bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P1-20-25: Impact of lumpectomy for diagnosis of primary tumor on disease free survival in women with operable breast cancer: An institutional audit
Authors: Nair Nita Sukumar , Hawaldar Rohini W , Chougle Quarratulain , Parmar Vani , Vanmali Vaibhav , Siddique Shabina , Devade Ashwini , Pandey Aarti , Joshi Shalaka , Gupta Sudeep , Badwe Rajendra A
Published: March 2020

Introduction: As a tertiary referral cancer centre, 20-30 % of patients seen in our breast clinic present after excision of the primary breast tumour without oncological principles maintained and no details on the excision margins. We evaluated the safety of excision biopsy (ExBx) as a diagnostic procedure by comparing the outcomes against patients who underwent definitive surgery after a core biopsy/FNAC (CxBx) for diagnosis.

Methods: We performed a retrospective audit of the case charts of women with breast cancer treated at our institution. We included women with operable breast cancer (OBC) who presented post ExBx of the primary tumour and those who were treatment naïve and operated after only a CxBx for diagnosis.

Results: Of the 1022 women included in the analysis, 551 underwent ExBx for primary diagnosis and 471 had CxBx prior to definitive breast surgery. The excision biopsy group were younger women (median age 44 years) with smaller tumours (median T size 2.5cm), lower HR ( hormone receptor) positive (58.3%) and less number were Her2+ve (16.7 %). In this group 17% received NACT, with 66.4% undergoing breast conservation surgery (BCS), and 37.6% node positive. While in the core biopsy group, the women were older women (median age 50 years) had larger tumours, median 3 cm, with 71.3% HR positive, 18.3% Her2 +ve, 72.8% underwent breast conservation surgery with 44.6 % node positive At a median follow up of 46 months, there was no difference in four year disease free survival (DFS) between ExBx group (83.8% versus 86.8%) and non-ExBx (HR=1.29,95%CI=0.93-1.79, p=0.13). When matched for T size, 699/1022 (69%) had T2 tumours and DFS in ExBx group was 80.7% in compared to 85.7% in non ExBx group. (HR=1.46, 95%CI=1.0-2.11, p=0.04). On multivariate cox regression, T size (HR=1.45,95%CI=1.02-2.07, p=0.03), HR negative (HR=1.61,95%CI=1.15-2.26,p=0.006), node positivity (HR=1.82,95%CI=1.31-2.53,p<0.01) and ExBx done (HR=1.40,95%CI=0.99-1.98,p=0.053) had a detrimental impact on disease free survival.

Conclusion: ExBx of the primary tumour as a diagnostic procedure not performed with oncological principles prior to definitive surgery has a detrimental impact on survival in women with operable breast cancer.

Citation Format: Nita Sukumar Nair, Rohini W Hawaldar, Quarratulain Chougle, Vani Parmar, Vaibhav Vanmali, Shabina Siddique, Ashwini Devade, Aarti Pandey, Shalaka Joshi, Sudeep Gupta, Rajendra A Badwe. Impact of lumpectomy for diagnosis of primary tumor on disease free survival in women with operable breast cancer: An institutional audit [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-20-25.
Abstract P1-20-27: Changes in the shoulder range of motion, strength after breast cancer surgery: An observational study
Authors: Min Jihee , Yeon Sujin , Min Jinjoo , Kim Jee Ye , Kim Seung Il , Park Ha-Nui , Lee Jeong min , Jeon Justin Y.
Published: March 2020

Purpose: The importance of rehabilitation after breast surgery is valued, yet changes in range of motion (ROM) and shoulder strength after surgery have not been elucidated. The aim of this study was to explore the shoulder ROM and strength in both surgery (SS) and non-surgery side (NSS) after breast cancer surgery for up to four weeks.

Methods: Twenty-five patients (7 total mastectomy, 18 partial mastectomy) were observed five times: the day before surgery, on discharge day (post operate day; POD 1 or 2), the 1st outpatient visit (POD 7-10), the 2nd outpatient visit (POD 14-15), and 3rd outpatient visit (POD 21-25). The primary outcomes were ROM and strength of both the SS and NSS.

Results: While ROM declined only in the shoulder of the SS, shoulder strength declined in both SS and NSS. Greatest reduction in shoulder strength was observed in flexion (SS: -43.9% to -45.3%, NSS: -14.2% to -35.8%) and abduction in both SS and NSS (SS: -41.1% to -52.5%, NSS: -16.3% to -30.6%). Shoulder strength on the SS decline immediately after surgery, which remained low after four weeks. Shoulder strength of the NSS continually declined after surgery up to four weeks.

Conclusion:These results provide preliminary evidence for clinicians to understand the changes of shoulder ROM, strength, and function after surgery in breast cancer patients. Rehabilitation exercises should be implemented in both SS and NSS.

Citation Format: Jihee Min, Sujin Yeon, Jinjoo Min, Jee Ye Kim, Seung Il Kim, Ha-Nui Park, Jeong min Lee, Justin Y. Jeon. Changes in the shoulder range of motion, strength after breast cancer surgery: An observational study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-20-27.
Abstract P2-05-07: Pan-cancer analysis of PARP inhibition reveals a suite of biomarkers that correlate with PARP1/2 activity in breast cancer
Authors: McDermott Martina SJ , Conklin Dylan F , O'Brien Neil A , Chau Kevin , Slamon Dennis J
Published: March 2020

The development of multiple PARP inhibitors in BRCA mutant cancers has been one of the most successful implementations of molecularly targeted therapies in oncology. The recent approval of niraparib in BRCA WT Ovarian cancers demonstrates the potential for expansion of PARP inhibitors to other BRCA WT indications. The successful development of PARP inhibitors into new cancer indications will depend on using molecular biomarkers to identify tumors with a unique dependency on PARP1/2 activity. We screened a large (N=523), diverse panel of human cancer cell lines for response to three approved PARP inhibitors: olaparib, niraparib, and talazoparib. Despite differences in relative potency, there was a strong correlation between sensitive and resistant cell lines to all three compounds. In vitro experimentation revealed the inhibitors share a similar biologic mechanism of response, namely a global decrease in PARylation, as well as PARP-trapping at DNA nicks leading to G2 arrest and ultimately cell death. A suite of baseline genomic and proteomic characteristics were found to be strongly associated with response to PARP1/2 inhibition, and were largely consistent between different cancer types. Special attention was paid to BRCA1/2 variants, which represent the only approved patient selection biomarkers. Notably, neither mutations in BRCA1 nor BRCA2 were found to be associated with response to PARP1/2 inhibition in our panel, even when restricting to those with confirmed deleterious ClinVar scores. The molecular predictors of response identified in our screen may ultimately be used to develop diagnostic tools for enrollment into biomarker-enriched clinical trials to expand the use of this promising class of drug into areas of high unmet need. Triple-negative breast cancer represents one of the most intriguing spaces for development. The clinical failures in this space may be partially explained by the lack of empirical predictive biomarkers in the trial design. Our diagnostics may finally allow for the efficacious deployment of PARP inhibitors to triple-negative breast cancer. In particular we have identified a panel of biomarkers that can predict for sensitivity to PARP inhibitors in breast cancer that could be used as patient selection criteria for the expanded clinical development of these compounds into PARP-naïve patient populations with high unmet need.

Citation Format: Martina SJ McDermott, Dylan F Conklin, Neil A O'Brien, Kevin Chau, Dennis J Slamon. Pan-cancer analysis of PARP inhibition reveals a suite of biomarkers that correlate with PARP1/2 activity in breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-05-07.
Abstract P2-09-08: Breast cancer tumor sequencing coupled with germline genetic testing aids the identification of at-risk individuals for hereditary breast cancer disorders
Authors: Pineda-Alvarez Daniel E , Michalski Scott T , Russell Meaghan , Yang Shan , Song Ihn Young , Nussbaum Robert L , Esplin Edward D.
Published: March 2020

Background: With the rise of precision medicine, hereditary cancer germline testing and tumor genetic testing have been increasingly used to inform the management of patients with cancer. Recent studies report that approximately 10% of patient’s tumors have clinically significant variants in genes known to predispose to a hereditary cancer syndrome. Here we report the concordance rate between tumor genetic testing and germline genetic testing in patients with breast cancer and review its impact on the patients’ management and implications for their relatives.

Methods: In this study, we used de-identified data from 101 consecutive patients with breast cancer who underwent tumor genetic testing followed by germline testing with NGS-based hereditary cancer gene panels.

Results: Tumor genetic testing results included likely pathogenic or pathogenic (LP/P) variants in BRCA2 (21%), BRCA1 (20%), TP53 (10%), CDH1 (7%), ATM (4.3%), PALB2,CHEK2, and PTEN (3.7% each), and PIK3CA (2.5%) among 22 other genes. In 33/101 cases (33%) the P/LP variant was also detected in the germline. Genes in which disease-causing variants were most frequently confirmed to be in the germline included: BRCA2 (36%), BRCA1(21%), PALB2 (12%), and CHEK2 (12%). Variants in ATM, FH, FANCA, and MSH6 were confirmed in the germline in <10% of patients with variants in these genes. Variants in the TP53, CDH1, and PIK3CA genes were detected in the tumor but not in the germline. In 1 case a pathogenic germline variant was detected in the BRIP1 gene but not reported in the tumor, because the gene was not included in the tumor testing panel.

Conclusions: A significant proportion (33%) of patients with clinically significant variants in tumors were identified to carry the same variant in the germline, uncovering a previously unknown risk of hereditary breast cancer disorder. Notably, some genes had a high probability of variants occurring in the germline, while others were primarily seen in tumors. Performing simultaneous germline and tumor testing may inform susceptibility to a hereditary cancer disorder, identify targets for precision therapy, early detection of secondary malignancies, and guide genetic counseling for relatives.

Citation Format: Daniel E Pineda-Alvarez, Scott T Michalski, Meaghan Russell, Shan Yang, Ihn Young Song, Robert L Nussbaum, Edward D. Esplin. Breast cancer tumor sequencing coupled with germline genetic testing aids the identification of at-risk individuals for hereditary breast cancer disorders [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-09-08.
Abstract P2-10-11: Participation of African Americans in clinical trials supporting FDA approval of breast cancer medications
Authors: Hadidi Samer Al , Mims Martha , Miller-Chism Courtney , Kamble Rammurti
Published: March 2020

BACKGROUND African Americans comprise 12% of the total United States population. Lifetime probability of developing cancer in African Americans is 37.55%. Lifetime probability of developing breast cancer in African Americans is 11.1%. African Americans have higher lifetime probability of dying because of breast cancer compared to Caucasians (3.3% versus 2.7%). Concerns exist that African Americans are underrepresented in trials of breast cancer medications. We sought to examine African Americans participation for pivotal breast cancer medications trials submitted to the U.S. Food and Drug Administration (FDA) supporting marketing applications. METHODS On the basis of publicly available FDA reviews, the authors assessed enrollment of African Americans in trials supporting 9 drug approvals from 2014 to 2018. Those trials resulted in approval of medications to treat breast cancer. Prevalence-corrected estimates for the participation of African Americans were calculated as the percentage of African Americans among trial participants divided by the percentage of African Americans in the disease population (participation to prevalence ratio [PPR]), with a range between 0.8 and 1.2 reflecting similar representation of African Americans in the trial and disease population. RESULTS A total of 22,075 patients enrolled in clinical trials, which resulted in subsequent FDA approval. The proportion of African Americans enrolled in the clinical trials that led to breast cancer medication approval in the 5-year period was 6.83%. The calculated PPR for participation of African Americans in clinical trials that led to drug approval for breast cancer was 0.29. CONCLUSIONS African Americans were under represented in trials of drugs for breast cancer. Efforts should be made to increase the proportion of participation of African Americans in clinical trials.

Citation Format: Samer Al Hadidi, Martha Mims, Courtney Miller-Chism, Rammurti Kamble. Participation of African Americans in clinical trials supporting FDA approval of breast cancer medications [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-10-11.
Abstract P2-12-11: Does goserelin have an effect on quality of life in women who have chemotherapy for early breast cancer? Results from the OPTION randomised trial
Authors: Leonard Robert CF , Mansi Janine , Yellowlees Ann , Fallowfield Lesley , Jenkins Valerie
Published: March 2020

The OPTION trial examined whether or not premenopausal women with early breast cancer receiving chemotherapy benefited from ovarian function protection with goserelin. This trial showed some preservation of ovarian function and fertility in women aged 40 years or less*. Additionally the OPTION trial examined the immediate and late impact of treatments on patients’ Quality of Life (QoL) over a 5 year period. Patients and Methods: In the OPTION trial 227 pre-menopausal patients with early stage breast cancer were randomly assigned to chemotherapy with or without goserelin. Patients were stratified by age into ≤40 years and > 40 years of age. QoL was assessed with the Functional Assessment of Cancer Therapy - Breast (FACT-B) and Endocrine Symptom checklist(ES) at baseline (pre- treatment), 3, 6, 12, 18 and 24 months, then annually to 5 years. Results:-Two hundred and thirteen patients were available for analysis of QoL results. There was a temporary increase in endocrine symptoms of menopause in the goserelin group that was statistically higher than in the controls (P = 0.02) and was associated with a decrease in the main outcome measure of global QoL, TOI. This contrasted with a longer term outcome favouring the intervention in terms of QoL and fewer adverse endocrine symptoms, though these later findings were not statistically significant. Conclusions: Cytotoxic chemotherapy with or without goserelin causes a short term decrement in QoL for up to 6 months in otherwise well women.* Ann Onc 2017 28 1811-1816.

Citation Format: Robert CF Leonard, Janine Mansi, Ann Yellowlees, Lesley Fallowfield, Valerie Jenkins. Does goserelin have an effect on quality of life in women who have chemotherapy for early breast cancer? Results from the OPTION randomised trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-12-11.
Abstract P2-13-20: Conditional survival of female breast cancer patients by treatment patterns: Evidence from the Korean nationwide registry
Authors: Song Eun Jin , Jung So-Youn , Kim Young Ae , Kong Sun-Young , Lee Eun Sook , Lee Eun-Gyeong , Jo Heein , Han Jae Hong , Lee Seeyoun , Kang Han-Sung
Published: March 2020

Objective: With the development of breast cancer treatment, the prognosis of breast cancer patients is getting better over time. Breast cancer patients want to get accurate information about prognosis according to the treatment pattern. In this study, we investigated the 5-year Conditiona relative survival (CRS) of Korean female breast cancer patients.

Materials and Methods: The data from this study was collected from the Korean Central Cancer Registry (KCCR) data, National Health Insurance Service (NHIS) data and Korean Statistical Information Service (KOSIS) data to certify relative survival and conditional relative survival for the female patients of breast cancer in the Korea. We identified 141,779 female breast cancer cases diagnosed between 2002 and 2013. The CRS was estimated for every year after diagnosis, according to age, stage at diagnosis, histologic type, year at diagnosis and treatment patterns within 1year after diagnosis.

Results: The 5-year RS at diagnosis was 91.0% and the 10-year RS was 85.9%. The 5-year CRS was 91.1% and 94.3% at 1 year and 5 years after diagnosis, respectively. Very young and very old patients had worse 5-year CRS after 5 years of survival than those of other age groups (89.6% in the <40-year and 84.4% in the ≥70-year groups vs. 92.6% in 40-54-year, and 90.3% in 55-69-year groups). Patients who underwent surgery within one year after diagnosis of breast cancer showed better 5-year CRS than those who did not (94.0% vs 65.6%). The 5-year CRS was 91.8% and 89.9% according to whether systemic therapy (chemotherapy and targeted therapy) was performed after diagnosis of breast cancer. The 5-year CRS of the anti-hormone treatment group was 95.2%, which was higher than that of the non-hormone treatment group. In the group without antihormonal therapy, there was a different 5-year CRS according to the histological characteristics (89.8% in NST type, 83.5% in lobular type, 97.3% in mucinous type, 98.5% in medullary type and 86.3% in metaplastic type).

Conclusions: This study shows that the improvement pattern of CRS may vary according to age group, treatment pattern, and histologic type. In the group without antihormone therapy, the histologic type seems to be a different aspect of CRS, which is useful information for clinicians and patients.

Key words: conditional survival, breast cancer, histology, age, stage, treatment pattern

Citation Format: Eun Jin Song, So-Youn Jung, Young Ae Kim, Sun-Young Kong, Eun Sook Lee, Eun-Gyeong Lee, Heein Jo, Jae Hong Han, Seeyoun Lee, Han-Sung Kang. Conditional survival of female breast cancer patients by treatment patterns: Evidence from the Korean nationwide registry [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-13-20.
Abstract P2-14-05: Adjuvant chemotherapy in elderly women with triple-negative breast cancer: Swedish registry data 2009-2017
Authors: Janeva Slavica , Zhang Chenyang , Kovács Anikó , Parris Toshima Z , Tzikas Anna-Karin , Pezzi Christopher M , Audisio Riccardo A , Bagge Roger Olofsson
Published: March 2020

Background: Breast cancer incidence is strongly related to age, with the highest incidence rates being in elderly women. Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer associated with worse survival. Due to competing mortality risks and co-morbidities, TNBC in the elderly is often under-treated with adjuvant chemotherapy. The aim of this study was to investigate if there is a gain in both breast cancer specific survival (BCSS) and overall survival (OS) with adjuvant chemotherapy in elderly patients with TNBC.

Method: Information from all patients 70 years and older diagnosed with primary TNBC during the years 2009-2017 were retrieved from the Swedish National Register for Breast Cancer, the Swedish Cause of Death Register and the Swedish Patient Register. Both a propensity score matched (PSM) model and a Cox-regression model was created examining the effect of age, tumor size, tumor grade, nodal status, co-morbidities (Charlson/Deyo) and chemotherapy treatment, on BCSS and OS.

Results: Of the 1421 patients included, 428 (30.1%) received chemotherapy. The 5-year BCSS was 84% vs. 62% in favor for patients receiving chemotherapy. The 5-year OS was 80% vs. 46% in favor for patients receiving chemotherapy. When adjusting for the co-variates using PSM, the 5-year BCSS was 84% vs. 73% (p<0.004) and the 5-year OS was 79% vs. 62% (p<0.001) favoring chemotherapy.

Discussion: In this PSM registry analysis including all patients ≥70 years in Sweden with TNBC during a 9-year period, we could show that there was a significant benefit in both BCSS and OS with adjuvant chemotherapy when adjusting for both age and co-morbidities.

Cox multivariate regression model for breast cancer specific survivalHazard Ratiop-value95% CIChemotherapy0.6020.0020.435-0.834Age (years)1.0510.0001.030-1.072Tumor size (mm)1.0170.0001.012-1.022Stage N11.9090.0001.488-2.450Stage N24.8550.0011.978-11.916Stage N31.9060.5210.266-13.637Grade 21.0140.9790.365-2.813Grade 31.6220.3400.601-4.374Charlson score1.1940.0570.995-1.433

Citation Format: Slavica Janeva, Chenyang Zhang, Anikó Kovács, Toshima Z Parris, Anna-Karin Tzikas, Christopher M Pezzi, Riccardo A Audisio, Roger Olofsson Bagge. Adjuvant chemotherapy in elderly women with triple-negative breast cancer: Swedish registry data 2009-2017 [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-14-05.
Abstract P2-14-21: Adjuvant chemotherapy-associated lipid changes in breast cancer patients: A retrospective analysis
Authors: He Tao , Wu Yunhao , Zhang Xinyi , Chen Jie
Published: March 2020

Background: Adjuvant chemotherapy may cause alterations in serum lipids in postoperative breast cancer (BC) patients, but the specific alterations caused by different chemotherapy modalities remain unclear. The aim of this study was to investigate the status of serum lipids pre- and post-chemotherapy and to compare lipid level alterations among different chemotherapy modalities. Methods: We retrospectively analysed the lipid profiles of 1934 consecutive postoperative BC patients who received one of the following chemotherapy modalities: doxorubicin and cyclophosphamide followed by paclitaxel (AC-T); epirubicin and cyclophosphamide followed by paclitaxel (EC-T); cyclophosphamide and paclitaxel (TC); and fluorouracil, cyclophosphamide and epirubicin (FEC). Results: The levels of triglycerides (TGs), total cholesterol (TC) and low-density lipoprotein (LDL) were significantly elevated in patients who received chemotherapy (p<0.01). With respect to different chemotherapy modalities, AC-T elevated the lipid profiles more than FEC in premenopausal patients (p<0.05), while in postmenopausal patients, FEC had the smallest effects in terms of high-density lipoprotein (HDL) and LDL compared with the effects of other chemotherapy modalities (p<0.05). In addition, premenopausal BC patients had a higher incidence of dyslipidaemia (18.84%) after chemotherapy than postmenopausal BC patients (12.27%). Moreover, after adjusting for multiple baseline covariates, AC-T chemotherapy modality was still statistically associated with a high level of TGs after chemotherapy. Conclusions: BC patients receiving chemotherapy may have a high risk of dyslipidaemia, but the effects vary with different chemotherapy modalities. Therefore, it is necessary to take lipid metabolism into consideration when making chemotherapy decisions and to monitor serum lipids regularly during chemotherapy.Key words: Breast cancer; Adjuvant chemotherapy; Dyslipidaemia

Citation Format: Tao He, Yunhao Wu, Xinyi Zhang, Jie Chen. Adjuvant chemotherapy-associated lipid changes in breast cancer patients: A retrospective analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-14-21.
Abstract P2-15-13: A time-and-motion study of chemotherapy administration in metastatic breast cancer
Authors: Schwartzberg Lee , Chatterjee Debanjana , Knoth Russel , Gibbs Sarah N , Ahmed K Hamzah , Broder Michael S , Yermilov Irina
Published: March 2020

Background: Ordering and delivering chemotherapy is complex, impacting patient and caregiver quality of life. Metastatic breast cancer (mBC) patients receive intravenous chemotherapy with variable administration times and patient satisfaction may differ by session length. We investigated common chemotherapy agents for mBC through a time and motion analysis. Methods: We conducted a prospective, observational time-and-motion study of adult females with mBC receiving ≥ 2nd-line eribulin, vinorelbine (VI), or gemcitabine (GC) at a large community oncology clinic. An observer documented times events occurred (Table). Patients completed a satisfaction survey adapted from Agency for Healthcare Research and Quality’s cancer care survey and the Cancer Therapy Satisfaction Questionnaire. Event times were compared using t-test. Spearman’s rank correlation was used to test correlations between time and satisfaction. Results: 17 patients (11 eribulin, 6 VI/GC) comprising 31 observations (20 eribulin, 11 VI/GC) were included in the preliminary analysis. Patients were 65 years on average, 71% white, and 94% post-menopausal; all were HER-2-. Mean years since mBC diagnosis was lower for eribulin than VI/GC patients (1.7 vs 5.0, p<0.009). Chemotherapy administration was shorter for eribulin patients (Table). 82% of patients were very satisfied with their cancer care experience; satisfaction did not correlate with event times. Conclusions: Eribulin administration time was significantly lower than VI/GC in mBC patients while maintaining similar satisfaction levels. These preliminary results demonstrate novel treatments for mBC can shorten treatment administration time while providing patient-centered, coordinated care. Table. Observation by event (mean minutes)

All observationsEribulin Vinorelbine/ GemcitabineP value *<0.05Chair time (total time patient was in chair)7367840.174Chemotherapy ordered to chemotherapy end5449610.080Chemotherapy ordered to discharge6557740.111Chemotherapy arrived chair-side to chemotherapy end1510230.003*Chemotherapy arrived chair-side to discharge2620370.007*Chemotherapy administration (medication start to end)116200.001*

Citation Format: Lee Schwartzberg, Debanjana Chatterjee, Russel Knoth, Sarah N Gibbs, K Hamzah Ahmed, Michael S Broder, Irina Yermilov. A time-and-motion study of chemotherapy administration in metastatic breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-15-13.
Abstract P2-15-15: Evaluation of the efficacy and safety of the combination of Gemcitabine and Nedaplatin for patients with metastatic breast cancer
Authors: Yue Jian , Yuan Peng , Hu Nanlin , Si Yiran , Wang Xue
Published: March 2020

Background: Owing to the need for the effective and tolerable new regimens for the treatment of patients with metastatic breast cancer (MBC) previously treated with anthracyclines and/or taxanes, we aimed to assess the activity and safety of the gemcitabine plus nedaplatin combination chemotherapy.

Methods: Forty-five patients were enrolled. All the patients received gemcitabine and nedaplatin from November 2014 to February 2019.Gemcitabine 1000mg/m2 was administered on days 1 and 8. nedaplatin 60mg/m2 was given over 60mins on day 2 and 3. The primary end point was the overall response rate (ORR). Secondary objectives included overall survival (OS), progression-free survival (PFS), toxicity, and predictive factors.

Results: Patients received treatment for a median of four Cycles. One of the 45 patients achieved a complete response, but 21 achieved a partial response, for an overall response rate of 48.9(95% confidence interval,33.7-64.1%). The median overall survival time was 17 months and the median progression-free survival was 5.0 months. Grades 3-4 hematological toxicities include leukopenia in 22.2% of patients, neutropenia in 28.9%, thrombocytopenia in 17.6%. Grade 3-4 nonhematological toxicities included nausea and vomiting in 31.1% of patients. There were no treatment-related deaths.

Conclusion: The combination of gemcitabine and nedaplatin is an effective and tolerable treatment for MBC previously treated with anthracyclines and/or taxanes.

Table 1 Patient characteristicPatient characteristicNumber of patients45Age53(29-72)Molecular subtypeLuminal A9Luminal B14HER2 positive1Triple negative21

Table 2: Response rateNumber of patients(n=45)%Complete response12.2Partial response2146.7Stable disease1635.6Progressive disease715.6

Table 3 Non-hematological toxicityToxicityGrade≥3(%)1234Nausea/vomiting1512204.4Elevation of transaminase173000Alopecia63000

Table 4 Hematological toxicityToxicityGrade≥3(%)1234Leukopenia14159122.2Neutropenia13129428.9Thrombocytopenia124417.8Anemia224000

Figure 1 progression-free survival time

Figure 2 Overall survival time from the start of treatment with gemcitabine and nedaplatin.

Citation Format: Jian Yue, Peng Yuan, Nanlin Hu, Yiran Si, Xue Wang. Evaluation of the efficacy and safety of the combination of Gemcitabine and Nedaplatin for patients with metastatic breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-15-15.
Abstract P2-16-20: Treatment outcomes in triple negative breast cancer patients undergoing neoadjuvant chemotherapy. The importance of Ki-67
Authors: Rapoport Bernardo Leon , Barnard-Tidy Jacqui , van Eeden Ronwyn , Smit Teresa , Nayler Simon , Benn Carol
Published: March 2020

Aim of study: The aim of this retrospective project is to evaluate the treatment outcomes including pathological complete response (pCR), time to progression and overall survival in patients (pts) treated with taxane, and/or anthracycline/alkylating agents based neoadjuvant chemotherapy (NAC).

Background: Ki-67 immunohistochemical determination is a widely used biomarker of cell proliferation in pts undergoing endocrine treatment for breast cancer. The role of Ki-67 in triple negative breast cancer (TNBC) pts undergoing NAC for early disease remains controversial. Pathological Complete Response following NAC has been proposed as a prognostic indicator of long-term outcome.

Methods: We analyzed retrospectively data on 86 pts with TNBC. Pathological complete response (pCR) was defined as the complete disappearance of the invasive cancer in the breast and absence of tumor in the axillary lymph nodes examined by axillary clearance. The purpose of this analysis was to investigate factors associated with combined pCR.

Results: There were 35 pCR’s (40.7%). At 2 years 82% of pts who attained a pCR were disease free compared to 67% of pts who did not attain a pCR (log rank test p < 0.0117). On univariate analysis factors associated with higher combined pCR included primary tumor size (T1=84% vs T2 and T3 =50% of pts, chi2= 6.81, p<0.03317), Ki67 (>30=68% vs. eq or < 30%= 18% of pts, p<0.00020), age (< than 50 =71% vs. equal or >50 =44% of pts), tumor grade (1=88% vs. 2=60% vs. 3=44% of pts, chi2 = 6.2560 p<0.04381) and stage (I= 89% vs. IIA=60% vs. IIB=46% vs. III=40% of pts, p<0.01350). Factors not associated with a higher pCR included menopausal status, extranodal spread and lympho-vascular invasion. In a logistic regression model Ki-67 as a continuous variable (p<0.012577) and age < than 50 (p<0.03318) retained its significance; while tumor size, stage of disease, tumor grade loss significance.

Conclusion: Ki67 and age are independent prognostic factors of pCR in pts with early TNBC undergoing NAC.

Citation Format: Bernardo Leon Rapoport, Jacqui Barnard-Tidy, Ronwyn van Eeden, Teresa Smit, Simon Nayler, Carol Benn. Treatment outcomes in triple negative breast cancer patients undergoing neoadjuvant chemotherapy. The importance of Ki-67 [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-16-20.
Abstract P2-18-09: Effects of diet after early breast cancer treatment: Systematic review and meta-analysis of clinical trials
Authors: Träsel Henrique AV , Falcetta Frederico S , Almeida Fernando K , Falcetta Mariana RR , Rosa Daniela D
Published: March 2020

Purpose: Randomized clinical trials are inconclusive regarding the role of dietary interventions in anthropometric measurements, quality of life, and survival in breast cancer patients. Our aim was to conduct a systematic review and meta-analysis to assess the effects of diet on these outcomes in women who went through curative treatment of early-stage breast cancer.Methods: Pubmed, Embase, Cochrane Library were searched for randomized clinical trial comparing dietary interventions (individualized dietary counseling, prescription of a specific diet or other) with usual care in women that were treated for breast cancer. Primary outcomes were overall survival and disease-free survival, secondary outcomes were weight loss and change in body mass index.Results: We found 12 clinical trials eligible for analysis. Only two of them reported overall and disease-free survival, whereas six reported data for body mass index and four for weight. The HR for mortality and disease-free survival was 0.91 (95% CI 0.77-1,07, p=0.25) and 0.92 (CI 95% 0.79-1.08, p=0.31) for the intervention group compared to the control group, respectively. Diet intervention was associated with body mass index reduction in those subjects who received a specific diet instead of counseling or other types of intervention (-0.67 CI 95% -1.14 to -0.21). The weight did not differ between intervention and control groups.Conclusions: Despite increasing survival among breast cancer patients there is still a lack of prospective data regarding the effects of dietary interventions in this population. We found positive association between prescription of specific diets in terms of anthropometric measure, but neither difference in overall nor disease-free survival.

Citation Format: Henrique AV Träsel, Frederico S Falcetta, Fernando K Almeida, Mariana RR Falcetta, Daniela D Rosa. Effects of diet after early breast cancer treatment: Systematic review and meta-analysis of clinical trials [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-18-09.
Abstract P3-02-06: Tracing glucose catabolism in human triple negative breast cancer tumors
Authors: Ghergurovich Jonathan Michael , O’Shaughnessy Joyce , Levin Maren K , Killian Aaron , Hendricks William , Espina Virginia , Rabinowitz Joshua D
Published: March 2020

Triple negative breast cancer (TNBC) is an aggressive tumor type for which few targeted treatments exist. Altered tumor metabolism may provide novel diagnostic and therapeutic opportunities. Recent genetic analyses in TNBC demonstrate augmented expression of pathways related to glucose metabolism, including glycolysis, the pentose phosphate (PPP), and serine biosynthetic pathways. No studies, however, have directly probed how glucose is utilized by TNBCs in vivo. Here, we trace these metabolic fates by infusing TNBC patients with isotopically labeled 1,2-13C-glucose, a tracer that can determine which of these pathways predominate. Upon achieving stable tracer enrichment in serum, patient primary TNBC biopsies were collected and flash frozen. Subsequent analysis by liquid chromatography mass spectroscopy (LC-MS) revealed most TNBC tumors locally ferment glucose to lactate, with limited exchange of pyruvate/lactate with the systemic circulation. This contrasts with lung cancer, where pyruvate/lactate exchange is extensive. In addition, isotopic labeling patterns indicate that glycolysis dominates the PPP in terms of total flux. Nevertheless, ribose-phosphate for nucleotide synthesis consistently arises from the oxidative branch of the PPP. Furthermore, a subset of patients demonstrated high levels of de novo serine production. To better understand these observations, next generation sequencing (NGS) and reverse phase protein array (RPPA) analyses on adjacent biopsies from these patients are underway. Together, these findings provide the first comprehensive in vivo characterization of glucose metabolism in TNBC and raise the potential to use tracing to guide development of metabolic therapeutics.

Citation Format: Jonathan Michael Ghergurovich, Joyce O’Shaughnessy, Maren K Levin, Aaron Killian, William Hendricks, Virginia Espina, Joshua D Rabinowitz. Tracing glucose catabolism in human triple negative breast cancer tumors [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-02-06.
Abstract P3-02-09: Vulnerabilities in glutamine metabolism define triple-negative from Luminal A breast cancer subsets
Authors: van Geldermalsen Michelle , Quek Lake-Ee , Turner Nigel , Balaban Seher , Hoy Andrew , Pang Angel , Guan Yi Fang , Wahi Kanu , Wang Qian , Holst Jeff
Published: March 2020

Although a nonessential amino acid in normal cells, the demand for glutamine is dramatically increased throughout malignant transformation to support increased metabolic demands; namely, provision of catabolic substrates for ATP production and anabolic substrates for the citric acid cycle and subsequent macromolecule biosynthesis, as well as potentiating the uptake of other critical amino acids by acting as an obligate exchange substrate. Elevated expression of glutamine metabolism-related genes, MYC-driven transcriptional events, and increased consumption and reliance on glutamine are all associated with aggressive breast cancers, including the high-risk triple-negative (TN) subtype. We recently showed that in breast cancer cells, glutamine uptake by the small neutral amino acid transporter, ASCT2, is required to sustain TN cell growth in vitro and in vivo. We therefore hypothesised that highly proliferative TN breast cancers that are sensitive to ASCT2 inhibition may have unique metabolic signatures that could be additionally exploited for therapeutic purposes. Using radiolabelled and stable isotope tracing methods, we analysed in detail glutamine catabolism and its conversion into various metabolic products such as tricarboxylic acid (TCA) cycle intermediates, lipids, nucleotides, and amino acids in human breast cancer cell lines in vitro and ex vivo. These analyses revealed distinct metabolic effects across cell lines representing different subtypes of breast cancer, both at baseline and when glutamine uptake was blocked in vitro by L-gamma-glutamyl-p-nitroanilide (GPNA), a pharmacological inhibitor of ASCT2. These data confirm a broad reliance on glutamine availability in TN breast cancers, where glutamine anapleurosis was significantly greater than in the Luminal A subtype. Analysis of gene expression data from the METABRIC and TCGA patient datasets and the CCLE cell line dataset showed a specific upregulation of multiple glutamine metabolism enzymes in TN breast cancer patient samples and cell lines compared to the Luminal A subtype. These data suggest a rewiring of glutamine metabolism in TN breast cancer that utilises their addiction to glutamine to fuel cell growth. Furthermore, these data provide an additional suite of glutamine metabolic enzymes that may be therapeutically targeted in the hard-to-treat TN breast cancer subset.

Citation Format: Michelle van Geldermalsen, Lake-Ee Quek, Nigel Turner, Seher Balaban, Andrew Hoy, Angel Pang, Yi Fang Guan, Kanu Wahi, Qian Wang, Jeff Holst. Vulnerabilities in glutamine metabolism define triple-negative from Luminal A breast cancer subsets [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-02-09.
Abstract P3-03-11: Notch inhibition promotes triple negative breast cancer growth
Authors: Saikumar Pothana , Singha Prajjal K , Venkatachalam Manjeri A
Published: March 2020

Notch1 and Transforming Growth Factor-beta (TGF-β) signaling pathways in cancer have a paradoxical roles as they were shown to have both tumor suppressive and tumor promoting activities. The interaction between these two signaling pathways in cancer progression was addressed in a systematic way. In these studies, we utilized primary human mammary epithelial cells (HMEC) and various triple negative breast cancer (TNBC) cells and examined the molecular cross-talk between TGF-β and Notch signaling pathways using biochemical, molecular and cell biology techniques. First, we noticed lower expression of Notch1 in most of the TNBC cells compared to normal cells. Second, most of these TNBC cells overexpressed TMEPAI (transmembrane prostate androgen induced) protein, which was shown to switch TGF-β from a tumor suppressor to a tumor promoter role in breast cancer. Surprisingly, treatment of TNBC cells with Notch inhibitors increased their growth rate both in the absence or presence of TGF-β. Moreover, Notch inhibition relieved the growth suppression by TGF-β in normal cells. Both normal and TNBC cells showed increased growth in the presence of Notch inhibitors with decreased TGF-β signaling activity. Normal cells that express very low levels of TMEPAI both at mRNA and protein levels, overexpressed TMEPAI protein in the presence of various Notch inhibitors, suggesting that Notch negatively regulates TMEPAI expression. Correspondingly, knockdown of TMEPAI in TNBC cell lines showed increased expression of Notch1 and Jagged 1 suggesting a negative regulation of Notch1 by TMEPAI. Consistent with these observations, TMEPAI, a known binding partner of E3 ligases, causes increased turnover of Notch1 protein. In fact, over expression of active Notch1 in MDA-MB-231 cells inhibited tumor cell growth both in vitro and in vivo. Our results clearly suggest that a crosstalk exists between TGF-β and Notch1 signaling through TMEPAI. Therefore, our studies clearly indicate that use of Notch inhibitors is contraindicated in triple negative breast cancer patients.

Citation Format: Pothana Saikumar, Prajjal K Singha, Manjeri A Venkatachalam. Notch inhibition promotes triple negative breast cancer growth [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-03-11.
Abstract P3-03-14: Screening strategies for Notch3-degradation-related E3 ligase in breast cancers
Authors: Liu Jing , Zhang Man-Li , Shen Jia-Xin , Xu Ya , Yuan Ming-Heng , Zhang Guo-Jun
Published: March 2020

BACKGROUND: The Notch pathway is very conserved and used iteratively during development and regulation of cell fates. Deregulation or loss of Notch signaling is associated with a wide range of human disorders, including breast cancer. It is accepted that ubiquitination events are linked to Notch receptors and their ligands where more than 10 E3-ligase and de-ubiquitination enzymes were implicated in this process. In this study, we attempt to apply a workflow to perform an E3-ligase RNAi screen focusing on the degradation system of Notch signaling pathway in breast cancer cells, hoping to further elaborate the pathogenesis of breast cancer and provide new ideas and schemes for its treatment.

MATERIALS AND METHODS: Breast cancer cell line MCF7 was treated with cycloheximide (CHX), an inhibitor of protein biosynthesis, to observe the half-life of Notch3 protein. Then a cell-based screening assay was utilized via a 4 × CSL-luc reporter gene, which reacted to a siRNA library targeting E3 ligases that when silenced inhibit proteasome function in Notch signaling pathway. Moreover, Western Blot and Real-Time PCR were conducted to measure various levels of Notch3 after over-expression of potential E3s. Immunoflourescence was checked for co-colonization of potential E3s and Notch3.

RESULTS: Since ubiquitination plays a major role in Notch, we performed a siRNA screen targeting human ubiquitin ligases in MCF7 cells. We quantified the activity of 4 × CSL-luc reporter gene as a read-out for Notch3 contents. From the screening results, we identified the APC/C ubiquitin ligase Cdh1 as a potential player in Notch3 degradation. Over-expressed Cdh1 led to decreased Notch3 levels in post-translational level. Moreover, Cdh1-triggered Notch3 led to a reversed accumulation when inhibited by proteasome inhibitor, MG132.

CONCLUSION: Taken together, the 4 × CSL-luc reporter system was effective for detecting the potential E3 ligase involved in the degradation of Notch3 through ubiquitination-proteasome system in breast cancer.

Citation Format: Jing Liu, Man-Li Zhang, Jia-Xin Shen, Ya Xu, Ming-Heng Yuan, Guo-Jun Zhang. Screening strategies for Notch3-degradation-related E3 ligase in breast cancers [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-03-14.