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Method for prediction of effectiveness of neoadjuvant automyelochemotherapy in patients with recurrent breast cancer

IPC classes for russian patent Method for prediction of effectiveness of neoadjuvant automyelochemotherapy in patients with recurrent breast cancer (RU 2393484):
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FIELD: medicine.

SUBSTANCE: prior to begin the therapy, the patient's blood is tested for oestradiol concentration. If the concentration is 18.40 to 29.40 nmol/l, tumour size loss after the neoadjuvant automyelochemotherapy by 67-70% is predicted, that is a partial regress of the tumour, while oestradiol concentration 208.50 to 1541.0 nmol/l enables to predict the tumour size loss by 5-45% that is process stabilisation.

EFFECT: use of the invention allows determining sensitivity of the recurrent breast cancer to the neoadjuvant automyelochemotherapy for an individual correction of treatment policy in patients with said pathology.

1 tbl, 3 ex

 

The invention relates to medicine, namely to biochemical research in Oncology, and can be used for the individualization of drug treatment of recurrent breast cancer on the basis of biochemical parameters.

Chemotherapy is an integral part of complex treatment of patients with malignant neoplasms. However, the actual problem along with the toxic effects of chemotherapy remain unpredictable until the end of treatment marked differences in the degree of sensitivity of the tumor to the drug effects for some patients. In this regard, one of the important directions of research in Oncology at the present stage is associated with the individualization of drug treatment, which is based, in particular, the use of biochemical indicators that can function as predictors of tumor response to the planned anti-tumor effect.

A known method for predicting the duration of recurrence-free period when radiation and chemoradiation therapy in patients with breast cancer (S.D. Ivanov and other Matters. on Oncology. 2008, No. 1. P.34). The authors of the study were determined in the patients before treatment radiosensitivity of DNA largest S-index, reflecting the radiosensitivity of all DNA-containing blood cells and DNA in the plasma after the test exposure ex vivo. Authors who becomes a positive linear relationship between indicators of the radiosensitivity of DNA and duration of recurrence-free period when different modes chemoradiation therapy. According to the results of the study patients with the magnitude of the S-index is more than 0,95 had significantly better disease-free survival than patients with an index value lower than 0,95. This index, the authors propose to use to predict before treatment the individual effectiveness of planned chemotherapy. The disadvantage of the proposed method for the individualization of treatment tactics is the impossibility of its application for predicting the effectiveness of chemotherapy in patients with recurrent breast cancer and, furthermore, the method evaluates the impact on the duration of recurrence-free period of the combined action of two anticancer agents, radiation and chemotherapy.

There is a method of forecasting resetstatistics and overall survival of patients with recurrent breast cancer, we selected as a prototype (Lopez-Guerrero lose A. et al. Cancer, 2006, t. S). The authors investigated the contents of the oncoprotein HER2 tissue recurrence of breast cancer using the Hercep Testa and method of fluorescent hybridization. It was found that amplification of this protein in the tissue of tumor recurrence is an adverse prognostic factor is the increase in the concentration of protein was negatively correlated with life expectancy of patients without metastases and their total duration of the LM is neither. Based on this, the authors propose to use an indicator of the level of HER2 tissue recurrence of breast cancer as a prognostic factor. The disadvantage of the proposed method is lack of communication specified index with the assessment of tumor response to radiation therapy, and therefore it cannot be used to individualize treatment plans for patients with recurrent disease.

Screening indicators able to perform the function of predictor factors of the effectiveness of chemotherapy, it is advisable to conduct additional biochemical compounds that play a role in the Genesis and development of tumors. For hormone-dependent organs, including the mammary gland, such compounds are sex steroid hormones, in particular the most active estrogen, estradiol.

The aim of the invention is a predictor to determine the sensitivity of recurrence of breast cancer to neoadjuvant automalaxoare for individual correction of tactics of treatment of patients with this pathology.

This goal is achieved by the fact that patients with relapse of breast cancer prior to treatment to determine radioimmunoassay method blood levels of estradiol and its concentration is 18.40 from to 29,40 nmol/l predict a decrease in tumor size under the influence of neoadjuvant the Noah of automalaxoare at 67-70%, according to the who recommendations on the evaluation of chimiotherapie is assessed as partial regression of the tumor, and when the concentration of estradiol from 208,50 to 1541,0 nmol/l predict a reduction in the size of tumors at 5-45%, which is considered as a stabilization process.

The invention of "a Method for predicting the effectiveness of neoadjuvant automalaxoare patients with relapse of breast cancer" is new, because it is unknown when the biochemical research in Oncology, related to the individualization of drug treatment of patients with breast cancer.

The novelty of the invention lies in the fact that prior to treatment to determine the blood levels of estradiol and its concentration is 18.40 from to 29,40 nmol/l predict a decrease in tumor size under the influence of neoadjuvant automalaxoare at 67-70%, a partial regression of the tumor, and when the concentration of estradiol from 208,50 to 1541,0 nmol/l predict a decrease in tumor size at 5-45%, i.e. the stabilization process.

The invention is industrially applicable as it can be used in health care, in hospitals, in research Institute of Oncology and oncologic dispensaries.

The invention of "a Method for predicting the effectiveness of neoadjuvant automalaxoare in patients with recurrent breast cancer" done which is as follows:

The study was conducted in 6 patients with local recurrence of breast cancer in the postoperative scar. Before treatment in the blood of patients was determined by the content of estradiol radioimmunoassay method using standard test kits of Immunotech (Czech Republic). The first stage of treatment of the patients was holding automalaxoare. Her course consisted of twice with an interval of 7 days of administration of the drugs doxorubicin, 5-fluorouracil and cyclophosphamide in total doses of 100 mg, 1500 mg and 1200 mg, respectively. Before the introduction of the preparations were incubated for 30 minutes at 37°C with bone marrow suspension of the patient obtained from the iliac bone. The impact of neoadjuvant automalaxoare tumor was evaluated by changing the size of the tumor, which was judged by the results of the ultrasound. Found that the decrease in tumor size in response to drug exposure varied among the examined patients within wide limits, ranging from 5 to 70%. When comparisons post tumor size with the content of estradiol in patients before therapy stated that the most pronounced decrease (67-70%) occurred in patients with a low level of hormone in the blood, formed is 18.40 and 29,40 nmol/l According to who recommendations for the evaluation of the effectiveness of chemotherapy such reduction nooob is adowanie considered as partial regression of the tumor. In contrast, in women with initially normal or higher than normal concentrations of estradiol, formed from 208,50 to 1541,0 nmol/l at norm 230,94±14.0 nmol/l, reduction of tumor response to treatment ranged from 5 to 45%, which is testified only about the stabilization process. The obtained data allow to consider background levels of estradiol in the blood of patients with relapse of breast cancer as a prognostic factor for the effectiveness of the applied method neoadjuvant drug therapy in these patients (see table). The largest concentrations of circulating estradiol, thus, should be considered when planning for adequate treatment tactics for patients with recurrent disease.

Table
The level of estradiol in the blood of patients with relapse of breast cancer and the effectiveness of chemotherapy
The concentration of estradiol The decrease in tumor size
(nmol/l) after chemotherapy (%)
1. 29,4 67
2. 18,4 70
3. 208,5 5
4. 234,8 45
5. 660,0 25
6. 1541,0 29

Examples of specific clinical application, "Method for predicting the effectiveness of neoadjuvant automalaxoare patients with relapse of breast cancer".

Clinical example 1

Patient F. Ko, born in 1936, IB No. 5221/h, was admitted to the Department of soft tissue tumors, bone and breast cancer, RNII 11.01.07 was diagnosed with cancer of the right breast pT2N3M0, St. III, the state after complex treatment in 2001, the Recurrence of breast cancer in the soft tissues of the postoperative scar, Cllr.

The process in the rumen cytologically verified (CA No. 11632-633)found groups of carcinoma cells.

The local status before treatment: in the left breast pathological entities is not defined. In place of the right breast p/o scar, above which is about 2 cm, in the soft tissues is determined by the tumor to 6.0 cm in diameter, dense consistency, without clear to the tours, painless to palpation, motionless.

The skin over the tumor is not changed. Data ultrasound examination before treatment: slightly above the scar in the soft tissues lazerette MultiSite hypoechoic education with an uneven contour to 58×64 mm - diffusely heterogeneous echo patterns, color Doppler mapping of weak intra-period. the blood flow.

Conclusion: a multi-site formation in the soft tissues of the chest wall on the right (echographically reci).

12.01.07, estimation of blood estradiol concentrations was - is 18.40 nmol/L.

With 16.01.07, the patient underwent a course of neoadjuvant automalaxoare drugs doxorubicin, 5-fluorouracil, cyclophosphamide, with the inclusion of bone marrow suspensions obtained from the rear wing of the Ilium. Before the introduction of chemotherapy were incubated with bone marrow suspension in an incubator for 30 minutes at 37°C.

Treatment the patient satisfactorily, there were no complications. 14 days after the end of drug therapy the patient was performed control ultrasound, found a decrease of tumor size by 70%. 12.02.07, the patient underwent an operation - excision of the formation of soft tissue p/o scar. HA No. 921919-921 - taken in the material metastasis infiltrating ductal cancer focal hyalinosis.

Thus, the patient and with the original concentration of estradiol in the blood is 18.40 nmol/l neoadjuvant automalaxoare was accompanied by a decrease in tumor size by 70%.

Clinical example 2

Patient K-m, born in 1942, IB No. 12946/, Diagnosis at admission: cancer of the right breast, the state after the combined treatment in 1995, the Recurrence of breast cancer in the soft tissues of the postoperative scar, CL gr. The process was cytologically verified (CA No. 6609-10) is Detected complexes of carcinoma cells.

Local status before treatment: the right breast p/o scar, swelling up to 10 cm in diameter, dense consistency, without distinct outlines, motionless, impacted, painless on palpation. Data ultrasonography before treatment: mastectomy on the right. Pronounced fibrosis in the outer and upper parts of postoperative scar in the right axillary area. In the soft tissues of upper parts of the chest wall on the right is defined hypoechoic solid education, heterogeneous structure, with irregular contours, sizes 5,02×4,45 cm, with dopplerography is logged pathological hypervascular arterio-arterial blood flow in the tumor. In the right axillary region in a deep divisions are determined by a single hypoechoic enlarged lymph nodes size to 1.0, see the medial and upper axillary area on the right is defined stenosis, infiltration of the outer branches of arteries and veins with the sprouting of blood vessels of the tumor in the area of adventitia, without invasion to illuminate the great vessels.

24.04.07) underwent determination in blood estradiol concentrations was 208,50 nmol/L.

25.04.07, had started a course of neoadjuvant automalaxoare drugs doxorubicin, 5-fluorouracil, cyclophosphamide, with the inclusion of bone marrow suspensions obtained from the rear wing of the Ilium. Before the introduction of chemotherapy were incubated with bone marrow suspension in an incubator for 30 minutes at 37°C.

Treatment the patient satisfactorily, there were no complications. 14 days after the end of drug therapy the patient was performed control ultrasound, found a decrease of tumor size by 5%.

25.05.07, the operation was performed in a volume - excision tumor soft tissue postoperative scar. The results of histopathological studies No. 943318-321. In fibrous tissue, adipose tissue, striated muscle - metastatic cancer of glandular-solid structure (infiltrating ductal cancer).

Thus, the patient with the original concentration of estradiol in the blood 208,50 nmol/l neoadjuvant automalaxoare was accompanied by a slight decrease in the size of the tumor (5%), said stabilization process.

Clinical example # 3

D-Ko, born in 1945 breast Cancer pT2N2M0, St IIIA. Condition after complex treatment in 2004, the Multiple is the recurrence of breast cancer in the soft tissues of the postoperative scar, CL gr. The process in the rumen was cytologically verified 16.01.07, (CA No. 1114-17) - carcinoma.

The local status before treatment: left breast cancer postoperative scar in the soft tissues which defined the tumor to 4.0 cm thick consistency, without distinct outlines, in the middle third postoperative scar tumor to 2.0 cm, without distinct outlines, thick consistency.

Data ultrasound examination before treatment from 16.01.06, In the medial part of the postoperative scar hypoechogenic education with linear strands. 2.4×3,3 see In the middle third hypoechoic education 1,1 see Regional l/have not increased.

Conclusion: reci in the projection of the postoperative scar.

30.01.07, estimation of blood estradiol concentrations was 660,50 nmol/L.

31.01.07, started a course of neoadjuvant automalaxoare drugs doxorubicin, 5-fluorouracil, cyclophosphamide, with the inclusion of bone marrow suspensions obtained from the rear wing of the Ilium. Before the introduction of chemotherapy were incubated with bone marrow suspension in an incubator for 30 minutes at a temperature of 37C.

Treatment the patient satisfactorily, there were no complications. 14 days after the end of drug therapy the patient was performed control ultrasound, found a decrease of tumor size is 25%.

28.02.07, the operation was performed in a volume - excision tumor soft tissue postoperative scar. The results of histopathological studies: HA No. 9252281-86. Infiltrating ductal cancer in fibrous and adipose tissue, vascular invasion (relapse). In adipose tissue foci of fibrosis.

Thus, the patient with the original concentration of estradiol in the blood 660,50 nmol/l neoadjuvant automalaxoare was accompanied by a decrease in tumor size by 25%.

Technical and economic efficiency "Way

predicting the effectiveness of neoadjuvant automalaxoare patients with relapse of breast cancer" is that predicting the effectiveness of treatment on the basis of biochemical parameters allows to determine the sensitivity of recurrence of breast cancer to neoadjuvant, automalaxoare for individual correction of tactics of treatment of patients with this pathology.

A method for predicting the effectiveness of neoadjuvant automalaxoare patients with relapse of breast cancer, including biochemical, characterized in that the patients before treatment to determine the blood levels of estradiol and its concentration is 18.40 from to 29,40 nmol/l predict a decrease in tumor size under the influence of neoadjuvant autokilometer the AI at 67-70%, that is, the partial regression of the tumor, and when the concentration of estradiol from 208,50 to 1541,0 nmol/l predict a decrease in tumor size at 5-45%, i.e. the stabilization process.

 

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