bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P4-08-33: The significance of Oncotype DX recurrence score in T1-2N1M0 ER positive HER2 negative breast cancer: An analysis combined with the prognostic stage in the updated AJCC 8th edition
Authors: Chen H , Wang M , Zhang P , Zhang M , Wu K
Published: May 2019

Purpose: Oncotype DX recurrence score (Oncotype DX RS) is applied in the prognostic stage in T1-2N0M0 ER+/HER2- breast cancer. But its significance is unclear in cases with T1-2N1M0 ER+/HER2- disease. Our study was to evaluate the prognostic significance of Oncotype DX RS in combination with the prognostic stage in the updated AJCC 8th edition. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was searched to identify invasive ductal breast cancer cases in T1-2N1M0 stage with ER positive HER2 negative status and Oncotype DX RS diagnosed between 2004 and 2012. Patients with unknown histologic grade or PR status, no or unknown surgery performed, or less than 6 months of follow up were excluded. Patients with RS 0-10, 11-25, >25 were categorized into low risk, midrange risk and high risk groups respectively. Comparisons of the distribution of RS groups among prognostic stages were performed using Pearson's chi-square. Breast cancer-specific survival (BCSS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared across RS groups using the log-rank statistic. Cox models were fitted to compare the association between RS groups, prognostic stages and BCSS or OS after adjusting for other characteristics. Results: Altogether 4059 cases were enrolled, which were categorized into prognostic stage IA-IIIA (only 357 cases in stage IIB and 35 cases in stage IIIA). More than 60% cases in prognostic stage IA-IIA had their RS in midrange risk group. There were decreasing proportion of low risk RS group and increasing proportion of high risk RS group with the ascending of prognostic stages (P<0.001). The median follow up was 59 months. There were significant differences in BCSS and OS among RS groups (log-rank P<0.001). In the subgroup analysis, there were also significant differences in BCSS and OS among RS groups in prognostic stages IA-IIA. In the multivariate Cox analysis, the RS group was an independent prognostic factor for BCSS (midrange risk vs. low risk, HR=3.647, 95% CI: 1.124-11.837, P=0.031; high risk vs. low risk, HR=15.372, 95% CI: 4.600-51.374, P<0.001) and OS (midrange risk vs. low risk, HR=1.718, 95% CI: 1.039-2.840, P=0.035; high risk vs. low risk, HR=4.225, 95% CI: 2.462-7.251, P<0.001) along with the prognostic stage. Conclusions: Oncotype DX RS has prognostic significance in T1-2N1M0 ER+/HER2- disease. Further prospective research is warranted.

Citation Format: Chen H, Wang M, Zhang P, Zhang M, Wu K. The significance of Oncotype DX recurrence score in T1-2N1M0 ER positive HER2 negative breast cancer: An analysis combined with the prognostic stage in the updated AJCC 8th edition [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 P4-08-33.
Abstract P4-10-04: Assessment of clinical trial participation on breast cancer survival
Authors: Parise C , Caggiano V
Published: May 2019

Background

Accredited cancer treatment centers offer clinical trials for patients since it is universally accepted that participation in these trials is advantageous.

Purpose

The purpose of this study was to assess whether clinical trial participation was associated with a survival advantage.

Methods

We identified 308,291 cases of first primary female invasive breast cancer from the California Cancer Registry 2000-2015. Participation in a clinical trial was documented. Clinical trials were defined as National Cancer Institute (NCI) sponsored studies such as National Surgical Adjuvant Breast and Bowel Project (NSABP) and Southwest Oncology Group (SWOG); pharmaceutical trials; and local investigator initiated studies.

The distribution of age, race/ethnicity, socioeconomic status (SES), and stage between clinical trial participants and non-participants was compared using contingency tables and the χ2 Test.

Kaplan-Meier Survival Analysis and the Log Rank test were used to compare differences in breast cancer specific survival between participants and non-participants. Cox Regression Analysis was used to estimate the risk of mortality between participants and non-participants after adjusting for age, race/ethnicity, SES, grade, and treatment. Analyses were conducted separately for each stage. Hazard ratios (HR) and 95% confidence intervals (CIs) were reported.

Results

There were 3,517 (1.1%) patients who participated in a clinical trial. Almost 50% of participants were enrolled in an NCI trial, 38% in a local/investigator initiated study, and 13% were in a trial sponsored by a pharmaceutical company. Trial participation was highest for patients less than 45 years of age (21.9%) and lowest in patients 70 years of age and older (12.3%). Most participants were in stage 2 (44.6%). Participation increased with increasing SES. Only 8.5% of participants were in the lowest SES whereas 35.4% were in the highest SES.

Unadjusted survival analysis indicated that there was no survival advantage for stage 1 patients (χ2 = 0.41, p=0.52) whereas study participants in stages 2, 3, and 4 had statistically significantly better survival. Adjusted hazard ratios indicated that stage 2 patients participating in a trial had a 23% reduced risk of mortality (HR=0.77; CI: 0.65 - 0.94). For patients in stage 4, the risk of mortality was reduced by 36% (HR=0.64; CI: 0.47 - 0.87). There was no risk reduction for patients in stages 1 and 3.

Conclusion

Only a small percent of patients enroll in breast cancer clinical trials and participation is correlated with age and SES. There is a survival advantage for participation in a clinical trial for stages 2 and 4 patients.

Citation Format: Parise C, Caggiano V. Assessment of clinical trial participation on breast cancer survival [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-10-04.
Abstract P4-10-09: The impact of Charlson comorbidity index on survival of triple negative breast cancer
Authors: Parise C , Caggiano V
Published: May 2019

Background

Patients with cancer and comorbidities have been found to have poorer survival since they may be unable to receive or complete treatments. It is not clear if comorbid conditions impact survival of patients in all stages of disease and all ER/PR/HER2 subtypes.

Purpose

The purpose of this study was to determine how the Charlson Comorbidity Index (CCI) affected the risk of mortality of triple negative breast cancer (TNBC) within each stage of disease.

Methods

We accessed 22,503 cases of TNBC and documented CCI from the California Cancer Registry 2000-2015. The CCI is a weighted index based on the presence of certain comorbid conditions twelve months prior through six months following the cancer diagnosis and weighted by the severity of those conditions. A score of 0 is interpreted as no significant comorbidity burden and scores of 3 or more are generally interpreted as a high comorbidity burden.

Kaplan-Meier Survival Analysis and the Log Rank test were used to compare differences in breast cancer specific survival between patients with a CCI of 1, 2 or higher (2+) versus a CCI of 0. Cox Regression Analysis was used to estimate risk of mortality of CCI after adjusting for age, race/ethnicity, socioeconomic status, grade, and treatment. Analyses were conducted separately for each stage. Hazard ratios and 95% confidence intervals (CIs) were reported.

Results

There 16,664 (74.1%) cases with a CCI of 0; 3,915 (17.4%) with a CCI of 1; 1,055 (4.7%) had a CCI of 2, and the remaining 869 (3.9%) cases of TNBC had a CCI of 3 or higher.

Unadjusted survival analysis indicated that for stages 2 and 3, there was increased survival with decreasing CCI score. For stages 1 and 4, survival was only better for patients with a CCI of 0 versus a CCI of 2+.

Cox regression analysis indicated that the CCI made no difference in risk of mortality for patients with stage 1 disease. Patients with a CCI of 2+ had an increased risk of mortality when compared with a CCI of 0 for stage 2 (HR = 1.48, CI: 1.25-1.77), stage 3 (HR=1.25, CI: 1.03-1.52) and stage 4 (HR = 1.53; CI: 1.22-1.92).

Conclusion

Comorbidity as measured by the CCI does not increase the risk of mortality for patients with stage 1 TNBC and only increases risk of mortality in higher stages for patients with a CCI score of 2 or higher.

Citation Format: Parise C, Caggiano V. The impact of Charlson comorbidity index on survival of triple negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-10-09.
Abstract P4-10-17: Plasma metabolomic signatures associated with long-term breast cancer risk in the SU.VI.MAX prospective cohort
Authors: Lucie L , Céline D , Bernard L , Aicha D , Adrien R , Marie-Paule V , Mélanie P , Marie L , Tom F , Delphine C , Laurent Z , Pilar G , Serge H , Mélanie D , Valentin P , Bernard S , Paule L-M , Emmanuelle K-G , Nathalie D-P , Claudine M , Stéphanie D , Estelle P-G , Mathilde T
Published: May 2019

Purpose: Breast cancer is a major cause of death in occidental women. Mechanisms involved in its etiology remain misunderstood. Metabolomics is a powerful tool which may help elucidating novel biological pathways and identify new biomarkers in order to predict breast cancer well before symptoms appear. The aim of this study was to investigate whether untargeted metabolomic signatures from blood draws of healthy women could contribute to better understand and predict the long-term risk of developing breast cancer.

Methods: A nested case-control study was conducted within the SU.VI.MAX prospective cohort (13 years of follow-up) to analyze baseline plasma samples of 211 incident breast cancer cases and 211 matched controls by LC-MS mass spectrometry. Multivariable conditional logistic regression models were computed.

Results: 83 ions were significantly associated (corrected-pvalue <0.05) with breast cancer risk. Notably, we observed that a lower plasma level of O-succinyl-homoserine and higher plasma levels of valine/norvaline, glutamine/isoglutamine, 5-aminovaleric acid, phenylalanine, tryptophane, γ-glutamyl-threonine, ATBC, 2-amino-cyanobutanoic acid and pregnene-triol sulfate were associated with an increased risk of developing breast cancer during follow-up. Corrected-pvalues ranged from 0.009 (OR=1.43[1.14-1.78] for phenylalanine and OR=1.45[1.15-1.83] for valine/norvaline) to 0.03 (OR=1.28[1.03-1.58] for 2-amino-cyano-butanoic acid).

Conclusion: Several pre-diagnostic plasmatic metabolites are strongly associated with long-term breast cancer risk. If confirmed in other independent cohort studies, these results could help to identify healthy women at higher risk of developing breast cancer in the subsequent decade and to propose a better understanding of the complex mechanisms involved in its etiology.

Trial registration: SU.VI.MAX, clinicaltrials.gov NCT00272428. Registered 3 January 2006

Keywords: Metabolomics, breast cancer, mass spectrometry, plasma, prospective study

Citation Format: Lucie L, Céline D, Bernard L, Aicha D, Adrien R, Marie-Paule V, Mélanie P, Marie L, Tom F, Delphine C, Laurent Z, Pilar G, Serge H, Mélanie D, Valentin P, Bernard S, Paule L-M, Emmanuelle K-G, Nathalie D-P, Claudine M, Stéphanie D, Estelle P-G, Mathilde T. Plasma metabolomic signatures associated with long-term breast cancer risk in the SU.VI.MAX prospective cohort [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 P4-10-17.
Abstract P4-14-10: Withdrawn
Authors: Ekholm M , Bendahl P-O , Fernö M , Nordenskjöld B , Stål O , Rydén L
Published: May 2019

This abstract was withdrawn by the authors.

Citation Format: Ekholm M, Bendahl P-O, Fernö M, Nordenskjöld B, Stål O, Rydén 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 P4-14-10.
Abstract P5-02-06: High-risk lesions diagnosed at MRI-guided vacuum-assisted breast biopsy: Imaging characteristics, outcome of surgical excision or imaging follow-up
Authors: Okamoto S , Covelli JD , DeMartini WB , Daniel BL , Ikeda DM
Published: May 2019

PURPOSE

To evaluate imaging characteristics, outcome of surgical excision or imaging follow-up on high-risk lesions diagnosed at MRI-guided vacuum-assisted breast biopsy (MRI-VAB).

MATERIALS AND METHODS

We retrospectively reviewed 581 lesions, to include benign, high-risk and malignant lesions, undergoing 9-gauge MRI-VAB from January 2015 to April 2018. We collected patient demographics, risk factors and indications, breast MRI BI-RADS descriptors, histopathological diagnosis at MRI-VAB and surgical excision, frequency of upgrade to malignancy and imaging follow-up of high-risk lesions found in this period.

RESULTS

101 patients with 107/581 (18.4% of all lesions) had high risk lesions at MRI-VAB, including atypical ductal hyperplasia (ADH)(n=19/107, 17.8%), lobular neoplasia (n=35/107, 32.7) including atypical lobular hyperplasia (ALH), lobular carcinoma in situ (LCIS), ALH plus LCIS, papillary lesions (n=44/107, 41.1%), radial scar/complex sclerosing lesion (RS/CSL)(n=8/107, 7.5%) and flat epithelial atypia (FEA)(n=1/107, 1%). 71/107 (66.4%) high risk lesions were excised. 16/71 (22.5%) were upgraded to malignancy (4 invasive cancer, 12 DCIS). The upgrade rate for ADH and lobular neoplasia was 5 /16 (31.3%) and 8/26 (30.8%) respectively. The upgrade rate for RS/CSL was 1/6 (16.7%). Of the 22 papillary lesions excised, 2 (9.1%) demonstrated pathologic atypia and were upgraded to DCIS. The other 20 papillary lesions had no upgrade or atypia. Excised high risk lesions showing upgrade varied from 0.4 to 6 cm in length (average 2.1 cm). Increasing size correlated with tendency towards increased upgrade to malignancy, but there were no other specific imaging features to predict malignancy upgrade.

CONCLUSION

There were no specific MRI imaging characteristics of high-risk lesions to predict malignancy upgrade. Therefore, surgical excision is recommended for high risk lesions especially ADH or lobular neoplasia. Additionally, non-atypical papillomas did not demonstrate malignancy upgrade in our small study. And further larger studies may demonstrate that these lesions may not need to be surgically excised.

Citation Format: Okamoto S, Covelli JD, DeMartini WB, Daniel BL, Ikeda DM. High-risk lesions diagnosed at MRI-guided vacuum-assisted breast biopsy: Imaging characteristics, outcome of surgical excision or imaging follow-up [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 P5-02-06.
Abstract P5-03-09: LINC00624 binding with SFPQ/MATR3/ NONO protein complexes enhances resistance to neoadjuvant therapy in HER-2 positive breast cancer by inhibiting tumor immune response
Authors: Zhang Q , Xiu B , Chi Y , Chi W-R , Wu J
Published: May 2019

Background

Neoadjuvant chemotherapy(NAC) has been widely used for its ability to downstage breast cancer. With anti-HER2 therapy, around half of the HER2 positive patients achieve pCR after NAC. However, treatment failure is still a concern and leads to a worse prognosis. New biomarkers and biological mechanisms are waiting to be discovered to tackle this problem.

Methods

RNA-Seq was performed to identify differently expressed RNAs between pCR and non-pCR group. The IC50 value was measured by CCK-8 assay in HER-2 positive cells (SK-BR-3 and JIMT-1). Quantitative RT-PCR (qRT-PCR) was used to detect the expression levels of LINC00624 and its potential target genes. RNA-seq and GSEA analysis was carried out to determine the target pathways regulated by LINC00624.

Results

Core needle biopsy tissue from HER-2 positive patients was collected before NAC. LINC00624 was found to be down regulated in pCR group compared with non-pCR group by RNA-seq. High expression of LINC00624 was associated with poor overall survival in TCGA database and our own patients cohort. Overexpression of LINC00624 promoted cell proliferation and colony-forming ability. Meanwhile, the IC50 values of Paclitaxel and Trastuzumab in HER-2 positive breast cells were decreased by LINC00624. Via RNA pull-down assay and mass spectrometry, the SFPQ/MATR3/NONO protein complex, which was reported to be associated with the innate immune system, was found to interact with LINC00624. RNA-seq further revealed that several immunological and inflammatory factors, including 'IFN-α response', 'IFN-γ response' and 'TNF-α via NF-κB' were suppressed by LINC00624. IFN downstream molecules were inactivated in LINC00624 overexpressing cells following TNF-α, IFN-α, IFN-β and poly (I:C) treatment, which implies the immune inhibition ability of LINC00624 .

Conclusion

LINC00624 is associated with resistance to NAC in HER-2 positive breast cancer. It binds with the SFPQ/MATR3/NONO complex and desensitizes cell response to chemotherapy and anti-HER2 agents via suppressing immunological and inflammatory effect. This study suggests that LINC00624 could serve as a biomarker to predict therapy response to NAC in HER-2 positive breast cancer.

Citation Format: Zhang Q, Xiu B, Chi Y, Chi W-R, Wu J. LINC00624 binding with SFPQ/MATR3/ NONO protein complexes enhances resistance to neoadjuvant therapy in HER-2 positive breast cancer by inhibiting tumor immune response [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 P5-03-09.
Abstract P5-04-29: Efficacy and safety of low-dose everolimus in Chinese HR-positive, HER2-negative metastatic breast cancer patients
Authors: Shao X , Wang X , Chen Z , Zheng Y
Published: May 2019

Background: Everolimus has been testified to be effective among postmenopausal women with hormone receptor-positive human epidermal growth factor receptor-2 negative (HR+/HER2-) metastatic breast cancer (MBC). However, everolimus at dose of 10mg was accompanied by a higher incidence of mTOR-inhibitor class-effect adverse events (AEs) which usually leading to dose reduction or interruption. Additionally, some studies suggested that there was no correlation between dose intensity (5 vs. 10 mg labeled dose) and efficacy. Consequently, we conducted the present study aiming to explore the efficacy and safety of everolimus at dose of 5 mg plus endocrine therapy in Chinese population.

Methods: 68 HR+/HER2- MBC patients were included in this exploratory study who received everolimus at the dose of 5mg in Zhejiang Cancer Hospital between September 2014 and September 2017. Progression free survival(PFS) and overall survival(OS) were estimated by the Kaplan- Meier method, and the hazard ratios(HRs) and corresponding 95% confidence intervals(CIs) were estimated using the Cox proportional harzard model. Besides, objective response rate(ORR), clinical benefitrate(CBR) and safety profile were also evaluated.

Results: After a median follow up of 14 months, PFS was 5.3 months (95%CI 4.2-6.4), and OS was immature. 16(23.5%) were at the first or second-line, 52(76.5%) were at third-line or later. PFS for the first and second-line is significantly longer than that for the third-line or later (12.9 months vs. 4.6 months, P=0.009, HR=0.395, 95% CI=0.192-0.811). 11(16.2%) achieved partial response (PR), 42(61.7%) had stable disease (SD), and 15(22.1%) reported progressive disease (PD). The ORR and CBR were 16.2%, 35.2%, respectively. Most common all grade adverse events were stomatitis(26.5%), fatigue(10.0%), infection(11.8%), thrombocytopenia(5.9%), anemia(4.4%), hyperglycemia(4.4%). The most common ≥3 grade adverse events were stomatitis(4.4 %), infection(2.2%) and thrombocytopenia(1.1%).

Conclusions: The combination of low-dose everolimus and endocrine therapy was highly effective especially at the earlier line in Chinese population. And the safety profiles were similar to previous studies but the incidences were greatly lower. The combination of low-dose everolimus and endocrine therapy may become a proper option for HR+/HER2- MBC.

Citation Format: Shao X, Wang X, Chen Z, Zheng Y. Efficacy and safety of low-dose everolimus in Chinese HR-positive, HER2-negative metastatic breast cancer patients [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 P5-04-29.
Abstract P5-07-09: Withdrawn
Authors: Ahirwar DK , Nasser MW , Shukla RK , Shilo K , Ganju RK
Published: May 2019

This abstract was withdrawn by the authors.

Citation Format: Ahirwar DK, Nasser MW, Shukla RK, Shilo K, Ganju RK. 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 P5-07-09.
Abstract P5-07-16: Role of collagen X in enhancing the metastatic potential of breast cancer cells using a MDA-MB-231 cell line model
Authors: McKiernan K , Jimenez H , McEachern M , Hubbard J , O'Connell M
Published: May 2019

Breast cancer is the second highest cause of cancer related deaths for women in developed countries. Breast cancer patients with distant metastasis at the time of diagnosis have an estimated 5-year relative survival rate of 26% as compared to a 99% survival rate of patients who have localized tumors. Evidence suggests that collagens play a role in enhancing the metastatic capability of breast cancer cells. Short chain collagen, collagen X, is encoded by the collagen type x alpha 1 chain (COL10A1) gene and is normally expressed exclusively by hypertrophic chondrocytes during endochondral ossification. Recently, COL10A1 gene expression has been found to be overexpressed in various tumor types, including breast tumors. It is hypothesized that an increase in COL10A1 expression may play a role in breast cancer metastasis. The goal of our project was to evaluate the role of collagen X in breast cancer metastasis using the MDA-MB-231 breast cancer cell line. Stable cell lines were generated to express either GFP only (MDA-VEC) or GFP tagged COL10A1 (MDA-COL). GFP and COL10A1 transcript and protein levels were examined to confirm overexpression of collagen X and transwell assays were used to determine changes in the invasive capability of the cells. Cells overexpressing collagen X demonstrated a higher rate of invasion suggesting that collagen X may play a role in enhancing the metastatic potential of breast cancer cells. Understanding the role collagen X plays in breast cancer metastasis may provide a mechanism for developing diagnostic and prognostic strategies for identifying patients whose breast cancer is more prone to metastasize.

Citation Format: McKiernan K, Jimenez H, McEachern M, Hubbard J, O'Connell M. Role of collagen X in enhancing the metastatic potential of breast cancer cells using a MDA-MB-231 cell line model [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 P5-07-16.
Abstract P5-09-12: Germline mutation in TP53 gene in a cohort of 2,561 Chinese high-risk breast cancer patients using multigene panel testing
Authors: Kwong A , Shin V , Au CH , Ho C , Slavin T , Weitzel J , Chan TL , Ma E
Published: May 2019

Background: Li-Fraumeni syndrome (LFS) is a rare autosomal genetic disorder with germline TP53 mutations. Patients with TP53 mutations have a higher risk of developing breast cancer than those harboring BRCA mutations. Although limited studies have shown that TP53 mutation carriers are less responsive to low dose radiation and more susceptible to induce new malignancies from radiotherapy. Moreover screening strategies allows early detection of a spectrum of cancers related to TP53 mutations. From work of BRCA mutations where over 40% novel mutations were detected in Chinese cohort, it is important to evaluate the frequency of TP53 mutation in Chinese to better understand the spectrum to guide appropriate clinical management of these high risk individuals.

Methods: TP53 gene mutation screening was performed on 2,561 high-risk breast cancer patients using multigene panel testing. The patients were accrued by Hong Kong Hereditary and High Risk Breast Cancer Program from March 2007 to May 2018. All detected pathogenic mutations were further validated by bi-directional DNA sequencing and analyzed by our in-house developed bioinformatics pipeline.

Results: Sixteen distinct pathogenic or likely pathogenic variants were identified, and 3 of them were de novo TP53 mutations (18.75%). The mean age of patients who harbored TP53 mutation was 30.44 years (range 18-44), and 50% of the tumors were bilateral breast cancer. Of sixteen different pathogenic mutations, majority of them were missense mutation (87.5%), and 2 were nonsense mutation (12.5%). Four of the sixteen TP53 mutation carriers had family history of breast cancer, while others had a family history of lung cancer (43.75%).

Conclusion: This study revealed that seven patients were found to habor TP53 mutation even when they did not meet the criteria of LFS of LFS-like phenotype, implicated the importance of using multigene panel test for probands and their relatives to offer a comprehensive surveillance programe for TP53 carriers.

Citation Format: Kwong A, Shin V, Au CH, Ho C, Slavin T, Weitzel J, Chan TL, Ma E. Germline mutation in TP53 gene in a cohort of 2,561 Chinese high-risk breast cancer patients using multigene panel testing [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 P5-09-12.
Abstract P5-10-01: Using whole genome sequencing and somatic mutation signatures to unravel insight into familial breast cancer aetiology
Authors: Simpson P , Nones K , Johnson J , Newell F , Patch A-M , Thorne H , Kazakoff S , De Luca X , Parsons M , Ferguson K , Reid L , McCart Reed A , Srihari S , Lakis V , Davidson A , Mukhopadhyay P , Holmes O , Xu Q , Wood S , Leonard C , Beasley J , Degasperi A , Nik-Zainal S , Ragan M , Spurdle A , Khanna KK , Lakhani S , Pearson J , Chenevix-Trench G , Waddell N
Published: May 2019

Approximately 10-15% of breast cancers are associated with a strong family history of disease. Pathogenic variants in BRCA1, BRCA2 or other moderate to highly penetrant susceptibility genes (e.g. TP53, ATM, CHEK2, PALB2 and PTEN) account for a number of breast cancer families. However, for over 50% of families the underlying genetic contribution to their risk remains unknown (termed here as non-BRCA1/2). This has a profound impact for how individuals and their families are managed in the clinic. We applied whole genome sequencing (WGS) to determine whether somatic mutation analysis can reveal insight into the aetiology of familial breast cancer. The full repertoire of somatic mutations was evaluated in 26 BRCA1, 22 BRCA2 and 32 non-BRCA1/2 tumours; including SNPs, indels, copy number changes and structural rearrangements, and mutational signatures. Genomes were also analysed using the HRD Index and HRDetect, as predictors of homologous recombination deficiency. BRCA1, BRCA2 and non-BRCA1/2 tumours exhibited a different burden of mutations, a different spectrum of mutational signatures and different telomere length. Based on collective patterns of mutation signatures, tumours were classified as 'BRCA1-like', 'BRCA2-like' or 'non-BRCA1/2-like' with a 15% rate of tumour re-classification from their original clinical BRCA status. The results demonstrate the power of WGS to differentiate between BRCA1 and BRCA2 driven tumours; in the identification of double-pathogenic germline mutation carriers based on the resulting somatic mutation signature; and in the interpretation of BRCA unclassified variants. WGS of tumour genomes reveals fascinating insights into tumour aetiology and could compliment current genetic testing of breast cancer families.

Citation Format: Simpson P, Nones K, Johnson J, Newell F, Patch A-M, Thorne H, Kazakoff S, De Luca X, Parsons M, Ferguson K, Reid L, McCart Reed A, Srihari S, Lakis V, Davidson A, Mukhopadhyay P, Holmes O, Xu Q, Wood S, Leonard C, Beasley J, Degasperi A, Nik-Zainal S, Ragan M, Spurdle A, Khanna KK, Lakhani S, Pearson J, Chenevix-Trench G, Waddell N. Using whole genome sequencing and somatic mutation signatures to unravel insight into familial breast cancer aetiology [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 P5-10-01.
Abstract P5-16-07: Short-term outcomes and QoL following autologous fat transfer in oncoplastic and reconstructive breast surgery
Authors: Bjelic-Radisic V , Oberfichtner K , Wurzer P , Trapp E , Rappl T , Reisniger J , Kamolz L-P , Tamussino K
Published: May 2019

Background: Breast cancer (BC) is with 30% among all cancers the most common cancer among women in Austria. Regarding therapy and management of BC, surgical treatments with resection and reconstruction play a crucial role. Breast-conserving therapy (BCT) represents a common procedure. However, mastectomy is still needed in about 30% of the patients with the diagnosis BC and as prophylactic surgery in indicated cases. Recently, autologous fat transfer (AFT, lipofilling) has been used to improve cosmesis in oncoplastic and reconstructive breast surgery. There is a gap of evidence for the oncological safety as well as the benefit for quality of life (QoL) in patients who had an AFT after the BC or prophylactic surgery.

Material and methods: We assessed peri-and postoperative results, oncological outcomes and QoL in 55 patients undergoing AFT after BCT or mastectomy at our department between 2013 and 2018. QoL was assessed with the EORTC QLQ C30 and QLQ-BRECON23 questionnaires.

Results: Overall, 55 patients (73 breasts) underwent AFT after BCT or mastectomy. 39 patients had a diagnosis of invasive BC (four bilateral) and six patients a diagnosis of DCIS. 24 mastectomies were done as prophylactic surgery. AFT was done in 22 cases with nipple sparing mastectomy (NSM), in 30 cases with skin sparing mastectomy (SSM), in 9 cases with simple mastectomy ± reconstruction and in 12 cases with BCT. The number of AFT sessions was 1-8 (mean 1.8). The injected fat volume per session was 30-390 ml. There were 10 (14%) complications: 3 hematomas (none needed reintervention), local inflammation requiring antibiotic therapy (n=3), formation of an oil cyst (n=1), and fat necrosis (n=3). In two cases of fat necrosis biopsy was performed to confirm the diagnosis. After a median follow-up of 34 months there was one recurrence (Paget´s disease after BC). QoL data will be presented at the meeting.

Conclusion: Lipofilling after mastectomy for cancer appears to be oncologically safe. Our complication rate is relatively high, although additional surgical intervention (biopsy) was only necessary in two cases. Patients considering AFT should be informed about additional risk for biopsy, as well as other common complications.

Citation Format: Bjelic-Radisic V, Oberfichtner K, Wurzer P, Trapp E, Rappl T, Reisniger J, Kamolz L-P, Tamussino K. Short-term outcomes and QoL following autologous fat transfer in oncoplastic and reconstructive breast surgery [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 P5-16-07.
Abstract P5-18-07: Withdrawn
Authors: Yang F , Wu S , Mo M , Liu Y , Liu G
Published: May 2019

This abstract was withdrawn by the authors.

Citation Format: Yang F, Wu S, Mo M, Liu Y, Liu G. 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 P5-18-07.
Abstract P6-02-04: Ultrasound assessment of residual disease after neoadjuvant chemotherapy (NACT) in node positive triple negative breast cancer (TNBC)
Authors: Adrada BE , Valero V , Reddy SM , Barcenas CH , Candelaria R , Wei W , Rauch GM
Published: May 2019

Purpose: To determine accuracy of preoperative ultrasound after NACT to predict residual disease in triple negative breast cancer (TNBC) patients with confirmed axillary nodal metastasis.

Methods: This is an institutional review board approved retrospective study of TNBC patients who received NACT at MD Anderson Cancer Center from January 1999 - June 2015. We identified 327 TNBC patients who had cytologically confirmed breast and nodal disease at baseline evaluation and had preoperative ultrasound evaluation of residual disease. Ultrasound response was divided in tree categories: radiologic complete response (rCR) - complete resolution of the malignant mass); near-rCR - no discernible mass, only an isoechoic flat tumoral bed); and residual disease (RD) - a discernible mass is seen. Axillary ultrasound images were evaluated for lymph node size, cortical thickness and residual morphological type after NAC (type I-VI). Ultrasound breast and axillary findings were compared with final surgical pathology.

Results: In 89 cases (27%), pCR was achieved. 74% (242/327) were unifocal and 26% (86/327) multifocal. Ultrasound rCR was seen in 11% patients (36/327). Of those, 64% (23/36) showed pCR and 36% (13/36) showed residual disease. Ultrasound near-rCR was seen in 26% (84/327). Of those, pCR was seen 49 % (41/84) and residual disease in 51% (43/84). Residual disease was seen in 63% (207/327), 12% (25/207) showed pCR and 88% (182/207) showed residual disease. Regarding axillary lymph nodes, long axis diameter mean was 1.57 cm for patients with pCR and 1.6 cm for no pCR, short axis diameter mean was 0.67 cm for pCR and 0.87 cm for no pCR. Cortical thickness mean was 2 mm for pCR versus 9 mm for no pCR.

Sensitivity of ultrasound for assessment residual disease (ultrasound was considered positive if either breast ultrasound or axillary ultrasound showed residual disease) was 97%. Specificity is 22.47% with a NPV of 74% and PPV of 77%.

Conclusion: Breast and axillary ultrasound performed after NACT showed low specificity but high sensitive to detect residual disease. rCR and near rCR were related with pCR in 64% and 49 % of the cases respectively.

Citation Format: Adrada BE, Valero V, Reddy SM, Barcenas CH, Candelaria R, Wei W, Rauch GM. Ultrasound assessment of residual disease after neoadjuvant chemotherapy (NACT) in node positive triple negative breast cancer (TNBC) [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 P6-02-04.
Abstract P6-07-03: A live tissue platform allows dynamic measurement of neovascularization and prediction of clinical response in human breast cancer samples, ex vivo
Authors: Smalley M , Alam N , Murmu N , Somashekhar S , Ulaganathan B , Thayakumar A , Maciejko L , Ganesh J , Lawson M , Gertje H , Shanthappa BU , Goldman A
Published: May 2019

Background: Outgrowth of new blood vessels (neovascularization) allows tumors to supply themselves with oxygen and nutrients, and to rapidly metastasize throughout the body. Triple negative breast cancer (TNBC) is particularly susceptible to neovascularization. However, success with anti-angiogenics is highly variable and often patient-specific. This is particularly true as anti-angiogenics are being combined with immunotherapies. Thus, there is a huge unmet need for clinicians to test and predict clinical efficacy of anti-angiogenics at the individual patient level, prior to treatment.

Methods: Here, we characterize a patient-autologous, ex-vivo tumor model, termed CANscript, as a platform to study the intratumor microvascular density (iMVD) of breast cancer samples (N=15). To profile iMVD we used immunohistochemical (IHC) analysis of CD34, an early biomarker of neovascularization. We then introduced anticancer and anti-angiogenic agents (e.g. Avastin) for 72 hours, and subsequently quantified phenotypic response to drugs by testing viability, cell death, proliferation and morphology. These quantitative data were then fed into a machine learning algorithm that provides a clinical response prediction (M-Score).

Results: We determined that ex-vivo culture reliably retains baseline heterogeneity of iMVD based on expression of CD34+ nodes per visual field by IHC. Furthermore, we show that anticancer and anti-angiogenic agents will dynamically alter iMVD, ex-vivo, in a patient-specific manner. Finally, we show that prediction of clinical response using the 'M-Score' algorithm associates with diminished expression of CD34 per visual field of IHC after drug pressure.

Summary: Neovascularization and iMVD are features of aggressive cancers, such as TNBC. CANscript provides a rapid assessment of clinical response to anticancer drugs, many of which induce their antitumor effect by targeting the tumor vasculature. We show that pharmacodynamics of antiangiogenics can be captured during acute ex-vivo culture under drug pressure, which associate to clinical response prediction. Therefore, we highlight the ability of CANscript as a platform to predict clinical response to anti-angiogenic drugs, and may therefore be a logical 'testing ground' to predict clinical efficacy of antiangiogenic drugs combined with immunotherapies.

Citation Format: Smalley M, Alam N, Murmu N, Somashekhar S, Ulaganathan B, Thayakumar A, Maciejko L, Ganesh J, Lawson M, Gertje H, Shanthappa BU, Goldman A. A live tissue platform allows dynamic measurement of neovascularization and prediction of clinical response in human breast cancer samples, ex vivo [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 P6-07-03.
Abstract P6-13-06: Estrogen-based hormone replacement [HRT] therapy is substantially more effective than tamoxifen in reducing breast cancer mortality and breast cancer case fatality ratio: Emergence of a new paradigm
Authors: Ragaz J , Shakeraneh S , Qian H , Wilson KS , Wong H , Spinelli JJ
Published: May 2019

OBJECTIVE: To compare, in the setting of breast cancer (BrCa) prevention, the impact of estrogen-based hormone replacement therapy (E-HRT) vs. tamoxifen (TAM) on breast cancer mortality (BrCa-M) and breast cancer case fatality ratio (BrCa-CFR), by analyzing data from the Women's Health Initiative Trial 2 (WHI HRT Trial 2, E-HRT vs. placebo [P])1 and the International Breast Cancer Intervention Study 1 (IBIS-1), TAM vs. P.2

METHODS: Hazard ratios (HR) and confidence intervals (CI) for BrCa incidence and mortality were extracted from the original WHI HRT Trial 2 and IBIS-1 trials.1,2 BrCa-CFRs were estimated by dividing the mortality HR by the incidence HR. Subsequently, to compare E-HRT vs. TAM outcomes, the ratios of HRs (HR1/HR2) between the two trials were estimated separately for BrCa-M and BrCa-CFR. The 95% CI was derived through logarithmic transformation of the 95% CI originally reported.

RESULTS:

Mortality and Case Fatality Outcomes: Impact of E-HRT versus TAM, expressed as ratio of HRs E-HRT vs. Placebo, HR1TAM vs. Placebo, HR2HR1/HR2pMortality0.55 (0.33-0.92)1.19 (0.68-2.10)0.46 (0.22-0.99)0.046Case Fatality0.70 (0.40-1.20)1.68 (0.93-3.01)0.42 (0.18-0.94)0.040

CONCLUSIONS: While acknowledging between-trial comparisons including eligibility differences, E-HRT yields significant reductions in BrCa mortality and case fatality as compared with TAM (54% and 58% respectively). These unexpected breast cancer mortality reductions represent major public health gains, additional to the already known superiority of E-HRT over TAM in terms of skeletal fracture rates and Alzheimer's dementia mortality reduction, and, in women entering menopause, also of cardiac and all-cause mortality reductions.

REFERENCES:

1. Manson JE, Aragaki AK, Rossouw JE, et al. Menopausal Hormone Therapy and Long-term All-Cause and Cause-Specific Mortality: The Women's Health Initiative Randomized Trials. JAMA 2017;318:927-38.

2. Cuzick J, Sestak I, Cawthorn S, et al. Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial. The Lancet Oncology 2015;16:67-75.

Citation Format: Ragaz J, Shakeraneh S, Qian H, Wilson KS, Wong H, Spinelli JJ. Estrogen-based hormone replacement [HRT] therapy is substantially more effective than tamoxifen in reducing breast cancer mortality and breast cancer case fatality ratio: Emergence of a new paradigm [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 P6-13-06.
Abstract P6-14-04: Not presented
Authors: Mohd Taib NA , Islam T , Su TT , Musthaffa S , Abdullah Din N , Rahman Z , Mohamed KNB , Kaur S , Filza J , Shaheera F , Ellsworth Beaumont C
Published: May 2019

This abstract was not presented at the conference.

Citation Format: Mohd Taib NA, Islam T, Su TT, Musthaffa S, Abdullah Din N, Rahman Z, Mohamed KNB, Kaur S, Filza J, Shaheera F, Ellsworth Beaumont C. 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 P6-14-04.
Abstract P6-14-07: Not presented
Authors: Lai J , Antill Y , Richardson G , Vereker M , David S
Published: May 2019

This abstract was not presented at the conference.

Citation Format: Lai J, Antill Y, Richardson G, Vereker M, David S. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-14-07.
Abstract P6-17-05: Independent validation of a combined biomarker based on the PAM50 HER2-enriched subtype and ERBB2 mRNA levels following HER2 blockade without chemotherapy in the PerELISA phase II trial
Authors: Prat A , Griguolo G , Dieci MV , Bisagni G , Frassoldati A , Bianchi GV , Pascual T , Pare L , Galvan P , Urso L , Conte P , Guarneri V
Published: May 2019

Background: A combined biomarker based on HER2-enriched subtype (HER2-E) and ERBB2 mRNA predicts response and survival in HER2+ breast cancer following trastuzumab +/- lapatinib in the absence of chemotherapy (Prat et al. ASCO 2018). Here, we tested the ability of the combined biomarker to predict pathological complete response (pCR) following neoadjuvant trastuzumab, pertuzumab and endocrine therapy.

Methods: RNA from 40 baseline tumor samples from the phase II PerELISA trial were evaluated. PerELISA evaluated the efficacy of a de-escalated, chemotherapy-free neoadjuvant regimen based on dual HER2 blockade with trastuzumab and pertuzumab in combination with letrozole in HER2+/hormone receptor-positive breast cancer selected on the basis of Ki67 response after short course letrozole-alone (Guarneri ASCO 2018). Ki67 response was defined by protocol as relative Ki67 reduction ≥20% from baseline at day 14. Gene-expression was measured using the nCounter platform. Intrinsic subtypes and ERBB2 levels were determined by the PAM50 gene expression predictor. A pre-specified ERBB2 cutoff was determined to define ERBB2-high. Univariate and multivariable logistic regression analyses were performed.

Results: The proportion of HER2-E disease within the ERBB2-high and ERBB2-low groups was 46.2% (6/13) and 18.5% (5/27), respectively. The discordance rate at the individual level was 30% (12/40). A total of 6 (15%) and 34 (85%) samples were HER2-E/ERBB2-high and others, respectively. The magnitude of Ki67 reduction of the HER2-E/ERBB2-high and others groups was 64.8% and 63.2%, respectively (p=0.88). The pCR rate of HER2-E/ERBB2-high was 66.7%. The pCR rate of the others group was 14.7%. The univariate odds ratio between HER2-E/ERBB2-high tumors and the others groups was 11.60 (95% CI 1.66-81.10; p=0.014). No other clinical-pathological variable was significantly associated with pCR.

Conclusion: The combined HER2-E/ERBB2-high biomarker can identify patients who might be good candidates to receive dual HER2 blockade alone without chemotherapy.

Citation Format: Prat A, Griguolo G, Dieci MV, Bisagni G, Frassoldati A, Bianchi GV, Pascual T, Pare L, Galvan P, Urso L, Conte P, Guarneri V. Independent validation of a combined biomarker based on the PAM50 HER2-enriched subtype and ERBB2 mRNA levels following HER2 blockade without chemotherapy in the PerELISA phase II 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 P6-17-05.
Abstract P6-17-18: Pathologic complete response (pCR) in locally advanced HER2+ (HER2+) breast cancer (BC) treated with anthracycline-free neoadjuvant therapy
Authors: Somlo G , Waisman J , Yuan Y , Kruper L , Frankel P , Jones V , Lusi T , Schmolze D , Yim J , Hurria A , Mortimer J
Published: May 2019

Background: Response to neoadjuvant therapy is a predictor of progression-free and overall survival in HER2+. To decrease treatment associated toxicities in patients with HER2+ breast cancers we utilized a non-anthracycline regimen with pertuzumab (pert), trastuzumab (trast), and nab-paclitaxel (nab). Pre- neoadjuvant therapy biopsies were procured to evaluated possible biological predictors of pathologic complete response (pCR).

Methods: Women with locally advanced HER2 positive breast cancers were recruited from our breast cancer clinics. After obtaining informed consent for this IRB-approved trial, patients were treated with 6 cycles of pertuzumab (day 1 every 21 days [d]), and weekly trastuzumab 2 mg/kg with and nab-paclitaxel 100 mg/m2. Formalin fixed paraffin embedded (FFPE) or frozen biopsies pre-NT and post-NT were collected, along with blood samples at pre-treatment, and at the end of study for correlative analysis.

Results: Accrual is complete, with 42 of the 45 HER2+ patients assessed for pCR rate (3 too early to evaluate). The median age was 54 yrs (range 31-77 years). 12 patients were stage 3, 26 stage 2, and 1 stage 1 patient. The pCR rate was 64.2% (27/42), with 73.7% (14/19) in ER/PR negative patients and 56.5% (13/23) in ER/PR positive patients. The initial primary tumor size was similar for in those who achieved pCR and non-pCR patients (mean 4.1 cm vs 3.2 cm, respectively). Most patients required dose modifications. Grade 3 AEs reported included 6 patients with hypertension, 3 patients with hematological AEs, 3 patients with elevated LFTs, and 2 patients with diarrhea.

Conclusions: This anthracycline-free regimen in HER2+ BC can achieve promising pCR response rates, with toxicities well-managed with dose modifications. Results of correlative analysis will be presented.

Citation Format: Somlo G, Waisman J, Yuan Y, Kruper L, Frankel P, Jones V, Lusi T, Schmolze D, Yim J, Hurria A, Mortimer J. Pathologic complete response (pCR) in locally advanced HER2+ (HER2+) breast cancer (BC) treated with anthracycline-free neoadjuvant therapy [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 P6-17-18.