Polygenic score
Influential genes: PTPRJ, BRCA1, BRCA2
Alterations in PTPRJ have been found in several types of cancer. It was found that low expression of PTPRJ is associated with worse prognosis in breast cancer patients.
Women with a BRCA1 mutation have a significantly higher lifetime risk of developing breast cancer compared to the general population.
Like BRCA1, mutations in BRCA2 significantly increase the risk of both breast and ovarian cancer.
Breast cancer is a disease which causes the cells in the breast to grow uncontrollably. It is the second most common cancer in women (accounting for approximately 15 - 30% of all malignancies).[1;2] Furthermore, it is currently estimated that around 7.8 million women have been diagnosed with it in the past five years.[3] Despite the common belief that it would only affect women, breast cancer can also develop in men. It usually occurs in postmenopausal women, however, genetic predispositions may cause it to arise earlier in life.
Certain factors may increase the risk of developing breast cancer, namely:
In addition, specific genetic mutations significantly increase the risk of developing the disease. The most prominent being mutations in the following genes
Breast cancer is most often painless, but lumps or hardening/thickening of the tissue might be palpable early on. Therefore self-examinations and regular medical check-ups are highly recommended.
Breast cancer is often diagnosed thanks to nationwide screening programs, allowing adequate treatment in the early stages, which has positively influenced the overall outcome for breast cancer patients over the past decade.
Approximately 2.3 million women were diagnosed with breast cancer in 2020.[3] It affects mainly postmenopausal women aged 50 and older. However, about 0.5-1% of all breast cancers are diagnosed in men.[1;2] Some risk factors are impossible to control, such as age, genetic mutations, reproductive history, breast density, family history of breast or ovarian cancer, and previous radiation therapy; nonetheless, there are multiple preventable risk factors that include:
It is essential to mention that having the risk does not mean one will develop the disease, but the chances are slightly increased.
The most important risk factor in breast cancer is inheritance, it is estimated that 15–20 % of breast cancer has a familial origin. The risk increases with the number of affected close relatives and the early age of onset. Different risk factors of the disease have also been identified, such as hormonal changes (e.g. high estrogen levels) and lifestyle (drinking alcohol, obesity, lack of physical activity). There is enough evidence proving that breast cancer is inherited as a polygenic disease, where more pathogenic variants with various effects increase the overall risk.[4]
BRCA1, on chromosome 17, was the first major gene identified in association with inherited breast cancer. BRCA2 was later located on chromosome 13. Their inheritance pattern is autosomal dominant (AD; only one abnormal allele (copy) of a given gene is enough to cause the disease). However, they act recessively on the cellular level as tumor suppressor genes (AR; both alleles must be affected for loss of function).
There are more causative genes that can be divided into the following groups:[5]
It has been stated that the risk of ovarian cancer is higher than 40% when BRCA1 mutations are present, and up to 20 % for carriers of the BRCA2 gene mutation. Research also suggests the role of BRCA genes in prostate cancer, although the mechanism of tumorigenesis remains unclear.[6]
Prevention in high-risk individuals is essential and genetic testing represents a great option to find out whether you’re at risk. Here, in Macromo, polygenic risk scores (PRS) are used to determine the genetic risk. The PRS is an estimate of the probability that an individual carries a given trait based on genetics, without considering environmental factors. Variants across their genome are summed and weighted according to their effect on the disease or trait.[7]
But since highly penetrative genes have been identified, they are also being used for identification and screening.
Breast cancer can present itself in various ways, so a complete medical examination is essential for a diagnosis. A painless lump or thickening in the breast are among the most common symptoms; however, it's important to mention that there are many other reasons for lumps in the breast, most of which are not cancerous. Women may notice persisting abnormalities (lasting more than one month) in size, shape, or appearance of a breast, redness/pitting or other alteration of the skin area, changes in nipple appearance, or abnormal nipple discharge.
Advanced cancers can erode the skin and cause ulceration (open sores). It can also spread to other areas and thus cause other symptoms. The most common site in which the spread of cancer is detectable is the axillary lymph nodes.
The possibility of breast cancer is usually investigated after manifesting symptoms or detecting a suspicious lesion in a preventive mammographic examination. Clinical assessment, radiographic imaging (breast ultrasound, mammography), and, if necessary, a biopsy of the tissue are important steps in diagnosing breast cancer. In cases of confirmed breast cancer, further imagining of both breasts, the skeleton, regional lymph nodes, and possibly other body parts is indicated to assess the possible spread of the mass.
The treatment depends on the results obtained by a biopsy (histopathological classification: how the cells look and what kind of receptors they express that could be targeted during treatment) and staging of the cancer. It can involve surgical management (removal of the mass and/or breast) and systemic therapy such as chemotherapy, hormone therapy, and/or targeted therapy. Luckily, breast cancer treatment can be very effective, achieving 90% or higher survivability, especially when the disease is diagnosed early.[2]
Prevention of breast cancer can be done by altering the modifiable risk factors mentioned in this article, such as limiting alcohol consumption, maintaining a healthy weight, being physically active, breastfeeding, and limiting postmenopausal hormone therapy. Self-examination or examination by a partner has limited evidence of improving the diagnosis and outcome of breast cancer but is still recommended by many sources.
You can find a guide on how to examine yourself here:
https://www.breastcancer.org/screening-testing/breast-self-exam-bse
Nonetheless, the most crucial step is to take advantage of your country’s screening programs and strictly follow them.
The prognosis of breast cancer will depend on its diagnosis stage. Diagnosis in the early-stage results in significantly greater survival chances, and over the last decades, mortality has steadily decreased thanks to screening programs and early interventions. The more cancer has spread, the harder it is to treat and the worse the outcome is.
The first step in preventing breast cancer is to maintain a healthy weight, stick to a healthy diet, and exercise regularly. It’s important not to smoke or use any other tobacco products and limit your alcohol consumption. Don’t forget to attend routine screenings and do regular self-examinations of your breasts.
Get the guidelines for a healthier and longer life. With Macromo tests, you'll learn your health risks and how to prevent them.
Continue to ShopThe first step in preventing breast cancer is to maintain a healthy weight, stick to a healthy diet, and exercise regularly. It’s important not to smoke or use any other tobacco products and limit your alcohol consumption. Don’t forget to attend routine screenings and do regular self-examinations of your breasts.