U.S.

An increase in mammographic density is much more common among women taking continuous combined (estrogen plus progesterone) hormonal therapy (seen in 21-43% of such women) than for those using oral low-dose estrogen (6%) or transdermal (2%) estrogen treatment. The increase in density is often apparent at the first visit after starting hormonal therapy. Due to the increased risk of breast cancer in women taking combined hormonal therapy, recommendations are that use not extend beyond 3 to 5 years [1-5].

Tamoxifen blocks the estrogen receptor in breast cells and in breast cancer cells which express the estrogen receptor. Tamoxifen may be recommended to reduce the risk of developing breast cancer in women who have had prior atypical biopsies. Tamoxifen is also prescribed for women who have had breast cancer that expresses estrogen receptors to decrease recurrence. One study [1] found that when breast density is carefully measured by computer software, women whose breasts became at least 10% less dense while taking tamoxifen had a 63% reduction in risk of developing breast cancer – whereas those whose breast density did not change did not see a decrease in their risk. Several similar studies [2, 3] in women who have had breast cancer showed that only women whose breast density decreased on tamoxifen had decreased risk of recurrence. Tamoxifen also carries about a 3% risk of blood clots (which could result in pulmonary embolism or stroke) and a smaller risk of endometrial cancer (if the woman still has her uterus).

If a woman is on hormone therapy for menopausal symptoms, her breast density may decrease if she stops taking hormone supplements.

Aromatase inhibitors block the body’s own production of estrogen and are prescribed for postmenopausal women who have had breast cancer where the tumor cells express receptors for estrogen. One study [1, 2] looked at women who have had breast cancer. When breast density is carefully measured by computer software, women who experienced a decrease in breast density while taking tamoxifen or aromatase inhibitors had a lower risk of recurrence than women who did not experience a decrease in breast density.

Yes. There is a 1.8-fold higher risk of cancer in the opposite breast among women with dense breasts [1], but density and associated risk can be reduced with treatment. A 10% decrease of mammographic density or more within the first two years after an original diagnosis, as a result of treatment, is associated with a significantly reduced risk of cancer in the opposite breast (known as contralateral breast cancer) [2]. This potential new risk predictor can thus contribute to decision-making in follow-up treatment – particularly the continuation of a chemoprevention drug, like tamoxifen or aromatase inhibitors, which reduce breast density in some women [3].

Not normally, though rarely men do get breast cancer. Normal male breasts are mostly fatty. Sometimes men’s breasts do become enlarged and develop glandular tissue due to a condition called gynecomastia. This enlargement, due to a hormonal imbalance, normally affects one breast more than the other. If a mammogram is performed, it is usually easy to distinguish gynecomastia from breast cancer.

Breast density is at least partially inherited, though it is complex to predict. If a patient’s mother had dense breast tissue, it is more likely the patient will too.

Yes. Changes in the breast during breastfeeding do reduce the accuracy of screening tests (like mammography or MRI). Unless the patient plans to be breastfeeding for more than one to two years and is at high risk, it is generally recommended to wait at least a few months after breastfeeding stops before resuming breast screening. Ultrasound is usually performed first if a patient is breastfeeding and there is a concern about breast symptoms. If a breastfeeding woman needs to undergo breast imaging, it is advisable to nurse or pump immediately before the exam.

There have been conflicting studies on whether Black women have denser breasts than women of other races. One study [1] indicated they do not, while a more recent study [2] indicated they do.

Black women are more likely to have disease-causing mutations in BRCA. The American College of Radiology recommends Black women be evaluated in a high-risk program by age 30, even in the absence of family history [1]. Further, it is more important for Black women and Hispanic women to start screening at least by age 40 as peak breast cancer incidence occurs in the mid 40s, compared to peak in the early 50s for Caucasian women [2].

Generally, Asian women do have denser breasts than women of other races.

Disease-causing BRCA gene mutations and dense breasts are each independent risk factors for the development of breast cancer; however, pathogenic BRCA1 or BRCA2 mutations are associated with a much higher risk than that of having dense breasts. As BRCA1 and BRCA2 mutations are associated with a higher risk, MRI is part of routine screening beginning at age 25 to 30 for women who have these mutations, regardless of breast density. Cancers are also more likely to develop at a younger age in women with disease-causing mutations in BRCA genes, and the breasts are usually dense at younger ages making mammography especially ineffective as a standalone test in such women.

National Comprehensive Cancer Network (NCCN) guidelines recommend annual screening MRI beginning by age 25, with the addition of mammography beginning at age 30, in women who are known to carry pathogenic mutations in BRCA1 or BRCA2 (unless the woman has had bilateral mastectomy), and in women who are first-degree relatives of known mutation carriers but who are themselves untested (see table below) [1].

Women who are known to carry or are first-degree untested relatives of individuals with less common disease-causing mutations [such as those associated with Li-Fraumeni syndrome (TP43); Bannayan-Riley-Ruvalcaba syndrome or Cowden syndrome (PTEN); hereditary diffuse gastric cancer (CDH1); Peutz-Jeghers syndrome (STK11); Neurofibromatosis type 1 (NF1); or Fanconi anemia (PALB2)] are also recommended for annual screening MRI beginning between ages 20-35, depending on the mutation (see table below). Women with known pathogenic mutations in ATM, CHEK2, or BARD1 should consider annual MRI starting at age 40 or 5-10 years before the earliest known breast cancer in the family (whichever comes first). Women with NF1 have elevated risk only through age 50: supplemental MRI should stop beyond age 50 for these women and at least by age 75 for women with other pathogenic mutations.*

In addition to disease-causing mutation carriers and their untested first-degree relatives, annual screening MRI is recommended in addition to mammography/tomosynthesis in the following subgroups of women:

• Women with a calculated lifetime risk (LTR) of breast cancer of 20% or greater are recommended to begin annual screening MRI by age 25-30 [2, 3]. Any of the models used to predict risk of a pathogenic mutation [Tyrer-Cuzick (IBIS), Penn II, BOADICEA, BRCAPRO], or the Claus model, but NOT the Gail model, can be used to estimate lifetime risk for purposes of screening MRI guidelines.
• Women with prior chest radiation therapy (such as for Hodgkin disease) between ages 10 and 30 are at high risk for developing breast cancer [2-5], similar to BRCA1 or BRCA2 carriers, and are recommended for annual screening MRI starting at age 25 or 8 years after the chest radiation therapy, whichever is later.
• Women with a personal history of breast cancer and dense breasts and/or diagnosis by age 50. All women diagnosed with breast cancer at or before age 50 and treated with breast-conserving therapy have a ≥ 20% risk for a new breast cancer [3, 5].
• Annual MRI may be considered in addition to annual mammography or tomosynthesis in women with a personal history of breast cancer diagnosed after age 50 or without dense breasts, and/or a history of LCIS or prior atypia (ADH, ALH, atypical papilloma) [3, 5].

* After 75 years of age, management should be considered on an individual basis [1].

NCCN Breast Cancer Screening Guidelines in Women Who Carry or Are First-Degree Untested Relatives of Individuals with Pathogenic Mutations Known to Increase Breast Cancer Risk [1]

Gene	Associated Hereditary Cancer Syndromes	NCCN Breast Cancer Screening Guidelines
		Starting age for MRI (yrs.)a	Starting age for mammogram (yrs)
TP53	Li-Fraumeni syndrome	20b	30b
BRCA1	BRCA-related breast and/or ovarian cancer syndrome	25c	30c
BRCA2	BRCA-related breast and/or ovarian cancer syndrome	25c	30c
STK11	Peutz-Jeghers syndrome	30d	30d
CDH1	Hereditary diffuse gastric cancer	30d	30d
NF1	Neurofibromatosis type 1	30d,e,f	30d,e
PALB2		30d	30d
PTEN	Cowden syndrome/PTEN hamartoma tumor syndrome, Bannayan-Riley-Ruvalcaba syndrome	30-35d	30-35d
ATM	Ataxia telangiectasia (A-T)	40d	40d
CHEK2		40d	40d
BARD1	BARD1-related cancer risk (women only)	40d	40d ©DenseBreast-info.org and Robin Seitzman, PhD

^aFor women with pathogenic/likely pathogenic variants who are treated for breast cancer and have not had bilateral mastectomy, screening should continue as described until age 75 (other than for women with NF1^f). After age 75, management should be considered on an individual basis [1].

^bStart at age 20 or the age of the earliest diagnosed breast cancer in the family if younger than age 20.

^cBegin at age 25, or starting age may be individualized based on family history of a breast cancer diagnosis before at 30

^dStart at stated age or 5-10 years before the earliest known breast cancer in the family (whichever comes first).

^eScreening recommendations only apply to individuals with a clinical diagnosis of Neurofibromatosis type 1 (NF1).

^fThere are currently no data to suggest an increased breast cancer risk after age 50 years in women with NF1; therefore, MRI screening may discontinue at 50 years of age in this group. In addition, the presence of breast neurofibromas may lead to false-positive MRI results; more data on sensitivity and specificity of MRI in women with NF1 is needed.

Dense breasts are mostly an issue affecting mammography performance so a patient generally does not need to know until they begin having mammograms. For women at normal risk, mammography is often recommended to begin at age 40. If a woman has a family history of breast cancer and has not begun mammography screening, she should speak to her doctor about personal risk factors and when mammography and possibly other screening should begin. As a general guide, if a woman’s mother or sister was diagnosed with breast cancer before age 50, she may want to begin annual screening 10 years before the relative’s age at diagnosis, but not before age 30.

European guidelines recommend double-read biennial screening digital mammography for average-risk women 50 to 69 years of age. Also encouraged are biennial screening for women 73 to 75 years of age, and annual screening for ages 40–45 to 49 [1].