A report put out by researchers from the University of Melbourne, St. Vincent’s Hospital, the Peter MacCallum Cancer Centre, University of Adelaide, the Centre for M.E.G.A. (the University of Melbourne), Seoul National University and St Vincent’s Institute has demonstrated a clear new breakthrough in the understanding of breast cancer risk.

The authors of the report, entitled Mammographic density—a review on the current understanding of its association with breast cancer, state that their intention was to “critically review the current literature” on high breast density, or as they refer to it here, mammographic density (‘MD’).

They outline a number of key areas regarding the understanding of high breast density and its association with breast cancer, namely;

• Historically, the concept that certain aspects of the appearance of a mammogram were associated with breast cancer (BC) risk was first proposed by Wolfe et al. in 1976.
• Since then (1976), many case–control studies, usually nested within a screening cohort, have consistently confirmed that after adjusting for age and BMI, MD as measured by Wolfe patterns and other methods, are risk factors for BC.
• Studies have shown that BC arising within areas of high MD is more commonly associated with factors indicative of a poor prognosis, including large tumour size, high histological grade, lympho-vascular invasion (LVI) and advanced stage, compared to those arising within low MD tissue.
• That high MD tumours have more aggressive features compared with low MD tumours.
• Mammographic density appears also to be associated with increased local recurrence and the risk of a second primary BC.
• The use of HRT appears to increase MD. A Norwegian study of 2,424 postmenopausal women found that MD was higher for women currently using combined progestogen and oestrogen therapy (E + P HRT) than for former or non-users, and the use of high-dose norethisterone acetate (NETA) was particularly associated with higher MD.
• In a review of 80,867 mammograms from 39,296 postmenopausal women, oestrogen-alone HRT was found to be associated with higher MD, although the association was not as strong as that seen with combined HRT and MD.
• Mammographically dense breast tissues have a higher composition of stroma, higher relative gland counts and a lower proportion of fat than low MD counterparts.
• To date, MD has not been reported systematically in the clinical setting due to the lack of an automated tool. Conventionally, assessments of MD are based on subjective reporting of mammographic parenchymal patterns, which can be time consuming and examiner dependent.
• The current trend of moving from film-based screening mammograms to digital ones has enabled alternative approaches to be developed, such as calibrated planar and volumetric measures, and automated variation measure, in the hope of achieving efficient and standardized reporting that is comparable across studies.
• MD can represent a preventative and therapeutic target. In the primary prevention IBIS-1 trial, women who received tamoxifen prophylaxis—and had a minimum of 10 % reduction in MD in the first 1.5 years of taking tamoxifen— were found to have a 63 % reduction in BC risk, whereas no effect on BC risk was observed for those women who had a less than 10 % decrease in MD.
• A recent retrospective study of 974 postmenopausal BC patients with a 15-year follow-up found a relative reduction of 20 % in MD for women who received adjuvant tamoxifen, and this MD reduction was associated with a 50 % risk reduction of BC-specific mortality.
• Overall, reduction in MD as a host response could be an effective and non-invasive biomarker to assess or predict the efficacy of tamoxifen for prevention and treatment. Women with dense breasts may benefit from a trial of tamoxifen for 12–18 months to help reduce MD, and therefore their BC risk. However, the current evidence is insufficient to make this recommendation at a population level, given potential side effects of endometrial cancer and thromboembolic events.
• The recent mandating of MD reporting in several states in the USA is raising awareness of the role of MD in increasing BC risk.
•  Ultrasound contributed to increased cancer detection yield (an additional cancer detection rate of 3.2 per 1,000 women screened) in women who have dense breasts and normal mammograms.
• Breast MRI has high sensitivity in women with increased benign parenchyma enhancement, the high false positive rate and cost may render it a less attractive modality for screening in women with high MD.
• Women aged 40–74 at the initial screening mammogram with MD in the BIRADS category 4 (extremely dense) or in the C50 % PMD category mea- sured by Cumulus should be considered for additional imaging such as US to help detect early small BC. Consideration should be given as to whether a woman with extremely dense parenchyma C75 % would be recommended for a single screening breast MRI at commencement.
• More studies are warranted to evaluate how MD can be best incorporated into clinical practice.
• Research to date has confirmed the importance of MD in BC risk prediction and outcomes.
• Evidence suggests that the underlying biological and genetic basis of MD is likely to be complex.
• Although tamoxifen appears to modify MD, this finding needs to be externally validated by further studies and the mechanisms behind this relationship explored. Further clinical and epidemiological studies are also needed to try to determine how to effectively employ MD in a clinical environment. In the future, measurement of MD — especially if it is automated as part of digital mammography for the purpose of personalized medicine — might be used to improve BC screening and treatment strategies.