Systemic Treatment Of Breast Cancer Research Articles

Local therapies for breast cancer.

SummaryDuring the San Antonio Breast Cancer Symposium in December 2016, the main topics were systemic treatment of breast cancer and molecular research. But several studies were also presented concerning local therapy: Surgical issues on evaluating resection margins, management of ductal carcinoma in situ (DCIS), surgical challenges after neoadjuvant therapy related to assessment of response or treatment of axillary lymph nodes, and studies about outcome after breast reconstruction and radiation therapy were discussed. In this short review, oral presentations of these topics are summarized.

Micro-RNAs as Potential Predictors of Response to Breast Cancer Systemic Therapy: Future Clinical Implications.

Despite advances in diagnosis and new treatments such as targeted therapies, breast cancer (BC) is still the most prevalent tumor in women worldwide and the leading cause of death. The principal obstacle for successful BC treatment is the acquired or de novo resistance of the tumors to the systemic therapy (chemotherapy, endocrine, and targeted therapies) that patients receive. In the era of personalized treatment, several studies have focused on the search for biomarkers capable of predicting the response to this therapy; microRNAs (miRNAs) stand out among these markers due to their broad spectrum or potential clinical applications. miRNAs are conserved small non-coding RNAs that act as negative regulators of gene expression playing an important role in several cellular processes, such as cell proliferation, autophagy, genomic stability, and apoptosis. We reviewed recent data that describe the role of miRNAs as potential predictors of response to systemic treatments in BC. Furthermore, upon analyzing the collected published information, we noticed that the overexpression of miR-155, miR-222, miR-125b, and miR-21 predicts the resistance to the most common systemic treatments; nonetheless, the function of these particular miRNAs must be carefully studied and further analyses are still necessary to increase knowledge about their role and future potential clinical uses in BC.

Justification Effectiveness of Systemic Treatment of Breast Cancer Depending On Body Mass Index1se "Dnipropetrovsk Medical Academy of Health Ministryof Ukraine"

Justification Effectiveness of Systemic Treatment of Breast Cancer Depending On Body Mass Index1se "Dnipropetrovsk Medical Academy of Health Ministryof Ukraine"

Does the extent of therapy differ between breast cancers detected by screening mammogram and non-screening methods?

1544 Background: There is ongoing debate about the role of screening mammography and its impact on overall survival in breast cancer. We hypothesized that women with screen-detected breast cancers (SDBC) receive less surgery, regional radiotherapy (RRT), and chemotherapy (CH) than women with non-screen-detected breast cancers (NSDBC). Less therapy equates to less personal and societal burden, including less time away from work, fewer side effects, lower health care and disability costs, and reduced psychosocial distress. These may be adequate justification for screening programs even in the absence of an overall survival benefit. Methods: Women aged 40-79 years with stage 0-III breast cancers diagnosed between 2007-2012 and referred to the British Columbia Cancer Agency were identified using the Breast Cancer Outcomes Unit database. Clinical and tumor characteristics and type/extent of treatment were extracted. Linkage with the Screening Mammography Program of British Columbia segregated cases into SDBCs and NSDBCs. Interval breast cancers arising in regularly screened women (minimum 2-year interval) were excluded. Results: We identified 12,393 women; 7807 with SDBC and 4586 with NSDBC. Compared with NSDBCs, SDBCs were lower stage, less often treated with mastectomy and CH, and occurred in slightly older women (Table 1). SDBC received more radiation than NSDBC. Conclusions: Women with NSDBC are more likely to present with higher stage breast cancer. Rates of mastectomy and CH were 20% higher in NSDBC whereas SDBC had a modest 5% higher rate of RRT. These findings suggest that screening mammography decreases the extent of local and systemic treatment for breast cancer. [Table: see text]

Justification Effectiveness of Systemic Treatment of Breast Cancer Depending on Body Mass Index

Justification Effectiveness of Systemic Treatment of Breast Cancer Depending on Body Mass Index

Changes in brain white matter integrity after systemic treatment for breast cancer: a prospective longitudinal study.

An increasing number of studies suggest chemotherapy for breast cancer may be neurotoxic. Cross-sectional MRI diffusion tensor imaging (DTI) studies suggest a vulnerability of brain white matter to various chemotherapeutic regimens. Up till now, this was confirmed in one prospective DTI study: Deprez et al. (2012) showed a widespread decline in fractional anisotropy (FA) of breast cancer patients after chemotherapy consisting of 5-fluorouracil (5-FU), epirubicin and cyclophosphamide (FEC) +/- taxanes +/- endocrine treatment. Our aim was to evaluate whether similar detrimental effects on white matter integrity would be observed with the currently widely prescribed anthracycline-based chemotherapy for breast cancer (predominantly doxorubicin and cyclophosphamide +/- taxanes +/- endocrine treatment (=BC+SYST; n=26) compared to no systemic treatment (BC; n=23) and no-cancer controls (NC; n=30). Assessment took place before and six months after chemotherapy, and matched intervals for the unexposed groups. DTI data were analyzed using voxel-based tract-based spatial statistics and region of interest (ROI) analysis. Voxel-based analysis did not show an effect of chemotherapy +/- endocrine treatment on white matter integrity. ROI analysis however indicated subtle detrimental effects of chemotherapy +/- endocrine treatment by showing a larger decline in WM integrity in the superior longitudinal fasciculus and corticospinal tract in BC+SYST than BC. Indications for relatively mild neurotoxicity in our study might be explained by patient characteristics and specific aspects of data analysis. The omission of 5-FU in current treatment regimens or the administration of doxorubicin instead of epirubicin is also discussed as an explanation for the observed effects.

Abstract P4-22-05: First-line ribociclib plus letrozole in patients with de novo HR+, HER2– advanced breast cancer (ABC): A subgroup analysis of the MONALEESA-2 trial

Abstract Background: Around 15,000 US patients per year are diagnosed with de novo ABC. Due to the absence of prior systemic treatment for breast cancer, tumors of patients with de novo ABC may exhibit a different disease biology, which could result in different tumor responses compared with patients who have relapsed breast cancer. Ribociclib is an orally bioavailable cyclin-dependent kinase (CDK) 4/6 inhibitor. Results from MONALEESA-2, a double-blind, placebo-controlled, randomized Phase 3 trial (NCT01958021), demonstrated that first-line therapy with ribociclib + letrozole significantly improved progression-free survival (PFS) vs placebo + letrozole in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) ABC. Many patients with de novo ABC receive endocrine therapy in the first line and in subsequent lines; here we present results from the MONALEESA-2 study in a subpopulation of patients with de novo ABC. Methods: Postmenopausal women (N=668) with HR+, HER2– ABC who had no prior systemic therapy for ABC were randomized 1:1 (stratified by liver and/or lung metastases) to receive ribociclib (600 mg/day; 3-weeks-on/1-week-off) + letrozole (2.5 mg/day; continuous) or placebo + letrozole. Patients with de novo ABC were eligible. Additional eligibility criteria included measurable disease or ≥1 predominantly lytic bone lesion, Eastern Cooperative Oncology Group performance status ≤1, and adequate bone marrow/organ function. Prior CDK4/6 inhibitors or systemic therapy for ABC were prohibited. Patients may have received ≤14 days of letrozole or anastrozole for ABC. The primary endpoint was locally assessed PFS; a predefined subgroup analysis evaluated PFS in patients with de novo ABC. Results: In total, 227 patients with de novo ABC were enrolled. Patients with de novo ABC were equally distributed with 114 (34%) and 113 (34%) in the ribociclib + letrozole and placebo + letrozole arms, respectively. Median duration of exposure to study treatment in the ribociclib + letrozole vs placebo + letrozole arms was 14.1 vs 12.8 months. Treatment was discontinued in 84 (37%) patients with de novo ABC (ribociclib + letrozole vs placebo + letrozole, n [%]; 34 [30%] vs 50 [44%]). Reasons for treatment discontinuation (ribociclib + letrozole vs placebo + letrozole, n [%]) included disease progression (21 [18%] vs 41 [36%]), patient/physician decision (5 [4%] vs 6 [5%]), and adverse events (6 [5%] vs 3 [3%]). PFS was increased in patients with de novo ABC who received ribociclib + letrozole vs placebo + letrozole (hazard ratio=0.448 [95% confidence interval: 0.267–0.750]). The 12-month PFS event-free probability in patients with de novo ABC was 82% in the ribociclib + letrozole arm vs 66% in the placebo + letrozole arm. Conclusions: The combination of ribociclib + letrozole significantly improved PFS compared with placebo + letrozole in postmenopausal women with HR+, HER2– de novo ABC at diagnosis and therefore may become an important treatment option in the de novo ABC setting. Keywords: Advanced breast cancer; CDK4/6 inhibitor; Letrozole; Ribociclib Citation Format: O'Shaughnessy J, Petrakova K, Sonke GS, André F, Conte P, Arteaga CL, Cameron DA, Hart LL, Villanueva C, Jakobsen EH, Lindquist D, Souami F, Li X, Germa C, Hirawat S, Hortobagyi GN. First-line ribociclib plus letrozole in patients with de novo HR+, HER2– advanced breast cancer (ABC): A subgroup analysis of the MONALEESA-2 trial [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-22-05.

Study protocol: A Randomized Controlled Trial of a Comprehensive Breast Cancer Treatment Patient Decision Tool (iCanDecide).

BackgroundPatients newly diagnosed with breast cancer face a series of complex decisions regarding locoregional and systemic treatment. There is a need to improve the quality of locoregional and systemic decisions for breast cancer patients, and to help patients understand the role of evaluative tests in this decision process. We are now conducting a randomized controlled trial (RCT) of an online decision tool—called iCanDecide, which we expect will help patients with these difficult decisions. Furthermore, the results of this RCT will be highly relevant to future breast cancer patients making these decisions and to their clinicians.MethodsThis is a two-arm randomized controlled trial with the target of 222 participants per arm. Participants are recruited from 25 surgical practices (total 40 surgeons) and 2 medical oncology practices (total 2 oncologists) in Michigan, Georgia, Tennessee, and California. Participants are newly-diagnosed female breast cancer patients between 21 and 84 years, with stage I-II invasive breast cancer or ductal carcinoma in situ (DCIS) and who are eligible for and considering either mastectomy or lumpectomy with radiation, and who may be eligible for adjuvant systemic treatment.The RCT tests an interactive, tailored website, called iCanDecide (intervention arm), compared to a static version of the website (control arm). The static control arm is designed to include the same basic content as the intervention version, but without tailoring and interactive features. The primary outcome includes the rate of making a high-quality decision. The hypothesis is that patients randomized to the interactive version of iCanDecide will have higher rates of high quality decisions (informed and values-concordant), and will appraise their decision-making process more positively, for both surgical and systemic treatment.DiscussionThe goal of this study is to evaluate the impact of the iCanDecide interactive website on decision-making for locoregional and systemic breast cancer treatments. The results of this study will be important for future breast cancer patients and their clinicians as we determine how to better individualize decision making across this complex treatment landscape.Trial registrationClinicalTrials.gov ID NCT01840163.

Justification effectiveness of systemic treatment of breast cancer depending on body mass index

Justification effectiveness of systemic treatment of breast cancer depending on body mass index

Chemotherapy decisions and patient experience with the recurrence score assay for early-stage breast cancer.

The 21-gene recurrence score (RS) assay stratifies early-stage, estrogen receptor-positive breast cancer by recurrence risk. Few studies have examined the ways in which physicians use the RS to recommend adjuvant systemic chemotherapy or patients' experiences with testing and decision making. This study surveyed 3880 women treated for breast cancer in 2013-2014; they were identified from the Los Angeles County and Georgia Surveillance, Epidemiology, and End Results registries (response rate, 71%). Women reported chemotherapy recommendations, the receipt of chemotherapy, testing experiences, and decision satisfaction. Registries linked the tumor data, RS, and surveys. Regression models examined factors associated with chemotherapy recommendations and receipt by the RS and subgroups. There were 1527 patients with stage I/II, estrogen receptor/progesterone receptor-positive, human epidermal growth factor 2-negative disease: 778 received an RS (62.6% of patients with node-negative, favorable disease, 24.3% of patients with node-negative, unfavorable disease, and 13.0% of patients with node-positive disease; P < .001). Overall, 47.2% of the patients received a recommendation against chemotherapy, and 40.5% received a recommendation for it. RS results correlated with recommendations: nearly all patients with high scores (31-100) received a chemotherapy recommendation (86.9%-96.5% across clinical subgroups), whereas the majority of the patients with low-risk results (0-18) received a recommendation against it (65.9%-78.2% across subgroups). Most patients with high RSs received chemotherapy (87.0%, 91.1%, and 100% across subgroups), whereas few patients with low scores received it (2.9%, 9.5%, and 26.6% across subgroups). There were no substantial racial/ethnic differences in testing or treatment. Women were largely satisfied with the RS and chemotherapy decisions. Oncologists use the RS to personalize treatment, even for those with node-positive disease. High satisfaction and an absence of disparities in testing and treatment suggest that precision-medicine advances have improved systemic breast cancer treatment. Cancer 2017;43-51. © 2016 American Cancer Society.

Influence of Hydroalcoholic Vehicle on In Vitro Transport of 4-Hydroxy Tamoxifen Through the Mammary Papilla (Nipple).

Majority of breast cancers originate from epithelial cells in the duct and lobules in the breast. Current systemic treatments for breast cancer are associated with significant systemic side effects, thus warranting localized drug delivery approaches. The aim of this study was to investigate the influence of hydroalcoholic vehicle on topical delivery of 4-hydroxy tamoxifen (4-HT) through the mammary papilla (nipple). The in vitro permeability of 4-HT through porcine mammary papilla was studied using different hydroalcoholic vehicles (0, 33.33, and 66.66% alcohol). Nile red was used as a model lipophilic dye to characterize the drug transport pathway in the mammary papilla. The penetration of 4-HT through the mammary papilla increased with increase in alcohol concentration in the vehicle. The solubility of 4-HT was enhanced by increasing alcohol concentration in the vehicle. On the other hand, the epidermis/vehicle partition coefficient decreased with increase in alcohol concentration. The mammary papilla served as a depot and slowly released 4-HT into the receptor medium. Highest drug penetration was observed with saturated drug solution in 66.66% alcohol, and 4-HT levels were comparable to IC50 value of 4-HT. Results from this study demonstrate the possibility of using mammary papilla as a potential route for direct delivery of 4-HT to the breast.

SPAG5 as a prognostic biomarker and chemotherapy sensitivity predictor in breast cancer: a retrospective, integrated genomic, transcriptomic, and protein analysis

Proliferation markers and profiles have been recommended for guiding the choice of systemic treatments for breast cancer. However, the best molecular marker or test to use has not yet been identified. We did this study to identify factors that drive proliferation and its associated features in breast cancer and assess their association with clinical outcomes and response to chemotherapy. We applied an artificial neural network-based integrative data mining approach to data from three cohorts of patients with breast cancer (the Nottingham discovery cohort (n=171), Uppsala cohort (n=249), and Molecular Taxonomy of Breast Cancer International Consortium [METABRIC] cohort; n=1980). We then identified the genes with the most effect on other genes in the resulting interactome map. Sperm-associated antigen 5 (SPAG5) featured prominently in our interactome map of proliferation and we chose to take it forward in our analysis on the basis of its fundamental role in the function and dynamic regulation of mitotic spindles, mitotic progression, and chromosome segregation fidelity. We investigated the clinicopathological relevance of SPAG5 gene copy number aberrations, mRNA transcript expression, and protein expression and analysed the associations of SPAG5 copy number aberrations, transcript expression, and protein expression with breast cancer-specific survival, disease-free survival, distant relapse-free survival, pathological complete response, and residual cancer burden in the Nottingham discovery cohort, Uppsala cohort, METABRIC cohort, a pooled untreated lymph node-negative cohort (n=684), a multicentre combined cohort (n=5439), the Nottingham historical early stage breast cancer cohort (Nottingham-HES; n=1650), Nottingham early stage oestrogen receptor-negative breast cancer adjuvant chemotherapy cohort (Nottingham-oestrogen receptor-negative-ACT; n=697), the Nottingham anthracycline neoadjuvant chemotherapy cohort (Nottingham-NeoACT; n=200), the MD Anderson taxane plus anthracycline-based neoadjuvant chemotherapy cohort (MD Anderson-NeoACT; n=508), and the multicentre phase 2 neoadjuvant clinical trial cohort (phase 2 NeoACT; NCT00455533; n=253). In the METABRIC cohort, we detected SPAG5 gene gain or amplification at the Ch17q11.2 locus in 206 (10%) of 1980 patients overall, 46 (19%) of 237 patients with a PAM50-HER2 phenotype, and 87 (18%) of 488 patients with PAM50-LumB phenotype. Copy number aberration leading to SPAG5 gain or amplification and high SPAG5 transcript and SPAG5 protein concentrations were associated with shorter overall breast cancer-specific survival (METABRIC cohort [copy number aberration]: hazard ratio [HR] 1·50, 95% CI 1·18-1·92, p=0·00010; METABRIC cohort [transcript]: 1·68, 1·40-2·01, p<0·0001; and Nottingham-HES-breast cancer cohort [protein]: 1·68, 1·32-2·12, p<0·0001). In multivariable analysis, high SPAG5 transcript and SPAG5 protein expression were associated with reduced breast cancer-specific survival at 10 years compared with lower concentrations (Uppsala: HR 1·62, 95% CI 1·03-2·53, p=0·036; METABRIC: 1·27, 1·02-1·58, p=0·034; untreated lymph node-negative cohort: 2·34, 1·24-4·42, p=0·0090; and Nottingham-HES: 1·73, 1·23-2·46, p=0·0020). In patients with oestrogen receptor-negative breast cancer with high SPAG5 protein expression, anthracycline-based adjuvant chemotherapy increased breast cancer-specific survival overall compared with that for patients who did not receive chemotherapy (Nottingham-oestrogen receptor-negative-ACT cohort: HR 0·37, 95% CI 0·20-0·60, p=0·0010). Multivariable analysis showed high SPAG5 transcript concentrations to be independently associated with longer distant relapse-free survival after receiving taxane plus anthracycline neoadjuvant chemotherapy (MD Anderson-NeoACT: HR 0·68, 95% CI 0·48-0·97, p=0·031). In multivariable analysis, both high SPAG5 transcript and high SPAG5 protein concentrations were independent predictors for a higher proportion of patients achieving a pathological complete response after combination cytotoxic chemotherapy (MD Anderson-NeoACT: OR 1·71, 95% CI, 1·07-2·74, p=0·024; Nottingham-ACT: 8·75, 2·42-31·62, p=0·0010). SPAG5 is a novel amplified gene on Ch17q11.2 in breast cancer. The transcript and protein products of SPAG5 are independent prognostic and predictive biomarkers that might have clinical utility as biomarkers for combination cytotoxic chemotherapy sensitivity, especially in oestrogen receptor-negative breast cancer. Nottingham Hospitals Charity and the John and Lucille van Geest Foundation.

The staging value of sentinel lymph node biopsy for breast cancer: translating pathologic findings to clinical practice.

Axillary nodal status is an important prognostic factor in guiding locoregional and systemic treatment for breast cancer. Sentinel lymph node biopsy (SNB) has revolutionized axillary staging by replacing axillary lymph node dissection (ALND) in node-negative women. Even in select patients whose sentinel lymph nodes (SLNs) contain metastases, SNB alone has become an accepted method of managing the axilla. Identification of micrometastases through immunohistochemical analysis of SLNs that are tumorfree on hematoxylin and eosin staining (H&E) does not confer additional clinical benefit. The use of SNB after neoadjuvant chemotherapy (NAC) remains controversial. In addition to axillary nodal status, tumor biology plays an increasingly important role in guiding therapeutic decisions.

Breast cancer. From molecular biology to personified therapy.

Advances in molecular biology had changed approaches to systemic treatment of breast cancer. Clinical decisions on the choice of optimal treatment regimens are performing on the basis of immunohistochemical and molecular genetic classifications. Their increasing uses have contributed changes of paradigm for cancer treatment - from the empirical to the individualized and personalized. The basis for such approaches is knowledge of molecular epidemiology, heterogeneity of expression of molecular subtypes, prognostic and predictive biomarkers of breast cancer. Breast cancer is a widely heterogeneous disease with 20 histological types, 8, molecular-genetic, 6 genomic subtypes, which are characterized by specific molecular and biochemical properties, different clinical course and different outcomes. Molecular genetic classification, created not on the basis of clinical, anatomical and morphological heterogeneity of tumor cells, and on the basis of their molecular-genetic heterogeneity is widely used in clinical practice. This allowed to separate the patients with breast cancer to molecular 4 subtypes - luminal A, luminal B, HER / 2 positive and triple-negative. The significant role of immunohistochemical tissue tumor markers, estrogen and progesterone receptors, HER / 2-neu, Ki-67, p53 for selection the optimal treatment strategy is analyzing in this review. To increase the effectiveness of breast cancer treatment is possible, using a differentiated and personalized approach based on new molecular genetic classification of breast cancer (gene profiling) or to its analogue - expression classification of breast cancer, based on the principle of diversity of immunohistochemical tumor tissue. Personification of cancer treatment involves a therapy based on the study of individual characteristics of tissue is not only the primary tumor but also its metastases.

Les traitements adjuvants des cancers du sein : dernières avancées et perspectives pour des cancers très différents

The most significant part of breast cancers is the localised stage diagnosis, which are widely curable through a combination of topical and adjuvant systemic treatments. The specific choice of these adjuvant treatments (type, duration and route of administration), as well as the decision whether or not to give them, taking into account the heterogeneity of breast cancer tumours and the improvement in the understanding of the natural history of this disease, plus discussion with the woman, results in increasingly personalised medical treatment. In this article, we are going to review the recent changes, the questions that have arisen and the outlook for adjuvant systemic breast cancer treatments.

The Japanese Breast Cancer Society Clinical Practice Guideline for systemic treatment of breast cancer, 2015 edition.

The Japanese Breast Cancer Society Clinical Practice Guideline for systemic treatment of breast cancer, 2015 edition.

Systemic treatment in breast cancer: a primer for radiologists.

Cytotoxic chemotherapy, hormonal therapy and molecular targeted therapy are the three major classes of drugs used to treat breast cancer. Imaging modalities such as computed tomography (CT), magnetic resonance imaging (MRI), 18F-FDG positron emission tomography (PET)/CT and bone scintigraphy each have a distinct role in monitoring response and detecting drug toxicities associated with these treatments. The purpose of this article is to elucidate the various systemic therapies used in breast cancer, with an emphasis on the role of imaging in assessing treatment response and detecting treatment-related toxicities.Teaching Points• Cytotoxic chemotherapy is often used in combination with HER2-targeted and endocrine therapies.• Endocrine and HER2-targeted therapies are recommended in hormone-receptor- and HER2-positive cases.• CT is the workhorse for assessment of treatment response in breast cancer metastases.• Alternate treatment response criteria can help in interpreting pseudoprogression in metastasis.• Unique toxicities are associated with cytotoxic chemotherapy and with endocrine and HER2-targeted therapies.

P71: The development of the test system for assessment of estrogen receptor status, progesterone receptor, HER2/neu and the proliferative factor Ki67 in breast cancer by real time PCR

Background Breast cancer is the most common cause of death from cancer among women aged 40–69 years. According to WHO, about 1 million new cases of breast cancer are diagnosed annually worldwide, and nearly 500,000 die from it. In Russia, more than 55,000 women are diagnosed with breast cancer annually, and more than 22,000 die from it. Diagnosis and treatment of breast cancer is the primary and important social and medical problem.The increased expression of: (a) ER and PgR (70–75% of all cases of breast cancer) is an indication for hormone therapy, which is one of the simplest and most effective methods of systemic treatment of breast cancer; (b) receptor HER2/neu is a marker of highly aggressive form of breast cancer and indication for the use of targeted therapy Gertseptin; (c) proliferative factor Ki-67 reflects the ability of a tumor to metastasize. Today, the “gold standard” of gene expression diagnostic of ER, PgR, HER2/neu and Ki-67 in breast cancer is immunohistochemistry (IHC) using foreign test systems (Ventana, Dako Inc, USA) . However, IHC diagnostics has some significant drawbacks. It leads up to 15–17% of cases of incorrect choice of drug therapy, which based on incorrect results of IHC studies. As a result, the significant group of patients do not receive effective treatment. Aim of the study Aim: the development a prototype of diagnostic test system for detection the receptor status of breast cancer, based on RT-PCR. Materials and methods Breast cancersamples consisted of 45 fresh-frozen tissue (FFT) samples of breast cancer (sites of malignant transformation and normal tissue from the same patients) and 59 FFPET sampleswere collected. All the samples had the IHC characteristic of receptor status of ER, PgR, HER2/neu and proliferation factor Ki-67 (Dako Inc., USA). Samples were submitted by SBIH NR “Novosibirsk Regional Oncology Center” (Novosibirsk, Russia). The experimental part of the study was divided into several stages: separation of mRNA from cells, obtaining cDNA (reverse transcription reaction), PCR in real-time and validation of the test system. Isolation of total RNA from FFT samples was performed using a set of “SV Total RNA Isolation system” according to the manufacturer’s instructions (Promega, USA). Isolation of total RNA from FFPET samples was performed using a set “ReliaPrep FFPE Total RNA Miniprep System” (Promega, USA) according to the manufacturer’s instructions. The concentration of total RNA was determined using a NanoDrop 1000 microspectrophotometer (Thermo Bioscience, USA) (RNA concentration were 15–660 ng/ml). Results For the reverse transcription reaction (RT) and PCR, the main parameters were selected. For RT: RNA incubation time and temperature of the reaction, enzyme concentration in the reaction mix. For PCR: the amount of DNA template, the number of primers, the concentration of magny ions, the concentration of the polymerase. Validation of the developed test system was carried out by comparing the results obtained by RT-PCR with the results of the IHC analysis of the same samples. Statistical processing of the research results was performed using the MedCalc program v.14.12.0 (Microsoft Corp.). Conclusion We have considered modern advanced methods of diagnostic of breast cancer receptor status. It was concluded that the use of RT-PCR in real time technology is the best alternative technology of the IHC, which currently is the standard definition of the expression of ER, PgR, HER2/neu and Ki-67. Prototype of test system for the detection of ER, PgR, HER2/neu and Ki67 proliferative factor in breast cancer samples was designed and optimized by RT-PCR.

Essential medicines for breast cancer in low and middle income countries.

BackgroundBreast cancer is the most common type of cancer among women worldwide. In low and middle-income countries (LMICs), appropriate selection of medicines on national essential medicines lists (NEMLs) is a first step towards adequate access to treatment. We studied selection of systemic treatments for breast cancer on NEMLs and assessed its alignment with treatment guidelines for different types of early and advanced breast cancer. Furthermore, influence of country characteristics on the selection was investigated.MethodNEMLs from 75 LMICs were studied for inclusion of all components of therapy in each stage of breast cancer according to international consensus guidelines. The results were then grouped by income level, WHO region and the NEMLs’ release date. Non parametric tests were used for statistical analysis.ResultsUnlike HER2-targeted therapies (<10 %), aromatase inhibitors (12 %) and taxanes (28 %); tamoxifen and first generation chemotherapeutic regimens (e.g., anthracycline-based regimens) were frequently found in the NEMLs (71–78 %). Consequently, all components of treatment for “Luminal A” early breast cancer and non HER2 overexpressed advanced breast cancer were found on the NEMLs of over 70 % of countries. However, 40 % of the low income countries did not have all the components of therapy for any type of early breast cancer in their NEMLs, and adequate treatment of HER2 overexpressed breast cancer was hardly possible with the current selections. Recent NEMLs were more aligned with the guidelines (p < 0.05). Eastern Mediterranean and African regions less frequently incorporated all components of breast cancer treatment in their NEMLs.ConclusionAlignment of selection with guidelines’ recommendations was inconsistent for different types of early and advanced breast cancer in NEMLs. Regular updates and more attention to clinical guidelines is therefore recommended.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1583-4) contains supplementary material, which is available to authorized users.

Genomic tumor evolution of breast cancer.

Owing to recent technical development of comprehensive genome-wide analysis such as next generation sequencing, deep biological insights of breast cancer have been revealed. Information of genomic mutations and rearrangements in patients' tumors is indispensable to understand the mechanism in carcinogenesis, progression, metastasis, and resistance to systemic treatment of breast cancer. To date, comprehensive genomic analyses illustrate not only base substitution patterns and lists of driver mutations and key rearrangements, but also a manner of tumor evolution. Breast cancer genome is dynamically changing and evolving during cancer development course from non-invasive disease via invasive primary tumor to metastatic tumor, and during treatment exposure. The accumulation pattern of base substitution and genomic rearrangement looks gradual and punctuated, respectively, in analogy with contrasting theories for evolution manner of species, Darwin's phyletic gradualism, and Eldredge and Gould's "punctuated equilibrium". Liquid biopsy is a non-invasive method to detect the genomic evolution of breast cancer. Genomic mutation patterns in circulating tumor cells and circulating cell-free tumor DNA represent those of tumors existing in patient body. Liquid biopsy methods are now under development for future application to clinical practice of cancer treatment. In this article, latest knowledge regarding breast cancer genome, especially in terms of 'tumorevolution', is summarized.