bluuebunny/crossref_metadata_2025 huggingface dataset:
Radiosensitization of HER2-positive breast cancer cell lines with trastuzumab.
Authors: Demirci Alanyali Senem , Bozkurt Emir , Alanyali Hilmi , Karaca Burcak , Uslu Ruchan
Published: March 2020

e11501

Background: HER2 is a member of the human epidermal growth factor (EGF) receptor family that is blocked by a monoclonal antibody, Trastuzumab (Herceptin). In daily clinical practice, Trastuzumab is being used concurrently with radiotherapy (RT) in breast cancer patients. Administration of Trastuzumab with RT appear to be safe in regard to cardiac morbidity and mortality in patients with relatively modest follow-up duration (less than 5 years). In this study we aimed to determine the possible interactions between RT and Trastuzumab in HER2 positive breast cancer cell line MDA-MB-453. Methods: MDA-MB-453 cells were treated with increased dose of Trastuzumab (10 – 200 µg/mL, 72 hours) and irradiation (0-8 Gy, 4 Gy/min, 48 hours). XTT (Roche) viability assay was used to measure the cytotoxicity of Trastuzumab, and trypan blue method was used to measure the cytotoxicity of irradiation. The sensitization of MDA-MB-453 cell lines was done by IC50 of Trastuzumab with 24 hours treatment followed by 6 and 8 Gy irradiation. Results: Cytotoxicity was increased in a dose and time dependent manner by Trastuzumab and irradiation treatment in MDA-MB-453 cell lines. IC50 values of Trastuzumab and irradiation were found to be 167 µg/mL and 8 Gy, at 48 hours, respectively.Cells were pretreated with IC25 and IC50 doses of Trastuzumab for 24 hours and then irradiated with 6 and 8 Gy doses. The cell viability at 24 and 48 hours were significantly decreased (p=0.0012) compared to single exposures (Trastuzumab or irradiation), indicating that Trastuzumab sensitizes HER2 positive breast cancer cells to irradiation. Conclusions: This preliminary study showed the sensitization effect of Trastuzumab to irradiation in HER2 positive breast cancer cells. Further studies are warranted for the optimal dosing and normal tissue toxicity of this combination.
AQP5 variant associated with prognosis in patients with early breast cancer.
Authors: Park Ho Yong , Lee Soo Jung , Chae Yee Soo , Kim Jong Gwang , Kang Byung Woog , Lee Yoo Jin , Jeong Ji Yun , Park Ji-young
Published: March 2020

e11505

Background: Our previous study showed the association of AQP5 expression with unfavorable prognosis in patients with early breast cancer (EBC). In addition, we analyzed the prognostic impact of polymorphisms of AQP5 gene in the chromosomal region 12q13 on breast cancer. Methods: The genomic DNA was extracted from paraffin-embedded tumor-free tissue from 609 early breast cancer (EBC) patients underwent curative surgery and then genotyped for 3 polymorphisms (rs3736309, rs1964676, and rs74091167) using the Sequenom Mass array system. Results: The median age of patients was 49 years (range 23-79). 106 (18.2%) patients underwent breast conserving surgery and adjuvant chemotherapy was given to 562 (92.3%) patients. Among enrolled subjects, 447 (73.3%) were hormone-responsive, 94 (15.3%) for HER2 overexpressed, and 98 (16.1%) for triple negative EBC. Among the 3 polymorphisms, AQP5 rs74091167 was significantly associated with disease-free survival (DFS) and distant disease-free survival (DDFS) in a dominant model (P < 0.001 and P = 0.021, respectively). Moreover, multivariate survival analysis revealed that the GG genotype of AQP5 rs74091167 was significantly associated with better DFS (HR = 0.377; 95% CI 0.179-0.793; P = 0.010) when compared with the combine GC/CC genotype adjusted to clinicopathological variables. However, no difference in AQP5 rs74091167 polymorphism was observed based on patient and tumor characteristics. Conclusions: AQP5 rs74091167 variant can be considered as a prognostic marker in patients with EBC after curative operation. In the future, functional relevance of this variant needs to be clarified.
Tolerability and cardiac safety of neo/adjuvant trastuzumab-based chemotherapy regimens for HER2+ breast cancer: A single institution experience.
Authors: Jitawatanarat Potjana , Kossoff Ellen , Riebandt Grazyna , Levine Ellis Glenn , O'Connor Tracey L. , Chittawatanarat Kaweesak , Ngamphaiboon Nuttapong
Published: March 2020

e11508

Background: Docetaxel/carboplatin/trastuzumab (H) (TCaH) and doxorubicin/cyclophosphamide/paclitaxel/H (AC-TH) and its variants are recommended by standard guidelines for neoadjuvant and adjuvant treatments for HER2+ breast cancer. Docetaxel/cyclophosphamide/H (TCyH) has also been used in clinical practice. Tolerability and cardiac safety among these regimens have not been well described. Methods: We retrospectively reviewed HER2+ early stage breast cancer who received neo/adjuvant H at RPCI between 2004-2011. Acute toxicities of different regimens (AC-TH and its variants, TCaH, TCyH) were evaluated. Cardiac events were defined as symptomatic congestive heart failure (CHF) and/or asymptomatic decline of ejection fraction (EF) that resulted in holding H. Results: 177 patients were identified (AC-TH=114, TCaH=39, TCyH=24). Patients who received AC-TH were younger, had less comorbidity, including cardiac history, and received less GCSF support. AC-TH regimens were associated with more febrile neutropenia (FN), grade 3-4 neutropenia, and dose delay (Table). Overall cardiac events were observed in 18% (anthracyclines 14% vs non-anthracyclines 9%; p=0.346). Termination of H was not significantly different between patients treated with anthracyclines (4%) vs non-anthracyclines (2%), nor was the CHF rate (4% vs 6%). Median absolute EF decline was also similar (5% vs 4%). After adjustment for age ≥65, cardiac history, baseline EF <55%, and Charlson Comorbidity Index, patients treated with anthracyclines showed a trend toward increased cardiac events (OR 4.53, 95% CI 0.99-20.5; p=0.05) in multivariate analysis. Conclusions: Although physician selection of patients for trastuzumab directed therapy lessens overall toxicity, the acute toxicity and cardiac event rate among those considered the most fit remains considerable when an anthracycline is introduced. [Table: see text]
Bond oracle HER2 IHC assay for identifying low to intermediate HER2-expressing breast cancer.
Authors: Reid Victoria Ann , Schwartz Mark W. , Kumar Sonia , White Yvonne Alexandra , Mazanet Rosemary
Published: March 2020

e11509

Background: HER2 targeted therapies are effective treatment for breast tumors that overexpress the HER2 protein to a high level (IHC score of 3+) or have amplification of the HER2 gene (HER2/CEP17 >2). However, the majority of breast tumors exhibit low to intermediate expression of HER2 (IHC 1+ and 2+), for which there are limited treatment options. A new cancer vaccine candidate, E75 or nelipepimut-S, offers prevention of reoccurrence in these patients by generating a specific immune response to a HER2 peptide. To date, no companion diagnostic test is validated to differentiate HER2 at these levels of expression. The BOND Oracle HER2 IHC assay (Leica Biosystems) is being validated to reliably identify IHC HER2 1+ and 2+ cases by correlating to independent analytical measures of HER2 expression. Methods: Quantitative PCR was used to determine HER2 DNA copy number and mRNA expression in eight breast cancer cell lines spanning HER2 IHC scores of 0 to 3+ and 45 formalin fixed, paraffin embedded (FFPE) invasive breast tumor samples. HER2 receptor load was determined for the eight cell lines by flow cytometry. Data was correlated to HER2 expression levels as determined by manual interpretation using the BOND Oracle HER2 IHC assay. Results: Previous testing by Leica Biosystems (Table) demonstrates the relationship between HER2 receptor load, HER2 copy number, and HER2 IHC status on four assay control breast cancer cell lines. Preliminary results also show that HER2 mRNA expression correlates with IHC staining with the BOND Oracle HER2 IHC Assay in FFPE breast cancer tissue samples. Conclusions: Improving the discrimination of HER2 protein expression (IHC 1+, 2+) using the Bond Oracle HER2 IHC assay in breast cancer tumors will identify patients for new treatments in development such as E75. [Table: see text]
Association of NBS1 expression with improved pathologic complete response rate in HER2-overexpressing breast cancer.
Authors: Sen Fatma , Yavuz Ekrem , Yegen Gulcin , Karanlik Hasan , Tuzlali Sitki , Aydiner Adnan
Published: March 2020

e11534

Background: Our aim was to investigate potential correlation between expression levels of Nijmegen breakage syndrome1 (NBS1) protein and phosphatidylinositol-3 kinase (PI3K) and pathologic complete response (pCR) rate to neoadjuvant treatment in locally advanced HER2+ breast cancer. We also assess possible association between NBS1 and PI3K expressions. Methods: Totally 42 patients (median age 49 years), received neoadjuvant treatment due to locally advanced HER2+ breast cancer, were included. Immunohistochemical analyses were performed on paraffin sections, obtained during initial diagnosis. Paraffin sections were stained with anti-NBS1 (P95-NBS1 antibody, Y112, ab32074) and anti-PI3K (PI3-Kinase p85 alpha+gamma antibody, ab741369) antibodies to determine positivity of related proteins. Results: NBS1 protein loss was detected in 19 (%45) patients whereas p85 loss was shown in 25 (%60). There was no initial clinicopathologic variable predicting pCR. Fifteen of 30 patients, received neoadjuvant trastuzumab, had pCR, whereas only 1 of 12 patients, not received trastuzumab, achieved pCR (P = 0.012). p85 loss did not predict treatment response, however NBS1 protein expression positively correlated with increased response rate to neoadjuvant treatment (P = 0.007). Conclusions: NBS1 protein expression associates with increased pCR rate in HER2+ breast cancer. However, P85 positivity did not associate with pCR rate or NBS1 overexpression.
Breast cancer biomolecular profile in 909 patients of a lower-incomes province in Argentina.
Authors: Holgado Silvia , Elias Adriana del Carmen , Zarba Juan Jose , Audi Raul , Vinuales Ana , Audi Viviana , Gonzalez Diego , Arcuri Jorge , Pedruzzi Hector , Gonzalez Adriana , Arrieta Fernanda
Published: March 2020

e11538

Background: Recent reports of the increasing incidence of BC in low and middle-income countries highlights the need to have a better understanding of prognostic biomarkers with clinical utility. The aims of this study were to analyze the biomolecular profile in a population with BC of Tucumán, Argentine. Methods: The study population consisted of 909 patients with primary or metastatic BC. The immunostainning results for hormones receptors (ER-PR) and Her2/neu protein expression in patients with histological breast diagnosis were assessed. The study design was cross sectional and the statistical study was exploratory. We compared the frequencies of patients with ER+/PR+/Her2-, ER+/PR-/Her2-, ER+/PR+/Her2+, ER+/PR-/Her2+, ER-/PR-/Her2+ and ER-/PR-/Her2- with those published in 2011 by St Gallen and relative variations were calculated to meet the relative percentages of the differences. Results: 893 were studied for all three. Molecular Expression (Population: 909): ER 58% (486/841); PR 48% (405/841); Her2 10% (85/893) Population Age: 21-89 years old (mean 58 yrs). Conclusions: The molecular profile in BC in our province seems to be different of the previously reported in western countries (St Gallen 2011), showing a more aggressive biomolecular profile with higher incidence of triple negative patients and lower incidence of Her2neu positive. With these results it is possible to assume that we are dealing with a population with particular characteristics. [Table: see text]
Clinical and pathologic characteristics of patients with breast cancer and a second non-breast primary tumor.
Authors: Atalay Basaran Gul , Yazar Aziz , Uras Cihan , Tezcanli Evrim , Cabuk Devrim , Atalar Banu , Ozyar Enis
Published: March 2020

e11539

Background: We aimed to investigate the clinical and pathologic characteristics of patients with breast cancer (BC) who had a non-breast primary tumor and treated in our hospital. Methods: We identified BC patients with a second non-breast primary tumor retrospectively in our database. The tumors arising in a sequence by less than 2 months are accepted as synchronous malignancies. We noted clinical and pathological characteristics of breast tumors and analyzed the relapse patterns, the frequency and type of second non-breast primary tumors. Results: A total of 48 patients were identified. Median age was 59 years old. Thirty-four patients were postmenopausal, 41 tumors were IDC, 2 were DCIS only, eight were multiffocal. Two patients had metastatic BC at the time of diagnosis. Ninety-three (n: 26) % patients had breast conserving surgery, 2 had bilateral BC. Twenty-eight patients had node negative disease, 12 had node positive disease and 2 had micrometatatic nodal involvement. Fifty-four % were T1, 31% were T2 tumors. Histological grade was 3 for 14, 2 for 15 and 1 for 7 breast tumors. Forty patients had ER positive disease, 4 had ER/ PR negative disease, 2 tumors were triple negative and 6 tumors were Her-2 positive. Among non-breast second primary tumors; 29 arose after, 11 arose before the diagnosis of BC and 8 arose synchronously with BC. The most common non-breast second primary tumors were as follows: 15% lung cancer, 20% colorectal cancers, 13% ovarian cancer, 10% thyroid cancer, and 8% lymphoma/leukemia. With a median follow up of 76 months, there were 6 relapses; 4 of them were BC relapses. Among these 4 BC relapses, 3 patients had brain metastases and one patient had bone metastasis. There were 4 deaths; 2 were due to BC metastases, one was due to rectal cancer metastasis and the other was due to relapse of sarcoma. Conclusions: Most breast tumors were at early stage and were hormone sensitive. The most common second non-breast primary tumors arising after diagnosis of BC were colorectal, thyroid and lung cancers. The most common second non-breast tumor arising synchronously with BC was lung cancer and the most common second non-breast tumor arising before diagnosis of BC was lymphoma/leukemia.
Re-biopsy in breast cancer recurrence: Is there really a clinical impact?
Authors: Collignon Joelle , Schroeder Helene , Rorive Andree , Colin Paul Emile , Hanocq Florence , Joskin Julien , Delvenne Philippe , Jerusalem Guy Heinrich Maria
Published: March 2020

e11549

Background: Several retrospective studies and 3 prospective studies have shown discordance in receptor status between primary tumor and metastasis leading to a treatment modification in about one out of 7 patients. However, some clinicians report unpublished data suggesting that these findings are not observed in all centers. We did prospectively a biopsy at suspicion of first relapse in our center and evaluated the impact of this biopsy on the management of our patients. Methods: Thirty four patients underwent a biopsy between October 2011 and January 2013. Hormonal receptor status was determined by the same IHC methodology for primary and metastatic tissue. Primary tumors were reanalyzed if necessary with our current IHC technique. A change in ER or PgR status was considered clinically significant if quantitative staining changed from <5 % to at least 10% of tumor cells expressing the hormonal receptor or if the opposite is observed. We tested HER2 status by IHC and/or FISH: HER2 3+ or 2+ and FISH positive cases were considered as HER2 positive. Results: Three of 34 patients were considered as screening failure. 1/31 (3.2 %) biopsies showed a benign disease, 2/31 (6.4 %) were non contributive and 5/31 (16 %) showed a metastasis of a second primary tumor. Two of these findings were totally unexpected according to clinical data. Changes in hormone receptor status were observed in 25 % but no change in HER2 status was observed. Time to recurrence was not significantly different between groups with or without modified hormonal status. No clinically significant complication was observed following the biopsies. Only patients presenting a second primary tumor had their management changed based on the new biopsy. Conclusions: We found discordance in hormone receptor status (25 %) but it did not change the treatment. Our study confirms the importance of re-biopsy in order to exclude benign disease or to find metastasis from an unknown and sometimes unexpected second primary tumor. Although our study does neither confirm changes in hormonal receptors resulting in the modification of the treatment strategy nor a change in HER2 status, our data suggest that a new biopsy at first relapse should be performed because unexpected second primaries can be discovered.
Adjuvant endocrine treatment in premenopausal patients with breast cancer: Clinical practice in an Italian cancer center.
Authors: Collovà Elena , Barni Sandro , Frassoldati Antonio , Amoroso Domenico
Published: March 2020

e11550

Background: Overall results from past and recent trials favor ovarian ablation, with luteinizing hormone-releasing hormone (LHRHa) analogues alone or in combination with the anti-estrogen tamoxifen (TAM), rather than with chemotherapy. The aim of this survey was to obtain more informations about the clinical practice of adjuvant endocrine therapy. Methods: 11 items electronic questionnaire was submitted to italian oncologists and 611 filled questionnaires were collected. The results were examined globally and according to sex, age, working institution and geographical origin of the oncologists. Results: 97.7% of patients less than 40 years needing only hormonal therapy would receive both TAM and LHRHa; 2.3% TAM or LHRHa alone. 93.6% of patients over 40 years would receive the combination with TAM or LHRHa When LHRHa would be added to TAM the treatment length would be: 5 years in 60% and 44%, 3 years in 20.8% and 26.4%, 2 years in 19.2% and 29.6%, in patients aged under and over 40 respectively. At least one risk factors like positive nodes, high ki-67, G3, vascular invasion, HER2 3+, influence neither the therapeutic options nor the length of LHRHa use. In patients under 40 with chemotherapy induced amenorrhea, the oncologists would prescribe: TAM in 22.4%, TAM and LHRHa in 68,1% (LHRHa for 5 years in 55.3%, for 3 years in 22.1%, for 2 years in 22.6%), aromatase inhibitor (AI) +/- LHRHa in 6.6%, LHRHa alone in 2.9%. A greater number of patients would be treated with AI among women aged over 40 (11%). The reasons to add LHRHa toTAM and the length of treatment would be: in higher efficacy of the combination: 45.5%; patient’s age: 30.1%; risk of recurrence: 20.8%; and, side effect: 3.6%. Conclusions: A high concordance between the Italian Oncologist attitude and the European Guidelines is confirmed by this large survey. However, a wide preference for a TAM/LHRHa combination is reported, as well as a significant preference for LHRHa and AI combination in women under 40 years with chemotherapy induced amenorrhoea.
Cardiotoxicity and cardiac monitoring during adjuvant trastuzumab in daily Dutch practice.
Authors: Tjan-Heijnen Vivianne C. , Seferina Shanly C. , De Boer Maaike , van den Berkmortel Franchette W.P.J. , Van Kampen Roel JW , Van de Wouw Agnes W , Joore Manuela A , Borm George F , Voogd Adri C
Published: March 2020

e11558

Background: In this study we assessed the cardiotoxic effects of adjuvant trastuzumab in daily practice after its introduction in the Netherlands in 2005. Methods: We included all patients with stage I-III breast cancer diagnosed in the years 2005 to 2007 in 5 hospitals in the South of the Netherlands. We studied guidelines adherence on left ventricular ejection fraction (LVEF) monitoring and the incidence of cardiotoxicity in patients with HER2 positive disease treated with adjuvant trastuzumab, using similar cardiac-endpoints as in prior randomized trials. In addition, we determined predictors of onset of cardiotoxicity. Results: Of 2685 patients included, 494 (18.4%) had a HER2 positive tumor. From these 494, 266 (53.8%) were treated with adjuvant chemotherapy and 228 (85.7%) received trastuzumab. Anthracycline based chemotherapy was given to 218 (96%) patients prior to trastuzumab treatment. LVEF measurements were done in 222 patients (97.4%). Fifty eight patients (25.4%) had ‘symptomatic cardiotoxicity’ during trastuzumab treatment, of whom 43 (18.9%) patients had a drop in LVEF of ≥ 10 percentage points. In 36 (15.8%) patients, cardiotoxicity led to permanent discontinuation of trastuzumab although in 50% LVEF recovered to levels permitting continuation, and in 22 (9.6%) patients treatment was temporary discontinued. No cardiac deaths were seen. The largest drops in LVEF occurred between baseline and the first 3-month assessment. Only 3.1% permanently discontinued treatment ≥ 6 months measurement. Patients with trastuzumab related cardiotoxicity did not show more cardiac comorbidities at baseline (14% vs. 24% p=0.12) and did not receive a higher cumulative dose of anthracyclines (mean 549mg vs. 546mg, p=0.48) than those without trastuzumab related cardiotoxicity. Conclusions: Regarding cardiotoxicity,trastuzumab was cautiously implemented in the Netherlands. In the first years, physicians based their decision to discontinue treatment frequently on patient ‘symptoms’ apart from LVEF outcome. Treatment discontinuation occurred mainly in the first three months after start of trastuzumab. Funding:Netherlands Organization for Health Research and Development and Roche Netherlands.
Relevance of rise in CA15.3 during fulvestrant therapy in advanced breast cancer patients.
Authors: Agrawal Amit , Balakrishnan B , Cheung Kwok-Leung , Robertson John Forsyth Russell
Published: March 2020

e11567

Background: Serum CA15.3 (assay for MUC1 mucin, a membrane glycoprotein of breast ductal epithelium) is elevated in 50-70% of patients with metastatic disease. Transient initial rise (i.e., spike) of CA15.3 due to partial agonistic or cytotoxic effects of tamoxifen and chemotherapy is known. We report differential expression of spike in ER+ breast cancer showing clinical benefit (CB) or progressive disease (PD) on fulvestrant therapy (250mg). Methods: Serial serum CA15.3 measured at therapy initiation (Rx), 1, 3, 6, 9, 12 months and at progression were correlated with clinical outcome (CB/PD). Results: 112 patients (median age=71.4 years) with DOR=10.7+ (median duration of response in months, range) showed 63%CB (DOR=19.2+, 7-120.8+; MBC=48, LAPC=23) and 37%PD (DOR=3, 1-6; MBC=38, LAPC=3). Conclusions: CA15.3 spike was a common feature during therapy regardless of baseline level or clinical outcome (2nd row). However, in those with abnormal baseline (3rd row), %rise was higher in CB than PD patients reflecting greater tumour lyses (and perhaps therapy effectiveness) suggesting continuing therapy beyond early months (1-2 months) even with rising CA15.3. However, on analysis of only patients with spike, the majority of either CB or PD (4th row) were patients with MBC (perhaps reflecting higher tumour load) but with much larger %change in PD. Therefore, though therapy may not be stopped at early rise of CA15.3 but additional interim imaging may be required in MBC patients. [Table: see text]
Treatment effectiveness in advanced breast cancer patients in Italy: Ten years experience.
Authors: Barni Sandro , Vallini Ilaria , Bonotto Marta , Brunello Antonella , Indelli Monica , Gori Stefania , Saggia Chiara , Petrella Maria Cristina , Generali Daniele Giulio , Di Pietro Paolo Marzia , Moretti Anna , Massari Francesco , Fausti Valentina , Pinotti Graziella , Puglisi Fabio , Borgonovo Karen , Zagonel Vittorina , Porcu Luca , Collovà Elena
Published: March 2020

e11573

Background: Several studies suggest that newer therapies can improve survival in MBC, but a different impact on overall survival (OS) is observed according to histology, extension of disease and prognostic factors. This survey was performed for evaluate Italian experience in cancer treatment in the last ten years. Methods: We collected data from 13 Italian Medical Oncology Unit; we registered all consecutive patients (pts) with breast cancer who have developed metastasis between 2000 and 2008. Demographic data, pathological characteristics and treatment were reported. OS was calculated from time of recurrence and stratified according to biological characteristics and to recurrence date. Results: 1542 pts was suitable for analysis; median age 61,7 (range 22-94); MBC at diagnosis 21,8%. Site of disease recurrence: bone 26,2%, visceral 25,4%, bone and visceral 20,7%, soft tissue 11,5%, soft tissue and visceral 8,4%, bone and soft tissue 7,8%. Molecolar classification: luminal A 66,3%, luminal B 14,5%, triple negative 11,5%, HER2+ like 7,7%. Pts received a median of 2 lines of chemotherapy (range 0-10) and 1 line of hormonal therapy (range 0-7); 22,5% received biological drugs. 15,5% of metastatic pts were enrolled in clinical trials. After a median follow up of 7.1 years 84,1% pts died (1297/1542 pts) and median OS was 2,7 years (range 2,6-2,9). We did not observe difference in OS for pts divided into 3 groups according to recurrence date (2000-2002, 2003-2005, 2006-2008). A longer median OS was observed in luminal B (3,8 years) versus luminal A and HER2+ like (2,8 years) and triple negative disease (1,2 years). Conclusions: Our survey describe a large number of MBC pts treated in 13 Italian Oncology Unit. OS analysis did not show significant differences according to recurrence date, but for different prognostic factors. OS data are superimposable to literature ones, showing a good transfer from clinical trials to clinical practice.
Breast cancer biomarker discordance between primary and sites of metastasis: A systematic review.
Authors: Yeung Isis Ching , Clemons Mark , Addison Christina L. , Hutton Brian , Zhu Xiaofu , Mazzerello Sasha , Arnaout Angel
Published: March 2020

e11574

Background: Systemic treatment choices for breast cancer patients with recurrent disease are usually based on the ER/PR/Her2 biomarker status of the primary cancer. Biomarker discordance between the primary and metastatic sites is well recognised and could have important therapeutic implications. A systematic review was conducted to assess the extent of biomarker discordance between the primary cancer and metastasis, and whether is influenced by the site of metastasis. Methods: An electronic search of multiple literature databases implemented by an information scientist was conducted to identify studies reporting outcomes of ER/PR/Her2 receptor stability between primary site and recurrent disease. Seven reviewers independently screened the 5034 abstracts and full text articles, which were identified according to pre-defined selection criteria. The same reviewers performed data collection from all included studies. Studies that were identified reported on receptor conversion between primary sites of breast cancer and various sites of metastasis including lymph node, liver, brain, lung, skin, GI sites and bone marrow. Results: Preliminary results from 385 eligible studies consistently demonstrated discordance between the primary and metastatic sites. When discordance occurred, the general trend was for loss of hormone receptor. ER hormone status was more stable (discordance 10.2-32.5%) than PR (discordance 25.5-40.7%). HER2 was found to have lower rates of discordance (2.6-14.5%). In general, higher ER/PR discordance was found in bone (40-68%) and liver (0-54%) when compared to other sites brain (36%), lung (9-18%), skin (6-22%), GI (15-40%). In the prospective studies, biomarker discordance led to change in patient management in up to 20% of the patient population. Conclusions: Our results demonstrate that biomarker discordance between primary and distant metastases does occur in breast cancer, occurs more frequently with PR, and the extent of discordance is influenced by the site of metastasis. Further research is required to have a better explanation about the pathophysiology of the biomarker status change and its clinical implications.
The potential benefit of trastuzumab-based therapy upon lapatinib progression in heavily preatreated patients with advanced HER2 positive breast cancer.
Authors: Boutis Anastasios L. , Chatzileontiadou Sofia , Diamantopoulos Nikolaos , Pouptsis Athanasios , Fotiou Chariklia
Published: March 2020

e11576

Background: Overexpression of human epidermal growth factor receptor 2 (HER2) occurring in about 20% of breast cancers is associated with increased risk of disease recurrence and worse prognosis. Despite the advent of therapies that target HER2, particularly, trastuzumab and lapatinib, that have altered the natural course of HER2-positive advanced breast cancer, tumor progression remains inevitable. New agents are in clinical development, but up to date there are limited data to direct the treatment of patients after lapatinib progression. Methods: We retrospectively searched for HER2-positive advanced breast cancer patients treated at our clinic, who received both trastuzumab-based therapy and lapatinib upon trastuzumab-progression in the metastatic setting. Thirty patients, all female, suffering from HER2-positive advanced breast cancer were identified. HER-2 positivity was assessed by immunohistochemistry (IHC 3+) or chromogenic in situ hybridization (CISH+). Results: Of the 30 patients, 83.3% had invasive ductal carcinoma; 60% had positive hormone receptor status, and 80% grade 3 tumours. Half of the patients received adjuvant trastuzumab. Median age was 57 years, range 37-79 years. 36.6% were switched to lapatinib after a median of three (range 2-6 lines) trastuzumab-based treatment lines. In 8 pts (37.5%) trastuzumab was re-started after lapatinib progression. In 7 of these patients, trastuzumab was combined with chemotherapy. Median progression free survival and overall survival in these patients was 4.75 and 8.87 months respectively. 3 patients received bevacizumab-based therapy upon lapatinib failure. Conclusions: Trastuzumab rechallenge after lapatinib progression may be active in a subgroup of heavily pre-treated patients. Clinical benefit of this strategy has to be balanced especially in limited resource settings with unavailability of novel agents or early phase clinical trials. As of now, there is no uniform accepted standard to define the optimal treatment approach of patients upon lapatinib progression showing the real need for new therapies in this population.
The impact of estrogen receptor (ER), progesterone receptor (PR), and HER-2 receptor status on treatment of patients with advanced breast cancer.
Authors: Bains Paramjot , Powell Erin Diana
Published: March 2020

e11580

Background: There are many variables that affect treatment options and outcomes in advanced breast cancer. The expression of ER, PR and HER2 are key in determining prognosis and management. The traditional management of breast cancer did not involve biopsy of metastatic sites. Recent studies indicate that, in a significant number of patients, there is a change in receptor status in the metastasis, and this may alter treatment. There have been many retrospective studies looking at the change in the ER/PR status of the metastatic site. Change in treatment as a result has been less of a focus. Our objective is to document the likelihood of a change in receptor status and the impact of this on treatment. Methods: This is a single center retrospective chart review. Ethics approval has been obtained through Memorial Univeristy of Newfoundland. The Dr. H. Bliss Murphy Cancer Centre database was used to identify 250 patients in Newfoundland who were diagnosed with metastatic breast cancer between January 2006 and November 2011. The review includes patients diagnosed with de novo metastases and those who developed metastases following adjuvant treatment. The information we are collecting includes ER, PR, and HER2 status of original tumour, whether metastases were biopsied and the results of the biopsy. We are also documenting all treatments administered. Results: The percentage of patients who underwent biopsy of metastases, the likelihood of change in receptor status and the likelihood of change in treatment will be calculated. Approximately half of the charts that met our criteria have been reviewed. Of those 125 patients, 35 had a biopsy specimen analyzed for ER/PR and HER2 status. 6 of these 35 patients had a change in their hormone receptor status, and 3 had a change in their HER2 status. The likelihood of change in treatment recommendations will be determined once all the data have been reviewed. These results will be available for the 2013 ASCO meeting. Conclusions: ER, PR and HER2 status may change from initial diagnosis of breast cancer to metastatic disease. This has important implications for treatment and prognosis, suggesting that biopsy of metastatic sites should be routine.
Higher volumetric breast density to predict risk for aggressive breast cancer subtype in postmenopausal Korean women.
Authors: Park In Hae , Ko Kyungran , Choi Ji Soo , Jung So-youn , Lee Seeyoun , Kim Seok Won , Kwon Youngmee , Shin Kyung Hwan , Kang Han Sung , Lee Eun Sook , Lee Keun-Seok , Ro Jungsil
Published: March 2020

e11584

Background: In Asian population, the peak incidence of breast cancer is women in their late forties. We investigated the association between volumetric breast density and breast cancer risk according to menstruation status and breast cancer subtypes in Korean women. Methods: We prospectively enrolled 509 newly diagnosed breast cancer patients and 1336 healthy control subjects who performed mammography at the National Cancer Center in Korea between Sep 2011 and Nov 2012. Breast density was estimated using volumetric breast composition measurement (VolparaTM). We collected clinical data including menstruation status, parity, BMI and use of postmenopausal hormones. For cancer patient, we additionally acquired following pathologic data: histologic type, tumor size and grade, receptor status, Ki-67, and nodal status. Results: Of a total of subjects, 1064 (57.7%) women were postmenopausal status. The risk of breast cancer increased progressively with increase in volumetric breast density (Ptrend <0.001) in all subjects. In addition, breast cancer risk increased in women < 60 years old (odds radio (OR) = 1.81), higher body mass index (BMI) (< 25kg/m2 vs. ≥ 25kg/m2) (OR = 2.41), and fewer childbirth (0/1 vs. ≥ 2) (OR=2.38). In postmenopausal women, higher breast density (category 4) showed a 3.00-fold (OR = 3.00, 95% confidence interval (CI) = 1.75-5.16, P<0.001) increased risk of breast cancer compared with lower breast density (category 1-2). In contrast, there was no such association in premenopausal women. The associations of volumetric breast density were stronger for HER2 positivity (Ptrend <0.019), and high Ki-67 (Ptrend <0.006) in postmenopausal breast cancer patients. There was a statistically significant association between lower breast density and hormone receptor (HR) positive/HER2 negative breast cancer (Ptrend <0.019). Conclusions: High volumetric breast density is associated with the risk of breast cancer having more aggressive tumor characteristics in postmenopausal women.
Long-duration chemotherapy, switch to endocrine therapy, or watch only? A single-center retrospective study of metastasis breast cancer with ER/PR(+) and CerbB2(-).
Authors: Jian Huang , Chen zhan-Hong , Cao Wenming , Ye Wei-Wu , Ping Huang , Xiying Shao ,   Zhejiang Cancer Hospital
Published: March 2020

e11589

Background: To evaluate the efficiency of long-duration chemotherapy used Capecitabine or switch to endocrine therapy in metastasis breast cancer (MBC) patients with ER/PR(+) and CerbB2(-). Methods: We retrospective analysis 112 patients of our center from 01/Jan/2009 to 30/April/2012, who with ER/PR(+) and CerbB2(-) MBC. All these patients accepted capecitabine -based regimen as first-line or 2nd-line chemotherapy. Three regimens included long-duration chemotherapy(LC) used capecitabine, switch to endocrine therapy(STET) or watch only(WO) were given after capecitabine-based regimen. We compared the differences among these three regimens. Results: 70/112 were first-line chemotherapy,52/112 were 2nd-line chemotherapy. All these patients used capecitabine-based regimen (include single-agent or in combination with another chemotherapy drug), and the response were: CR, PR, SD≥24 weeks. 29 patients were LC,28 patients were STET and 55 patients were WO after capecitabine-based regimen. The median progression-free survival (mPFS) was 7 months, one year survival rate was 32.0%, response rate(RR) was 35.7% in all these patients. The mPFS were 22 months, 12 months and 5 months in LC group, STET group and WO group respectively. The one year survival rate were 67.6%,46.5% and 5.1% in these three groups respectively. WO group was significantly worse than LC and STET groups on mPFS (p<0.0001) and one year survival rate (p<0.05). LC group and STET group was no significant difference in mPFS(p=0.1832) and one year survival rate (p=0.5012). The RR were 51.7%, 39.3% and 25.5% in these three groups respectively. LC group was significantly better than WO group (p=0.0287). No significant difference between LC and STET groups (p=0.4287) or STET groups and WO group (p=0.2145). Conclusions: Long-duration treatment is better than watch only(WO).Patients with ER/PR(+) and CerbB2(-) MBC used capecitabine-based regimen (include single-agent or in combination with another chemotherapy drug), and the response were: CR, PR, SD≥24 weeks maybe get more benefits from long-duration chemotherapy used capecitabine. A multicenter prospective study is going on.
Human epidermal growth receptor-2 overexpressing early operable primary breast cancers in older (≥70 years) women: Biology and clinical outcome in comparison with younger (<70 years) patients.
Authors: Syed Binafsha Manzoor , Green Andrew R. , Morgan Dal , Ellis Ian O. , Cheung Kwok-Leung
Published: March 2020

e11608

Background: There is dearth of literature reporting the prevalence and biological characteristics as well as the long-term clinical outcome of HER2 positive tumors in older women. This study aimed to analyse their biological characteristics and compare them with their younger counterparts from a single centre with long-term clinical follow-up. Methods: Over 37 years (1973-2010), 1,758 older (≥70 years) women with early operable (<5cm) primary breast cancer were managed in a dedicated clinic and have complete clinical information available. Of these 813 patients underwent primary surgery and 575 had good quality tumour samples available for tissue microarray (TMA) analysis using immunohistochemistry. Comparison was made with data from a well-characterised younger (<70years) series (N=1,711) treated between1986 - 1998 (before adjuvant trastuzumab became standard) in our institution. Thirty-nine (7.6%) and 140 (8.2%) patients from the older and younger series respectively (p=0.56) had HER2-positive tumours. Results: See Table. Conclusions: The HER2 positive tumours in older women showed relatively less aggressive phenotype and did not show any inferior long-term clinical outcome despite not having received chemotherapy as compared to the younger patients. The precise role of different adjuvant systemic therapies in this population needs to be delineated. [Table: see text]
Results of a novel neoadjuvant chemotherapy (NAC) regimen for breast cancer.
Authors: Rivera-Rodriguez Noridza , Cabanillas Fernando , Lawrenson Lesley , Negron Viviana , Pavia Orestes Antonio , Bruno Margarita , Echenique Miguel M. , Carlo Victor , Liboy Idalia
Published: March 2020

e11610

Background: Achieving a pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) has been associated with improved disease free survival (DFS) and overall survival (OS). The Residual Cancer Burden Score (RCB) method is a useful tool that predicts DFS and OS after NAC. We present the results of pts with either triple negative or HER2 positive breast cancer treated with a novel NAC. Methods: 34 pts with localized breast cancer >1 cm with HER2+ (N=19) or triple negative breast cancer (TNBC) (N=15) were treated with this novel regimen consisting first of TEC (docetaxel 75 mg/m2, epirubicin 80 mg/m2, and cyclophosphamide 500 mg/m2) + PEG Filgrastim x 4 cycles. Following the 4th course, TNBC patients received 4 additional TEC cycles if they achieved CR by MRI, or were switched to a non cross-resistant regimen (vinorelbine, bevacizumab, capecitabine) if they had < CR. HER2+ pts received TEC x4 followed by docetaxel + trastuzumab x 4. RCB score was used to measure pathologic response. Pretreament PET scan was done and repeated after course 1 in order to correlate with RCB. Results: Median age was 56 (58 for Her2+ and 49 for TNBC). RCB= 0 (pCR) was achieved in 76%, while only 1 responded poorly (RCB=3). There was no significant difference in the pCR rate between Her2+ and TNBC patients (74% vs 80% respectively), but there was a difference in the rate of pCR without DCIS and invasive cancer between these two (see table, p=0.034). Pts with SUV drop > 5% after 1st TEC had 84% pCR while none with < 5% achieved pCR (p=0.001). Comparison of our results with other NAC regimens reported in the literature is summarized in the table below. Conclusions: This novel chemotherapy approach results in a high pCR rate and RCB 0-1, which have been associated with improved clinical outcomes. Early PET can predict pCR. Although sample size is modest, results are encouraging and deserve further evaluation. Clinical trial information: NCT 00830544. [Table: see text]
Use of locoregional treatment to improve survival in de novo stage IV breast cancer patients with luminal-like and HER2-rich subtypes.
Authors: Chen Pengyu , Cheng Skye H Hong-Chun
Published: March 2020

e12003

Background: Breast cancer has three major subtypes, including luminal-like (hormone receptor positive, no HER2 overexpression), HER2-rich (HER2 overexpression), and triple negative (hormone receptor negative and no HER2 overexpression). This study is to analyze the prognosis in each subtype of stage IV breast cancer patients. Methods: We reviewed 246 patients with de novo stage IV breast cancer treated at our hospital between 1990 and 2009. Multivariable Cox analysis was used to determine the survival associated the subtypes and clinicopathologic factors. Results: Patients with luminal-like subtype are mostly premonopausal (66.9%, P=0.0002), with abnormal CA 15-3 level at initial diagnosis (58.7%, P=0.01), with higher rate of bone mets (78.1%, P=0.02), and less rate of liver mets (23.1%, P<0.0001). Patients with HER2-rich and triple negative had higher rate of nuclear grade III of primary breast tumor, up to 35% and 40%, respectively (P=0.01). There is no difference in the systemic chemotherapy (82.2~95%, P=0.09) and locoregional treatment (40.0~51.2%, P=0.23) among three groups. The median overall survival of 246 patients was 23.1 months. The median overall survival in patients with luminal-like, HER2-rich, and triple negative subtype were 39.6, 17.9, and 13.3 months, respectively (P<0.0001). In multivariate analysis, hormone receptor and HER2 status were significant independent factors associated with survival (P<0.0001). Other significant factors associated with survival included liver mets (Hazard Ratio 2.3, P<0.0001), lung mets (Hazard Ratio 1.7, P=0.0004), and brain mets (Hazard Ratio 1.5, P=0.03). In subgroup analysis, locoregional treatment to primary breast tumor had significant survival benefit in patients with luminal-like (P=0.0001) and HER2-rich(P=0.0012) subtype. In triple negative subtype, local treatment did not improve outcome (P=0.9575). Conclusions: Hormone receptors and HER2 status are the most important factors affecting survival for these patients. Locoregional treatment to primary breast tumor may provide better outcome, especially those with luminal-like or HER2-rich subtype.
Estimating long-term efficacy of multi-catheter brachytherapy in Japanese breast cancer patients.
Authors: Sato Kazuhiko , Mizuno Yoshio , Shimo Takahiro , Kato Masahiro
Published: March 2020

e12009

Background: The efficacy of an accelerated partial breast irradiation (APBI) has been investigated as an alternative method to whole breast irradiation (WBI) in breast-conserving treatment (BCT). We have previously reported that multi-catheter brachytherapy as APBI using intra-operative open-cavity implant (IOCI) technique is feasible for Japanese patients. Since the follow-up period of this technique was relatively short, a long-term efficacy has been evaluated using an individualized-case-control (ICC) analysis. Methods: 179 consequent patients with 183 lesions were treated with BCT using IOCI from October 2008 to January 2013. Patients with bilateral breast cancer were included in the database twice. After the confirmation of the free margin and negative sentinel-nodes for metastases using frozen section analysis, applicators were inserted. APBI was started the same day of the operation, delivering 32 Gy in 8 fractions. We performed an ICC analysis to estimate the number of patients with an ipsilateral breast recurrence (ILBR). The 10-year risk of ILBR for each patient if treated by BCT with WBI was calculated with web-based decision-making tool (IBTR!) and it was adjusted by the actual follow-up period using EBCTCG overview’s data. Results: 123 patients with pN0 and longer than 1 year follow-up were enrolled in this analysis. Their mean age was 54.9 years. Most tumors (94.3%) were 2 cm or less in diameter. The median follow-up period was 3.0 years (1.0-4.3 years). All toxicities related to radiation therapy were mild. When BCT was performed with and without WBI, we estimated that there should be 1.2-2.4 and 4.9-9.1 ILBR in this group, respectively. Although one ILBR was observed, there was no tumor-bed recurrence in this treatment group. Conclusions: There was only one ILBR (no tumor-bed recurrence), which was within an estimated range of local recurrences. Multi-catheter brachytherapy using this technique is expected to offer the same rates of long-term local control than WBI using ICC analysis.
Prospective, randomized trial comparing harmonic scalpel and electrocautery in breast surgery.
Authors: Mori Tsuyoshi , Abe Hajime , Kawai Yuki , Murakami Koichiro , Akabori Hiroya , Yamaguchi Tsuyoshi , Sonoda Hiromichi , Shimizu Tomoharu , Shiomi Hisanori , Kubota Yoshihiro , Naka Shigeyuki , Murata Satoshi , Yamamoto Hiroshi , Umeda Tomoko , Tani Tohru
Published: March 2020

e12014

Background: The objective of this study was to compare the potential advantages of the harmonic scalpel with those of electrocautery for axillary lymph node dissection in breast surgery. Methods: A prospective randomized study of axillary lymph node dissection procedures performed between March 2011 and September 2012 was conducted. Primary breast cancer patients with axillary node-positive status (n = 25) were randomly assigned to the harmonic scalpel (group A, n = 13) or electrocautery (group B, n = 12) groups.The patients underwent breast-conservation surgery or mastectomy with a level I and II axillary dissection, which was performed by one surgeon. The time required for resection and the blood loss during the lymphadenectomy were recorded. The HARMONIC FOCUS (Ethicon Endo-Surgery, Inc.) was used as the ultrasonic scalpel. A low-pressure vacuum drain was placed in the axilla and removed when the drainage volume reduced to less than 50 ml over 24 hours. After the operations, the patients were assessed for the presence of seroma in an outpatient setting. Results: Resection timein group A was significantly shorter than that in group B (mean, 28.6 ± 5.1 vs. 40.3 ± 5.6 min; P = 0.0001). Similarly, blood loss in group A was significantly lower than that in group B (mean, 7.9 ± 5.3 vs. 22.9 ± 11.5 ml; P = 0.001). Duration of drain placement in group A was significantly lower than that in group B (mean, 3.5 ± 1.1 vs. 5.0 ± 0.9 days; P = 0.01), and the seroma rate in group A was lower than that in group B (23% vs. 66%; P = 0.04). Conclusions: For axillary lymph node dissection, the harmonic scalpel is more effective in terms of resection time, blood loss, duration of drain placement, and postoperative seroma formation.