Biomarkers for Breast Cancer

Jan 17

By Jordan Berger, Sabina Vitola, and Aria Moss

Breast Cancer is a form of cancer that targets the cells within breasts. It can affect both men and women, but is significantly more common in women, with 1 out of 8 women being diagnosed at some point of their life. It is the most commonly diagnosed cancer for women in the US and there are an estimated 43,600 women estimated to pass away from this disease in the year 2021 [5]. In order to effectively treat breast cancer it is imperative that the diagnosis be made early on (before the cancer spreads) and one way to do this is preemptively screen women who may be at high risk of developing cancer and share this information so the patients can be proactive about their possible diagnosis. A possible medium to be used in order to execute these precautionary screenings is through the use of biomarkers.

Biomarkers are indicators of biological processes and responses. They are measurable and can be used to “mark” indicators of genetic diseases like cancers [2]. There are many biomarkers for breast cancer. Knowing about these biomarkers can be helpful to predict and treat the different types of cancers they express. Using biomarkers to identify genes and develop tests to identify them and treatments is a huge step towards progress in medical science.

The most commonly tested biomarkers are molecular, where the expression of certain genes or groups of genes is examined to “provide both a useful prognostic tool, able to determine whether the cancer is likely to be indolent or aggressive and a possible therapeutic target” [6]. For example, biomarker testing can be performed on “estrogen receptor[s] (ER), progesterone receptor[s] (PR), and human epidermal growth factor receptor 2 (HER2)... to establish hormone receptor status, which provides both prognostic and predictive value” [7]. These work because some forms of breast cancer are impacted by the hormone receptors; through molecular testing, physicians can compare how these hormone receptors behave, compare to healthy patients, and develop a predictive or prognostic tool.

Biomarkers have a variety of predictive and medical uses. When it is said that ER, PR and HER2 biomarkers can be used in both predictive and prognostic ways this means that they can be used to determine the likelihood of a patient developing the disease and to determine how the disease may progress or worsen, respectively [8]. For the purpose of this discussion the research will be focused on the predictive characteristics of the HER2 biomarker.

HER2 is a particular form of breast cancer, which is known to primarily be linked to the HER2 gene. HER2 makes HER2 receptor proteins in breast cells, and in healthy individuals, this process is vital to the growth of the cells. HER2 “provides the cell with potent proliferative and anti-apoptosis signals” [3], which is important in healthy cells, in the correct quantity. However, in cancerous cells, the HER2 gene is overexpressed, a process known as gene amplification. In this event, the receptors are overproduced, which cause increased and less predictable cell growth and division, and those proliferative signals instead cause malignant tumors.

The HER2 biomarker is present in about 20 percent of patients with a diagnosis of primary breast cancer [10], and has become one of the most prominent biomarkers when it comes to genetic detection. It is commonly detected by one of two methods: sometimes, immunohistochemistry is used on a tissue sample of the primary tumor, staining it with a fluorescent dye that reacts to molecules present in HER2 tumors. Alternatively, a blood sample can be used, and serum from the sample is tested with an enzyme-linked immunosorbent assay (ELISA) to detect the same molecules [9].

These methods to identify and test for cancer genes may be the key to developing effective treatments, and it is important to note that they are also the best way to catch cancer in its earliest stages, which consequently is when it is most treatable. The implications of further research with HER2 and adjacent biomarkers would be to hopefully save the lives of thousands of women around the country and the world. Page Break

Glossary

Assay: “An analytic procedure for detecting or measuring the presence, amount, state or functional activity of a biomarker. An assay is one component of a test, tool, or instrument” [2].

Biomarker: Biomarkers are indicators of biological processes and responses. They are measurable and can be used to “mark” indicators of genetic diseases like cancers [2].

HER2: A biomarker for a cancer gene that comprises approximately 30% of all newly diagnosed cancers in women and is the second leading cause of cancer deaths in women [1].

Gene: “The gene is the basic physical unit of inheritance. Genes are passed from parents to offspring and contain the information needed to specify traits. Genes are arranged, one after another, on structures called chromosomes. A chromosome contains a single, long DNA molecule, only a portion of which corresponds to a single gene” [4].

Molecular Testing: A laboratory method that uses a sample of tissue, blood, or other body fluid to check for certain genes, proteins, or other molecules that may be a sign of a disease or condition, such as cancer.[11]

Hormone receptors: A cell protein that binds a specific hormone. The hormone receptor may be on the surface of the cell or inside the cell. Many changes take place in a cell after a hormone binds to its receptor.[11]

Predictive Biomarker: “A biomarker used to identify individuals who are more likely than similar individuals without the biomarker to experience a favorable or unfavorable effect from exposure to a medical product or an environmental agent” [2].

Prognostic Biomarker: “A biomarker used to identify likelihood of a clinical event, disease recurrence or progression in patients who have the disease or medical condition of interest” [2].

Immunohistochemistry: A laboratory method that uses antibodies to check for certain antigens (markers) in a sample of tissue. The antibodies are usually linked to an enzyme or a fluorescent dye. After the antibodies bind to the antigen in the tissue sample, the enzyme or dye is activated, and the antigen can then be seen under a microscope. Immunohistochemistry is used to help diagnose diseases, such as cancer. It may also be used to help tell the difference between different types of cancer.[11]

References

[1] https://www.fda.gov/drugs/biomarker-qualification-program/about-biomarkers-and-qualification#what-is

[2] https://www.fda.gov/drugs/biomarker-qualification-program/about-biomarkers-and-qualification

[3]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3242418/

[4] https://www.genome.gov/genetics-glossary/Gene

[5]https://www.breastcancer.org/symptoms/understand_bc/statistics

[6]https://www.intechopen.com/chapters/62000

[7]https://arupconsult.com/content/breast-cancer

[8]https://www.fda.gov/files/BIOMARKER-TERMINOLOGY--SPEAKING-THE-SAME-LANGUAGE.pdf

[9]https://pubmed.ncbi.nlm.nih.gov/29788570/

[10]https://oncologypro.esmo.org/education-library/factsheets-on-biomarkers/her2-in-breast-cancer