[Influence of neoadjuvant therapy on VEGFR-2 levels in tumor and blood serum from breast cancer patients].

Degree and trends of changes taking place in the angiogenic factors VEGF and VEGFR-2 were studied in cytosols and blood serum sampled from breast cancer patients in the course of neoadjuvant therapy. Such evidence was evaluated vis-alpha-vis basic indices for clinic-morphological features of the disease. The study included 30 cases of locally-advanced tumors. Our results pointed to an influence produced by preoperative therapy on the levels of angiogenic factors both in tumor and serum. However, trends of development of such parameters are different and independent of therapeutic modality. Correlation was established between VEGF and VEGFR-2 levels in residual tumor, on the one hand, and degree of therapeutic pathomorphosis, on the other.

[The use of 1H-NMR spectroscopy for the prognosis of overall survival of breast cancer patients].

The pool of low-molecular metabolites in untreated breast cancer patients was investigated by high-resolution 1H-NMR spectrometry. It was found that the delta = 1.75 m.d signal can serve as a prognostically significant negative factor. Beside other markers, its absence in tumor sample extracts may indicate favorable prognosis.

[Contemporary treatment methods in primary breast carcinoma]. / Sovremennye printsipy lecheniia pervichnogo raka molochnoi zhelezy.

Surgery for primary breast carcinoma is the method of choice. The use of the so-called conservative (sparing) techniques greatly improves late outcomes. Thus, five-year survival in patients with early cancer stages after radical resections followed by radiation therapy was 87.6% and relapse-free survival was 80.4%. Six courses of adjuvant chemotherapy in 400 patients with Stage IIb provided 5-year overall survival in 81.3% of cases and relapse-free survival in 73.7%. Neoadjuvant chemo- and radiation therapy followed by radical mastectomy preserving both breasts and adjuvant chemo- and hormone therapy increases five-year overall and relapse-free survival up to 71.6 and 41.6%, respectively. The promises of improving therapeutical outcomes are associated with early and, in some cases, preclinical diagnosis.

[Tumor markers CEA, CA 15-3, MCA, TPA, ferritin and PTH in the diagnosis and monitoring of primary breast cancer]. / Opukholevye markery REA, CA 15-3. MCA, TPA, ferritin i PTG v diagnostike i monitoringe pervichnogo raka molochnoi zhelezy.

Sera from 254 females were assayed for markers of tumor growth, such as cancer embryonal antigen (CEA), breast cancer-associated antigen (CA 15-3), mucinoid cancer antigen (MCA), ferritin, tissue polypeptide antigen (TPA), parathyroid hormone (PTH) by means of monoclonal antibody kits by using radioimmunoassay and enzyme immunoassay. Forty nine patients were diagnosed as having benign breast neoplasms, 171 patients were admitted to the clinic for primary breast cancer of varying severities, 34 patients without any breast abnormalities and somatic diseases comprised a control group. There was a close correlation between the higher levels of markers and the stage of a tumorous process. Various therapies-induced decreases in the levels of the markers serve as an objective criterion for the efficiency of the latter. Steady increases in the mean concentrations of tumor markers in the intra- and post-therapeutical periods are indicative of an extremely poor prognosis in this group of patients.

[Expression of epidermal growth factor receptors and their ligands in malignant tumors of the breast]. / Ekspressiia retseptorov épidermal'nogo faktora rosta i ikh ligandov v zlokachestvennykh opukholiakh molochnoi zhelezy.

Epidermal growth factor receptors (EGFR) have been investigated in the tumors of 166 breast cancer patients and concentrations of their ligands (alpha-TGF and EGF) were measured in 104 tumors by radioimmunoassay. EGFR and both growth factors were simultaneously detected in 18% and EGFR and one of the ligands were found in 11%. There were trends to higher frequency of EGFR expression in advanced tumors, in ductal and lobular infiltrative cancers with high grade of malignancy and in estrogen receptor negative breast cancers. A possible role of the parameters studied in the prediction of breast cancer and in the choice of therapy is discussed.

[Evaluation of the effectiveness of tamoxifen in malignant breast tumors: new approaches]. / Opredelenie éffektivnosti deistviia tamoksifena na zlokachestvennye opukholi molochnoi zhelezy: novye podkhody.

It has been shown that 17 beta-estradiol stimulates the cycle of phospholipid conversion in the breast tumor cells. The action of tamoxifen on antiestrogen cells is not limited by weakening the stimulating effect of 17 beta-estradiol on the exchange of intracellular phospholipids, but gives rise to a more complicated pattern of changes: inhibited incorporation of 32-P-phosphatidylcholine (PC) and activated exchange of phosphoinositides (PI). The experimental findings of 53 breast tumors have indicated that in 47.2% of cases Tamoxifen alters the PC/PI ratio and causes its 2-fold increase. Such alterations have been found to be induced by the ability of Tamoxifen to suppress the activity of protein kinase C that regulates the synthesis of PC and PI. It is suggested that the revealed capacity of Tamoxifen to change the rate of intracellular phospholipid conversion might be used for evaluating the efficiency of this agent on malignant tumors.

[DNA ploidy of tumor cells in prognostication of the course of malignant neoformations]. / Ploidnost' DNK opukholevykh kletok v prognozirovanii techeniia zlokachestvennykh novoobrazovanii.

DNA flow cytometry (FCM) was used for the clinical prognosis in patients undergone surgical removal of a tumor. The relationship between the structure of the tumor cell population (ploidy) and the frequency, time of a relapse onset (recurrence, metastasis), and the survival length were analyzed. All the patients had presurgical treatment (chemo- and/or radiotherapy). The patients were followed up for 5 to 9 years after surgery. The groups under study included 177 cases of breast cancer, 81 cases of larynx cancer, and 62 cases of colon cancer. Among the patients, the onset of a relapse was earlier and occurred more frequently in cases of aneuploid tumors among the patients regardless of the tumor type. In patients with aneuploid tumors, the most unfavorable prognosis was inherent in the hyperdiploid and multiclonal ones. The probability of 5-year survival for patients with aneuploid tumors appeared to be 20-30% lower than that in cases of diploid ones.

[The effect of steroid hormones and tamoxifen on the rate of phospholipid turnover in the cells of uterine and breast tumors]. / Vliianie steroidnykh gormonov i tamoksifena na skorost' obrashcheniia fosfolipidov v kletkakh opukholei matki i molochnoi zhelezy.

The cycle of phospholipid turnover has been found to be under the negative control of hormonal cytostatics (progesterone) and under the positive control of proliferation stimulants (17 beta-estradiol, epidermal growth factor). Specific changes in the synthesis of phospholipids are shown when tamoxiphen, an antiestrogen and an inhibitor of protein kinase C, was used. The findings suggest that changes in the turnover rate of phospholipids are one of the key stages of steroid action on target cells and may be regarded as an additional criterion of tumor genetic sensibility.

[The experience in the use of DNA flow cytometry to predict the natural history of malignant neoplasms]. / Opyt primeneniia protochnoi DNK-tsitometrii dlia prognozirovaniia techeniia zlokachestvennykh novoobrazovanii.

The aim is to study the pattern of a cell population (ploidy) and to evaluate the latter's significance in the prognosis of different carcinomas. A total of 467 patients with primary carcinomas of the breast (n = 177), lung (n = 88), head and neck (n = 140), and colon and rectum (n = 62) were examined. All the patients underwent surgery alone or in combination with radiotherapy (X-ray)/chemotherapy. A follow-up lasted 6 to 120 months. DNA was measured in the operative tumor tissue specimens by using an ICP-22 flow cytometer. Diploid and aneuploid cancers occurred in 20.4-53.6 and 43.6-79.6% of cases, respectively. The frequency of recurrences was mainly associated with aneuploidy and it was more than thrice higher than that with diploidy (21.0-43.2 versus 4.5-14.4%). Five-year survival was twice worse in patients with aneuploid tumors than in those with diploid ones. The survival rates after one operation, preoperative, and postoperative radiation therapy was greater in patients with diploid tumors than in patients with aneuploid ones. Thus, DNA-ploidy of the study neoplasms is of high informative value in predicting the course of a tumorous process and in choosing treatment policy on an individual basis.

[The specificity of expression of molecular biological markers in tumors of the mammary gland]. / Osobennosti ékspressii molekuliarno-biologicheskikh markerov v opukholiakh molochnoi zhelezy.

Data are described on a retrospective immunohistochemical study of the Ki-67, PCNA, Bcl-2, BAX, BclX and VEGF expression in tumors of two groups of patients with breast cancer (BC) and with the favorable and unfavorable clinical courses. A reliably high level of VEGF expression was detected in tumors of patients with an early BC relapse. Apart from VEGF, higher levels of the Ki-67 and PCNA expression were registered in tumors of the discussed patient's category. It can be suggested that the expression parameters of VEGF, Ki-67 and PCNA in the primary tumor can be made use of in evaluating the BD prognostications or describing the features of high-risk groups with a high probability of early disease relapses.

[The role of epithelial antigens in diagnosis and staging of breast cancer]. / Rol' épitelial'nykh antigenov v diagnostike i stadirovanii raka molochnoi zhelezy.

The study of different epithelial antigen expression has been performed in 183 breast cancers. In 73 patients regional lymph nodes were studied as well. Panepithelial antigen Egp-34 (Mab HEA-125) was expressed in 100% of primary tumors and metastases. Antigen MUC-1 (Mab ICO-25) was identified in 93% of breast cancers. Monomorphic type of expression in tumor cells was typical for Egp-34, MUC-1 being in certain cases expressed as a proportion of cells. Additional immunohistochemical study of regional lymph nodes with Mab to Egp34 and MUC-1 provides a 10% increase in the rate of breast cancer metastases detection compared to histological examination alone. The carcinoembryonic antigen (CEA) was useful in identification of metastases only in CEA-positive breast cancers.

[Multicentric cancer of the breast]. / O mul'titsentricheskom rake molochnykh zhelez.

Multicentric breast carcinoma was identified in 3.7% of 119 patients operated on at the Center Clinics. A slow growth, small size of tumors and infrequent lesions in the regional lymph nodes were registered. A correlation between the degree of malignancy and the number of tumor nodes in breast tissues was established. The best end results--a survival rate of 16.8% at 10 years--were obtained after radical mastectomies. A classification of multicentric breast cancers is suggested.

[Neurological disorders in patients with metastases of breast cancer to the cranial bones]. / Nevrologicheskie rasstroistva u bol'nykh s metastazami raka molochnoi zhelezy v kosti cherepa.

The paper presents data on 52 cases of breast cancer disseminated into cranial vault bones (2 into the orbit). Metastases into the brain (11) and meninges (6) were detected in 17 cases with the aid of computed tomography of the brain and examination of cerebrospinal fluid. The latter cases were not included into the study group. Metastases into cranial bones were identified by craniography and scanning of the skeleton. Half the patients (18 out of 35) revealed the following neurologic syndromes which were determined by the site of metastases into cranial vault bones and tumor growth pattern (into cranial cavity or soft tissues of the head): lesions in ramus primus nervi trigemini, greater occipital nerve, migraine, pseudotumorous and pseudoencephalitic syndromes. Cases of such neurologic disorders require an all-round examination including ophthalmooscopy, EEG, computed tomography of the brain, craniography and scanning of the skeleton.

[The immediate results of the combined treatment of stage-III breast cancer]. / Neposredstvennye rezul'taty kompleksnogo lecheniia raka molochnoi zhelezy III stadii.

Immediate results of complex treatment were studied in 185 patients with stage IIIa, b (T1-2N2M0 and T3N0-2M0) nodular breast cancer. Preoperative chemoradiation treatment incorporated microwave procedure. All patients had been radically mastectomized after Patey. The analysis included assessment of response and degree of treatment-induced pathomorphosis, versus age, menstrual function, site and histologic structure of tumor. Microwave procedure proved an effective component of complex treatment of stage IIIa, b breast cancer. Good results were obtained in patients aged 51-60 suffering adenocarcinoma.

[The role of tumor receptor status in choosing adjuvant therapy for breast cancer patients of reproductive age]. / Rol' retseptornogo statusa opukholi v vybore ad''iuvantnoi terapii u bol'nykh rakom molochnoi zhelezy reproduktivnogo vozrasta.

Estrogen (ER) and progesterone (PR) receptor levels were assayed in primary tumor samples from 271 premenopausal patients suffering T1,2N1M0 (stage II) breast cancer. Four clinical groups were identified according to steroid receptor levels in which results of adjuvant treatment (chemotherapy or complex treatment) were assessed. ER and PR positivity was associated with longer disease-free and overall survival. Adjuvant hormone therapy proved beneficial in ER+PR+ tumor patients. The latter group was also characterized by a lower relapse rate, particularly, in those aged over 40. It is recommended that: (1) T1,2N1M0 breast cancer patients be given adjuvant chemotherapy whatever tumor receptor status, (2) these patients should not be given adjuvant hormone therapy unless tumor receptor status has been established since prophylactic oophorectomy and subsequent hormone therapy are not justified for operable breast cancer, (3) complex therapy be administered to premenopausal patients aged over 40 years with ER+PR+ tumors only, and (4) PR-positivity be considered a good predictor of hormone sensitivity of cancer.

[Current approaches to hormonal therapy of breast cancer in men]. / Sovremennye podkhody k gormonoterapii raka molochnoi zhelezy u muzhchin.

The content of steroid hormone receptors was measured in 22 men with mammary gland carcinoma. The content of estrogen receptors appeared high in both primary tumor and cancer metastasis. It was not dependent on the process extent or patients' age. In some cases the tumor remained "receptor-positive" after preoperative treatment. The data obtained indicate a possibility of a sound approach to the hormonal therapy of men with mammary gland carcinoma.

[The practical use of the determination of relative 32P accumulation in the tumor in breast cancer]. / Prakticheskoe ispol'zovanie opredeleniia otnositel'nogo nakopleniia 32P v opukholi pri rake molochnoi zhelezy.

The level of relative accumulation of a 32P radionuclide was measured in 180 tumor samples obtained from 148 patients with stage I--IV breast cancer. Mean initial relative accumulation level (IRAL) was 1477 +/- 174% whereas that following effective conservative treatment (posttreatment) (PRAL)--486 +/- 81% (P < 0.01). The prognostic value of IRAL was established: in a group of stage III breast cancer, those with a high IRAL survived 2 years with no evidence of disease in 55.1 +/- 12.1% whereas those with a low IRAL--in 94.1 +/- 5.7% (P < 0.02). In patients undergoing conservative treatment, low PRAL proved predictive of complete response while high PRAL--of tumor progression. In patients with stage III breast cancer who had responded to preoperative treatment and had had a low PRAL, two-year locoregional recurrence rate was only 13% as compared to 68% in a similar group of patients with high PRAL (P < 0.02).

[Metastases in the axillary lymph nodes as the first manifestation of cancer]. / Metastazy v podmyshechnye limfaticheskie uzly kak pervoe proiavlenie opukholevogo zabolevaniia.

The paper discusses the procedures used for detecting primary tumor in 27 patients who presented with regional lymph node involvement. Both clinical data and those of the histologic and electron microscopic examination of tissue samples from the breast and involved lymph nodes were used. The examination established neoplasm in 15 cases and failed in 12. Most commonly, axillary lymph node metastases resulted from breast carcinoma. Relevant procedures for examination and treatment were developed versus type, size and site of tumor.

[An experience with the conservative treatment of breast cancer in middle-aged and elderly women]. / Opyt konservativnogo lecheniia raka molochnoi zhelezy u zhenshchin pozhilogo i preklonnogo vozrasta.

Advantages of conservative treatment of inoperable breast cancer in old and elderly age are discussed on the basis of an analysis of data on 30 cases. A split-course radical radiotherapy was combined with a prolonged tamoxifen treatment. Complete regression of tumor was registered in 16 out of 23 followed-up patients, while more than 50% regression--in I case. The study should be continued.

[Natural antitumor cytotoxicity of the whole blood of donors and cancer patients]. / Estestvennaia protivoopukholevaia tsitotoksichnost' tsel'noi krovi donorov i onkologicheskikh bol'nykh.

Natural antitumor resistance of cancer patients and healthy subjects was studied on the basis of whole blood natural cytotoxicity (WBNC) assay. A correlation between WBNC and mononuclear leukocyte cytotoxic activity in healthy donors was established (r = 0.912; p less than 0.001). WBNC levels in colonic, breast and gastric cancer patients were decreased as compared with healthy controls.