Number Of Breast Cancer Patients Research Articles

Assessment of Anticancer Effect of Alendronate in Breast Cancer: An In vitro Study

Breast cancer has high incidence in women from both developed and developing countries. Approximately 2 million women are diagnosed with breast cancer in 2018. In Asia, unfortunately Pakistan leads the highest number of breast cancer patients. Various treatment strategies are present but they are not well developed. There is a great need to develop effective methods for early detection and treatment of the disease. For cancer treatment chemotherapeutic interventions have always been a method of choice. One of the mechanisms involved in cancerous cell proliferation is Mevalonate (MVA) pathway. It is hypothesized that arresting MVA pathway leads to cell death hence cancer cell growth is suppressed. Various inhibitors of MVA pathway have been studied that can suppress cell proliferation. Nitrogen containing bisphosphonates are MVA pathway inhibitor and clinically used for treatment of bone diseases. Their anticancer efficacy is also reported. Current study focuses on alendronate, a nitrogen containing bisphosphonate to examine their anticancer effect on breast cancer cell line. Results of this study may help in addition of new anticancer drug for breast cancer.

Pregnancy-Associated Breast Cancer: A Realistic Approach.

The number of cancers diagnosed during pregnancy is on the rise, and breast cancer is the most common malignancy. Presently, there are very limited resources and no clear guidelines for managing this peculiar patient population both worldwide and in India. The objective of this study was to find out the incidence of pregnancy-associated breast cancer (PABC) in a tertiary care referral centre and to compare the epidemiological, diagnostic and prognostic factors as well as maternal and foetal outcomes with the most recent literature worldwide. We conducted a retrospective descriptive study of women diagnosed with breast cancer in pregnancy and post-partum period at a tertiary care centre in southern India during the period of 10years (total number of breast cancer patients were 10). We studied the diagnostic and prognostic factors as well as maternal and foetal outcome in patients diagnosed with breast cancer for the first time in pregnancy. Overall incidence of PABC was found to be 0.6% (n = 10). Mean age at the time of presentation was 30.7 ± 4years. All cases suspected clinically or on imaging (USG) were confirmed with FNAC, excision biopsy or Trucut biopsy. Out of 10 patients, 70% (n = 7) had an advanced-stage disease on diagnosis. Histopathology suggested 90% (n = 9) had invasive ductal carcinoma and 55.5% (n = 5) had a triple negative receptor status. 20% (n = 2) of our patients had opted for a breast conservation surgery (BCS), and 70% (n = 7) of our patients underwent modified radical mastectomy with neoadjuvant or adjuvant chemotherapy/radiotherapy. One patient had a second trimester MTP in view of stage 4 disease. 77.7% (n = 7) of the nine patients who continued pregnancy underwent LSCS, out of which 57.4% (n = 4) were elective, and MRM was done concurrently with LSCS in 50% (n = 2) of the elective LSCS. The mean birth weight of the 9 neonates was 2.2 ± 0.5kg. Intrauterine growth retardation was seen in 22.2% (n = 2) neonates. 33.3% (n = 3) of the neonates required NICU support, and one baby expired on post-natal day 16. With the increasing number of elderly primigravida amongst the urban population, a clear understanding of PABC is becoming more important. A multidisciplinary team approach shall help the clinician not only in reducing the heavy burden of patient responsibility but more importantly, in guaranteeing better quality of treatment, avoiding unnecessary delays in providing interventions and providing adequate treatment.

Construct Validity and Reliability of Indonesian Version of RAND SF-36 Quality of Life Questionnaire in Breast Cancer Patients

Background: The number of breast cancer patients in Indonesia is increasing but there are still only a few researches that assess their quality of life. RAND SF-36 is a quality of life instrument that is widely used. In Indonesia, the validity and reliability of the instrument is still under development, especially in breast cancer patients. Various health status questionnaires have been used in physical rehabilitation studies involving patient with pacemaker, but for women with breast cancer, the usefulness of these questionnaires as measures of physical, mental, and social well-being has not been firmly established. Methods: A previously validated RAND SF-36 questionnaire in patients with pacemaker was given to 252 breast cancer survivor community members. We assessed the construct validity and the reliability by referring to its Pearson’s r table value and Cronbach’s α coefficient. Results: One hundred and fourteen breast cancer survivor community members participated and completed all 36 questions of the instrument between September- November 2018. Questions number 2, 28, and 35 showed lower Pearson’s r value (r<0,300) than other questions but still showed r value of >0.1548 indicating that these questions were valid. Cronbach’s α coefficient >0.90 indicated good internal consistency. Conclusions: The Indonesian version of the SF-36 quality of life questionnaire is a suitable instrument and can be used for research in Indonesian breast cancer patients.

Abstract P4-09-08: Shared-patient physician networks and their impact on the uptake of genomic testing in early-stage breast cancer

Abstract Background: Oncotype DX (ODX) or 21-gene recurrence score genomic testing is used to stratify risk and determine appropriate treatment in women with early-stage breast cancer (BC). Diffusion of ODX by way of physician networks has not been studied. Objective: To determine the association between physician network connections, defined by shared patients, and the use of ODX testing. Methods: SEER-Medicare claims from 2008-2012 were used to identify a cohort of woman with a diagnosis of BC from registry/ICD codes, continuously enrolled in Medicare fee-for-service Part A and B one year prior to and one year following diagnosis. We identify receipt of ODX from the associated CPT code, claim reimbursement, and performing NPI. To look at the influence of network connections on ODX use, we split the study into two time periods: early adoption from 2008-2009, and late from 2010-2012. Medical oncologists with a BC-related claim in the cohort above, and any rendered BC-related service are considered 'connected' if they shared two or more BC patients. Analyses describe these connections and explore the association between connectedness to an early adopting medical oncologist and ODX use in parallel physician and patient-level analyses using generalized linear mixed models with a hospital referral region-specific random effect. Models control for physician and patient-level characteristics where applicable. Results:24,463 women met study criteria; 12,874 were diagnosed with BC in the early adoption time period (1,790 received ODX) and 11,589 were diagnosed in the late period (2,334 received ODX). 2,073 medical oncologists treated these patients from 2008-2009. The mean number of BC patients treated per medical oncologist was 86.8 during the early adoption period, and medical oncologists had a median number of peer connections of 11 (IQR: 7-18). Early adopting medical oncologists had higher numbers of peer connections and higher average patient counts than non-early adopters. A higher percentage of female medical oncologists were early adopters (39%) then male medical oncologists (33%) (p<0.02). Among non-early adopting oncologists, peer connection to at least two early adopting providers in 2008-2009 is associated with a 3.2 (95% CI: 2.0-4.9) times increase in the odds of ordering ODX in 2010-2012 after adjustment for physician gender and time in practice. In patient-level models with controls for physician and patient characteristics, seeing a medical oncologist with connections to at least two early adopting physicians is associated with a 1.6 times (95% CI: 1.1-2.2) increase in the odds of receiving ODX testing in 2010-2012. Conclusions: We observe a positive adjusted association between connectedness to an early-adopting physician and ODX prescribing/use in both physician-level and patient-level analyses. These results suggest that provider networks may help diffuse new technologies, and that BC genomic testing is likely to be an area of shared practices between providers. Efforts to increase testing, where appropriate, may benefit from a range of peer-to-peer connection strategies. Citation Format: Rotter J, Wilson L, Greiner M, Pollack C, Dinan M. Shared-patient physician networks and their impact on the uptake of genomic testing in early-stage breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-09-08.

Germline variation in BRCA1/2 is highly ethnic-specific: Evidence from over 30,000 Chinese hereditary breast and ovarian cancer patients.

BRCA1 and BRCA2 play essential roles in maintaining the genome stability. Pathogenic germline mutations in these two genes disrupt their function, lead to genome instability and increase the risk of developing breast and ovarian cancers. BRCA mutations have been extensively screened in Caucasian populations, and the resulting information are used globally as the standard reference in clinical diagnosis, treatment and prevention of BRCA‐related cancers. Recent studies suggest that BRCA mutations can be ethnic‐specific, raising the question whether a Caucasian‐based BRCA mutation information can be used as a universal standard worldwide, or whether an ethnicity‐based BRCA mutation information system need to be developed for the corresponding ethnic populations. In this study, we used Chinese population as a model to test ethnicity‐specific BRCA mutations considering that China has one of the latest numbers of breast cancer patients therefore BRCA mutation carriers. Through comprehensive data mining, standardization and annotation, we collected 1,088 distinct BRCA variants derived from over 30,000 Chinese individuals, one of the largest BRCA data set from a non‐Caucasian population covering nearly all known BRCA variants in the Chinese population (https://dbBRCA-Chinese.fhs.umac.mo). Using this data, we performed multi‐layered analyses to determine the similarities and differences of BRCA variation between Chinese and non‐Chinese ethnic populations. The results show the substantial differences of BRCA data between Chinese and non‐Chinese ethnicities. Our study indicates that the current Caucasian population‐based BRCA data is not adequate to represent the BRCA status in non‐Caucasian populations. Therefore, ethnic‐based BRCA standards need to be established to serve for the non‐Caucasian populations.

Evaluation of the safety profiles of estrogenic Chinese herbal medicines in breast cancer

BackgroundAn increasing number of breast cancer patients in Asian countries has been found to consume dietary supplements including phytoestrogen-rich Chinese herbal medicines with an expectation to alleviate the side effects of conventional cancer therapies. PurposeThe question of whether estrogenic Chinese herbal medicines are beneficial or detrimental to the health of breast cancer patients remains uncertain. Study DesignThe present study aimed at establishing a systematic approach to look at the safety profiles of estrogenic Chinese herbal medicines (CHM). MethodsThe effects of estrogenic CHM on the growth of human breast cancer cells as well as the progression of breast tumors in mice have been investigated. ResultsOur results demonstrated that among 10 selected estrogenic CHM, the aqueous extracts of Cistanche deserticola (CD) and Dioscorea opposita (DO) at 0.4 to 1.6 mg/ml significantly stimulated cell viability in both estrogen receptor (ER)-positive (MDA-MB-361 and MCF-7) and ER-negative (SKBR3 and MDA-MB-231) breast cancer cells. However, results from animal studies showed that no significant difference was found on the size of mouse 4T1 breast tumors in CD- and DO-treated mice when compared with the control group, while the number of proliferative cells were found to be increased in DO-treated group. Besides, CD and DO treatments induced significant immunomodulatory effects on 4T1 tumor-bearing mice by increasing the production of cytokines IL-2 and IFN-γ and modulation of regulatory T-cells. Furthermore, CD and DO treatments did not stimulate, but in fact suppressed human triple-negative MDA-MB-231 breast xenografts growth in immunodeficiency mice. ConclusionThe considerable concerns on the use of CD and DO in breast cancer patients could be relieved to some extents upon the findings of this pre-clinical study. The potential harmful effects of estrogenic Chinese herbal medicines on breast cancer growth should be verified in both cell-based and tumor-bearing mice models.

PO-497 Microtubule regulatory proteins as predictive biomarkers of taxane-based chemoresistance in breast cancer?

IntroductionNeo-adjuvant chemotherapy combining taxanes and anthracyclines represents an interesting option for a number of breast cancer patients. However, the proportion of patients who achieve a pathological complete response (pCR) after treatment remains low, reaching 15%–20% in the whole population. Thus, identifying predictive biomarkers of drug resistance is necessary to select the patients who are most likely to benefit from chemotherapy. Taxanes (paclitaxel, docetaxel) are potent stabilisers of the microtubule cytoskeleton, which functions are tightly regulated by a panel of MT-associated proteins and mitotic kinases. In the present study, we evaluated whether taxane resistance in breast cancer may be associated with alterations of genes encoding MT-regulatory proteins.Material and methodsExpression levels of 411 MT-related genes were analysed from Affymetrix U133 microarray of breast tumours from three independent multicentered clinical trials, namely REMAGUS-02 (115 patients), REMAGUS-04 (142 patients) and MD Anderson (133 patients). Only patients treated with neoadjuvant taxane-based chemotherapy were included in this study. Expression level of MT-related genes in tumours was compared with the ability to achieve pCR.Results and discussionsBy comparing expression levels of 411 MT-related genes in three independent cohorts of breast cancer patients treated with taxane-based neo-adjuvant chemotherapy, we have identified a total of 94 MT-related genes that are differentially expressed in tumours with pCR. Among those, 18 MT-related genes are common to the three cohorts. Interestingly, all these genes appear as potential prognostic biomarkers of overall survival. Ongoing studies aim at functionally validating these candidates using siRNA screening in two different breast cancer cell lines.ConclusionThis study should lead to the identification of novel predictive biomarkers to select breast cancer patients who are likely to benefit from taxane-based chemotherapy. This should also pave the way for future targeted treatments of chemoresistant breast tumours.

Triple-Negative Breast Cancer: A Comparison of Race and Survival

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a high prevalence in blacks. South Carolina demographically has a high percentage of blacks. This study examines survival and recurrence associated with TNBC in black and white women. A retrospective review of breast cancer patients within the Palmetto Health Cancer Registry was performed from 1999 to 2015. Patient demographics and tumor characteristics were collected and correlated with outcomes. Overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were analyzed. The total number of breast cancer patients in the registry was 1723 (1085-white and 638-black). The median follow-up was 48.4 months. The majority of cancers diagnosed in both cohorts were early stage (I, IIA, IIB, 93.4% vs 90.4% P = NS). We identified 332 patients with TNBC. Of those 332 patients, 144 (43.4%) were whites and 188 (56.6%) were blacks. Older age (P = 0.01), high-grade (P < 0.001), and black race (P < 0.001) were significantly associated with TNBC on multivariate analysis. Five- and 10-year OS was significantly worse in blacks with TNBC (P < 0.001). There was no difference in DSS or RFS between the two cohorts. TNBC disproportionately affects black women and is an aggressive subtype of breast cancer with limited treatment options compared with receptor-positive breast cancer. Black patients with TNBC in our study had statistically worse OS. These findings are similar to what has been reported in the literature and prompts further research in newer targeted therapies.

SELF EFFICACY PEREMPUAN USIA 35 - 44 TAHUN DALAM UPAYA PENCEGAHAN KANKER PAYUDARA

Based on data from Health Department of Surabaya on Reports Puskesmas in Surabaya at 2015 discovered that the number of breast cancer patients over the years also increased. More than 30% of cancer can be prevented with breast self examination (BSE). Puskesmas with BSE declining coverage in a row is a big health center coverage is Puskesmas Tembok Dukuh with 1.89% in 2014 and then declined in 2015 to 1.22%. This study used observational research and cross sectional design. Researchers took samples with simple random sampling with 33 respondents. Independent variables in this study is performance accomplishment, vicarious experience, social persuasion dan physiological and emotional states. And the dependent variables in this study is self effi cacy and BSE. Data analysis using cross tabulations. And the result that good performance accomplishment, vicarious experience, social persuasion dan physiological and emotional states it will have an impact on his self effi cacy. The conclusion of this study is the majority of respondents with good self effi cacy have a good BSE. Therefore it is necessary to increase the numbers of BSE coverage by increasing self effi cacy by providing values of motivation to be concerned about her reproductive health.

Complementary and Alternative Medicine use: Influence of Patients’ Satisfaction with Medical Treatment among Breast Cancer Patients at Uganda Cancer Institute

Introduction: Use of Complementary and alternative medicine (CAM) is high among cancer patients especially breast cancer patients. This study sought to evaluate Complementary and alternative medicine use in breast cancer patients and how its use is influencedby patient’s satisfaction with conventional medical treatment among breast cancer patients attending Uganda Cancer Institute. Patients and Methods: A cross-sectional study design was used in this study. Participants who were diagnosed histologically with breast cancer at Uganda Cancer Institute took part in the study. A questionnaire was developed and used to interview the participants and medical records of the respondents were also reviewed. Results: A total of 235 participants completed the study. The prevalence of CAM use was 77%. CAM therapies used included herbal medicines, prayer for health, vitamins/minerals, native healers, Chinese medicines, massage, yoga, Ayurvedic medicine, Acupuncture, reflexolog, Support group attendance, meditation, Magnetic and Bio-fieldmanipulation. Satisfaction with medical treatment was significantlyassociated with CAM use. Patients who are not satisfiedwith medical treatment were more likely to use CAM. Conclusion: There is a high number of breast cancer patients using CAM, various categories of therapies are being used and patients’ satisfaction with medical treatment triggers off a patients decision to use CAM therapies.

Landscape of oncoplastic breast surgery across Poland.

Oncoplastic and reconstructive techniques are essential tools in the armamentarium of contemporary breast surgeons. The aim of the study was to identify oncoplastic reconstructive patterns in breast cancer centers across Poland. A questionnaire of 18 questions was sent by email to the members of the Polish Society of Surgical Oncology and the Polish Society of Plastic, Reconstructive and Esthetic Surgery via their dedicated websites. The numbers of breast cancer patients operated on in each center ranged from 120 to 904 per year. Breast-conserving surgery (BCS) predominated in all but one center (range 50-70%). Immediate breast reconstructions (IBR) accounted for 6-42% of procedures, The most frequent type of IBR was either a two-stage expander followed by a permanent implant or one-stage implant- based with or without synthetic mesh. The most frequent type of delayed breast reconstruction (DBR) was a two-stage expander followed by implant-based reconstruction. None of the surveyed cancer centers performed free flap reconstruction. Deep inferior epigastric perforator (DIEP) flaps were performed in the plastic surgery department. Reconstructions based on pedicled flaps were performed in cancer centers. Acellular dermal matrices (ADM) and fat transfer were used in selected centers. In the clinical scenario of adjuvant radiotherapy, delayed breast reconstruction was favored. The full range of oncoplastic BCS was performed. Patient-reported outcome measures (PROM) and complications were assessed. Our findings can act as a platform for further improvement in skills, certification, data collection and audit, including patient reported expectation measures. There is also an urgent need to address pan-European inconsistencies in procedural reimbursement.

Prostate-specific membrane antigen (PSMA) expression in breast cancer and its metastases.

The present study was undertaken to investigate the expression of prostate-specific membrane antigen (PSMA) in normal breast tissues, in cancerous breast tissues and in distant metastases from patients with breast cancer. Immunohistochemical analysis was performed to determine PSMA expression and angiogenic activity using anti-PSMA mAb and anti-CD31 mAb respectively. Immunofluorescence staining was applied to confirm the exact co-localization of PSMA and CD31. We observed different patterns of PSMA expression between normal and cancerous tissues. Normal breast tissues showed PSMA expression only in normal glandular cells. However, primary breast tumors and distant metastases showed PSMA expression in tumor cells and in tumor-associated neovasculature. PSMA score group status in primary breast tumors was significantly associated with histologic type and tumor grade (p = 0.026 and p = 0.004 respectively). Distant metastases showed higher PSMA expression in tumor-associated neovasculature comparing with primary tumors. Moreover, brain tumor-associated neovasculture had significantly higher expression of PSMA comparing with bone tumor-associated neovasculture. The localized binding of PSMA mAb to the neovasculature endothelium was confirmed with the double Immunofluorescence staining. 68Ga-PSAM imaging of a patient with metastatic breast cancer showed strong tracer uptake in all known skeletal metastases. To the best of our knowledge, this study is the second one that has assessed PSMA expression in a large number of breast cancer patients. Our findings showed that PSMA is particularly expressed in tumor-associated neovasculature of breast tumors and its distant metastases, thus enhancing the evidence on the potential usefulness of PSMA as a therapeutic vascular target.

Breast Cancer Associated Mutations Reported Among Malaysian Malay, Chinese and Indian Patients

Breast cancer among women has reached an alarming stage compared to 20 years ago. It was found that single nucleotide polymorphisms (SNPs) play an important role in the development of breast cancer. SNPs may suppress or activate the functional genes, which then leads to an increased survival of cells due to the suppression of tumour suppressor genes or increased activity in detrimental proteins, resulting in cancers. Recently, breast cancer research is given significant attention due to the increasing number of breast cancer patients in Malaysia each year. However, breast cancer researches in Malaysia are mainly focused on well known breast cancer genes such as BRCA1 and BRCA2. There is less emphasis on the other breast cancer contributing genes. This paper was aimed to review the research findings on mutations associated with breast cancer in Malaysian Malay, Malaysian Chinese and Malaysian Indian as it has never been cumulatively reported and to ascertain the common mutations found in these three major Malaysia ethnicity.

Clinical Impact of 21-Gene Recurrence Score Test Within the Veterans Health Administration: Utilization and Receipt of Guideline-Concordant Care

IntroductionEnsuring guideline-concordant cancer care is a Department of Veterans Affairs (VA) priority, especially as the number of breast cancer patients at VA medical centers (VAMCs) grows. We assessed the utilization and clinical impact of the 21-gene Recurrence Score test, which predicts 10-year risk of breast cancer recurrence and the likelihood of chemotherapy benefit, on veterans newly diagnosed with breast cancer. Patients and MethodsWe conducted a retrospective cohort study using 2011-2012 VA Central Cancer Registry, chart review, and laboratory test data. Independent variables assessed included patient and site-of-care characteristics. The outcome of interest was whether newly diagnosed, eligible (node negative, hormone-receptor positive, human epidermal growth factor receptor 2 [HER2] negative) veterans underwent the 21-gene test. We performed descriptive statistics on all patients and multivariate logistic regression to determine associations. We correlated treatments received with test results. ResultsAmong 328 eligible veterans, 82 (25%) had the 21-gene test; 100 eligible veterans (30%) sought care at a VAMC where no tests were ordered. Receiving care at a VAMC that had women's health services (odds ratio [OR], 1.84, 95% confidence interval [CI], 1.05-3.22) and having tumor characteristics meeting the National Comprehensive Cancer Network 2010 test criteria (OR, 3.06, 95% CI, 1.69-5.57) were positive predictors of testing; increasing age (OR, 0.93, 95% CI, 0.91-0.96 per year) and fee-based care (OR, 0.46, 95% CI, 0.26-0.82) were negative predictors. The majority of tested patients received guideline-concordant care. ConclusionSite of care and tumor characteristics were important predictors of test uptake. Facilitating delivery of guideline-concordant cancer care requires improved laboratory informatics and clinical decision support.

HER2 FISH results in breast cancers with increased CEN17 signals using alternative chromosome 17 probes - reclassifying cases in the equivocal category.

HER2 testing of invasive breast cancer by in-situ hybridization guides therapy decisions. Probing HER2 and centromere of chromosome 17 (cen17) simultaneously is supposed to reveal both a potential HER2 gene amplification and polysomy 17. However, a considerable number of breast cancer patients with quasi polysomy 17 are considered 'equivocal', which is diagnostically meaningless. Moreover, patients with equivocal/false polysomic tumours are prevented from a potentially beneficial anti-HER2 treatment. Here we evaluated the RAI1, D17S122 and TP53 hybridization markers to indicate true polysomy reliably and to reclassify equivocal samples accurately as HER2-positive. Samples with (n = 82) and without (n = 52) increased cen17 copy numbers and 78 evidently HER2-amplified specimens were analysed using dual and triple marker hybridization probes. Selected putative polysomic samples were subjected to array-based comparative genomic hybridization (aCGH). We found that 37.8% samples with putative polysomy 17 did not show any gain in RAI1, D17S122 or TP53. Accordingly, aCGH revealed evidence for the presence of HER2/cen17 co-amplification rather than for true polysomy in those cases. Reflex testing using alternate 17p markers reclassified up to 56.3% equivocal cases as HER2-positive and the combined assessment of a 17p and 17q locus allows the differentiation of true versus false polysomy. An increased cen17 copy number does not necessarily reflect polysomy, and reflex testing facilitates the reclassification of 'equivocals'. Nevertheless, the prognostic and predictive value of a HER2/cen17 co-amplification versus HER2 gene amplification alone must still be evaluated prospectively.

Controversies about fertility and pregnancy issues in young breast cancer patients: current state of the art.

For trying to help physicians in counseling their young patients with breast cancer interested in fertility preservation and future reproductive plans, this manuscript aims to perform an overview of the main available data on 10 controversies in this field. Thanks to the improvement in patients' prognosis, a growing attention towards fertility and pregnancy issues has been given over the past years and is currently provided to young breast cancer patients. However, several grey zones persist in many domains of this field and some physicians are still uncomfortable to deal with these issues. Despite the great number of breast cancer patients experiencing fertility and pregnancy concerns at the time of diagnosis, the pursuit of fertility preserving strategies is realized only for a small proportion of them. The lack of adequate oncofertility counseling at the time of anticancer treatment decisions and the high costs of fertility preserving procedures can be considered the main explanations for these findings. The several ongoing registries and prospective studies investigating fertility and pregnancy issues in young breast cancer patients are crucial to acquire more robust data and try to address and solve the still unmet controversies in this field.

Abstract 3329: Combinatorial blockade of ERBB receptors in HER2 low breast cancer

Abstract Large number of breast cancer patients clinically classified as HER2 negative, show low/moderate levels of HER2 along with other ERBB receptors. Concomitant blockade of EGFR, ERBB2 and ERBB3 with specific therapeutic antibodies (cetuximab, trastuzumab/pertuzumab and lumretuzumab, respectively) appears as a beneficial approach to improve survival of patients who have failed to previous treatment strategies. Additionally, ERBB3 expression has been reported as a trastuzumab resistance mechanism in HER2 positive subtypes.We have confirmed a specific pattern of ERBB receptors expression in different breast cancer subtypes. Individual and combined blockade of the receptors with therapeutic antibodies has been tested in vitro using a metabolic viability assay (Cell Titer Glo) and their effects in cell cycle status measured by BrdU staining. All four therapeutic antibodies bind to the respective extracellular domains inhibiting downstream signaling pathways. Response to individual treatment is cell dependent and correlates with EGFR expression in the triple negative MDA-MB-468 but not in luminal T47D cancer cell line. Response of T47D cells to lumretuzumab is higher when combined with pertuzumab or trastuzumab, suggesting ERBB2/ERBB3 dimer as the most relevant one, an effect more evident upon ectopic addition of NRG1 (only ligand for ERBB3). Long exposure of MDA-MB468 cells to cetuximab induces ERBB3 expression and increases its sensitivity to cetuximab when combined. As well as, in the HER2+ BT474 cancer cell line resistant to trastuzumab, higher levels of ERBB3 also make cells more sensitive to alternative anti-ERBB therapies. To establish the role of ERBB4 (no specific therapeutic antibody) in the whole ERBB network, stable knock-down regulation (shRNA) has been performed in T47D cells. Although treatment of HER2 overexpressing breast tumors has been successful, targeting other ERBB members in a HER2 moderate/low scenario seems to be a promising approach in combinatorial therapies; even in resistant cell lines. Thus, better characterization of ERBB network should help to pave the way for a personalized treatment of HER2 low breast cancer. [U.K.: Deceased March, 2016] Citation Format: Mireia Berdiel-Acer, Eileen Reinz, Khalid Abnaof, Sara Burmester, Rainer Will, Ulrike Korf, Stefan Wiemann. Combinatorial blockade of ERBB receptors in HER2 low breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3329. doi:10.1158/1538-7445.AM2017-3329

159P - Endoscopy-assisted breast surgery for breast cancer: updated results from study conducted by the Taiwan Endoscopic Breast Surgery Cooperative Group

Endoscopy-assisted breast surgery (EABS) performed through minimal axillary and/or peri- areolar incisions is a possible alternative to open surgery for certain patients with breast cancer. In this study, we report the early results of an EABS program in Taiwan. The medical records of patients who underwent EABS for breast cancer during the period May 2009 to December 2015 were collected from the Taiwan Endoscopic Breast Surgery Cooperative Group database. Data on clinicopathologic characteristics, type of surgery, method of breast reconstruction, complications and recurrence were analyzed to determine the effectiveness and oncologic safety of EABS in Taiwan. A total of 345 EABS procedures were performed in 320 patients with breast cancer, including 25 (7.2%) patients with bilateral disease. The number of breast cancer patients who underwent EABS increased initially from 2009 to 2012 and then stabilized during the period 2012–2015. The most commonly performed EABS was endoscopy-assisted total mastectomy (EATM) (85.8%) followed by endoscopy-assisted partial mastectomy (EAPM) (14.2%). Approximately 76% of the EATM procedures involved breast reconstruction, with the most common types of reconstruction being implant insertion and autologous pedicled TRAM flap surgery. During the seven-year study period, there was an increasing trend in the performance of EABS for the management of breast cancer when total mastectomy was indicated. The positive surgical margin rate was 1.4 %. Overall, the rate of complications associated with EABS was 13.2 % and all were minor and wound-related. During a median follow-up of 31.7 (4.2–75.6) months, there were 3 (1%) cases of local recurrence, 5 (1.4%) case of distant metastasis and 2 (0.5%) death. The updated results from the EABS program in Taiwan show that EABS is a safe procedure and results in acceptable cosmetic outcome. These findings could provide an alternative in surgical technique for certain breast cancer patients.

Patterns of clinical practice for sentinel lymph node biopsy in women with node-negative breast cancer: the results of a national survey in Japan

Sentinel lymph node (SLN) biopsy is now accepted as the standard of care for axillary staging in women with node-negative breast cancer. Currently, dye, radioisotope (RI), and fluorescence indocyanine green (fICG) are tracers available. Importance of these three tracers has been recognized for SLN biopsy but the trend for SLN mapping has not been reported. Aim of this national wide survey was to evaluate practice patterns of SLN biopsy in Japan. This survey was conducted to examine the clinical practice of SLN biopsy in centers where one or more Japanese Breast Cancer Society (JBCS) board-certified surgeons practice breast cancer care. Their responses were recorded from 1 to 30 Oct 2014 and received by mail or fax in Japan. The questionnaire included three items: the number of breast cancer patients treated per year, the number of SLN biopsy procedures in a single year, and the methods for SLN detection. A total of 412 responses excluding the 63 centers that do not perform the surgery were analyzed. Out of them, 206 (50%) centers had a gamma probe, 118 (29%) had an NIR fluorescence imaging system, and both were available at 49 (12%) of the centers. Neither RI nor fICG was available in 137 (33%). The dye method was preferentially used in private hospitals. In 412 centers, a total of 36,221 patients underwent SLN biopsy per year and 23,038 (64%) received radioactive tracer. fICG was co-applied with RI in 83 and 13% of patients, respectively. Single mapping with RI alone was used in only 4% of patients. The non-radioactive method was used for routine SLN biopsy in 13,183 (36%) patients [8533 (24%) for dye alone and 4650 (12%) for fICG alone]. A radioactive tracer was used in 64% of women with early breast cancer for SLN biopsy while approximately 24% received dye alone, which was especially prevalent in PHs. The fICG was used in only 12% as a non-radioactive method but incentive package for fICG by national health insurance plan could increase the number of NIR imaging systems and improve the sensitivity for SLN biopsy in Japan.

Prediction of Female Breast Cancer Incidence among the Aging Society in Kanagawa, Japan

Owing to the increasing number of elderly “baby boomers” in Japan, the number of cancer patients is also expected to increase. Approximately 2 million baby boomers from nearby local areas are residing in metropolitan areas; hence, the geographical distribution of cancer patients will probably markedly change. We assessed the expected number of breast cancer (BC) patients in different regions (urban, outer city, town, rural) using estimates of the nation’s population and Kanagawa Cancer Registry data. To estimate future BC incidence for each region, we multiplied the 2010 rate by the predicted female population for each region according to age group. The incidence cases of BC in those aged ≥65 years is expected to increase in all areas; in particular, compared to rates in 2010, the BC incidence in urban areas was predicted to increase by 82.6% in 2035 and 102.2% in 2040. Although the incidence in all BC cases in urban areas showed an increasing trend, until peaking in 2040 (increasing 31.2% from 2010), the number of BC patients would continue to decrease in other areas. The number of BC patients per capita BC specialist was 64.3 patients in 2010; this value would increase from 59.3 in 2010 to 77.7 in 2040 in urban areas, but would decrease in other areas. Our findings suggest that the number of elderly BC patients is expected to increase rapidly in urban areas and that the demand for BC treatment would increase in the elderly population in urban areas.