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Abstract
New legislation in several states requiring breast density notication in all mammogram reports has
increased awareness of breast density. Estimates indicate that up to 50% of women undergoing
mammography will have high breast density; thus, with increased attention and high prevalence of
increased breast density, it is crucial that primary care clinicians understand the implications of dense
breasts and are able to provide appropriate counseling. This review provides an overview of breast density,
specically by dening breast density, exploring the association between breast density and breast cancer
risk, both from masking and as an independent risk factor, and reviewing supplemental screening options
as part of a larger framework for counseling patients with dense breasts.
2014 Mayo Foundation for Medical Education and Research
548
Description
Glandular tissue
<25%
Approximately 25%-50%
Approximately 51%-75%
>75%
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549
FIGURE 1. Mediolateral oblique mammographic views depicting the 4 BI-RADS density categories: (A) almost entirely fat (BI-RADS 1
density); (B) scattered broglandular densities (BI-RADS 2 density); (C) heterogeneously dense (BI-RADS 3 density); (D) extremely
dense (BI-RADS 4 density). BI-RADS Breast Imaging Reporting and Data System.
often compare the 10% of women with extremely dense breasts with the 10% of women
with almost entirely fatty breasts.26 When
comparing women with dense breasts with
women with scattered broglandular densities
(D2), the relative risk is 1.2 to 1.5 for heterogeneously dense breasts (D3) and 2.1 to 2.3 for
extremely dense breasts (D4).14,21,24,27-29 Breast
density has also been associated with an
increased risk of local and locoregional recurrence of breast cancer but not distant metastasis
or survival.30,31 This nding is consistent with 2
recent large studies that found that breast density was not associated with increased breast
cancer mortality or all-cause mortality rates32,33;
however, additional research is needed because
of the limited studies on this topic.
Breast density decreases with advancing age;
a large study found that 74% of women in their
40s had dense breasts (D3 or D4) as compared
with 36% of women in their 70s.34 One study
of 1900 women aged 49 to 69 years found that
breast density decreased by an average of 11%
over a 10-year period.35 Nevertheless, high
breast density increases breast cancer risk across
all age groups, but the association is strongest in
premenopausal women and women receiving
postmenopausal hormone therapy (HT).22 In
postmenopausal women with the highest breast
density, HT use was associated with a higher risk
April 2014;89(4):548-557
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of breast cancer than was no HT use (hazard ratio, 1.38; 95% CI, 1.25-1.50).22 Hormone therapy not only is associated with increased breast
cancer risk among increased density categories
but also increases breast density. The Womens
Health Initiative study36 found that HT users
on a combination of estrogen and progestin
had a 6% increase in mammographic breast density after 1 year compared with a 0.9% decrease
in the placebo group. Similar to the relationship
between breast density and age, breast density
also decreases with increasing body mass index
(BMI), though breast density and BMI are independent risk factors for breast cancer.37-39
Breast Density as a Potential Surrogate
Marker of Treatment Response
Breast density is a potential indicator of treatment
response for certain types of breast cancer prevention and treatment. Tamoxifen is efcacious in
both breast cancer treatment and prevention,
and it has been suggested that some of its
therapeutic effect may be mediated through
reductions in breast density. In the primary
prevention International Breast Cancer Intervention Study-1 trial, 46% of high-risk women
randomized to tamoxifen experienced a more
than 10% reduction in breast density compared
with 25% of those taking placebo. Women
treated with tamoxifen with more than 10%
reduction in breast density experienced a
63% decrease in breast cancer risk compared
with no change in risk in women in the placebo
group and women treated with tamoxifen with
no change in breast density.40,41 Reductions in
breast density have also been associated with a
reduced risk of recurrence in patients with
breast cancer treated with tamoxifen as adjuvant therapy.42 A recent Swedish study with
15 years of follow-up found that women with
breast cancer treated with tamoxifen as adjuvant therapy who experienced a reduction of
more than 20% in breast density had a 50%
reduced risk of breast cancer mortality
compared with women treated with tamoxifen
with no reduction in breast density.43 Thus,
breast density may be an important marker of
response to tamoxifen therapy for chemoprevention and adjuvant therapy for breast cancer.
Conversely, this nding has not been consistently found in studies of aromatase inhibitors
(AIs). Multiple studies have examined the effect
of AIs on breast density with largely negative
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Woman with
heterogenously dense or
extremely dense breasts
Yes
Annual screening
MRI and digital
mammogram
Consider referral
for genetic
counseling if
appropriate
Yes
No
Yes
No
Consider medications
for breast cancer risk
reductionsc
Abbreviations: ABUS = automated whole-breast ultrasound; LCIS = lobular carcinoma in situ; MBI = molecular based imaging;
MRI = magnetic resonance imaging.
a Significant family history includes a first-degree relative with breast or ovarian cancer, multiple relatives with breast or ovarian cancer on one
side of the family, especialy premenopausal or in male relatives.
b Risk assessments should be done by clinicians with expertise in using breast cancer risk prediction models.
c Breast cancer risk reduction medications include tamoxifen, raloxifene, and exemestane.
d MBI is not available at many centers. Currently there is little consensus as to when or which additional screening test should be used.
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