How PCR can permit early diagnosis of breast cancer?

Breast cancer is one of the most common cancer types in the world. While it is known to be more common among older women it can actually affect women of all ages. According to World Health Organisation 2.3 million women around the world were diagnosed with breast cancer last year and 685 000 died [1]. It is also the world’s most prevalent cancer [1]. Despite the increase in treatment methods and survival rate in the past 40 years [1], learning how to prevent breast cancer completely has been proven more difficult. Here we are going to take a look into some methods that could help diagnose breast cancer early or even prevent it. 
 
Types of breast cancer
To know how to prevent, diagnose or cure breast cancer it is important to know which type of breast cancer you are dealing with. There are many types and subtypes of this disease. Each type may be inherited or induced by the environment, aggressive or less aggressive, appearing early in life or later in life. 
 
Non-invasive breast cancers also known as carcinoma in situ are contained within the milk ducts (ductal carcinoma) or lobules (lobular carcinoma) in the breast. These types of cancers aren’t life-threatening, but can increase the risk of developing an invasive breast cancer later in life. [2][3]
 
Invasive breast cancers have spread outside the milk ducts or lobules into surrounding breast tissue, lymph nodes or armpit. Invasive ductal carcinoma makes up about 80% of all breast cancers. Other invasive cancer types are known as invasive lobular carcinoma, Paget's disease of the nipple and inflammatory breast cancer. The last one is a rare and aggressive form of breast cancer. Then there are also phyllodes tumours, locally advanced tumours and metastatic breast cancer. The latter is an advanced breast cancer that has spread into more distant parts of the body like bones, liver and/or lungs. [2][3]
 
About 5-10% of all breast cancers are hereditary and associated with some inherited gene mutation (most commonly BRCA1 and BRCA2 gene mutations). This type of breast cancer tends to occur more often among younger people and can be more aggressive. People, who have an unfortunate gene mutation for breast cancer, also have a higher probability of developing other types of cancer. [4]
 
Breast cancer also has subtypes. About 2/3 of breast cancers need female hormones to grow and are therefore called hormone receptor positive. Some breast cells have too much growth factor receptor 2 on their surface that promotes the growth of the cancer cells. These are called HER2-positive cancer cells and they may or may not be hormone receptor positive. The third subtype is a type that doesn’t have any of the previous two characteristics and is therefore called triple negative (no receptors for oestrogen, progesterone and HER2). [2][3]
 
Symptoms of breast cancer
Symptoms mostly depend on the type of breast cancer. The most common one is a breast lump, although it may not always be present in case of cancer. Other symptoms that may be present are redness and/or swelling of part of the breast, skin irritation, pain, nipple bleeding and/ or discharge and nipple looking flatter or caved in. [5][6]
 
Diagnosing breast cancer
The most common method for diagnosing breast cancer is mammography, but also ultrasound, MRI, breast biopsy and just regular breast exams are used [7].
Once breast cancer has been confirmed there are following tests to determine the stage or the extent of the cancer. For this again mammography and MRI can be used in addition to blood tests, bone scan, CT and PET scan. Appropriate tests are done depending on the symptoms. [7][8]
 
PCR in diagnosing and discovering breast cancer 
To treat breast cancer successfully it is very important to first accurately diagnose the type and stage of the disease. One type of breast cancer that has gotten the most attention when it comes to PCR, is HER2-positive cancer that is observed in 10-35% of all cases. HER2 protein is expressed by the HER2/neu gene. The amount of HER2/neu overexpression is very important in choosing the correct treatment for the patient [9]. So far it has been proven that qPCR can support accurate protein and gene quantification and interpretation of results when it comes to correctly diagnosing patients who have overproduction of HER2 protein [9][10][11]. While qPCR can be used as a complementary method to immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH), it can also be used as an alternative since it is less expensive, faster, has higher sensitivity and is considered more accurate and reliable[10][11]. So far there are still multiple methods used to give an accurate diagnosis and high concordance rate between IHC and PCR is recommended [9].
 
Other than HER2-positive cancer diagnosis, qPCR can be used to detect gene duplications or deletions and identify small mutations when analysing different cancer markers. It is also possible to multiplex and therefore easy to analyse multiple genes in a single reaction. When a person does his or her genome analysis and mutations are discovered that could promote breast cancer, then this will allow taking preventive measures to avoid the disease. [12]
 
One of the most common genes where a mutation can occur and therefore lead to breast cancer are BRCA1 and BRCA2 genes [13]. These mutations are in most cases hereditary, which is why women with family history of breast cancer often have themselves genetically tested for BRCA1 and BRCA2 mutations [14]. Unfortunately these can largely vary between individuals and because of thousands of different variations it is often difficult to accurately detect the mutation within the gene [13]. This can be made easier with the help of PCR, qPCR or long-range PCR together with Next-Generation sequencing [13][14][15]. 
 
Another thing that qPCR can be applied for is to detect viral causes of cancer like mouse mammary tumor virus, bovine leukemia virus, human papillomavirus and Epstein-Barr virus [16][17].
 
Treatment methods for breast cancer
The first cancer ever to be reported was breast cancer in Egypt around 1600 BC [18]. Back then it was considered untreatable. Nowadays there are many different methods to cure this cancer and the success rate is around 90% in the developed countries, if the cancer is discovered early [1]. 
 
Treatment methods once again depend on the type of breast cancer. Cancer can be surgically removed, if it is still in the breast. Chemotherapy is used to get rid of cancer cells that may have been left behind after the surgery or to destroy cancer cells as much as possible, when they have already spread in the body. Radiation therapy is used when cancer can’t be removed with surgery and also for the same reasons as chemotherapy. Hormonal therapy is used to treat hormone receptor positive breast cancers. Targeted therapies are a newer type of treatment that target specific characteristics of a cancer cell in order to kill it. This type of treatment is less harmful for healthy cells than chemotherapy. Immunotherapy, also known as biological therapy, uses the body's own immune system to fight cancer cells. [19]
 
There are of course always new treatment methods under development, which may improve the survival rate even more, for example viroimmunotherapy that uses viruses to treat breast cancer [20]. 
 
In conclusion it can be said that when it comes to breast cancer things are improving, but there is still a long way to go. There are many ways to diagnose and treat this disease with new methods being developed continuously. We hope that Solis BioDyne’s products for PCR and qPCR can make this development a little easier for everyone.
 
References:
 
[1] Breast cancer. (2021). Retrieved 16 October 2021, from https://www.who.int/news-room/fact-sheets/detail/breast-cancer
 
[2] Types of Breast Cancer: Non-Invasive, Invasive and More. (2021). Retrieved 16 October 2021, from https://www.breastcancer.org/symptoms/types
 
[3] Types of breast cancer. (2021). Retrieved 16 October 2021, from https://www.bcna.org.au/understanding-breast-cancer/what-is-breast-cancer/types-of-breast-cancer/
 
[4] Genetics: Breast Cancer Risk Factors. (2021). Retrieved 16 October 2021, from https://www.breastcancer.org/risk/factors/genetics
 
[5] What are the Symptoms and Signs of Breast Cancer?. (2021). Retrieved 16 October 2021, from https://www.cancercenter.com/cancer-types/breast-cancer/symptoms
 
[6] Breast Cancer: Symptoms, Diagnosis, Types, and More. (2021). Retrieved 16 October 2021, from https://www.breastcancer.org/symptoms
 
[7] How Is Breast Cancer Diagnosed?. (2021). Retrieved 16 October 2021, from https://www.cdc.gov/cancer/breast/basic_info/diagnosis.htm
 
[8] Breast cancer - Diagnosis and treatment - Mayo Clinic. (2021). Retrieved 16 October 2021, from https://www.mayoclinic.org/diseases-conditions/breast-cancer/diagnosis-treatment/drc-20352475
 
[9] Gheni, N., & Westenberg, D. (2020). Quantitative real-time PCR assay with immunohistochemical evaluation of HER2/neu oncogene in breast cancer patients and its correlation with clinicopathological findings. Indian Journal Of Pathology And Microbiology, 63(5), 123. doi: 10.4103/ijpm.ijpm_136_19
 
[10] MENDOZA, G., PORTILLO, A., & OLMOS-SOTO, J. (2012). Accurate breast cancer diagnosis through real-time PCR her-2 gene quantification using immunohistochemically-identified biopsies. Oncology Letters, 5(1), 295–298.doi:10.3892/ol.2012.984 
 
[11] Wasserman, B. E., Carvajal-Hausdorf, D. E., Ho, K., Wong, W., Wu, N., Chu, V. C., … Rimm, D. L. (2017). High concordance of a closed-system, RT-qPCR breast cancer assay for HER2 mRNA, compared to clinically determined immunohistochemistry, fluorescence in situ hybridization, and quantitative immunofluorescence. Laboratory Investigation, 97(12), 1521–1526.doi:10.1038/labinvest.2017.93 
 
[12] Bernard, P. S., & Wittwer, C. T. (2002). Real-Time PCR Technology for Cancer Diagnostics. Clinical Chemistry, 48(8), 1178–1185.doi:10.1093/clinchem/48.8.1178
 
[13] Ellison, G., Huang, S., Carr, H., Wallace, A., Ahdesmaki, M., Bhaskar, S., & Mills, J. (2015). A reliable method for the detection of BRCA1 and BRCA2 mutations in fixed tumour tissue utilising multiplex PCR-based targeted next generation sequencing. BMC Clinical Pathology, 15(1).doi:10.1186/s12907-015-0004-6 
 
[14] Hernan, I., Borràs, E., de Sousa Dias, M., Gamundi, M. J., Mañé, B., Llort, G., … Carballo, M. (2012). Detection of Genomic Variations in BRCA1 and BRCA2 Genes by Long-Range PCR and Next-Generation Sequencing. The Journal of Molecular Diagnostics, 14(3), 286–293.doi:10.1016/j.jmoldx.2012.01.013 
 
[15] Toland, A. E., Forman, A., Couch, F. J., Culver, J. O., Eccles, D. M., … Brody, L. C. (2018). Clinical testing of BRCA1 and BRCA2: a worldwide snapshot of technological practices. Npj Genomic Medicine, 3(1).doi:10.1038/s41525-018-0046-7 
 
[16] Lawson, J. S. (2009). Do Viruses Cause Breast Cancer? Cancer Epidemiology, 421–438.doi:10.1007/978-1-59745-416-2_21 
 
[17] Lawson, J. S., Salmons, B., & Glenn, W. K. (2018). Oncogenic Viruses and Breast Cancer: Mouse Mammary Tumor Virus (MMTV), Bovine Leukemia Virus (BLV), Human Papilloma Virus (HPV), and Epstein–Barr Virus (EBV). Frontiers in Oncology, 8.doi:10.3389/fonc.2018.00001 
 
 
[18] Faguet, G. B. (2014). A brief history of cancer: Age-old milestones underlying our current knowledge database. International Journal of Cancer, 136(9), 2022–2036.doi:10.1002/ijc.29134 
 
[19] Treatment and Side Effects. (2021). Retrieved 16 October 2021, from https://www.breastcancer.org/treatment
 
[20] Chaurasiya, S., & Fong, Y. (2020). Viroimmunotherapy for breast cancer: promises, problems and future directions. Cancer Gene Therapy.doi:10.1038/s41417-020-00265-6