REGISTRO DOI: 10.69849/revistaft/cl10202012011017
Graziella Galvão Gonçalves
Abstract
Breast cancer is one of the leading causes of death among women worldwide, and early detection, along with effective treatments, is essential to reduce mortality. The risk factors associated with the disease are varied and can be classified into genetic, hormonal, environmental, and lifestyle-related factors. Women with a family history of breast cancer, especially those with first-degree relatives, are at a higher risk of developing the disease. Mutations in the BRCA1 and BRCA2 genes significantly increase the risk of breast and ovarian cancer. In terms of hormones, prolonged exposure to estrogen, such as in women who experience early menarche or late menopause, is associated with an increased risk. Additionally, prolonged use of hormone replacement therapy can also elevate the risk of breast cancer. Environmental factors such as obesity, smoking, and excessive alcohol consumption have a considerable impact, as they can affect estrogen levels and induce genetic alterations. Lack of physical activity and stress also contribute to an increased risk. Reproductive factors, such as late childbearing or nulliparity, also play an important role. Exposure to radiation and a history of radiotherapy treatments also increase the risk. Ongoing research into these risk factors is crucial for the development of personalized prevention strategies. The implementation of regular screening programs and the promotion of healthy habits are key to reducing the incidence of breast cancer and improving survival rates.
Keywords: Breast Cancer; Risk Factors; Genetics; Hormones; Prevention.
Breast cancer is one of the leading causes of death among women worldwide, and early detection and effective treatments are crucial for reducing mortality. Understanding the risk factors associated with the development of the disease is essential for prevention, screening strategies, and guiding the choice of the most appropriate treatments. These factors are diverse and can be classified into genetic, hormonal, environmental, and lifestyle-related categories.
Genetic factors play a significant role in breast cancer risk. Women with a family history of the disease, especially those with first-degree relatives such as mothers, sisters, or daughters, are more likely to develop it. The presence of mutations in the BRCA1 and BRCA2 genes is one of the most well-known genetic factors, associated with a considerably higher risk not only for breast cancer but also for ovarian cancer. Other genetic mutations, such as in the TP53 and PTEN genes, though less frequent, also increase the risk of the disease.
Hormonal factors, particularly estrogen, the female sex hormone, play a central role in the development of breast cancer. Women who experience menarche before the age of 12 or enter menopause after the age of 55 are exposed to estrogen for longer periods, increasing their chances of developing breast tumors. Prolonged use of hormone replacement therapy, especially with estrogens after menopause, may also elevate the risk of breast cancer.
Moreover, environmental and lifestyle-related factors have a substantial influence on the disease risk. Obesity, particularly after menopause, is associated with an increased risk due to the excessive production of estrogen by adipose tissue. Alcohol consumption and smoking are other known risk factors, as alcohol can raise estrogen levels in the body, while smoking can cause genetic changes in breast cells. A lack of physical activity is also relevant, as inactivity can contribute to elevated estrogen levels and promote obesity, both of which favor the development of breast cancer.
Reproductive factors also play a crucial role in breast cancer risk. Women who have children later in life or remain childless have a higher risk of developing the disease, possibly due to fewer menstrual cycles during their reproductive years, resulting in lower exposure to estrogen. On the other hand, breastfeeding has been associated with a reduced risk of breast cancer, likely because it decreases estrogen exposure during lactation.
Exposure to radiation, particularly during childhood and adolescence, is also a risk factor for breast cancer. Women who have received radiation therapy for previous cancer treatments, such as leukemia, have a higher risk of developing breast cancer later in life, as radiation can damage the DNA of breast cells, increasing the likelihood of tumor development.
Figure 1: Risk factors and preventions of Breast Cancer.
Source: International Journal of Biological Sciences.
Although breast cancer is a multifactorial disease and not all risk factors are preventable, understanding these factors allows for the implementation of more effective prevention and screening strategies. Women with elevated risk factors should be encouraged to follow regular screening programs and adopt healthy habits, such as maintaining a healthy weight, engaging in physical activity, avoiding excessive alcohol consumption, and not smoking. Additionally, discussing the possibility of genetic testing may be relevant for women with a significant family history or genetic traits that indicate an increased risk.
Ongoing research on breast cancer risk factors, along with awareness of the importance of screening and adopting healthy lifestyles, is crucial for the development of new prevention, diagnosis, and treatment strategies. It is expected that this will not only reduce the incidence of the disease but also improve survival rates and the quality of life for affected women.
The study by Momenimovahed and Salehiniya (2019) investigated breast cancer incidence and mortality rates, as well as identifying the associated risk factors worldwide. The research was conducted through a search in PubMed, Web of Science, and Scopus databases, without time restrictions, and included 142 articles published in English addressing various aspects of breast cancer, including its epidemiology and risk factors. The results showed that the incidence rate varies significantly among races and ethnicities, being higher in developed countries, while mortality is higher in less developed regions. Additionally, the study identified several risk factors, such as demographic, reproductive, hormonal, hereditary, breast-related, and lifestyle factors. Based on the findings, the authors emphasized the importance of implementing screening programs and controlling risk factors, as breast cancer incidence and mortality rates continue to rise.
The study by Singletary (2003) aimed to update and summarize the evidence on risk factors for breast cancer. The research highlighted the importance of accurately assessing the patient’s risk profile to select the most appropriate treatment options, such as surveillance, prophylactic surgery, and chemoprevention. The study reviewed key articles and updated relative risk estimates with data from recent reports, using large samples and meta-analyses. The findings revealed that commonly discussed factors, such as hormone use, alcohol consumption, obesity, and nulliparity, present a relatively modest relative risk for breast cancer (less than 2). In contrast, factors such as a history of neoplastic disease, atypical hyperplasia, and genetic predisposition significantly increase the risk, with relative risks ranging from 3 (for positive family history) to 200 (for premenopausal women with BRCA mutations). Singletary concluded that more accurate tools, especially those based on molecular biology techniques like microarray analysis, would be necessary for a more precise breast cancer risk assessment.
The study by Nelson et al. (2012) aimed to identify specific risk factors for breast cancer in women aged 40 to 49 years, in order to guide screening decisions. By reviewing data from various sources, including MEDLINE, the Cochrane Central Register of Controlled Trials, and the Breast Cancer Surveillance Consortium, the study focused on systematic reviews and studies in English on breast cancer risk factors in this age group. The results revealed that factors such as extremely dense breasts on mammography and having first-degree relatives with breast cancer were associated with at least a 2-fold increase in breast cancer risk. Other factors, such as previous breast biopsy, second-degree relatives with breast cancer, and heterogeneously dense breasts, were associated with a 1.5 to 2.0 times increased risk. Additionally, the study identified a 1.0 to 1.5 times increased risk in women who used oral contraceptives, were nulliparous, or had their first child at 30 years or older. Nelson et al. (2012) concluded that recognizing these risk factors could help guide personalized mammography screening strategies for women in their 40s, although the study also noted the variability of the included studies and the potential for bias due to differences in study design and confounding factors.
The study by Yang et al. (2011) investigated the association between risk factors for breast cancer and the expression status of estrogen (ER) and progesterone (PR) receptors in tumors. By compiling data from 35,568 invasive breast cancer cases in 34 studies from the Breast Cancer Association Consortium, the researchers used logistic regression models to examine the relationship between various epidemiological factors and tumor subtypes. The findings revealed that early menarche was less common in patients with PR-negative tumors, while factors such as nulliparity and older age at first pregnancy were less frequent in ER-negative tumors. Additionally, obesity in younger women (≤50 years) was more common in ER-negative/PR-negative tumors, while in older women (>50 years), obesity was less frequent in PR-negative tumors. In case-control analyses, nulliparity, older age at first pregnancy, and obesity in younger women were associated with an increased risk of ER-positive or PR-positive tumors, but not with triple-negative or central basal phenotype (CBP) tumors. The study concluded that reproductive factors and body mass index (BMI) were more strongly associated with hormone receptor-positive tumors, while triple-negative tumors and CBP may have a distinct etiology.
The study by Rudolph et al. (2018) explored the joint associations of polygenic risk scores (PRS) for breast cancer with various environmental risk factors, including reproductive history, alcohol consumption, postmenopausal hormone therapy, and BMI. The results suggested that polygenic risk had a greater effect among women with higher environmental risk factors. This implies that genetic and environmental risk factors may interact to affect the overall risk of breast cancer, providing a basis for future personalized prevention strategies.
The study by Low et al. (2015) addressed the analysis of genetic risk for breast cancer in women with a family history of the disease. The authors argued that genetic risk tools could help identify women who would benefit from preventive strategies, such as chemoprevention or prophylactic mastectomy, and provide guidance on early screening for women at elevated risk due to genetic predisposition.
In conclusion, breast cancer remains one of the leading causes of death among women worldwide, making early detection and effective treatment crucial for reducing mortality rates. Understanding the diverse risk factors associated with the disease is essential for the development of targeted prevention strategies, screening programs, and personalized treatment plans. Genetic, hormonal, environmental, and lifestyle-related factors all play a significant role in shaping an individual’s risk. By identifying and addressing these factors, particularly through regular screening, genetic testing, and the adoption of healthy lifestyle habits, it is possible to improve early detection rates and reduce the incidence of the disease. Ongoing research into these risk factors, along with advancements in screening and prevention, will be key to further reducing the impact of breast cancer and improving survival rates for affected women.
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