Você está na página 1de 23

breast, skin, and soft tissue

BENIGN BREAST DISEASE


Helen Cappuccino, MD, FACS, Ermelinda Bonaccio, MD, and Shicha Kumar, MD*

Clinicians should have an understanding of the evaluation CBE as part of the physical examination performed on every
and management of breast disorders. One in two women female patient [see Figure 2, Figure 3, and Figure 4].
will consult a health care provider for a breast-related com-
plaint during her lifetime.1 The fundamental task facing a screening mammography
physician who is evaluating a patient with a breast concern Screening mammography refers to the imaging of asymp-
is to determine whether the abnormality is benign or malig- tomatic women to detect early, clinically occult breast
nant. Even though most breast complaints do not result in a cancers. Mammography is the only breast imaging modality
diagnosis of cancer, any woman presenting with a breast proven to reduce mortality from breast cancer in multiple
complaint should receive a comprehensive evaluation. In randomized clinical trials.5 The Swedish Two-County Trial
this chapter, we focus on the evaluation and management of updated its data in 2000 and demonstrated a 32% reduction
benign breast conditions. in breast cancer mortality in women invited to screening.6
Based on the findings from these trials, women should begin
annual screening mammography at age 40. There are sub-
Screening Recommendations
groups of women at high risk for breast carcinoma who may
In the absence of a specific breast complaint, breast cancer benefit from screening at a younger age or from the addition
can be detected by screening. The three main methods of of MRI to their screening, although no randomized con-
breast cancer screening are breast self-examination (BSE), trolled trials support these recommendations.7 Currently,
clinical breast examination (CBE), and screening mammo- there is no accepted upper age limit for mammographic
graphy [see Table 1].2 American Cancer Society (ACS) screen- screening; however, the presence of significant comorbidi-
ing guidelines for women age 40 years and older specify that ties reducing life expectancy to less than 10 years should be
mammography and CBE should be included as part of an considered when ordering a screening mammogram in
annual health examination.3 Health care providers should women over the age of 70.
stress to patients the importance of promptly reporting any Most breast imaging centers in the United States use
new breast symptoms or findings. There is currently no role digital mammography. The results from a large prospective
for routine screening ultrasonography or screening mag- multicenter trial comparing digital to conventional film
netic resonance imaging (MRI) in the general population. mammography demonstrated no significant difference in
breast self-examination cancer detection rates.8 However, digital mammography
was found to be more sensitive than film in three subgroups:
In BSE, the patient inspects and palpates both breasts and women less than 50 years of age, women with radio-
axillae. There is not yet conclusive evidence that BSE is of graphically dense breasts, and women who were pre- or
significant value in improving breast cancer detection rates. perimenopausal.9
Many self-detected tumors are found incidentally, not
during BSE. Furthermore, the best technique for BSE and
optimal frequency has not been established. The ACS Evaluating Breast Complaints and Masses
recommends counseling patients on the benefits and limita-
history
tions of BSE as part of the breast cancer screening process
that also includes mammography and CBE.3 Evaluation of a woman with a breast complaint should
In BSE, the patient inspects and palpates both breasts and include a thorough history, a physical examination, and
axillae. Although strong evidence supporting the benefit of appropriate diagnostic studies. A complete history of the
BSE to reduce mortality from breast cancer is lacking, many current complaint should include onset, duration, and
cancers are still self-detected. If women choose to do BSE, progression of symptoms. Precipitating and ameliorating
their technique should be reviewed [see Figure 1]. factors should be noted, as should the relationship of pal-
pable abnormalities, pain, and tenderness to the menstrual
clinical breast examination cycle. A recent history of trauma to the breast, previous
In CBE, a qualified health care professional carries out a infections, fine-needle aspirations (FNAs), core biopsies, and
complete examination of the breasts and axillae. As with surgical biopsies should also be recorded. Medical records,
BSE, there is not yet conclusive evidence indicating that including operative reports and corresponding pathology
annual or semiannual CBE increases breast cancer detection and radiographic reports, should be reviewed carefully. The
rates.4 Nevertheless, it is prudent for the clinician to include treating clinician should obtain and review previous breast
imaging as part of the patients history.
* The authors and editors gratefully acknowledge the contribu- Symptoms or complaints involving the breast should be
tions of the previous authors, Swati Kulkarni, MD, FACS, evaluated in the context of historical breast cancer risk data
Doreen M. Agnese, MD, FACS, Stephen P. Povoski, MD, FACS, [see Table 2]. The remainder of the patients general history
and Wiley W. Souba, MD, ScD, FACS, to the development should be evaluated with a focus on significant medical
and writing of this chapter. problems that may impact surgical planning. Medications

Red text is tied to a SCORE learning objective. Scientific American Surgery


2014 Decker Intellectual Properties Inc DOI 10.2310/7800.2043

04/14
breast benign breast disease 2

Table 1 Three Main Methods of Breast Cancer Screening2,3


Method ACS Screening Guideline
Breast self-examination Counsel patients on the benefits and limitations of BSE as part of the breast cancer screening process
Clinical breast examination Should be included as part of an annual health examination
Screening mammography Should be included as part of an annual health examination
ACS = American Cancer Society; BSE = breast self-examination.

and supplements that may contain estrogen-like substances examination of the breast tissue can facilitate identification
and social history (especially tobacco, alcohol, work, exer- of masses in women with dense breast tissue. In the supine
cise, and even sexual history as it pertains to breast stimula- position, turning the patient to either side to disperse breast
tion) can be relevant. It is also important to note if a patient tissue facilitates a more thorough examination for women
is of Ashkenazi Jewish lineage. with larger breasts. For the ptotic breast, palpation of the
breast tissue between the thumb and index finger of the
physical examination same hand may be useful. The location, mobility, and
The breasts and axillae should be thoroughly examined in characteristics of masses and thickening should be noted,
the upright and supine positions. Breast asymmetry and including size, firmness, presence of smooth or irregular
overall appearance of the skin, nipples, and areola should be borders, overlying skin changes, consistency, and areas of
observed with the patient upright. Any erythema, indura- tenderness [see Table 3]. Drawings or digital images can be
tion, edema, peau dorange [see Figure 5], nipple retraction, made to document physical findings. All tissue between
and ulceration should be noted. Occult skin retraction can be the clavicle and costal margins should be palpated, from the
demonstrated by having the woman raise her hands above lateral sternal border to the posterior axillary line. Patients
her head and then place them against her hips. Bimanual should also be checked for nipple discharge with manual

a b c

Visual Inspection
Seated with Arms
Relaxed Asymmetry

Visual Inspection
Seated with Arms
Raised Above Head

Nipple
Retraction

e f g

Dimpling
Erythema
Edema of Skin

Figure 1 Visual inspection of the breasts. The breasts are inspected with the patient in a seated position with arms relaxed (a) and raised over
the head (b). Pertinent findings include asymmetry (c), nipple retraction (d), edema (e), erythema (f), and dimpling of the skin (g).

Scientific American Surgery

04/14
breast benign breast disease 3

a b

Axillae examined with


patient seated and
ipsilateral arm supported
to relax pectoral muscle

Up and
Clock
Down
Pattern
Pattern

Figure 2 Physical examination of the breasts. The breast tissue is examined in a systematic fashion to determine the presence of a dominant
mass (a). The axilla is examined with the patient in the seated position with the ipsilateral arm supported by the examiner (b).

Pads (not tips)


of first 3 fingers
used for palpation

Ipsilateral arm should be


placed behind head to spread
breast tissue across chest wall

Figure 3 Breast palpation technique. The breast is palpated in the supine position to spread the
breast tissue against the breast wall. The pads of the first three fingers are used to scan the texture of
the breast tissue.

Scientific American Surgery

04/14
breast benign breast disease 4

Diagnostic Studies
Abnormal screening mammogram
with normal physical examination

Additional imaging including ultrasonography


Additional mammogram views

BI-RADS 1, 2 BI-RADS 3 (probably benign) BI-RADS 4, 5


Back to routine screening schedule Do 6-month mammogram Do image-guided biopsy
follow-ups for 1 year, up to 24 months

Skin and Nipple Changes


Skin and nipple changes

Blanching erythema
Fever, warmth, pain (elevated white blood cells) Nipple excoriation
Consistent with infection

Empiric antibiotics to cover gram- Topical steroids for 714 days


positive cocci

Resolution No improvement Improvement No improvement


Revert to normal screening Imaging and skin punch biopsy Short-term clinical follow-up Skin punch biopsy
Imaging per screening protocol Imaging

Scientific American Surgery

04/14
breast benign breast disease 5

Management of Specific Benign Breast Complaints


Abnormal physical examination

Breast pain Nipple discharge Palpable mass or thickening

No mass Mass
Physiologic Pathologic
Screening per standard recommendation See workup for mass Bilateral Bloody
Multiple ducts Single duct
Milky Single breast
Heme-negative Spontaneous
Normal Abnormal
Reassure; holistic measures Per abnormal mammogram
Mammography
Mass No mass
Ductography
See workup for mass Endocrine workup Excision (see text)

Cystic < 28 year old > 28 year old


Aspirate (discard fluid) if symptomatic Ultrasonography Mammography + ultrasonography

Normal Worrisome physical Nonsuspicious solid Suspicious solid Solid or complex Simple cyst Normal
examination (consistent with Bilateral mammography Core biopsy
Short-term Aspirate
fibroadenoma) + core-needle biopsy
clinic follow-up Mammography (discard fluid) if
Follow-up by physical symptomatic
examination and
ultrasonography in 6
months

High suspicion Low suspicion


Core biopsy 6-month follow-up

Scientific American Surgery

04/14
breast benign breast disease 6

Lymph Vessel

Lymph Node

Fat

Lobules Areola

Lactiferous Duct Nipple

Suspensory
Ligament

Figure 4 Normal breast anatomy.

Table 2 Historical Breast Cancer Risk Data


History Factors to Consider
History of hormone use Duration
Estrogen vs estrogen + progesterone
Type, including oral contraceptives and hormone replacement therapy
Reproductive history Age at menarche
Age at menopause
Age at first live birth
Number of gestations and completed pregnancies
Lactation history
Family history Malignancies on maternal side, including age at diagnosis
Malignancies on paternal side, including age at diagnosis
History of predisposing genetic mutations in family members (i.e., BRCA)
Ashkenazi heritage
Medical history History of radiation to the chest
Personal history of genetic abnormalities
History of previous breast disease, surgeries, or abnormalities/symptoms/findings or trauma
Social history History of smoking
History related to alcohol intake
Dietary factors
Exercise and activity history
History of drug abuse (patients occasionally inject into breast veins, causing phlebitis)

Scientific American Surgery

04/14
breast benign breast disease 7

imaging directed by a radiologist, who determines if the


perceived abnormality is a real lesion. Spot and rolled views
(with or without magnification) can sometimes differentiate
between overlapping glandular tissue and an actual under-
lying lesion. The diagnostic mammogram report would then
be given a final Breast Imaging, Reporting and Data System
(BI-RADS) assessment.
When an abnormality is detected and the patient needs
additional mammographic and/or sonographic imaging [see
Figure 6], the initial screening mammogram in these patients
is given a final assessment 0 [see Table 4]. Once the diagnos-
tic workup is complete, the radiology report will have a final
assessment of 1 through 5. Women with a BI-RADS 1 or 2
should continue to undergo routine annual mammography.8
Women with a BI-RADS 3 should undergo short-term
followup, which typically involves an ipsilateral mammo-
gram in 6 months followed by a bilateral study at 12 and
24 months. A finding in this category should have a less than
2% risk of malignancy based on morphologic and distribu-
tion features.10,11 Any interval progression at follow-up
should prompt a biopsy. Patients with a BI-RADS category
4 or 5 lesion require a tissue diagnosis.
As an adjunct to diagnostic mammography, high-frequency
Figure 5 Peau dorange. breast ultrasonography is often used in the diagnostic
workup of a mass and can distinguish between a solid and
a cystic lesion. If a solid mass is visualized sonographically,
ultrasound-guided core-needle biopsy (CNB) can be
compression of the nipple. Axillary, clavicular, and cervical
performed for pathologic diagnosis.
lymph node basins should also be palpated in the upright
and supine positions. The presence of adenopathy, includ- FNA, Percutaneous Core/Needle, Excisional Biopsies
ing the size, consistency (hard versus soft), number, lateral-
Breast biopsies should be performed percutaneously
ity, location, and mobility of the lymph nodes, should be
whenever possible, using stereotactic, ultrasound, or MRI
documented.
guidance [see Table 5]. Such biopsies are preferable over
diagnostic studies open surgical biopsies and allow for better surgical planning
for definitive management. CNB [see Figure 7] with a spring-
Diagnostic loaded or vacuum-assisted device has been confirmed in
Mammography multiple studies to be a reliable alternative to surgical exci-
and Targeted sion.12,13 Stereotactic (mammographic) guidance is typically
Ultrasonography used to biopsy indeterminate or suspicious calcifications as
As mentioned previ- well as masses or densities that are sonographically occult.
ously, screening mam- Ultrasound guidance is used to biopsy masses that can be
mography refers to imaging of an asymptomatic woman. visualized sonographically and is the most cost-effective
Diagnostic mammography, on the other hand, refers to type of image-guided core biopsy.14 MRI-guided CNB is
imaging a woman with either a clinical complaint (a palpa- reserved for lesions that are occult to conventional imaging.
ble lump, thickening, focal pain, discharge) or an abnormal CNB is preferable over FNA [see Figure 8] because it
screening mammogram. The initial workup of an abnormal provides tissue for evaluation of histology, the presence of
screening mammogram involves additional mammographic invasion, and receptor status.

Table 3 Physical Characteristics of Benign and Malignant Breast Masses81*


Characteristic Benign Malignant
Borders Well circumscribed Irregular
Texture Firm or rubbery, supple Hard
Mobility Mobile Fixed to surrounding tissue
Skin changes None Dimpling, retraction
Nipple changes None Retraction, bloody discharge, scaling
*Although the above characteristics may imply benign disease, their presence should not be used as justification for not thoroughly working up lesions that are
worrisome.

Scientific American Surgery

04/14
breast benign breast disease 8

Cable to
Imaging Computer

Ultrasound Transducer

Growth/Tumor

Figure 6 Sonogram of the breast.

Table 4 American College of Radiology Breast Imaging Reporting and Data System (BI-RADS)
Category Assessment Description/Recommendation
0 Additional imaging evaluation required Additional imaging recommended
1 Negative finding Nothing to comment on; routine screening recommended
2 Benign finding Negative mammogram, but interpreter may wish to
describe a finding; routine screening recommended
3 Probably benign finding Very high probability of benignity; short-interval follow-up
suggested to establish stability
4 Suspicious abnormality Probability of malignancy; biopsy should be considered
5 Abnormality highly suggestive of malignancy High probability of cancer; appropriate action should be
taken
6 Known malignancy Known biopsy-proven malignancy
The report generated after the diagnostic workup is completed will have a final assessment of 1 to 5. The Breast Imaging Reporting and Data System (BI-RADS) lexicon was
developed to standardize mammographic reports.6 It defines the final assessment categories, which informs the referring physician about the likelihood of malignancy.

Percutaneous needle biopsies are not always feasible


Table 5 Guidance of Percutaneous Breast Biopsy
due to anatomic considerations such as the proximity of the
Guidance Target
lesion to skin, the nipple, or chest wall or if the patients
Stereotactic Indeterminate or suspicious calcifications as well breast tissue is not compressible. In such cases, open or
as masses or densities that are sonographically
occult surgical excisional biopsy [see Figure 9] is an alternative
and may require localization if the finding is not palpable.
Ultrasound Masses that can be visualized sonographically
Localization can be done with wires or newer appoaches,
MRI Lesions that are occult to conventional imaging such as radioactive seed localization [see Figure 10]. When

Scientific American Surgery

04/14
breast benign breast disease 9

Growth/Tumor
Core Biopsy Needle

~ 2 cm

Core Samples of
Breast Tissue

Figure 7 Core-needle biopsy.

Growth/Tumor
Syringe with Fine Needle

Sample Cells on
Microscope Slide

Figure 8 Fine-needle aspiration.

Scientific American Surgery

04/14
breast benign breast disease 10

Growth/
Tumor

Excised Breast Lump


with Margin of Normal Tissue

Figure 9 Excisional biopsy.

excisional biopsies are done, they should be done through Although a promising technology, the role of tomography in
incisions along the lines of minimal skin tension [see Figure 11]. clinical breast imaging is not yet determined.1517
Incisional biopsies should be avoided [see Figure 12]. At present, there is no indication for the use of positron
With any image-guided approach, it is important to emission tomography in the diagnostic workup of breast
confirm that the pathologic results are concordant with the diseases outside a clinical trial. A number of new modalities
imaging findings. Treatment decisions should be based are being investigated, such as positron emission mammo-
on both pathologic findings and the appearance of the graphy, breast-specific gamma imaging, and coned-beam
abnormality on diagnostic imaging. Discordant imaging and computed tomography. Although some of these modalities
pathologic findings should prompt a surgical biopsy. are approved by the Food and Drug Administration (FDA),
they are not currently standard practice.
Other Imaging Modalities
MRI is an imaging modality that uses strong magnetic
fields to create a cross-sectional image. Breast MRI requires General Management of Clinical Findings in the Breast
a specific coil and peripheral intravenous injection of a palpable mass
gadolinium-based contrast medium. Contrast-enhanced
breast MRI has been shown to have a high sensitivity for Palpable masses can cause considerable anxiety in
detection of invasive breast cancer and can find both inva- patients and require appropriate evaluation with a thorough
sive and in situ carcinomas that are occult to conventional history and physical examination [see Table 6]. A dominant
imaging. In practice, the use of breast MRI is predominantly breast mass is defined as a discrete lump that is distinctly
limited to women diagnosed with breast carcinoma and different from the surrounding breast tissue. Overall,
women at increased risk for developing breast cancer. approximately 10% of dominant breast masses are malig-
To date, there are no studies supporting the role for MRI nant. The workup and management of a discrete breast mass
screening in the general population. are governed by the age of the patient, the patients family
Tomosynthesis is a type of digital mammography that and medical history, the physical characteristics of the
uses low-dose images acquired in an arc [see Figure 13 and palpable lesion, and findings on diagnostic imaging. These
Figure 14]. These images are then reconstructed into slices, factors should not be used to dismiss the findings of a
allowing for visualization in layers. This technology reduces palpable mass, however.
the issue of overlapping tissue, which can obscure a breast
cancer or mimic lesion. Recent studies suggest that the addi- solid masses
tion of tomosynthesis to standard digital mammography Evaluation of a palpable lump in a woman over 30 years
can increase detection rates and decrease recall rates. of age should include mammography and ultrasonography.

Scientific American Surgery

04/14
breast benign breast disease 11

therefore, imaging-guided aspiration, biopsy, or both should


be performed. For asymptomatic simple cysts, no further
intervention is required. For symptomatic cysts, FNA is
appropriate. If the mass does not disappear completely after
aspiration, then biopsy of any residual solid component
should be performed. Clear fluid should not be sent for
cytologic analysis because of the high likelihood of a false
positive result. Bloody fluid obtained from a cyst aspiration
should be sent for cytologic examination.

vague thickening or nodularity


Normal breast texture is often heterogeneous, particularly
in premenopausal women. Vague thickening or tender or
nontender areas of nodularity are frequently detected by the
patient or the clinician. It is important to distinguish this
vague breast thickening or nodularity from a discrete or
dominant breast mass. In clinical practice, the first step in
evaluating a nodular area is to compare it with the corre-
sponding area of the opposite breast. Symmetrical tender
nodularityfor example, in the upper outer quadrant of
both breastsis rarely pathologic. These areas often repre-
sent fibrocystic changes that may resolve with time and thus
should be followed clinically. Asymmetrical areas of vague
thickening in premenopausal women should be reexamined
after one or two menstrual cycles. If the asymmetry persists,
the patient should undergo mammography and ultrasonog-
raphy if she is 30 years of age or older and has not under-
gone a mammogram within the last 6 months. If the mass
is clinically suspicious, a surgical biopsy with specimen
orientation should be performed even in the setting of
negative imaging.

Management of
Specific Benign Breast
Complaints

Figure 10 Radioactive seed localization. mastalgia


One of the most
common complaints for
If she has a significant family history of breast cancer but which a woman seeks a doctors opinion is mastalgia.
has not yet reached the age for routine bilateral screening, Mastalgia (breast pain) can be cyclical or noncyclical and
contralateral mammography is indicated to rule our syn- may be idiopathic. Often it is related to other common
chronous lesions. Increased concern is appropriate in the processes that occur in the breast, such as fibrocystic change
case where a solid mass is hard, fixed, and immobile and has or infection. Two thirds of women will complain about
irregular borders clinically. For women less than 30 years mastalgia during the course of their lives.18 Its cause is poorly
old, workup begins with ultrasonography, and mammogra- understood. A history of the onset and course of the pain is
phy is included depending on the sonographic and clinical important, especially as it relates to a womans menstrual
findings. If the mass is clinically suspicious, CNB (or surgi- cycle. Although rarely a presenting complaint of breast
cal biopsy if CNB is not feasible or unsuccessful) should cancer, mastalgia often causes considerable concern for
be performed for tissue diagnosis even in the setting of patients. Mastalgia resolves spontaneously in 20 to 30% of
negative imaging. cases but can recur in up to 60% of women. Some studies
suggest a relationship with caffeine intake, saturated fat
cystic masses intake, premenstrual syndrome, and serum hormone
Cysts are a common cause of dominant breast masses, levels.19 Frequently, after a complete history and physical
particularly in premenopausal women, and can present as a examination to rule out a malignancy, the clinician is left
mass or pain. They can be differentiated from solid lesions treating mastalgia of unknown etiology. Many women
by means of ultrasonography. Sonographically, simple cysts respond well to reassurance18,20 and simple interventions,
are anechoic, well-circumscribed masses [see Figure 15]. such as wearing a properly fitted bra and reducing caffeine
Complex cysts with indistinct walls or solid components are and saturated fat intake. Commonly used remedies, includ-
more likely to be associated with carcinoma [see Figure 16]; ing evening primrose oil, vitamin E, and vitamin B6, have

Scientific American Surgery

04/14
breast benign breast disease 12

Biopsy Incisions

Figure 11 Breast biopsy incision.

Growth/
Tumor

Excised Wedge of
Breast Lump

Figure 12 Incisional biopsy image.

Scientific American Surgery

04/14
breast benign breast disease 13

Table 6 Breast Lesions that May Present as a


Palpable Abnormality81
Fibrocystic change
Simple and complex cysts
Pseudoangiomatous stromal hyperplasia
Fat necrosis
Lipomas
Abscesses
Adenopathy
Ductal ectasia
Fibroadenomas
Hamartomas
Ductal carcinoma in situ
Invasive carcinoma
Gynecomastia
Sarcomas
Phyllodes tumors
Sarcoidosis
Idiopathic granulomatous mastitis
Hematomas
Seromas
Mucoceles
Galactoceles
Amyloidosis
Focal fibrosis
Lactating adenomas
Epidermal inclusion cysts
Lymphadenopathy
Hemangiomas

Figure 14 Mediolateral oblique tomosynthesis.

Figure 15 Breast sonogram showing a well-circumscribed oval mass


with a thin wall and posterior acoustic enhancement consistent with
Figure 13 Craniocaudad tomosynthesis. a simple cyst.

Scientific American Surgery

04/14
breast benign breast disease 14

Table 7 Noncancerous Processes that Cause


Nipple Discharge
Process Characteristics
Physiologic discharge Milky
Bilateral
Ductal ectasia Nonbloody but darker green or brown
Dilated ducts resulting from obstruction
with keratin plugs
Subsequent inflammation and secretions
Intraductal papilloma Bright red, rusty, brown, or green
Unilateral
Persistent
Eminates from a single duct

question to the patient should be whether the discharge is


spontaneous or self-induced. If self-induced, the patient
should be counseled to stop eliciting the discharge. If
spontaneous, the characteristics are important in determin-
Figure 16 A mammary carcinoma that has irregular borders, is ing the cause, including whether it is unilateral or bilateral,
hypoechoic, and shows irregular posterior shadowing. in single or multiple ducts, milky, bloody, clear, posttrau-
matic, or cyclical. The history should also include questions
pertaining to symptoms associated with an endocrine
limited evidence supporting their use to relieve symp- disorder (hypothyroidism) or to an intracranial etiology
toms.21,22 If simple interventions are not successful, consider- such as a pituitary tumor (amenorrhea, visual disturbances,
ation can be given to pharmacologic agents including and headache). A history of recent medication changes
nonsteroidal antiinflammatory drugs (NSAIDs), danazol, should also be taken because numerous medications are
bromocriptine, and tamoxifen.19,22,23 In very extreme and associated with galactorrhea [see Table 8].25
otherwise completely nonresponsive cases, surgical excision To understand physiologic nipple discharge, an under-
of the tender area can be considered, but such intervention standing of breast physiology is critical. During pregnancy,
is rarely appropriate, especially since pain often persists high circulating levels of estrogen result in development of
even after surgery.24 the breast into a predominantly glandular structure. With
parturition, estrogen production decreases, resulting in
fibrocystic change
prolactin secretion and increased secretory activity, whereas
Fibrocystic change is often referred to by the misnomer oxytocin results in letting down or ejection of milk into the
fibrocystic disease. It is a common finding in women who ducts. A suckling infant or similar stimuli (i.e., sexual breast
are menstruating, occurring almost exclusively between the stimulation, postthoracotomy syndrome)26 may result in
ages of 30 and 50. Fibrocystic change is characterized by oxytocin release. Any of these conditions can result in
lumpy or cobblestone breasts with ridges of tissue appre- physiologic discharge, which is usually milky and bilateral.
ciated on palpation. The change is considered a normal Pregnancy can result in galactorrhea from the second
variant. If a dominant mass is found in a woman with fibro- trimester to as late as 2 years postpartum. Elevated thyroid-
cystic breasts, diagnostic imaging and biopsy should be stimulating hormone (TSH) levels can also be associated
undertaken to rule out malignancy. Symptoms generally with elevated prolactin levels.
improve with oral contraceptive use and abate with meno- Nipple discharge characterized as nonbloody but darker
pause. Treatment is geared toward symptomatic relief using green or brown is associated with ductal ectasia, a benign
the agents listed above for mastalgia and reassuring the condition characterized by dilated ducts resulting from
patient that there is no worrisome etiology or increased risk obstruction with keratin plugs and subsequent inflamma-
of developing breast cancer. tion and secretions. Ductal ectasia [see Figure 17] can arise in
one or multiple ducts. Dilated ducts are visualized on ultra-
nipple discharge: papillomas, ductal ectasia, and
sonography and on ductography. The characteristics of the
galactorrhea
discharge from ductal ectasia can be similar to those seen
Nipple discharge is the third most common breast com-
plaint after mastalgia and breast mass.25 In the majority of
cases, the discharge is caused by noncancerous processes,
including (1) physiologic discharge, (2) ductal ectasia, and Table 8 Medications Associated with
(3) intraductal papilloma [see Table 7]. However, malignancy Galactorrhea25
should be ruled out as part of the workup for nonphysiologic H2 receptor antagonists
discharge.25 For women presenting with this concern, the Antihypertensives
clinician should elicit a history that includes the characteris- Antidepressants
Antidopaminergic agents
tics, frequency, and time frame of the discharge. The initial

Scientific American Surgery

04/14
breast benign breast disease 15

Normal Duct

Duct with Ectasia

Figure 17 Ductal ectasia.

with papillomas and ductal carcinoma in situ (DCIS) and are For patients who are found to have pathologic discharge,
therefore included in the differential diagnosis of pathologic the diagnostic workup should begin with bilateral diagnos-
nipple discharge. tic mammography. If imaging reveals a focal lesion or
Bloody nipple discharge can appear as bright red, rusty, microcalcifications, tissue diagnosis should be obtained.
brown, or green and is considered pathologic. It is charac- Ductography may be able to identify an intraductal lesion
teristically unilateral and persistent and emanates from a and guide surgical planning. Ductography involves cannu-
single duct. Although the most common etiology of this lating the discharging duct with a small catheter and then
remains a solitary intraductal papilloma, DCIS and invasive injecting a small amount of radiographic contrast medium.
breast cancer can also present with pathologic discharge. Magnified mammographic views are then obtained, and
Of patients presenting with such a discharge, 17% have lesions within the duct are identified as either a filling defect
malignancy, 65% have papillomas, and the remainder have or an abrupt cutoff. Ductoscopy, which uses a flexible or
other benign lesions.27 rigid fibroscopic ductoscope to cannulate the nipple, can be
A thorough physical examination that includes a search used to isolate areas of pathology for excision. In skilled
for signs of an endocrine disturbance should be conducted hands, it can be combined with ductal lavage or (brush)
(e.g., thyromegaly, visual field defects). As part of the breast cytology for improved accuracy.28,29 However, studies
evaluation, if nipple discharge is not apparent, the clinician supporting ductoscopy and ductal lavage remain limited,
should gently squeeze the nipple to determine whether the and these techniques remain investigational.
discharge is coming from a single duct or multiple ducts Cytologic analysis of nipple fluid or discharge has little
and whether the discharge is bilateral. The breast should be clinical value. Heme testing nipple discharge for blood can
evaluated for the presence of a discrete mass that may be raise the suspicion of malignancy, but the absence of blood
associated with an underlying carcinoma. does not rule out malignancy. FNA is also unreliable in
Historical and physical findings suggestive of an endo- evaluating patients with drainage and/or papillomatous
crine disorder should prompt the clinician to order TSH and disease30 (and many feel that even CNB of endoductal
prolactin levels. An MRI of the brain should be ordered lesions remains inadequate for definitive diagnosis of these
to rule out a prolactin-secreting tumor of the pituitary if lesions).3134 Therefore, surgical excision is recommended
prolactin levels are elevated. In women of childbearing age, given the incidence of concomitant premalignant and malig-
a pregnancy test should also be ordered as part of the nant disease in the setting of pathologic nipple discharge.31,35
workup of galactorrhea. Women with medication-induced When the location of the intraductal pathology is identified
bilateral discharge should be counseled about the etiology prior to surgical resection, a more limited resection (i.e.,
and reassured. single duct excision) of the disease is possible.36 If the duct

Scientific American Surgery

04/14
breast benign breast disease 16

is peripheral in the breast, the duct can be localized via imaging characteristics as FAs but, unlike FAs, are charac-
needle localization. When possible, single duct excision is terized by a clinical history of rapid growth and have larger
preferred because it preserves nipple sensation and the abil- dimensions. With increased screening, more PTs are being
ity to breast-feed. In cases where the focal pathology cannot discovered mammographically. Given that these lesions do
be isolated preoperatively, or in the case of multiduct not have any features on imaging that would be helpful
involvement, a major duct excision is more appropriate. This in differentiating them from FAs, CNB is recommended.
involves removing all of the central lactiferous ducts and However, it can be difficult to differentiate between FA and
sinuses, preventing further discharge. Both procedures can PT on CNB. A pathologic diagnosis of a fibroepithelial
be done on an outpatient basis and require only local anes- lesion on CNB necessitates excision to rule out a PT. Tumors
thetic and monitered anesthesia care (MAC) with sedation. are classified histologically as low, intermediate, or high
grade. Although most PTs have minimal metastatic poten-
fibroepithelial lesions: fibroadenoma and tial, they have a proclivity for local recurrence and should
phyllodes tumor be excised with at least a 1 cm margin. Local recurrence has
Fibroepithelial lesions encompass a spectrum of breast been correlated with excision margins but not with tumor
abnormalities ranging from the fibroadenoma (FA) [see grade or size.38 The most common site of metastasis from
Figure 18] to the phyllodes tumor (PT). FAs are the most malignant PT is the lung.
common benign breast lesions and occur most frequently in
the second and third decades of life. Their natural history is atypical hyperplasias, radial scar, lobular
one of stability or slow growth. Patients will often give a neoplasia, and papillomas
history of a solitary nontender nodule. Physical examination During the course of a patients workup for a suspicious
will usually demonstrate a well-defined solitary, rubbery, physical finding or image-detected abnormality, CNB or
and mobile nodule. Ultrasonography is particularly useful FNA may be performed. A pathologic diagnosis demon-
in younger women and demonstrates a well-defined oval or strating atypia, atypical ductal hyperplasia (ADH), atypical
round hypoechoic mass with discrete margins. Mammogra- lobular hyperplasia (ALH), lobular carcinoma in situ (LCIS),
phy should be obtained (in addition to ultrasonography) in papilloma [see Figure 20], or radial scar requires formal sur-
women over 35 years of age and typically demonstrates gical excision with preoperative localization to rule out the
a well-defined radiopaque mass with smooth borders [see presence of invasive carcinoma or DCIS. CNB of these
Figure 19]. If the history, physical examination, and imaging lesions understages findings related to these diagnoses in up
are consistent with an FA, careful clinical follow-up is rea- to 30% of cases.3943 These lesions may be an independent
sonable with ultrasonography and CBE at 6-month intervals risk factor for the development of carcinoma [see Evaluation
to assess the stability of the lesion. When the diagnosis of Patients at High Risk for Breast Cancer, below] [see
is uncertain, CNB should be performed. For women who Figure 21, Figure 22, and Figure 23].38
request excision of a benign FA, enucleation of the lesion is
adequate. Conversely, if the lesion increases in size during fat necrosis
clinical follow-up, surgical excision is recommended to rule Fat necrosis can masquerade as breast cancer. It often
out a PT. presents as a firm, irregular mass within breast tissue, which
PTs are uncommon, representing only 0.3 to 0.5% of breast is occasionally tender. The patients history is helpful in
neoplasms.37 They have the same clinical appearance and providing clues to this diagnosis and will often include a

Figure 18 Fibroadenoma.

Scientific American Surgery

04/14
breast benign breast disease 17

galactocele
In the pregnant patient with complaints of a mass or ten-
derness, the clinician should bear in mind the hormonally
stimulated status of the breast, resulting in increased tender-
ness. However, any mass or thickening in the breast requires
prompt evaluation in the pregnant patient. Malignancy
should always be ruled out, particularly in older,
childbearing-age women. A galactocele, which is a collection
of milk within an obstructed, dilated duct, can form during
pregnancy, lactation, or recent postlactation. A patient may
complain of a tender nodule within the breast tissue.
A mammogram will demonstrate a well-circumscribed
mixed-density lesion, and ultrasonography will reveal a
corresponding partially cystic mass. Simple aspiration
can be both diagnostic and therapeutic, providing relief.
Malignancy should always be in the differential diagnosis,
particularly in older women of childbearing years.
mondor disease
Mondor disease is thrombophlebitis of the superficial
Figure 19 Mammogram depicting a smoothly marginated mass
veins of the breast. It is characterized by the finding of a
with benign coarse calcifications consistent with a fibroadenoma. tender and often inflamed cord palpated on the patients
breast. After a thorough history and physical examination of
the patients breasts, reassurance is appropriate because
most cases will resolve spontaneously. If particularly symp-
tomatic or unresolved over a period of time, treatment
history of trauma, reduction mammoplasty, or previous should consist of NSAIDs, analgesics, and antibiotics. If
breast surgery. Large cavity size, postoperative hematoma, there is evidence of infection, or should the condition fail
or infection, as well as adjuvant radiation, can increase the to improve, surgical excision is appropriate for definitive
likelihood of fat necrosis. A compromise to the surrounding management and diagnosis.46
parenchymal blood supply is thought to be the underlying
factor in its development. Breast imaging can often be diag- gynecomastia
nostic of fat necrosis.44 Ultrasonography and/or stereotactic Gynecomastia, or benign proliferation of male breast
CNB is appropriate if there is doubt about the diagnosis and tissue, is usually a benign condition in adolescent males and
will reveal chronic inflammatory cells, lymphocytes, histio- presents as discoid, subareolar, rubbery thickening of the
cytes, fat necrosis, and saponification. Should the physician breast tissue. Mammography can often be diagnostic of
opt for short-term clinical follow-up (1 to 2 months) instead gynecomastia, demonstrating a typical fan- or flame-shaped
of biopsy, it is important to have a patient who will be density extending from the nipple toward the upper outer
compliant with keeping follow-up visits.45 quadrant. In the absence of any other findings, such as
testicular pathology, liver disease. or a history of ingestion
or use of substances associated with gynecomastia, these
patients should be reassured and reexamined. In the case of
especially prominent, large, long-standing, or symptomatic
gynecomastia, surgical excision is reasonable. It may even
require a subcutaneous mastectomy. In the mature male
population, a physical examination and history are vitally
important. Soft, diffuse enlargement is a result of medica-
tion in 20 to 25% of cases.47 Gynecomastia can also be due to
hormonal, physiologic, or idiopathic factors and can usually
be managed nonoperatively and with serial examinations.
Many medications resulting in gynecomastia are felt to
do so by elevating prolactin levels comparatively. If the
gynecomastia is attributable to medication, switching the
patient off the medication will often result in regression
over the course of a few months. For men who would like
to avoid surgery, some success has been noted in treating
gynecomastia with tamoxifen, raloxifene, and aromatase
inhibitors.48,49 However, a finding of a solitary hard mass,
especially with findings of adenopathy and skin changes,
requires aggressive workup to rule out cancer, including
mammography and tissue diagnosis, usually with percuta-
Figure 20 Papilloma. neous biopsy, especially if the finding is peripherally located.

Scientific American Surgery

04/14
breast benign breast disease 18

Normal Duct Cells

Ductal Hyperplasia

Figure 21 Ductal hyperplasia.

Normal Duct Cells

Atypical Hyperplasia

Figure 22 Atypical hyperplasia.

Scientific American Surgery

04/14
breast benign breast disease 19

Figure 23 Normal duct anatomy.

skin and nipple quently seen in women with a history of diabetes, rheuma-
changes toid arthritis, chronic steroid use, chronic granulomatous
Common breast skin lobular mastitis, and trauma.50 Treatment includes antibiot-
and nipple changes ics and identification of an underlying abscess followed by
include bacterial infec- aspiration or drainage. Aspiration should always precede
tions (mastitis, cellulitis, drainage. Intravenous antibiotics should be considered for
with or without under- women with an elevated temperature and white blood cell
lying abscess), fungal count or in immunosuppressed patients. Other skin condi-
infections, and dermatitis. Women will often give a history tions in the breast include sebaceous cysts and hidradenitis
of an abrasion or crack in the nipple preceding an episode suppurativa. Appropriate antibiotics should be given, and
of mastitis. Symptoms typically include erythema, tender- surgical excision is often required for resolution of the symp-
ness, and swelling of the breast. Staphylococcus aureus is the toms. Fungal (candidal) infections involving the breast are a
most common organism identified. Treatment involves common complaint in women with large, pendulous breasts.
continued breast-feeding and antibiotics. The choice of The lower breast and inframammary crease are common
antibiotics should take into consideration the safety of the locations for the characteristic erythematous moist patches.
breast-feeding infant.50 Nonresolution of the infection with a Treatment includes keeping the area clean and dry and
course of appropriate antibiotics should prompt the surgeon topical antifungal powders or creams.
to consider the presence of an antiobiotic-resistant organism In nonlactating women, benign processes involving the
or underlying abscess, which may require incision and nipple are often the result of trauma or damage to the nipple
drainage. Fluid from an abscess should be sent for Gram or subareolar ducts. Smoking is associated with periductal
stain and culture to ensure the appropriate choice of antibi- mastitis, which can present with pain, inflammation, nipple
otic. If the symptoms persist in the absence of the above retraction, breast abscess, and discharge. Appropriate
causes, inflammatory breast cancer should be considered, antibiotics and abscess aspiration or drainage are the recom-
followed by appropriate imaging, punch biopsy of the skin, mended treatments. Trauma, dry skin, or dermatitis can
and percutaneous biopsy of any underlying lesion. lead to excoriation of the nipple. Allergic or atopic dermati-
In nonlactating women, cellulitis of the breast typically tis frequently occurs as a result of allergies to clothing, dyes,
occurs in the lower half of the breast and is more commonly perfumes, and detergents. Treatment is symptomatic, with
found in women who are overweight, smoke, and/or have removal of the offending agent and a course of topical
large, pendulous breasts. Breast abscesses are more fre- steroids. Short-term clinical follow-up (1 to 2 weeks) is

Scientific American Surgery

04/14
breast benign breast disease 20

essential to ensure resolution of the symptoms. Breast Any personal history of cancer should be recorded, with
cancer, including Paget disease of the nipple, can present particular attention paid to breast, ovarian, and endometrial
with these symptoms, and it is vital that the surgeon cancers.
conduct a thorough investigation including history, physical BRCA1 and BRCA2 account for the majority of hereditary
examination, diagnostic imaging, and biopsy to make an breast cancers. The lifetime risk of breast cancer in these
accurate diagnosis. If there is no improvement in the symp- individuals can be as high as 85%. Mutations in these
toms in 2 weeks, punch biopsy of the nipple should be done. genes are associated with other malignancies, most notably
ovarian, pancreatic, and prostate cancer. Specific founder
mutations in BRCA1 and BRCA2 occur within certain ethnic
Evaluation of Patients at High Risk for Breast Cancer
groups (e.g., Ashkenazi Jews).61 Surgeons should also be
Significant morbidity and cost are associated with breast aware of mutations in other genes that are commonly associ-
cancer treatment. Approximately one third of women diag- ated with an increased risk of breast cancer, including muta-
nosed with breast cancer will succumb to the disease. This tions in TP53 (Li-Fraumeni syndrome), mutations in the
has led to efforts to provide primary prevention to high-risk PTEN gene (Cowden syndrome), and hereditary diffuse
women. A number of factors have been identified that gastric cancer syndrome (CHD1). Tests that detect mutations
increase breast cancer risk [see Table 9].51 These risk factors in these genes are commercially available. Clinicians
include (1) mutations in genes that confer a predisposition should consult a licensed genetic counselor to determine
to breast cancer52; (2) hormonal and reproductive factors51,5355; appropriate candidates for testing.
(3) environmental factors, including diet and lifestyle Genetic testing has significantly improved our ability to
characteristics of developed Western nations56; (4) previous define breast cancer risk for the subset of women who have
radiation to the chest wall as a teenager or young adult57; a mutation. For women without a known genetic predispo-
(5) a history of previous breast cancer, radial scar, or other sition, the Gail,62 Claus,63 BRCAPRO, and Cuzick-Tyrer
premalignant lesions41,58,59; and (6) increased mammographic models are tools that can screen women who may be at
density.60 Recognition of factors that increase breast cancer increased risk and would therefore benefit from enhanced
risk facilitates appropriate screening and clinical manage- surveillance and chemoprevention. It should be noted that
ment of individual patients. It must be recognized, however, these mathematical models define population-based risk,
that most women have none of the known risk factors for not individual risk.
breast cancer, and the absence of these risk factors should Histologic markers of risk include both ductal and lobular
never prevent full evaluation or biopsy of a suspicious atypia, radial scar, and LCIS. Atypia and radial scar confer
breast lesion. a fourfold increased risk of developing breast cancer.64,65
Approximately 10% of all breast cancers are hereditary.61 LCIS is associated with an increased lifetime risk of subse-
Hereditary breast cancer is characterized by early age at quent carcinoma between 20 and 25%. Pleomorphic LCIS, a
onset, bilateral disease, and disease in other organ sites. pathologically distinct entity of LCIS, appears to be associ-
Therefore, an accurate and complete family history, includ- ated more frequently with invasive cancer.66,67 At present,
ing all malignancies, is essential for quantifying a womans women with these high-risk lesions should be offered
genetic predisposition to breast cancer. Questions about screening and chemoprevention.
breast cancer in family members should go back several Currently, there are three options for women to manage
generations, with age at diagnosis recorded if available. their risk: (1) enhanced surveillance, (2) chemoprevention, and
(3) risk-reducing surgery (i.e., prophylactic mastectomy).
For women with LCIS or a family history of breast carcinoma,
surveillance should include twice-yearly CBE. Mammogra-
Table 9 Magnitude of Known Breast Cancer phy should be performed annually after the diagnosis of
Risk Factors82 LCIS or atypical hyperplasia. Women with a family history
Relative risk < 2 of breast cancer should have screening mammography per-
Early menarche formed annually, beginning 10 years before the earliest age
Late menopause at which cancer was diagnosed in a first-degree relative.68
Nulliparity For women with known genetic mutations and other
Age > 35 at first birth
Hormone replacement therapy
women from families with an autosomal dominant pattern
Obesity of breast cancer transmission, annual mammographic screen-
Alcohol use ing should begin at age 25.68 There are several prospective
Proliferative breast disease nonrandomized trials that were designed to assess the
Previous breast biopsies benefit for adding yearly screening breast MRI for women at
Relative risk 24
One first-degree relative with breast cancer high risk for breast cancer.6973 These studies demonstrated
Radiation exposure that breast MRI is more sensitive than mammography. In
Previous breast cancer 2007, the ACS published recommendations for the use
Mammographic density of screening breast MRI as an adjunct to mammography.
Relative risk > 4
Two first-degree relatives with breast cancer
Annual screening with breast MRI is recommended for the
Gene mutation candidates listed in Table 10 [see Table 10].
Lobular carcinoma in situ It is important to remember that although the sensitivity
Ductal carcinoma in situ of breast MRI for cancer is high, the specificity is relatively
Atypical hyperplasia low and can result in high recall and biopsy rates.74 Breast

Scientific American Surgery

04/14
breast benign breast disease 21

Whether any of these compounds will play a clinically


Table 10 Candidates Who Should Be
useful role in preventing breast cancer remains to be seen.
Considered for Annual Screening with Additional consideration needs to be given to lifestyle
Breast MRI74 factors (avoiding excess alcohol, consuming a balanced diet,
BRCA mutation carriers exercising, maintaining an ideal body mass index [BMI]),
First-degree relatives of a BRCA mutation carrier who have which may play a role in risk management as well.
never been tested For those women at significant risk for breast cancer
Women with a lifetime risk of 20 to 25% based on risk models
that are predominantly dependent on family history
attributable to genetic predisposition, bilateral prophylactic
Women with a history of radiation to the chest between the ages mastectomy can be considered. High-risk women who
of 10 and 20 years underwent this procedure, compared with those who did
Women with Li-Fraumeni syndrome (mutations in the TP53 not, had their breast cancer risk reduced by at least 90%.78
gene) Oopherectomy also confers up to a 50% breast cancer risk
First-degree relatives of women with Li-Fraumeni syndrome
Women with Cowden and Bannayan-Riley-Ruvalcaba reduction in premenopausal women.79 The benefits of pro-
syndromes (mutations in the PTEN gene) phylactic mastectomy must be weighed against the irrevers-
First-degree relatives of women with Cowden and Bannayan- ibility and the psychosocial consequences of the procedure.
Riley-Ruvalcaba syndromes Research involving high-risk women is challenging
MRI = magnetic resonance imaging. because of the large numbers of women who must be
recruited and followed for many years and because of the
cost associated with such an undertaking. Improved risk
assessment tools that can aid in improved risk stratification
MRI should be used as an adjunct to mammography and are under active investigation.80 Current trials are focused
not a replacement. Mammography and MRI can be done on identifying and using intermediate biomarkers of breast
simultaneously or alternating with each other at 6-month cancer risk to test potential chemopreventive agents.
intervals to coincide with the CBE. Given the specificity of
breast MRI and the fact that many enhancing lesions seen on Financial Disclosures: Helen Cappuccino, MD, FACS, Ermelinda Bonaccio, MD,
breast MRI are occult to conventional imaging modalities, it and Shicha Kumar, MD, have no relevant financial relationships to disclose. This
chapter was previously authored by Swati Kulkarni, MD, FACS, Doreen M. Agnese,
is essential that any facility performing screening breast MRI MD, FACS, Stephen P. Povoski, MD, FACS, and Wiley W. Souba, MD, ScD,
should have the capability for MRI-guided breast biopsy. FACS, with disclosure made at the time of initial publication. This chapter has been
Chemopreventive strategies are designed either to block reviewed, updated, and rereleased by the authors listed.
the initiation of the carcinogenic process or to prevent
(or reverse) the progression of the premalignant cells to an
References
invasive cancer.75 Selective estrogen receptor modulators
(SERMs), tamoxifen, and raloxifene are currently FDA 1. Seltzer MH. Breast complaints, biopsies, and cancer corre-
approved for chemoprevention in breast cancer. Large lated with age in 10,000 consecutive new surgical referrals.
multicenter randomized trials demonstrated the efficacy of Breast J 2004;10:1117.
these agents in the primary prevention setting for women at 2. Vahabi M. Breast cancer screening methods: a review of the
increased risk for breast cancer based on a Gail score of 1.67 evidence. Health Care Women Int 2003;24:77393.
or a personal history of ADH or LCIS. The overall risk of 3. Smith RA, Saslow D, Sawyer KA et al. American Cancer
invasive breast cancer was reduced by 50% after treatment Society guidelines for breast cancer screening: update 2003.
for 5 years and limited to estrogen receptor (ER)-positive CA Cancer J Clin 2003;53:14169.
breast cancers in these high-risk women. Raloxifene is 4. Jatoi I. Screening clinical breast examination. Surg Clin
currently approved only for postmenopausal women and North Am 2003;83:789801.
5. Smith RA, Duffy SW, Gabe R, et al. The randomized trials
has the added benefit of treating postmenopausal osteopo-
of breast cancer screening: what have we learned? Radiol
rosis. It is noteworthy, however, that raloxifene was not
Clin North Am 2003;42:793806.
found to prevent noninvasive breast cancers in this trial.76
6. Tabar I, Vitak B, Chen HH, et al. The Swedish Two-County
The aromatase inhibitor exemestane has been shown to be
Trial twenty years later. Updated mortality results and new
effective in the chemoprevention of breast cancer in high-
insights from long-term follow-up. Radiol Clinic North Am
risk women and is increasingly used for this indication; 2000;38:62551.
however, it is not yet FDA approved in this setting.77 7. Bevers TB, Anderson BO, Bonaccio E, et al. NCCN clinical
The hot flashes, deep vein thrombosis, and endometrial practice guidelines in oncology: breast cancer screening and
cancer associated with tamoxifen have made it an unattrac- diagnosis. J Natl Compr Canc Netw 2009;7:106096.
tive option for many women. This has generated interest 8. Pisano ED, Gatsonis C, Hendrick E, et al. Diagnostic
in identifying other chemopreventive agents. Aromatase performance of digital versus film mammography for
inhibitors, which are used to treat ER-positive breast cancers breast-cancer screening. N Engl J Med 2005;353:177383.
in postmenopausal women, reduce the risk of contralateral 9. American College of Radiology (ACR). ACR BI-RADS
cancers and may have a role to play in chemoprevention as mammography. In: ACR Breast Imaging Reporting and
noted above. In addition, gonadotropin-releasing hormone Data System, breast imaging atlas. 4th ed. Reston (VA):
agonists, monoterpenes, lignans, retinoids, rexinoids, vita- American College of Radiology; 2003. p. 1937.
min D derivatives, and inhibitors of tyrosine kinase are all 10. Sickles AE. Periodic mammographic follow up of probably
undergoing evaluation in clinical or preclinical studies with benign lesions: results in 3184 consecutive cases. Radiology
a view to assessing their potential chemopreventive activity. 1991;179:4638.

Scientific American Surgery

04/14
breast benign breast disease 22

11. Varas X, Leborgne F, Leborbne JH. Nonpalpable, probably 30. Saad RS, Kanbour-Shakir A, Syed A, Kanbour A. Sclerosing
benign lesions: role of follow-up mammography. Radiology papillary lesion of the breast: a diagnostic pitfall for malig-
1992;184:40914. nancy in fine needle aspiration biopsy. Diagn Cytopathol
12. Schueller G, Jaromi S, Ponhold L, et al. US-guided 14-gauge 2006;34:1148.
core-needle breast biopsy: results of a validation study in 31. Rizzo M, Lund M, Oprea G, et al. Surgical follow-up and
1352 cases. Radiology 2008;248:40613. clinical presentation of 142 breast papillary lesions diag-
13. Brenner RJ, Bassett LW, Fajardo LL, et al. Stereotactic core- nosed by ultrasound-guided core-needle biopsy. Ann Surg
needle breast biopsy: a multi-institutional prospective trial. Oncol 2008;15:10407.
32. Ueng SH, Mezzetti T, Tavassoli FA. Papillary neoplasms
Radiology 2001;218:86672.
of the breast: a review. Arch Pathol Lab Med 2009;133:
14. Liberman L, Feng TL, Dershaw DD, et al. US-guided core
893907.
breast biopsy: use and cost-effectiveness. Radiology 1998;
33. Mercado CL, Hamele-Bena D, Oken SM, et al. Papillary
208:71723.
lesions of the breast at percutaneous core-needle biopsy.
15. Skaane P, Bandos AI, Gullien R, et al. Comparison of digital Radiology 2006;238:8018.
mammography alone and digital mammography plus 34. Jaffer S, Nagi C, Bleiweiss IJ. Excision is indicated for intra-
tomosynthesis in a population-based screening program. ductal papilloma of the breast diagnosed on core needle
Radiology 2013,267:4756. biopsy. Cancer 2009;115:283743.
16. Zuley ML, Bandos AI, Ganott MA, et al. Digital breast 35. Brookes MJ, Bourke AG. Radiological appearances of
tomosynthesis versus supplemental diagnostic mammo- papillary breast lesions. Clin Radiol 2008;63:126573.
graphic views for evaluation of noncalcified breast lesion. 36. Van Zee KJ, Ortega PG, Minnard E, Cohen MA. Preopera-
Radiology 2012;266:10413. tive galactography increases the diagnostic yield of major
17. Brandt KR, Craig DA, Hoskins TL, et al. Can digital breast duct excision for nipple discharge. Cancer 1998;82:187480.
tomosynthesis replace conventional diagnostic mammogra- 37. Roa JC, Tapia O, Carrasco P, et al. Prognostic factors of
phy views for screening recalls without calcifications? A phyllodes tumor of the breast. Pathol Int 2006;56:30914.
comparison study in a simulated clinical setting. AJR Am J 38. Mangi AA, Smith BL, Gadd MA, et al. Surgical manage-
Roentgenol 2013;200:2918. ment of phyllodes tumors. Arch Surg 1999;134:48793.
18. Olawaiye A, Withiam-Leitch M, Danakas G, Kahn K. 39. Brem RF, Behrndt VS, Sanow L, Gatewood OM. Atypical
Mastalgia: a review of management. J Reprod Med 2005;50: ductal hyperplasia: histologic underestimation of carcinoma
in tissue harvested from impalpable breast lesions using 11-
9339.
gauge stereotactically guided directional vacuum-assisted
19. Norlock FE. Benign breast pain in women: a practical
biopsy. AJR Am J Roentgenol 1999;172:14057.
approach to evaluation and treatment. J Am Med Womens
40. Harvey JM, Sterrett GF, Frost FA. Atypical ductal hyperpla-
Assoc 2002;57:8590.
sia and atypia of uncertain significance in core biopsies
20. Bundred NJ. Breast pain. Clin Evid (Online). 2007. Avail- from mammographically detected lesions: correlation with
able at: http://www.clinicalevidence.com (accessed April excision diagnosis. Pathology 2002;34:4106.
5, 2010). 41. Jacobs TW, Byrne C, Colditz G, et al. Radial scars in benign
21. Neilann KH, Johanna WL. Potential mechanisms of diet breast-biopsy specimens and the risk of breast cancer.
therapy for fibrocystic breast conditions show inadequate N Engl J Med 1999;340:4306.
evidence of effectiveness. J Am Diet Assoc 2000;100: 42. Kennedy M, Masterson AV, Kerin M, Flanagan F. Pathol-
136880. ogy and clinical relevance of radial scars: a review. J Clin
22. Qureshi S, Sultan N. Topical nonsteroidal anti-inflamma- Pathol 2003;56:7214.
tory drugs versus oil of evening primrose in the treatment 43. Youk JH, Kim EK, Kim MJ. Atypical ductal hyperplasia
of mastalgia. Surgeon 2005;3:710. diagnosed at sonographically guided 14-gauge core needle
23. Rosolowich V, Saettler E, Szuck B, et al. Mastalgia. J Obstet biopsy of breast mass. AJR Am J Roentgenol 2009;192:
Gynaecol Can 2006;28:4971. 113541.
24. Pain JA, Cahill CJ. Management of cyclical mastalgia. Br J 44. Stavros AT, Parker SH, Rapp LC. Breast ultrasound.
Clin Pract 1990;44:4546. Philadelphia: Lippincott Williams & Wilkins; 2004.
25. Hussain AN, Policarpio C, Vincent MT. Evaluating nipple 45. Hughes LE, Mansel RE, Webster DJT. Benign disorders and
diseases of the breast: concepts and clinical management.
discharge. Obstet Gynecol Surv 2006;61:27883.
2nd ed. Philadelphia: WB Saunders; 2004.
26. Morley JE, Dawson M, Hodgkinson H, Kalk WJ. Galactor-
46. Catania S, Zurrida S, Veronesi P, et al. Mondors disease
rhea and hyperprolactinemia associated with chest wall
and breast cancer. Cancer 1992;69:226770.
injury. J Clin Endocrinol Metab 1977;45:9315.
47. Caocci G, Atzeni S, Orru N, et al. Gynecomastia in a male
27. Cabioglu N, Hunt KK, Singletary SE, et al. Surgical decision after dasatinib treatment for chronic myeloid leukemia.
making and factors determining a diagnosis of breast carci- Leukemia 2008;22:21278.
noma in women presenting with nipple discharge. J Am 48. Shulman DI, Francis GL, Palmert MR, Eugster EA, for the
Coll Surg 2003;196:35464. Lawson Wilkins Pediatric Endocrine Society Drug and
28. Beechey-Newman N, Kulkarni D, Kothari A, et al. Breast Therapeutics C. Use of aromatase inhibitors in children
duct microendoscopy in nipple discharge: microbrush and adolescents with disorders of growth and adolescent
improves cytology. Surg Endosc 2005;19:164851. development. Pediatrics 2008;121:e97583.
29. Liu GY, Lu JS, Shen KW, et al. Fiberoptic ductoscopy com- 49. Fradet Y, Egerdie B, Andersen M, et al. Tamoxifen as
bined with cytology testing in the patients of spontaneous prophylaxis for prevention of gynaecomastia and breast
nipple discharge. Breast Cancer Res Treat 2008;108:2717. pain associated with bicalutamide 150 mg monotherapy

Scientific American Surgery

04/14
breast benign breast disease 23

in patients with prostate cancer: a randomised, placebo- 69. Warner E, Plewes DB, Hill KA, et al. Surveillance of BRCA1
controlled, dose-response study. Eur Urol 2007;52:10614. and BRCA2 mutation carriers with magnetic resonance
50. Dixon JM. ABC of breast diseases: breast infection. BMJ imaging, ultrasound, mammography, and clinical breast
1994;309:9469. examination. JAMA 2004;292:131725.
51. Henderson IC. Risk factors for breast cancer development. 70. Leach MO, Boggis CR, Dixon AK, et al. Screening with
Cancer 1993;71 Suppl 6:212740. magnetic resonance imaging and mammography of a UK
52. Slattery ML, Kerber RA. A comprehensive evaluation of population at high familial risk of breast cancer: a prospec-
family history and breast cancer risk: the Utah Population tive multicentre cohort study (MARIBS) [published erratum
Database. JAMA 1993;270:15638. appears in Lancet 2005;365(9474):1848]. Lancet 2005;365:1769
53. Squitieri R, Tartter PI, Ahmed S, et al. Carcinoma of the 78.
breast in postmenopausal hormone user and nonuser 71. Kriege M, Brekelmans CTM, Boetes C, et al. Efficacy of MRI
control groups. J Am Coll Surg 1994;178:16770. and mammography for breast-cancer screening in women
54. Newcomb PA, Storer BE, Longnecker MP, et al. Lactation with a familial or genetic predisposition. N Engl J Med
and a reduced risk of premenopausal breast cancer. N Engl 2004;351:42737.
J Med 1994;330:817. 72. Kuhl CK, Schrading S, Leutner CC, et al. Mammography,
55. Colditz GA, Stampfer MJ, Willett WC, et al. Prospective breast ultrasound, and breast magnetic resonance imaging
study of estrogen replacement therapy and risk of breast for surveillance of women at high familial risk for breast
cancer in postmenopausal women. JAMA 1990;264: cancer. J Clin Oncol 2005;23:846976.
264853. 73. Lehman CD, Blume JD, Weatherall P, et al. Screening
56. Cummings SR, Tice JA, Bauer S, et al. Prevention of breast women at high risk for breast cancer with mammography
cancer in postmenopausal women: approaches to estimat- and magnetic resonance imaging. Cancer 2005;103:1898
ing and reducing risk. J Natl Cancer Inst 2009;101:3848. 905.
57. Travis LB, Hill D, Dores GM, et al. Cumulative absolute 74. Saslow D, Boetes C, Burke W, et al. American Cancer Soci-
breast cancer risk for young women treated for Hodgkin ety guidelines for breast screening with MRI as an adjunct
lymphoma. J Natl Cancer Inst 2005;97:142837. to mammography. CA Cancer J Clin 2007;57:7589.
58. Frykberg ER, Bland KI. Management of in situ and mini- 75. Zujewski J. Selective estrogen receptor modulators (SERMs)
mally invasive breast carcinoma. World J Surg 1994;18: and retinoids in breast cancer chemoprevention. Environ
4557. Mol Mutagen 2002;39:26470.
59. Page DL, Jensen RA. Evaluation and management of high 76. Vogel VG, Costantino JP, Wickerham DL, et al. Effects of
risk and premalignant lesions of the breast. World J Surg tamoxifen vs raloxifene on the risk of developing invasive
1994;18:328. breast cancer and other disease outcomes: the NSABP Study
of Tamoxifen and Raloxifene (STAR) P-2 trial. JAMA 2006;
60. Martin L, Boyd N. Mammographic density. Potential mech-
295:272741.
anisms of breast cancer risk associated with mammographic
77. Goss PE, Ingle JN, Ales-Martinez JE, et al. Exemestane
density: hypotheses based on epidemiological evidence.
for breast-cancer prevention in postmenopausal women.
Breast Cancer Res 2008;10:201.
N Engl J Med 2011;364:238191.
61. Quan ML, Petrek JA. Clinical implications of hereditary
78. Hartmann LC, Schaid DJ, Woods JE, et al. Efficacy of
breast cancer. Adv Surg 2003;37:197212.
bilateral prophylactic mastectomy in women with a family
62. Gail MH, Brinton LA, Byar DP, et al. Projecting individual-
history of breast cancer. N Engl J Med 1999;340:7784.
ized probabilities of developing breast cancer for white
79. Rebbeck TR, Kauff ND, Domchek SM. Meta-analysis of risk
females who are being examined annually. J Natl Cancer
reduction estimates associated with risk-reducing salpingo-
Inst 1989;81:187986.
oophorectomy in BRCA1 or BRCA2 mutation carriers.
63. Claus EB, Risch N, Thompson WD. Autosomal dominant
J Natl Cancer Inst 2009;101:807.
inheritance of early-onset breast cancer. Implications for
80. Fabian CJ, Kimler BF, Mayo MS, Khan SA. Breast-tissue
risk prediction. Cancer 1994;73:64351.
sampling for risk assessment and prevention. Endocr Relat
64. Page DL, Dupont WD, Rogers LW, Rados MS. Atypical
Cancer 2005;12:185213.
hyperplastic lesions of the female breast. A long-term
81. Plitas G, Morrow M. Womens health. Approach to the
follow-up study. Cancer 1985;55:2698708.
patient with a breast mass. In: Nabel EG, editor. ACP med-
65. Simpson P, Gale T, Fulford L, et al. The diagnosis and
icine [online]. Philadelphia: Decker Intellectual Properties;
management of pre-invasive breast disease: pathology of
January 2013. Available at: http://www.acpmedicine.com
atypical lobular hyperplasia and lobular carcinoma in situ. (accessed October 4, 2013).
Breast Cancer Res 2003;5:25862. 82. Morrow M, Jordan VC. Managing breast cancer risk. 1st ed.
66. Sneige N, Wang J, Baker BA, et al. Clinical, histopathologic, Hamilton (ON): BC Decker Inc; 2003. p. 302.
and biologic features of pleomorphic lobular (ductal-
lobular) carcinoma in situ of the breast: a report of 24 cases.
Mod Pathol 2002;15:104450. Acknowledgments
67. Fadare OMD, Dadmanesh FMD, Alvarado-Cabrero IMD,
et al. Lobular intraepithelial neoplasia [lobular carcinoma in Figures 1 through 9, 11, 12, 17, 21, 22, and 23 Christine Kenney
situ] with comedo-type necrosis: a clinicopathologic study Figures 15 and 19 Courtesy of George Plitas, MD, and Monica
of 18 cases. Am J Surg Pathol 2006;30:144553. Morrow, MD, FACS.
68. Dershaw DD. Mammographic screening of the high-risk Figure 16 Courtesy of Angela Gucwa, MD, J. Garrett Harper,
woman. Am J Surg 2000;180:2889. MD, and D. Scott Lind, MD.

Scientific American Surgery

04/14