bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P1-06-08: A p53-independent DNA damage response that regulates breast cancer phenotypes
Authors: Fagan-Solis KD , Simpson DA , Kapustina M , Martelotto L , Reis-Filho JS , Petrini JH , Gupta GP
Published: May 2019

Defects in the DNA damage repair system result in increased genomic instability and have recently been implicated as being drivers of tumorigenesis in both familial and sporadic breast cancers. To maintain genomic integrity, cells have a DNA damage response (DDR) mechanism that functions to repair damaged DNA efficiently and commits cells to death if damage is irreparable. Failure of this mechanism results in genomic instability and cancer predisposition. Widespread chromosomal instability is a characteristic feature of Triple-Negative Breast Cancer (TNBC), making it difficult to decipher between genes that drive cancer development from those that play a bystander role. Little is known about what gives rise to the extensive genomic instability of TNBC, and presents a major deficit in our scientific and clinical knowledge.

Oncogene induced hyper-proliferation results in replication-associated double strand breaks (DSBs) that engage an Mre11-Rad50-Nbs1 complex-dependent DDR. Classically, the oncogene induced DDR is believed to suppress tumorigenesis due to downstream activation of p53. Using genetically engineered primary mammary epithelial cell models, we demonstrate p53-independent effects of the Mre11-dependent DDR in suppressing proliferation and DNA damage induced by diverse oncogenic drivers. Single cell whole genome sequencing in Her2/Neu expressing primary mammary epithelial cells reveals a landscape of stochastic copy number aberrations induced by oncogenic stress that becomes enriched for a genomic scar pattern of larger-size deletions in cells with Mre11 hypomorphism. We identify Mre11 pathway hypomorphism in a subset of basal-like breast cancers (BLBC), which confers vulnerability to specific DNA damaging agents and DDR inhibitors in murine models of p53-deficient BLBC. Thus, assessing the functional status of the Mre11-dependent DDR pathway in p53-mutant breast cancers may provide an opportunity for therapeutic exploitation.

Citation Format: Fagan-Solis KD, Simpson DA, Kapustina M, Martelotto L, Reis-Filho JS, Petrini JH, Gupta GP. A p53-independent DNA damage response that regulates breast cancer phenotypes [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 P1-06-08.
Abstract P1-08-04: Withdrawn
Authors: Trabert B , Bauer DC , Brinton LA , Buist DS , Cauley JA , Dallal CM , Gierach GL , Falk RT , Hue TF , Lacey JV , LaCroix AZ , Tice JA , Xu X
Published: May 2019

This abstract was withdrawn by the authors.

Citation Format: Trabert B, Bauer DC, Brinton LA, Buist DS, Cauley JA, Dallal CM, Gierach GL, Falk RT, Hue TF, Lacey, Jr. JV, LaCroix AZ, Tice JA, Xu X. 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 P1-08-04.
Abstract P1-08-06: Changes in breast cancer diagnosis and treatment after Medicaid expansion in Pennsylvania
Authors: Spada N , Geramita E , van Londen G , Sabik L
Published: May 2019

Background: In January 2015, Pennsylvania expanded Medicaid eligibility to all legally present adults in the Commonwealth of Pennsylvania with household incomes up to 138 percent of the federal poverty level under the Affordable Care Act. Pennsylvania is the most populous state to expand Medicaid that did not previously have a large expansion of the program to adults, making it an ideal setting to study the impacts of the program. By March 2017, an estimated 716,000 people had enrolled in Pennsylvania's expanded Medicaid program. We aim to determine how Pennsylvania's Medicaid expansion has impacted breast cancer diagnosis and treatment in the state.

Methods: The Pennsylvania Cancer Registry was queried for all women aged 18 to 64 years newly diagnosed with breast cancer between 2007 and 2015. Demographic, tumor, and treatment characteristics were evaluated for each year during this time span. In order to assess the impact that Medicaid expansion had on these variables, they were compared for the years 2007 to 2014 (before Medicaid expansion) and the year 2015 (after).

Results: Between 2007 and 2015, 49,606 cases of invasive breast cancer were diagnosed among women aged 18-64 and residing in the state of Pennsylvania, 43,920 of which were diagnosed and treated between 2007 and 2014, and 5,686 of which were diagnosed and treated in 2015. Initial analysis indicates that more women were diagnosed with localized breast cancer (SEER summary stage 1) following Medicaid expansion in 2015 compared to the period of 2007 to 2014 (63.07% v. 60.62%, p = 0.0004). Meanwhile, the proportion of women diagnosed with metastatic breast cancer did not change before and after Medicaid expansion (6.52% v. 6.86%, p = 0.3298). Subsequent analysis will assess changes in treatment outcomes including time to treatment and receipt of guideline-concordant care.

Conclusion: The expansion of Medicaid in Pennsylvania in 2015 under the Affordable Care Act resulted in an increase in the proportion of localized (SEER summary stage 1) breast cancer diagnoses, though there was no change in the proportion of metastatic cases in the first year following expansion. The results suggest a possible increase in earlier stage diagnosis associated with increased access to health insurance. Additional analysis will examine the impact on treatment-related outcomes.

Citation Format: Spada N, Geramita E, van Londen G, Sabik L. Changes in breast cancer diagnosis and treatment after Medicaid expansion in Pennsylvania [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 P1-08-06.
Abstract P1-08-09: Breast cancer-related deaths according to grade in ductal carcinoma in situ: A Dutch population-based study on patients diagnosed between 1999 and 2012
Authors: van Maaren MC , Lagendijk M , Tilanus-Linthorst MM , de Munck L , Pijnappel RM , Schmidt MK , Wesseling J , Koppert LB , Siesling S
Published: May 2019

Background

The incidence of ductal carcinoma in situ (DCIS) has drastically increased over the past decades. Since DCIS is resected after diagnosis similarly to invasive breast cancer, the natural cause and behaviour of DCIS is not well known. We aimed to determine breast cancer-specific (BCSS) and overall survival (OS) according to grade in DCIS patients after surgical treatment in the Netherlands.

Patients and methods

All DCIS patients diagnosed between 1999-2012 were selected from the Netherlands Cancer Registry. Cause of death was obtained from 'Statistics Netherlands'. BCSS and OS were estimated using multivariable Cox regression in the entire cohort and stratified for grade.

Results

In total, 12,256 patients were included, of whom 1,509 (12.3%) presented with grade I, 3,675 (30.0%) with grade II, 6,064 (49.5%) with grade III and 1,008 (8.2%) with an unknown grade. During a median follow-up of 7.8 years, 1,138 (9.3%) deaths were observed, and 179 (1.5%) were breast cancer-related. Of these, 10 patients had grade I, 46 grade II, 95 grade III and 28 an unknown grade. After adjustment for confounding, grade II and III were related to worse BCSS compared to grade I with HRs of 1.92 (95% CI:0.97-3.81) and 2.14 (95% CI:1.11-4.12), respectively. No association between grade and OS was observed.

Conclusion

BCSS and OS rates in DCIS patients are excellent. Since superior rates were observed for low-grade DCIS, and earlier studies have shown that low-grade DCIS have a very low chance on recurrence or upstage to invasive cancer, it seems justified to investigate whether active surveillance may be a balanced alternative for conventional surgical treatment.

Citation Format: van Maaren MC, Lagendijk M, Tilanus-Linthorst MM, de Munck L, Pijnappel RM, Schmidt MK, Wesseling J, Koppert LB, Siesling S. Breast cancer-related deaths according to grade in ductal carcinoma in situ: A Dutch population-based study on patients diagnosed between 1999 and 2012 [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 P1-08-09.
Abstract P1-08-13: A prospective evaluation of HLA expression in breast implant associated anaplastic large cell lymphoma to identify disease susceptibility
Authors: Tevis SE , Hunt KK , Miranda RN , Butler CE , Clemens MW
Published: May 2019

Background: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare T-cell lymphoma found to occur in association with breast implants. Proposed pathogenic factors for BIA-ALCL include immunologic reaction to textured implants, bacteria and biofilm, chronic inflammation, autoimmune disease, or genetic predisposition. While HLA alleles have been found to be associated with other forms of lymphoma, the frequency of HLA allele polymorphisms have not been described for BIA-ALCL. The aim of this study is to evaluate the frequency of HLA alleles in patients with BIA-ALCL.

Methods: We prospectively evaluated HLA alleles in 13 patients with BIA-ALCL seen at a single institution from 2017 to 2018. HLA testing was carried out using probe based sequence specific testing and sequence based typing. The frequency of HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 were evaluated in the study population. Allele frequencies in the Caucasian European general population were obtained from the National Marrow Donor Program for normative controls. We estimated the relative risk of BIA-ALCL with 95% confidence intervals for each HLA allele using a t test. All statistics were performed using SPSS.

Results: Thirteen patients with BIA-ALCL and HLA testing were identified with ages ranging from 37 – 76 years. We identified 10, 11, and 9 HLA A, B, and C alleles respectively. There were 8 DRB1 alleles and 5 DQB1 alleles in the BIA-ALCL patients. The following alleles occurred more than two times more frequently in patients with BIA-ALCL as compared with the general population: A*31, A*32, A*68, B*27, B*39, B*49, B*51, and C*15. Conversely, the A*01, A*24, and B*35 alleles occurred less frequently in patients with BIA-ALCL. The A*26 allele was found to occur significantly less often in BIA-ALCL patients (0.2992 vs. 0.07692, p<0.001) versus normative controls.

Conclusions: Our results identify differences in the frequency of specific HLA alleles in patients who develop BIA-ALCL compared with the general population. These alleles may signify genetic susceptibility factors for germline genetic variation in HLA in Caucasian patients with BIA-ALCL. Further work is needed to elucidate if these alleles confer susceptibility or resistance and are predictive for the disease in women with textured surface breast implants.

Citation Format: Tevis SE, Hunt KK, Miranda RN, Butler CE, Clemens MW. A prospective evaluation of HLA expression in breast implant associated anaplastic large cell lymphoma to identify disease susceptibility [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 P1-08-13.
Abstract P1-08-17: Pharmacy refill synchronization and oral endocrine therapy adherence
Authors: Neuner JM , Fergestrom N , Nattinger AB , Laud PW , Pezzin L
Published: May 2019

Background: One-third to one-half of patients prescribed adjuvant endocrine therapy with tamoxifen or an aromatase inhibitor either discontinue early or skip a substantial number of pills. Research to improve this has been disappointing. We investigated whether poor pharmacy synchronization of medications is an unrecognized barrier to adherence. Methods: A cohort of women aged 66-90 years old with Stage 0-3 hormone receptor-positive breast cancer were identified from the Surveillance, Epidemiology and End Result (SEER)-Medicare claims-linked cancer registry. Women with Medicare pharmacy claims documenting at least one endocrine therapy prescription fill and at least one other medication fill were identified, and the 3-month synchronization of their medication fills was calculated as the quotient of the number of pharmacy visits and the number of filled medications subtracted from one. Logistic regression was used to assess the association between synchronization stratified by the number of medications and adherence to endocrine therapy (defined as medication possession ratio >80%) over the subsequent year. Results: The study cohort included 3,112 women treated with endocrine therapy for breast cancer (Table 1) . Over 31% were age 70 or younger, and 38.0% had stage 2 or 3 disease. During the three months after the first endocrine therapy prescription, the mean number of unique medications was 8.0 (S.D. 6.0) and the mean number of pharmacy visits was 8.6 S.D. 4.7) for a mean synchronization of 0.3 ( (S.D. 0.2) . In adjusted model, compared with the highest synchronization, those in the lowest synchronization quantile were less likely to be adherent (MPR >=80%) (Odds Ratio 0.71 (95% CI 0.57, 0.88)) as were those in the second-lowest (0.81 (0.65, 0.99). Neither age nor race/ethnicity were associated with adherence, and results were unchanged with inclusion of information about duration of fills (30 vs 90 days). Conclusions: Prescription fill synchronization is strongly associated with adherence to endocrine therapy. Research into interventions to improve adherence should include prescription synchronization and other health systems barriers.

Citation Format: Neuner JM, Fergestrom N, Nattinger AB, Laud PW, Pezzin L. Pharmacy refill synchronization and oral endocrine therapy adherence [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 P1-08-17.
Abstract P1-08-23: Not presented
Authors: Zang Y-S , Qi F , Qin W-X
Published: May 2019

This abstract was not presented at the conference.

Citation Format: Zang Y-S, Qi F, Qin W-X. 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 P1-08-23.
Abstract P1-08-24: Conditional survival of breast cancer patients: Korean nationwide registry
Authors: Jung S-Y , Jung K-W , Won Y-J , Kwon Y , Ha J , Kim YA , Kong S-Y , Lee ES
Published: May 2019

Purpose: Conditional relative survival (CRS) could provide more relevant information on the current prognosis of cancer survivors than standard 5-year relative survival (RS). This study aimed to estimate the 5-year CRS of Korean breast cancer patients.

Patients and Methods: We identified 145,083 breast cancer cases with diagnosis between 2002 and 2013 in the Korea Central Cancer Registry. The CRS was estimated for every year after diagnosis, according to sex, age, histologic types, stage, and year of diagnosis.

Results: The 5-year RS at diagnosis was 90.8% and 10-year RS was 85.7%. Five-year CRS was 91.0% and 94.3% at 1-year and 5-year after diagnosis. Women had better 5-year CRS than men after 5 years of survival (94.3% vs. 79.5%), and very young and very old patients had worse 5-year CRS after 5 years of survival than other age groups (92.2% in <40yr, 92.6% in ≥70yr vs. 95.4% in 40-49, 94.3% in 50-59, and 93.7% in 60-69, relatively). In histologic types, CRS of metaplastic carcinoma has improved from 82.0% to 95.2%, compared to CRS of lobular carcinoma (from 93.1% to 92.5%). Hardly any excess mortality (5-year CRS ≥ 95%) was seen since 7 years after diagnosis. There was hardly any excess mortality at 5 years of survival, for the patients with 40-49 years (95.4%), with localized disease (97.8%), and with metaplastic carcinoma (95.2%).

Conclusion: This study showed that CRS of breast cancer survivors in Korea has been improved, which varied by sex, age, stage, and histologic types. These CRS analysis could provide a more detailed information for survival to breast cancer survivors and clinicians.

Citation Format: Jung S-Y, Jung K-W, Won Y-J, Kwon Y, Ha J, Kim YA, Kong S-Y, Lee ES. Conditional survival of breast cancer patients: Korean nationwide registry [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 P1-08-24.
Abstract P1-08-25: Withdrawn
Authors: Zhao H , Gong Y , Ye F , Ling H , Hu X
Published: May 2019

This abstract was withdrawn by the authors.

Citation Format: Zhao H, Gong Y, Ye F, Ling H, Hu X. 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 P1-08-25.
Abstract P1-08-34: Withdrawn
Authors: Kang Y-J , Han J , Ko E
Published: May 2019

This abstract was withdrawn by the authors.

Citation Format: Kang Y-J, Han J, Ko 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 P1-08-34.
Abstract P1-11-16: Efficacy and safety of acupuncture for the hot flashes in breast cancer patients taking adjuvant tamoxifen: A multicenter study in Korean women
Authors: Choi H , Jeong Y-j , Park S-H , Kwak M-A , Kim K-S , Lee Y , Park S
Published: May 2019

Background : Tamoxifen is widely used in premenopausal patients with estrogen receptor positive (ER+) breast cancer. Among the side-effects of tamoxifen, hot flashes is a common and challenging one. Previous pilot study suggested the effectiveness of acupuncture for relief of symptoms. This study was performed to evaluate the efficacy and safety of acupuncture for treatment of hot flashes in Korean women breast cancer patients taking tamoxifen as adjuvant endocrine therapy.

Methods : Thirty(30) breast cancer patients taking tamoxifen and reported moderate to severe hot flashes were enrolled from two institutes. Patients were randomly assigned into acupuncture group(n=15) and control group(n=15). The acupuncture group received acupuncture 3 times a week for 4 consecutive weeks, at 5 predefined points(GV 20, M-HN-3, HT 8, KI 10 and LV 2) for 20 ± 5minutes at each session. Control group received no treatment. The score of hot flash visual analogue scale(VAS) and total hot flash score, EORTC QLQ-C30 and QLQ-BR 23 questionnaire were recorded before treatment, once every treatment week and 4 weeks after treatment for both groups.

Results : Acupuncture group showed significantly reduced severity of hot flashes during treatment assessed with either VAS and total hot flash score (p=0.000 and p=0.008, respectively). Also, acupuncture group showed improvement of global health status and physical functioning score assessed with EORTC QLQ-C30 (p=0.004 and p=0.027, respectively). Four weeks after the treatment, these trends were retained. No adverse events were notified

Conclusion : Acupuncture may have feasibility and safety for alleviate hot flashes of Korean women breast cancer patients taking tamoxifen as an adjuvant endocrine therapy. Long-term follow up results and further study with a larger sample size is required.

Citation Format: Choi H, Jeong Y-j, Park S-H, Kwak M-A, Kim K-S, Lee Y, Park S. Efficacy and safety of acupuncture for the hot flashes in breast cancer patients taking adjuvant tamoxifen: A multicenter study in Korean women [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 P1-11-16.
Abstract P1-11-18: Measuring severe anxiety in patients with metastatic breast cancer: Living up to the PROMIS
Authors: Marquez C , Li Y , Huang C-Y , Rugo H , Rabow M , Melisko M , Esserman L
Published: May 2019

Purpose/Objective(s):

Symptom burden in the advanced cancer patient can be substantial. PROMIS (Patient Reported Outcome Measurement Information System) is a powerful PRO symptom assessment tool that is increasingly being utilized at the point of care through patient-facing electronic health record (EHR) systems. However, the PROMIS threshold (T-score) for detecting severe anxiety has not been previously validated for patients with advanced breast cancer. The sensitivity/specificity of current expert derive threshold T-score of >/=75 in this specific population is not known. In this study, we compared PROMIS scores with the PRO-CTCAE anxiety instrument—a standard PRO tool used in the setting of clinical trials that assesses anxiety frequency, severity, and interference with usual activities—to examine the best T-score to use for PROMIS to guide management in advanced breast cancer care.

Materials/Methods:

A total of 84 unique visits of 74 English speaking patients on active cancer treatment for metastatic breast cancer were assessed using electronic PROMIS CAT (Computer Adaptive Test) and PRO-CTCAE at the UCSF Carol Buck Breast Cancer Center. Assessment forms were displayed on a touch screen tablet and completed by the patient at check-in for weekly treatment visits. PRO-CTCAE anxiety questions were graded on a scale of 1 (none) to 5 (disabling). Any score of grade >/=4 (severe to disabling) for frequency, severity or interference was defined as severe anxiety.

Results:

There was a strong correlation of PROMIS T-score and maximum PRO-CTCAE grade (highest grade of frequency, severity, or interference); Spearman correlation coefficient = 0.77 (P= <0.001). No patients reached the expert derived severe threshold of PROMIS T-score 75. Highest PROMIS T-score was 69 (range, 33-69). 11 patients reported severe or disabling anxiety by PRO-CTCAE at one visit. Area under the ROC analysis identified a cutoff that maximizes Youden's index at 55.05—sensitivity = 100% (95% CI) and specificity = 63% (95% CI).

Conclusion:

Electronic systems with integrated patient reported outcomes (PROs) along with validated thresholds to identify severe anxiety will allow for systematic identification of symptoms at point of care and the opportunity to respond rapidly to those symptoms most distressing to patients.

Citation Format: Marquez C, Li Y, Huang C-Y, Rugo H, Rabow M, Melisko M, Esserman L. Measuring severe anxiety in patients with metastatic breast cancer: Living up to the PROMIS [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 P1-11-18.
Abstract P1-12-02: Withdrawn
Authors: Chung IY , Hur H , Lee J , Lee JW , Youn HJ , Han K , Kim NW , Jung S-Y , Kim Z , Kim KS , Lee MH , Han S-H , Jung SH
Published: May 2019

This abstract was withdrawn by the authors.

Citation Format: Chung IY, Hur H, Lee J, Lee JW, Youn HJ, Han K, Kim NW, Jung S-Y, Kim Z, Kim KS, Lee MH, Han S-H, Jung SH. 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 P1-12-02.
Abstract P1-13-10: Comparison of overall and recurrence-free survival between four and six cycles of adjuvant docetaxel and cyclophosphamide in early stage breast cancer
Authors: Mehmi I , Wight CE , Hill JL
Published: May 2019

Background: The ABC trials and the WSG Plan B trial demonstrated that certain early stage breast cancer patients can be appropriately treated with docetaxel and cyclophosphamide (TC) rather than doxorubicin and cyclophosphamide (AC); however both of these trials utilized six cycles of TC as the comparator. TC is given for 4 cycles based on the US Oncology 9735 trial. To our knowledge, there is no available data that has compared adverse events or outcomes of four versus six cycles of TC.

Methods: This was a single-center, retrospective study evaluating recurrence-free survival, overall survival, and occurrence of toxicities between four and six cycles of docetaxel and cyclophosphamide adjuvant chemotherapy for early stage breast cancer at West Virginia University Cancer Institute.

Results: 112 patients were included; 81 received four cycles and 31 received six. Recurrence free survival rates of patients that received four and six cycles of chemotherapy were 94% and 90%, respectively, at three years (P=0.68). Overall survival at three years was 99% versus 97% (P=0.49), respectively. The incidence of peripheral neuropathy requiring treatment was 42% in patients that received six cycles and 19% in patients that received four (P=0.015).

Conclusion: The addition of two cycles of docetaxel and cyclophosphamide adjuvant chemotherapy for early stage breast cancer provides no additional recurrence-free or overall survival benefit but does increase the incidence of peripheral neuropathy requiring treatment.

Table 1.Baseline Characteristics 4 Cycles (n=81)6 Cycles (n=31)P-valueAge, median years (range)57 (37-75)48 (32-71)0.001Receptor status, n (%)  0.63HR positive, HER2 negative61 (75)25 (81) Triple negative20 (25)6 (19) Cancer stage, n (%)  0.031I39 (48)9 (29) II39 (48)17 (55) III3 (4)5 (16) Lymph node involvement, n (%)24 (30)20 (65)0.001Ki67 (%), median (range)23 (2-99)23.5 (4-99)0.99Tumor grade, n (%)  0.07212 (2)4 (13) 242 (52)12 (39) 337 (46)15 (48) Surgery, n (%)   Breast conservation35 (43)14 (45)0.99Unilateral mastectomy32 (40)9 (29)0.38Bilateral mastectomy14 (17)8 (26)0.43

Table 2.Adverse Events 4 Cycles (n=81)6 Cycles (n=31)P-valueDose reductions, n (%)17 (21)8 (26)0.62Dose delay, n (%)3 (4)1 (3)0.99Inpatient admissions, n (%)22 (27)8 (26)0.99Treatment for peripheral neuropathy, n (%)15 (19)13 (42)0.015

Citation Format: Mehmi I, Wight CE, Hill JL. Comparison of overall and recurrence-free survival between four and six cycles of adjuvant docetaxel and cyclophosphamide in early stage 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 P1-13-10.
Abstract P1-14-03: Withdrawn
Authors: Dodwell D , Lawton S , Wong K , Twelves C
Published: May 2019

This abstract was withdrawn by the authors.

Citation Format: Dodwell D, Lawton S, Wong K, Twelves C. 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 P1-14-03.
Abstract P1-15-02: Withdrawn
Authors: Schwab R , Clark A , Yau C , Wolf D , Chien AJ , Majure M , Ewing C , Wallace A , Roesch E , Helsten T , Forero A , Stringer-Reasor E , Vaklavas C , Nanda R , Jaskowiak N , Boughey J , Haddad T , Han H , Lee C , Albain K , Isaacs C , Elias A , Ellis E , Shah P , Lang J , Lu J , Tripathy D , Kemmer K , Yee D , Haley B , Korde L , Edmiston K , Northfelt D , Viscusi R , Khan Q ,   I-SPY 2 Consortium, Symmans WF , Perlmutter J , Hylton N , Rugo H , Melisko M , Wilson A , Singhrao R , Asare S , van't Veer L , DeMichele A , Berry D , Esserman L
Published: May 2019

This abstract was withdrawn by the authors.

Citation Format: Schwab R, Clark A, Yau C, Wolf D, Chien AJ, Majure M, Ewing C, Wallace A, Roesch E, Helsten T, Forero A, Stringer-Reasor E, Vaklavas C, Nanda R, Jaskowiak N, Boughey J, Haddad T, Han H, Lee C, Albain K, Isaacs C, Elias A, Ellis E, Shah P, Lang J, Lu J, Tripathy D, Kemmer K, Yee D, Haley B, Korde L, Edmiston K, Northfelt D, Viscusi R, Khan Q, I-SPY 2 Consortium, Symmans WF, Perlmutter J, Hylton N, Rugo H, Melisko M, Wilson A, Singhrao R, Asare S, van't Veer L, DeMichele A, Berry D, Esserman L. 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 P1-15-02.
Abstract P1-15-18: Not presented
Authors: Choi HJ , Kim SW , Ryu JM , Kim I , Nam SJ , Yu J , Lee SK , Lee JE
Published: May 2019

This abstract was not presented at the conference.

Citation Format: Choi HJ, Kim SW, Ryu JM, Kim I, Nam SJ, Yu J, Lee SK, Lee JE. 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 P1-15-18.
Abstract P1-15-22: Clinicopathological significance of diversity index for c-MYC copy number variation after primary systemic therapy in breast cancer
Authors: Kim G , Chung YR , Kim HJ , Kim M , Ahn S , Park SY
Published: May 2019

Background: Chemotherapy can alter tumor cell populations by exerting selection pressure. This study was performed to evaluate the change in Shannon diversity index for c-MYC copy number variation after primary systemic therapy (PST) and its clinical implications in breast cancer patients treated with PST.

Materials and Methods: One hundred and forty-four breast cancer patients who had residual disease after anthracycline- or anthracycline and taxane-based PST were included in the study. Associations between Shannon index for c-MYC copy number variation in pre- and post-PST breast cancer samples and clinicopathologic features of tumors as well as patient survival were analyzed.

Results: Among the 119 patients with both pre- and post-PST samples available for comparison, 17 (14.3%) underwent change in c-MYC amplification status and 40 (33.6%) in c-MYC copy number gain status with most cases showing positive to negative conversion. In the whole group, Shannon index for c-MYC copy number variation was decreased in post-PST specimens compared to pre-PST specimens. Especially, the chemo-responsive group showed a more significant decrease in Shannon index after PST. However, there was no difference in diversity indices between pre- and post-PST specimens in the chemo-resistant group. c-MYC copy number gain and high Shannon indices for c-MYC copy number variation in both pre- and post-PST specimens were associated with adverse clinicopathologic features of breast cancer. In survival analyses, high Shannon indices for c-MYC copy number variation in post-PST samples as well as pre-PST samples were revealed as an independent prognostic factor for decreased disease-free survival. Upon subgroup analysis according to hormone receptor status, high Shannon indices before and after PST were associated with adverse clinical outcome in hormone receptor-positive group but not in hormone receptor-negative subgroup.

Conclusions: These results suggest that a change in Shannon index for c-MYC copy number variation after PST reflects chemo-responsiveness and that Shannon index after PST can be used as a prognostic factor in breast cancer patients who receive PST.

Citation Format: Kim G, Chung YR, Kim HJ, Kim M, Ahn S, Park SY. Clinicopathological significance of diversity index for c-MYC copy number variation after primary systemic therapy in 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 P1-15-22.
Abstract P1-15-25: Prognostic factors associated with pathological complete response in early breast cancer patients undergoing neoadjuvant chemotherapy. The importance of Ki-67 and molecular subtype
Authors: Rapoport BL , Barnard-Tide J , Smit T , Nayler S , Benn C-A
Published: May 2019

Background: Ki-67 immunohistochemical determination is a widely used biomarker of cell proliferation in patients (pts) undergoing endocrine treatment for breast BC. The role of Ki-67 in pts undergoing neoadjuvant chemotherapy (NAC) for early BC remains controversial.

Methods: We analyzed retrospectively data on 137 patients undergoing taxane and/or anthracycline, transtuzumab based NAC. Luminal A was documented in 6 pts, Luminal B in 29 pts, Her-2 positive in 30 pts and triple negative breast cancers (TNBC) in 72 pts. 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.

Results: The pCR rate of the entire cohort was 41.6%. At 2 years 92% of pts who attained a pCR were disease free compared to 80% of pts who did not attain a pCR (log rank test p < 0.0147).

On univariate analysis factors associated with higher pCR included primary tumor size (T1 68% vs. T2 41% vs. T3 or T4 0%, Chi2=20.05, p<0.00017), nodal disease (N0 49% vs. N1 39% vs. N2 8%, p<0.02948), ER receptor status (negative 59% vs. positive 14%, p<0.00000), PR receptor status (negative 53% vs. positive 17%, p<0.00002), molecular subtype (TNBC 53.4%, Her2=50% and Luminal A + B was 8.5%, p<0.00002), Ki67 (>40=55% vs. 15-39=34% vs. <15=0%, p<0.00060) and Stage (I= 85% vs. IIA=49% vs. IIB=36% vs. III=5%, p<0.00006). Factors not associated with a higher pCR included age, menopausal status, extranodal spread and lympho-vascular invasion. In a logistic regression model Ki-67 as a continuous variable (p<0.01203) and molecular subtype (p<0.02228) retained its significance; while tumor size, stage of disease, nodal status, ER and PR loss significance.

Conclusion: Ki67 and molecular subtype (Her-2 positive disease and TNBC) are independent prognostic factors of pCR in pts with early BC undergoing NAC.

Citation Format: Rapoport BL, Barnard-Tide J, Smit T, Nayler S, Benn C-A. Prognostic factors associated with pathological complete response in early breast cancer patients undergoing neoadjuvant chemotherapy. The importance of Ki-67 and molecular subtype [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 P1-15-25.
Abstract P1-17-04: Long-term safety follow-up of patients with early stage breast cancer treated with scalp cooling on the Dignitana scalp cooling trial
Authors: Rugo HS , Klein P , Melin SA , Hurvitz SA , Melisko ME , Moore A , D'Agostino RB , Deluca A , Cigler T
Published: May 2019

Background

Scalp cooling has demonstrated efficacy in preventing hair loss in women with early stage breast cancer receiving neo/adjuvant chemotherapy. Data from 2 prospective trials (Rugo et al, and Nangia et al, JAMA 2017) led to FDA clearance of 2 automated scalp-cooling devices to prevent chemotherapy induced alopecia (CIA). Although scalp metastases from breast cancer are rare, historical concerns about scalp cooling included a theoretical increase in risk of recurrence in scalp due to reduced delivery of chemotherapy to the scalp.

Methods

We conducted a multicenter prospective trial evaluating the efficacy and safety of the DigniCap in women with stage I-II breast cancer receiving neo/adjuvant chemotherapy excluding sequential or combination anthracycline/taxanes with concurrent matched controls. The primary endpoint was unblinded patient self-assessment of 5 photographs using the Dean scale to estimate hair loss 4 weeks following the last dose of chemotherapy, with success defined as a Dean score of 0-2 (≤ 50% hair loss); additional endpoints included quality of life (QOL) and both short and long-term safety.

Results

106 patients using the scalp cooling device and 16 concurrent controls were enrolled. As previously reported, the use of scalp cooling was associated with less alopecia and improvement in several measures of QOL (Rugo et al, JAMA 2017). 91 patients have follow-up (FU) out to 3 years; 73 with estrogen receptor (ER) positive and 18 with ER negative disease. 5 DigniCap patients have developed recurrent breast cancer in breast (n=1), liver (n=1), bone, liver and breast (n=1), bone, liver, lung, and nodes (1), and bone, breast, GI tract and bladder (n=1). Of 12 control patients with available FU, 1 developed metastases to liver. 2 patients have died of metastatic disease, one in the DigniCap arm and one in the control arm. No new safety signals have been detected.

Conclusion

Scalp cooling using the DigniCap system in patients with early stage breast cancer receiving taxane based neo/adjuvant chemotherapy is safe and effective. No scalp metastases have been reported 3 years following completion of study treatment. 4 year FU data will be presented.

The study was funded by The Lazlo Tauber Family Foundation (UCSF), the Anne Moore Breast Cancer Research Fund (Weil Cornell), and the Friedman Family Foundation (Mount Sinai Beth Israel), as well as partially by Dignitana.

Citation Format: Rugo HS, Klein P, Melin SA, Hurvitz SA, Melisko ME, Moore A, D'Agostino, Jr. RB, Deluca A, Cigler T. Long-term safety follow-up of patients with early stage breast cancer treated with scalp cooling on the Dignitana scalp cooling trial [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 P1-17-04.
Abstract P1-17-06: Breast cancer in elderly women: Ageism or primum non nocere?
Authors: Muzaffar M , Vohra N , Wong J
Published: May 2019

Background: The risk of breast cancer increases with advancing age. Routine use of screening mammogram in women after 75yrs and its impact on overall survival is controversial. Studies have also found that elderly breast cancer patients are underrepresented among clinical trials and a tendency for undertreatment may result in inferior outcome.

Method and Material:Female patients with breast cancer who were 75 years or older and diagnosed from 2000-2015 were identified from Surveillance, Epidemiology, and End Results (SEER) 18 database. We excluded patients with unknown stage and race. We performed multivariate and survival analysis using JMP pro 13.

Results: 186,682 women with breast cancer of ≥ 75 yrs. were identified from the SEER. 167,802 patients met the inclusion criteria. Mean age was 81.27 years (CI 95% 81.25-81.30). Most of the patients were white (88%), and had Stage I/II (83%) breast cancer.78% of patients had estrogen receptor positive cancer, while 66% had grade 1/2 disease. The 5-year overall survival was 74% for Stage I,60% for Stage II,38% for stage III and 11% for Stage IV cancer(p<0.0001). The disease specific survival (DSS)for stage I (96%), Stage II (88%), Stage III (64%), and Stage IV (23%).Out of the patients who were deceased at the time of analysis only 24% of deaths were attributed to this cancer. Cox proportional hazards regression model of overall survival [Table:1]

Cox proportional hazards regression model of overall survivalVariableHazard ratio( 95% CI)p value75—79 80-84 85+1 1.22 1.7<0.0001Race White Black Others1 1.14 0.95<0.001ER Positive Negative unknown1 1.19 1.2<0.001Stage I Stage II Stage III Stage IV1 1.17 1.66 3.7<0.001

Conclusion: Early breast cancer continues to be the most common presentation for patients ≥75 yrs. of age. Historical prognostic factors of breast cancer like race, hormone receptor status, stage and grade continue to impact cancer outcome among elderly patients. Only 24% of deaths among the deceased were attributed to this breast cancer highlighting the concern for over diagnosis. Nonetheless once diagnoses is established a multidisciplinary comprehensive geriatric assessment should be the cornerstone of the management.

Citation Format: Muzaffar M, Vohra N, Wong J. Breast cancer in elderly women: Ageism or primum non nocere? [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 P1-17-06.
Abstract P1-18-06: First-line treatment for endocrine sensitive bone-only metastatic breast cancer: Is more always better?
Authors: Toss A , Venturelli M , Sperduti I , Isca C , Molinaro E , Barbieri E , Piacentini F , Omarini C , Cortesi L , Cascinu S , Moscetti L
Published: May 2019

The standard first-line for endocrine sensitive metastatic breast cancer (BC) is represented by endocrine therapy. Several phase III clinical trials searched for more effective endocrine strategies. Nevertheless, the use of combinations for the first-line treatment of bone-only disease (BoD) is widely discussed, due to its indolent course. Our meta-analysis aims to explore the role of new endocrine strategies in BoD.

A systematic review of electronic databases was conducted to identify the phase III clinical trials comparing the standard AI to novel experimental strategies. The hazard ratios (HR) for PFS were pooled in a meta-analysis. The heterogeneity of the data was evaluated by Chi-square Q test and I2 statistic.

8 studies were included in the analyses. 4 trials explored the role of CDK4/6 inhibitors (Monaleesa2 and 7, Monarch3 and Paloma2), 2 trials analyzed Fulvestrant + AI (SWOG and FACT), one trial studied Fulvestrant monotherapy (FALCON), while one trial evaluated the association between Bevacizumab and Letrozole (ALLIANCE). 6 trials reported data regarding the BoD, while 2 trials included the BoD in the non-visceral disease. Overall, the meta-analyses showed a PFS advantage for the experimental arms [HR 0.70 p 0.012], with a significant moderate/high heterogeneity [I2 66.48% p 0.004]. Only the FALCON and Paloma2 showed a significant improvement in PFS, respectively for Fulvestrant and Palbociclib + Letrozole. Considering only trials reporting data for BoD, the experimental arms significantly improved the PFS [HR 0.66 p 0.005], with a low/moderate non-significant heterogeneity [I2 44.95% p 0.106].

The novel strategies showed to be able to improve the PFS of BoD. Nonetheless, only Palbociclib + Letrozole provided statistically significant data of advantage in this setting. In clinical trials, BoD is often included in the non-visceral disease subgroup. Future clinical trials should take into account the differences in natural history and better prognosis of BoD, in order to define the best approach to these patients.

Citation Format: Toss A, Venturelli M, Sperduti I, Isca C, Molinaro E, Barbieri E, Piacentini F, Omarini C, Cortesi L, Cascinu S, Moscetti L. First-line treatment for endocrine sensitive bone-only metastatic breast cancer: Is more always better? [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 P1-18-06.
Abstract P1-19-06: The prognostic value of HER2, YKL-40 and IL-6 in cerebrospinal fluid in trastuzumab naïve breast cancer patients diagnosed with meningeal carcinomatosis
Authors: Ryberg M , Johansen JS , Grantzau TL , Dehlendorff C , Nielsen DL
Published: May 2019

Background

With the improvements in treatment of patients with metastatic HER2-positive breast cancer (BC) the development of CNS metastases has become a major limitation of life expectancy and quality of life for many patients. Meningeal carcinomatosis represents approximately 10-20% of CNS metastases. The prognosis of meningeal carcinomatosis remains extremely poor. In the present study, we analysed the prognostic value of HER2, YKL-40 and IL-6 in cerebrospinal fluid (CSF) of meningeal carcinomatosis.

Methods

Between June 1985 and August 1992 sixty-nine CSF samples were collected at Herlev Hospital from trastuzumab naïve BC patients suspected of meningeal carcinomatosis. The cohort was composed of BC patients from two previous studies. Meningeal carcinomatosis was confirmed by tumour cells in CSF (or autopsy/scans). The samples were centrifuged, frozen and kept at -80oC. The concentrations of YKL-40, IL-6 and HER2 in CSF were measured by commercial ELISA (Quidel and R&D) or Luminez (HER2 in second study). Overall survival in meningeal carcinomatosis was analysed with Kaplan-Meier curves and log rank tests using the median CSF value of HER2, YKL40 and IL-6 as cut off.

Results

20 patients (29%) had meningeal carcinomatosis (18 patients had tumour cells in CFS, one was diagnosed by autopsy and one by CT scan; 13 of these patients participated in the first study and 7 in the second).10 patients had concomitant brain metastasis. The median survival was 35 days (4-305 days).

The median [IQR] CSF concentration of YKL-40 was 284 ng/ml (187-597), IL-6 was15.9 pg/ml (6.5-51.0) and HER2 was 1.5 (0.36-8.70) in the patients with meningeal carcinomatosis. The survival was significantly shorter in patients with high levels of YKL-40 (p=0.03) and IL-6 (p=<0.01). The CSF HER2 level (p=0.51) or presence of brain metastasis (p=0.77) were not associated with survival.

Conclusion

In this cohort high levels of YKL-40 and IL-6 in CSF were associated with short survival in patients with BC and meningeal carcinomatosis. This was not found for HER2 in CSF or concomitant brain metastasis.

Citation Format: Ryberg M, Johansen JS, Grantzau TL, Dehlendorff C, Nielsen DL. The prognostic value of HER2, YKL-40 and IL-6 in cerebrospinal fluid in trastuzumab naïve breast cancer patients diagnosed with meningeal carcinomatosis [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 P1-19-06.
Abstract P1-20-01: Intraoperative ketorolac in high-risk breast cancer patients with and without inflammation. A prospective, randomized, placebo-controlled clinical trial
Authors: Berliere M , Bouche G , Duhoux F , Coulie P , De Cloedt J , Dekleermaker A , Guillaume J-E , Ledent M , Machiels J-P , Mustin V , Swinnen W , Vander Essen L , Van Maanen A , Verougstraete J-C , De Kock M , Forget P
Published: May 2019

Introduction: Perioperative events may affect the risk of breast cancer recurrence after surgery. Ketorolac, a non-steroidal anti-inflammatory drug routinely used to improve pain control postoperatively has been associated with better breast cancer outcome in retrospective studies. However, it is still unknown whether a single dose of pre-incisional ketorolac may be sufficient to prolong recurrence-free survival.

Patients and methods: The KBCt trial (NCT01806259) is a national, multicenter, prospective, double-blind, placebo-controlled, randomized phase III trial in high risk breast cancer patients. Each patient was assigned to the ketorolac or the placebo group. Patients were given one dose of ketorolac tromethamine (Taradyl®, N.V. Roche S.A., Belgium) or a matching placebo 30 minutes before surgery. Eligible patients were ≥18 and ≤75 years old with histologically or cytologically confirmed, invasive ductal or lobular breast carcinoma planned for curative breast cancer surgery, and with at least one of these 3 criteria: a Neutrophil-to-Lymphocyte Ratio ≥4, node-positive disease (cN1-N3) or a triple-negative histology. The primary endpoint of the study was Disease-Free Survival (DFS). Secondary endpoints included safety, pain assessment and overall survival.

Results: Two hundred and three patients were assigned to ketorolac (n=96) or placebo (n=107). Baseline characteristics were similar between arms. Patients had a mean age of 55.7 (SD 14) years. Both intra- and post-operative blood losses were not different between groups and there was no difference in pain at day 1 after surgery. There was no difference between the 2 arms for DFS (p=0.52) nor for OS (p=0.88).

Discussion and conclusion: This study shows that a single administration of 30 mg of ketorolac tromethamine before surgery does not increase disease-free survival in high risk breast cancer patients. Overall survival is also comparable. No safety concerns were observed in this study.

Citation Format: Berliere M, Bouche G, Duhoux F, Coulie P, De Cloedt J, Dekleermaker A, Guillaume J-E, Ledent M, Machiels J-P, Mustin V, Swinnen W, Vander Essen L, Van Maanen A, Verougstraete J-C, De Kock M, Forget P. Intraoperative ketorolac in high-risk breast cancer patients with and without inflammation. A prospective, randomized, placebo-controlled clinical trial [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 P1-20-01.