Clinical Update - Breast Cancer
Mammographic density and risk of breast cancer
Commentary by Associate Professor Mary Rickard
The article
Boyd NF, Guo H, Martin LJ, et al. Mammographic density and the risk and detection of breast cancer. N Engl J Med 2007;356:227-36.
Reviewer
Associate Professor Mary Rickard is Chief Radiologist at the Sydney Breast Clinic.
Summary
Abbreviations
Confidence Interval (CI), Computed Radiography (CR), Direct Radiography (DR), National Breast Screening Study (NBSS), Ontario Breast Screening Program (OBSP), Odds Ratio (OR), Screening Mammography Program of British Columbia (SMPBC).
Study design
The purpose of this study was to examine the association between mammographic density in the baseline mammogram and the subsequent risk of breast cancer, according to method of cancer detection, time since study entry and age. This article includes data from three Canadian case-control studies of mammographically screened populations: the Canadian National Breast Screening Study (NBSS), the Screening Mammography Program of British Columbia (SMPBC), and the Ontario Breast Screening Program (OBSP). Information was available for 1112 case-control pairs. Mammographic density was assessed independently by two radiologists and by a computer-assisted method.
Findings
Women with density in ≥75% of their mammogram had an increased risk of breast cancer compared to women with density in <10% (OR: 4.7; 95% CI: 3.0, 7.4). The risk was increased whether the cancer was detected by screening (OR: 3.5; 95% CI: 2.0, 6.2) or detected <12 months after a negative screening examination (OR: 17.8; 95% CI: 4.8, 65.9). The increased risk persisted for at least 8 years after study entry.
For women 56 years or younger, the prevalence of density in ≥50% of their mammogram was higher than in women older than 56 (37% vs 12%). For all breast cancers detected, density in ≥50% of the mammogram attributed to a higher risk in women 56 years or younger than for older women (26% vs 7%).
Conclusion
The authors concluded that extensive mammographic density is strongly associated with the risk of breast cancer.
Commentary
What does this article add to existing clinical evidence in this area?
This article has convincingly shown a strong association between mammographic breast density and the risk of invasive breast cancer, regardless of how it is diagnosed, and that this risk persists for a considerable time. There have been numerous published studies examining the association of mammographic breast density and risk of breast cancer. Most of these studies plus a meta-analysis have supported the finding identified by Wolfe in the late 1970s, that increased density is associated with increased risk.1,2
Boyd and colleagues estimated the extent of density in the entry mammograms of women attending for mammography screening and showed that for those women with the most extensive mammographic density, >75% of their mammogram, compared with those with the least extensive density, <10%, the odds ratio for breast cancer overall was 4.7 (95% CI: 3.0, 7.4).3 Odds ratios were raised for all detection methods and were 3.5 (95% CI: 2.0, 6.2) for incident screen detected cancer, 17.8 (95% CI: 4.8, 65.9) for cancer detected within 12 months of a negative incident screen, and 5.7 (95% CI: 2.1, 15.5) for cancer detected >12 months post screening. For all detection methods the increased risk persisted for at least 8 years after entry into the programme.
As the authors note, in comparison with earlier publications, the mammography used in this study was modern, the methods used to categorise density were quantitative rather than qualitative, and all methods of diagnosis were examined.
The attributable risk due to density was high and greater for younger women. Density categorised as >50% accounted for 16% of all cancers and 16% of those detected more than 12 months after screening. It accounted for 40% of cancers detected within the first 12 months after screening compared with only 12% of those detected at screening. The attributable risk in all categories of detection was around three times higher for women 56 years or younger than for women older than 56.
How adequate was the methodology used in addressing the aim of the study?
Cases and controls, 1112 matched pairs, were selected from three mammography screening programmes and matched for age, year of entry, screening centre and follow-up duration. No differences were identified between the results overall and those of the three programmes.
The mammographic density was categorised both by radiologists and by a computer-assisted measure, and similar risk results were obtained with the two techniques.
The characteristics usually associated with breast cancer were all more frequent in the cases than in the controls, and included earlier age at menarche, later age at first birth, nulliparity, smaller number of live births, later age at menopause, family history of breast cancer and use of hormone replacement therapy. Calculations of odds ratios were adjusted for these factors, as well as for the screening programme and observation time.
The study findings are convincing and cannot be explained by confounding, bias or chance.
What are the implications of this study for clinical practice in Australia?
In the Editorial to this article, Kerlikowske noted that "only two other factors increase the risk of breast cancer more than mammographic density: age and mutations in the breast cancer-susceptibility genes BRCA1 and BRCA2“.4 Mammographic density assessment could provide information for use in risk assessment and counselling and risk reduction strategies might be advised.
BreastScreen Australia screens using mammography alone every two years. Given such findings should the screening technique or the frequency of its use be modified? Digital mammography (both direct digital, DR, and computed mammography, CR) has been shown to significantly improve the rate of screen-detected cancer in women with dense breasts when compared with film-screen mammography.5 While digital technology will become more widespread, its current availability is limited in Australia due to its relative newness and expense. The addition of other techniques such as clinical examination, ultrasound and magnetic resonance imaging might potentially improve diagnosis in women with dense breasts, but are of unproven benefit. Shortening the screening interval from two yearly to annual is unlikely to be of major benefit, given that most interval cancers in this study were identified within 12 months of a negative screen.
References
1. McCormack VA, dos Santos Silva I. Breast density and parenchymal patterns as markers of breast cancer risk: a meta-analysis. Cancer Epidemiol Biomarkers Prev 2006;15:1159-69
2. Wolfe JN. Breast patterns as an index of risk for developing breast cancer. AJR Am J Roentgenol 1976;126:1130–7
3. Boyd NF, Guo H, Martin LJ, et al. Mammographic density and the risk and detection of breast cancer. N Engl J Med 2007;356:227–36
4. Kerlikowske K. The mammogram that cried Wolfe. N Engl J Med 2007;356:297–300
5. Pisano ED, Gatsonis C, Hendrick E, et al. Diagnostic performance of digital versus film mammography for breast cancer screening. N Engl J Med 2005;353:1773–83
Editor: Dr Karen Luxford, Deputy Director NBCC.
Editorial Committee: Mr John Collins - Surgeon,
Dr Sue-Anne McLachlan - Medical Oncologist,
Dr Sue Pendlebury - Radiation Oncologist,
A/Prof Martin Stockler - Medical Oncologist, Ms Jo Keyser - Specialist Breast Nurse, Dr Sally Meade - Breast Surgeon, Dr Warwick Lee - Radiologist, Dr Penny Schofield - Senior Research Fellow.
Disclaimer
Clinical Update - Breast Cancer is produced by the National Breast Cancer Centre (NBCC) and is intended to provide health professionals with timely expert commentary on new research in breast cancer. Commentaries included in Clinical Update - Breast Cancer do not replace recommendations included in NBCC clinical practice guidelines.
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