Cancer Research UK : Breast Cancer risk factors

Breast Cancer risk factors

This page contains information on breast cancer risk and

age
reproductive history including age at menarche, age at first birth, parity, breastfeeding and age at menopause
exogenous hormones
endogenous hormones
bodyweight
physical activity
alcohol
diet
height
ionising radiation
socio-economic status
mammographic density
benign breast disease
and personal or family history of breast cancer

A substantial proportion of the breast cancer cases experienced in developed countries can be explained by factors which influence exposure to oestrogen, including reproductive and hormonal factors, obesity, alcohol and physical activity1.

Age and risk of breast cancer

The strongest risk factor for breast cancer (after gender) is age: the older the woman, the higher her risk. Risk by age is shown in Table 4.12.

Table 4.1: :Risk of developing breast cancer by age,females, England, 1996

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Reproductive history and breast cancer risk

Women in developed countries are at increased risk of breast cancer compared with women from less developed countries. Much of this variation can be explained by the fact that women in developed countries have fewer children and a limited duration of breastfeeding.

It is estimated that the cumulative incidence of breast cancer in developed countries would be reduced by more than half, from 6.3 to 2.7 per 100, if the average number of births(6.5 instead of 2.5 births) and lifetime duration of breastfeeding (breastfeed each child, on average, for 24 months instead of a lifetime mean of 8.7 months) prevalent in developing countries in the 1990s were to occur3 (Figure 4.1).

Figure 4.1: Estimated cumulative incidence of breast cancer in developed countries if women had family sizes and breastfeeding patterns typical of developing countries

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Reproductive factors that influence breast cancer risk

Age at menarche
Early age at menarche has been consistently associated with an increased risk of breast cancer. Average age of menarche in developed countries fell from around 16-17 years in the mid 19th century to 12-13 today4. Relative risk for premenopausal breast cancer is reduced by an estimated 7% for each year that menarche is delayed after age 12 years, and by 3% for postmenopausal breast cancer5. Low risk countries such as China have a later average age at menarche (16-17 years). Nutrition in early life strongly influences age of menarche.
Age at first birth
The younger the woman is when she begins childbearing, the lower her risk of breast cancer. The relative risk of developing breast cancer increases by 3% for each year of delay3. For example, a woman who has her first baby at age 28 would have a 3% lower risk of breast cancer than a woman who had her first baby at 29, all other factors being equal.
Parity
The effect of parity on reducing the risk of breast cancer has long been recognized. In the 18th century Bernado Ramazzini (1633-1714) reported the high rate of breast cancer in nuns compared with married women and speculated that this might be associated with their lack of children. In one meta-analysis nulliparity was associated with a 30% increase in risk compared with parous women6. The higher the number of full-term pregnancies, the greater the protection. There is a reduction in risk of 7% for each birth after the first, in the absence of breast feeding3.
Breastfeeding
Women who breastfeed reduce their risk compared with women who do not breastfeed3. The longer a woman breastfeeds, the greater the protection: risk is reduced by 4.3% for each year a woman breastfeeds3.
Age at menopause
Late menopause increases the risk of breast cancer7. For each year menopause is delayed, there is an approximate 3% increase in breast cancer risk8. Postmenopausal women have a lower risk of breast cancer compared to premenopausal women of the same age. This is true for both natural menopause or menopause induced through surgery8.

Exogenous hormones and breast cancer risk

The Pill

The use of oral contraceptives (OCs) slightly increases the risk of breast cancer in current and recent users, but there is no significant excess risk ten or more years after stopping use (Table 4.29).

Table 4.2: Oral contraception and the relative risk of breast cancer

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These estimates are based on a collaborative analysis of 54 studies in 25 countries, with data on over 50,000 women with breast cancer. Cancers diagnosed in women who have used OC tend to be less clinically advanced than those detected in never-users. OC users are generally younger women whose breast cancer risk is comparatively low, so the small excess risk in current users will result in a relatively small number of additional cases.

The formulation of OCs has changed considerably since use became widespread in the 1960s but current evidence suggests that this does not affect risk9. The risk of oral contraceptive use in women is similar regardless of a woman’s family history, ethnic origin, years of education, age at menarche, height, weight, menopausal status and alcohol consumption9.

Hormone Replacement Therapy (HRT)

HRT use increases the risk of breast cancer and reduces the sensitivity of mammography10-13. The risk of breast cancer for current or recent users of HRT increases by 2% per year of use. For women who had used it for at least five years (average 11 years) the risk increase was 35%. 45).

The effect is substantially greater for oestrogen-progestagen combinations than for oestrogen only HRT. Risk increases with duration of use: the risk for current users of oestrogenprogestagen combinations for 10 or more years was 2.31 (CI 2.08-2.56) compared to 1.74 (CI 1.60-1.89) for 1-4 years of use. Risk decreases with cessation of use; past users have a similar risk to never users13.

In the UK over the past ten years, it is estimated that 20,000 extra breast cancer cases have occurred among women aged 50-64 as a result of HRT use and threequarters (15,000) of these additional breast cancers are due to the use of oestrogenprogestagen HRT13.

HRT is used by over 20 million women in western countries14 to counteract menopausal symptoms and is an important source of exogenous oestrogen and in some cases progestagen exposure. A recent review concluded that the excess incidence of breast cancer, stroke and pulmonary embolism in postmenopausal women who use HRT for 5 years was greater than the reduction in incidence of colorectal cancer and hip fracture14.

HRT should not be used for prevention of cardiovascular disease but the risks and benefits for treating menopausal symptoms should be evaluated on an individual basis.

Endogenous Hormones and breast cancer risk

Higher levels of endogenous hormones have long been hypothesized to increase breast cancer risk. A pooled analysis of nine prospective cohort studies found a statistically significant increased risk of breast cancer in postmenopausal women with higher levels of sex hormones15. The risk was approximately double for women whose oestradiol levels were in the top quintile compared with women whose oestradiol levels were in the bottom quintile. Evidence for premenopausal women is inconclusive.

Bodyweight and breast cancer risk

Overweight and obesity, as measured by high body mass index (BMI), moderately increases the risk of postmenopausal breast cancer and is one of the few modifiable risk factors for breast cancer16. BMI is calculated by dividing weight in kg by height in metres². A BMI under 20 is classified as underweight, 26-30 as overweight, and over 30 as obese.

About 8% of breast cancer cases in the UK may be attributable to overweight and obesity17. In one pooled analysis the risk of developing breast cancer was increased by around 30% in postmenopausal women with a BMI >28kg/m2 compared to a BMI of less than 21kg/m216.

There is some evidence that the effect of BMI is stronger in women who do not use HRT17. In a prospective mortality study the risk of breast cancer death increased with increasing BMI reaching a two-fold increased risk of death for the highest (>=40kg/m2 ) compared to lowest BMI category (< 24.9kg/m2)18.

After the menopause, when the ovaries stop producing oestrogen, adipose tissue is the primary source of endogenous oestrogen so obese and overweight women are exposed to higher levels of oestrogen. Obesity is also associated with lower levels of sex hormonebinding globulin (SHBG) which increases the amount of bioavailable oestradiol19. In premenopausal women, some but not all studies have observed that a higher BMI is associated with a slightly lower risk of breast cancer – possibly because it results in decreased exposure to endogenous oestrogens through increased anovulatory cycles.

Physical activity and breast cancer risk

A recent report from the International Agency for Research on Cancer concluded that physical activity has a preventive effect on breast cancer20. This may be an indirect effect with exercise lowering BMI, or a direct effect on hormonal and growth factor levels.

The magnitude of this effect varies between studies; a typical result is a 30-40% reduction in the risk of breast cancer with a few hours per week of vigorous activity versus none1.

Alcohol and breask cancer risk

A significant association between alcohol intake and breast cancer has been found, with an increase of risk of 7% for each additional 10 grams of alcohol consumed on a daily basis (Figure 4.221).

Figure 4.2: Estimated cumulative incidence of breast cancer per 100 women in developed countries,according to the number of alcoholic drinks consumed each day

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Around 4% of breast cancers in women in developed countries may be attributable to alcohol. Although alcohol and tobacco smoking are closely related social habits, there is no direct association between tobacco and breast cancer.

Diet and breast cancer risk

A diet high in fat has been positively associated with breast cancer in international correlation studies22, animal studies23 and case control studies24. However, pooled analyses of cohort studies generally found no important association between fat intake and breast cancer risk25-26 while a meta-analysis found a modest positive relation with both total and saturated fat intake27.

A recent prospective study suggests these differences may be due to the difficulties of accurately recording fat intake28. In this study the use of a detailed 7- day food diary revealed a significant association between saturated fat (found mostly in high fat milk, butter, meat, cakes and biscuits) and breast cancer risk, which the more commonly used food frequency questionnaire did not.

Overall, the evidence suggests fat intake, particularly animal fat, may cause a small increased risk of breast cancer but probably does not play as large a role as was once thought.

Height and breast cancer risk

Taller women have an increased risk of breast cancer29. A pooled analysis estimated that the relative risk for women 1.75 metres or taller compared with women shorter than 1.6 metres was 1.22 for all women and 1.28 for postmenopausal women16. There was an approximate increase in relative risk of 7% for each additional 5 centimetres in height for postmenopausal women and 2% for premenopausal women.

The underlying mechanism for the association between height and breast cancer risk is unclear, and it is likely that height may be a marker for other exposures that influence breast cancer risk30.

Ionising Radiation and breast cancer risk

Ionising radiation is an established risk factor for breast cancer and excessive exposure to radiation should be avoided. The effect of radiation on the breast is strongly related to age at exposure ie the younger the woman is exposed the greater the excess risk.

A recent study estimated that exposure to diagnostic xrays may be responsible for 29 cases per year of female breast cancer before the age of 75 in the UK, an attributable risk of 0.1%31 Overall 0.6% of the cumulative risk of cancer to age 75 might be radiation-induced in the UK– approximately 700 cases of cancer each year. This was low compared to the other developed countries studied.

Another group at increased risk are women treated for Hodgkin’s disease by mantle irradiation where there is an approximate doubling of lifetime risk.51 Women treated in this way before age 35 are being recalled nationally and offered special surveillance.

Socio-economic status and breast cancer risk

Breast cancer is one of the few cancers to have a higher incidence in the more affluent social classes (Figure 4.332). The age standardised incidence rate is 115.1 per 100,000 women in the least deprived quintile compared to 97.3 in the most deprived quintile. This is probably a reflection of other factors including reproductive history and early nutrition.

Figure 4.3: Incidence, mortality and cause-specific survival at 5 years by deprivation quintile, Scotland, female breast cancer patients diagnosed 1991-95

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Mammographic density and breast cancer risk

Mammographic density is related to the risk of breast cancer. (Density relates to the relative amounts of fat, connective tissue and epithelial tissue in the breast. Breasts with a higher proportion of fatty tissue are less dense. Cancer is less easily detected in denser breasts.) Women with denser breasts have 2-6 times the risk of breast cancer compared to women with less dense breasts33. It is estimated that 20-30% of the variation in breast density is accounted for by menopausal status, weight and parity34 and there is growing evidence that the more important determinant of breast density is inherited34, 35.

Finding the gene or genes responsible for breast density may lead to a better understanding of the development of breast cancer36, 37.

Benign breast disease and breast cancer risk

Benign breast disease34 is a generic term describing all non-malignant breast conditions. As such it encompasses diseases associated with an increased risk of breast cancer and others that do not have a raised risk.

The commonest breast lump in young women is a fibroadenoma which is not associated with an increased risk of breast cancer.

Women in their 30s and 40s may develop cysts and those that suffer multiple cysts are at slightly increased risk of breast cancer.

Women who have had biopsies that showed proliferative breast disease without atypia have a 2-fold increased risk, while women with atypical hyperplasia have a 2-5 fold increased risk37-39.

The presence of lobular carcinoma in situ increases the risk of developing cancer in either breast whereas DCIS may progress to invasive cancer within the affected breast.

Personal history of breast cancer

If a woman has had breast cancer, her risk of developing a second primary breast cancer is 2-6 times the risk seen in the general population of developing a primary breast cancer40.

Family History of Breast Cancer

A woman with one affected first degree relative (mother or sister) has approximately double the risk of breast cancer of a woman with no family history of the disease; if two (or more) relatives are affected, her risk increases further41,42.

However, over 85% of women who have a close relative with breast cancer will never develop the disease, and more than 85% of women with breast cancer have no family history of it42. In developed countries it is estimated that hereditary factors contribute around a quarter of inter-individual differences in susceptibility to breast cancer, while environmental and lifestyle factors contribute the remaining three-quarters1.

A small proportion of women have a particularly strong family history of breast cancer and are at very high risk. Mutations in the breast cancer susceptibility genes BRCA1 and BRCA2 account for the majority of families with four or more affected members and 2-5% of all breast cancers43. Women carrying such a mutation have a 50-80% chance of developing the disease.

Genetic testing for faulty BRCA genes is available on the NHS for women with a very strong family history. Increased susceptibility to breast cancer is also a feature of several rare, familial cancer syndromes (Table 4.4).

Table 4.4: Rare familial cancer syndromes associated with breast cancer

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Since breast cancer affects one woman in nine there will be many women who have a mother or sister with the disease. But only if there are several family members with early onset breast cancer is there a likelihood of a significant inherited predisposition to the disease44.

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