In 2018, the FDA approved the reporting of three specific mutations in the BRCA1/BRCA2 genes for breast cancer risk. These are common in people of Ashkenazi (Eastern European) Jewish descent. There are more than 1000 different mutations in the BRCA genes. So an absence of the three tested mutations does not rule out the chances of developing breast cancer. However, the FDA has stated that these three markers can be used to identify women with increased risk for breast and ovarian cancer or men at increased risk for breast and prostate cancer.
The BRCA1 gene produces proteins that are responsible for controlling and suppressing tumor cells. These proteins prevent uncontrollable growth and division of cells. The BRCA1 proteins also help repair damages to the DNA. The damages can be a result of errors in the DNA replication process or due to environmental agents like UV and ionizing radiation. Inherited mutations in the BRCA1 gene are responsible for about 40-45% of hereditary breast cancers. Changes in this gene are also responsible for other cancers like ovarian and prostate cancer.
The BRCA2 gene produces proteins that are responsible for controlling and suppressing tumor cells. These proteins prevent uncontrollable growth and division of cells. The BRCA2 protein helps repair damages to the DNA. The damages can be a result of errors in the DNA replication process or due to environmental agents like UV and ionizing radiation. BRCA2 germline mutations are seen in approximately 35% of families with early-onset breast cancer in women and also cause an increased risk of ovarian cancer in women and breast cancer in men.
The development of malignant cells in the breast tissue is called breast cancer. The main risk factors for breast cancer are gender - women are at a much greater risk than men, age - 50 years and older, family history, and genetics. About 5% to 10% of breast cancer cases are thought to be hereditary. The inheritance mostly occurs through two genes, BRCA1 and BRCA2. However, having a mutation in this gene does not mean that the individual will be diagnosed with breast cancer. These mutations just indicate high risk and warrant further investigation and close monitoring.
Hereditary breast and ovarian cancer syndrome is characterized by a strong family history of breast and ovarian cancer. It results in an increased risk of incidence among other family members, including the men. BRCA1 and BRCA2 genes, which are associated with breast cancer risk, also play a role in ovarian cancer risk. BRCA1 mutations are found in 35 to 70% of women with ovarian cancer. For women with BRCA2 mutations, the risk has been estimated to be between 10% and 30% by age 70.
In this section, genetic variants associated with breast cancer, which are also known to be associated with other cancers are considered. Specifically, genetic variants associated with an increased risk for breast and other cancers like adenocarcinoma of lung, brainstem glioma, colorectal neoplasms, hepatocellular carcinoma, malignant melanoma of skin, neoplasm of brain, neoplasm of the breast, oesophageal carcinoma, ovarian serous cystadenocarcinoma, pancreatic adenocarcinoma, small cell lung cancer, squamous cell carcinoma of lung, squamous cell carcinoma of the head and neck and uterine carcinosarcoma have been considered in this section.
Breast cancer is usually diagnosed around 50 years of age. But certain risk factors can put women at a higher risk of getting breast cancer at a young age. Some of them include a family history of breast cancer, Ashkenazi Jewish heritage, and previous exposure to radiation therapy. Other risk factors include some non-cancerous breast diseases such as atypical hyperplasia or lobular carcinoma in situ. Certain genetic markers in the BRCA1 and BRCA2 gene can put young women at a higher risk of early onset of breast cancer.
Estradiol levels are strongly associated with the risk of breast cancer in postmenopausal women. Estradiol is an estrogen steroid hormone naturally produced in the body. It is a major female sex hormone. According to a study, 36% of women with estradiol levels of more than 10 pmol/L had a 3% four-year risk of breast cancer. CYP19A1 gene produces the enzyme aromatase that regulates the levels of estradiol. Certain types of the CYP19A1 gene are associated with higher estradiol levels and an increased risk for breast cancer.
Around one percent of all breast cancer cases develop in men. A family history of breast cancer is the major risk factor for breast cancer in men. The relative risk of breast cancer for a woman who has an affected brother is approximately 30% higher than for a woman with an affected sister. Nearly 10% of male breast cancer cases are due to mutations in the BRCA2 gene. Mutations in the BRCA1 gene are reported less frequently for male breast cancer. CHEK2, PTEN, and PALB2 genes are some of the other genes studied.
With early detection and treatment, most cases of breast cancer have a good prognosis. According to the National Cancer Institute, 90 percent of women with breast cancer survive five years after diagnosis. However, there is considerable variation in survival due to genetic influence. The RAD51B gene is responsible for DNA repair. According to a study, low levels of RAD51B resulted in a 6% decrease in the survival rate. Other non-genetic factors like medical history, response to treatment, the type and stage of cancer, and the specific characteristics of cancer also influence the prognosis.
Bevacizumab is a drug commonly used in cancer treatments. It works by constricting the blood vessels to cut the blood flow to cancerous cells. Since the narrowing of blood vessels increases the pressure of blood flow in them, hypertension is a common complication of treatment with bevacizumab. In fact, research studies suggest that the development of hypertension could be predictive of improved clinical outcomes. Certain genetic factors increase the risk of hypertension when on bevacizumab therapy. Identifying these variants can help manage the adverse side effects of chemotherapy.
Breast size and its morphology is associated with the risk for breast cancer. The mammographic density (the non-fat breast tissue percentage) is also one of the risk factors for breast cancer. According to a study published in the International Journal of Cancer, lean women with larger breast size may have a higher likelihood of breast cancer. Genetic factors that influence breast development also play a role in breast cancer risk. A study identified seven single-nucleotide polymorphisms (SNPs) significantly associated with breast size, three of which have strong links to breast cancer.
Estrogen is called the female sex hormone is since it is responsible for the development of female reproductive organs. A cancer is called estrogen-receptor-positive (or ER-positive) if it has receptors for estrogen. Testing for hormone receptors is important to assess the response to hormonal therapy. Estrogen receptor-negative (ER-negative) cancers do not have the receptors to recognize estrogen and do not need estrogen to grow. Hence, hormonal therapy with estrogen may not be effective against these cancers. Certain genetic markers are associated with an increased risk of ER-negative breast cancer.
Estrogen is a sex hormone responsible for the development of female reproductive organs. It is also called the female sex hormone. A cancer is called estrogen-receptor-positive (or ER-positive) if it has receptors for estrogen. ER-positive breast cancer constitutes 80% of all breast cancers. Testing for hormone receptors is important to assess the response to hormonal therapy. Treatment options for ER-positive breast cancer involve reducing estrogen levels or stopping it from encouraging the growth of cancerous cells. Certain genetic markers are associated with an increased risk of ER-positive breast cancer.
Hair loss (Alopecia) is a distressing side-effect of chemotherapy—the drugs used in chemotherapy target the cancerous cells and the healthy hair follicle cells. According to a study, 8% of women refuse chemotherapy because of the risk of losing their hair. Most of the cytotoxic agents cause alopecia, but the severity in individual patients differ significantly. A research study identified four genes that play a role in hair loss during chemotherapy. CACNB4 gene, involved in calcium transport, showed the strongest association with hair loss. Analyzing these genes can help develop prevention strategies to manage chemotherapy-induced alopecia.
The hormone estrogen stimulates breast cell growth; prolonged exposure to estrogen can increase the risk for breast cancer. All women have lower levels of estrogen during the breastfeeding periods. This is because breastfeeding delays menstrual periods. The longer the breastfeeding duration, the lower the lifetime exposure to estrogen, which decreases the risk for breast cancer. Studies have estimated that the heritability of breastfeeding duration ranges from 44 to 54%. People with certain genetic types may tend to breastfeed their children for a longer duration than others.
According to a study published in the Journal of Adolescent Health, early-onset puberty in adolescent girls may increase their risk of developing breast cancer. The age of menarche or the first menstrual period influences your lifetime exposure to estrogen. There is considerable variation between the timing of puberty onset, with a mean of 4 to 6 years between individuals. The variations in the onset of puberty have also been associated with risk for hormone dependant cancer, diabetes, cardiovascular disease, and obesity. People with certain genetic types are at a higher risk of reaching puberty early.
Menopausal hormone therapy is widely prescribed for postmenopausal women to alleviate symptoms of menopause like hot flashes, vaginal dryness, and sleep disturbances. This therapy involves the administration of estrogen in the form of pills, patches, or topical creams. However, it has been associated with an increased risk for cardiovascular disease and breast cancer. Some genes promote higher growth of estrogen receptors during menopausal hormone therapy. This increases the risk of ER-positive breast cancer. A study revealed two regions in the POMP gene showing an interaction with hormone therapy that increases the risk of breast cancer.