Rositch AF, Chao CA, Masalu N, Visvanathan K. The breast cancer care continuum in Tanzania: From accessing care for breast concerns to cancer diagnosis and treatment [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-03-09.
Abstract P1-04-02: Not presented
Authors: Lin C-Y , Hazar-Rethinam M , Thangavelu P , Dray E , Duijf PH
Published: May 2019

This abstract was not presented at the conference.

Citation Format: Lin C-Y, Hazar-Rethinam M, Thangavelu P, Dray E, Duijf PH. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-04-02.
Abstract P1-06-01: Regulation of BRCA1 by SIRT2
Authors: Minten EV , Zhang H , Li C , Head PE , Yu DS
Published: May 2019

We are constantly exposed to a variety of both external and internal DNA damaging agents, such as UV light from the sun and reactive oxygen species created as by-products of aerobic respiration. As a result, our DNA accumulates thousands of instances of damage per cell per day. DNA damage response (DDR) pathways, which include DNA repair and cell-cycle checkpoints, are responsible for the repair of DNA damage and are critical for protecting against mutagenesis and maintaining genome integrity. DNA double-stranded breaks (DSBs) are the most deleterious type of DNA damage and are repaired by one of two pathways: Non-homologous end-joining (NHEJ), an error-prone mechanism of repair active throughout the entire cell cycle, or homologous recombination (HR), considered to be an 'error-free' method for DSB repair that occurs in the S and G2 phases of the cell cycle. Deficiencies in NHEJ or HR can result in genomic instability via genomic incorporation of chromosomal aberrations, which can ultimately lead to an increased risk of cancer. However, in many cases, the mechanisms by which defects in these pathways lead to an increased risk of developing cancer is unknown, making preventative care and treatment of resulting cancers more difficult. Breast Cancer 1 (BRCA1), an established tumor suppressor, is a protein necessary for the proper repair of DNA DSBs through the HR pathway. Defects in BRCA1, whether genetically inherited or spontaneously developed, have been linked to different types of cancer in both men and women, including breast, ovarian, and pancreatic cancer. Yet, the regulation of BRCA1 in HR is not well understood and thus highlights a major a gap in our understanding of how deficiencies in HR contribute to the development of cancer. Our lab has discovered that SIRT2, a class III NAD+ dependent histone deacetylase and putative human tumor suppressor, plays a crucial role in the DDR and repair of DNA DSBs. We have shown that depletion of SIRT2 impairs HR and increases cell sensitivity to ionizing radiation in a deacetylase-dependent manner. A mass spectrometry analysis showed SIRT2 interacts with several proteins involved in DDR, including BRCA1. We validated the interaction between SIRT2 and BRCA1 and found SIRT2 deacetylates BRCA1 both in vitro and in cells. Depletion of SIRT2 and subsequent deacetylation of BRCA1 decreases BRCA1 protein levels in cells, impairing HR. Our results show SIRT2 is a novel regulator of BRCA1 and is critical for the repair of DNA DSBs through HR. These findings provide invaluable insights into how to exploit the interplay between SIRT2 and BRCA1 as a novel therapeutic approach for the prevention and treatment of cancer.

Citation Format: Minten EV, Zhang H, Li C, Head PE, Yu DS. Regulation of BRCA1 by SIRT2 [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-06-01.
Abstract P1-06-09: Withdrawn
Authors: Yu Y , Zhen Y , Zhang Y
Published: May 2019

This abstract was withdrawn by the authors.

Citation Format: Yu Y, Zhen Y, Zhang Y. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-06-09.
Abstract P1-08-01: Withdrawn
Authors: Schoemaker MJ , Nichols HB , Wright LB , Brook MN , Jones ME , O'Brien KM , Adami H-O , Baglietto L , Bernstein L , Bertrand KA , Boutron-Ruault M-C , Chen Y , Connor AE , Dorronsoro M , Dossus L , Eliassen AH , Giles GG , Gram IT , Hankinson SE , Kaaks R , Key TJ , Kirsh VA , Kitahara CM , Koh W-P , Larsson SC , Linet MS , Ma H , Masala G , Merritt MA , Milne RL , Overvad K , Ozasa K , Palmer JR , Riboli E , Rohan TE , Sadakane A , Sund M , Tamimi RM , Trichopoulou A , Ursin G , Van Gils CH , Visvanathan K , Weiderpass E , Willett WC , Wolk A , Yuan J-M , Zeleniuch-Jacquotte A , Sandler DP , Swerdlow AJ
Published: May 2019

This abstract was withdrawn by the authors.

Citation Format: Schoemaker MJ, Nichols HB, Wright LB, Brook MN, Jones ME, O'Brien KM, Adami H-O, Baglietto L, Bernstein L, Bertrand KA, Boutron-Ruault M-C, Chen Y, Connor AE, Dorronsoro M, Dossus L, Eliassen AH, Giles GG, Gram IT, Hankinson SE, Kaaks R, Key TJ, Kirsh VA, Kitahara CM, Koh W-P, Larsson SC, Linet MS, Ma H, Masala G, Merritt MA, Milne RL, Overvad K, Ozasa K, Palmer JR, Riboli E, Rohan TE, Sadakane A, Sund M, Tamimi RM, Trichopoulou A, Ursin G, Van Gils CH, Visvanathan K, Weiderpass E, Willett WC, Wolk A, Yuan J-M, Zeleniuch-Jacquotte A, Sandler DP, Swerdlow AJ. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-08-01.
Abstract P1-08-08: Not presented
Authors: Rapiti E , Schaffar R , Bouchardy C , Neyroud-Caspar I , Benhamou S
Published: May 2019

This abstract was not presented at the conference.

Citation Format: Rapiti E, Schaffar R, Bouchardy C, Neyroud-Caspar I, Benhamou S. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-08-08.
Abstract P1-08-28: Impact of surgery and time to surgery on breast cancer survival in the United States, 2004–2014 (N=2,211,245)
Authors: Singh M , Konduri SD , Bobustuc GC , Rovin RA , Kassam AB
Published: May 2019

Background: Surgery is very common for patients diagnosed with breast cancer. Its impact on survival depends on diagnostic, patient, tumor-related, and other-treatment factors. Moreover, time to surgery from the date of diagnosis is also a critical factor affecting outcome.

Objective: In this study we investigated the impact of surgery on survival in breast cancer patients using two methods: (1) multivariate regression; and (2) propensity score matching. For the patients undergoing surgical intervention, we aimed to identify the optimum time from diagnosis to surgery.

Methods: The study population was taken from the National Cancer Database over the years 2004 through 2014. Of 2,211,245 patients, 99.1% were female, 0.9% male, 85% non-Hispanic white, 10.5% black, 0.7% Hispanic, and 14.5% other races. Mean age of the patient population was 60.0 ± 13.4 years (range: 18–90). The majority of the patients (92.9%) underwent a surgical procedure.

Results: Overall, the patients who did not undergo surgery were 6.7 times more likely to die within the study time period (95% confidence interval [CI]: 6.7–6.8, p<0.001) than those who did. However, after adjusting for patients' demographics, tumor-related factors, cancer stages, and combination of other treatments, the risk for dying of patients without surgery was 2.3 times higher (hazard ratio [HR]: 2.3, 95% CI: 2.3–2.4, p<0.001). In the propensity-matched cohort of 51,630 patients that was divided equally into two groups — those who underwent surgery and those who did not — the risk of mortality remained 2.4 times higher for patients without surgery (HR: 2.4, 95% CI: 2.3–2.4, p<0.001). Regarding time to surgery from the date of diagnosis, patient survival was best for the patients whose time to surgery ranged from 31 to 60 days. The next best timeframe was 61 to 90 days, followed by 30 days or fewer, then 91 to 120 days, and finally 120 and more days (p<0.001).

Conclusion: Using two different statistical methods, surgery is clearly an independent predictor of survival for patients with breast cancer. After matching for other factors, patients not having surgery were more than twice as likely to die as their surgical counterparts. Time to surgery from the date of diagonosis confirmed ealier findings that surgery is most benificial within 2–3 months from the date of diangosis. These findings can provide clinical guidance to clinicians and patients for planning treatment.

Citation Format: Singh M, Konduri SD, Bobustuc GC, Rovin RA, Kassam AB. Impact of surgery and time to surgery on breast cancer survival in the United States, 2004–2014 (N=2,211,245) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-08-28.
Abstract P1-08-30: Triple negative breast cancer: Does ethnicity impact survival?
Authors: Rushton-Marovac M , Zhang T , Song X
Published: May 2019

Background:

Triple negative breast cancer (TNBC) is a heterogeneous disease with poor outcomes relative to hormone positive breast cancer. Observations in the clinical setting lead to the hypothesis that there may be phenotypic differences among ethnic groups. Previous studies have conflicting results; some suggesting no differences, others showing inferior outcomes for black patients (pts). The purpose of this study was to use a population-based approach to examine survival amongst different ethnicities in triple negative breast cancer (TNBC).

Methods

Retrospective population-based study using data from the surveillance epidemiology and end results (SEER) database to identify TNBC cases diagnosed 2010 - 2014. We divided pts into 6 ethnic groups: White, Black, American Indian/Alaskan Native (AIAN), Pacific Islander (PI), Asian and Asian Indian (AI). Primary outcome: overall survival (OS); secondary outcome: breast-cancer specific survival (BCSS). Survival analysis was performed using Cox proportional hazards and Kaplan-Meier models.

Results

31482 pts were included; 22752 (72.3%) were white, 6319 (20.4%) black, 1720 (5.5%) Asian, 262 (0.8%) AI, 179 (0.6%) AIAN, and 150 (0.5%) PI. Asian pts had the best OS (HR 0.82, 95% CI 0.72-0.94), while Black pts had the worst (HR 1.21 95% CI 1.13-1.29) when compared with White pts. Differences between other ethnicities were not statistically significant for OS. Black pts had significantly worse BCSS (HR 1.20, 95% CI 1.12 -1.29); no other ethnicity had statistically significant differences compared to Whites. Comparing Asian with Black pts in multivariate analysis the HR was 0.68 (95% CI 0.59 – 0.79) for OS and 0.71 (95% 0.61 – 0.84) for BCSS. Older age, advanced stage, male sex, and lack of chemotherapy, radiation or surgery were also found to be statistically significant variables in multivariate analysis.

Conclusions

In this large population study, we found Asian pts had significantly better OS and Black pts had significantly worse OS and BCSS. These findings confirm the clinical observation and warrant closer molecular analysis of TNBC phenotypes based on patient's ethnicity. Findings may offer insight into the biology of TNBC and lead to development of innovative treatment options.

Citation Format: Rushton-Marovac M, Zhang T, Song X. Triple negative breast cancer: Does ethnicity impact survival? [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-08-30.
Abstract P1-09-03: Withdrawn
Authors: Kotsopoulos J , Zaman T , Lubinski J , Sun P , Salmena L , Narod SA
Published: May 2019

This abstract was withdrawn by the authors.

Citation Format: Kotsopoulos J, Zaman T, Lubinski J, Sun P, Salmena L, Narod SA. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-09-03.
Abstract P1-09-12: TP53 expression in relation to clinical and etiologic factors in breast cancer subtypes
Authors: Yang XR , Abubakar M , Guo C , Koka H , Sung H , Guida J , Deng J , Zhou B , Hu N , Lu N
Published: May 2019

TP53 is a well-known tumor suppressor gene and mutations in TP53 are the most frequent genomic event in most cancers including breast cancer. Recent studies have shown that the frequency, spectrum, timing, and clinical implications of TP53 mutations varied in different molecular subtypes of breast cancer. For example, the frequency of TP53 mutations is the highest in basal-like subtype and lowest in luminal A tumors. However, the evaluation of TP53 protein expression, as a surrogate for TP53 mutations, in large studies in the context of tumor subtypes is limited. In addition, the etiologic relevance of TP53 expression is yet to be investigated. The goal of this study is to evaluate the association of clinical and breast cancer risk factors with TP53 expression, measured using immunohistochemistry (IHC), in breast cancer molecular subtypes. The analysis included 7,226 women with invasive breast cancer who were diagnosed and treated in a tertiary hospital in Beijing, China. Subtypes were defined as Luminal A: ER+ and PR+, HER2–, and low grade (grades 1 or 2); luminal B/HER2–: ER+ and/or PR+, HER2–, and high grade (grade 3); luminal B/HER2+: ER+ and/or PR+, HER2+ (regardless of grade); HER2-enriched: ER–, PR–, and HER2+; Triple-negative (TN): ER–, PR–, and HER2–. As expected, positive TP53 staining showed the lowest frequency in the luminal A (46%) and highest in the TN (61%) and HER2-enriched (63%) subtypes (P-value <0.001). Overall and particularly in luminal A patients, positive TP53 staining was associated with higher frequencies of aggressive tumor features such as higher grade, larger tumor size, higher proliferative index, and EGFR expression. Compared with TP53– patients, TP53+ patients were more likely to have younger ages at onset and increased parity, but these associations were largely driven by the luminal A subtype [OR (95% CI) vs nulliparity = 2.67 (1.59, 4.51); 2.63 (1.52, 4.55); 3.68 (2.01, 6.72) for 1, 2, and ≥3 children, respectively (P-trend = 0.006)]. Luminal A/TP53+ patients were also more likely to have breastfed [OR (95% CI) ever vs never = 1.38 (1.03, 1.85)] than luminal A/TP53– patients. These findings suggest that TP53 IHC staining might be used to further refine the classification of luminal A breast cancer into subgroups with distinct clinical and etiologic relevance.

Citation Format: Yang XR, Abubakar M, Guo C, Koka H, Sung H, Guida J, Deng J, Zhou B, Hu N, Lu N. TP53 expression in relation to clinical and etiologic factors in breast cancer subtypes [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-09-12.
Abstract P1-11-14: Efficacy and quality of life analysis of palonosetron vs ondansetron for high and moderate emetogenic chemotherapy for breast cancer
Authors: Arce-Salinas C , Deneken-Hernandez Z , Flores-Diaz D , Gonzalez-Serrano JP , Matus-Santos JA , Ruiz-Garcia E , Calderillo-Ruiz G , Macedo O , Santamaría-Galicia J , Aguilar-Ponce JL , Reynoso-Noverón N
Published: May 2019

Background: Nausea and vomiting are common complications on the chemotherapy (CINV) and can affect the quality of life of the patients. There are various antiemetic regiments that varies in both cost and effectiveness. The aim of this trial is to evaluate the efficacy in acute and delayed CINV of ondansetron vs palonosetron.

Patients and methods: In his was a randomized, open label trial, we included breast cancer patients' candidate to (AC, TC, TCH regimens); arm A received palonosetron, dexamethasone and fosaprepitant and arm B ondansetron, dexamethasone, fosaprepitant; patients who had received previously any chemotherapy or radiotherapy were excluded.Presence of CINV were investigated, as well the ER visits due for CINV and QoL (EORTC QLQ 30 and EORTC B-23) were analyzed during the first cycle of treatment. Local ethics committee approved the trial.

Results: 262 patients were included, 87% received AC and 13% TC; acute control was achieved in 87% and 94% respectively, p=ns and delayed control was achieved in 76% and 86% p=ns, toxicity was similar in both arms. QoL analysis showed no differences in family interaction, social life and financial troubles. ER visits due to severe symptoms were similar p=ns

Conclusions: Palonosetron or ondansetron are equally effective in prevention acute and delayed CINV and they also maintain similar quality of life.

Citation Format: Arce-Salinas C, Deneken-Hernandez Z, Flores-Diaz D, Gonzalez-Serrano JP, Matus-Santos JA, Ruiz-Garcia E, Calderillo-Ruiz G, Macedo O, Santamaría-Galicia J, Aguilar-Ponce JL, Reynoso-Noverón N. Efficacy and quality of life analysis of palonosetron vs ondansetron for high and moderate emetogenic chemotherapy for breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-11-14.
Abstract P1-12-01: Withdrawn
Authors: Bjelic-Radisic V , Bottomley A , Cardoso F , Cameron D , Brain E , Kuljanic K , de Costa RA , Conroy T , Deville V , Inwald E , Serpentini S , Pinto M , Bleiker E , Arrares J , Duhoux F , Weiss J , Morag O , Lindviksmoen Astrup G , Tomaszweksi K , Velikova G , Pogoda K , Nagele E , Bliem B , Sinai P , Sprangers M , Aaronson N , Greimel E
Published: May 2019

This abstract was withdrawn by the authors.

Citation Format: Bjelic-Radisic V, Bottomley A, Cardoso F, Cameron D, Brain E, Kuljanic K, de Costa RA, Conroy T, Deville V, Inwald E, Serpentini S, Pinto M, Bleiker E, Arrares J, Duhoux F, Weiss J, Morag O, Lindviksmoen Astrup G, Tomaszweksi K, Velikova G, Pogoda K, Nagele E, Bliem B, Sinai P, Sprangers M, Aaronson N, Greimel E. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-12-01.
Abstract P1-12-13: Initial report of a prospective, pilot study of patient-reported upper extremity dysfunction in women undergoing radiation for breast cancer
Authors: Healy E , Pan X , Beyer S , Washington I , Bazan J , White J
Published: May 2019

Objectives: Upper extremity dysfunction (UED) is a known side effect of breast cancer treatment. It is unclear, however, to what degree radiation contributes to this morbidity. We aimed to characterize the level of UED using patient-reported outcomes (PROs) prior to, during, and after treatment with radiation for breast cancer. Our secondary aims were to evaluate the association of UED with pain scores.

Methods: This is a single-institution, prospective, longitudinal cohort study of patients treated with radiation for breast cancer. The validated patient-reported outcome measure, Quick Disabilities of the Arm, Shoulder and Hand (QD) was used to capture UED prior to radiation, at the end of radiation, and 1 month following the completion of radiation. Pain scores were also collected at these intervals using the numeric pain reporting scale (NPRS) from 0 (no pain) to 10 (worst pain).

Results: Forty-four patients were enrolled on this study and 43 (97.7%) had completed radiation at the time of analysis. Thirteen patients (29.5%) were treated with mastectomy, axillary lymph node dissection and regional nodal irradiation in the supine position. The other 31 (70.5%) patients underwent lumpectomy and sentinel lymph node biopsy. Of these patients, 26 (83.9%) were treated in the prone position and 30 (96.8%) received whole breast irradiation. Median time from surgery to radiation was 69 days (range 35 – 212 days), 76 days for mastectomy and 68 days for lumpectomy. Median time from start to end of radiation was 38 days for mastectomy and 28 days for lumpectomy. Pre-treatment median QD score prior to radiation was 12.5 (11.4 for lumpectomy, 15.9 for mastectomy), 9.1 at the end of radiation (9.1 for lumpectomy, 18.2 for mastectomy), and 2.4 at 1 month after radiation (2.3 for lumpectomy, 2.5 for mastectomy). Median NPRS scores at pre-treatment, post-treatment and 1 month follow-up were 1, 1, and 1 for lumpectomy and 0, 1, 0 for mastectomy patients, respectively.

Conclusion: In this initial pilot study with 1 month of follow up, patient-reported UED as demonstrated by QD scores were higher pre-radiation and decreased by one month after. This likely reflects recuperation after surgical procedure. Median average pain scores were low at all time points. Further evaluation of UED over time to characterize the long-term effect of radiation and correlation with quality of life and other clinical factors is planned.

Citation Format: Healy E, Pan X, Beyer S, Washington I, Bazan J, White J. Initial report of a prospective, pilot study of patient-reported upper extremity dysfunction in women undergoing radiation for breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-12-13.
Abstract P1-13-04: Efficacy of adjuvant 5-Fluorouracil in residual HER2-negative breast cancer following neoadjuvant chemotherapy
Authors: Owusu-Brackett N , Scott S , Yuca E , Evans KW , Tapia C , Meric-Bernstam F
Published: May 2019

Background: Patients with residual disease following neoadjuvant chemotherapy have an increased risk of relapse. Recently the CREATE-X trial demonstrated that adjuvant capecitabine (oral prodrug of 5'deoxy-5-fluorouridine), prolonged disease-free survival and overall survival among patients with HER2-negative breast cancer who had residual invasive disease after neoadjuvant chemotherapy containing anthracycline, taxane, or both. Therefore, we sought to evaluate the antitumor efficacy of 5-fluorouracil (5-FU) in patient-derived xenografts (PDXs) from residual tumors resistant to neoadjuvant chemotherapy.

Methods: Antitumor efficacy of 5-FU was assessed in vivo in three PDXs varying in hormone receptor status (0, 4% and 11% respectively), generated from residual tumors of primary breast cancer patients treated with neoadjuvant chemotherapy containing anthracycline, and taxanes. In addition, significance of timing of therapy was also assessed, comparing efficacy of initiating treatment upon implantation (immediate start cohort; mimicking treating residual disease with adjuvant therapy), with initiating treatment upon establishment of PDX (standard start cohort).

Results: 5-FU was efficacious in established PDX models that are triple negative (0% ER; p< 0.0001), low ER positive (4% ER, p=0.0213) and ER-positive (11% ER; p= 0.0390), decreasing growth compared to the cohort. However, there was no statistically significant difference between the immediate start cohort and standard start cohort. Western blot analysis of the treatment-naïve derived mouse tumors recognized RB as a predictive biomarker for 5-FU response.

Conclusion: 5-FU has anti-tumor activity in residual HER2-negative PDX models resistant to taxanes, and anthracyclines in the neoadjuvant setting.

Citation Format: Owusu-Brackett N, Scott S, Yuca E, Evans KW, Tapia C, Meric-Bernstam F. Efficacy of adjuvant 5-Fluorouracil in residual HER2-negative breast cancer following neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-13-04.
Abstract P1-13-08: A prospective non-randomized clinical trial of adjuvant carboplatin chemotherapy in triple negative breast cancer
Authors: Hamm C , Kulkarni S , Gupta R , Mathews J , Amin K , Hussein A , Porter L
Published: May 2019

Background: The addition of carboplatin in the neoadjuvant setting has demonstrated improved outcomes in patients with triple negative breast cancer (TNBC). Carboplatin in the adjuvant setting has not been demonstrated to be an accepted regimen to date. This trial addresses this issue.

Methods: The primary objectives of this study were to assess the toxicity of an adjuvant carboplatin-containing regimen for early stage TNBC patients, and to correlate outcomes with molecular markers including Spy-1. Secondary objectives included determination of progression free (PFS) and overall survival (OS), and comparing these to our institutional historical controls. Patients received the backbone of a dose dense anthracycline, taxane, cyclophosphamide (DD ACT), with the addition of carboplatin.

Results: Ninety patients with stage I to III patients with triple negative breast cancer were accrued to this trial between Jan 2011 and June 2017. We discovered that DD ACT with carboplatin with an AUC of 5 given on the second and last paclitaxel was well tolerated. Chemotherapy delays were minimized when the parameters for administration of the carboplatin was to allow chemotherapy to proceed if the platelet count was >/= 70,000 x10^9/L and dose adjustment of paclitaxel was allowed based on neuropathy. There were no grade 4 adverse events. 4% of patients had grade 3 peripheral neuropathy (PN), 28% had grade 2 PN and 45% had grade 1 PN. Results of molecular profiles will be reported. Univariate analysis are reported, and were found to be very promising. Using log-rank statistic, a trend to improvement in overall survival was found when compared to historical controls (p=0.089). Median follow-up is 24 months. Longer follow-up is necessary to determine PFS and overall survival benefit.

Conclusion: If considering an adjuvant regimen for triple negative breast cancer patients DDAC/TC with the carboplatin administered with an AUC of 5 on the second and fourth taxol of DDACT is a well-tolerated regimen.

Univariate Analysis Comparing Carboplatin vs Historical Controls that did not receive CarboplatinVariableHistorical (no carbo)Carbo containing chemop overall n = 179n = 82 Age56.3 (13.1)49.8 (11.0)< 0.001Stage0.188Stage I47 (26.3%)15 (18.3%) Stage II88 (49.2%)50 (61.0%) Stage III44 (24.6%)17 (20.7%) Grade0.011Grade 18 (4.5%)0 (0.0%) Grade 233 (18.4%)7 (8.8%) Grade 3138 (77.1%)73 (91.2%) Remission Status0.009In Remission126 (70.4%)70 (86.4%) Relapsed53 (29.6%)11 (13.6%) Survival< 0.001Alive121 (67.6%)73 (90.1%) Deceased58 (32.4%)8 (9.9%) 

Citation Format: Hamm C, Kulkarni S, Gupta R, Mathews J, Amin K, Hussein A, Porter L. A prospective non-randomized clinical trial of adjuvant carboplatin chemotherapy in triple negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-13-08.
Abstract P1-15-01: Withdrawn
Authors: Metzger Filho O , Janiszewska M , Guo H , Yardley D , Mayer I , Spring L , Arteaga C , Wrabel E , DeMeo M , Freedman R , Tolaney S , Waks A , Bardia A , Parsons H , Partridge A , Mayer E , King T , Polyak K , Viale G , Winer E , Krop I
Published: May 2019

This abstract was withdrawn by the authors.

Citation Format: Metzger Filho O, Janiszewska M, Guo H, Yardley D, Mayer I, Spring L, Arteaga C, Wrabel E, DeMeo M, Freedman R, Tolaney S, Waks A, Bardia A, Parsons H, Partridge A, Mayer E, King T, Polyak K, Viale G, Winer E, Krop I. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-15-01.
Abstract P1-15-24: Randomized phase II trial to evaluate chemoradiotherapy vs radiotherapy among non-responders breast cancer patients treated with chemotherapy
Authors: Ramos M , Arce C , Lara F , Alvarado A , Castañeda N
Published: May 2019

Background:

Among patients with locally advanced breast cancer (LABC), preoperative systemic treatment is the standard of care; approximately 80% of the patients treated with neoadjuvant chemotherapy present partial or complete clinical response, however there are patients who progress during this therapy or at the end of it, the tumors remain inoperable, this confers a worse prognosis, with an increase in the rates of metastasis and decrease overall survival. The benefit of concomitant chemoradiotherapy in local control is controversial. The objective of this trial is to analyze the efficacy of local control and survival in patients with locally advanced breast cancer who received systemic treatment plus chemoradiotherapy or radiotherapy alone preoperatively.

Patients and Methods

Prospective, randomized, open label trial; patients with LABC whom after neoadjuvant chemotherapy based con anthracyclines and taxanes have disease progression or inoperable disease. Arm A (standard) received radiotherapy (RT) 50 Gy in 25 fractions or chemoradiotherapy (CRT)(gemcitabine 100 mg/m2 plus cisplatin 30 mg/m2) weekly during radiation. The primary endpoint was local recurrence. Secondary end points included systemic recurrence, overall survival and -surgical complications. Statistical analysis was done with SPSS v 20.0, groups comparison was done with X2, survival was analyzed with Kaplan-meier method and comparison among groups with log-rank. Proportional Cox model associate clinical variables with recurrence and death. Local ethics committee approves the trial.

Results:

78 patients were included, median follow-up was 116 months (110-121) at this time, 37 patients had recurrence (local, systemic or both) of which 18 were treated with CRT vs 19 RT alone (51.4 vs 44.2%, p=0.34). Higher rates of local recurrence were in RT alone 63.1% vs 38.9% with chemoradiotherapy with significance difference (p=0.004).

There were no differences in disease free survival (p=0.542) and overall survival was found (p=0.303), 57.1 vs 53.5% respectively. Proportion of surgical complications were similar 71.4% for CRT vs 69.8% for RT (p=0.848). However hematological and gastrointestinal toxicity were more prevalent in patients treated with CRT p<0.005

Conclusion:

Chemoradiotherapy it´s a feasible option to reduce the risk of local recurrence, however without any additional benefit to improve the recurrence-free survival or overall survival. Surgical complications are still the same.

Citation Format: Ramos M, Arce C, Lara F, Alvarado A, Castañeda N. Randomized phase II trial to evaluate chemoradiotherapy vs radiotherapy among non-responders breast cancer patients treated with chemotherapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-15-24.
Abstract P1-19-04: Withdrawn
Authors: Fitzpatrick A , Isacke C , Tutt A
Published: May 2019

This abstract was withdrawn by the authors.

Citation Format: Fitzpatrick A, Isacke C, Tutt A. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-19-04.
Abstract P1-20-03: Withdrawn
Authors: Dillon SR , Evans LS , Rickel E , Lewis KE , Swanson R , Levin SD , Wolfson M , Peng SL , Swiderek KM
Published: May 2019

This abstract was withdrawn by the authors.

Citation Format: Dillon SR, Evans LS, Rickel E, Lewis KE, Swanson R, Levin SD, Wolfson M, Peng SL, Swiderek KM. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-20-03.
Abstract P2-01-06: Intravital imaging of the lung reveals the efficiency of the metastatic cascade
Authors: Coste AH , Boriello L , Wang Y , Oktay M , Condeelis JS , Entenberg D
Published: May 2019

Background: Breast cancer is the leading cause of cancer related-death in women[1] with over 90% of these deaths due to metastasis. In these cases, the lung is the most common anatomical site of metastasis found at autopsy[2]. For the last 100 years, the process of metastasis has been studied through the use of an experimental metastasis (EM) assay [3] consisting of tail vein injection of tumor cells into tumor-free mice, followed by histopathological analysis of the lung weeks later to gain insight into tumor cell arrival, survival, and the growth of metastases. These studies have concluded that metastasis is an inefficient process[4]. Using a new technology developed at Albert Einstein College of Medicine, called the Window for High Resolution Imaging of the Lung (WHRIL)[5], we have directly compared EM to the more clinically relevant process of tumor cells spontaneously metastasizing (SM) from a primary tumor in situ to the lung and have found significant differences in metastatic efficiency between EM and SM.

Methods: Real-time images of tumor cell dissemination were captured using the WHRIL (Figure 1) in both EM and SM models. Metastatic potential was analyzed, and compared between the models, the percentage of tumor cells surviving in the lung over time, their endothelial crossing-time, their frequency of interaction with macrophages, the fraction of cells which are dormant, and the percent of cells that developed into metastases.

Results: Tumor cells which spontaneously metastasize from primary tumors show a ten-fold higher rate of survival in the lung and three times greater efficiency in forming metastases compared to those directly injected into the lung vasculature. Most of SM tumor cells are dormant indicating that the residual disease phenotype is programmed by the primary tumor either directly in the primary site or indirectly at the secondary site.

Conclusion: These results indicate that experimental metastasis does not accurately reflect the true clinical process and that spontaneous dissemination from a primary tumor has significant influence on the survival and growth of disseminated cells. This suggests that the tumor microenvironment of the primary tumor educates disseminating tumor cells for survival, dormancy and growth at the primary site, and/or prepares the pre-metastatic niche, in the secondary site. Understanding where and how disseminated tumor cells are educated is critical to preventing their survival and growth.at secondary sites. This discovery will open the door to new strategies for the treatment of metastatic tumors to prevent metastatic progression and death.

Citation Format: Coste AH, Boriello L, Wang Y, Oktay M, Condeelis JS, Entenberg D. Intravital imaging of the lung reveals the efficiency of the metastatic cascade [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-01-06.
Abstract P2-01-14: Adipocytes and cancer cell interactions promote leptin receptor expression and drive β-catenin-mediated progression in triple negative breast cancer
Authors: Feng Z , Tao Z , Hu X
Published: May 2019

Background Triple negative breast cancer (TNBC) patients suffer from poor prognosis due to short-term recurrence and/or metastasis. Obesity is reported to predict poor prognosis of TNBC. However, the mechanisms connecting obesity to progression of TNBC remain unclarified.

Methods We co-cultured TNBC model cells with adipocytes differentiated from human adipose-derived mesenchymal stem cells (hMSC-ad) and TNBC patients derived primary adipocytes to examine migration, invasion and metastasis abilities using Transwell assays and tail vein injection xenograft mouse model, respectively. Expression levels of leptin receptor (LEPR) , epithelial-mesenchymal transition (EMT) markers and β-catenin signaling pathway related molecules in the control and co-cultured TNBC model were analyzed by real time quantitative polymerase chain reaction (RT-qPCR) and western blot assays. Downregulation of LEPR by LEPR specific short hairpin RNA (shRNA) and upregulation of the downstream pathway with continuous activated β-catenin were applied to access their roles in adipocytes and cancer cell interactions. Degree of adipocytes infiltration in tumor tissue was evaluated by histopathology. LEPR mRNA expression level in breast cancer and corresponding patients' information was retrieved from The Cancer Genome Atlas (TCGA) database.

Results Here we first reported that both hMSC-ad- and patients-derived adipocytes promoted migration and invasion of TNBC model cells in vitro and lung metastasis in vivo. Adipocytes were then confirmed to induce upregulation of LEPR in each TNBC model cell compared to the control groups (p<0.0001), resulting in higher expression of EMT markers and molecules related to β-catenin signaling pathway.Afterwards, LEPR knockdown led to decreased migration, invasion and metastasis capacities, as well as reduced expression of EMT markers and molecules related to ?-catenin signaling pathway, while activation of ?-catenin could restore robust EMT and metastatic abilities of TNBC model cells. Last, clinical specimen analyses showed that infiltration of adipocytes to tumor tissue was significantly associated with shorter DFS of TNBC patients (p<0.05) and upregulated LEPR in breast cancer tissue indicated poor prognosis (median OS of 7.43 vs 10.81 years of the LEPR-low group, p < 0.05).

Conclusions To our knowledge, adipocytes are first shown to promote progression of TNBC via previously uncharacterized LEPR-β-catenin signaling pathway.

Citation Format: Feng Z, Tao Z, Hu X. Adipocytes and cancer cell interactions promote leptin receptor expression and drive β-catenin-mediated progression in triple negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-01-14.
Abstract P2-01-18: Withdrawn
Authors: Abdullah A , Tao A , Wendt MK
Published: May 2019

This abstract was withdrawn by the authors.

Citation Format: Abdullah A, Tao A, Wendt MK. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-01-18.