Introduction 

Cancer is the leading cause of death worldwide, with breast cancer being one of the most common cancers, having caused 670,000 deaths globally in 2022, according to the World Health Organization. In the UK, 1 in 7 people assigned female at birth (AFAB) are at risk of developing breast cancer in their lifetime. The majority of breast cancer cases occur in people AFAB, however, there is a 0.5%–1% risk of breast cancer occurring in people assigned male at birth (AMAB).

Breast cancer is a disease that occurs when abnormal cells in the breast grow and divide uncontrollably, forming tumours. The breasts are made up of different structures and cancer can start from any cells in any part of the breast, most commonly the cells of the milk ducts. 

There are many types of breast cancer, and an early diagnosis often results in better outcomes and a higher survival rate. There is no single cause of breast cancer, but multiple risk factors can increase the possibility of getting breast cancer. However, having these risk factors does not automatically mean one has cancer until a diagnosis is confirmed. These risk factors are divided into non-modifiable and modifiable risk factors.

Non-modifiable risk factors

Non-modifiable risk factors are factors that are not under one’s control but can be managed and monitored through screenings and early diagnosis. These factors include: 

• Gender 
• Age 
• Genetic factors 
• Family history of cancer
• Previous history of cancer 
• Reproductive history 
• The density of breast tissue 
• Radiation exposure

Sex or gender

Being AFAB is one of the major factors linked to an increased risk of developing breast cancer due to hormonal stimulation, particularly the hormones oestrogen and progesterone (also known as the female sex hormones). 

Oestrogen is known to have a positive association with the risk of breast cancer – any irregular alteration of the hormone levels in the body results in a higher risk, both, in pre-menopausal (before menopause) and post-menopausal women.¹ Unlike people assigned male at birth (AMAB), who have minimal oestrogen levels, they carry the hormone testosterone (also known as the male sex hormone). An increased risk of breast cancer is seen in pre-menopausal women who present with higher levels of testosterone and in post-menopausal women with higher levels of oestrogen and testosterone.² Similarly, higher oestrogen levels in people AMAB are linked to a higher risk of breast cancer.

Although people AMAB constitute 1% of breast cancer patients, there has been a trend toward an increase in cases.³ Since breast cancer in people AMAB is rare and often overlooked, diagnosis is only often made at an advanced stage of the disease.

Age

The risk of breast cancer increases with advancing age. 

Here are some statistics from the UK: 

• 82% of breast cancer patients are aged 50 or older; 18% of patients are under 50 
• Although 24% of breast cancers occur in women over 75, they contribute to almost 50% of total deaths caused by breast cancer

The poor survival observed in patients under 75 years old is due to existing medical conditions like diabetes mellitus, coronary heart disease, hypertension, stroke, among others.⁴ 

Genetic factors

The two main genes linked to breast cancer are the BRCA1 (Breast Cancer gene 1) and BRCA2 (Breast Cancer gene 2). 

Everyone has two copies of each of these genes – one from each parent. These genes are responsible for repairing any damaged DNA when cells are dividing. Therefore, any mutation to these genes would be harmful as one no longer has the repair mechanism in place, leading to uncontrollable growth of cells and thus, cancer. 

The mutated or faulty genes can be inherited from birth and increase the risk of developing breast cancer.⁵ Besides the increased risk of breast cancer, BRCA1 and BRCA2 mutations also increase the risk of ovarian cancer in people AFAB and prostate cancer in people AMAB.^6,7

Other inherited mutated genes associated with an increased risk of breast cancer include:⁸ 

• TP53 gene 
• PALB2 gene 
• ATM gene 
• CHEK2 gene 
• PTEN gene
• STK11 gene

Family history

A family history of breast cancer is one major risk factor that increases the chance of developing breast cancer. 

Women have a 1.75-fold higher risk of breast cancer if a first-degree relative has been affected.⁹ 

First-degree relatives include: 

• Mother
• Father 
• Daughter 
• Son 
• Sister 
• Brother 

If more than one first-degree relative has been affected, the risk of developing breast cancer is significantly increased to 2.5-fold, with an even higher risk when the affected relatives are were under 50 years old at the time of their diagnosis.⁹ 

Previous history of cancer

Having already had breast cancer increases the risk of subsequent breast cancer, either in the same or different breast.¹⁰ Other non-cancerous breast conditions, such as atypical hyperplasia, intraductal papilloma, and lobular carcinoma in situ (LCIS), are also associated with a significant increase in the risk of developing breast cancer.¹¹

There is a high risk of breast cancer among people who previously had any of the following cancers:

• Melanoma skin cancer
• Lung cancer
• Bowel cancer
• Womb cancer
• Chronic lymphocytic leukaemia

Reproductive history

The age at which someone AFAB has her first menstrual period (also known as menarche) could be indicative of the risk factor associated with breast cancer. 

The earlier the first menstrual period, the higher the risk of breast cancer due to longer exposure to the hormone oestrogen. Research has found that in females who had their first period before the age of 12, the oestrogen expression in each menstrual cycle was higher compared to females who had their first period after the age of 13.¹² Comparatively, people AFAB who experience menopause before the age of 55 are at a lower risk of breast cancer.¹³ 

Pregnancy and breastfeeding history are other hormonal markers of breast cancer risk. 

People AFAB who experience a first-full-term pregnancy before the age of 30, have a lower risk of breast cancer. A narrow birth interval between first and second childbirth is also associated with risk reduction. The cancer-protective effects are provided by the pregnancy itself, which was observed from the 34th pregnancy week.^14,15 Similarly, the protective effect is provided via prolonged breastfeeding. Women who breastfeed for a longer period have a lower risk of breast cancer.¹⁶ The reduced risks of breast cancer are due to reduced activity of oestrogen in the body.

Density of breast tissue

Women with a higher density of breast tissue have a 4-to 6-fold higher risk of developing breast cancer, compared to women with low density breast tissue.¹⁷ Dense breast tissue consists of more breast cells, connective tissues, and less fat tissue. Therefore, dense breast tissue is more commonly seen in younger females as breast density typically decreases with age. Breast density can only be determined through a mammogram – dense breast tissue cannot be felt via self-examination and is different from breast lumps.¹⁷

Exposure to radiation

Tests such as X-rays, CT scans, and radiotherapy treatment, expose oneself to radiation, which can increase the risk of breast cancer. 

Generally, X-rays and CT scans are ordered by medical professionals on a when-needed basis, and the amount of radiation used is very small hence, the risk is usually negligible. A mammogram is another radiation test that is used as part of a breast screening programme, with minimal radiation. 

Furthermore, the risk of developing breast cancer is higher if one undergoes radiotherapy treatment for breast cancer. The risk is small and is justified by successful treatment of the original breast cancer. Similarly, any other type of cancer that requires radiotherapy to the chest area, increases the risk of developing breast cancer, compared to someone who has not had radiotherapy. It is commonly seen in patients who had chest radiotherapy for Hodgkin lymphoma – breast screening is usually offered upon completion of treatment if a patient is at high risk.

Modifiable risk factors

Modifiable risk factors are those that can be changed or controlled by a person. An early intervention to modify these risk factors could reduce the risk of developing breast cancer. They mainly consist of lifestyle factors and the use of hormone replacement therapy (HRT).

Lifestyle factors

Diet and nutrition

Diet plays an important role, as what we consume daily can either promote or prevent the development of breast cancer. 

Poor dietary habits can lead to obesity, which is a major risk factor for breast cancer. An example of poor dietary habits is the consumption of highly processed meat, which is classified as a Group 1 carcinogen – a cancer-causing product. Similarly, highly processed food predisposes one to obesity and increases the risk of breast cancer, as these foods are rich in fats and sugar. Examples of the most commonly eaten ultra-processed foods in the UK are:

• Factory-made bread 
• Pre-packed meals
• Breakfast cereals
• Sausages and other reconstituted meat products
• Confectionery
• Biscuits
• Pastries, buns and cakes
• Factory-made chips and fries
• Soft drinks, fruit drinks and fruit juices
• Salty snacks including crisps
• Sauces, dressings and gravy

On the contrary, a diet high in fruits, vegetables, whole grains and lean protein is linked to a reduction in breast cancer risk. 

There are many different types and sources of fats with differing effects on breast cancer risk. A great example is omega-3 fatty acids like alpha-linolenic acid (ALA). ALA from fruit and vegetable oils reduces the risk of breast cancer, while ALA from nut mixes and processed foods increases the risk of breast cancer. Overall, a healthy and balanced diet is required to maintain a healthy body weight as the risk of breast cancer is associated with obesity or being overweight.¹⁸

Several studies suggest that green tea and turmeric may reduce the risk of breast cancer due to the anti-cancer effects found in the specific compounds of the plants.^19,20

Alcohol intake

Excessive alcohol intake is associated with an elevated risk of breast cancer, as it causes an increased level of oestrogen. Besides triggering a hormonal imbalance, it also causes excessive fat gain with higher BMI levels, which further adds to the risk.²¹

Physical activity

Physical activity is associated with a reduced risk of breast cancer, although the mechanism remains unknown. Regular physical activity is essential to living a healthy life. There are different types of physical activities available for different age ranges. Examples of some physical activities in general are:

• Walking
• Cycling
• Swimming
• Walking up the stairs
• Sports, like football, rugby, netball and hockey
• Yoga
• Pilates

Smoking

Smoking tobacco increases the risk of breast cancer. 

Carcinogens found in tobacco reach the breast tissues, increasing the likelihood of mutations within the genes that play a vital role in cancer. The longer the duration of being a smoker and the higher the smoking frequency (number of cigarettes per day), the higher the risk of developing breast cancer.²²

Hormone replacement therapy (HRT)

Women usually start hormonal replacement therapy (HRT) to reduce the symptoms of menopause. Women who use HRT for longer than five years are at an increased risk of developing breast cancer. There are two types of HRT:

• Combined HRT (oestrogen and progestogen) 
• Oestrogen-only HRT

The risk of breast cancer is higher for people AFAB who use combined HRT, than those who take an oestrogen-only HRT. However, once the use of HRT is stopped, the elevated risk of breast cancer reduces within two years.²³

Oral contraceptives

Current or recent use of oral contraceptives has been associated with an increased risk of breast cancer. 

This includes both the combined oral contraceptives containing oestrogen and progesterone, and progesterone-only contraceptives. The risk associated with oral contraceptives, however, is smaller in younger women who use them. Nevertheless, the risk has to be weighed against the benefits before deciding on using contraceptives long-term.²⁴

Summary

• There are multiple risk factors associated with breast cancer; while some reduce the risk, a majority of them increase the risk 
• Risk factors associated with an increased risk of breast cancer include hormonal imbalances, ageing, family history and personal history of cancer 
• As these factors are non-modifiable, one can only manage them by doing early screening or regular medical check-ups 
• However, there are risk factors that can be controlled, for instance, lifestyle habits – healthy and balanced diet, limited alcohol intake and not smoking, lead to a reduction in the risk of breast cancer and promote longevity