Introduction

Breast cancer is a complex disease that develops when cells in the breast tissue begin to grow abnormally and uncontrollably and form tumours. It also stands as the leading cause of cancer-related deaths among people assigned female at birth (AFAB). Despite extensive laboratory, epidemiological, and clinical research over the years, the rate of breast cancer continues to escalate.

The origins of breast cancer are multifaceted, involving a complex interplay of genetic, environmental, dietary, hormonal, and hereditary components. Various risk factors have been identified that increase the likelihood of developing this disease. These include a personal history of breast cancer, genetic predisposition within the family, adiposity, tobacco use, regular alcohol intake, precocious menarche, late-onset menopause, sedentary lifestyle, nulliparity, and the use of hormone replacement therapies. Each of these factors contributes to the overall risk profile for breast cancer, highlighting the complexity of its aetiology.¹

Understanding the causes of breast cancer is crucial for several reasons. First, it helps identify individuals who may be at higher risk, allowing for more targeted screening and prevention strategies. Second, this knowledge can guide lifestyle choices that may help reduce the risk of developing the disease. Lastly, understanding the underlying causes can lead to better treatment approaches and potentially new ways to prevent breast cancer altogether.

Genetic factors

Genetic factors play a significant role in breast cancer development. While only about 5-10% of breast cancers are thought to be hereditary, these cases often occur at younger ages and can be more aggressive.¹

Inherited genes and family history

BRCA1 and BRCA2 genes: are two highly penetrant genes strongly linked to increased breast cancer risk. These major genes play a crucial role in breast carcinogenesis, significantly elevating the likelihood of developing breast cancer when mutated. Their identification has been pivotal in understanding hereditary breast cancer susceptibility.² 

Other high-risk genes: high penetrant genes associated with elevated breast cancer risk are TP53, PTEN, STK11, and PALB2 gene.³

Research has revealed a significant correlation between family history and breast cancer risk, even in cases without BRCA gene mutations. People AFAB with two or more relatives who have had breast cancer, but who do not carry BRCA mutations themselves, face an elevenfold increase in breast cancer risk compared to the general population. 

Additionally, individuals who carry BRCA1 or BRCA2 mutations and have close relatives diagnosed with early-onset breast cancer are at an even higher risk. Notably, the increased likelihood of developing breast cancer persists across all age groups for those with a family history of the disease.⁴

Hormonal factors

Hormones, particularly oestrogen and progesterone, play a crucial role in breast cancer development.

• Oestrogen exposure and early menstruation: prolonged exposure to estrogen is associated with an increased risk of breast cancer. This is because oestrogen stimulates the growth of breast cells, and the more a cell divides, the more opportunities there are for genetic mistakes to occur. Women who start menstruating before age 12 have a slightly higher risk of breast cancer, likely due to longer lifetime exposure to oestrogen^5,6
• Late menopause: AFAB who experience menopause after age 55 have a higher risk, due to longer exposure to oestrogen⁷
• Hormone replacement therapy: long-term use of combined oestrogen-progestin hormone therapy for menopausal symptoms can increase breast cancer risk⁸

Lifestyle factors

• Obesity: Epidemiological studies show obesity increases the risk of developing breast cancer. In postmenopausal women, excess fat raises oestrogen levels, which can promote hormone-responsive tumours. Obesity also causes insulin resistance, affecting cancer growth. Changes in fat-related proteins, inflammation, and DNA damage further increase cancer risk, influenced by genetics and differing by menopausal status and cancer type^2,9,10
• Alcohol consumption: The risk of breast cancer is notably elevated by 4–15% with light alcohol consumption¹¹
• Lack of physical activity: regular physical activity lowers the risk of breast cancer for all women, regardless of family history. A study with over 230,000 cases shows daily exercise reduces risk compared to inactivity. It affects BMI, which is linked to breast cancer risk in post-menopausal women, and it reduces oestrogen and insulin levels, further decreasing breast cancer risk¹²
• Smoking: Carcinogens present in tobacco are transported to breast tissue, increasing the probability of mutations occurring in oncogenes and suppressor genes, particularly p53. As a result, both active and passive smoking play significant roles in initiating processes that promote cancer development²

Environmental factors

• Radiation exposure: The mammary gland is particularly vulnerable to radiation-induced malignancies, especially when exposure occurs at a younger age. According to a large population-based study, women exposed to radiation for diagnostic or therapeutic purposes, such as tuberculosis screening, pneumonia monitoring, or previous cancer treatment, face two to three times higher risk of developing breast cancer. Those who have undergone whole-lung irradiation or received radiation during childhood cancer treatment also face the highest risk. Additionally, survivors of sarcoma or leukaemia treated with high-dose alkylator and anthracycline chemotherapy are at significant risk of developing breast cancer at a younger age⁴
• Occupational hazards and environmental pollutants: Risk factors associated with an increased likelihood of breast cancer include exposure to both ionising and non-ionising radiation, working night shifts, and contact with pesticides, polycyclic aromatic hydrocarbons (PAHs), and certain metals. These factors are thought to elevate breast cancer risk via various mechanisms such as DNA damage, disruption of hormonal balance, and cellular stress

For example, radiation can cause direct damage to DNA, which may result in cancerous mutations. Both pesticides and PAHs frequently function as endocrine disruptors, compromising normal hormonal activities that could foster cancer proliferation. Certain metals have the potential to induce oxidative stress and inflammation, thereby creating an environment that is favourable for cancer development. The increased risk observed in younger individuals indicates that exposures during early life may have more significant effects, highlighting the urgent necessity for robust occupational safety practices and environmental regulations to reduce these risks.⁴

Reproductive factors

• Age at first pregnancy: Women who experience their first full-term pregnancy at a younger age, especially before the age of 20, have a considerably lower chance of developing breast cancer later on compared to those who give birth for the first time after the age of 30. Nevertheless, this protective benefit is seen only in cases of hormone receptor-positive breast cancer and does not affect the risk of hormone receptor-negative breast cancer¹³

Age and gender

• Increased risk with age: The incidence rate of breast cancer gradually rises with age, reaching its highest levels during menopause and the postmenopausal period. Approximately 80% of all breast cancer cases occur in women over the age of 50, and about 40% are in those older than 67²
• Higher prevalence in women: The greatest risk factor for breast cancer is female gender. About 99% of breast cancer cases are diagnosed in women, whereas only 0.5–1% are found in men. This disparity is largely due to differences in breast tissue composition and hormonal influences, particularly oestrogen and progesterone, which play a crucial role in the development and growth of most breast cancers^1,11

Other risk factors

• Previous breast conditions: Women who have had certain benign breast conditions, such as atypical hyperplasia, have an increased risk of breast cancer¹⁴

FAQs

Does wearing a bra cause breast cancer?

No, there is no scientific evidence to support the claim that wearing a bra increases breast cancer risk.

Can birth control pills cause breast cancer?

Some studies suggest a slightly increased risk of breast cancer in current users of hormonal contraceptives, but the risk appears to return to normal after stopping use.

Is breast cancer preventable?

While it is not possible to prevent all breast cancers, maintaining a healthy lifestyle, limiting alcohol consumption, staying physically active, and maintaining a healthy weight can help reduce risk.

How often should women get screened for breast cancer?

Guidelines vary, but many organisations recommend starting regular mammograms at the age of 40 or 50.

Summary

Breast cancer develops when cells in the breast tissue grow abnormally and form tumours, and it is the leading cause of cancer deaths among people assigned female at birth. The rates of breast cancer are still rising despite the research. The causes of breast cancer are complex and vary, including genetic, environmental, dietary, hormonal, and hereditary factors. Risk factors include a history of breast cancer, family genetics, obesity, smoking, alcohol use, early menstruation, and others. Understanding these causes is essential for two main reasons: it helps identify high-risk individuals for targeted screening and can guide lifestyle changes to reduce risk. 

Genetic factors, such as mutations in the BRCA1 and BRCA2 genes, significantly increase breast cancer risk, as do other high-risk genes like TP53 and PTEN. Additionally, a family history of breast cancer raises risk levels, even without BRCA mutations. 

Hormones also play a significant role where high levels of oestrogen increase risk. Lifestyle factors such as obesity, alcohol consumption, lack of physical activity, and smoking further raise the likelihood of developing breast cancer. Environmental exposures, like radiation and certain occupational hazards, are also linked to increased risk. 

Lastly, age, gender, and previous breast conditions contribute to breast cancer risk. Women over 50 are more likely to develop breast cancer, and the disease predominantly affects females due to hormonal influences. Some factors remain uncertain, including diet, stress, and the effects of cosmetic breast implants.