Do we understand the effect of mammography screens on breast cancer incidence and mortality?

Mammographic screening is widely used to identify significant breast cancer risk in women. However, the utility of screening in improving breast cancer mortality rates is often an issue for debate. This article provides a snapshot of current opinions regarding this issue.

Mammography as a breast screen tool

Mammography is the best screening tool for breast cancer used today. With mammographic screening, tumours can be identified at an early stage, thereby increasing chances of survival. The National Cancer Institute and American Cancer Society recommend mammographic screening every year from age 40. Women with higher risk of breast cancer, with a genetic predisposition for the disease or a strong family history need to be screened earlier and more frequently. High mammographic density is also assessed by mammograms and is linked to a six-fold increased risk of breast cancer^1,2.

Breast density refers to breast tissue composition: epithelial cells from glandular structures and connective tissue or stroma of glandular and connective tissue in the breast appear light while breast adipose appears dark in mammography screens. Standard mammography using X-ray images and digital mammography are currently used. Ultrasound or magnetic resonance imaging is often used in combination with mammography as a breast cancer screening tool.^3,4 Genetic factors,^5,6 pregnancy and lactation, age and menopause, and body weight are all factors which can account for changes in mammographic density. The exact cellular mechanisms involved in high mammographic density and its link to tumour incidence are largely unknown but the focus of current research worldwide. The use of mammographic screening for high breast density identifies a significant risk factor for breast cancer in women.

Mammographic screens and cancer-associated mortality: do we have enough evidence to conclusively understand this relationship?

There are contradicting reports in the literature as to the benefits and harm associated with mammographic screening and over-diagnosis of breast cancer. Differing opinions on this issue arise from the analysis and interpretation of different datasets.

Data from several randomised trials show a reduction of 25% in breast-cancer mortality among women in the screening group as compared with the control group.^7-9 Randomised trials of mammographic screens have also reported that this reduction in the risk of death from breast cancer is directly correlated with reductions in the risk of receiving a diagnosis of advanced breast cancer.¹⁰ In addition, reduction in breast cancer-associated mortality is also likely to be due to the combined effects of mammographic screening and better treatments.¹¹

A recent epidemiological analysis of data from the National Health Interview Survey in the United States highlights issues currently surrounding the utility of mammographic screens in terms of reduction in cancer-related deaths and the harm of over-diagnosis.¹¹ Since the first introduction of mammography screens, the reported cases for early-stage cancer has increased from 112 to 234 cancers per 100,000 women; and a decrease in late-stage cancer (including ductal carcinoma in situ) from 102 to 94 cases per 100,000 women.¹¹ The authors discuss that 8 of the 122 additional early diagnoses are potentially destined to progress to advanced disease; and conclude that breast-cancer screening involved substantial harm of excess detection of early-stage cancers that was not matched by reduction in late-stage cancers. Similar findings are reported in studies in other populations.^12,13

It is important to understand why such discrepancies occur, in particular between randomised trials and general population screening datasets. Closer assessment of confounding factors must be taken into consideration when assessing epidemiological data. Some confounding factors, such as improvements in treatment and heightened awareness of breast cancer, may be associated with a reduction in breast-cancer mortality. Breast screening is designed to improve prospects of early detection of cancers and decrease mortality. The term “over-diagnosis” includes all scenarios where women with screen-detected cancers are destined to die earlier due to other causes before development of their breast tumours. In addition, disease progression cannot be predicted with diagnosis and hence may not be reflected in numbers assessed as cancer-associated mortality.

Summary

The use of screening mammography is often debated, and it is important to realise that this debate occurs primarily due to methodology limitations in the epidemiology studies. In addition, the overall benefits of mammography screening programs remain poorly quantified and we should be thinking of alternate ways to address this. To date, the majority of the literature globally and in Australia^14,15 indicate that mammographic screening does result in decreased cancer-related deaths in women. The phrase “over-diagnosis” refers to a diagnosis of cancer that would not have otherwise been diagnosed during the woman’s lifetime. As the future possibility of disease cannot be predicted with certainty, it is not possible to determine to which category of women this might apply. Therefore, continued evaluation of breast-cancer screening programs is warranted in order to better quantify outcomes. To date breast screens have proven to be useful in the early detection of breast tumours and in establishing breast cancer risk in women.

Kindly contributed by Editorial Advisory Board Member Dr Ashwini Chand.

Reference

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