bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of sequence order of anthracyclines and taxanes in neoadjuvant chemotherapy for breast cancer: Results from a prospective institutional database.
Authors: Tesch Megan , LeVasseur Nathalie , Simmons Christine E. , Chia Stephen K. L. 
Published: May 2020

e12619 Background: There has been growing interest in the optimal sequencing of anthracyclines and taxanes in neoadjuvant chemotherapy (NACT) for breast cancer. However, data comparing efficacy of administering taxanes prior to anthracyclines as opposed to the opposite sequence remains limited and inconsistent. The objective of our study was to assess the impact of sequence order on pathologic and clinical outcomes in a real-world setting. Methods: A prospective institutional database was analyzed to identify all HER2-negative breast cancer patients treated with NACT from 2012 to 2019. Rates of pathologic complete response (pCR), down-staging, and breast-conserving surgery were compared between patients who received anthracyclines followed by taxanes (AC-T) to those who received taxanes followed by anthracyclines (T-AC). Chi-square and independent sample non-parametric tests were used to test for associations between variables and outcomes. Results: Of the 270 patients who met eligibility criteria, 175 (65%) received AC-T and 95 (35%) received T-AC. Median age was 55 (IQR 24-86). Overall, 83% of patients had stage IIB or greater tumors, 40% had grade 3 histology, and 36% had triple-negative disease. Characteristics were balanced between the AC-T and T-AC groups (all p < 0.05). Median duration of treatment with NACT was 102 days (IQR 29-203). Rates of pCR (19% vs 21%, p = 0.750), down-staging (68% vs 61%, p = 0.188), and conversion to breast-conserving surgery (26% vs 20%, p = 0.314) were similar for AC-T vs T-AC, respectively. pCR was higher in triple-negative compared to hormone-positive cases (33% vs 13%, p < 0.001). Conclusions: In this small population-based cohort, sequence order of anthracyclines and taxanes did not demonstrate statistically significant differences in evaluated outcomes from NACT for breast cancer. This supports the current variation in prescribing practice and highlights the need for further studies in this area.
The long-lasting anti-tumor activity of cisplatin affecting the sustainable systemic immune alteration may improve distant-disease free survival of triple-negative breast cancer in patients with a substantial residual tumor following preoperative chemotherapy: A retrospective analysis with translational research.
Authors: Yamaguchi Ayane , Kawaguchi Kosuke , Ishiguro Hiroshi , Kataoka Tatsuki R , Torii Masae , He Chenfeng , Kawaguchi-Sakita Nobuko , Kawashima Masahiro , Takada Masahiro , Suzuki Eiji , Toi Masakazu 
Published: May 2020

e12631 Background: Residual disease after preoperative chemotherapy is known to be a poor prognostic factor in triple-negative breast cancer (TNBC). Perioperative use of cisplatin (CDDP) is a well-known, standard treatment for most tumors except breast cancer. In this study, we explore the long-lasting anti-tumor activity of CDDP for TNBC patients. Methods: This research was based on consecutive study of seventy-nine previously untreated stage I–III TNBC patients treated with or without CDDP-based preoperative chemotherapy from 2007 to 2018 at the Kyoto University Hospital. We calculated the residual cancer burden (RCB) using the RCB calculator. All patients were sorted according to their RCB class: the pathological complete response (pCR), and RCB class I (minimal), II (moderate) or III (extensive). Distant disease-free survival (DDFS) was analyzed using the Kaplan-Meier method. Using mass spectrometry, we measured platinum concentrations in serum and normal breast tissue removed during surgery from patients treated with any platinum agents. We examined multiplex cytokine assays from serum sequentially, comparing CDDP and non-CDDP groups. Results: Forty-seven cases were treated with CDDP, and thirty-two did not have CDDP. The pCR rate was 53.2% for the CDDP group and 21.9% without CDDP. Patients with pCR and RCB class I were all distant disease-free. There was no significant difference between each RCB class using CDDP. However, patients belonging to RCB classes II and III with CDDP showed a better prognosis than the same RCB classes without CDDP (hazard ratio = 0.12). Platinum concentrations in serum were correlated with the time from the last dose of platinum agents, but platinum was even detected in serum two years after CDDP. No significant difference was found in the platinum concentrations of serum or normal breast tissue in the pCR and non-pCR groups. We also found that there were significant cytokine expression alteration related to T-cell infiltration only in the CDDP group one year after operation. It is suggested that CDDP may even affect the systemic immune alteration one year after operation. Conclusions: Our data shows that CDDP- based chemotherapy improves DDFS in patients with a substantial residual tumor. CDDP seems to sustain anti-tumor activity for a number of years and interaction with the systemic immune alteration.
Pathological complete response rates in HER2 amplified breast cancers based on levels of HER2 amplification.
Authors: Patel Ina , Hashimie Yasmeen , Hall James , Bhat Ashwini 
Published: May 2020

e12632 Background: Untreated HER2 (Human Epidermal Growth Factor) amplified breast cancer has poorer prognosis, compared to those with HER2 negative status with shorter time to relapse and increased incidence of metastases and higher mortality. Both Trastuzumab and Pertuzumab (humanized monoclonal antibodies against HER2) have shown to improve PCR (Pathological Complete Response) rates when used in the neoadjuvant setting. However, whether the quantitative level of HER2 amplification affects PCR rates or disease-free survival/overall survival has not been well studied. If the level of HER2 amplification correlates with PCR rates, this could be a tool for clinicians to use as a predictive marker for response to therapy. Methods: This is a retrospective chart review of community oncology clinic patients with HER2 amplified breast cancer Stage I-III to evaluate the rates of PCR after HER2 targeted neo-adjuvant therapy categorized by HER2 CISH (Chromogenic in situ hybridization) amplification and stratified based on levels of amplification of < 3, 3 to 5, or > 5. Pathology reports were reviewed for report of PCR. Inclusion criteria was women age 19 to 90, HER2 positive biopsy proven breast cancer, Stage I-III, patients treated with neoadjuvant chemotherapy, adequate renal function, and left ventricular ejection fraction within normal range. Exclusion criteria was pregnancy, metastatic disease, history of other malignancies, and impaired renal or cardiac function. Results: The data consisted of 36 unique patients, 25% of whom had a HER2 below 3, 22.2% had a HER2 between 3 and 5, and 52.8% had a HER2 value > 5. There was found to be a statistically significant association between the level of HER2 amplification and PCR rates with increased amplification of HER2 relates with increased PCR rates (p value < 0.0176). Both three-year disease-free survival and three-year overall response rates were not statistically significantly associated with HER2 category (p value -0.2691 and 0.4692 respectively). Conclusions: The information from this study may introduce a future systematic approach to further risk stratify patients based upon their quantitative HER2 amplification level to help predict response to therapy. We have noted that a level of HER2 amplification > 5 led to significant association with PCR compared to < 3 and 3-5 values.
Variability in metabolic cross-feeding behaviors in breast cancer and response to neoadjuvant chemotherapy.
Authors: Peterson Joseph R , Cole John A , Earnest Tyler M , Hallock Micahel J , Pandey Tushar , Ritchie Katherine , Braun Eduardo 
Published: May 2020

e12645 Background: Success of neoadjuvant chemotherapy (NACT) varies by intrinsic subtype of a patient’s breast cancer (e.g., Normal-like, Luminal A/B, HER2-enriched, Triple Negative). The metabolic rate of a given tumor is implicated in response to chemotherapies, as many act by killing rapidly dividing cells. Metabolic dis-regulation opens avenues for cancer cells to exploit environmental niches arising in the tumor microenvironment (TME). Focusing on the role the TME plays in defining cancer behavior, we undertook a theoretical investigation to uncover how metabolic cross-feeding affects subtype behavior and patient response. Methods: An in silico analysis of cross-feeding variability arising from metabolic differences breast cancers was undertaken. TME community models consisting of fatty, glandular, and cancerous tissues’ metabolic behaviors were created. Expression levels of metabolic enzymes for 1222 community patients in TCGA BRCA were used to create models. Models were used in 3D simulations of tumors for 300 patients from the TCIA (Clark et al., J. Digital Imaging, 2013). Cross-feeding trends within each intrinsic subtype were analyzed. Results: Predicted TME metabolic capabilities were compared to literature: LA/LB had lower amino acid consumption than TNBC/HER2+ for asparagine, glutamine (Glu), tryptophan, phenylalanine (van Geldermolsen et al. Oncogone 2016; Furuya et al. Cancer Sci. 2012). Additionally, TNBC tumors produced Glu which was consumed by adipose tissue ( Cao et al. BMC Cancer, 2014), TNBC produced methionine and proline (Kanaan et al. Can. Gen. Prot. 2014), and TNBC/HER2+ cancers consumed high density lipoprotein produced by adipose (Balabum et al. Cancer Met. 2017). The simulations revealed novel cross-feeding behaviors. In general, TNBC/HER2+ relied on glucose as the primary energy source, while LA/LB relied on the amino acids alanine, glycine and Glu. TNBC/HER2+ cancers produced high levels of lactate which was consumed by adipose tissues. Uniquely, glycine produced by cancer was consumed by fat in TNBC cancers Several environmental niches were induced in the healthy tissue by the presence of the cancer; for example, ornithine was predicted to be cross-fed from fatty to glandular tissues in TNBC/HER2+ cancers, and glutamate and inosine from glandular to fatty tissues in HER2+ cancers. Conclusions: Metabolic niches provide opportunities for cancer subtypes. These results suggest that metabolic pathway usage can lead to difference in growth, cross-feeding, and drug efficacy.
Real-world data analysis of next generation sequencing and protein expression in metastatic breast cancer patients.
Authors: Hempel Dirk , Ebner Florian , Milani Valeria , Janni Wolfgang , De Gregorio Amelie , Gaumann Andreas , Trepotec Zeljka , Garg Arun , Hempel Louisa 
Published: May 2020

e13005 Background: Next generation sequencing (NGS) together with protein expression analysis is back bone of molecularly targeted therapy in precision medicine. The present study shows the retrospective analysis of our experience with NGS using a panel of 324 genes in combination with protein expression in patients with metastatic breast cancer (mBC) over the last 18 months. The primary objective of this study was to analyze the prevalence of individual genetic alterations combined with protein expression to define potential targets for an individualized therapy. Methods: We analyzed 41 patients with advanced BC using solid tumor genomic profiling test. The test was used to detect clinically relevant genomic alterations (point mutations, indels, rearrangements, CNAs, tumor mutation burden (TMB) and microsatellite instability (MSI)) and to support the selection of appropriate targeted therapy. The protein expression (hormon receptors, ERBB2 and PDL1) of tumors was analyzed by immunohistochemistry (IHC). Results: The most common BC subtypes were HR+/ERBB2- (n = 20), followed by triple-negative (n = 15), and HER2+ BC (n = 9). 41 different genetic alterations were reported. Most patients had more than one genetic alteration (n = 27), as determined by NGS. The most common alterations were PIK3CA (n = 14), out of which 11 (78%) were hormone-receptor positive/ERBB2 negative. Conclusions: The NGS of mBC supports the decision for the most promising treatment option in 58,5% of our patients with a Tier I evidence. For an appropriate treatment decision it is necessary to evaluate gene alterations und protein expression of metastases in account. For an appropriate interpretation of rare gene alterations in mBC basket trials on basis of real world data are necessary. We founded the OnkoVision alliance to bring MTB into clinically routine and to identify appropriate patients for basket trials.
Cardiotoxicity manifestations in metastatic breast cancer patients treated with trastuzumab as first line.
Authors: Sherman Shira , Barkan Tamar , Yerushalmi Rinat 
Published: May 2020

e13011 Background: Trastuzumab is a monoclonal antibody that targets the human epidermal growth factor receptor-2 (HER2). Its use may result in cardiotoxicity. There are no formal guidelines for left ventricular ejection fraction (LVEF) monitoring in patients with metastatic disease treated with trastuzumab. Our local guideline include an echocardiogram every 3 months for these patients. Methods: We collected data from electronic records and hard copy files of patients treated with Trastuzumab as first line, between the years 2011-2014. Results: One hundred patients met the inclusion criteria. Median treatment duration of all patients was 30 months, with an average of 12 echocardiogram follow-ups per patient. Ninety-nine patients (99%) received additional chemotherapy. Thirty patients (30%) also received Pertuzumab. Ten (10%) of the eligible 100 patients showed significant decline in EF (≥10%) to a final LVEF of < 50%. The median follow-up duration of these patients was 52 months. Median EF at the beginning of treatment was 61.5% in all patients. Cardiotoxicity occurred at an average of 23 months [median 18 months] after beginning of Trastuzumab treatment (range; 3-54 months), with an average EF decline of 14% (range; 10-18%). Three patients (30%) required treatment change due to the decline in EF. Temporary cessation of treatment was necessary in 4 (40%) of the patients for a period of time between 4 weeks to 8 months. The remaining 3 patients (30%), although developing significant decline in EF, did not require treatment cessation or change. None of the 10 patients presented any other clinical sign of cardiotoxicity. In the group with cardiac events, there were no previous reports of congestive heart failure (CHF), ischemic heart failure (IHF), myocardial infraction (MI) or diabetes. Only one patient was a smoker and another received hormone replacement therapy. The average age of this group at the time of diagnosis of metastatic disease was younger (50.6 vs. 55.8, P-value 0.5). Conclusions: Monitoring heart function by trimonthly echocardiogram does not seem to be the optimal monitoring modality in metastatic breast cancer patients who receive a trastuzumab-containing regimen as first line. This study results suggest that less frequent monitoring may be sufficient, thus diminishing patients' inconvenience and allowing better allocation of health care resources.
Distribution of oncotype recurrence scores in invasive lobular carcinomas.
Authors: Suchman Kelly , Zimmerman Brittney Shulman , Ru Meng , Cascetta Krystal Pauline , Tiersten Amy 
Published: May 2020

e13025 Background: Invasive lobular carcinomas (ILC) account for approximately 10-15% of all invasive breast cancers, with the majority of cases presenting as ER/PR positive and HER2 negative. As a result, they often exhibit more robust responses to hormone therapy than adjuvant chemotherapy. Oncotype Recurrence Score (RS) RS is a 21-gene assay used to predict the rate of distant recurrence and response to chemotherapy in women with node-negative, hormone-positive breast cancers. Limited evidence exists regarding oncotype scores for ILC tumors, thus the aim of this study was to examine the distribution and risk stratification of Oncotype RS in ILC tumors. Methods: We analyzed patient and tumor characteristics of 492 patients- 417 (85%) IDC (intraductal carcinoma) and 75 (15%) ILC. Chi-square tests and Wilcoxon rank-sum tests were used to compare categorical and numerical outcomes, respectively. Results: No significant difference was found between IDC and ILC in terms of age and ER/PR positivity. The RS raw scores were also not significantly different between the two groups (both had median scores of 16). ILC patients were significantly more likely to be in the lower RS risk groups using the traditional (Paik) cutoff than ILC patients (61%, 39% and 0% in low, medium and high-risk groups as compared to 57%, 33% and 10% in IDC, p < 0.01). Of 417 patients with IDC, there were 16 recurrences (4%) with a median time from diagnosis to recurrence of 43 months (IQR: 28 Ð 58 months), while 1 in 75 ILC patients had recurrence at 50 months. Conclusions: Oncotype RS scores have the potential to guide treatment decisions in node-negative breast cancers. Though mean RS were similar between ILC and IDC patients, ILC were more likely to be distributed in low-risk groups. Our study was limited by a small sample size and a single ILC recurrence. Further research is needed to determine oncotype RS and recurrence rates. Future studies with longer term follow up can help better elucidate patterns of recurrence scores and recurrence rates based on histologic tumor type. [Table: see text]
A retrospective analysis of CDK4/6 inhibitors among adult female patients with metastatic breast cancer.
Authors: Comis Silvia , Kandasamy Thenmozhi , Perrin Alysa J , Kent Kelley , Dulawat Mahendra , Chhikara Arun , Ranjan Nitish 
Published: May 2020

e13028 Background: The aim of this study is to examine the behavior pattern of cyclin-dependent kinase (CDK4/6) inhibitor combinations in adult females with de novo metastatic breast cancer as first therapy or following adjuvant hormonal therapy. Methods: Using United States open health claims and prescription data we analyzed metastatic breast cancer from 2015 Q1 to 2019 Q4, adult female patients (age ≥18). Patients were classified into 3 groups based on their first therapy: Group 1-Hormonal, Group 2-CDK4/6 Inhibitor Combinations, and Group 3-Everolimus Combination. Analysis was completed using the Chi-Squared goodness of fit test assessing the patients moving to next therapy by time period. We also compared the overall CDK4/6 group as a base for probability distribution to study the pattern of therapy change in individual groups. Results: Of 37,351 patients on CDK4/6 inhibitors as first therapy or following adjuvant hormonal therapy for advanced/metastatic diseases, the percentage of patients who moved to next therapy was 3.2% (1,200 patients). For most patients, change in therapy occurred within a 2-year period (87%) and those who remained on their first therapy continued for an extended duration. In both Groups 1 and 2 no statistically significant difference was found in the treatment pattern compared to the overall CDK4/6 inhibitor patient population. However, most patients in Group 3 (90%) compared to the overall patient population on CDK4/6 inhibitors moved to Chemotherapy within the first year of treatment (statistically significant at p-value = 0.02). Further analysis of granularity in individual patient pathways showed about 90% of patients with CDK4/6 inhibitors remained on therapy for about 1 year and, interestingly, about 2% extended beyond 2 years up to 4.5 years. Conclusions: The results show most patients on CDK4/6 inhibitors (95%) had progression free survival (PFS) for the period we analyzed. Overall, patients on CDK4/6 inhibitors behaved similarly when used as first therapy or following adjuvant hormonal therapy.
Real-world treatment patterns among metastatic breast cancer patients by BRCA status and phenotype.
Authors: Sebby Wendy , Liede Alexander , Mazumder Debasish , Ghosh Anirban , Papademetriou Eros , Potluri Ravi C. , Bach Bruce Allen , Tyczynski Jerzy Edward 
Published: May 2020

e13046 Background: BRCA1/2 mutations account for 5-10% of breast cancer (BC) patients. BRCA1 mutations are associated with aggressive tumors, often triple negative (TNBC) (HER2, estrogen-receptor [ER], progesterone-receptor [PR] negative) and are mainly treated with combination chemotherapy or platinum agents. This study aimed to compare real world treatment patterns in breast cancer patients who were BRCA-mutation positive (BRCA+) and those who were BRCA-mutation negative (BRCA-), focusing on hormone-receptor positive (HR+) and TNBC subgroups. Methods: Optum’s Humedica electronic health records (EHR) database was used to identify a cohort of women with 1) confirmed BC ICD-9/ICD-10 diagnosis between 2008 and 2018, 2) at least 12 months of history in EHR, 3) at least one distant metastasis diagnosis (per ICD-9/ICD-10 or physician notes), and 4) no previous diagnosis of other primary cancers in previous 12 months. HR and HER2 test results were used to create relevant subgroups. Distinct lines of therapy (LOT) in the post-metastatic period were established using business rules. Treatment patterns and duration of treatment were analyzed. Results: Among 65,934 metastatic BC patients identified, 7941 were BRCA+, of whom 5366 (68%) were HR+ and 1323 (17%) had TNBC phenotype, while 4027 were BRCA-, of whom 2859 (71%) were HR+ and 561 (14%) had TNBC phenotype. Seventy-one percent of BRCA+ women underwent drug treatment, compared to 65% of BRCA- women. Drug treatments included hormonal treatment (+/-other agents), targeted therapy, and chemotherapy only, and varied across the different cohorts (Table). Mean (median) duration of treatment in LOT1 in the BRCA+ and BRCA- cohorts was 117 (73) and 117 (72) days, respectively. Conclusions: Real-world evidence on treatment patterns in BC patients revealed substantial differences across important biomarker and hormonal status BC phenotypes. As a preponderance of women with TNBC are still being treated exclusively with chemotherapy, these data highlight how the need for development of effective treatment options for TNBC remains high. [Table: see text]