Description

Title: breast cancer detection kit or device and detection method

Technology areas

[0001]

This invention relates to how to detect breast cancer, said miRNA expression amount measuring Kit for detection of breast cancer, including specific miRNA in the subjects used to test for the presence or absence of breast cancer incidence, and nucleic acids that can be merged into specific or device, and the nucleic acids including.

His innovations.

[0002]

Consists of breast milk ducts carry separate milk from mammary gland and mammary glands produce milk separate leaflets, leaflet and from FAT to support them. 90% of breast cancer from the milk ducts and an breast cancer of about 5-10% from the small leaves that occur (non-patent literature 1). National Research Development Corporation National Cancer Research Center for cancer of cancer in Japan to disclose information center 2011 up 12731 people according to mortality statistics, the number of breast cancer deaths, affected one in 14 Japanese women and cancer incidence in women with the most area. Also, has been in the United States, eight people at the rate of one women develop breast cancer, breast cancer incidence estimates in 2014, up to 232670 and fatality about 40000 people are (non-patent literature 1).

[0003]

Breast cancer progression is provided for non-patent literature 2 the size of the tumor and invasive, lymph node metastasis, distant metastases and classified as stage 0, IA, IB, IIA, IIB, IIIA, IIIB, IIIC, IV. In stage 0 and stage 1 breast cancer five-year relative survival rates of cancer progression depends on, 100% in stage 2, 93% in stage 3 at 72%, stage 4 and 22% reported (non-patent literature 1). Therefore, providing the lead to improve the survival rate of breast cancer be found early, to enable early detection means highly coveted.

[0004]

Breast cancer treatment is surgery in principle, progression and metastasis, General conditions, breast cancer classification combination drug therapy and radiation therapy. In some cases, especially stage 1 or 2 early breast cancer, in combination with radiation therapy breast-conserving therapy is available (non-patent literature 1).

[0005]

Have a valid preliminary tests for breast cancer, according to the non-patent literature 1, in addition to palpation, in private breast x-ray mammography, ultrasonography (ECHO) imaging. Perform a biopsy if the findings in primary breast cancer is suspected, poke the needle through the lesion as a secondary test, cells and tissues collected and examined under a microscope. Also to examine the State of the disease and spreading to perform imaging procedures such as CT, MRI, abdominal ultrasound, bone scintigraphy, PET if necessary.

[0006]

Tumor marker for breast cancer detection, for example, is known include CEA, CA-15-3 and CA27-29. Its usefulness is limited, and does not rise by patients has been reported to rise when these tumor markers in serum, breast cancer has spread to other organs such as bone, liver and the (non-patent literature 1).

[0007]

In the research phase, patent literature 1-is reported to detect breast cancer by combination of micro RNA (miRNA) is shown in 4 on blood and other biological samples in gene or miRNA gene and expression of protein markers for others and.

[0008]

How to detect prostate cancer and other cancers including breast cancer, specifically to the patent literature 1 with known protein markers hsa-miR-135a-3p and hsa-miR-602 in the blood have been shown.

[0009]

In the patent literature 2 blood and has been shown to detect various cancers including breast cancer, in conjunction with five other miRNA in hsa-miR-23b-3p and hsa-miR-135a-3p.

[0010]

Includes how to detect breast cancer in blood cells hsa-miR-92a-3p, hsa-miR-92a-2-5p, hsa-miR-92b-5p, using patent literature 3.

[0011]

How to patent literature 4 hsa-miR-in 451 a, hsa-miR-296-5p, hsa-miR-16-5p and breast cancer to detect has been shown.

[0012]

Shown in non-patent literature 3, hsa-miR-760 in the blood in patients with breast cancer can develop significantly.

[0013]

Is shown in the blood hsa-miR-423-5p and hsa-miR-486-5p after breast cancer surgery reduced to non-patent literature 4.

[0014]

Shown in non-patent literature 5 blood hsa-miR-4257, hsa-miR-1915-3p and hsa-miR-718 in patients with breast cancer can develop significantly.

[0015]

Shown in non-patent literature 6, hsa-miR-940 in the blood in patients with breast cancer can develop significantly.

Prior art documents

Patent documents

[0016]

Patent literature 1: advanced table 2012-507300 issue public report
Patent literature 2: advanced table 2008-500837 of public information
Patent literature 3: international publication 10 / 123043 No.
Patent literature 4: United States patent application publication No. 2008 / 0076674 of specification

Non-patent literature

[0017]

Non-patent literature 1: American Cancer Society "Breast Cancer", supervised by 2013, p. 6-9, 13, 27-28, 41-46, 52-54 and 63-64, 106
Non-patent literature 2: Sobin, l. The TNM Classification of Malignant Tumours, 7th Edition 2010, p. 171-181
Non-patent literature 3: Godfrey, AC. From 2013, Breast Cancer Research, vol 15 (3), p. R42
Non-patent literature 4: Cookson, VJ. By 2012, the Cellular Oncology, volume no. 35 (4), p. 301-8
Non-patent literature 5: Schrauder, MG. By 2012, PLoS One, vol. 7 (1), p. e29770
Non-patent literature 6: Leidner, RS. From 2013, PLoS One, vol. 8 (3), p. e57841
Non-patent literature 7: Tamaki, K. From 2013, Japanese Journal of Clinical Oncology, vol. No. 43 (2), p. 208-213
Non-patent literature 8: Guadagni, F. Et al, 2001, Clinical Cancer Research, Vol 7, p. 2357-2362

Summary of the invention

Inventors are trying to solve a problem

[0018]

Challenges of the present invention is to provide how to detect breast cancer effectively using nucleic acid heading a new breast cancer tumor marker, said marker specific to join. There is, as described in the non-patent literature 1, preliminary tests for breast cancer, she, in addition to palpation, in private breast x-ray mammography and ultrasound imaging. Mammography examinations, women over 40 years old to as breast cancer screening is effective and United States Cancer Institute has recommended to consult a doctor every year (non-patent literature 1). On construction of a small early breast cancer and breast cancer, however, exists in the Premenopausal Breast mammography the test limit be (non-patent literature 1). Also, in Japan, mammography rates in 2010, 24... 3 percent will be infrequent and to improve screening rates with improved breast cancer survival rate for (non-patent literature 7).

[0019]

Tumor marker for breast cancer detection of known previous CEA, CA-15-3 and CA27-29. I assumed that may help, however, these tumor markers in verify treatment of breast cancer recurrence in early breast cancer is designed as a breast cancer screening not useful (non-patent literature 1). In addition, according to the non-patent literature 8 sensitivity of specific CEA and ca15-3 respectively in the stage 1 is 6. 4 percent and 12. 2 percent and almost useless, stage 4 25. 0 percent and 62. 5%, meaning as a preoperative tumor marker measurement. In addition, because these tumor markers in blood to rise even for reasons other than breast cancer, to determine the presence or absence of breast cancer is difficult. Will force the economic and physical burden on patients by applying the wrong medical mistake other cancer get diagnosed with breast cancer, and discontinuing treatment appropriate.

[0020]

Reports also determine breast cancer using mRNA is in the research stage blood and other biological samples in micro RNA (miRNA) that have shown below, but none yet practical.

[0021]

How to detect prostate cancer and other cancers including breast cancer, with known protein markers in the blood hsa-miR-602 and hsa-miR-135a-3p patent literature 1 are shown. However, both types of miRNA and protein markers to measure can bring increased inspection costs and complexity of process undesirable. Also, this discovery method is description of exact accuracy to detect breast cancer, sensitivity, specificity, accuracy, poor industrial utility.

[0022]

In the patent literature 2 blood and description of exact precision is described how to detect various cancers including breast cancer, in conjunction with five other miRNA in HSY-Mir-23B-3p and HSY-Mir-135y-3p to determine the breast cancer, sensitivity, specificity, accuracy, poor industrial utility.

[0023]

Description of exact accuracy to determine the breast have described how to patent literature 3 indicated otherwise, to detect breast cancer using hsa-miR-92a-3p, hsa-miR-92a-2-5p, hsa-miR-92b-5p, sensitivity, specificity, accuracy, poor industrial utility. For above miRNA markers are not validated in an independent sample group, lacks credibility.

[0024]

How to patent literature 4 hsa-miR-in 451 a, hsa-miR-296-5p, hsa-miR-16-5p and breast cancer to detect has been shown. However, this detection method sample available for tissue ablation surgery is required and a heavy physical burdens of patients with this stage testing approach is not desirable. Also, this discovery method is description of exact accuracy to detect breast cancer, sensitivity, specificity, accuracy, poor industrial utility.

[0025]

Description to determine breast cancer have shown that in the non-patent literature 3 hsa-miR-760 in the blood, such as expressed in breast cancer patients significantly, precision, sensitivity, specificity, accuracy and also for not mentioned a specific breast cancer detection methods, poor industrial utility.

[0026]

Description to determine breast cancer is shown in the blood HSY-Mir-423-5p and HSY-Mir-486-5p after breast cancer surgery reduced to non-patent literature 4, precision, sensitivity, specificity, accuracy and also for not mentioned a specific breast cancer detection methods, poor industrial utility.

[0027]

And using miRNA is 240 to detect breast cancer shown to non-patent literature 5 blood hsa-miR-4257, hsa-miR-1915-3p and hsa-miR-718 in patients with breast cancer can develop significantly, but are concerned about increased inspection costs and discrimination algorithm complexity and impractical on the industry.

[0028]

Conclude and lack of reproducibility is the author for this marker is shown to non-patent literature 6, hsa-miR-940 in the blood in patients with breast cancer can develop significantly, and eventually rejected. Description to determine breast cancer further precision, sensitivity, specificity, accuracy and also for not mentioned a specific breast cancer detection methods, poor industrial utility.

[0029]

Thus, in the detection of breast cancer tumor marker for existing lower performance, also have the possibility to overlook the positives, yomimasu and breast cancer patients to use these markers in the research stage performance and detection methods are not shown specifically to waste additional inspections conducted by, or breast cancer patients treatment opportunities lost. In addition, several dozen-difficult to use large scale screening for increased inspection costs measure the miRNA consisting of several hundred pieces of health such as. To removal of breast tissue to measure tumor markers to give patients less invasive and undesirable. As a result, low breast cancer markers detected from blood samples can be invasive, breast cancer patients breast cancer patients and the healthy yomimasu and healthy yomimasu correctly can determine the high precision is required. In particular, breast cancer is found early, treatment, high-sensitivity can be detected even less advanced breast cancer is breast-conserving therapy becomes available that can dramatically reduce the risk of recurrence by breast cancer markers are coveted. Also expected to provide a simple breast cancer primary screening, mammography screening rate increased