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Volum 11 Numarul 4, 2005

208 Editorial

In this issue, predominantly focused on breast patology, the tumor biology presentation is welcome. In the chapter General Articles, I. Cotârlã presents BRCA 1 Knockput Mice – Modeling Mammary Tumorigenesis. BRCA 1 gene structure and its functional groups, hereditary risk, production of experimental models, p53 mutations, and possible future therapeutic implications are described.

After almost five years, we meet again about the biannual conferences in breast pathology from Oradea. This journal issue includes the majority of the presentations from the “Biannual Symposium of Cancer: Benign Breast Pathology, Breast Cancer Precursors and Prevention”, held on May 26-28, 2005, at Bãile Felix, Oradea. As expected, the agenda started with the diagnostic theme. A. Ungureanu presents a review of the literature regarding “Breast Cancer Screening” with a focus on mamographic examination. For women with increased mammographic breast density, Angela Chiorean presents an alternative: “Magnetic Resonance Imaging (MRI) and Ultrasound Screening for Breast Cancer in Women with High Risk”. Although the MRI is a promising procedure, its disadvantages allow the high-resolution ultrasonography, that can detect clinical or mammographical occult lesions, to excel. In “The Modern Imaging of Breast Tumors”, Natalia Rotaru presents an analysis of imaging techniques (mammography, ultrasound, magnetic resonance), used for the diagnostic of malignant and benign tumors, used by clinics at two French universities (Henry Mondor University and Saint Louis University Paris) and at the Chişinãu Oncological Institute. For subclinical lesions, the interventional imaging techniques, allow for histopathologic diagnostic and for the surgical intervention within oncological security limits. In Stereotactic Preoperative Needle Localisation“, Carmen E. Lisencu describes a remarkable experience of the “I. ChiricutaOncological Institute, Cluj-Napoca. In the treatments section, A. Eniu presents “Principles of Non-Hormonal Treatment Principals in Benign Breast Pathology”. An important proportion of breast cancer patients respond favorable to simple life style changes (i.e. dietary changes, decrease of fat intake, quitting smoking and methylxanthine. For the minority of patients with persistent symptomatology, the medical treatment with Primula oil, non-steroidal anti-inflammatory drugs, vitaminAand E is recommended. Larisa Ciule presents an alternative therapy in her article “Hormonal Treatment of Benign Breast Pathology”. She emphasizes the individualized approach, based on women’s reproductive periods, and describes the advantages and risks of various hormonal products: estrogen- progesterone oral contraceptives, natural progesterone, and synthetic progesterone, anti­prolactine hormones, anti-gonadotrop agents, anti-estrogen hormones, thyroid hormones, progesteron local treatment. In “Breast Cancer Chemoprevention Trials” article, Cristina Vitoc reviews the most important clinical studies with tamoxifen and non-tamoxifen hormones, which have the purpose of defining the current standard in this field. The clinical practice guidelines, which take into consideration the benefits/adverse effects and cost/efficiency analyses, represent an important tool for the oncologists, providing maximum efficiency and minimal risks, at optimal societal costs.

In the section “Case Studies”, Iolanda Sicoe discuses a patient’s uncommon disease evolution, analyzing the clinical, investigative and therapeutic implications of an “Epidermoid Carcinoma of the Cervix, Stage II.B, Treated with Radiotherapy and Surgery, with Extensive Vertebral and Costal Bone Metastasis”.

In Oncological life in Romania” Dana Cernea, the executive president of the Oncological Society , reviews “The XVth Congress of Romanian Society of Radiotherapy and Medical Oncology”, held on September 22-24, 2005, in Cluj-Napoca. The Congress themes: “The primary tumors of the central nervous system” and “The adverse reactions of the oncological treatments”, brought together valuable experiences of the two Oncological Institutes. Surgery followed by radiotherapy was established as standard treatment for cerebral tumors; however, for specific types of tumors, the place of chemotherapy identification with new molecules was attempted. Short and long term adverse effects of various oncological treatments and modalities to minimize them were discussed.

In the Oncological News” chapter, Ioana Brie discusses the works of the 34th European Radiation Research (ERR) Congress, which was held on September 5-8, 2005, at the Leicester University, UK. She presents the most recent results and the new directions of the radiotherapy and radiobiology research: genetic instability, radio-induced carcinogenesis, normal tissue lesions, DNA damaging and DNA repair, new experimental techniques, bio-dosimetry, radiation physics and radioprotection. A pragmatic aspect regarding the radiobiological practice regulation in the clinical units is presented by I Chereji, who summarizes the works of the annual training for staff with academic degrees from the State Health Department laboratories and ionizing radiation centers. The event held on June 1-2, 2005, at Timişoara.

Cristina VITOC

209 BRCA1 Knockout Mice – Modeling Mammary Tumorigenesis

  1. Cotârlã

Georgetown University, Lombardi Cancer Center, NW Washington, USA

BRCA1 is the first susceptibility gene to be identified in hereditary breast carcinoma on the chromosome 17q21 in 1990. These mutations have a high incidence in the families involved (50-55%) in contrast with the sporadic cases which represent 90-95% from all breast cancers. Through protein-protein interactions, BRCA1 has an important role induced in response to DNA damage. BRCA1 is involved in diverse interactions with tumor suppressors, oncogene products, DNA damage repair proteins, cell cycle regulatory proteins, etc. That point out at a crucial role in many biological pathways and so the lesions of the gene are a potential cause for genomic instability. The expression and the activity of the gene are controlled through methylation, ubiquitinqtion and phosphorylation. The structure of the gene and the functional groups are presented as well experimental mouse models with a single allelic mutation of the BRCA1 gene that have shown many interesting correlations especially with p53, that might have interesting implications for future new therapeutic developments.

Key words: BRCA1 mutations, Hereditary risk, Experimental model.

Radioterapie & Oncologie Medicală, 2005, 4:209-214

215 Breast Cancer Screening

  1. Ungureanu1, D. Ciurescu1,2,

1Braşov County Hospital, Dept. of Oncology Hospital, 2 „Transilvania” University, Faculty of Medicine, Braşov

Breast cancer screening is based on three methods: mammography, self-examination and physical examination. The present review is aiming to evaluate the efficiencies of each of these methods as a screening method. For this we have used trials analyses, guidelines, meta-analyses, studies of the breast cancer screening, studies of the mammography as screening method as well as diagnosis method and prognostic factor.

Key words: Breast cancer, Screening, Mamography

Radioterapie & Oncologie Medicală, 2005, 4: 215-218

219 Breast Cancer Screening with Magnetic Resonance Imaging and Ultrasound in High-Risk Women

Angela Chiorean1, Raluca Roman2, Ildiko Agoston2, Maria Retegan-Turdean3, Larisa Ciule3

1UMPh „Iuliu Haţieganu” Cluj-Napoca, Dept. of Radiology; 2Clinical and Emergency County Hospital Cluj, Dept. of Radiology; 3Clinical and Emergency County Hospital Cluj, Dept. of Oncology

The risk of developing breast cancer is about 10% in general population, and much higher in high-risk women. Although mammography is the main modality in depicting breast cancer in early stage, the presence of fals negative results, especially in women with dense breast, represents a limit of mammography wich led to the use of other complementary techniques such as magnetic resonance imaging (MRI) and ultrasound, very useful in following up for breast cancer of this women at high risc and dense breast. The MRI is the most promissing technique in depicting breast carcinoma in early stage, not being influenced by the dense breast structure, having a high sensitivity, but a low specificity and the existence of some disadvantages of this technique allows ultrasound, because of the existing machines improvements, to find its place in screening this category of women, being able to detect very small tumors, otherwise mammograpycally ocult.

Key words: Breast cancer, Screening, High-Risk Women, Magnetic Resonance Imaging (M. R. I.)

Radioterapie & Oncologie Medicală, 2005, 4: 219-225

226 The Modern Imaging of Breast Tumors

Natalia Rotaru1, V. Jovmir2, V. Machidon2

1UMPh Chişinãu, 2Cancer Institute Chişinãu, Republic of Moldavia

Objectives: morphological and dynamic study of the breast pathology through imagistic methods (mammography, echography magnetic resonance imaging -MRI). Material & methods: 395 patients seen in two French university centers (Henri Mondor and Saint Louis, Paris) and Cancer Institute Chiºinãu (Republic of Moldova). The imagistic techniques are described with details on the MRI (a special emphasis on the dynamic techniques). Results: from the total number of cases 231 were breast cancers, 53 benign tumors, 3 local recurrences after total mastectomy, 54 after conservative treatments and 20 healthy subjects. The study underlines the value of the MRI techniques in differentiating rhe malignant vs benign lesions, and describes the main diagnostic characteristics. In malignant tumors, the contrast uptake is early and intense, with a maximal peak in the first minute. The benign tumors have 3 types of uptake curves: no uptake, exponential uptake and early & intens uptake or blooming effect. The later has a 94% specificity and 73% sensitivity for malignant lesion but the efficacy of MRI can still to be increased by combining several characteristic signs as wash out type of uptake curve, central uptake or uptake intensity > 130% in the first 2 minutes. Comments: a comparative review of international literature and a synthesis of the MRI signs of benign breast pathology are presented. The physiopathology of the blooming effect is described as well the possible errors in interpreting the MRI images are detailed. Conclusions: the imaging techniques have an ewssential role in diagnosis of breast pathology. The advantage of MRI vs mammography and echography is the possibility to complete the morphological analysis of the breast with a dynamic study of the contrast uptake that permit to identify some characteristic traits for malignancy as the blooming and wash out effects or the pattern and the intensity of the uptake.

Key words: Breast cancer, Mamography, Echography, Magnetic Resonance Imaging.

Radioterapie & Oncologie Medicală, 2005, 4: 226-232

233 Stereotactic Preoperative Needle Localization

Carmen E. Lisencu, R. Buigã, C. Lisencu, OrsolyaMezey, Aurora Oltean

Cancer Institute „Prof. I. Chiricuţã”, Cluj-Napoca

Early detection of malignant breast lesions presumes their recognition in infraclinical stages, mostly by using the mammography. Meeting this kind of lesions require a special attitude, which have to result in a complete and correct histopathologic diagnosis, needed for the decision concerning the therapy to follow. A good decision will be reflected by good results expressed through overall survival and the quality of life, assuming the preservation of the breast. Purpose: to describe the advantages of performing a preoperative needle localization in infraclinical breast lesions, with malign suspicion on mammography, using a stereotactic guidance. Methods: from October 2004 to April 2005, in the Institute of Oncology “I. Chiricuþã” Cluj-Napoca, 24 stereotactic preoperative needle localization were performed. The lesions were represented by micro-calcifications (75%), and opacities (25%), that were included in BIRADS category 3, 4, and 5, for mammography diagnosis. A mammograph “Senograph DMR +” was utilized, equipped with: stereotactic plate, computerized unit designed in this purpose, and metallic hook-wire “simple hook”. Results: in all cases the lesion was excised. In one case the procedure had to be repeated, and in three cases an additional excision was needed due to the close margins (in one of this cases a mastectomy has been practiced). 33.3% of the lesions were malign (62.5% in situ carcinomas, 37.5% invasive carcinomas), 20.8% intraductal atypical hyperplasia, all the other lesions excised being benign lesions. In the case of invasive lesions, an axillary lymphadenectomy and adjuvant radiation therapy has been performed. No patient required chemotherapy. There were no adverse reactions or important incidents reported. The cosmetic result was a very good one in the majority of cases. Conclusions: preoperative localization of infraclinical lesions using the stereotactic method is a precise method that results in an accurate and limited surgical act, a complete and correct histopathological analyze, with a minimal disadvantage for the patient.

Key words: Infraclinical Lesion, Preoperative needle localization, Stereotactic method.

Radioterapie & Oncologie Medicală, 2005, 4: 233-241

242 Principles of Non-Hormonal Treatment in Benign Breast Disease

  1. Eniu

Cancer Institute „Prof. I. Chiricuţã”, Breast Tumors Dept., Cluj-Napoca

Benign breast disease represents a conglomerate of nosologic entities, with a variety of clinical presentations. We present in short elements of the pathophysiology, and non-hormonal means of intervention in benign breast diseases. Excluding the presence of malignancy in the breast is the most important procedure, which enables the physician to reassure the patient. Changes in the dietary behaviour, by quitting smoking and eliminating methilxantines, and by diminishing the fat intake, can control the symptoms in an important number of cases. For those patients whose disease is refractory to these interventions, treatment with evening primrose oil, non-steroidal antiinflammatory drugs and vitamins A and E is indicated.

Key words: Benign breast disease, Non-hormonal treatment.

Radioterapie & Oncologie Medicală, 2005, 4: 242-245

246 Hormonal Treatment in Benign Breast Pathology


Cluj Clinical and Emergency County Hospital, Dept. of Oncology

Benign breast pathology includes all non-malignant breast diseases and it occurs most frequently in period of genital activity. It is constituted from a variety of entities, sometimes associated: only functional symptoms without a histological etiology, intensifications of physiological events, single or diffuse benign lesions, which are almost 90% of all cases that are examinated by oncologist. Hormonal treatment is destinated to fibrocyistic mastophaty, galactorrhea, fibroadenoma and most of all to mastalgia that represents the major symptom in bening breast disease (cyclical or non-cyclical). Hormonal therapy is represented by oral contraceptives (“low-dose pills”), progestatives, antiprolactinic agents (bromocriptine and cabergoline), antigonadotrop agents (LHRH agonists, danazol), antiestrogens (tamoxifen), thyroid hormones (tiroxine) and local treatments with progesterone. The therapy must be selected in terms of female reproductive periods and the risks caused by utilization of these drugs.

Key words: Fibrocystic mastopathy, Mastalgia, Hormonotherapy

Radioterapie & Oncologie Medicală, 2005, 4: 246-251

252 Chemoprevention Trials of Breast Cancer

Cristina Vitoc

Cancer Institute „Prof. I. Chiricuţã”, Cluj-Napoca

After more than 13 years of research, the results from the clinical trials on breast cancer (BC) chemoprevention with TAM 20mg/day for 5­year period, in women at high-risk, are available, and may be synthesized in Clinical Guidelines. This paper describes the four major multicentric, randomized, double-blinded, placebo vs. TAM trials, the results of which lead to the approval by the USFDA, in 1998, of TAM chemoprevention (NSABP-1992- 1997; Royal Marsde Trial 1986, 1993; European Institute of Oncology Trial –1992, International Breast Cancer Intervention Study- 1992, 1993). The population size, eligibility criteria, and length of follow-up, as well as the results from each of these trials (relative risks and adverse reactions) are reviewed. Four years later, in 2002, US Preventive Task Force (USPTF) formulated the Clinical Practice Guidelines, indicating that the candidates to chemoprevention should be identified based on a risk / benefits assessment. Another, pragmatic point of view, regarding the high costs the society has to pay for BC chemoprevention, resulting from the cost-effectiveness analysis, justify the selection of high-risk patients for BC chemoprevention with TAM. Several finalized, as well as on-going, non-TAM trials are also reviewed here: MORE (The Multiple Outcomes of Raloxifene); STAR (The Study of TAM and Raloxifen), Efficacy vs. tolerance, RUTH (Raloxifene in the use of the heart); Randomized trial of Fenretinid to prevent second breast malignancy in women with early breast cancer, 1987; IBIS-2 Anastrazol vs TAM; The ovarian suppression with LH-RH for patients with BRCA-1 and BRCA-2 mutations; experimental studies with cyclooxigenaze inhibitors.The conclusions from these studies constitute the basis of the current standard in BC chemoprevention, which provides the physician with a useful tool, and represents, perhaps, a new beginning for our country.

Key words: Chemoprevention, Clinical Guidelines

Radioterapie & Oncologie Medicală, 2005, 4: 252-258

259 Stage IIB Epidermoid Carcinoma of Cervix Treated with Radioterapy and Surgery Extended. Bone Metastases

Iolanda Sicoe1, Maria Radu2, Liliana Resiga1, Viorica Nagy1,3

1Cancer Institute „Prof. I. Chiricuţã”, Cluj-Napoca 2, Sibiu County Hospital, Dept. of Oncology, 3UMPh „IuliuHaţieganu”, Cluj-Napoca

In presents the case of 38 years patient with stage IIB epidermoid carcinoma of cervix, treated by radiotherapy, followed by surgery. After an event-free period about 32 months, the patient experiences bone metastases. The metastatic lesion is extended from pulmonary apex to the dyaphragma, with the invasion of the vertebrae, the ribs and involving at the same time extrathoracic tissues. It is discussed the questions of differential diagnosis and the appropriate treatment of this gross metastases from cervical cancer.

Key words: Cervical cancer, Bone metastases.

Radioterapie & Oncologie Medicală, 2005, 4: 259-262

263 The 15th Annual Congress of the Romanian Society of Radiation Therapy and Medical Oncology. September 22-24, 2005, Cluj-Napoca, Romania

Dana Cernea

264 The 34th Congress of European Radiation Research (ERRR), Septeber 5-8, 2005, Leicester, U.K.

Ioana Brie

266 The Settlement of Radiology Practice in Medical Unit

  1. Chereji


270 TOPIC’S INDEX 2005