Method for predicting relapse of mammary cancer

FIELD: medicine, biochemical oncology.

SUBSTANCE: in the course of surveying in menopausal women after complex therapy one should state the development of mammary cancer at decreased ratio of estriol concentration to the sum of estrone and estradiol urinary concentrations from 1.68±0.23 in relapse-free patients up to 0.74±0.12 - in patients living without relapses for less than a year, up to 0.65±0.13 in patients living without relapse from 2 up to 6 years and up to 0.50±0.10 in patients with relapse-free period from 6 to 10 years. The innovation provides pre-clinical detection of mammary cancer relapse.

EFFECT: increased accuracy and simplicity of the technique applied.

1 tbl

 

The invention relates to medicine, namely to biochemical research in Oncology, and can be used for a diagnostic study of the occurrence of relapse in menopausal patients with breast cancer after multimodality treatment.

The ability to predict relapse in breast cancer patients in the post period is important in terms of timely correction of tactics of treatment and in this respect represents the current trend in clinical Oncology.

The well-known "Method for the diagnosis of acute myeloid leukemia (see Catini S. and other Histochemical journal, 1997, No. 33, R. 141-151), by using the indicator of the content of histamine in uniform elements of blood (basophils, neutrophils, eosinophils) in patients with myeloid leukemia in the phase of exacerbation and remission. The study established that increasing the concentration of histamine in the blood cells in acute myeloid disease. However, the proposed method does not have prognostic significance. In addition, it was revealed that the increased levels of histamine established for patients with malignant lesions of the hematopoietic system, which limits the use of the results of this diagnostic method.

The well-known "Method for the diagnosis of breast cancer (see Sahtain CENTURIES and other Matters. on Oncology., 1992, Vol.3, 38, No. 4, s) chosen as a prototype, by determining the blood in the monitoring of breast cancer opukholeobrazovanie antigens MSA and CA-125. Found that the progression of the process in most cases, the observed increase in blood concentrations of the two tumor markers. Universal tumor marker, which was found to be in all patients with cancer and would be absolutely specific, as yet unknown. In this regard, with the aim of increasing the information content, requires the definition of two tumor markers. The disadvantage of this method of determining tumor markers, in addition to the above, is the high cost of analysis, which is especially important when multiple repeated during the monitoring of patients after radical treatment.

The aim of the invention is preclinical detection of recurrent breast cancer in patients treated menopausal age.

This objective is achieved in that in the dynamics monitoring menopausal patients with breast cancer after multimodality treatment ascertain the development of recurrent breast cancer by reducing the ratio of the concentration of estriol to the sum of the concentrations of estrone and estradiol in urine with 1,68±0,23 patients without recurrence to 0,74±0,12 in patients lived without recurrence of less than one year, to 0.65±0,13 at ill is x, lived without recurrence from 2 to 6 years and to 0.50±0,10 patients with relapse-free period of 6 to 10 years.

The invention of "a Method for predicting the recurrence of breast cancer" is new, because it is unknown in the field of medicine in biochemical research in Oncology with the aim of pre-clinical detection of disease recurrence in patients with breast cancer in menopausal period after combined treatment.

The novelty of the invention lies in the fact that the dynamics monitoring menopausal patients with breast cancer after multimodality treatment ascertain the development of recurrent breast cancer by reducing the ratio of the concentration of estriol to the sum of the concentrations of estrone and estradiol in urine with 1,68=0,23 patients without recurrence to 0,74±0,12 in patients lived without recurrence (less than 1 year to 0.65±0,13 patients lived without recurrence from 2 to 6 years and to 0.50±0,10 patients with relapse-free period of from 6 to 10 years.

The invention of "a Method for predicting the recurrence of breast cancer is industrially applicable, as may be used in health care, in hospitals with cancer, oncologic dispensaries, cancer research institutes. "A method for predicting the recurrence of breast cancer is as follows.

Onethe endogenous factors, able to influence neoplastic transformation of breast cells and tumor growth is hormonal homeostasis, in particular, the state of the synthesis and secretion of female sex steroid hormones estrogen. Currently, there is reason to believe estrogens cancer risk factors, because it was established that breast cancer is characterized by estrogenozawisimami, and in addition, sex hormones are involved in the activation of several oncogenes that stimulate the proliferation of breast cancer cells (Vessela Nedelcheva Kristensen, Nobuhiro Harada, Tom Kristensen, Anne Zise Brresen-Dale. Genetic polymorphism and variability of the metabolism of steroid hormones: relationship with risk of developing breast cancer. The matters. on Oncology., 2001, t, No. 2, s). The facts determine the feasibility of finding predictors of recurrence for breast cancer among the indicators of this class of hormones, which includes three connections - estrone (e1), estradiol (e2) and estriol (e3).

To this end the study of the level of daily excretion of urine estrone, estradiol and estriol, 23 menopausal patients with breast cancer stage III before treatment and then in dynamic observation of patients within six months to 10 years after combined treatment. The concentration of hormones were determined by conventional biochemical what Ecodom (Savchenko, O.N. The ovarian hormones and gonadotrophic hormones. L., 1967, s-225).

To identify the characteristic features of excretion of estrogens in the development of recurrence of breast cancer was carried out the comparative analysis of indicators in patients who have recurrence of the disease occurred in the period up to one year after completion of treatment (5), from 2 to 6 years (7 people) and from 6 to 10 years after treatment (5 people) with indices in treated patients living in these periods without recurrence, as well as from their original level before the start of remedial measures. Calculate the ratio of the concentrations of estriol concentrations of estrone and estradiol (e3/E1+E2). It is established that regardless of the length of relapse in the post period, the ratio of e3/E1+E2in these patients is statistically significantly decreased as compared with its initial value, and even more compared with the number of treated patients without relapse.

It is important to emphasize that the value of the ratio e3/E1+E2patients with relapse was not dependent on the time of its development and did not differ significantly between all the groups of patients with disease recurrence, averaging 0,74±0,12, 0,65±0.13 and 0.50 in±0.09, respectively.

The data obtained indicate a strong link between the development of relapse and low ratio e3/E1+E2that can be considered as characteristic features of hormonal homeostasis, creating the necessary conditions for recurrence. The existence of closely related relapse of low concentrations of estriol and, accordingly, the lowest of his relationship with the content of estrone and estradiol can serve as a reliable test for the preclinical detection of recurrence of breast cancer when monitoring patients 3 clinical groups. The decrease in the ratio of e3/E1+E2to values less than 1.0 in these patients in any for the duration of the observation period is a sign of an emerging disease recurrence and indicates the need for further examination and commencement of appropriate treatment measures.

The specific examples of the application of the Method for predicting the recurrence of breast cancer patients.

Patient Lytvyn A.F., 1937 birth, asked for help in RNII in January 1992. The tumor in the left breast found for 6-7 months before that, practiced self-treatment (rubbing tumor camphor alcohol).

Upon admission to the hospital for treatment of General condition was satisfactory. Above the light - vesicular breathing, muffled heart sounds, rhythmic. Pulse 76 per minute, BP 130/80 mm RT. Art. the Abdomen is soft, painless. The liver is not enlarged. Physiological functions are normal. Menopause 5 years. The breast is developed correctly. In the lower quadrants of the left breast is palpated dense hilly tumor 6 cm in diameter with incomplete fixation of skin over it with indrawing of the nipple. In the left axillary region is not fully offset dense lymph node more than 3 cm in diameter. When biopsy of the tumor - cytological analysis No. 137-138: fragmentation and complexes detected atypical cells are moderately differentiated carcinoma.

The survey found no signs of metastatic tumors of other organs and systems (lungs, liver, bone, skin).

Was diagnosed with breast cancer with metastases in the left axillary lymph nodes, T3N2M0, phase III, clinical group 2.

Researched content in daily MOC the estrogen - the ratio of e3/E1+E2=1,64.

From 11 to 23 January 1992 the first course of chemotherapy, total entered 75 mg methotrexate 60 mg of doxorubicin, 1600 mg of cyclophosphamide, 2750 mg of 5-fluorouracil. From 13 to 27 February 1992 - 2nd course of chemotherapy in the same doses. 21 March 1992 made surgery radical mastectomy on the left. Histogenesis No. 642535-37 - infiltrating ductal cancer in the breast, axillary, subclavian, subscapularis lymph nodes - metastasis of cancer. 3 through 30 April 1992 postoperative remote gamma-therapy on the path of regional lymph and five courses of adjuvant combination chemotherapy CMF-schema.

At follow-up in March 2003 - the condition is pretty good, no complaints shows signs of local recurrence was not detected: postoperative scar smooth, regional lymph nodes are not enlarged, metastases to distant organs and systems are not defined.

14 March 2003 investigated the levels of estrogen in daily urine, found the content of estrone 6,53 nmol/day, estradiol - 4.0 nmol/day estriol - 16,11 nmol/day. E3/E1+E2=1,53.

Thus, the high value of the ratio of e3/E1+E2combined with the absence of recurrence of breast cancer for over 10 years.

Patient Ivanov M.I., 1941 birth is possible. Case history No. 3446/Y. Asked RNII when they found the tumor in the right breast of 5.5 cm in diameter, axillary lymph node 2.5 cm in diameter. Menopause 2 years.

When biopsy of the tumor detected cell carcinoma. Diagnosed with cancer of the right breast with metastasis to axillary lymph nodes on the right, T3N2M0stage III, group II.

From 25 February to 23 March 1990 conducted preoperative polychemotherapy CMFV scheme, total entered 4 mg vincristine, 100 mg of methotrexate, 6000 mg of 5-fluorouracil, 2800 mg of cyclophosphamide. Tumor and axillary lymph node decreased by 50%. From 23 March to 20 April 1990 - preoperative remote gamma-therapy to the breast and axillary field 40 Gr.

15 may 1990 performed surgery radical mastectomy on the right. Histogenesis No. 231382-385 - infiltrating ductal cancer in axillary lymph nodes metastases. From June 15 to July 13 - postoperative remote gamma-therapy on the path of lymphatic drainage - parasternal and over-subclavian field 40 Gr.

Until February 1999 felt pretty well. Signs of recurrence of the disease was not found. When viewed 25 February 1999 a tumor in the left breast up to 3 cm in diameter under the areola and 4 cm in diameter in the outer quadrants. On the right is acrylaway area metastatic lesion of skin and soft tissue tumor 3 cm in diameter in the course of the postoperative scar at the site of the right breast. When biopsy of the tumor No. 4293-95 - atypical cell carcinoma. Thus, simultaneously diagnosed with recurrent cancer of the right breast and cancer in the second breast.

February 26, investigated the estrogen in daily urine: estrone - 10.2 nmol/day, estradiol - 7.2 nmol/day estriol - 8.9 nmol/day. The ratio of e3/E1+E2or =0.51.

Therefore, the low value of the ratio e3/E1+E2the patient after 9.5 years after radical surgery combined with the development of relapse of breast cancer.

Patient Kuznetsova L.I., born in 1943, the case history No. 11533/20, asked RNII in December 1990, when he discovered the tumor in the left breast about 3.5 cm in diameter. When needle biopsy - cancer cells are not found, therefore the treatment is started with the operation. The duration of menopause 2 years.

11 January 1991 produced lumpectomy followed by mastectomy with axillary-if the lad. Histological analysis No. 294413, 294806-813: infiltrating ductal cancer in infraclavicular lymph nodes - metastasis of cancer. Was diagnosed with breast cancer with metastases in infraclavicular lymph nodes, T2N3M0stage III, group II.

After the operation performed remote gamma-therapy on the path of lymphatic drainage by 40 Gy on each field, and yuantou chemotherapy in CMFV scheme was performed in 4-week mode, until June of 1991.

At follow-up the patient 20-22 October 1992 clinical signs of recurrence of the cancer is not detected. Investigated the estrogen in the urine. Estrone - 7,11 nmol/day, estradiol 5.8 nmol/day estriol - 9.2 nmol/day. The ratio of e3/E1+E2=0,71.

Due to the significant reduction of e3/E1+E2compared with the rate in patients without recurrence of the disease re-appointed turnout for inspection and thorough examination after 1 month. When examining a month were found pockets of hyperfixation radiopharmaceutical in different parts of the skeleton, indicating the appearance of metastases in the bone.

Thus, a significant reduction in the values of e3/E1+E2was a sign of the emergence of metastatic breast cancer patients to their clinical manifestations.

Technical and economic efficiency of the Method for predicting the recurrence of breast cancer" is that on the basis of biochemical studies identify pre-clinical recurrence of breast cancer after multimodality treatment of patients with menopausal age. Prediction of relapse in a certain period of time based on the relative hormone levels of estrone, estradiol and estriol provides exact the spine diagnostics, the simplicity of the study, the minimum cost for biochemical research. Received the prognostic factors for recurrence indicate the need to start the appropriate treatment and help plan the stages of effective treatment.

The way preclinical diagnosis of recurrence of breast cancer, including biochemical study of the biological fluid of the patient, characterized in that menopausal women after complex treatment of breast cancer in dynamics determine the concentration of estriol, estrone and estradiol in urine, calculate the ratio of estriol to estrone and estradiol and when is it 1,68±0,23 ascertain the absence of relapse, and when it is reduced to values 0,74±0,12 patients living without recurrence (less than 1 year to 0.65±0,13 of the patients lived without recurrence from 2 to 6 years, and to 0.50±0,10 patients who have lived without recurrence from 6 to 10 years, state the development of a relapse.



 

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Up!
Table
Dynamics of excretia of estrogens in patients with breast cancer, depending on the presence or absence of recurrence
GroupEstrogens (nmol/day)With the attitude

E3/E1+E2
EstroneEstradiolEstriol
Patients before treatment7,35±0,727,0±0,6919,98±1,681,39±0,21
Relapse
diseases:
in the period up to 1 year7,50±0,774,45±0,458,70±1,120,70±0,12*
from 2 to 6 years9,63±1,055,95±0,5610,15±1,050,65±0,13*
from 6 to 10 years11,38±1,197,14±0,669,31±1,010,50±0,09*
Patients without
relapse (3-I
clinical group)6,58±0,213,78±0,1117,43±1,751,68±0,28
* - statistically significant difference compared with before treatment and 3 clinical group