bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biological analysis of HER2 equivocal (2+) cases in primary breast cancer.
Authors: Nishimura Reiki , Osako Tomofumi , Okumura Yasuhiro , Nakano Masahiro , Fujisue Mamiko , Arima Nobuyuki 
Published: May 2020

e12555 Background: Overexpression and/or amplification of HER2 is observed in 15–20% of all invasive breast cancer cases. Breast cancer patients with HER2 overexpression can benefit from anti-HER2 therapy. HER2 IHC results are generally divided into four values (range, 0 to 3+). The cases with a HER2 (2+) value should be assessed using FISH. The aim of this retrospective study was to evaluate the biological variables and prognosis of HER2 (2+) cases according to the FISH status. Methods: Primary breast cancer patients (n = 5419) were enrolled in this study from January 2002 to September 2019. The factors investigated included nodal status, tumor size, nuclear grade, ER/PgR and HER2 status, p53 overexpression, and the Ki-67 index values. Positive for HER2 is categorized as having a HER2 value of 3 + or FISH amplified in equivocal cases. Results: The HER2 3+ rate in non-invasive carcinoma was higher than the rate in the invasive carcinoma cases (16.4% vs 12.9%; p < 0.0001). The distribution of HER2 IHC status in invasive carcinoma cases was 3+ (12.9%), 2+ (5.8%) and negative (84.3%). The FISH positive rate of the HER2 2+ cases was 57.0 % (158 cases). HER2 positivity significantly correlated with ER/PgR negative, p53 overexpression, higher Ki-67 value and nuclear grade. The FISH positivity of the HER2 2+ cases significantly correlated with PgR negative, p53 overexpression and higher grade. There were significant differences in biological variables between IHC 3+ and 2+/FISH positive, and between IHC 2+/FISH negative and IHC negative. Patients with HER2 3+ had significantly worse disease-free survival (DFS) rates than the cases before the approval of trastuzumab in Japan. However, there was no difference after trastuzumab was approved. Moreover, there was no difference in DFS according to the FISH status in HER2 2+ cases. Conclusions: HER2 positivity indicated a higher degree of malignancy. HER2 2+ had different independent biological characteristics from HER2 negative (0 & 1+) or positive (3+) cases. Therefore, the difference in biology of HER2 2+ cases may influence the prognosis and should be reconsidered in breast cancer cases.
The association between breast density and HER2-positive breast cancer: A population-based case-control study.
Authors: Tan Vivian , Payne Jennifer , Paquet Nicole , Iles Sian , Rayson Daniel , Barnes Penny , Abdolell Mohamed 
Published: May 2020

e12556 Background: Little is known about the association between mammographic breast density and the subtypes of breast cancer including HER2-positive breast cancers (HER2-BrCa). The objective of this study was to assess the strength of association between breast density and HER2-BrCa in a population-based screening program. Methods: This is a population-based case-control breast cancer study of women aged 40 to 75 who underwent digital breast screening from 2009 to 2015 in Nova Scotia, Canada. Cases included women diagnosed with HER2-BrCa at screen or before their next screen (interval); controls included women without screen-detected cancer matched to cases by age and year of screen. Measures of mammographic breast density (percent density, BI-RADS-4th and -5th edition) were obtained from automated software (densitasai) and linked with clinical risk factor data (age, parity, total breast volume, post-menopausal status, hormone replacement therapy, family history and history of core biopsy). The association between breast density and cancer risk was assessed by calculating the odds ratios [OR] with 95% confidence intervals using multivariable logistic regression. Results: A total of 209 cases (median age, 58.8 years) and 6812 controls (median age, 59.4 years) were included. The risk of HER2-BrCa increased with increasing levels of percent breast density. High breast density according to BIRADS-4th and -5th editions was significantly associated with HER2-BrCa: BIRADS -4th 3/4 vs 1: OR 2.50 (1.68 - 3.68); BIRADS-5th C/D vs A: OR 2.58 (1.71 - 4.01). The association between higher breast density and increased risk of HER2-BrCa remained after adjustment for clinical factors. Conclusions: The risk of HER2-BrCa was associated with progressively higher mammographic breast density, although to a lesser extent than breast cancer in general. Accurate risk models including breast density may support the development of more breast-screening protocols that can lead to more strategic use of healthcare resources.
Immunogenicity and transcriptomic biology in Nottingham histologic grade 3 breast cancer.
Authors: Takahashi Hideo , Oshi Masanori , Asaoka Mariko , Yan Li , Takabe Kazuaki 
Published: May 2020

e12563 Background: Cancer biology dictates disease progression and prognosis of a tumor. Histological grade has been used as a proxy of tumor biology in various cancer types, although it depends on morphological analysis of the tissue. As such, Nottingham histological grade is recently incorporated into the 8th edition of the AJCC Breast Cancer Staging. Herein, we hypothesized that Nottingham histological Grade3 breast cancer (BC) demonstrate strong immunogenicity in response to aggressive phenotypes, reflecting worse clinical outcomes. Methods: Clinicopathological data and transcriptomes were obtained from Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), The Cancer Genome Atlas (TCGA) Invasive breast carcinoma (BRCA) cohort, and GSE25066. While METABRIC was used as a training cohort, the other two cohorts served as validation cohorts. As TCGA did not contain pathological information, Nottingham histological grade was manually collected through the Text Information Extraction Systems (TIES). Results: 2876 patients were analyzed in this study. Grade1 tumors were 274 patients (9.5%), Grade2 tumors 1185 patients (41.2%), and Grade3 tumors 1417 patients (49.3%). Grade3 tumors were common in patients with Estrogen receptor (ER) negative (p < 0.001), with Her2 and Basal molecular subtypes by the PAM50 classifier (p < 0.001), and associated with increased MKI-67 expression (p < 0.001). Disease-free survival (DFS) was significantly worse in Grade3 tumors in all cohorts. Gene set enrichment analysis (GSEA) demonstrated that Grade3 tumors significantly enriched immune activity related gene sets as well as cell proliferation and cell cycle related gene sets. CIBERSORT also demonstrated that Grade3 BCs were infiltrated with anti-cancer macrophage M1, follicular helper T cells, and activated NK cells (all p < 0.001). Furthermore, Grade3 tumors were associated with more diverse T cell receptor (p = 0.001) and increased cytolytic activity (p < 0.001). Lastly, T cell exhaustion markers, including PD-L1, PD-1, and CTLA4, were significantly elevated in Grade3 BCs (all p < 0.001) as a negative feedback loop. Conclusions: Grade3 BCs demonstrated enhanced immunogenicity as well as aggressive transcriptomic features.
Correlation of hormonal receptor level and survival outcome in HER2-positive nonmetastatic breast cancer.
Authors: Chen Mengdi , Wu Jiayi , Zhu Li 
Published: May 2020

e12568 Background: In human epidermal growth factor 2 (HER2)-positive breast cancer, emerging evidences imply that clinical behavior and prognosis differ according to hormone receptor (HR) status. However, there is no conclusion about the relevance between estrogen receptor (ER) or progesterone receptor (PR) expression and clinical outcome of HER2-positive breast cancer. Our study is designed to determine the effect of different ER/PR levels on survival benefit of HER2-positive early breast cancer. Methods: 984 non-metastatic HER2-positive breast cancer patients between January 2009 and December 2016 were retrospectively reviewed and HR+/HER2+ patients were further classified into several subgroups based on ER expression level (Low/L: 1-9%; Median/M: 10-74%; High/H: 75-100%) and PR expression level (Low/L: 0-19%; High/H: 20%-100%). Clinical features and survival outcomes were evaluated. Results: A total of 461 HR+/HER2+ and 523 HR-/HER2+ breast cancer patients were included in our study and 69.8% of them received target therapy (HR+ 67.5%, HR- 71.9%). While HR+/HER2+ breast cancer showed better survival than HR-/HER2+ subtype in 5-year disease free survival (DFS, 92.6% vs 87.6%, p = 0.002), no significant difference was observed between 5-year DFS rates in ER+/PR+ and ER+/PR- subgroup (94.3% vs 89.7%, p = 0.150). However, a possible correlation was found between ER/PR levels and DFS both in HR+/HER2+ (p = 0.057) and all HER2+ (p < 0.001) breast cancer. In HR+/HER2+ breast cancer, all subgroups showed DFS improvement trend versus M-ER/L-PR patients and hazard ratio of H-ER/H-PR subtype had a statistical difference (0.36, 95%CI 0.13-0.99, p = 0.047). In all HER2+ patients, hazard ratio of H-ER/H-PR compared with HR- subtype was 0.32 (95% CI, 0.13-0.80, p = 0.015). M-ER/L-PR presented similar DFS outcome with HR- subtype in our study. Conclusions: ER/PR expression may become a predictor of survival benefit in HER2-positive non-metastatic breast cancer and a higher ER/PR expression level might be associated with better DFS.
Survival outcomes of metaplastic breast carcinoma: An Indian tertiary care center data.
Authors: Puii Lalnun , Sarathy Vinu , Sangi Lalram , Thomas Beulah Elsa , Koramati Samuel Luke , Varayathu Hrishi , Mufti Suhail Sayeed , Mathew Smruthy Ann , Thungappa Satheesh Chiradoni , Naik Radheshyam , Ajaikumar Basavalinga Sadasivaiah 
Published: May 2020

e12579 Background: Metaplastic breast carcinoma is a rare histological subtype that has basal like characteristics and is reported to have a poorer prognosis than no specific type/ductal carcinoma (ductal/NST). We aimed to investigate clinicopathological features and outcome from a single institution based registry. Methods: Clinical records of breast cancer patients treated during 2012-2019 were screened and 31 cases of metaplastic breast carcinoma were found. Descriptive analysis was done for patients’ demographics and clinicopathological features. Kaplan Meier method was used to assess survival outcomes. Results: The incidence of metaplastic breast cancer was 0.5% (31/6180) in our study out of which the most common histopathological differentiation was squamous (45.16%). The second most common was sarcomatoid histology (32.25%), followed by chondroid (9.68%) and mixed histology (12.9%). The median age at diagnosis was 60 years ranging from 28 to 82 years. 64.15% of patients were post-menopausal. At presentation, three (9.67%) patients had metastatic disease while the rest were diagnosed with early (51.61%) and locally advanced cancers (38.72%). Triple negative cancers (ER/PR/Her2 negative) constituted the vast majority with 22 cases (80.6%) while hormone receptor positive (ER/PR positive, Her-2 negative) and Her-2 neu positive (ER/PR negative) made up the rest with three patients (9.67%) each group respectively. The median overall survival was found to be 39 months (95% CI 25.46 - 52.53). Conclusions: After a thorough search in PubMed and Google Scholar, we could not find a larger case series from India with clinical outcomes for metaplastic breast carcinoma. Our results suggest that metaplastic breast carcinoma is a heterogenous disease. Outcomes of metaplastic breast carcinoma are relatively worse when compared with literature for triple negative breast cancer and breast cancer in general. Further biological understanding may offer valuable insights for newer targets and therapeutic approaches to metaplastic breast cancer.
Recurrence score (RS) differences between primary and second-primary breast cancer (BC): Exploratory analysis of the Clalit Health Services (CHS) registry.
Authors: Shachar Shlomit , Rizel Shulamith , Fried Georgeta , Leviov Michelle , Yerushalmi Rinat , Ben-Baruch Noa , Tokar Margarita , Soussan-Gutman Lior , Dvir Addie , Bareket-Samish Avital , Yablonski-Peretz Tamar , Sonnenblick Amir , Kaufman Bella , Hammerman Ariel , Liebermann Nicky , Stemmer Salomon M. 
Published: May 2020

e12587 Background: In the phase 3 TAILORx study, the first invasive disease-free survival event (in all arms) was often opposite BC or other second primary cancer. Our goal was to investigate differences in the 21-gene RS results between the primary BC and a second primary BC, as well as the association with clinicopathological characteristics. Methods: This analysis of the prospectively-designed CHS registry included all CHS pts with estrogen receptor (ER)+ HER2-negative BC who underwent RS testing between 1/2006 and 6/2019 and for whom ≥2 RS results were identified which were > 1 year apart. Results: Of the 10,244 RS assays ordered in this time frame, 371 involved pts for whom the assay was performed at least twice. Our analysis focused on the 42 pts for whom the assays were performed > 1 year apart. All pts were females; 76% were initially diagnosed with node-negative BC; median (interquartile range [IQR]) age at first diagnosis was 56 (43-64) yrs. Tumor characteristics for the first and subsequent primary BC are presented (Table). The median time (IQR) between the first and latest RS assay was 4.5 (2.9-6.4) yrs. In 28 pts (67%), the latest primary BC was ipsilateral and in 14 (33%) it was contralateral. The median (IQR) difference between the first and latest RS value was 7 (1-12). The second/third primary BC had higher RS than the first BC in the majority (76%) of pts. Higher RS in the latest primary BC (compared to the first primary BC) was more common when the latest primary BC was ipsilateral than when it was contralateral (86% vs 57%, P= 0.04). Conclusions: In ER+ HER2-negative BC pts, second/third primary BC is generally associated with higher RS result (compared to the first primary BC), particularly if the later primary BC is ipsilateral. [Table: see text]
The association between race and intrinsic subtype on hormone receptor-positive breast cancer among young black women.
Authors: Reid Sonya , Moore Jaleesa , Tezak Ann , Weidner Anne , Mayer Ingrid A. , Pal Tuya 
Published: May 2020

e12591 Background: Hormone receptor-positive, HER2-negative breast cancer (HR+/HER2- BC) has the highest incidence and mortality rate across all racial/ethnic groups. HR+/HER2- BC is clinically and biologically heterogenous. Gene expression profiling assays can provide prognostic information and predict risk of late recurrence among women with HR+/HER2- BC. Prior studies have shown worse clinical outcomes among black women with HR+/HER2- BC. We sought to compare the distribution of intrinsic subtypes among young black women with HR+/HER2- BC, compared to published data from a young white cohort in the Carolina Breast Cancer Study (CBCS). Methods: Two population-based cohorts of black women diagnosed with BC between 2002 to 2012 at or below age 50 years were analyzed. Participants were recruited from twelve Southeastern states. All participants were asked to complete release of medical records and tissue/tumor forms to verify clinical information and to obtain primary tumor samples for future analyses. We compared the distribution of intrinsic subtypes and associations to clinical characteristics as compared to white female counterparts using Pearson chi-squared test. Results: Of 569 black participants, 124 women had HR+/HER2- BC and tumor samples available for analysis. There were 66 Luminal A (53%), 35 Luminal B (28%), 19 Basal (15%), and 4 HER2-enriched (3%) tumors. Black women with non-Luminal A tumors were younger ( < 40) with larger tumors ( > 2cm) and had higher risk of recurrence (ROR-T) scores as compared to black women with Luminal A tumors (p = 0.065, 0.006, and < 0.001, respectively). Compared to young white women in the CBCS, black women in our study had a significantly higher percentage of non-Luminal HR+/HER2- BC (p = 0.037). Conclusions: Our results suggest that among young women with HR+/HER2- BC, black women have a higher proportion of non-Luminal tumors compared to their white counterparts. Non-Luminal HR+/HER2- tumors (i.e., basal and HER2-enriched) are more aggressive and may be less sensitive to endocrine therapy. These results suggest that overrepresentation of aggressive HR+/HER2- BC subtypes may contribute to the racial survival disparity observed among black women.
Validation of the Van Nuys Prognostic Index in 737 patients with ductal carcinoma in situ (DCIS) treated at Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
Authors: Kunkiel Michal , Niwinska Anna , Jagiello-Gruszfeld Agnieszka I. , Michalski Wojciech 
Published: May 2020

e12603 Background: To assess the value of the Van Nuys Prognostic Index (VNPI) used in Maria Sklodowska-Curie National Research Institute of Oncology (MSCNRIO) to select the most adequate method of the treatment of DCIS patients. Methods: The database covered 737 subsequent DCIS patients treated in MSCNRIO in the years 1996 -2011. The results of the treatment with and without compliance with the VNPI index were compared. Results: In the group of 737 patients 66 (9%) failures were reported. There were 4 (0.5%) deaths due to DCIS progression. After 15 years of observation of patients treated in compliance with VNPI, the percentage of failures after local excision (4-6 VNPI points), breast conserving treatment (7-9 VNPI points) and mastectomy (10-12 VNPI points) was 29%, 21% and 9%, respectively. No differences in the overall survival was observed. In patients with 4-6 VNPI points the percentage of recurrences in the group treated in compliance with the VNPI (without radiotherapy) was 29% while in the group treated without compliance with the VNPI (with radiotherapy) - 2%. Conclusions: The Van Nuys prognostic index (VNPI) does not seem to be an ideal tool in patients with DCIS. It shows too high percentage of recurrences in the low risk group (VNPI of 4, 5 or 6 points), treated exclusively with a sparing surgery. Almost all patients after surgical excision should be irradiated.
Predictors of post-mastectomy radiation (PMRT) in node-negative breast cancer patients.
Authors: Sheriff Laura , Cordeiro Erin , Hardy Jacob , Roberts Amanda 
Published: May 2020

e12608 Background: Post-mastectomy radiation (PMRT) reduces the risk of locoregional failure for women with an elevated risk of recurrence from breast cancer. Therefore, PMRT is often indicated for women with node positive breast cancer including those with only 1-3 nodes involved. The need for PMRT in node negative breast cancer patients is less established. The objective of our study was to review the predictors of PMRT in women with node-negative breast cancer and evaluate the overall recurrence rates. Methods: A retrospective chart review was completed. Women with node-negative breast cancer who underwent mastectomy and sentinel lymph node biopsy at a regional breast cancer center between January 1st,2011 and December 31st, 2017 were included. Patient and tumor characteristics, treatment details and recurrence data were recorded. The primary outcome was recommendation of PMRT. Univariate analysis was completed and then a multivariable logistic regression was completed to determine independent predictors for PMRT. Results: Overall, 235 women with node-negative breast cancer underwent mastectomy and sentinel lymph node biopsy during the study period. Forty-three (18.3%) patients were recommended to undergo PMRT, with 39 of the 43 patients completing the recommended treatment. PMRT was offered more often to younger women (p<0.001), women with multifocal/centric disease (p=0.002), large tumors (p<0.001), high grade tumors (p < 0.001), lymphovascular positive tumors (p=0.04) and estrogen-negative disease (p =0.017). On multivariable analysis, the odds of radiation recommendation were highest for patients with high grade disease (OR 5.81, 95%CI: 2.08 – 16.20) followed by multifocal/centric disease (OR 3.12, 95%CI: 1.26 – 7.70). There were no differences in overall recurrence between patients who underwent PMRT versus those who did not have PMRT (p = 0.31). Conclusions: A moderate percentage of node negative patients are offered PMRT. Independent predictors for recommendation of PMRT in node negative patients are: decreasing age, increasing tumor size, multifocal/centric disease and higher grade disease. Surgeons can use this information to counsel patients regarding the possible need for PMRT, especially in the setting of planned immediate reconstruction.
Patients over 65 with early breast cancer and preference for intraoperative radiation despite no survival benefit.
Authors: Tang Annie , Kelly Jason F. , Cureton Elizabeth , Shim Veronica 
Published: May 2020

e12612 Background: Patients over 65 years of age with early-stage hormone receptor (HR)-positive breast cancer have many radiation treatment options based on the PRIME II and CALGB 9343. Our study aims to evaluate treatment preference of patients over 65 years of age when intraoperative radiation therapy (IORT) is offered. Methods: A retrospective chart review was conducted among patients over 65 years old diagnosed with early-stage HR-positive breast cancer during 2016-2019 in a single breast program in a large integrated healthcare system. At our institution, every breast cancer patient is reviewed at a weekly multi-disciplinary breast conference for IORT eligibility and tracked prospectively. All patients in this study met with breast surgeons and radiation oncologists prior to their locoregional treatment decisions. We identified patients who were offered IORT as an option. The tumor board discussion, treatment team recommendation, and the final patient decision for radiation were obtained from the chart review. Demographics including age, race, hormone therapy, and co-morbidities (Charlson Comorbidity Index) were collected. Logistic regression analysis was used to evaluate if any factors were associated with patients’ radiation treatment choice. Results: Among 225 patients who were over 65 with early endocrine responsive breast cancer, 63 patients met the IORT guideline (28%). Their ages ranged from 65-86 with a mean of 70.4 years. 74.6% of patients chose IORT compared with 14.3% who opted for whole breast radiation. Only 4.8% of patients chose to omit radiation after breast-conserving surgery, and 6.3% chose mastectomy. Patients who chose IORT was also more likely to take endocrine treatment (OR 4.76 CI 1.42-16.0, p = 0.01). Age, race, and co-morbidities were not associated with preference for IORT (OR 0.95 p = 0.34, OR 1.09 p 0.92, and OR 1.15 p = 0.53, respectively). Conclusions: Early-stage breast cancer patients over age 65 with HR-positive disease overwhelmingly desired radiation treatment even after being counseled that it does not confer an overall survival benefit. IORT was strongly preferred over whole breast radiation. This finding indicates that these women choose to maximize their local cancer control, regardless of its impact on overall survival, and prefer the convenience of single fraction, integrated radiation delivery. Further studies need to be completed on patient reported outcomes in this study population.