bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P4-09-13: Spectrum analysis of the inherited mutations of BRCA1/-2 genes that associated with high risk breast cancer in Saudi population
Authors: Hawsawi Yousef MohammedRabaa , Meliti Abdelrazak , Cupler Edward , Sobahy Turki , Zailaie Samar , Baghdadi Mohammed , Alardati Hosam
Published: March 2020

Background: Breast cancer (BC) is the most common prevalent cancer among female worldwide, despite the advances in molecular biology. In Saudi Arabia, the disease represents 19.9% of the total cancer-related deaths in women. Inherited mutations of BRCA1/-2 are well documented to be associated with higher risk of breast cancer.

Aim: To investigate the role of inherited mutation in BRCA1/-2 genes that associated with breast cancer in Saudi population.

Methodology: A total of 41 FFPE samples were collected from BC patients admitted to KFSHRC-Jeddah from 2013 to 2018. Genomic DNA was extracted using the Qiagen FFPE kit. A100ng of each DNA samples were used for library preparation using Ion AmpliSeq™ Library Kit Plus with Saudi Inherited Cancer Panel. Ion Torrent Proton platforms were used for DNA sequencing on Ion Torrent PGM using Ion PI™ Hi-Q™ Sequencing 200 Kit.

Results: A total of 26 distinct heterozygous BRCA1/-2 variants were identified in Saudi population, 15 variants in BRCA1 gene and 11 in BRCA2 gene. In BRCA1, one variant was nonframeshift deletion and 11 were missense, 3 variants likely benign, while in BRCA 2, one was stopgain and 6 were missense and 4 variants likely benign.

Conclusion: Screening of BRCA1/-2 genes mutations helps in understanding the risk associated with mutations of other forms of cancer in Saudi population. The preliminary data is used as an establishing of a high-throughput NGS molecular profiling for Saudi breast cancer patients

Citation Format: Yousef MohammedRabaa Hawsawi, Abdelrazak Meliti, Edward Cupler, Turki Sobahy, Samar Zailaie, Mohammed Baghdadi, Hosam Alardati. Spectrum analysis of the inherited mutations of BRCA1/-2 genes that associated with high risk breast cancer in Saudi population [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-09-13.
Abstract P4-09-14: Evaluation of the relationship between antioxidant gene polymorphisms and breast cancer
Authors: Topcu Turkan Ozturk , ısıksacan Nilgun , Kilic Zisan Asal , Pehlivan Sacide , Gunaldi Meral
Published: March 2020

Background: Myeloperoxidase (MPO) is a lysosomal enzyme found in monocytes, macrophages and primary granules of neutrophils. MPO participates in the biotransformation reaction of specific carcinogens by catalyzing the formation of hypochloric acid. The destruction of malignant and non-malignant cells is achieved via MPO enzyme. An important mechanism in oxidative stress regulation is the function of uncoupling proteins (UCP), which are among the mitochondrial membrane proteins. They control free radical formation. Theaim of thisstudywastodeterminetherelationshipbetweenpolymorphisms of myeloperoxidase (MPO), uncoupling protein 2 (UCP-2)genesanddevelopment of breastcancer. Methods: Thedistributions of genotypeandallelefrequencywascomparedamongthe groups.Thirty-seven caseswithbreastcancerandseventyhealthycontrolswereenrolled in thepresentstudy. Thestudyfocused on threefunctionalvariants; a variant in a variable number of 27 bp tandem repeatsin a variant in thepromoter region (G463A) of MPO gene and a variant in thepromoterregion(-866G/A) of UCP-2 gene. Wegenotypedthesevariantsusingthepolymerasechainreaction (PCR) and/or PCR- restrictionfragmentlengthpolymorphism (RFLP) method. Thedistribution of alleleand genotype in MPO and UCP-2 geneswerecomparedbetweencaseswithbreastcancer andhealthycontrolsusingchi-square test. Results: Significantlydecreasedbreastcancerriskswerefoundfor UCP-2 AA, and AG polymorphisms(For UCP-2 AA polymorphism OR=8.167; 95%CI:2.785-23.951; p=0.001, for UCP2 AG polymorphism OR=4.341; 95%CI:1.679-11.222; p=0.002).Significantly increasedbreastcancer risk wasfoundfor UCP-2 GG polymorphism (OR:5.0; 95%CI:2.207-11.327; p=0.001).Therewerenostatisticallysignificantdifference in any genotype of MPO whencaseswithbreastcancerandhealthycontrolswerecompared. Conclusion: In the current study, UCP-2 AA, AG and GG genotypes were found to be associated with breast cancer. In contrast, MPO GG, GA genotypes were not associated with breast cancer. Further studies are needed to determine whether these gene polymorphisms have a place in diagnosis or determining the risk of disease.

Citation Format: Turkan Ozturk Topcu, Nilgun ısıksacan, Zisan Asal Kilic, Sacide Pehlivan, Meral Gunaldi. Evaluation of the relationship between antioxidant gene polymorphisms and breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-09-14.
Abstract P4-10-11: PIK3CA status as a predictor of benefit from drugs targeting the PI3K/AKT/mTOR pathway: A meta-analysis of randomized trials
Authors: Almugbel Fahad A , Saleh Ramy , Ocana Alberto , Pandiella Atanasio , Amir Eitan
Published: March 2020

Introduction: A number of different drugs have been developed to target the PI3 kinase/AKT/mTOR pathway. Most randomized trials in breast cancer have been performed in patients unselected for pathway activation although aberrations of components of this pathway are common. Here we explore the predictive value of PIK3CA and AKT mutations in randomized trials of drugs targeting this signaling route.

Methods: We searched PubMed for randomized trials of drugs targeting the PI3 kinase/AKT/mTOR pathway in metastatic breast cancer. The search was supplemented by a manual search of recent ASCO and ESMO meetings. Eligible studies needed to report efficacy data based on presence or absence of PIK3CA or AKT status measured either in tumor specimens or in circulating DNA. Hazard ratios (HR) for progression-free survival (PFS) in PIK3CA or AKT mutant and wild-type groups were extracted and pooled in a meta-analysis using generic inverse variance and random effects modeling. Sensitivity analyses were performed based on the mechanism of action of the experimental drug.

Results: Of the 15 studies identified, 10 studies comprising of 3615 patients were eligible for analysis. Studies included pan-PI3kinase inhibitors (n=5), alpha-specific PI3kinase inhibitors (n=1), AKT inhibitors (n=2) and mTOR inhibitors (n=2). Approximately 38% of patients had either PIK3CA or AKT mutations. The addition of drugs targeting the PI3 kinase/AKT/mTOR pathway was associated with a significantly longer improvement in PFS in patients with PIK3CA or AKT mutations than in those with wild-type status (HR 0.61, 95% CI 0.50-0.75 versus HR 0.83, 95% CI 0.67-1.02, p for difference = 0.04). Similar results were observed in sensitivity analyses (see Table).

Conclusion: Benefit from drugs targeting the PI3 kinase/AKT/mTOR pathway in breast cancer appears to occur exclusively in those with PIK3CA or AKT mutations. Future trials of these drugs should be designed only in biomarker selected patients.

TableGroupPIK3CA or AKT mutationPIK3CA and AKT wildtypep for differenceHR95% CIHR95% CIExcluding AKT inhibitors0.640.52-0.790.810.63-1.030.16Excluding pan-PI3 kinase inhibitors0.580.47-0.710.710.51-1.150.24Excluding AKT and alpha-specific PI3 kinase inhibitors0.690.48-1.000.980.83-1.150.09Excluding mTOR inhibitors0.620.49-0.800.920.80-1.060.008

Citation Format: Fahad A Almugbel, Ramy Saleh, Alberto Ocana, Atanasio Pandiella, Eitan Amir. PIK3CA status as a predictor of benefit from drugs targeting the PI3K/AKT/mTOR pathway: A meta-analysis of randomized trials [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-10-11.
Abstract P4-10-16: Reactive stroma and trastuzumab resistance in HER2-positive early breast cancer
Authors: Sonnenblick Amir , Salmon-Divon Mali , Salgado Roberto , Pondé Noam , Loibl Sibylle , Denkert Carsten , Joensuu Heikki , Kellokumpu-Lehtinen Pirkko-Liisa , Azaria Amos , Loi Sherene , Michiels Stefan , Sotiriou Christos
Published: March 2020

Purpose

We investigated the value of reactive stroma as a predictor for trastuzumab resistance in patients with early HER2-positive breast cancer receiving adjuvant therapy.

Experimental Design

The pathological reactive stroma and the mRNA gene signatures that reflect reactive stroma in 209 HER2-positive breast cancer samples from the FinHer adjuvant trial were evaluated. Levels of stromal gene signatures were determined as a continuous parameter, and pathological reactive stromal findings were defined as stromal predominant breast cancer (SPBC; ≥50% stromal) and correlated with distant disease-free survival (DDFS).

Results

Gene signatures associated with reactive stroma in HER2-positive early breast cancer (N=209), were significantly associated with trastuzumab resistance in estrogen receptor (ER)-negative tumors (HR=1.27 p-interaction=0.014 [DCN], HR=1.58, p-interaction=0.027 [PLAU], HR=1.71, p-interaction=0.019 [HER2STROMA, novel HER2 stromal signature]), but not in ER-positive tumors (HR=0.73 p-interaction=0.47 [DCN], HR=0.71, p-interaction=0.73 [PLAU], HR=0.84; p-interaction=0.36 [HER2STROMA]).

Pathological evaluation of HER2-positive/ER-negative tumors suggested an association between SPBC and trastuzumab resistance. Reactive stroma did not correlate with tumor-infiltrating lymphocytes (TILs), and the expected benefit from trastuzumab in patients with high levels of TILs was pronounced only in tumors with low stromal reactivity (SPBC <50%).

Conclusions

Reactive stroma in HER2-positive/ER-negative early breast cancer tumors may predict resistance to adjuvant trastuzumab therapy.

Citation Format: Amir Sonnenblick, Mali Salmon-Divon, Roberto Salgado, Noam Pondé, Sibylle Loibl, Carsten Denkert, Heikki Joensuu, Pirkko-Liisa Kellokumpu-Lehtinen, Amos Azaria, Sherene Loi, Stefan Michiels, Christos Sotiriou. Reactive stroma and trastuzumab resistance in HER2-positive early breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-10-16.
Abstract P4-10-21: Utility of HER2 IHC intensity in selecting areas for FISH testing in equivocal (2+) cases
Authors: Hertel Johann D , Kaiser-Rogers Kathleen A , O'Connor Siobhan , Calhoun Benjamin
Published: March 2020

Intro: The 2018 ASCO/CAP HER2 guidelines eliminated the equivocal category for in situ hybridization (ISH). Additional workup is recommended for definitive classification of tumors that are sorted into ISH groups 2, 3 or 4. Evaluation of HER2 IHC using sections from the same tissue sample used for ISH is recommended to guide the selection of areas to score by ISH. Here we seek to evaluate the utility of selecting the area for ISH testing in IHC equivocal (2+) cases based on the staining intensity of the IHC staining.

Methods: A total of 66 cases with equivocal HER2 IHC (2+) and reflexed to FISH were prospectively collected from 8/22/18 to 6/26/2019. The areas of most and least intense HER2 IHC staining were separately identified and scored by FISH. The mean HER2:CEP17 ratio and mean HER2 signals/tumor cell were calculated for both populations and statistical significance was evaluated using the Wilcoxon Ranked Sum test.

Results: The distribution of the high intensity area was 58 ISH group 5, 4 ISH group 4, and 8 ISH group 1. The distribution of the low intensity area was 51 ISH group 5, 9 ISH group 4, 2 ISH group 2, and 5 ISH group 5. In the high and low intensity areas, 59 of 66 (95.5%) cases sorted into the same ISH group and 7 (10.6%) sorted into different ISH groups. Of these 7, 3 (4.5%) had different final FISH categorizations. All 3 cases were ISH Group 1 (amplified) in the high intensity area and ISH group 2, 4 or 5 (not amplified in the absence of 3+ IHC) in the low intensity area. The other 4 cases with different ISH groups did not have different final HER2 categorizations. The mean HER2/CEP17 ratios for the high and low intensity areas were 1.50 and 1.39 (p = 0.075). There was no statistically significant difference in mean HER2 copy number for the high and low intensity areas (p = 0.92).

Discussion: When areas with high and low HER2 IHC intensity were compared, there was a small difference in the mean HER2:CEP17 ratio with a trend toward statistical significance. However, the absolute difference in the means was small (0.11) and only a minority of cases (4.5%) showed discordant final HER2 categorization between the two groups. All of the cases with discordant HER2 categorization were amplified (ISH Group 1) in the IHC high intensity area and not amplified (ISH Groups 2, 4 and 5) in the low intensity area. The data suggests that using HER2 IHC to guide selection of areas for ISH testing may identify amplified tumors (or clones) in a minority of cases (4.5%). Additional analysis of a larger number of cases is required to validate these findings.

Citation Format: Johann D Hertel, Kathleen A Kaiser-Rogers, Siobhan O'Connor, Benjamin Calhoun. Utility of HER2 IHC intensity in selecting areas for FISH testing in equivocal (2+) cases [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-10-21.
Abstract P4-10-31: Patterns of protein expression and signaling assessed by reverse phase protein array (RPPA) in estrogen-receptor negative (ER-), HER2-amplified breast cancer (BC) that was primary-refractory to preoperative (preop) HER2-directed therapy
Authors: Pierobon Mariaelena , Levin Maren K , Baldelli Elisa , Kim Leslie SL , Liotta Lance , Petricoin Emanuel F , O'Shaughnessy Joyce
Published: March 2020

Background: ER- HER2+ BC is comprised of a heterogeneous mix of intrinsic BC subtypes which have differential responsiveness to preop HER2-directed therapies combined with chemotherapy. Patients (pts) with ER- HER2+ BC whose disease progressed while on or who had no response to preop HER2-directed therapy are uncommon and the mechanisms of resistance within this primary-refractory disease are unknown. We utilized RPPA-based protein pathway activation mapping to map the drug target signaling architecture in pts’ primary-refractory ER- HER2+ BCs to begin to assess mechanisms of resistance. Methods: Eight primary-refractory ER- HER2+ FFPE BC tissues obtained from 5 pts (preop biopsies n=4 and/or post-treatment surgical resection n=4) underwent laser capture microdissection to isolate pure tumor epithelium followed by RPPA-based analysis of the levels and/or activation/phosphorylation of approximately 130 key signaling proteins known to be involved in tumorigenesis and metastatic progression. Results: Pts were all treated with preop trastuzumab, pertuzumab, docetaxel, and carboplatin (TCHP) with no response and/or with progression of disease. Three pts also received preop doxorubicin/cyclophosphamide without response. RPPA-based analysis revealed that post-TCHP surgical samples had higher activation of a number of drug targets including receptor tyrosine kinases (RTK) such as MET and ALK, as well as HER family signaling proteins phospho-HER3 and phospho-EGFR compared to the matched pre-TCHP samples. Conclusions: In these ER- HER2+ BCs that were primary-refractory to preop TCHP, in those pts with patient-matched pre/post treatment samples, activation of several potential resistance pathways such as alternative RKT signaling as well as EGFR and HER3 signaling was observed. These data are hypothesis-generating and require exploration in additional ER- HER2+ primary-refractory tissues.

Citation Format: Mariaelena Pierobon, Maren K Levin, Elisa Baldelli, Leslie SL Kim, Lance Liotta, Emanuel F Petricoin, Joyce O'Shaughnessy. Patterns of protein expression and signaling assessed by reverse phase protein array (RPPA) in estrogen-receptor negative (ER-), HER2-amplified breast cancer (BC) that was primary-refractory to preoperative (preop) HER2-directed therapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-10-31.
Abstract P4-12-06: Long-term follow-up of patients with invasive breast cancer treated with catheter-based accelerated partial breast irradiation following lumpectomy
Authors: Chen Cynthia , Do-Nguyen Chi Chi , Poole Lisa , Sizer Lina , Carter William B , Frazier Thomas G.
Published: March 2020

Introduction: A large number of breast cancer patients who are eligible for breast-conserving therapy (radiation following complete resection via lumpectomy) elect to undergo mastectomy to avoid radiation - with treatment length being the most significant deterrent. The development of accelerated partial breast irradiation (APBI) tailored treatment to target tissue at greatest risk of recurrence, balancing treatment-associated benefits with radiation exposure risk while shortening therapy duration from 6 weeks to 5 days. This study analyzed rates of ipsilateral breast tumor recurrence (IBTR) in patients with invasive breast cancer treated with resection followed by APBI delivered via catheter-based brachytherapy.

Methods: Retrospective data was collected on 406 patients with primary invasive breast cancer diagnosed from January 2007 to February 2014, treated with lumpectomy and adjuvant APBI catheter-based brachytherapy. Follow-up data was available for 390 patients (97.5%). Mean and median follow-up were 80.9 and 83.5 months respectively. 193 patients (49.4%) had at least 7 years of follow-up.

Results: 21 patients (5.4%) were found to have an IBTR. Of these patients, 14 (66.7%) experienced an IBTR in the same quadrant as their index cancer. 7 patients (33.3%) experienced an IBTR in a different quadrant. Only one patient (4.8%) experienced an IBTR within the first two years after conclusion of their primary treatment. Of the entire cohort, 7 patients (1.8%) were found to have a metastatic recurrence (one which occurred within the first two years after primary treatment) and 7 patients (1.8%) experienced new primary cancers diagnosed in their contralateral breasts.

Conclusion: The results of this investigation demonstrate catheter-based brachytherapy APBI delivered after breast-conserving surgery carries a relatively low risk for IBTR in patients with invasive breast cancer. We support its' use as an effective and valid alternative for selected early breast cancer patients desiring a significantly shorter, more convenient course of treatment in the adjuvant setting without increased risk of recurrence.

Citation Format: Cynthia Chen, Chi Chi Do-Nguyen, Lisa Poole, Lina Sizer, William B Carter, Thomas G. Frazier. Long-term follow-up of patients with invasive breast cancer treated with catheter-based accelerated partial breast irradiation following lumpectomy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-12-06.
Abstract P4-12-08: Evaluation of acute toxicity in triple negative breast cancer patients receiving concurrent capecitabine and radiation
Authors: Modi Chirag , Yehia Zeinab Abou , Haffty Bruce
Published: March 2020

Purpose: The addition of capecitabine is shown to improve survival in patients with Triple Negative Breast Cancer (TNBC). Administration of adjuvant capecitabine and radiation therapy sequentially after surgery for TNBC patients prolongs the time from surgery to radiation treatment. The purpose of this study was to evaluate the rate of acute loco-regional toxicity in patients with triple negative breast cancer who received concurrent adjuvant capecitabine and radiation.

Materials and Methods: We performed a retrospective chart review of all patients diagnosed with breast cancer who were treated with capecitabine and radiation therapy at the Rutgers Cancer Institute of New Jersey between January 2010 and January 2019. Patients who had a previous radiation treatment course, hormone-receptor positive breast cancer and patients who received treatment sequentially were excluded. A total of 11 patients with TNBC who received concurrent capecitabine and RT were identified. Patient demographics, disease characteristics, radiation and capecitabine details, toxicity profile and treatment breaks were recorded. Toxicity was scored by the Common Terminology Criteria for Adverse Events version 5.

Results: Median age was 52 years [34- 65]. Median Follow up from last Radiation treatment was 12 months [1- 63]. All patients had locally advanced disease and were treated with neoadjuvant chemotherapy. Adjuvant capecitabine dose ranged between 1000-3000 mg daily concurrent with a definitive course of radiation treatment ranging between 45 Gy- 50.4 Gy followed by an additional 10-14 Gy boost. All patients received radiation to the elective regional lymph nodes. Grade 1 or 2 radiation dermatitis was seen in all patients (11/11). Of the 11 patients, 2 patients (18%) experienced Grade 3 radiation dermatitis within the treatment field. One of these patients had a one week treatment break in which capecitabine was withheld; she then continued to a reduced boost dose. The second patient had grade 3 moist desquamation after completion of her radiation dose. No grade 4 or 5 toxicities were reported. In 10/11 (91%) patients had grade 1 or 2 skin hyperpigmentation. In 2 of the 11 patients, capecitabine was held at one point during treatment.

Conclusion: Our study revealed an acceptable toxicity profile of receiving concurrent capecitabine and RT. These data support future prospective evaluation of this approach.

Citation Format: Chirag Modi, Zeinab Abou Yehia, Bruce Haffty. Evaluation of acute toxicity in triple negative breast cancer patients receiving concurrent capecitabine and radiation [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-12-08.
Abstract P4-12-12: Outcomes of exclusive radiation therapy for breast cancer in older women according to age and comorbidity status: An observational retrospective study
Authors: Waechter Lorraine , Cao Kim , Carton Matthieu , Kirova Youlia , Fourquet Alain
Published: March 2020

Introduction: This study aimed to assess the efficacy, tolerance and impact of comorbidities on outcomes in older women treated by exclusive radiation therapy (RT) for non-metastatic breast cancer (BC). Material and methods: We studied retrospectively female patients older 70 years at diagnosis, treated by exclusive RT for their BC between 2003 and 2013 in our Department. We analysed overall survival (OS), progression free survival (PFS), and specific survival (SS). Comorbidities were evaluated with the Charlson Comorbidity Index (CCI), and toxicities with the CCTCAE v3.0. Results: Between 2003 and 2013, there were 978 patients older than 70 treated for BC in our Hospital, and 817 received RT. Hypofractionated RT was delivered in 90.2% of patients. Of them, 66 patients underwent exclusive RT after refusal of surgery. The median age was 84.8 [71.3-91.7]. The median follow-up was 51.9 months [0.5- 99]. OS, SS and PFS at 5 years were 65.5% CI 95% [54.1-79.3], 86.3% CI 95% [77.2-96.4]), and 58.4% CI 95% [46.9-72.7], respectively. Five-year OS was statistically different according to age younger or older than 85 years: 72.9% CI 95% [58.4-91.1] and 57.1%, IC 95% [40.8-79.8], (p = 0.0026). Similar results were found for 5-year PFS: 64.5% CI 95% [49.5-84.1] and 51.6% CI 95% [35.8-74.5] (p = 0.014). The 5-year OS was also statistically different according to CCI score, respectively 70.8% CI 95% [57.0-87.9] and 59.8% CI 95 % [42.4-84.3] (p = 0.039) for a score of 0 or ≥ 1. Median CCI score was 1. There were 10.6% of the patients who experienced no toxicities; there were 59% who presented grade 1 and 2 radiodermatitis. Late toxicities were mainly fibrosis, observed in 39.4% of the patients, mostly of grade 1 and 2.Conclusion: Exclusive radiation therapy for non-metastatic BC in older women is feasible and well tolerated when adapted techniques are used, but the prognostic is strongly impacted by age and comorbidities.

Citation Format: Lorraine Waechter, Kim Cao, Matthieu Carton, Youlia Kirova, Alain Fourquet. Outcomes of exclusive radiation therapy for breast cancer in older women according to age and comorbidity status: An observational retrospective study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-12-12.
Abstract P4-12-13: Correlation of radiotherapy with the prognosis of elderly patients with hormone receptor-positive breast cancer according to immunohistochemical subtyping
Authors: Zhang Jin
Published: March 2020

Objective:The present study examined the effect of radiotherapy on recurrence and survival in elderly patients with hormone-receptor-positive early breast cancer.

Methods:A retrospective analysis of 327 patients aged ≥65 years with stage I-II, hormone receptor positive breast cancer who underwent breast conserving surgery and received endocrine therapy (ET) or radiotherapy plus endocrine therapy (ET+RT) was performed. Both groups were divided into luminal A type and luminal B type subgroups. Evaluation criteria were 5-year disease free survival (DFS), local relapse rate (LRR), overall survival (OS), and distant metastasis rate (DMR).

Results:There were significant differences in 5-year DFS (HR 1.59, 95% CI 1.15-2.19, P=0.005) and LRR (HR 3.33, 95% CI 1.51-7.34, P=0.003), whereas there were no significant differences in OS and DMR between the two groups. In luminal A type, there was no significant difference in 5-year DFS, LRR, OS, and DMR between the ET group and the ET+RT group. In luminal B type, there were statistically significant differences in 5-year DFS (HR 2.188, 95% CI 1.37-3.49, P=0.001), LRR (HR 5.447, 95% CI 1.65-17.98, P=0.005), and OS (HR 1.752, 95% CI 1.01-3.054, P=0.048) between the two groups. In the ET group, there were significant differences between luminal A type and luminal B type in 5-year DFS (HR 1.841, 95% CI 1.23-2.75, P=0.003) and OS (HR 1.763, 95% CI 1.07-2.91, P=0.026).

Conclusions:After breast conserving surgery, radiotherapy can reduce the LRR and improve the DFS and OS of luminal B type elderly patients, whereas luminal A type elderly patients do not benefit from radiotherapy. Without radiotherapy, luminal A type patients have better DFS and OS than luminal B type patients.

Keywords: disease-free survival (DFS), distant metastasis rate (DMR), endocrine therapy, local relapse rate (LRR), overall survival (OS), radiotherapy

Citation Format: Jin Zhang. Correlation of radiotherapy with the prognosis of elderly patients with hormone receptor-positive breast cancer according to immunohistochemical subtyping [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-12-13.
Abstract P4-12-33: Frequency of radiation-induced malignancies post-adjuvant radiotherapy for breast cancer in patients with Li-Fraumeni syndrome
Authors: Le Anh N , Powers Jacquelyn , Zelley Kristin , Bradbury Angela , Shah Payal , Freedman Gary , Nathanson Katherine , Domchek Susan M , MacFarland Suzanne P , Maxwell Kara N
Published: March 2020

Background. Women with Li-Fraumeni syndrome (LFS), a cancer predisposition syndrome caused by germline mutations in TP53, have an over 50% risk of developing breast cancer (BC) by age 70. Providers often avoid adjuvant radiotherapy to treat BC in LFS patients due to a reported high risk of radiation-induced malignancies of over 30%. We aimed to investigate the characteristics of LFS-associated BC and the risk of subsequent malignancy in BC patients with LFS following adjuvant radiotherapy.

Methods. A single institution retrospective chart review was conducted for female BC patients with a confirmed germline TP53 mutation. Statistical analyses were performed to compare the frequency of radiation-induced malignancies in LFS patients to non-LFS BC cases reported in the Penn Medicine Cancer Registry (PMCR) (n=6607 patients total, 3863 who received radiation).

Results. Among 95 patients with LFS, we identified 51 female BC patients with 74 primary BC diagnoses. Of 51 patients, 57% had a history of BC only, and 25% had BC as their presenting diagnosis of LFS. LFS-associated BCs were predominantly invasive ductal carcinoma (48%) and HER2+ (58%). We analyzed 20 LFS BC patients who underwent adjuvant radiotherapy with an average follow up of 11.1 (2-20) years. Of 18 patients who received radiation in a curative setting, one (6%) patient developed thyroid cancer and one (6%) patient developed sarcoma in the radiation field. The incidence of thyroid cancer did not significantly differ between LFS-associated and non-LFS BCs. The incidence of radiation-induced sarcoma in patients with LFS is significantly higher than in non-LFS BC patients (0.03%, p=0.01).

Conclusion. We found a 6% (one in 18 patients) risk of radiation-induced sarcoma in LFS BC patients, lower than the previously reported rate of 33%. Adjuvant radiotherapy should be considered in LFS BC patients when the potential risk for locoregional recurrence (LRR) or the mortality benefit to radiation is greater than 6%.

Citation Format: Anh N Le, Jacquelyn Powers, Kristin Zelley, Angela Bradbury, Payal Shah, Gary Freedman, Katherine Nathanson, Susan M Domchek, Suzanne P MacFarland, Kara N Maxwell. Frequency of radiation-induced malignancies post-adjuvant radiotherapy for breast cancer in patients with Li-Fraumeni syndrome [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-12-33.
Abstract P4-13-09: Oncoplastic breast conserving surgery (OBCS): A meta-analysis of real-world data
Authors: Kosasih Sebastian , Tayeh Salim , Mokbel Kefah , Kasem Abdul
Published: March 2020

Background: The role of oncoplastic breast conserving surgery (OBCS) is that of a middle ground between standard breast conserving surgery (SBCS) and mastectomy - it allows adequate resection margins of tumours unsuitable for traditional breast conserving surgery whilst allowing for a better cosmetic outcome and a reduced morbidity rate when compared to a traditional mastectomy. However, due to this being a relatively new type of procedure, there is limited evidence on its oncological safety, which is the ultimate goal of any breast cancer surgery.

Methods: This study aims to compare oncological safety of OBCS with SBCS and mastectomy by examining the relative risk of cancer recurrence and re-operation rates through meta-analysis. Literature search of Pubmed and Web of Science databases was conducted looking for studies up until February 2019. Meta-Analysis was performed using R Statistical Software (www.r-project.org).

Results: Initial finding of 645 studies was narrowed down to a pool of 19 studies including 18,163 patients. For the primary outcome measure of recurrence there was found to be no significant difference between the OBCS and SBCS or mastectomy (RR 0.861; 95% CI 0.640-1.160; p<0.296). The secondary outcome measure of re-operation was initially found to be significant in favour of OBCS (RR 0.64; 95% CI 0.46-0.89; p<0.01), however after adjustment for publication bias this was attenuated to an insignificant difference between the two study groups (RR 0.86; 95% CI 0.56-1.31; p>0.05).

Conclusions: For both recurrence of cancer and re-operation rate, there was not found to be a significant difference between OBCS and more traditional techniques. This would suggest that OBCS is of comparable oncological safety to more established operations and a useful option in suitable patients.

Citation Format: Sebastian Kosasih, Salim Tayeh, Kefah Mokbel, Abdul Kasem. Oncoplastic breast conserving surgery (OBCS): A meta-analysis of real-world data [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-13-09.
Abstract P4-13-12: Impact of an image fusion technique for preoperative planning in breast conserving surgery in patients with non -mass enhancement on MRI
Authors: Nakano Shogo , Fujii Kimihito , Mouri Yukako , Kousaka Junko , Ando Takahito , Ido Mirai , Goto Manami , Ito Yukie , Banno Hirona , Suzuki Kenjiro
Published: March 2020

[Objective] The potential benefit of preoperative MRI is still being controversial and international guidelines do not recommend MRI for routine preoperative assessment. However, when breast conserving surgery (BCS) is considered for non-mass enhancement (NME), an area of enhancement without an associated space occupying mass or focus, biopsy-proven malignancy, the precise localization in surgical position is required. Although breast ultrasound (US) plays an adjunctive role in evaluation of MRI findings in preoperative planning for BCS, the US morphology least likely to have an US correlation was NME, not a mass enhancement or a focus, and the identification rate of NME in second look US was heterogeneous. Recently, real-time virtual sonography (RVS), which coordinates US with MRI that uses an image fusion technique by using magnet position tracking system, has been introduced in breast imaging. The purpose of this study was to evaluate the effect of preoperative planning using RVS on BCS in patients with NME. [Methods] We enrolled 12 consecutive patients who had lesions with NME that exceeded the US hypoechoic area, in which it was particularly difficult to evaluate the tumor margin. During preoperative planning before BCS, RVS was used to delineate the enhancing area on the breast surface after additional supine breast MRI was performed. We analyzed both the surgical margin positivity rate and the reoperation rate. [Results] The preoperative diagnosis by core needle biopsy were 7 DCIS and 5 invasive ductal carcinoma. NME distribution types were 5 segmental, 4 branching-ductal and 3 regional. The median diameters of the NME and hypo-echoic lesions were 24 mm (range: 12-39 mm) and 8.0 mm (range: 4.9-18 mm), respectively (p = 0.0002). After RVS-derived skin marking was performed on the surface of the affected breast, 7 lumpectomy and 5 quadrantectomy were conducted. The surgical margins were positive in 2 (17%) patients. The patients with positive margins were found to have ductal carcinoma in situ. None of the patients required additional resection. [Conclusion] Although further prospective studies are required, the findings of our preliminary study suggest that preoperative planning using RVS for BCS in patients with NME could improve both a surgical margin positive rate and a reoperation rate.

Citation Format: Shogo Nakano, Kimihito Fujii, Yukako Mouri, Junko Kousaka, Takahito Ando, Mirai Ido, Manami Goto, Yukie Ito, Hirona Banno, Kenjiro Suzuki. Impact of an image fusion technique for preoperative planning in breast conserving surgery in patients with non -mass enhancement on MRI [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-13-12.
Abstract P4-14-12: Effects of hepatitis C virus infection on the safety of chemotherapy for breast cancer patients: A retrospective chart analysis
Authors: Ghosh Saptaparni , Chen Minghua L , Weinberg Janice , Ko Naomi Y
Published: March 2020

Background: Hepatitis C virus (HCV) infection is a major health problem in the United States and breast cancer is the second most common cancer in US women. Despite these prevalent diseases, there is limited information available on the effects of a concurrent HCV infection among breast cancer patients receiving chemotherapy and the problems they face during their treatment. There are limited guidelines for chemotherapy treatment in HCV positive breast cancer patients. Methods: We performed a retrospective 2:1 matched case control analysis on breast cancer patients with a confirmed active HCV infection who received chemotherapy at Boston Medical Center between January 2000 and April 2015. Cases with HCV infection (n=6) were matched with controls (n=12) who were HCV negative. The controls were matched on age (decade) of diagnosis, stage of breast cancer, and intended chemotherapy regimen. We investigated dose delays, dose changes, hospitalization, hematologic reasons for dose delays, and variation in blood counts during the treatment period in these patients from their medical records. Statistical analysis was done using R version 3.4.0 to compare these outcomes of interest between the two groups. Fisher’s exact and Wilcoxon rank sum tests were used to compare the categorical and continuous variables respectively. Results: The HCV positive group was at a significantly higher risk of dose delays (100% vs. 33%, p = 0.01), dose changes (67% vs. 8%, p = 0.02), and hospitalization during chemotherapy (83% vs. 25%, p = 0.04) than their HCV matched controls. The risk of getting a dose delay due to hematotoxicity was significantly higher in the HCV positive group than the HCV negative group (83% vs. 8%, p = 0.003). The HCV positive patients took longer time to complete their treatment cycles than the HCV negative group. Conclusions: Chronic HCV infection in breast cancer patients receiving chemotherapy may be complicated by their active HCV infection. Treatment challenges due to dose changes, dose delays and hospitalizations were significantly more common when compared to controls. Chemotherapy delays and dose changes during breast cancer treatment has a negative consequence. In the era of curative treatment for HCV, future studies focused on the effect and treatment of concurrent HCV and breast cancer treatment is warranted.

Citation Format: Saptaparni Ghosh, Minghua L Chen, Janice Weinberg, Naomi Y Ko. Effects of hepatitis C virus infection on the safety of chemotherapy for breast cancer patients: A retrospective chart analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-14-12.
Abstract P4-17-05: Survival and clinicopathologic characteristics of male breast cancer patients using Korea national cancer incidence database
Authors: Lee Eungyeong , Jo Heein , Han Jai Hong , Jung So-Youn , Lee Seeyoun , Kang Han-Sung , Lim Myong Cheol , Won Young-Joo , Lee Eun Sook , Lee Eun Sook
Published: March 2020

Background: Male breast cancer (MBC) is a very rare disease. There are ambiguous opinions about treatment outcomes and survival outcome. This study aimed to investigate the incidence and survival outcome of male breast cancer in Korea. Additionally, we evaluated the differences between male and female breast cancer (FBC).

Method: We identified 226,612 breast cancer cases diagnosed between 1999 and 2016 in the Korea Central Cancer Registry (KCCR). We retrospectively analyzed the data that patient demographics and clinical information between MBC and FBC. Overall survival (OS) was estimated according to sex, age, histologic type, stage.

Results: Of the 226,612 patients, 1,052 had male breast cancer patient and 225,560 had female breast cancer patients. The ratio of male to female was 0.0047. MBC patients were diagnosed the most frequently in those aged 60-69 years. In contrast, FBC was diagnosed the most frequently in those aged 40-49 years (p<.0001). Male patient received less adjuvant therapy than female patients (radiotherapy, MBC vs. FBC = 8% vs. 22%, chemotherapy, 41.9% vs. 55.7%, p<.0001). The 5-years OS rates after the diagnosis of breast cancer were 88.8% for all patients. MBC has a lower 5-years OS rate than FBC (76.2% for men, and 88.9% for women, p<.0001). Both groups showed lower survival in patients aged ≥60 years. The 5-years OS rates of invasive type were 75.8% for men and 89% for women. The OS rate was lower in both groups as the stage increased.

Conclusion: We found that there is a difference between MBC and FBC. The survival outcomes in MBC were worse than that of FBC. This study showed the different OS patterns according to the age, histology, and stage. Based on these results, clinicians need to recognize the difference from FBC when treating MBC.

Citation Format: Eungyeong Lee, Heein Jo, Jai Hong Han, So-Youn Jung, Seeyoun Lee, Han-Sung Kang, Myong Cheol Lim, Young-Joo Won, Eun Sook Lee, Eun Sook Lee. Survival and clinicopathologic characteristics of male breast cancer patients using Korea national cancer incidence database [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-17-05.
Abstract P4-17-07: Demographics and survival in male breast cancer: An updated analysis of SEER database
Authors: Khoury John , Anusim Nwabundo , Macari David , Jaiyesimi Ishmael
Published: March 2020

Background: Male breast cancer is rare accounting for less than 0.5% of all cancer diagnoses in men. Previous epidemiological studies reported conflicting results regarding the prognosis of male breast cancer in comparison to female breast cancer. As treatment for breast cancer has improved significantly, we conducted this study to evaluate male breast cancer characteristics and mortality.

Methods: All patients diagnosed with breast cancer between 2010 and 2015 from the population-based cancer registries of the Surveillance Epidemiology and End Results program (SEER) were analyzed. Descriptive statistics, Kaplan-Meier analysis and COX regression model were used to examine the data.

Results: A total of 380,116 cases of breast cancer were found including 2,978 cases of male breast cancer. The age-adjusted incidence rate for male breast cancer during the study period was 1.2 per 100,000 individuals per year which is slightly higher than the rate during the 10 years period preceding our study date (1.1 per 100,000 per year). Out of all male breast cancer patients, 80.7% of them were white, 14.6% black and 4.7% from other races. The median age of diagnosis was 68. 34% of male breast cancer patients were diagnosed with stage I, 41.6% with stage II, 16.2% with stage III and 8.2% with stage IV. 97% of male breast cancer cases were ER/PR positive and 11.9% were HER2 positive. 5-year survival rate for male breast cancer patients was 90% for stage I, 86% for stage II, 78% for stage III and 28% for stage IV. Cox proportional-hazards model revealed a slight increase in mortality associated with male breast cancer in comparison to female breast cancer (adjusted hazard ratio, 1.15; 95% confidence interval, 1.06 to 1.24; P<0.01).

Conclusions: Male breast cancer represents less than 1% of breast cancer cases. Its age-adjusted incidence rate has slightly increased. It is mostly diagnosed as early stage with positive hormone receptors status. After controlling for other risk factors, male breast cancer patients have a worse survival outcome than female patients.

Citation Format: John Khoury, Nwabundo Anusim, David Macari, Ishmael Jaiyesimi. Demographics and survival in male breast cancer: An updated analysis of SEER database [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-17-07.
Abstract P5-02-06: Improved histologic grading of breast cancer by a novel deep learning-based model
Authors: Rantalainen Mattias , Wang Yinxi , Ácz Balázs , Robertson Stephanie , Hartman Johan
Published: March 2020

Breast cancer histologic grade is a well-established prognostic factor utilized in clinical decision making. In current clinical practice grading is conducted manually by pathologists and this procedure is associated with a substantial inter-observer variability. Furthermore, patients classified as histologic grade 2 has been reported to exhibit an intermediate recurrence risk, resulting in less prognostic value. With the aim of improving patient stratification, we have developed a model-based approach for histological grading using deep convolutional neural networks (CNNs). In this study, we developed a CNN model for improved histologic grading, with a focus on further stratification of grade 2 patients into high and low risk groups.

Histopathology images from the Clinseq breast cancer study and the Cancer Genome Atlas (TCGA) containing 730 patients were scanned at 40X magnification and tiled into patches at 20X. In total, we obtained 5.3 million patches of size 299 × 299 pixels. Using image annotations of invasive cancer regions in Clinseq study, we trained a deep CNN model to segment cancer regions in TCGA data. Subsequently, the cancer regions from both Clinseq and TCGA were used to optimize a second deep CNN model for classification of grade 1 and 3, this model was applied to re-classify 291 patients with histologic grade 2 into low and high risk.

The CNN model classified cancer and non-cancer with area under the receiver operating characteristic curve (AUC) of 0.941. The second CNN model achieved an AUC of 0.910 in terms of classification of grade 1 and 3 tumors (cross-validation). For grade 2 tumors (independent test data), 184 were re-classified into the lower risk group whereas 107 were classified as high risk. The risk of recurrence for the grade 2 higher risk group is significantly higher than that in lower risk group, with an estimated hazard ratio of 2.86 (95% confidence interval: 1.21-6.69) after adjusting for age, tumor size, estrogen receptor status and lymph node status.

In conclusion, we found that the deep CNN model demonstrated a high capability to distinguish between breast cancer with histologic grade 1 and 3. We also found that re-stratification of Grade 2 patients into high and low risk groups was significantly associated with risk of recurrence. Improved histological grading, and further risk stratification of grade 2 patients, by deep CNN models could contribute towards a reduction of both over- and under-treatment of breast cancer patients.

Citation Format: Mattias Rantalainen, Yinxi Wang, Balázs Ácz, Stephanie Robertson, Johan Hartman. Improved histologic grading of breast cancer by a novel deep learning-based model [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-02-06.