bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting Oncotype DX score with clinicopathological variables.
Authors: Ramos-Lamboy Valmarie , Cabanillas Fernando , Echenique Miguel M. , Carlo Victor , Negron Viviana , Pavia Orestes Antonio , Bruno Margarita , Santiago Karen J. 
Published: March 2020

e11015 Background: Oncotype Dx (OD) is a commercially available gene-profiling test that has been shown to be effective in predicting risk of recurrence after therapy with CMF or Tamoxifen. The aim of our study is to develop a method that uses easily available clinical data to predict cases with favorable OD category (ODC). Methods: We identified 145 ER+/Her-2 neg cases that had information on histologic grade (HG), PR status and Oncotype Dx Category (ODC). Of these, 75 also had information on Ki-67. We evaluated HG, ER status, PR status, Nottingham score and tumor size for their correlation with ODC using multiple regression analysis. Results: The median tumor size was 12.0 mm (0.6-45). 33.7% were HG 1, 54% were grade 2, and 12% were grade 3. 88% were invasive ductal carcinomas, 9% were invasive lobular carcinomas, 3% were other types. The median OD score was 15 (0-57) with 86 (59%) ODC=1, 53 (37%) ODC=2 and 6 (4%) ODC=3; median Ki-67 was 11% (1-50). In a multivariate analysis excluding Ki-67, the only factors that were significantly correlated with ODC were PR status and HG (p= 0.004). PR status had the strongest overall association with ODC (P=0.008). Defining PR> 60% with HG=1 as a positive result we calculated the positive predictive value (PPV) or the capacity to predict cases with ODC=1, as 85% and negative predictive value (NPV) as 46%. None of the cases with PR> 60% and HG=1 had an ODC=3 (high risk). A patient with a favorable ODC=1 was considered as a positive case for purpose of calculating PPV, NPV, sensitivity and specificity. Sensitivity to detect positive cases was 26% and specificity was 93%. We explored a 2nd model that included Ki-67 and found that only PR >60% and Ki-67 >11% significantly correlated with ODC (p=0.004). PR status again had the strongest overall association with ODC (P=0.007) followed by Ki-67 (P=0.019). HG was not significant in the 2nd multivariate model because of its strong correlation with Ki-67. PPV for this 2nd model was 79% and NPV=50%. Conclusions: 1-Pts who have PR>60% with HG=1 are highly likely to have a favorable ODC=1, however the ODC of pts with either PR<60% or HG>1 is not predictable with either of our two models. 2- The use of Ki-67 doesn’t add much to the capacity of the model to predict ODC. 3- PR is the strongest predictive factor in the model.
Association of response to neoadjuvant chemotherapy (NAC) in premenopausal patients with hormone receptor-positive early breast cancer with chemotherapy-induced ovarian function suppression by NAC.
Authors: Yamamoto Yutaka , Yamaguchi Risa , Fujiki Yoshitaka , Ibusuki Mutsuko , Murakami Keiichi , Iwase Hirotaka 
Published: March 2020

e11017 Background: The purpose of this study is to assess the additive endocrine effect by chemotherapy-induced ovarian function suppression (CIOS) for premenopausal women with early breast cancer in neoadjuvant chemotherapy (NAC). Methods: We retrospectively compared the clinical efficacy to NAC between premenopausal and postmenopausal patients with early breast cancer to evaluate the endocrine effect by CIOS. One-hundred twenty two patients received NAC with anthracycline-containing regimen and/or taxane in Kumamoto University Hospital between April 2004 and March 2011. Results: Objective response rate by NAC in premenopausal ER-positive/HER2-negative patients is greater than that in postmenopausal ER-/HER2+ patients (premenopausal 93% vs. postmenopausal 63%, p=0.0121). Reduction rate of primary tumor by NAC on imaging studies in premenopausal ER+/HER2- patients is greater than that in postmenopausal ER-/HER2+ patients (premenopausal 54% vs. postmenopausal 40%, p=0.006). However, no significant difference in response rate between in premenopausal patients with other subtypes and postmenopausal patients with those was found (ER+/HER2+; premenopausal 50% vs. postmenopausal 48%, ER-/HER2+; premenopausal 43% vs. postmenopausal 77%, Triple-negative; premenopausal 86% vs. postmenopausal 65%). All of premenopausal women were suppressed ovarian function within two months after initiation of NAC. Expression levels of progesterone receptor on primary tumor in premenopausal ER+ cancer were significantly decreased after NAC compared with that in postmenopausal ER+ cancer (premenopausal -40.3% vs. postmenopausal +3.6%, p<0.001). Conclusions: These data suggests that CIOS by NAC contributes the additive effects through the endocrine fashion in premenopausal patients with ER+/HER2- breast cancer.
Estimation of maximum tolerated dose and minimum efficient dose of BP-C1 in the treatment of stage IV breast cancer patients: A phase I response surface pathway designed study.
Authors: Larsen Stig Einride , Dewi Sagita , Srimuninnimit Vichien , Lu Yen-Shen , Manuaba Tjakra , Jensen Steen Lindkaer 
Published: March 2020

e11022 Background: The aims were to establish a treatment routine and to estimate the Maximum Tolerated Dose (MTD) and the Minimum Efficient Dose (MED) of a novel anti-cancer agent named BP-C1. Methods: The material consists of 15 Stage IV breast cancer patients with a mean age of 51 years. The study was performed as a non-randomized multi-centre trial with between patient 3-level Response Surface Pathway design. BP-C1 was given intramuscularly once daily during 32 days. The given cumulative dose window was 0.16 to 1.12 mg/kg bw, resulting in a starting dose of 0.64 mg/kg bw. The main variable was the National Cancer Institute common toxicity criteria (NCI-CTC) Bethesda. If the increase in toxicity was classified as moderate or less, the next patient in the sequence was allocated to an increased dose. In case of severe toxicity increase, the dose was reduced. Patients receiving cumulative dose of 0.96 mg/kg bw or higher was defines as the high-dose group. Results: Three of the five patients on the first design level recorded unchanged toxicity, one mild and one moderate increased Max NCI-CTC. Of the four patients receiving 0.96 mg/kg bw, three obtained no change and one a mild toxicity increase. The four patients on the third design level received the maximal dose of 1.12 mg/kg bw without any change in Max NCI-CTC. The Sum NCI-CTC increased (p= 0.07) in the low-dose group, but reduced (p=0.09) in the high-dose group. The cumulative dose of BP-C1 was found significantly (p=0.048) and negatively correlated (r = - 0.52) to the increase in toxicity. Only mild to moderate Adverse Events were reported and the prevalence was found largest in the high dose group (p=0.06). In the high-dose group 62.5% of the patients were classified as responders compared to 28.6% in the low-dose group. One of the patients in the high-dose group was classified as complete responder. The development in both Karnofsky Scale of Performance Status and patient wellbeing was found obviously better in the high-dose group. Conclusions: BP-C1 can safely be administrated continuously during a period of 32 days. The MTD seem to be at least 1.12 mg/kg bw and the MED to be 0.96 mg/kg bw.
Comparison of breast cancer subtypes detected by mammography screening and tumors diagnosed with palpable masses.
Authors: Gomez Raposo Cesar , Suarez-Garcia Ines , Lopez-Gomez Miriam , Esteban Isabel , Andreu Monica , Vazquez Osorio Jose Lorenzo , Sereno Maria , Zambrana Tevar Francisco , Merino Maria , Carballo Mar , Garcia de Santiago Clara , Heras Javier , Pelayo Eva , Dominguez Franjo Purificacion , Alvarez Bernardi Julio , Casado Enrique 
Published: March 2020

e11028 Background: Recent studies have reported a greater mean breast density associated with estrogen receptor (ER)-positive disease than with ER-negative tumors, but controversial results have been published. The purpose of our study was to compare the difference in the distribution of breast cancer subtypes detected either by mammography screening or tumors diagnosed with clinically palpable masses in our centre. Methods: Between June 2008 and December 2011 157 patients with age between 40 and 70 years-old were diagnosed of early stage breast cancer. Tumors were classified in three major breast cancer subtypes by immunohistochemistry: TN (ie, ER, PR and Her2 negative), Her2-positive (ie, Her2 positive; ER and PR may be positive or negative), and ER-positive/Her2 negative (ie, ER positive, Her2 negative, PR may be positive or negative) types. Tumor characteristics and type of diagnosis (mammography screening or palpable masses) were obtained by retrospective chart review. Associations between categorical variables were evaluated with the X2 test. Results: Seventy patients (44.6%) were diagnosed of breast cancer with screening mammography, whereas 85 (54.1%) cases were detected by clinical suspected masses. Distribution according to molecular subtype defined by IHC were as follows: 123 (78.3%) ER-positive/Her2-negative tumors, 15 (9.6%) TN tumors, and 19 (12.1%) Her2-positive tumors. Less Her2-positive and TN tumors were significantly diagnosed with mammography screening (p=0.039 and p=0,020, respectively). No statistical differences were showed between ER-positive/Her2-negative tumors diagnosed with mammography screening and clinical palpable masses (p=0.78). Conclusions: The results presented in our study suggest that biologically aggressive subtypes of breast cancer are less frequently diagnosed with mammography screening in comparison with ER-positive/Her-2 negative tumors. Nevertheless, given the limited number of patients included and the bias related to retrospective studies these results must be interpreted with caution.
The effect of cholesterol depletion in resistant breast cancer cells.
Authors: Villeda Virgilio Alexander , Benakanakere Indira , Freter Carl 
Published: March 2020

e11031 Background: A leading cause of breast cancer chemotherapeutic treatment failure is resistance of cancerous cells towards current anti-estrogen agents. This project investigated the relationship between inhibition of cholesterol synthesis and its effect on resistant breast cancer cells. Methods: MCF-7 cells were maintained in phenol red free media and pretreated with charcoal stripped media for 24 hours prior to the experiments (ensure all exogenous estrogen was taken out). Cells were plated in 96 well plates at 10,000 to 15,000 cells/well. MCF-7 cells were tested for their sensitivity to BIBB515 and whether the proliferation of cells with estrogen could be blocked with BIBB515. The cells were grown for 6 days, on day 7 the cell proliferation was determined by adding MTT and read at 570nM. Results: Estrogen, tamoxifen and anastrazole induced cell proliferation that was controlled by 10µM BIBB515. Inhibiting the cholesterol pathway in combination with tamoxifen induced cell death in MCF-7 cells (cell proliferation of 0.13 ±0.15) compared to tamoxifen alone (0.57±0.041) p<0.001 by one way ANNOVA and multiple comparison by DUNN test. Anastrozole alone induced statistically significant cell proliferation 0.403 ±0.03 compared to combination treatment with BIBB515 (0.05 ± 0.007 p<0.001 by one way ANNOVA and multiple comparison by DUNN test). BIBB515 treatment could also inhibit the estrogen induced cell proliferation in MCF-7 cells. These results indicate that cholesterol inhibitors can be developed to fill a niche area in breast cancer disease management where clinicians would prolong treatment on first-line anti-hormone therapies of tamoxifen and anastrazole for advanced disease patients. Conclusions: Results show that inhibition of cholesterol sensitizes resistant cells to current anti-estrogen chemotherapeutic agents. This finding is significant because it could potentially translate into reduce rates of breast cancer relapse due to regiment failure. Exploiting this mechanism could alter the current treatment regimens, leading to control of the diseases in advanced stages by either inducing tumors to be static or to regress. This strategy may also limit the toxicities involved with chemotherapy.
Evaluation of the Oncotype Dx recurrence score (RS) in hormone-positive ipsilateral breast tumor recurrences.
Authors: Wapnir Irene , Florero Marilyn 
Published: March 2020

e11032 Background: IBTR (ipsilateral breast tumor recurrence) is considered a marker of risk for metastasis. Most IBTRs occur in the vicinity of the index tumor while elsewhere recurrences may represent new primaries. Oncotype DX®, 21-gene expression assay, quantifies a recurrence score (RS) in node negative, ER+ breast cancer. This modality can guide treatment decisions and has been extended to select node positive patients. Concordance of RS between the primary and IBTR is presented here. Methods: Archival blocks corresponding of 11 patients were obtained but only 8 were evaluable. The blocks were submitted using a blinded identification scheme to link the primary and recurrent tumor blocks. All were ER positive breast cancers. Six were N0, one N1, and one NX. Some assay results were preexisting. RS and single gene expression profiles for ER, PR and HER2 were compared. Scatterplots and descriptive statistics were produced for this exploratory hypothesis-generating (but not hypothesis-testing) study. Results: The time interval between primary and recurrence ranged from 12 to 216 months (mean 73.5 months). Among the 8 paired samples, RS’s were similar in 5 and different in 3. In the latter, RS shifted from 2 to 29, 15 to 23 and 25 to 14. These IBTRs occurred in a different quadrant, were simultaneous with axillary recurrence, or appeared after trastuzumab therapy. Overall, the Pearson correlation coefficient was 0.68 (95% CI -0.09, 0.93). Only one case shifted from ER+ to ER-; two cases from PR+ to PR- and one from PR- to PR+. No change in HER2 status was noted. The paired differences for ER were -0.01 (95% CI -1.09, 1.07), PR -0.74 ( 95% CI -2.43, 0.96) and HER2 -0.51 (95% CI -1.20, 0.17). The Pearson correlation coefficients and 95% CI were ER 0.72 (-0.02, 0.94); PR 0.61 (-0.22, 0.91); and HER2 0.89 (0.45, 0.98) respectively. Conclusions: The RS of the IBTR was similar to primary breast cancer in 5 of 8 cases in this exploratory pilot study. Hormone receptor status changed in only one of 8 cases. The clinical significance of these observations and the utility of these results in guiding therapeutic strategies is unknown.
Safety of trastuzumab, alone or in combination, in elderly patients with HER2-positive breast cancer: A 5-year case series.
Authors: Adamo Vincenzo , Ricciardi Giuseppina R. R. , Adamo Barbara , Ferraro Giuseppa , Franchina Tindara , Rossello Rosalba , Zanghì Mariangela , Russo Antonio , Valerio Maria Rosaria , Caristi Nicola 
Published: March 2020

e11056 Background: Breast cancer (BC) is frequent in the elderly and is burdened by high recurrence and death rates, due mostly to undertreatment. Trastuzumab (T), in combination with chemotherapy (CT) or hormonotherapy (HT), is a well-established treatment strategy for early and advanced HER2-positive (HER2+) breast cancer, but has been poorly studied in the elderly setting due to its infrequency. The aim of our study is to assess the safety of T in elderly patients with HER2+ BC. Methods: Between 2005 and 2010, consecutive HER2+ breast cancer patients of ≥70 years of age referred to two oncology centers and that received T-based therapy were retrospectively reviewed. All patients were treated according to multidimensional geriatric assessment (MGA) and clinical criteria. Results: Of 59 patients, 51 were evaluable with a mean age of 76 years (range 70-86). Trastuzumab was well tolerated overall. Median left ventricular ejection function (LVEF) at baseline was 61% and at the end of treatment was 55%. The most relevant adverse events consisted of only one case (2%) of symptomatic congestive heart failure, which required treatment withdrawal and six (12%) asymptomatic decreases of LVEF (3 pts >15% and 3 pts >10% versus baseline). Mild to moderate hypersensitivity reactions associated with T-containing infusions occurred in 3 patients (5.8%). Hypertension, obesity and previous anthracycline-based treatment and combination with CTs gave a trend towards a higher incidence of toxic events. Previous radiotherapy, concurrent HT and the different T schedules did not influence toxicity. Conclusions: Our data shows a good trastuzumab safety profile in non-frail women age 70 and older. These favourable findings may be related to the limited number of anthracycline pre-treatments, a substantial patient selection by MGA and close cardiologic monitoring. [Table: see text]
Hormone replacement therapy and its effect on HER2 neu status in primary breast cancer.
Authors: Khair Tina Ashley , Mittar Priyanka , Boolbol Susan K. , Boachie-Adjei Kwadwo , Klein Paula 
Published: March 2020

e11057 Background: Controversy has developed over the use of hormone replacement therapy (HRT) and its association with the future risk of breast cancer. The biology of breast cancer diagnosed after the use of HRT is different than in non HRT users. One such pathologic feature that may be affected by the use of HRT is HER2 neu. While there is existing data illustrating the relationship between HRT and breast cancer, there is little data examining the relationship between HRT and HER2 neu. The purpose of this study is to investigate that relationship and determine whether or not the use of HRT has any effect on the HER2 neu status of primary breast cancers. Methods: A retrospective review of a prospective database identified 2,928 patients with primary breast cancer with a history of prior/current HRT use. Tumor specimens were evaluated for HER2 neu expression at the time of surgery using either IHC or FISH. Pearson’s χ² test along with evaluation of odds ratios were used to determine whether or not there was an association of HER2 neu expression with HRT use. Results: Table 1A illustrates the lack of a correlation between increasing HER2 expression and HRT. There was no significant change in odds of HRT use as HER2 expression increased. After confirming HER2 neu status using FISH, the odds of HER2 positivity among HRT users was OR= 1.05 times the odds of HER2 neu positivity among non-HRT users [C.I. 0.85, 1.29; p = 0.63] (Table 1B). Conclusions: Contrary to our expectation of an inverse relationship between HRT use and HER2 negative phenotype, we found no clear association between the two. Limitations of this study include the inability to discriminate from our data set between current and prior users, and between estrogen alone and combination estrogen/progesterone supplementation. Additionally, the definition of HER2 positivity by membranous staining has changed over the last decade, which may be contributory. We plan on determining the relationship between HER2 status and ER status as it relates to HRT use in future studies. [Table: see text] [Table: see text]
Development of preclinical models of human BT474 and MDA-MB-361 breast cancer that endogenously overexpress HER2 and that respond to trastuzumab.
Authors: Francia Giulio , Rodriguez Cynthia , Xu Ping , Man Shan , Cruz-Munoz William , Bocci Guido , Kerbel Robert S 
Published: March 2020

e11061 Background: The anti-Her-2 antibody trastuzumab can be effectively combined with chemotherapy to treat Her-2 positive metastatic breast cancers. However, Her-2 positive breast cancers readily develop resistance to trastuzumab based therapies, and new models are needed to study such resistance, and to find new therapeutic options. Methods: We began the in vivo selection of human Her-2 positive breast cancer cell lines, BT474 and MDA-MB-361, in Severely Compromised Immunodeficient (SCID) mice. Tumor cells were implanted orthotopically into the mammary fat pad of SCID mice, and resulting tumors were serially passaged into new hosts over a 3 year period. Results: The resulting variants grow rapidly in SCID mice. Variants of both BT474 and MDA-MB-361 respond in vivo to trastuzumab monotherapy (20mg/kg twice weekly, i.p.) compared to controls (p<0.05). After 2-6 months of trastuzumab monotherapy, all variants developed resistance to trastuzumab; such resistant variants were adapted to tissue culture. BT474 variants produced a spontaneous lymph node metastasis in SCID mice, 10 months after the surgical resection of the orthotopically implanted primary tumor; this metastatic variant was also adapted to tissue culture. BT474 variants were tagged with luciferase and then implanted intracranially into SCID mice; the progressive growth of the tumors cells in the mouse brain was thereafter monitored for 3 months by bioluminescence imaging, which provides ample opportunity to test new treatments for brain metastases. MDA-MB-361 variants growing orthotopically responded (i.e. p<0.05 vs. controls) to the combination therapy of trastuzumab (20mg/kg twice weekly, i.p.) plus chemotherapy; chemotherapy consisted of a bolus of cyclophosphamide (CTX, 100mg/kg, i.p) followed by a maintenance metronomic CTX (20mg/kg/day, p.o.) regimen. Conclusions: We developed two preclinical models of human Her-2 positive breast cancer which may be used to study trastuzumab based therapies, Her-positive metastatic breast cancer, the growth of Her-2 positive breast cancer at a secondary site (i.e. the brain), as well as the evolution of tumor resistance to trastuzumab based therapies.
New insights into HER2 expression in breast cancer patients analyzed by qRT-PCR.
Authors: Yu Rong , Chiu Kung Y. , Lu Sunny , Lee Zi-jia , Zhang Peter , Hsieh Wen Chuan , Wu Han-chieh , Su Ih-jen 
Published: March 2020

e11068 Background: HER2 gene status is a key determinant for anti-HER2 therapy with Herceptin. The common methods used for HER2 test in breast cancer patients are IHC and FISH, which are time-consuming and often generate variable results. Quantitative real-time PCR (qRT-PCR) has emerged as a new gold standard technique for quantifying gene expression in different cells and tissues. In this study, we explored the potential of utilizing this technique to determine HER2 expression status in breast cancer patients. Methods: We collected both freshly-frozen and formalin-fixed paraffin-embedded (FFPE) breast tumor samples at three locations. The total RNA was isolated with a RNA extraction kit and was quantified by RiboGreen method. Each sample was normalized against its total RNA concentration and analyzed by a real-time PCR method with inclusion of the Standards and RNA Control. The HER2 expression level was determined by the copy number, Ct value, as well as the ΔCt against RNA control. The significance of HER2 expression and correlation among the different groups were analyzed by statistical methods. Results: A total of 80 samples have been tested. We noticed that the RT-PCR method generated very consistent results with little intra- and inter-assay variance. We also noticed that HER2 expression in the fresh tumor samples exhibited two distinct populations, although HER2 expression in the normal fresh samples showed the continuous distribution. Similar results were obtained with the FFPE samples. Study of the other breast cancer-related genes, such as EGFR, ER-a, BRCA1, and BRCA2, revealed that their expression, unlike HER2, followed a pattern of continuous distribution. In comparison with FISH test, qRT-PCR method not only produced consistent results, but also able to differentiate breast tumors into two distinct groups, HER2 positive vs. HER2 negative. Conclusions: The qRT-PCR is a more reliable method than the currently used IHC and FISH for HER2 test. Showing two distinct groups of HER2 expression by qRT-PCR further warrants its application in testing HER2 gene status for breast cancer patients.