Understanding Breast Cancer: Overview and Insights

Breast cancer is the most common form of cancer among women in industrialized countries, accounting for about 18% of all female cancers. Although mortality is declining in some countries, breast cancer remains the leading cause of death among women aged 35-55 years.

Classical epidemiological studies repeated worldwide have established risk associations with this. These associations have been bolstered by laboratory tissue and animal studies.

The incidence of breast cancer increases with age. Approximately 50% occur in women aged 50-64 years, and a further 30% occur in women over the age of 70 years. There are also marked geographical variations in incidence; in general, the highest incidences are seen in Western countries and the lowest in Asian and African countries. This illustrates the importance of environmental risk factors, as women from low-risk countries, such as Japan who emigrate to higher-risk countries ultimately develop a higher risk associated with their new country. Genetic factors are also important, however as the natural history of this cancer appears to vary between populations.

Age is the greatest risk factor for this cancer. Of the approximately 60% for which identifiable risk factors can be found, age accounts for more than half.

Family History:

The risk of this cancer is increased 2-3 fold in women with a first-degree relative with breast; the risk is also increased, but to a lesser extent, in women with a second-degree relative who is affected.

The risk is particularly great if :

The affected relative is on the maternal side of the family
Two first-degree relatives are affected
The relative has a bilateral
The relative’s cancer was diagnosed before the age of 50 years.

Overall about 10-15% of cancers are attributable to family history, and half of these can be attributed to specific susceptibility genes

Demography – the risk of breast is increased in women from higher socioeconomic classes and in women living in urban areas.

The risk of breast cancer is increased in women who begin menstruating at an early age < 12 years or who undergo menopause at a relatively advanced age >55 years. Age at first full-term pregnancy appears to be the most important factor in reducing the risk of breast cancer. For women who have their first child before the age of about 25 years, the risk of breast cancer is approximately half that for women who have their first child after 30 years of age, or who remain childless. Similarly, multiparous postmenopausal women have a lower risk of breast cancer than nulliparous women.

Obesity is associated with an increased risk of breast cancer in postmenopausal women. This increased risk may be due to the conversion of adrenal androgens to estrogens in adipose tissue. High consumption of animal fats has also been linked to breast cancer.

A recent meta-analysis involving over 150000 women has examined the influence of oral contraceptive use on the risk of breast cancer. The relative risk was slightly increased in women who had used OCs more than 10 years previously. Although the incidence of breast cancer was increased in OC users, the disease mortality remained constant because the cancers tended to be more of a favorable type. This slight increase in risk should, however, be viewed in the context of women’s health in general. It is likely that OCs substantially diminish the risk of ovarian and endometrial carcinoma.

They are also highly effective as a form of conception and as a means of relieving menses-related morbidity. There is no evidence that current formulations of OCs affect breast cancer risk. However, this will not be known for certain for another 30 years, since the cohort of women who have taken the pill are only now reaching the age at which they are at risk of breast cancer.

The long-awaited results of several important trials have recently been published, To some extent these studies have confirmed and refined the risk of breast cancer associated with hormone replacement therapy (HRT), but many unanswered questions have to be resolved.

The consumption of approximately 15 g or more of alcohol each day increases the risk by about 50%. This may be attributable to reduced hepatic estrogen metabolism. However, the increased risk associated with alcohol is small; it has been estimated that if 1000 women over 30 years of age maintained a moderate regular alcohol intake for 2 years one additional case of breast cancer might develop. This should be set against the potential reduction in ischemic heart disease associated with moderate alcohol consumption and the contribution that alcohol could make to the quality of life.

With the rise of modern genetics research, a subcellular and molecular understanding of familial factors in breast cancer is emerging. New technologies have allowed detailed comparisons to be made between the chromosome patterns of normal populations and those at high risk, which meant initially women with very strong family histories.

From these studies, the first genes that were strongly associated with this were identified notably BRCA1(17q21) and BRCA2 ( 13q14). The risk of this cancer with these two genes in the absence of family history is high. These genes are implicated in more than 4% of breast cancer and are up to 25% of patients diagnosed before the age of 40 years. They are also linked to ovarian cancers. The risk associated with BRCA2 appears less than that with BRCA1, but the presence of the gene mutation carries additional smaller risks of male breast and prostate cancers and perhaps others.

Genes represent predisposition. The internal hormonal and regulatory milieu of the body and life events such as diet, drugs, pregnancies, and levels of activity are stimuli in a dynamic homeostatic process. The interaction between predisposition and provocation is when malignancy appears. It is reasonable to hypothesize that genes influence susceptibility. Even in these early days, there is evidence that gene expression signatures can predict.

Risk of disease
Relapse and survival risk
Patterns of recurrence
Response to therapy

When these regulatory pathways are better understood, establishing the point at which intervention is necessary will pose a substantial challenge and will profoundly influence our preventive and treatment strategies in the future.

Published Articles by Dr Radheshyam Naik