Breast cancer: risk and prevention

According to the National Cancer Registry, cancer prevalence is growing in Mauritius with 2286 new male and 3280 new female cancer cases registered between 2005 and 2008. The types of cancer in Mauritius are as follows: in males - colon-rectum (14%), prostate (10.5%), oral cancer (8%) and lung (9.6%); among females, breast cancer (38%) is the most prevalent cancer accounting for a total of 1239 new cases followed by cancer of the uterine cervix (10%), colon-rectum (4.8%) and ovaries (5.6%). 1950 males and 1900 females died of cancer during the period 2005–2008. In Mauritius, around 1500 new cases for breast cancer & 350 related-deaths are registered every year. The highest incidence of breast cancer was recorded for women above 50 years.

At the international level, the incidence of breast cancer is rising in most countries and is projected to rise further over the next 20 years despite current efforts to prevent the disease.

There is cause for concern, the reason we chose to highlight this topic for the Mauritian public and summarize hereunder an interesting article entitled ‘Risk determination and prevention of breast cancer’ by Howell et al. Breast Cancer Research 2014, 16:446

What are risk factors for breast cancer?

  • Age-related factors

The Collaborative Group on Hormonal Factors in Breast Cancer (2002) 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 women, by age 70 if women had on average more children and breastfed for longer periods.

Lower age of menarche (first menstrual cycle), late age of first pregnancy, fewer pregnancies, shorter or no periods of breastfeeding, and a later menopause.

  • Lifestyle factors

Increase in obesity, alcohol consumption, inactivity, and hormone replacement therapy (HRT).

Many hormones (steroid hormones such as estradiol, testosterone, and sex hormone-binding globulin in pre-and post-menopausal women) and growth factors (insulin-like growth factor-1) are associated with an increased risk of breast cancer.

  • Inherited (hereditary) factors

The impact of hereditary breast cancer has also increased. However, mutations in breast cancer genes such as BRCA1/2 affect only small numbers of women.

 What methods of risk assessment exist?

  • Computer models

These models are based on family history and non-familial risk factors and they can predict with some degree of accuracy the probability that a woman with a particular combination of risk factors will develop breast cancer over time.

Limitation of models: a woman can be informed with some accuracy that she has a 1 in 3 lifetime risk of breast cancer, but the model cannot say whether she is the one who will develop the disease or whether she is one of the two women who will not.

  • Data correlation with risk factors

More knowledge is required that include other risk factors to current models such as mammographic density, single nucleotide polymorphisms (SNPs), estimation of hormone levels, and lifestyle factors. For instance, visually assessed mammographic density indicated that the relative risk of breast cancer for women with 70% or more density was 4.64-fold greater compared with women with less than 5% density.

Single Nucleotide Polymorphisms (SNPs) are common alterations in the DNA code. The number of validated SNPs associated with breast cancer risk is currently over 70, but it is thought that there may be hundreds more that increase breast cancer risk.

  • New biomarkers

New biomarkers* for risk prediction will probably come in the near future from measures in blood or tissues but there are none at present.

*Biomarkers- molecules that can be detected and measured in parts of the body like the blood or tissue. They may indicate either normal or diseased processes in the body.

 Chemoprevention as preventative therapy

The use of selective estrogen receptor modulators (SERMs) by women at increased risk of breast cancer has proven to be positive. A reduction of 38% was noted using tamoxifen 20 mg per day. Tamoxifen acts by blocking the estrogen receptor (ER). Tamoxifen was significantly superior to raloxifene for preventing invasive breast cancer.

The development of orally active ER downregulators similar to fulvestrant – ‘Faslodex’ - (which has to be given intramuscularly) may be superior to tamoxifen.

Aromatase inhibitors (AIs) (suppress estrogen formation) – exemestane and anastrozole - can also reduce breast cancer incidence.

 Life style/energy restriction/weight control/physical activity

The World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) has estimated that over 40% of post-menopausal breast cancer could be prevented by reductions in alcohol, excess body weight, and inactivity.

It is estimated that for each 5 kg/m2 increase in body mass index (BMI) the risk of breast cancer was increased by 12%.

In general, dietary pattern and diets composed of vegetables, fruit, fish, and soy are associated with a decreased risk of breast cancer.

A recent review of 73 observational studies indicated that moderate (150 minutes) to vigorous (75 minutes) physical activity reduces breast cancer risk by an average of 25% in pre- and post-menopausal women compared with inactive women.

Women who drank alcohol or smoked (or both) during the period between menarche and first pregnancy are the most susceptible for carcinogenesis due to an increase in premalignant lesions in the breast.

Hormonal chemoprevention is suggested for women at increased risk, whereas lifestyle factors can be applied to all women since all are at some risk of breast cancer.

Conclusions 

  • Risk of developing breast cancer may be estimated by standard computer models making use of mammographic density and appropriate single-nucleotide polymorphisms.
  • Potentially 50% of breast cancer cases could be prevented in the subgroup of women at high and moderate risk of breast cancer by using current chemoprevention (tamoxifen, raloxifene, exemestane, and anastrozole)
  • In all women, lifestyle measures, including weight control, exercise, and moderating alcohol intake, could reduce breast cancer risk by about 30%.

In the light of this article, it is clear that we need data related to cancer risks of the Mauritian population that could guide preventive and curative actions in a more efficient manner.

A report on breast cancer statistics prepared by the Ministry of Health and Quality of Life can be accessed at www.uom.ac.mu/medicalupdate/files/2013/.../DrShyamMANRAJTalk.pdf

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