bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of MSKCC nomogram for prediction of metastasis to nonsentinel lymph nodes in carcinoma breast in Indian patients.
Authors: Somashekhar S. P. , Rauthan Amit
Published: March 2020

e11510

Background: Sentinel node biopsy has emerged as the standard of care in clinically node negative breast cancer (cT1,T2 N0). In cases where sentinel node is negative, ALND can be avoided. In nearly 30-50% cases, the sentinel lymph nodes is the only site of metastases, demonstrated in Indian population too. In ASCOG ZOO11 trial, patients who had metastases in sentinel node did not undergo ALND. Patients in the trial received radiation as part of breast conservation surgery. In Indian patients, this is not applicable as most of the patients undergo mastectomy. It would be highly beneficial to identify the subset of patients, where the sentinel node is the only site of metastasis. Various nomograms have been used to predict the risk of metastasis in non sentinel nodes. MSKCC nomogram has been validated in many studies in the USA and Netherlands. Methods: The records of 240 breast cancer patients between 2007 and 2011 who underwent SLN and / or ALND were selected. Serial hemotoxylin and eosin (HE) analysis and immunohistochemistry were routinely performed on each sentinel node. Various factors like T size, histology and grade, lymphovascular invasion, number of +ve and –ve sentinel nodes, hormonal status, multifocality were recorded. Risk of non sentinel node metastasis were calculated by nomogram. Results: 63 out of 240 patients had sentinel node positivity and underwent ALND 20 out of 63(31%) had metastasis in non sentinel nodes also. Mean predictive risk as per nomogram for SLN was 53% and non SLN mets was 68%. None of our patients had low risk of non sentinel node metastasis as per MSKCC nomogram. Conclusions: MSKCC nomogram is not validated for Indian Breast Cancer patients, in our study population as it could not differentiate between patients having metastasis in sentinel node only from those having non sentinel node metastasis based on risk stratification. Because in India, the mean Tumour (T) size is big and Grade is usually high grade and one of the reason the present MSKCC nomogram is not applicable to Indian Breast cancer patients. In Indian populations, a different nomogram is required to correctly predict the non sentinel node metastasis.
Retrast: Retreatment after adjuvant trastuzumab—Our regional southern Italy experience.
Authors: Caruso Michele , Adamo Vincenzo , Tralongo Paolo , Giuffrida Dario , Gebbia Vittorio , Leonardi Vita , Soto Parra Hector J. , Valenza Roberto , Borsellino Nicolo , Sanò Maria Vita , Priolo Domenico , Di Mari Anna Maria , Prestifilippo Angela , Ricciardi Giuseppina , Miano Eleonora , Zacchia Alessandra , Ferraú Francesco
Published: March 2020

e11526

Background: Trastuzumab (T) is the standard of care for pts with HER2+ve BC. Relapse after adj T remains a rare event. Since the large use of T in adj setting, becomes crucial to evaluate advantages of retreatment with T for pts who relapsed after treatment in early stage. There is still lack of clinical evidence and poor data from CT to say that there is a benefit in T re-exposure after relapse following adj T. Methods: Since Jun 2006 and Dec 2011, we reviewed pts with early BC treated with T in adj therapy, relapsed and re-treated with T in first line therapy, in 10 departments of medical oncology in Sicily. We aimed to study feasibility, responses and treatment outcome. Results: 62 pts with HER2+ve fulfilled the criteria for this analysis and 47 were evaluated. Pts had a median age of 53 ys (29-79). ER/PgR-ve cases were 16 (34 %). Ki67 was > 20% in 34 pts (74%). 31 pts (64%) had >3 nodes+ve. All the pts received adj therapy with anthra+/-taxane. 55% of pts had >2 metastatic sites. 12 (25,5%) pts were revalued for HER2: 10 pts confirmed 3+ and two pts 2+ were FISH+. Median time from diagnosis to relapse was 25 mos (7 – 36). Median time from last dose of T to relapse was 10 ms (2 – 35). 33 (70,2%) pts and 14 pts (29,8%) had early (< 12 ms) and late progression (≥ 12 ms) respectively after adj T. First line of therapy was T in combination with mono/polychemotherapy in 42 pts (89,3%) and 5 pts (10,6%) respectively. 27 pts (57,4%) had objective responses (CR 5, PR 22) and 7 pts (14,8%) stable disease. 13 pts (27,6%) had progression: all of these pts had early progressive disease after adj T, 9 pts (69,2%) had Ki67>20%, 5 pts (38,4%) were ER/PgR-ve and 8 pts (61,5%) ER/PgR+ve. Median TTP was 4 mos (range 2-7). Median TTP for early and late relapses pts were respectively 3,7 and 4,8 mos, (p = 0,4). Median OS from relapse to death was 23 mos (r 12 – 37). LVSD G1 (EF < 60-50%) was observed only in 7 pts (14%). Conclusions: Our data confirm the feasibility and safety of treatment with T after adj T therapy and is active for a disease control rate in 72,4% of cases. These results demonstrate that relapses after adj T occurred early (<12 ms) in 70% of pts. However pts with primary resistance (27,6%) should be well categorized using biomolecular markers to receive up-front drugs that overcome the resistance to T.
Neoadjuvant trastuzumab and sequential chemotherapy with cisplatin, vinorelbine, and docetaxel for stage II-III breast cancer patients: Final results of a single institution phase II study.
Authors: Carillio Guido , Aiello Rosa Anna , Chiarenza Maurizio , Alì Marco , Mazzola Antonella , Di Marco Rosanna , Taibi Eleonora , Fallica Giuseppina , Casella Tiziana , Zacchia Alessandra , Castiglione Gaetano , Caruso Francesco , Caruso Michele ,   Humanitas Centro Catanese di Oncologia
Published: March 2020

e11527

Background: Several studies demonstrated the efficacy of neoadjuvant trastuzumab in breast cancer patients. However, cardiotoxicity intrinsic and increased by combining anthracyclines or chest wall radiotherapy remains a ticklish issue, mainly when is durable and occurs in potentially healable young patients. Methods: A phase II study of neoadjuvant trastuzumab and sequential chemotherapy was started in the late 2007 at Humanitas CCO and enrolled 42 patients with stage II-III HER2-positive breast cancer. Treatment consisted of 18 administrations of weekly trastuzumab combined with a sequential regimen including 3 courses of cisplatin 80 mg/m2 d1 + vinorelbine 25 mg/m2 d1 and d8 q3w followed by 3 courses of docetaxel 100 mg/m2d1 q3w. Peg-filgrastim was given in each course. Postoperative trastuzumab q3w was administered for one year. Radiant and endocrine therapy were delivered according to standard practice. Primary objective was the rate of pathologic complete response (pCR), now defined as no evidence of residual invasive cancer, both in breast and lymph nodes. A first report of the study was presented as poster at ASCO 2010. Results: With regard to real patient characteristics observed in the daily clinical practice, no restrictive sample selection was established and the eligible patients were accrued consecutively. Median age was 48 (range 23-71). Twenty-three patients (55%) had stage III tumors and 7 of them stage IIIB, including 4 cases of tumor spreading to skin (T4b) and 3 cases of inflammatory carcinoma (T4d). Seventeen patients (40%) had tumor with no expression of hormone receptors and 36 (86%) with ki67≥14%. The rate of pCR was 26% (11/42). Among 29 women initially candidate to radical mastectomy, 13 of them (45%) finally received breast-conserving surgery and 8 skin-sparing mastectomy. Treatment was well tolerated and produced only moderate alopecia and no case of significant LVEF decrease. Conclusions: Neoadjuvant trastuzumab combined with the above non-anthracycline-containing sequential chemotherapy may be considered a safe and effective regimen in HER2-positive breast cancer patients. Clinical trial information: 2006 000392 15.
Association of the neutrophil to lymphocyte ratio with survival patients with in metastatic breast cancer.
Authors: Unlu Ozan , Aygun Sevda , Petekkaya Hilbrahim , Gecmez Gizem , C. Roach Emir , Babacan Taner , Sahin Ugur , Keskin Özge , Kertmen Neyran , Aksoy Sercan , Altundag Kadri
Published: March 2020

e11544

Background: Identification of simple and measurable prognostic factors is an important issue in treatment evaluation of breast cancer. Although various markers are considered while making a decision to treatment modality, clinicians investigate for new prognostic factors for reason of highly variable responses of individuals. Therefore, this study estimates the survival probability of the neutrophil to lymphocyte ratio (NLR) for patients with metastatic breast cancer. Methods: We included the patients with metastatic breast carcinoma who were treated for metastasis. NLR were calculated and patients were divided into four quartiles (25th, 50th and 75th NLR; the lowest being the 1st quartile, the highest being 4th quartile ). Survival status was retrieved from our cancer registry. Survival analysis, stratified by NLR quartiles, was used to evaluate the predictive value of NLR. Results: Eighty-one patients with metastatic breast cancer were included in this study. Median age of diagnosis of the patients was 47 (26-83), the majority of them had grade II (%37) and grade III (%29.6) tumors and were metastatic at the time of their initial diagnosis. ER (+), PR (+) and HER2 (+) percentages were confirmed as 82%, 73% and 24% ,respectively. Ten percent of the patients were triple negative. Median follow-up time was 26 months and 29 patients died during the follow up period. We analyzed the overall survival among NLR quartiles. When we compared the quartiles with the highest and lowest NLR values, the quartile with the lowest NLR values had longer median overall survival than the quartile with the highest NLR values (212 vs. 27 months; p=0.01). The second and third quartiles, however, showed no statistically significant difference of overall survival between four quartiles. Conclusions: NLR can be a prognostic factor for overall survival in metastatic breast cancer patients.
Impact of enriched environment on tumor growth and adipokines secretion in a mouse model of mammary cancer.
Authors: Basu Samar , Combe Kristell , Nachat-Kappes Rachida , Farges Marie-Chantal , Rossary Adrien , Goncalves-Mendes Nicolas , Vasson Marie-Paule
Published: March 2020

e11552

Background: Enriched environment (EE) by promoting physical activity and social communication reduces development of tumors such as in colon cancer. It seems to act particularly through a decrease of leptin production which linked to breast cancer risk. Thus, the aim of this study was to investigate the effect of EE on the mammary tumor development and to identify the molecular pathways in relation to adipokines secretion. Methods: 3-week-old female C57BL/6 mice were housed in standard environment (SE) or in EE for 9 weeks. A half of EE and SE mice received either EO771 syngeneic cells injection into the inguinal mammary fat pad (EE and SE tumor) or vehicle (EE and SE control). After 3 weeks, the mice were sacrificed for blood and tumor analysis : expression of leptin, COX-2 (inflammation), Ki-67 (proliferation) and caspase 3 (apoptosis) were determined using immunostaining and western blotting. Plasma adipokines were quantified by immunoassay (ELISA, Luminex). Results: Tumor volume and weight were lower in EE mice vs SE tumor (-29% and -26% respectively). COX-2 and Ki67 expressions were decreased (20% and 40% of positive cells respectively) while caspase-3 levels were increased (450% of positive cells) relative to SE tumor (100%). EE control mice showed a significant increase in adiponectin levels but no change in those of leptin, IL-6, TNF-α, PAI-1, MCP-1 and resistin vs SE control. No significant difference between EE and SE tumor groups were observed for these inflammatory markers. Conclusions: These data showed for the first time that EE housing inhibits mammary tumor growth which results in a marked intratumoral COX-2 under-expression and an increase in the plasma adiponectin/leptin ratio without any change in inflammatory response. So, COX-2 and adipokines seem to be key regulating factors in breast carcinogenesis. [Table: see text]
Activation of P38MAP kinase in estrogen-positive invasive breast cancers: Relation with HER2 and downstream signaling phosphorylated proteins expression.
Authors: Merlin Jean-Louis , Harle Alexandre , Lion Maeva , Chrétien Anne-Sophie , Ramacci Carole , Leroux Agnès
Published: March 2020

e11560

Background: P38 kinases are members of the mitogen-activated protein kinase (MAPK) family. In breast cancers MAPK, as well as PI3 kinase-AKT pathway signaling proteins have major implication in molecular oncogenesis and are extensively investigated as putative targets for therapy. The present study reports the investigation of the expression of P38MAPK and its phosphorylated form (p-P38MAPK) in clinical specimens of invasive breast carcinomas in relation with estrogen receptor and HER2 expression, as well as MAPK and PI3K signaling phosphorylated proteins. Methods: The expression of P38MAPK and p-P38MAPK as well as p-AKT, p-GSK3β, p-S6 kinase, p-MEK1, p-ERK1/2 were semi-quantitatively assessed using multiplex bead immuno-assay. The analyses were performed retrospectively in frozen specimens from 46 invasive breast tumors classified according to estrogen receptor (ER) and HER2 status. Results: All specimens were taken at diagnosis and validated for tumor content >50%. Twenty-nine were ER+, 17 were HER2+, 10 were triple negative (TN) tumors. Analyses were performed in triplicate from total protein extracts and were achievable in all specimens. P38MAPK was found to be expressed in all tumor specimen and significantly (P=0.002) overexpressed in ER+ tumors. P38MAPK was lower in TN tumors than in all others. The median expression of phosphorylated-P38MAPK was also higher in ER+ than in ER- tumors and lower in TN tumors than in all others. HER2 status had no influence on P38MAPK and p-P38MAPK expression. No variation in the phosphorylation rate of P38MAPK was observed in relation with ER, HER2 or TN status. Significantly higher (P=0.0048) expression of p-AKT tumors was observed in HER2+ tumors. No significant difference in p-MEK1, p-GSK3β and p-S6K expression was evidenced in any other comparisons based on ER and HER2 expression subtypes. Conclusions: Investigation of the expression of multiple phosphorylated signaling proteins can be used as molecular biomarkers for personalized targeted therapy. In ER+ invasive breast cancer, the overexpression of P38MAPK could serve as biomarker for evaluation of P38MAPK inhibitors.
Treatment patterns and survival in elderly women with HER2-negative, hormone receptor positive metastatic breast cancer: Analysis of the SEER-Medicare database.
Authors: Karve Sudeep , Pawaskar Manjiri , Davis Keith L. , Dalvi Tapashi , Deeter Robert
Published: March 2020

e11570

Background: Although metastatic breast cancer (MBC) is a leading cause of death in elderly women, there is limited population-based data available on treatment patterns and survival in post-menopausal women with HER2 negative, hormone receptor (HR) positive MBC. This study therefore examined real-world treatment patterns and survival in this population Methods: A retrospective analysis was conducted using the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database, which comprised 13,170 women aged ≥65 years diagnosed with HER–, HR+ MBC between 1/1/2000 and 12/31/2009. The index date was defined as MBC diagnosis date or date of progression to MBC. Patients were followed from index date to death or end of database. Absence of trastuzumab and lapatinib treatment, and use of immunohistochemistry and fluorescence in-situ hybridization tests, was utilized as a proxy measure for HER2– status. Descriptive statistics were used to assess treatment patterns. Kaplan-Meier curves were used to examine survival in this patient population. Results: Over 78% of women (mean age 76.7 years, 88% white) were both ER+ and PR+ and 61% had ductal histology. The majority of patients had surgery (54%), followed by radiation (50%), hormone therapy (49%) and chemotherapy (40%). Among patients receiving hormonal therapy, megestrol (20%), anastrazole (16%) and fulvestrant (11%) were the most commonly used agents. Among patients receiving chemotherapy, cyclophosphamide (21%), doxorubicin (17%) and paclitaxel (14%) were most common agents. Median overall survival in these patients was 50 months and the 5-year survival rate was 45%. Median survival was lowest for patients aged >85 years (25 months), ER– PR+ (24 months), and distant stage at diagnosis (21 months). Conclusions: In spite of advances in treatment of MBC, survival remains lower in older and ER– PR+ women with MBC. This could be due to the limited access to effective treatments in elderly with HER2– and HR+ MBC patients.
Study of lapatinib (T) in combination with trastuzumab (T) in women heavily pretreated with HER2-positive metastatic breast cancer (MBC).
Authors: Salvador Javier , Ruiz Borrego Manuel , Valero Maria , Bayo Juan L. , De La Cruz-Merino Luis , Carabantes FRancisco , Rodriguez de la Borbolla Maria
Published: March 2020

e11577

Background: The anti-HER2 monoclonal antibody trastuzumab and the tyrosine kinase inhibitor lapatinib have complementary mechanisms of action and synergistic antitumour activity in models of HER2-overexpressing breast cancer.In heavily pre-treated pts, L+T is associated with improved outcomes compared to L alone and significantly improved progression-free survival (PFS), offering a chemotherapy-free option for patients with heavily pretreated human epidermal growth factor. (Kimberly L et al, 2012 JCO). Methods: We evaluated the safety and efficacy of L+T in patients with 1-4 prior (Median 3) lines of chemotherapy (CT) for HER2+ MBC.: 20 Pts with measurable, HER2+ MBC were eligible. Pts received every 3 weeks T (8 mg/kg loading then 6 mg/Kg) and daily L 1000 mg. Results: The characteristic of the all of pts included (20) are: median age 51.4 (32-68) Total number of cycles administered was 141. The median cycles administered per pts was 6 (range 1-18). Median follow-up was 6 months. Of the 18 pts with response assessment, the clinical benefit obtained was: 76,1% (5,9% PR + and 70,6% disease stabilization) with 95% CI 71.3%-80.9%. Disease progression was 17,6%. Of the 20 pts with a median follow up of 13,32 m (3-32), median PFS for these pts was 6 m. The one year OS % was 64,70% (56,7-72,7). All pts had received al least one line lapatinib prior (1-3). Toxicity was generally manageable. No major cardiac dysfunctions ocurred. Grade 3/4 treatment-related toxicities were uncommon (grade 3 diarrhea, 18%; grade 3 hepatic 7%. All others < 3 %). Conclusions: L+T is an active regimen in HER2+ MBC. L+T showed high clinical benefit with manageable safety profile. Dual inhibition of HER2 might be a valid approach to treatment of Her-2 positive metastatic breast cancer.
Adherence rates to endocrine therapy among African American women with stage I-III, hormone receptor-positive breast cancer treated at Grady Memorial Hospital in Atlanta, Georgia.
Authors: McKee Megan Jean , Nguyen Danny , Al Haddad Seham , Paplomata Elsa , Curry Marjorie Adams , Liu Yuan , O'Regan Ruth , Zelnak Amelia Bruce
Published: March 2020

e11582

Background: Breast cancer mortality has historically been higher in African American (AA) women compared to Caucasian women. Controlling for tumor characteristics, biological markers and comorbidities does not account for the disparity. Previous studies have shown that AA women are more likely to have a high 21-gene recurrence score compared to Caucasian women. Another potential variable affecting treatment outcomes is adherence to adjuvant endocrine therapy (ET). We conducted a retrospective review of pharmacy records at Grady Memorial Hospital (GMH) to examine the non-adherence rate among predominantly AA patients (pts). Methods: Pharmacy database records were examined for pts filling prescriptions for tamoxifen, anastrozole, or letrozole at GMH in Atlanta, Georgia from 2004-2009. Baseline characteristics were obtained by chart review. Pts were excluded if they had metastatic disease, DCIS, less than 60 days of eligible prescription, were male, deceased during the study period, benign disease, or no documentation of breast cancer in the electronic medical record (EMR). Non-adherence was defined as those filling less than 80% of eligible days covered by her prescription. Results: 679 pts were identified who filled prescriptions for tamoxifen, anastrozole, or letrozole at Grady pharmacy from 2004-2009. Pts who were excluded had metastatic disease (152), DCIS (101), had less than 60 days of eligible prescription (65), had no documentation of breast cancer in the EMR (25), were male (6), deceased before 2009 (5), or had benign disease (9). Of the 316 pts eligible for the study, median age was 60 (26 to 94) at time of diagnosis, 86% were AA, and 39% were node positive. 167 pts filled prescriptions for tamoxifen, 95 for anastrozole, and 54 for letrozole. The non-adherence rate for tamoxifen was 50%, anastrozole 38%, and letrozole 48%. Overall non-adherence rate was 46%. Conclusions: The overall non-adherence rate to adjuvant ET among a predominately AA population seen in a county hospital was similar to previously reported rates. Non-adherence to ET in this underserved AA pt population does not fully account for disparate outcomes.
Evaluation of anthracycline incuced cardiotoxicity by speckle tracking echocardiography.
Authors: Dogru Atalay , Cabuk Devrim , Sahin Tayfun , Dolasik Ilhan , Uygun Kazim
Published: March 2020

e11585

Background: Anthracyclines have been widely used in the treatment of solid and hematologic malignancies. Cardiotoxicity is the most serious adverse effect that limits anthracycline treatment. Cardiotoxicity is classified by time of onset as acute, subacute and chronic. Conventional echocardiography is not sensitive enough for early detection of cardiotoxicity. In this study we aimed to evaluate anthracycline induced cardiac toxicity by speckle tracking echocardiography (STE) before left ventricular dysfunction occurs. Methods: The study included newly diagnosed breast cancer (BC) and lymphoma patients (pts) who were treated with an anthracycline containing chemotherapy (CT) regimen. They had examination with conventional echocardiyography, STE before and after anthracycline treatment. Longitudinal strain values were assessed by automated function image (AFI). Results: Thirty five pts with BC and 15 pts with lymphoma were included in the study. Ejection fraction (EF) and fractional shortening values were decreased in lymphoma pts receiving high dose anthracycline treatment (346 mg/m2) compared to BC pts receiving low dose (168 mg/m2) anthracycline. There was statistically significant increase in myocardial performance index in both groups after anthracycline CT (p=0.001 and p=0.004 for BC and lymphoma group respectively). In STE measurements, apical long axis, apikal 4 chamber and global peak systolic strain showed significant reduction in lymphoma group who had a post-therapy EF <55% (p=0.002, p=0.041, and p=0.004, respectively). Apical long axis and global peak systolic strain were also significantly decreased among the lymphoma pts with normal systolic function after CT (p=0.01 and p=0.05, respectively). Conclusions: STE can display the effect of anthracycline induced cardiotoxicity early before left ventricular dysfunction occurs. Larger prospective studies are needed to verify these data and direct the treatment of pts receiving anthracycline.
Factors that predict pathologic complete response in patients receiving neoadjuvant chemotherapy for locally advanced breast cancer.
Authors: Hulikal Narendra , Thomas Joseph , Fernandes Donald J. , Ray Satadru
Published: March 2020

e11588

Background: Locally advanced breast cancer (LABC) accounts for 30-60% of all breast cancer patients presenting to the public hospitals in India. The neoadjuvant chemotherapy is reported to achieve a pathological complete response (pCR) rate of 35-60% depending on the receptor subsets and the chemotherapeutic drugs employed. The patients who achieve a pCR are expected to do better in terms of progression free survival. Hence we reviewed our data base to know pCR rates, to compare pCR rates among various receptor subgroups, and to determine the factors which predict pCR. Methods: All patients with LABC (defined as Stage III, AJCC, 7th edition, 2010) and agreed by the hospital tumor board to receive preoperative chemotherapy were included. At each visit, clinical response was assessed according to RECIST criteria. Re-staging work up and mammography were done prior to surgery. Results: Total 84 patients received preoperative chemotherapy. Most common regimen used was 4 courses of AC followed by 4 courses of 3 weekly paclitaxel. Two patients developed systemic metastasis during chemotherapy and were not considered for surgery. Median age was 46 years (ranged from 28 to 66), 46 patients were premenopausal, and 43 % of the tumors were hormone receptor negative. Her 2nu amplification defined as immunohistochemistry 3 + or FISH positive was seen in 27% of patients. Thirty nine patients were stage IIIB, 38 were III A and 5 were IIIC. Total 72 patients completed full course of chemotherapy before surgery. Clinical response was complete in 26, partial in 52, 3 had local progression, one stable and two patient developed distant metastasis (not considered for surgery). Forty eight patients underwent modified radical mastectomy and breast could be conserved in 34 patients. The pCR rate was 36%. Of all the factors (cT status, hormone receptor status, menopausal status, age) cT status was found to be statistically significant factor to predict pCR (p<0.005). Conclusions: Overall pCR rate in the study was 36%, maximum response was noted in ER/PR negative, Her 2nu positive subset. Only factor which was found to be associated with pCR on univariate analysis was cT size.
Demographic and clinicopathologic characteristics in patients with invasive breast cancer receiving metformin.
Authors: Aksoy Sercan , Sendur Mehmet Ali Nahit , Altundag Kadri
Published: March 2020

e11593

Background: There was contradictory data with metformin use on breast cancer risk, but there is growing evidence that the use of metformin in diabetic patients was associated with lower risks of breast cancer mortality and incidence. The effect of metformin on clinical and pathological properties of breast cancer was not known exactly, we aimed to investigate the demographic and clinico-pathological characteristics of patients with metformin users at the time of breast cancer diagnosis. Methods: Patients with breast cancer diagnosed from 2000 to 2012 in our clinic were retrospectively analyzed. Patient’s demographics, including survival data and tumor characteristics were obtained from medical charts. Breast cancer patients who were taking metformin at the time of breast cancer diagnosis were enrolled as metformin users (n=148), where the patients matched with the same age who were not taking metformin were included as a control group (n=636). Results: A total of 784 patients were included in this study. Median age of both metformin users and nonusers was 57 (23-87). There were no significant differences in baseline tumor size (P=0.60), tumor stage (P=0.76) node positivity (P=0.13) between the two groups. Metformin user patients compared to nonusers had significantly lower incidence of histological grade III tumor (P=0.03). A similar significant trend for lower incidence of triple-negative (P=0.01) and higher incidence ER positivity (P=0.008), PR positivity (P=0.01) was also seen in metformin users. In survival analysis the estimated median disease free survival (DFS) was 118 months in metformin users whereas 69 months in nonusers (P=0.09). Median overall survival (OS) could not be obtained due to low events. In patients with metformin users OS rate was 98.4%, 97.1%, and 93.8% and in nonusers was 99.6%, 94.4% and 90.5% the first, third, and fifth years, respectively. Conclusions: The use of metformin at the time of breast cancer diagnosis was associated with better clinico-pathological properties and non-significantly improved disease free survival in patients with breast cancer.
Association of expression of aquaporin 5 (AQP5) with prognosis in hormone-responsive early breast cancer patients.
Authors: Lee Soo Jung , Chae Yee Soo , Lee Yoo Jin , Kim Jong Gwang , Park Ho Yong , Kang Byung Woog , Jeong Ji Yun , Park Ji-young , Kwon Tae-Hwan , Jung Hyun Jun
Published: March 2020

e11594

Background: Our previous study showed the association of AQP5 up-regulation with cancer proliferation and migration in hormone-responsive breast cancer cell lines (MCF-7) and with unfavorable prognosis in a small number of patients with breast cancer. Accordingly, we analyzed the prognostic impact of AQP5 expression in a number of patients with early breast cancer (EBC). Methods: We enrolled 447 patients who underwent operation for EBC between June 2003 and August 2008 and performed immunohistochemical (IHC) stain for AQP5 expression in tissue microarray (TMA) collected from tumor tissue. Two pathologists independently scored staining intensity (IS, 0 through3) and percentage of positive tumor cells (PC, 0 through 4) and categorized as negative (0 through 2), weak (3 through 5), and strong (6 or more) according to the sum. Results: The median age of patients was 49 years (range 23-82). 80 (17.9%) patients underwent breast conserving surgery and adjuvant chemotherapy was given to 406 (90.8%) patients. Among enrolled subjects, 298 (66.7%) were hormone-responsive, 64 (14.3%) for HER2 overexpressed, and 79 (17.7%) for triple negative EBC by ER, PgR, and HER2 expression. AQP5 expression (staining score >2) was observed in 267 (59.7%) patients including 123 (27.5%) overexpression (stating score >5). In univariate analysis, AQP5 overexpression was associated with survival in patients with hormone-responsive and HER2 overexpressed EBC. Moreover, multivariate survival analysis revealed that AQP5 overexpression was an independent prognostic marker for survival in patients EBC, which was prominent in patients with ER/PgR-positive tumor type. However, no difference in AQP5 expression was observed based on patient and tumor characteristics. Conclusions: Consistent with our previous study with breast cancer cell lines, AQP5 expression in tumor tissue can be considered as a prognostic marker in patients with EBC after curative operation.
Trial of concurrent versus sequential tamoxifen with radiotherapy in breast cancer patients with study of the combination of pentoxifylline and tocopherol for prevention of radiation-induced lung fibrosis.
Authors: Ismail Soheir Sayed , Abdel-Hafeez Zeinab Mohamed , El Khodary Dalia Abd-Elghany , Kelany Mohamed rada
Published: March 2020

e11599

Background: Although the efficacy of both radiation and tamoxifen (TAM) in early-stage breast cancer is well established, data are lacking about the impact of this sequence on outcomes, including local recurrence and complications of therapy. These are questions of practical importance in the treatment of breast cancer patients, many of whom require both radiation (RT) and adjuvant TAM. Methods: 160 eligible patients were prospectively randomized 1:1 into two groups: The control group (80 patients) , containing one arm (C) received sequential TAM and RT and the intervention group which was further subdivided into arm (A) (40 patients), received concurrent TAM 20 mg/day with RT, arm( B) (40 patients), received concurrent TAM + Pentoxifylline (PTX) ( 800 mg/day )+ Alpha-Tocopherol (AT) (1000 U/day) and RT. The primary endpoint was to compare the radiation induced pulmonary fibrosis using serial high resolution computed tomography (HRCT) and the role of the PTX and AT combination in reduction of pulmonary fibrosis, the secondary endpoint was to evaluate loco-regional control in the three arms usingChi-Square test, Fisher’s exact test, Log rank test andAnova test. Results: Analysis of the incidence of clinical pneumonitis was 25% in arm A ( TAM) , 12.5% in arm B (TAM+PTX+AT) and 18.8% in arm C (control) with p=.110. The incidence of lung fibrosis was 26.5% in arm A( TAM) , 12.9% in arm B (TAM+VIT.E) and 23.4% in arm C (Control) with p=.608. As regard loco-regional relapse, the preliminary result, revealed no significant difference in the 3 arms (1.3% in control arm, 5 % in TAM, 2.5% in TAM+VIT) (p=.827). Conclusions: It seems that the interaction between tamoxifen and radiotherapy could affect the tissue remodeling rather than the damage induction step of the radiation pathogenesis. In this case, temporal separation of the two modalities (Concurrent Versus Sequential) may not make much difference in the incidence of radiation induced lung fibrosis.
Periodontal disease prevalence in patients treated with tamoxifen.
Authors: Brusca Marisa Isabel , Blanco Villalba Marcelo , Grandinetti Jose , Re Juan Pablo , PINI Alejandra , Streich Guillermo Juan , Molinas Emiliano , Gonzalez Palacios Carlos , Bramajo Marina Paula
Published: March 2020

e11600

Background: Periodontal diseases arise from inflammatory diseases involving the periodontal connective tissue as a common factor. Estrogen produces inflammatory changes that worseness the periodontal preexistent status; and alters the microbiologic environment acting as a nutrient. The objective of this study is to determinate the relation between the treatment with tamoxifen and the prevalence of periodontal disease in women with breast cancer. Methods: Observational study. Sample: 70 postmenopausal patients, distributed in the following groups: Group 1 (N: 17) patients with breast cancer diagnosis and treated with tamoxifen less than one year; Group 2 (N: 18) patients with breast cancer and treated with tamoxifen for 1 to 2 years; Group 3 (N: 18) patients with breast cancer and treated with tamoxifen for 2 to 5 years; Group 4 (N:17) patients with breast cancer that have finalized their treatment with tamoxifen. A poll was performed between these patients, a periodontal scale and a mouth hispid was performed. Microbiologic standard tests were performed for Candida and also molecular biologic tests. Results: Group 1: health: 0%, severe periodontal diseases: 22% Group 2: health: 0% severe periodontal disease: 25% Group 3: health: 25% severe periodontal disease: 10% Group 4: health: 35% severe periodontal disease: 5%. Microbiologic cultives: presence of Candida albicans, tropicalis, parapsilosis, dubliniensis and glabrata. The maoyor variety of species were isolated from Group 1. Conclusions: The time frame with Tamoxifen treatment shows differences in the Periodontal status and reveals differences in the growth of Candida species because a decrease in number and species of yeast, this means an additional benefit in the studied population. We believe it is important to run this study with larger populations in order to determine the benefits of the treatment with Tamoxifen.
Hormone receptor alterations and treatment responses after neoadjuvant therapy in patients with ER+/HER2- breast cancer.
Authors: Maeda Shigeto , Tohyama Hiroaki , Tokai Yukiko , Nakashima Kazuaki , Kamohara Yukio , Nagata Yasuhiro , Ito Masahiro , Fujioka Hikaru
Published: March 2020

e11605

Background: Hormone therapy is recommended for treating patients with luminal A type early breast cancer by the International Conference in St. Gallen, 2011. However, precisely which neoadjuvant therapeutic strategies are optimal for such patients still remains controversial. We retrospectively evaluated the treatment responses to neoadjuvant chemotherapy (NAC) or neoadjuvant endocrine therapy (NAE) in patients with ER (+)/HER2 (-) breast cancer. Methods: Four hundred and sixty-one patients with primary breast cancer underwent surgery between November 2007 and October 2012. Of 243 patients with hormone receptor (+)/HER2 (-) breast cancer, 63 with ER (+)/HER2 (-) breast cancer were preoperatively treated with either NAC (n=47, median age: 49 years) or NAE (n=16, median age: 63 years). Four cycles (c) of FEC 100 (epirubicin 100 mg/m2 + 5-fluorouracil and cyclophosphamide 500 mg/m2) followed by 4 cycles of Docetaxel (75 mg/m2) every 3 weeks were administered for the NAC treatment regimen, while Letrozole was administered for 6 months for the menopausal patients in the NAE treatment protocol. Results: NAC did not alter the ER status, while the ER status was decreased by NAE (from 83% to 62%). NAE altered the ER status (positive rate; from 83 % to 62 %), but NAC did not. The PR status was decreased by both NAC and NAE (from 51% to 30% and from 63% to 9%, respectively). ER (P=0.0327) and PR (P=0.0019) were statistically decreased after NAE compared to that observed after NAC. The response rates determined by RECIST {PD/SD/PR/CR (%)} in the NAC- and NAE-treated patients were 2/34/58/6 and 0/50/50/0, respectively. The rate of tumor shrinkage was 41% (3.9 to 2.3 cm) after NAC and 39% (2.3 to 1.4 cm) after NAE. The pathological complete response rate was 9% after NAC and 6% after NAE. The recurrence rate in the stage I/II patients was 5% (2/38) after NAC and 0% (0/16) after NAE for short-term outcomes. Conclusions: The hormone status significantly changed after NAE compared to that observed after NAC. Both of the NAC and NAE treatment protocols caused a decrease in the tumor size. As a result, both of these therapeutic modalities were found to improve the rate of breast-conserving surgery.
Community use of anthracyclines for adjuvant HER2-positive breast cancer (BC).
Authors: Kumar Akhil , Fishman Marc L. , Shimp William S. , Bobolts Laura Rose , Krook James Edward , Fishman Val , Davis Sharon , Huff Dinah , Anthony Carol , Walton Robert , Hrushesky William J.
Published: March 2020

e11609

Background: Anthracyclines remain among the most active agents for the treatment of BC. NSABP B-31, NCCTG N9831 and HERA, each employing anthracyclines followed by trastuzumab in adjuvant HER2+ BC, demonstrated significant reduction in the risk of recurrence and improvement in survival. A fourth study, BCIRG-006, compared a non-anthracycline containing regimen, TCH, to an anthracycline based regimen, AC-TH. Both arms had similar overall survival, but there was a higher incidence of cardiac events in patients who received anthracycline. HER2-analyses in randomized adjuvant trials, in the pre-trastuzumab era, comparing anthracycline with non-anthracycline chemotherapy regimens, show that HER2+ BC derives greater benefit from anthracycline use. TOP2A coamplification, which occurs in 35% of HER2-positive patients, has shown a direct association with anthracycline benefit in several studies. We investigate and report, herein, the ways in which community oncologists are currently treating these patients. Methods: All treatment requests for adjuvant trastuzumab were examined, from 2009 through 2012. Chi-square analysis at 0.05α was used to test for interaction of age group to type of treatment. Results: During this span, oncologists requested adjuvant trastuzumab for 121 patients. In 10% (12/121) of patients, adjuvant trastuzumab alone, without chemotherapy and with or without hormonal therapy, was requested. Among patients who also received adjuvant chemotherapy (109), 35% (38/109), received anthracyclines. There was no relationship of anthracycline-usage with BC stage (data not shown) or patient age (Chi Sq p = 0.73). Adjuvant trastuzumab, without chemotherapy, was requested more often for the elderly (20% versus 4%; Chi Sq p = 0.003). Conclusions: Anthracyclines are utilized in adjuvant HER2+ BC in only about a third of patients, regardless of BC stage or patient age. The availability of a reliable, inexpensive, and convenient test to predict which patients are most likely to benefit from anthracyclines, over other options, would be useful. [Table: see text]
Evaluation of tobacco use and HER2 receptor expression in breast cancer in an ethnically diverse inner-city population.
Authors: Ambros Tadeu Frantz , Hansra Damien Mikael , Patel Ravi , Koru-Sengul Tulay , Zhao Wei , Miao Feng , Tannenbaum Stacey , Monedero Alicia P , Lee David J , Byrne Margaret M , Hurley Judith
Published: March 2020

e11611

Background: Tobacco is the leading cause of preventable death in the United States and is linked to many cancers. Despite overwhelming biological plausibility and over four decades of epidemiological studies, no definite association has been established between tobacco and breast cancer. Ovarian, stomach, and uterine cancer are associated with tobacco consumption and these cancers express HER-2. Although estrogen receptor status has been looked at as a variable there has been no evaluation of the role of HER-2 and smoking in breast cancer. Methods: A retrospective review of medical records from patients treated at the University of Miami/Jackson Memorial Hospital from 1998-2012 was undertaken after IRB approval. The incidence of smoking and HER-2 expression in a population of 1255 women was evaluated. Data was analyzed by age, race, ethnic group, menopausal status, tumor stage, and ER/PR/HER-2 receptor status. Results: 1255 charts were analyzed with 1094 having full information. Median age was 56 (range 22 to 94). Smoking rates were significantly higher in Caucasian versus African American women (47.4% vs. 17.1%, P<0.01) and in Latin versus African American women (24.7% vs. 17.1%, P<0.01). Overall rate of HER-2 expression 18.1%. The rate of HER-2 expression was 21.4% in smokers and 17.0% in non-smokers (p=0.10). The rate of HER-2 expression was 10.8% in Caucasian smokers and 9.8% in Caucasian non-smokers (p=0.88); 24.5% in smokers of African descent and 17.3% in non-smokers of African descent (p=0.24); 22.9% in Latino smokers and 17.4% in Latino non-smokers (p=0.10). The rate of HER-2 /ER expression was 9.4% in smokers and 7.9% in non-smokers (p=0.42); 5.4% in Caucasian smokers and 4.9% in Caucasian non-smokers (p=0.916); 12.2% in smokers of African descent and 5.9% in non-smokers of African descent (p=0.11); 9.5% in Latin smokers and 8.8% in Latin non-smokers (p=0.77). Conclusions: We found non-statistically significant positive associations in all analyses between HER-2 expression with or without ER expression and tobacco exposure when analyzed by ethnicity. A larger number of patients needs to be investigated in order to clarify this relationship.
Pathologic complete response (pCR) to predict patients’ survival in luminal breast cancer.
Authors: Wang-Lopez Qian , Kwiatkowski Fabrice , Abrial Catherine , Mouret-Reynier Marie-Ange , Dubray-Longeras Pascale , Van Praagh-Doreau Isabelle , Radosevic-Robin Nina , Durando Xavier , Penault-Llorca Frederique , Chollet Philippe J. M.
Published: March 2020

e11615

Background: Gene expression studies have demonstrated that breast cancer can be divided into three major subgroups : Luminal, Human Epidermal Growth Factor Receptor-2 (HER2) over-expression and Oestrogen negative (ER-). Luminal breast cancer is well known for its better prognosis compared with the other types. Conversely, response is less effective by pCR criteria after chemotherapy. This work aimed to evaluate if pCR could still be considered as a surrogate marker in luminal subgroup according to immunohistochemical classification : Hormonal receptor positive and HER2 negative (HR+HER2-). Methods: All 132 luminal early breast cancer patients treated by neo-adjuvant chemotherapy (NAC), in our institution from 2001 to 2007 were included in this study. NAC treatment comprised anthracycline alone, taxotere alone or sequential use of these two drugs. Survival curves have been established according to the Kaplan-Meier’s method. Comparison of curves were performed in using Log-rank test. The median of follow-up was 102 months (range 59 – 142 months) in October 2012. Results: Median age was 53.5 (range 34–78) years and median initial tumor size was 4cm (range 1-10). Objective response rate was 65% (86 patients), of which 8% (10 patients) had a complete response after 6 courses. One hundred and six (80%) underwent breast conservation surgery. Seven patients (5%) and ten patients achieved pCR (8%) according to Chevallier and Satatloff’s classification, respectively. Twenty patients did relapse and 18 patients died. At 10 years, Disease-free survival (DFS) and overall survival (OS) rate was 81% and 84%, respectively. All pCR patients, regardless of classification, did not relapse. However, the patients who achieved a pCR had not a significant difference in DFS and OS compared to the patients who did not. Conclusions: pCR was not a surrogate marker after a relatively short survey of 100 months for luminal breast cancers, who have generally late relapses. However, sixty five percent of patients had >50% reduction in primary tumor and 80% of patients had a breast conservation. Further studies are needed to identify new markers able to predict patients’ survival.
ABCG2 as a potential cancer stem cell marker in breast cancer.
Authors: Tiezzi Daniel Guimaraes , Sicchieri Renata D. , Mouro Larissa R. , Oliveira Tatiane M. G. , Silveira Willian A. , Antonio Heriton M. R. , Muglia Valdair Francisco , de Andrade Jurandyr Moreira
Published: March 2020

e12007

Background: The identification of cancer stem cell (CSC) markers gives opportunity to develop new target therapies. ABCG2 protein is reported as a predictive marker for breast cancer resistance to chemotherapy and as a potential marker for CSC in solid tumors. Methods: We included prospectively 41 patients with locally advanced or metastatic (LAMBC) invasive ductal carcinomas treated with NACT. The expression of CD44/CD24 and ABCG2 was analyzed by flow cytometry after fresh tumor sample digestion. The mammosphere assay (Mammocult) was carried out in 23 samples. We analyzed the correlation between the percentage of ESA+/ABCG2+ and ESA+/CD44+/CD24- cells within the primary tumor with the number of spheres in culture and their relationship with clinical and pathological parameters. ABCG2+ and ABCG2- cells from four primary tumors and from MDA-MB231 cell line were sorted and cultured in triplicate in Mammocult medium for 7 days. The ability to form sphere was analyzed. Patients’ mean age was 52.8 ± 10.3 yo. The ER, PgR and HER2 positive expression rates were 65%, 58% and 45%, respectively. Patients were treated with docetaxel/anthracycline combination (n = 33) of FEC75 combination (n = 8). Results: Complete pathological response was observed in 10 patients (24%). ER negative patients and patients with lower percentage of ABCG2+ cells within the tumor were more likely to achieve near pCR (44% versus 11%, p = 0.04; and 50% versus 14%, p = 0.04, respectively). We did not observe a significant association between pCR and PgR and HER2 expression or the percentage of CD44+/CD24- cells within the tumor. There was a strong correlation between the percentage of ESA+/ABCG2+ cells and the number of mammospheres in culture (r = 0.63; p= 0.0007). This correlation was not significant comparing to CD44+/CD24- cells. Additionally, ABCG2+ cells from primary tumors and MB-231 cell line form a higher number of spheres in culture than ABCG2- (mean difference = 1.15±0.45 /1000 cells, p = 0.04; mean difference = 0.48±0.04 /1000cells, p = 0.008, respectively). Conclusions: ABCG2 is a potential marker for CSC in breast cancer, and the percentage of ABCG2+ cancer cells within the tumor is a predictive factor for pCR in LAMBC patients subjected to NACT.