New evidence on breast Magnetic Resonance Imaging (MRI) screening has become available since the American Cancer Society (ACS) last issued guidelines for the early detection of breast cancer in 2003. A guideline panel has reviewed this evidence and developed new recommendations for women at different defined levels of risk. Screening MRI is recommended for women with an approximately 20-25% or greater lifetime risk of breast cancer, including women with a strong family history of breast or ovarian cancer and women who were treated for Hodgkin disease. There are several risk subgroups for which the available data are insufficient to recommend for or against screening, including women with a personal history of breast cancer, carcinoma in situ, atypical hyperplasia, and extremely dense breasts on mammography. Diagnostic uses of MRI were not considered to be within the scope of this review.

https://onlinelibrary.wiley.com/doi/pdf/10.3322/canjclin.57.2.75

American Cancer Society Guidelines for Breast Screening with MRI as an Adjunct to Mammography

Methods We carried out three nested case–control studies in screened populations with 1112 matched case–control pairs. We examined the association of the measured percentage of density in the baseline mammogram with risk of breast cancer, according to method of cancer detection, time since the initiation of screening, and age. Results As compared with women with density in less than 10% of the mammogram, women with density in 75% or more had an increased risk of breast cancer (odds ratio, 4.7; 95% confidence interval [CI], 3.0 to 7.4), whether detected by screening (odds ratio, 3.5; 95% CI, 2.0 to 6.2) or less than 12 months after a negative screening examination (odds ratio, 17.8; 95% CI, 4.8 to 65.9). Increased risk of breast cancer, whether detected by screening or other means, persisted for at least 8 years after study entry and was greater in younger than in older women. For women younger than the median age of 56 years, 26% of all breast cancers and 50% of cancers detected less than 12 months after a negative screening test were attributable to density in 50% or more of the mammogram. Conclusions Extensive mammographic density is strongly associated with the risk of breast cancer detected by screening or between screening tests. A substantial fraction of breast cancers can be attributed to this risk factor.

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Mammographic Density and the Risk and Detection of Breast Cancer

Cells within tissues are continuously exposed to physical forces including hydrostatic pressure, shear stress, and compression and tension forces. Cells dynamically adapt to force by modifying their behaviour and remodelling their microenvironment. They also sense these forces through mechanoreceptors and respond by exerting reciprocal actomyosin- and cytoskeletal-dependent cell-generated force by a process termed 'mechanoreciprocity'. Loss of mechanoreciprocity has been shown to promote the progression of disease, including cancer. Moreover, the mechanical properties of a tissue contribute to disease progression, compromise treatment and might also alter cancer risk. Thus, the changing force that cells experience needs to be considered when trying to understand the complex nature of tumorigenesis.

/pdf/a-tense-situation-forcing-tumour-progression-4myf9i89al.pdf

A Tense Situation: Forcing Tumour Progression

The connection between breast cancer and estrogen has been recognized for more than 100 years, since George Beatson demonstrated that bilateral oophorectomy resulted in the remission of breast cancer in premenopausal women.1 Subsequent evidence has implicated both endogenous and exogenous estrogen in the pathogenesis of breast cancer. In this article, we review the relation between estrogen and the risk of breast cancer. Estrogen and Breast Carcinogenesis Experimental data strongly suggest that estrogens have a role in the development and growth of breast cancer.2 Although the exact mechanisms remain to be fully elucidated, the alkylation of cellular molecules and the generation . . .

Estrogen and the Risk of Breast Cancer

The radiological appearance of the female breast varies among individuals because of differences in the relative amounts and X-ray attenuation characteristics of fat and epithelial and stromal tissues Fat is radiolucent and appears dark on a mammogram, and epithelium and stroma are radiodense and appear light We review here the evidence that these variations, known as mammographic parenchymal patterns, are related to risk of breast cancer Studies that used quantitative measurement to classify mammographic patterns have consistently found that women with dense tissue in more than 60-75% of the breast are at four to six times greater risk of breast cancer than those with no densities These risk estimates are independent of the effects of other risk factors and have been shown to persist over at least 10 years of follow up Estimates of attributable risk suggest that this risk factor may account for as many as 30% of breast cancer cases Mammographically dense breast tissue is associated both with epithelial proliferation and with stromal fibrosis The relationship between these histological features and risk of breast cancer may by explained by the known actions of growth factors that are thought to play important roles in breast development and carcinogenesis Mammographically dense tissue differs from most other breast cancer risk factors in the strength of the associated relative and attributable risks for breast cancer, and because it can be changed by hormonal and dietary interventions This risk factor may be most useful as a means of investigating the etiology of breast cancer and of testing hypotheses about potential preventive strategies

/pdf/mammographic-densities-and-breast-cancer-risk-7nnhghbyey.pdf

Mammographic densities and breast cancer risk.

Variations between individuals in the radiographic appearance, or mammographic pattern, of the female breast arise because of differences in the relative amounts and X-ray attenuation characteristics of fat and connective and epithelial tissue. Studies using quantitative methods of assessment have consistently shown these variations to be strongly related to risk of breast cancer. Individuals with extensive areas of radiologically dense breast tissue on the mammogram have been found to have a risk of breast cancer that is four to six times higher than women with little or no density. In this paper, we propose a model for the relationship of mammographic densities to risk of breast cancer. We propose that the risk of breast cancer associated with mammographically dense breast tissue is due to the combined effects of two processes: cell proliferation (mitogenesis), induced by growth factors and sex hormones and influenced by reproductive risk factors for breast cancer; and damage to the DNA of dividing cells (mutagenesis) by mutagens generated by lipid peroxidation. We review the evidence that each of these processes is associated with mammographic densities and propose further work that we believe should be done to clarify these relationships.

Mammographic densities and breast cancer risk

To examine the effects of dietary fat intake on breast cancer risk, we are conducting a randomized trial of dietary intervention in women with extensive areas of radiologically dense breast tissue on mammography, a risk factor for breast cancer. Early results show that after 2 years on a low-fat, high-carbohydrate diet there is a significant reduction in area of density, particularly in women going through menopause. In women who went through menopause during the 2-year follow-up, the mean decreases in area of density and percentage of density in the intervention group were 11.0 cm2 and 11.0%, respectively, whereas the control group decreased 4.5 cm2 and 5.2%. The purpose of this analysis was to determine whether changes in intake of specific macronutrients could account for the observed reduction in breast density in these women.

Differences between 2-year and baseline values of macronutrients (averaged over 3 nonconsecutive days of food intake) were calculated. We examined the effect of dietary variables, adjusted for changes in total calorie intake and weight and for family history of breast cancer, on changes in area of density and percentage of density using linear regression. Reduction in total or saturated fat intake or cholesterol intake was significantly associated with decreased dense area (p ≤ .004). The most significant dietary variable associated with reduction in percentage of density was reduction in dietary cholesterol intake ( P = 0.001), although reducing saturated fat intake was of borderline significance ( P = 0.05). The effect of the membership in the intervention and control groups on change in area of density or percentage of density was reduced by models that included changes in intake of any fat, or cholesterol, or carbohydrates.

The observation of an effect of diet at menopause on breast density, a marker of increased risk of breast cancer, may be an indication that exposures at this time have an enhanced effect on subsequent risk.

https://cebp.aacrjournals.org/content/cebp/8/2/123.full.pdf

Macronutrient intake and change in mammographic density at menopause: results from a randomized trial.

The Cooperative Familial Registry for Breast Cancer Studies: design and first year recruitment rates in Ontario.

The population-based Ontario Breast Screening Program (OBSP) provides two-yearly screening by both nurse examiner clinical breast examination (CBE) and two-view mammography to women aged 50 to 69. CBE alone accounts for about 5% of cancer detection. The purpose of this study was to determine whether CBE information affects radiologists' interpretation of mammography. Interpretation was defined by 1) radiologists' referral rates for diagnostic evaluation and 2) radiologists' accuracy in distinguishing cancer from non-cancer on mammograms. Mammograms were obtained from women randomly selected from those screened in the OBSP between 1990 and 1992. Selection was stratified by whether or not the nurse examiner had independently referred for diagnostic evaluation. Additional women diagnosed with breast cancer were selected to increase the precision of the receiver-operating characteristic (ROC) curve. Each participating OBSP radiologist read a set of mammograms twice, approximately three weeks apart. The first reading was based on mammograms alone. At the second reading, the CBE report was included on the reporting form. Among 620 women referred by the nurse, radiologist referral rate increased from 37.7% to 40.8% (p = 0.079) when CBE information was available. Among the 637not referred by the nurse, radiologist referral rate decreased from 29.8% to 25.6% (p = 0.005). There was little effect on the sensitivity and specificity of radiologist referral and the areas under the two ROC curves (with and without CBE information) were not significantly different (p = 0.571). Although there was some effect of CBE information on radiologists' pattern of referral, there was no effect on accuracy of cancer detection.

Julia A. Knight

Papers

Mammographic densities and breast cancer risk

Macronutrient intake and change in mammographic density at menopause: results from a randomized trial.

The Cooperative Familial Registry for Breast Cancer Studies: design and first year recruitment rates in Ontario.

An assessment of the influence of clinical breast examination reports on the interpretation of mammograms in a breast screening program.