Method for predicting the development of metachronic mammary cancer

FIELD: medicine, oncology.

SUBSTANCE: one should study the activity of catalase in the tissue of malignant mammary tumor and its perifocal area, and at ratio coefficient of catalase activity in the tissue of malignant mammary tumor to that in the tissue of perifocal area being equal to 1.0 ± 0.2 one should predict the chance for the development of new foci of lesion before their clinical manifestation, that provides necessary treatment in due time.

EFFECT: higher efficiency of prediction.

1 ex, 1 tbl

 

The invention relates to medicine, specifically to Oncology, and can be used for early detection of developing metachronous lesions breast cancer. The increase of the contingent of patients with primary multiple tumors requires the definition of a fundamental positions in the choice of medical tactics, based primarily on the early diagnosis of developing metachronous malignant tumors.

You know the study was to develop guidelines for the identification and genetic predict the development of hereditary forms of cancer of the organs of the female reproductive system. These results, in order to identify individuals with hereditary determination of predisposition to cancer of the organs of the female reproductive system, including metachronous breast cancer (Akulenko L.V. Principles of identification and genetic prediction of hereditary forms of cancer of the organs of the female reproductive system.//1 Congress of oncologists of CIS 3-6 December. Proceedings of the Congress., M., 1996. - P.98).

However, identifying such a way metachronous cancers arise from preventive examinations, medical examinations of persons from high-risk groups should be held for a long time, up to age 55 years. Current economic the conditions do not allow everywhere to organize and conduct adequate clinical supervision for patients.

A known method for predicting the development of metachronous breast cancer based on the study of clinical characteristics of patients (Primary multiple malignant tumors.//Edited by Cisowa VI, Trakhtenberg AH, M, Medicine, 2000. - P.75). These authors include: younger age of the patients at the first detection of the tumor compared with the age of patients with unilateral cancer; less than high first stage of the tumor when it is identified, than in the group of patients with unilateral cancer; dependence on the histological structure of the first tumor.

However, the authors themselves note that cancer in the second breast occurs in patients on the background of significant changes in the body's defense mechanisms, and it is usually diagnosed late because of the loss cancer awareness. All this leads to reduced 5-year survival. In General, the prognosis for metachronous bilateral breast cancer is much worse than with synchronous bilateral.

There is a method of identifying biochemical markers associated with genetically determined breast cancer, we selected as a prototype (Sorokin V.M., Telkama G.M., Ustinov, H.E. and other Clinico-genetic analysis and some indicators of lipid metabolism in breast cancer".//1 Congress of oncologists of CIS 3-6 December. the materials of the Congress., M., 1996. - P.106). The analysis of the levels of total lipids, cholesterol and phospholipids in the serum of patients with primary multiple and solitary breast cancer. Based on previously obtained results on the possible genetic conditions metachronous cancer in patients with an earlier age of onset of tumor growth, the authors conducted a formal genetic analysis of 67 patients primary multiple breast cancer with early disease before 55 years of age (group 1), 45 patients with manifestation of the disease after the age of 55 (group 2) and in 91 patients with solitary breast cancer and early tumor growth after 55 years of age (group 3).

It is established that the accumulation of cancer cases observed significantly more often in families of patients of groups 1 and 2 than that detected in patients 3 groups. Segregation analysis frequency defeat cancer relatives of 1st degree relatives showed that among the patients of the 1st group inheritance of this trait, as cancer in parents and siblings, 25% higher than in the other groups, indicating a higher genetic burden of families of patients of the 1st group. However, as pointed out by themselves, the authors, the levels of segregation frequencies do not correspond monogenic inheritance model tumors in all groups of patients.

In the serum of patients of the 1st group of authors nide what about the higher content of total lipids and lower levels of phospholipids and cholesterol, which is the biological precursor of steroid hormones, in particular estrogen, which allowed the authors to indicate the desirability of further study of the relationship between genetic component and content of lipids in these patients.

However, the correct formal genetic research currently difficult to hold in all patients, given the difficult socio-economic conditions of the present time. A large number of single-parent families and children growing up in orphanages, it is not possible to collect a complete genetic history. The known genetic diversity of points does not allow us to explain the reasons for the development of localised process or the occurrence of clinical forms with multiple lesions.

Another drawback of this study is that changes in the level of these lipids in the blood serum may be associated with a number of associated pathological processes, because it is not specific analysis.

The aim of the invention is the early identification of risk groups for the development of metachronous emerging foci of breast cancer.

This objective is achieved in that in the tissue of malignant mammary gland tumors removed during surgery, and perifocal zone determine the activity of the enzyme catalase and Russ is icyhot the ratio of enzyme activity in the tissue malignant tumor activity in perifocal tissue located tissue. Upon receipt of the ratio above or equal to 1.0±0.2 to predict the possibility of developing metachronous breast cancer.

The invention of “a method for predicting the development of metachronous breast cancer” is new, because it is not known from the level of medicine in the field of forecasting development opportunities of developing metachronous lesions breast cancer. The novelty of the invention lies in the fact that remote in time transactions tissue malignant tumors of the mammary gland and its perifocal zone determine the catalase activity, calculate the value and value of 1.0±0.2 to predict the probability of development of metachronous breast cancer.

In the available sources of information Russia, CIS and abroad indications for a similar method for predicting the development of metachronous breast cancer we have not identified.

The invention is industrially applicable as it can be reproduced and repeated many times in the specialized medical health care institutions.

Under our observation were 20 patients whose admission was diagnosed with a second primary focus-multiple metachronous breast cancer with a gap between the first and second tumor from 2 to 5 years, 420 patients with single localized the process is in the breast. In all patients the diagnosis was verified by cytological analysis: in 67% of patients ductal cancer, 33% of invasive lobular breast cancer is of various degrees of differentiation. All patients surveyed level of catalase activity in tissue removed tumor mammary gland and its perifocal zone by calculating the ratio of enzyme activity in tumor tissue of catalase activity in tissue perifocal zone, the results of which are presented in table No. 1.

Retrospectively found that patients with metachronous process breast cancer ratio of catalase activity in tissue of a second malignant tumor activity of the enzyme in the tissue of the perifocal its area was 1.0±0,2.

Of the 420 patients in age from 39 to 47 years with a solitary breast cancer, treated in the Department of General Oncology, Rostov research Institute, 405 level of the studied parameters was 0.5±0,04, 15 patients he did not differ from values in the group of patients with metachronous primary multiple breast cancer (table 1). The level ratio of catalase activity in tissue malignant tumor activity of the enzyme perifocal zone of the patients did not depend on histotype tumors. These 15 patients were identified in a group of intensive surveillance. One RA is in 6 months they conducted in-depth clinical examination, including ultrasound, echo and mammography,

Table 1.

The ratio of catalase activity in tissue malignant tumors of the breast to the activity of catalase in the perifocal area of the tumor.
The analyzed indicatorPatients metachronous cancerSick solitary cancer
  group 1group 2
Catalase tumor/catalase parity1,1±0,06 (n=20)0,5±0,041(n=405)1,0±0,2 (n=15)
Note: significantly at p<0,05

1 - compared with patients with primary multiple cancer.

Dynamic monitoring of these patients revealed the appearance of 12 of them metachronous emerged foci of breast cancer, confirmed by cytological study periods ranging from 2 to 4 years.

The method is as follows.

A portion of tissue malignant tumors of the mammary gland and its perifocal zone in the amount of 100 mg of each tissue was ground in homogenisator with 1 ml of cold saline. The resulting homogenates were centrifuged for 30 min at 3000 Rev/min the Precipitate was discarded, and supernatant was determined and the activity of catalase.

The process of determining the activity of catalase: in the experimental sample add 2 ml of 0.33% H2O2and 0.1 ml of homogenate of tissue (tumor or perifocal zone); in the control sample instead of hydrogen peroxide, add 2 ml of distilled water in blank sample add 2 ml of 0.33% H2About2and 0.1 ml of distilled water. All samples incubated for 10 min at 37°C. Then all samples add 1 ml of ammonium molybdate and 0.1 ml of 100% trichloroacetic acid. Centrifuged 10 min at 3000 rpm Spectrophotometery at a wavelength of 410 nm. Calculate the activity of catalase by loss of hydrogen peroxide (Korolyuk M.A., Ivanova L.I., Mayorova I.G., Tokarev V.E. Method for the determination of catalase activity.// Lab. case. 1988.No. 1. P.16-18.). Calculate the ratio of catalase activity in tissue malignant tumor activity of catalase in the perifocal area of the tumor.

Upon receipt of the value of 1,0±0,2, the patient had predicted the possibility of developing metachronous breast cancer and took her to the group of intensive observation.

A specific example of the method can serve as an extract from a case history:

Patient P., born in 1929, he enrolled in the Department of General Oncology, RNII 28.01.99 was diagnosed with cancer of the right breast T2N1M0The tumor was located in the lower outer quadrant of the breast. 08.02.99, the donkey sectoral resection of the right breast received urgent histological response - carcinoma, after which the operation took place: mastectomy on Pati right. Histological analysis No. 525446 - infiltrative lobular cancer, tumor metastases in axillary lymph nodes. A study was conducted of the level of catalase activity in tissue removed tumor mammary gland and its perifocal zone, which was equal to 0.9. In the postoperative period, the patient underwent a course of remote gamma-therapy on postoperative scar and area regional lymph flow to the total focal dose of 40 Gy. In a satisfactory condition the patient was discharged from the hospital and identified as intensive monitoring. Once in 6 months ill have conducted in-depth clinical examination, including ultrasound, echo and mammograms.

In August 2002 with a regular clinical examination, the patient was found to education left breast. Held needle biopsy is not indicated the presence of a malignant process. However, given the results of study of the ratio of catalase activity in tissue malignant tumor activity of catalase in the perifocal area of the tumor, the patient was admitted to hospital with a preliminary diagnosis of clinically: metachronous breast cancer, breast cancer T2N0M0for the surveyed what I and treatment. 16.09.02, the patient was performed sectoral resection of the left breast. Received urgent histological analysis carcinoma and performed a mastectomy on Pati left. The histological conclusion No. 27696-98; 28012-21 - infiltrative ductal cancer with invasion of fatty tissue and metastases in lymph nodes no. On postoperative scar and the way regional lymph held gamma-ray therapy to the total focal dose of 40 Gy. In a satisfactory condition the patient was discharged from the hospital. Up to the present time the patient is under medical supervision without signs of distant metastasis.

Thus, the data presented clinical observations illustrate the prognostic value determine the ratio of catalase activity in tissue malignant tumor and its perifocal zone for the development of metachronous malignancies in the breast.

Technical and economic efficiency of the claimed “method of forecasting of development of metachronous breast cancer” allows you to:

- conduct an objective monitor the condition of the patient;

- to take timely measures to ensure new and emerging foci of breast cancer;

to suggest the development of new lesions to their clinical manifestations.

A method for predicting the development of metachronous what about breast cancer, includes the study of catalase activity in tissue malignant tumors of the mammary gland and its perifocal zone, characterized in that when the ratio of catalase activity in tissue malignant tumor of catalase activity in tissue perifocal zone tumors, equal to 1.0±0.2 to predict the probability of development of metachronous breast cancer.



 

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