Breast Infections: Principles, Pathology and Management

Breast Infections
Principles, Pathology and management
Dr. Mahmoud W. Qandeel

Outlines
• Lactational and non-lactational
– Mastitis
– Breast abscess
• Zuska’s disease
• Mondor’s disease

Breast infections
• Uncommon outside of the postpartum period
• Classified as lactating or nonlactating infections
• Staphylococcus aureus and Streptococcus species are the organisms most

common.

Lactating breast infections
• Occur commonly during the initial 6 weeks of breast-feeding and during
the process of weaning.
• It may range from mild superficial mastitis to deep abscesses.
• In the initial stages of infection, a mastitis or cellulitis is typically found,

with associated
1. Pain
2. Erythema
3. Induration
4. Fever

Treatment:
1. Pain management (acetaminophen, NSAIDs)

2. Warm compresses
3. Antibiotics such as dicloxacillin. Alternative antibiotics include cephalexin
and erythromycin.
• Improves within 24-48 hours after initiation of antibiotics.

• Breast feeding?

• If symptoms or fever persists, an abscess should be ruled out.
• For small or superficial abscesses, needle aspiration may be attempted.
• Incision and drainage should be considered for large or complex
abscesses, understanding the risks associated with milk fistula
formation
• Delay or inadequate management may lead to tissue destruction,

chronic infections, periductal fistulas and breast deformities.

Non-lactating breast infections
• Can present as mastitis , peri-areolar abscesses or less commonly as

peripheral abscesses.
• An underlying clinical condition should always be sought and treated.
• Indeed, in addition to cultures, radiological modalities such as

ultrasonographic imaging may provide specific diagnosis and aid the
management.

m

Non-lactating breast abscess
• For small abscesses < 3 cm, needle aspiration and/or drain placement
can be performed.
• For larger and/or deeper abscesses, incision and drainage may be

indicated.
• I&D can be performed under local anesthesia if small and superficial,

but if deep or large it needs to be done under GA.

• A preoperative ultrasound can be obtained to better evaluate the size and
location of the abscess.
• Biopsy of the cavity should always be considered, as breast infection may be

an unusual breast cancer presentation.
• For a subareolar abscess, removal of the sinus tract as well as the segmental
duct should be considered.

• In the setting of recurrent or persistent abscess formation or
inflammatory changes despite adequate surgical management, other
etiologies need to be considered including
1. Malignancy
2. idiopathic granulomatous mastitis
3. Wegener’s granuloma
4. Sarcoidosis
5. Tuberculosis
6. histoplasmosis.

Zuska’s disease
• Also called recurrent periductal mastitis,

is a condition of recurrent retroareolar
infections and abscesses.
• Smoking has been implicated as a risk

factor for this condition.
• This syndrome is managed

symptomatically by antibiotics coupled
with incision and drainage as necessary.
Mondor’s Disease
• A variant of thrombophlebitis that involves the
superficial veins of the anterior chest wall and breast.
• Also called “string phlebitis,” a thrombosed vein

presenting as a tender, cord-like structure.
• Frequently involved veins include the lateral thoracic

vein, the thoracoepigastric vein.
• Typically, a woman presents with acute pain in the

lateral aspect of the breast or the anterior chest wall.
• A tender, firm cord is found to follow the distribution

of one of the major superficial veins.
• This benign, self-limited disorder is not indicative of a cancer.
• When the diagnosis is uncertain, or when a mass is present near the tender
cord, biopsy is indicated.
• Therapy for Mondor’s disease includes the liberal use

of anti-inflammatory medications and application of
warm compresses along the symptomatic vein.
• The process usually resolves within 4 to 6 weeks.
• When symptoms persist or are refractory to therapy, excision of the

involved vein segment may be considered.
Idiopathic granulomatous mastitis Periductal mastitis
More in non white people White people
Non-smoker Smokers
Responds to steroids No response to steroids
Present as hard lump without systemic
signs
Mimicking inflammatory breast cancer
clinically and mammographic
Could be bilateral

Benign Breast Disorders
Made simple !

Outlines
• Classification
• Non proliferative disorders of the breast
• Proliferative disorders of the breast without atypia
• Proliferative disorders of the breast with atypia

1. NONPROLIFERATIVE BREAST LESIONS
• Cysts
• Duct ectasia
• Fibroadenoma

Cysts
• Arise from the terminal duct lobular unit when fluid accumulates because of
distension and obstruction of the efferent ductile occur mainly during lobular
development, menstrual cyclic changes, and lobular involution in
premenopausal and postmenopausal women
• Peak between 35- 50 years of age

A- Simple cysts
• Anechoic and do not have solid components or Doppler signals.
• By definition benign and do not require further intervention
• Aspiration if symptomatic.
• If the aspirated fluid is:
1. Non bloody
2. The palpable mass completely resolves
• No further diagnostic evaluation is required.
• A follow-up CBE with or without ultrasound can be performed in 3 to 6 months to

document stability

B- Complicated cysts
• (<1% risk of malignancy)
• On ultrasound, complicated cysts appear as

1. Masses with homogenous low-level internal echoes due to echogenic debris.
2. No solid components, thick walls, or thick septa
• Management:
– biopsy through FNA, core biopsy, or excisional biopsy. Or
– ultrasound and mammography with CBE every 6 months for 2 years to document
stability.
• If any change occurred (solid component, increasing in size, etc) biopsy should be
performed

C- Complex cysts
• Characterized by:
1. Solid components
2. Thick walls
3. Thick septa
4. Absence of posterior wall enhancement on ultrasound
5. Mixed echgenicity
Management:
• Biopsy (of the solid part) with metallic clipmarking the biopsy site
• then follow-up with CBE and ultrasound imaging every 6 to 12 months for 1 to 2 years to
document stability.
• For any concerning changes in the appearance of the lesion or increase in size, excisional
biopsy should be performed.
Fibroadenoma
• The most common breast lump in young females
• Are benign solid tumors made of glandular as well as fibrous tissue
• Abundant stroma with normal cellular element
• Peak 15-35 years
• Present as well-circumscribed mobile masses not fixed to the surrounding breast tissue
(mouse of the breast) Usually 1-2 cm
• Hormonal dependence
• Cancer risk is 0.2 %
• Giant form more than 4 cm
• More than 5 in one side is a disease

• Management:
• About 30% disappear spontaneously
• If benign imaging characteristics and asymptomatic either:
– Follow up with serial CBE and ultrasound to ensure stability
– Core needle biopsy to confirm the diagnosis.

• Indications for surgical excision:
1. Symptomatic
2. Increases in size
3. Couldn’t rule out malignancy (phyllodes tumor)
4. Complex fibroadenomas (atypical features clinically or on biopsy)
5. Giant fibroadenomas (> 4 cm)
6. Juvenile fibroadenomas (ages 10-18 years)
• Cryoablation and ultrasound-guided vacuum assisted biopsy are approved treatments

for fibroadenomas of the breast, especially lesions <3 cm.

Apocrine metaplasia
• It is a reversible transformation of cells to an apocrine phenotype.
• It is common in the breast in the context of fibrocystic change.
• It is seen in women mostly over the age of 50 years.
• Metaplasia happens when there is an irritation to the breast (breast cyst).
• This type of metaplasia represents an exception to the common rule of metaplasia
increasing the risk for developing cancer; apocrine metaplasia doesn't increase at
all the possibility of getting breast cancer.

Breast calcifications
Lobular calcifications
- These calcifications fill the acini.

- This results in uniform, homogeneous and sharply outlined calcifications, that are often round.
- When the acini become very large, as in cystic hyperplasia, 'milk of calcium' may fill these
cavities.
- However when there is more fibrosis, as in sclerosing adenosis, the calcifications are usually
smaller and less uniform.
- In these cases it can be difficult to differentiate them from intraductal calcifications.
- Lobular calcifications usually have a diffuse or scattered distribution, since most of the breast is
involved in the process that forms the calcifications.
- Lobular calcifications are almost always benign.

Intraductal calcifications
- These calcifications are calcified cellular debris or secretions within the intraductal lumen.
- The uneven calcification of the cellular debris explains the fragmentation and irregular
contours of the calcifications.
- These calcifications are extremely variable in size, density and form (i.e. pleomorphic)
- Sometimes they form a complete cast of the ductal lumen.
- This explains why they often have a fine linear or branching form and distribution.
- Intraductal calcifications are suspicious of malignancy.
Lobular calcifications Intraductal calcifications
Benign Calcifications
Skin Calcification (Tattoo sign) Vascular Calcification
Coarse or (Popcorn-like) Round and punctate calcifications

fibrocystic changes or adenosis ,rarely DCIS.
Benign Calcifications
Eggshell Calcification (Fat Necrosis, oil cyst)
Dystrophic calcifications (lava like) (Fat Necrosis)

Malignant Calcifications
Fine Linear Branching (DCIS)
Coarse heterogeneous
• Fibroadenoma
• Fibrosis
• Post-traumic representing evolving dystrophic
calcifications (fat necrosis)
• DCIS Fine Pleomorphic (DCIS)
2. PROLIFERATIVE BREAST LESIONS WITHOUT ATYPIA
• Intraductal papillomas
• Ductal hyperplasia
• Radial scars

Intraductal papillomas
• Often present with pathologic nipple discharge
• Consist of a monotonous array of papillary cells that grow from the wall of a duct or
cyst into its lumen.
• Can harbor areas of atypia or DCIS
• Management:
– Surgical excision
– If no atypia or DCIS is found at the time of excision, no further treatment is
necessary.
Ductal hyperplasia
• Often an incidental finding on biopsy
• Characterized by an increased number of benign looking cells within the ductal space
• Not associated with a significant risk for breast cancer
• No additional treatment is necessary

Radial scars
• Often found incidentally when a breast mass or radiologic abnormality is biopsied or
excised.
• These lesions are characterized by a fibroelastic core with radiating ducts and lobules, and
can appear speculated on mammography.
– Lesions larger than 1 cm are referred as complex sclerosing lesions
– Lesions smaller than 1 cm are referred as radial scars.
• Low risk for malignancy. (8-30%)
• Management:
– Surgical excision
– If the surgical excisional biopsy confirms a radial scar, no additional treatment is
needed.
Sclerosing adenosis
• May be found in patients with fibrocystic changes and refers to an
increased number of small terminal ductules associated with stromal
tissue proliferation.
• These lesions may be confused with carcinoma; however, there is no

increased cancer risk.
• Observation is appropriate when concordance exists between imaging

and pathologic findings on biopsy.

3. PROLIFERATIVE BREAST LESIONS WITH ATYPIA
• Atypical ductal hyperplasia (ADH)
• Atypical ductal hyperplasia (ALH)

Atypical ductal hyperplasia (ADH)
• Characterized by a proliferation of uniform epithelial cells with monomorphic round

nuclei filling part, but not all, of the involved duct.
• Often presents as suspicious microcalcifications seen on mammography.

• Increase breast cancer risk 4 folds.
• The annual risk of developing breast cancer with ADH is 0.5-1% per year
• Management:
• Surgical excision, as an upgrade to DCIS or invasive breast cancer can occur in 10% to
20% of cases.

Atypical lobular hyperplasia (ALH)
• ALH is characterized by a proliferation of monomorphic, evenly spaced,

dyshesive cells filling part, but not all, of the involved lobule
• Often an incidental finding found on breast biopsies performed for other

reasons, such as an abnormal mammogram or breast mass.
• Risk of malignancy 1-3%

• Increase breast cancer risk 4 folds.

Atypical lobular hyperplasia (ALH)
Management:
• If adequate sample, no role for excision.
• Instead, the patient should be counseled toward risk reduction strategies

that include
1. CBE every 6 to 12 months
2. Annual screening mammography
3. Consideration for chemoprevention with a selective estrogen receptor modulator
(SERM) or an aromatase inhibitor (AI).

Lesion Risk for upgrading on excision
ALH 1-20%
ADH 10-20%
LCIS 4-25%
Flat Epithelial Hyperplasia 10-15%
Intraductal papilloma 10%
Radial Scar 8-30%

Breast Cancer
Screening, Risk factors, Diagnosis and Evaluation
DCIS, LCIS

Outlines
• Screening
• Risk Factors
• Symptoms and signs
• Hereditary breast cancer
• Evalution of breast cancer
– Staging
– Histological subtypes
– Grading
– Biomarkers
– Genetic subtypes
• DCIS
• LCIS
• Paget’s disease
• Male breast cancer Dr. Mahmoud W. Qandeel
Breast cancer
• Most common cancer in women
• 2nd commonest cause of cancer death in women.
• 50 % of all cancers in women between 40-55 y
• Annual incidence of 250.000 new patient per y
• Life time risk is one in every eight women
• Probability of developing invasive breast cancer is 12.3% or 1 in 8
• 70% of women have no risk factor

Breast Cancer Screening
• Breast Self-Examination
• BSE has not been shown to have an impact on the rates of breast cancer diagnosis,
stage at diagnosis, or breast cancer mortality.
• In addition, BSE may result in higher rates of breast biopsy for benign disease.
• Clinical Breast Examination

• Women should undergo CBE as part of their annual physical examination.
• It has been suggested that CBE may modestly improve early detection of breast
cancer but at the risk of increased false-positives

Screening Mammography
• Routinely two views (craniocaudal (CC) and mediolateral oblique (MLO).
• Significant reduction in breast cancer mortality with mammographic screening in women

aged 40 to 69 years (RR reduction of 20%).
• Most guidelines suggest routine screening mammography at the age of 40 years then
annually.
• If the patient has positive family history, mammography should start 10 years earlier
than the age her relative was diagnosed at
• Some guidelines recommend stopping screening after the age of 74

Mammographic Features of Breast Cancer:
• Asymmetry
• Architectural distortion
• Areas of skin thickening
• Mass (irregular, spiculated)
• Microcalcifications
Asymmetry
Architectural distortion Spiculated Mass Dr. Mahmoud W. Qandeel

• Left, Stellate mass in the breast.
The combination of density with
spiculated borders and distortion
of surrounding breast
architecture suggests a
malignancy.
• Right, Clustered
microcalcifications. Fine,
pleomorphic, and linear
calcifications that cluster
together suggest the diagnosis of
ductal carcinoma in situ

• Mammogram revealing a
small, spiculated mass in
the right breast
• left. A small, spiculated

mass is seen in the right
breast with skin tethering
(CC view).
• right. Mass seen on oblique
view of the right breast.
• Mammography is less sensitive in younger women ( under age 30) due to dense breast
fibroglandular tissue

Breast Imaging Reporting And Data System
(BIRADS)

Benign mammographic findings that might be mistaken for
malignancy
• Radial scar
• Fat necrosis
• Milk of calcium

Breast and axillary ultrasound
• Best used in adjunct to Mammography
• Can be used alone in young patients screening due to difficulty in obtaining

mammography due to dense breast tissue
• Can differentiate cysts or abscesses.
• Very important for evaluation of the axillary LNs

Screening MRI
• More sensitive but less specific than

mammography
• Commonly used by providers as an adjunct

to mammography to screen women at high
risk for breast cancer

• Indications of annual MRI in addition to mammography
1. BRCA mutations
2. First degree relatives of known BRCA mutation carriers
3. Those with a lifetime risk of breast cancer that is estimated to be ≥20%
based on risk prediction models
4. Patients who received radiation treatment to the chest between ages 10
and 30 and
5. TP53 (Li–Fraumeni syndrome) mutations
6. PTEN genetic (Cowden syndrome) mutations.

Risk Factors for breast cancer
Gender
• 100 times more frequently in women than in men.
• In the US, annually
– 200,000 in women
– 2000 in men
Increasing Age
85 % of breast cancers occur after 50 years of age.
Estrogen Exposure
1. Early age of first menarche

2. Late age of menopause
3. Late age of first live birth
4. Nulliparity
5. hormone replacement therapy
6. breast-feeding can reduce breast cancer risk

Environmental and Lifestyle Factors
A- Radiation exposure
• Ionizing radiation of the chest, such as for treatment of Hodgkin lymphoma,
especially in prepuberty stage (age 10 to 14 years)has the most effect
B- Alcohol use: increases the risk

C- Smoking
D- Regular physical exercise and a diet composed mainly of fruits and
vegetables likely provide protection against breast cancer.
Family History
• The number of first-degree relatives with breast cancer is strongly associated

with a woman’s risk for the future development of breast cancer.
– If one first-degree relative is affected >> two fold increase

– if two first-degree relatives are affected >> threefold increase
• The age at diagnosis of the first-degree relative is also important, risk is 3 fold
higher when the diagnosis occurs before age 30 , 1.5-fold higher if the diagnosis
is after age 60

Personal history of breast cancer
• Increased risk for contralateral breast cancer

• With in situ lesions
– The 10-year risk of developing a contralateral invasive breast cancer is 5 percent
• With invasive breast cancer

– 1 % per year for premenopausal
– 0.5 % per year for postmenopausal women

Weight and body mass index
• Opposite influences on postmenopausal as compared to premenopausal

breast cancer.
Postmenopausal
• women with BMI >33 had 27% increased breast cancer risk compared to
those with a BMI <21
Premenopausal
• women with BMI ≥31 were 46% less likely to develop breast cancer than
those with a BMI <21

Role of dietary factors ?
• Deficiency of essential fatty acids.
• Low consumption of vegetables.
• Low vitamin A
• Increase consumption of read meat
• Higher levels of saturated fatty acids.
• Cigarette smoking.
• Alcoholic drinks

Socioeconomic status
• Women of higher socioeconomic status are at greater risk for

breast cancer
– Reflect differing reproductive patterns

– Utilization of screening mammography
Night shift work !

RFs

Breast cancer risk reduction
✓ Planning for first birth before the age of 30
✓ Breastfeeding for at least six months
✓ Avoidance of postmenopausal hormone therapy
✓ Avoidance of unnecessary exposure to radiation
✓ Cessation of smoking
✓ Limiting alcohol intake
✓ Maintenance of a healthy weight
✓ Limiting nocturnal shift work
✓ Adopting a physically active lifestyle.

Chemoprevention
• For women who are at higher risk, their risk of developing breast cancer
can be reduced by at least 50 % or more by taking Tamoxifen or
Raloxifene for five years.
• Tamoxifen and raloxifene are both approved by the FDA for the
prevention of breast cancer
• Recent studies showed similar results with aromatase inhibitors

Symptoms and signs

Signs
Obvious lump or
thickening in breast
Redness or pitting of skin

Discharge or over the breast, (Oedema)
bleeding Dimpling & peau d'orange ,
infiltration Ulceration
Change in size
(asymmetry) or contours Change in color or
of breast appearance of areola (Erythema,
Erosion and ulceration
89
Edema & peau d'orange (note location and extent)
Erythema
infiltration
Ulceration
Dimpling seen by
muscle
contraction

Inversion
Erosion &ulceration Erythema Retraction
Discharge (specify) Dr. Mahmoud W. Qandeel

Breast CA can be
A- Sporadic
• The majority of breast cancers are caused by sporadic mutations (mutations
that occur in somatic cells that cannot be inherited).
B- Hereditary breast cancer

Less than 10% of breast cancers are hereditary
The family tree is characterized by :
1. Earlier onset of breast cancer
2. Bilateral breast cancer
3. Greater frequency of primary cancers such as breast and ovary
4. Autosomal dominant inheritance pattern
• C- Familial breast cancer
• For women who have first- or second-degree relatives with breast cancer
but do not meet the hereditary breast cancer definition noted above.
• It is likely that both genetic and environmental factors play a role in their
susceptibility.

Hereditary breast cancer
BRCA mutations
• Most patients with hereditary breast cancer have mutations in the BRCA1
(chromosome 17)or BRCA2 genes (chromosome 13)
• Both serve as tumor suppressor genes and function as gatekeepers in

controlling gene transcription, regulating repair of DNA damage, and may
play a role in the maintenance of genomic stability.
• The lifetime risk of breast cancer in BRCA1 and BRCA2 mutation carriers is
85%, (compared to 12% in the general population)
Ovarian cancer risk
• BRCA1 :40% to 60%
• BRCA2 : 15%.
• In males with breast cancer who have a BRCA mutation, One third of mutations
involve BRCA1 and two-thirds involve BRCA2.
• The risk of breast cancer in males is

– General population: 0.1%
– BRCA1 : 1% to 5%
– BRCA2 : 5% to 10%
• In addition, prostate and pancreatic cancer is more common in patients with BRCA2
mutations
Other hereditary associated breast cancer
• p53 (Li–Fraumeni syndrome) broad spectrum of cancers including

– sarcoma,
– breast cancer
– brain tumors,
– lung and laryngeal cancer,
– leukemia, lymphoma,
– adrenal cortical carcinoma
• ATM mutations:
– childhood neurologic disorder referred to as ataxia—telangiectasia, with growth
retardation
– 5 times higher risk for developing breast cancers
• CDH1 or E-cadherin mutations:
– 70% lifetime risk for diffuse gastric cancer
– 40% risk for lobular breast cancer
• PTEN mutations (Cowden disease)

– Distinctive mucocutaneous lesions referred to as trichilemmomas
– Increased risk of breast, thyroid, and genitourinary tract cancers in women

EVALUATION OF THE PATIENT WITH BREAST
CANCER

AJCC TNM Staging

Histologic Subtype
Histologic subtypes:
1. Infiltrating ductal carcinoma (IDC) (76%)

2. Invasive lobular (ILC) (8%)
3. Mixed ductal/lobular carcinoma (7%)
4. Mucinous/colloid (2.4%)
5. Tubular (1.5%)
6. Medullary (1.2%)
7. Papillary (1%)
8. Metaplastic carcinoma

• ILCs have been observed in families that carry germline mutations in
CDH1, the gene that encodes for the E-cadherin protein.

Breast CA grading
• This system is based on three parameters including tubule formation, nuclear

pleomorphism, and mitotic activity
1. Grade 1 (well differentiated): Cells that infiltrate the stroma as solid nests of glands and
where the nuclei are relatively uniform with little or no evidence of mitotic activity.
2. Grade 2 (moderately differentiated): the tumor cells infiltrate as solid nests with some
glandular differentiation and nuclear pleomorphism is present, the mitotic activity is
moderate.
3. Grade 3 (Poorly differentiated): solid nests of neoplastic cells without evidence of gland
formation are present with marked nuclear atypia and high mitotic activity

Biomarker Profile (ER, PR, HER2)
• Using immunohistochemistry and image analysis, ER and PR are considered

positive if 10% of cells or greater stain positive.
• The receptor tyrosine kinase protein HER2 is a member of the epidermal

growth factor receptor family.
• Those biomarkers are important due to the availability of targeted

endocrine therapy against them in positive patients

Molecular Subtyping
1. Luminal A (ER+, PR+, HER2−, Ki-67 <14%),

2. Luminal B (ER+ and or PR+, HER2+/−, Ki-67 ≥14%),
3. HER2 (ER and PR−, HER2+)
4. Basal-like (ER, PR, and HER−)
• Luminal A has a much better overall survival.
• Luminal B HER2+ and HER2 subtypes benefit from targeted therapies against
HER2.
• Basal like or Triple negative breast cancer has the worst prognosis
Diagnostic Breast MRI
• No data from prospective randomized trials demonstrating improved outcomes with the addition
of MRI to the diagnostic evaluation of newly diagnosed breast cancers,
• However NCCN guidelines suggest that diagnostic MRI should be considered in patients with
newly diagnosed breast cancer :
1. When the clinical extent of disease appears larger than what is observed on mammography
2. When there is concern about pectoralis muscle involvement
3. When there is no evidence of a breast primary in the presence of axillary lymph node
metastases
4. When there is no disease identified on physical examination or mammography in the
presence of Paget’s disease of the breast
5. In women at very high risk for contralateral breast cancers such as those with BRCA1/2
mutations
Ductal Carcinoma In Situ (DCIS)
• Defined as the proliferation of malignant epithelial cells within the mammary ductal
system with no evidence of invasion into the surrounding stroma on routine light
microscopic examination
• Histologic subtypes:
1. Comedo (Worst prognosis)
2. Non-comedo:
1. Micropapillary
2. Papillary
3. Cribriform
4. Solid
• DCIS is designated as Tis (DCIS) by the TNM staging system and considered a stage 0
breast cancer
• More than 90% of all cases of DCIS are detected incidentally on imaging
studies – commonly as microcalcifications on mammography (most are
asymptomatic).
• Management options
A. Breast-conserving surgery as a component of breast conservation therapy (BCT) (partial
mastectomy and post op radiation therapy) OR
B. Simple mastectomy with breast reconstruction
• Mastectomy is curative in 98% of patients with DCIS, regardless of the tumor

grade or the size of the lesion.

• Given that partial mastectomy is a much less invasive surgical procedure,
BCT is typically recommended over mastectomy.
• Mastectomy should be performed if BCT is contraindicated, or based on

patient preference.
• Contraindications of BCT:
1. Multicentric disease
2. Extensive disease where resection would result in poor cosmesis
3. Patients who cannot receive radiation therapy.

• Treatment for DCIS after breast conserving surgery is not considered
complete without adjuvant radiation therapy
• Tamoxifen after surgery for ER and PR positive DCIS significantly reduces

recurrence of both ipsilateral and contralateral DCIS.

Lobular Carcinoma In Situ (LCIS)
• Noninvasive lesion that arises from the lobules and terminal ducts of the
breast.
• Not a premalignant lesion

• Patients have increased risk for breast cancer 2-3 folds in both breasts
• More prevalent in premenopausal women and white women.

• Often diagnosed as an incidental finding on a breast biopsy

Management:
• No role for surgical excision unless pleomorphic LCIS is identified at a

surgical margin on excisional biopsy, then wide local excision with
negative margins is recommended as pleomorphic LCIS can be hard to
differentiate from DCIS.
• Options:
a) Careful lifetime surveillance protocol
b) Chemoprevention with a SERM and/or AI
c) Prophylactic bilateral mastectomy

Paget’s disease of the nipple
• 1% or less of breast malignancies

• Characterized clinically by nipple erythema and
irritation with associated pruritus and may
progress to crusting and ulceration.
• The condition may spread outward from the

nipple and onto the areola and surrounding skin
of the breast
• The differential diagnosis of scaling skin and

erythema of the nipple-areola complex includes
eczema, contact dermatitis, postradiation
dermatitis, and Paget disease.
• Diagnosis:
– Biopsy of the skin of the nipple should be performed; a specimen containing Paget
cells confirms the diagnosis.
• More than 95% of patients with Paget disease have an underlying breast
carcinoma
• Treatment options of Paget disease :

A. Mastectomy with axillary staging or
B. Wide local excision of the nipple and areola to achieve clear margins, axillary staging,
and radiation therapy.

Male Breast Cancer
• Breast cancer infrequently occurs in men; it accounts for just 0.8% of all breast
cancers and less than 1% of all newly diagnosed cancers in men.
• The median age at diagnosis is 68 years, 5 years older than that in women.
• Risk factors include

• Increasing age, radiation exposure, factors related to abnormalities in estrogen and
androgen balance (testicular disease, infertility, obesity, and cirrhosis), and genetic
predisposition, including Klinefelter syndrome, family history, and BRCA2 gene
mutations.

• Ninety percent of male breast cancers are invasive ductal carcinomas.
• The majority of men with breast cancer have a breast mass, and when
matched for age and stage, survival is similar to that in women.
• Treatment of carcinoma in the male breast is similar to that in the

female breast, and prognostic factors include nodal involvement, tumor
size, histologic grade, and hormone receptor status.

Breast Cancer
Surgical and non-surgical management
Special types

Outlines
• Surgical therapy of breast cancer
• Surgical therapy of the axilla
• Radiotherapy
• Chemotherapy
• Endocrine therapy
• Targeted therapy
• Special types of breast cancer
– Inflammatory breast cancer
– Phyllodes Tumor
– Medullary breast cancer
– Tubular breast cancer

Treatment of breast cancer
Treatment of breast cancer has multiple aspects:

1. Surgical management of the breast
2. Surgical management of the axilla
3. Chemotherapy
4. Radiotherapy
5. Endocrine therapy

Surgical Therapy of the Breast

Partial Mastectomy / Wide Local Excision
• BCT consists of breast-conserving surgery (partial mastectomy) followed by

radiation therapy
• Factors that increase local recurrence rate following partial mastectomy

include
1. Young age
2. LN involvement
3. ER− disease
4. Absence of radiation therapy
Absolute contraindications of BCT:
1. Multicentric disease
2. Diffuse suspicious micro-calcifications on mammography
3. A history of XRT that includes a portion of the affected breast such that
when combined with the current proposed treatment would result in an
excessively high total radiation dose to the chest wall,
4. Pregnancy (although if in the third trimester, partial mastectomy can be
performed with planned breast irradiation deferred postpartum),
5. Inflammatory Breast Cancer
6. Persistently positive margins after multiple attempts at BCS

• Partial mastectomy is sometimes referred to as a WLE (wide local excision),
lumpectomy, or segmental mastectomy.
• It is best to keep the incision within the boundaries of a potential

mastectomy incision.
• A recent multidisciplinary consensus panel supports the use of “tumor at

ink” as the criteria for positive margin/re-excision, also a negative margin
can be considered as tumor free margin ≥2 mm.

Mastectomy
• Indications of mastectomy:
1. Patients who are not candidates for BCT
2. Tumors that are large relative to breast size
3. Tumors with extensive calcifications on mammography
4. Tumors for which clear margins cannot be obtained on wide local excision
5. Patients preference
6. Prophylactic mastectomy for women at high risk for the development of breast
cancer
7. Inflammatory breast cancer
• If immediate reconstruction is planned, a skin-sparing incision can be made.

Types of mastectomy
• Simple mastectomy removes all breast tissue, the nipple–areola complex, and
necessary skin
• SSM (skin-sparing mastectomy) : removes all breast tissue, the nipple–areola

complex, and only 1 cm of skin around excised scars.
• NSM (nipple sparing mastectomy) removes only breast tissue and preserves
the whole skin and the nipple-areola complex.
• MRM (Modified Radical Mastectomy) removes all breast tissue, the nipple–
areola complex, necessary skin, and the level I and II axillary lymph nodes.

Breast Reconstruction
• All patients undergoing mastectomy should be offered consultation with a

plastic surgeon for consideration of breast reconstruction.
• The two main types of breast reconstruction include

1. Implant-based reconstruction (silicone or saline implants).
2. Autologous tissue reconstruction
A. Transverse rectus abdominis myocutaneous (TRAM) flap
B. Deep inferior epigastric perforator (DIEP) flap.
• Breast reconstruction can also be immediate or delayed.

Surgical Therapy of the Axilla

Approach To the Axillary Nodes
• LN mets rate (axilla): 15-30%

• Currently, Sentinel LN biopsy is the procedure of choice for staging of the axilla in breast CA.
• The sentinel lymph node is the hypothetical first lymph node or group of nodes draining a
cancer.
• Localization of the SLN is done through injection of radioactive technetium sulfur colloid
and/or blue dye (eg. methylene) peritumorally, intradermally, or into the subareolar plexus .
• The specimen is sent for frozen section and the result guide whether to stop or to proceed to
axillary LN dissection/clearance

Axillary Lymph Node Dissection
• Currently, ALND is limited to patients with:

1. Those with a contraindication to SLNB such as those with
clinically palpable pathologic lymph nodes
2. Patients with IBC (inflammatory breast cancer)
3. Positive SLNBx
• ALND in breast cancer involves removal of the level 1 and 2 lymph nodes
• Level 3 nodes are palpated and only in the presence of gross disease is
dissection performed.
• Typically, a minimum of 10 axillary LNs must be achieved with ALND

Complications from ALND include
1. Injury to the long thoracic nerve may result in winged scapula

2. Injury to the thoracodorsal nerve leads to weakness of internal
rotation and extension, characterized by the functional inability to
hold a book under the arm.
3. Seroma formation
4. Infection
5. Lymphedema (13% at one year, 30% lifelong)
6. Sensory loss (intercostobrachial nerves supply sensation to the
medial–posterior aspect of the arm)

Radiation Therapy
• Aim of XRT: to reduce the risk of a locoregional recurrence following surgery and
potentially improve survival by eradicating persistent locoregional disease that may be
resistant to systemic therapy.
• Postmastectomy radiation therapy is often recommended for women at high risk for
locoregional recurrence, including women with:
1. ≥ 4 positive lymph nodes (stage III)
2. Tumor size > 5 cm (stage III)
3. Positive surgical margins
4. Skin or chest wall involvement
5. Inflammatory CA
• In these instances, postmastectomy radiation can reduce the rate of chest wall
recurrence by 65% to 75%.
Chemotherapy
• Mostly given as adjuvant therapy and often initiated 4 to 6 weeks after surgery
• If adjuvant radiation therapy is indicated, it is administered starting 3 to 4 weeks after

completion of chemotherapy
• For patients at high risk for recurrence, a regimen based on the combination of an
anthracycline and taxane has been proven to be the most effective.
• The goal of neoadjuvant therapy is to shrink the primary breast cancer prior to surgery,
facilitating BCT.

Indications of chemotherapy
• Positive nodes – everyone gets chemo except
– postmenopausal women with positive estrogen receptors → they can get
hormonal therapy only with aromatase inhibitor (anastrozole)
• > 1 cm and negative nodes – everyone gets chemo except

– patients with positive estrogen receptors → they can get hormonal therapy
only with tamoxifen if they are premenopausal or aromatase inhibitor
(anastrozole) if they are postmenopausal
• < 1 cm and negative nodes – no chemo; hormonal therapy as above

if positive estrogen receptors

• For metastatic breast cancer, extending chemotherapy duration is associated
with improved progression-free and overall survival, however it can cause
more serious toxicities such as neutropenia and neuropathy.
• If adjuvant chemotherapy is recommended, then endocrine therapy is given

after completion of chemotherapy

When to Use Adjuvant Chemotherapy in HR +ve Ca?
OncotypeDX:
21-gene signature RT-PCR assay to calculate RS—predicts 10-y distant
recurrence rate;
– Low (RS <18) 6.8%;
– Intermediate (RS 18–30) 14.3%;
– High (RS ≥31) 30.5%.

• Chemo recommended for high RS,
• Unknown chemo benefit for intermediate RS.

MammaPrint:
70-gene signature to categorize into 2 groups—good or poor prognosis
irrespective of ER status;
– if high clinical risk including 1–3 LN, but good prognosis genetic risk,
may be able to avoid chemo (MINDACT, Lancet 2005, updated NEJM
2016)

Use of Adjuvant Chemotherapy in Triple Negative Disease:
• In general, use anthracycline & taxane-based adjuvant chemotherapy

regimens.
• 3 most common regimens:

• CMF(cyclophosphamide, MTX, 5-FU),
• TC(docetaxel [=Taxotere], cyclophosphamide ), &
• dd(dose-dense) AC → T (doxorubicin + cyclophosphamide x4, followed by
paclitaxel ×4 or weekly paclitaxel ×12).

Endocrine/Hormonal Therapy
• Patients with all stages of breast cancer that express the ER or PR are
candidates for endocrine therapy.
• In the premenopausal setting, the focus is on blocking ovarian function

and the effects of estrogen.
• In postmenopausal women, the ovaries are no longer the predominant

source of estrogen, but instead estrogen is synthesized mainly from
nonglandular sources such as subcutaneous fat.
– As such, blocking estrogen production is very effective in the postmenopausal
population.

• As SERMs, tamoxifen and raloxifene competitively bind to the ER and
prevent estrogen from binding.
• In premenopausal women, the preferred agent is tamoxifen

– If they cannot tolerate tamoxifen secondary to side effects ovarian suppression
should be considered and can be accomplished through surgical resection of
both ovaries or by administration of a LHRH agonist such as leuprolide or
goserelin (but not as effective as tamoxifen).
• The enzyme aromatase converts androgenic substrates to estrogen,

and, therefore, its inhibition can effectively decrease plasma levels of
estrogen, and thus are more used in postmenopausal patients
• An example of Aromatase Inhibitors is Anastrazole

• In ER+ disease, continuing tamoxifen to year 10 rather than just to
year 5 produces further reductions in recurrence, from year 7 onward,
and breast cancer mortality after year 10

• All people with ER positive tumors respond well to Tam ?
• P-450 enzyme deficiency

• Side effects include hot flushes, vaginal discharge, nausea and weight gain.
• It is, however, linked with a small but significant risk of thromboembolism

and stroke so should not be used in anyone who has a thrombotic tendency.
• There is a small risk of endometrial cancer in postmenopausal women.

Aromatase inhibitors (AIs)
• In ER/PR +ve postmenopausal women only.
• ↓ serum estradiol by inhibiting the p450 enzyme aromatase which

converts androgens into estradiol in peripheral tissues.
• The three most common drugs are:

– Anastrozole, Letrozole (non-steroidal aromatase inhibitors) and
– Exemestane (steroidal aromatase inhibitor).

• Side effects include arthralgia, osteoporosis and hypercholesterolaemia.
• NICE guidelines recommend that all women starting on aromatase

inhibitors should have a baseline DEXA scan to assess their bone density.
• If this detects osteopenia or osteoporosis then appropriate treatment

should be given together with the aromatase inhibitor.
• Consider Bisphosphonates

• Zoledronic acid & denosumab(60 mg twice yearly)
• Adjuvant denosumab 60 mg twice per year reduces the risk of clinical fractures
(50%) in postmenopausal women with breast cancer receiving aromatase
inhibitors, and can be administered without added toxicity.
• This treatment should be considered for clinical practice.

• For patients with ER-/PR-/HER2- or TNBC, chemotherapy is
critical as no targeted therapies exist for these patients.
• In HER2-positive breast cancer, HER2-directed therapy such as

trastuzumab (Herceptin , H) is indicated.
– 1 year of treatment provides a significant disease-free and overall
survival benefit compared with observation and remains the standard
of care.

• Addition of H to adj chemo ↓ recurrence risk by 40–50%
• Main SE of HER2-targeted therapy is cardiac toxicity.
• Monitor cardiac function w/ECHO/MUGA at

• Baseline,
• Post-anthracycline, &
• Serially
→ If symptomatic decrease in EF or asymptomatic decrease in EF ≥10% to
below the lower limit normal or ≥16%,
– hold H & reassess in 3–4 wk

Special types of breast cancer

Inflammatory Breast Cancer
• A common clinical presentation for IBC is peaud’
orange, characterized by edema, warmth, and
erythema
• Unlike other types of breast cancer, patients with IBC

often have associated pain and tenderness with an
enlarged and firm breast.
• The nipple can also be involved with flattening,
erythema, crusting, blistering, and retraction.
• IBC is an aggressive form of LABC (locally advanced

breast cancer) that effects approximately 1% to 5%
of women with breast cancer
Inflammatory Breast Cancer
• It is designated as primary tumor stage T4d
• Diagnosis of IBC is made with:

1. Clinical examination findings
2. Breast imaging: mammography, ultrasound and breast MRI to help detect sites within the breast that
can be biopsied to confirm the breast cancer and to determine extent of disease.
3. Biopsy
• Nearly all women have lymph node involvement at the time of presentation and
approximately a third of patients will have distant metastases

Treatment on IBC
1. Neoadjuvant chemotherapy (anthracycline- and taxane-based) until all

signs of skin inflammation have resolved and the breast and axillary
masses are deemed operable.
2. Surgical management with MRM
3. Adjuvant radiation therapy
• The prognosis for patients with IBC remains poor with 5-year disease-free
survival rates of 20% to 45% and an overall survival of 30% to 70%.

Phyllodes Tumor
• Phyllodes tumors are uncommon (<0.5% of all

breast malignancies) fibro-epithelial breast
tumors
• The malignant potential of phyllodes tumors

differs widely, with some behaving like
fibroadenomas and others that can degenerate
histologically into sarcomatous lesions and
metastasize distantly.

Phyllodes Tumor
• They are histologically classified as
1. Benign (50%)
2. Borderline (25%)
3. Malignant (25%)
• Classification is done based upon

1. The degree of stromal cellularity and atypia
2. Mitotic rate
3. The presence or absence of stromal overgrowth
4. Infiltrative margins

Phyllodes Tumor
• Patients with phyllodes tumors present with a smooth, multinodular, well-demarcated,
firm mass that is both mobile and painless.
• Imaging is notable for a smooth multilobulated mass that resembles a fibroadenoma.

• Phyllodes usually present with larger size and rapidly growing
• Lymph node involvement is rare.

• If suspected, excisional biopsy (WLE) is better than core biopsy.

Phyllodes Tumor
Management:
• WLE with negative margins
• No need for ALND unless a suspicious ALND was noted and

the biopsy was positive for mets (which is very rare)

• The use of adjuvant radiation therapy and chemotherapy is controversial;
however, in the setting of a large borderline or malignant phyllodes tumor,
these treatments should be considered
• If systemic therapy for malignant phyllodes tumor is undertaken, it is based on

guidelines for treating sarcomas.
• Similar to breast sarcomas, malignant phyllodes tumors can metastasize to the

lungs and as such patients should undergo chest x-ray every 6 months for 2 years
and then annually.
• Unfortunately, once metastasis develops, the mean overall survival is 30 months.

Medullary breast cancer
• It is usually manifested as a palpable mass with smooth borders on

imaging that can mimic benign conditions.
• On ultrasound, medullary carcinoma often has the same findings that
one would expect with a fibroadenoma.
• These tumors are characterized by an infiltrate of small mononuclear
lymphocytes, are less likely to be associated with axillary node
metastasis, and have a better than average prognosis.

Tubular carcinoma
• Is present in its pure form, the distant metastatic potential is very low.
• The diagnosis is made when characteristic angulated tubules, composed of cells
with low-grade nuclei, constitute at least 90% of the carcinoma.
• Tubular carcinoma has a better prognosis than other varieties of IDC

• It has the biologic correlates of a low-grade cancer (ER positive, diploid, low S
phase, and no expression of c-erbB-2), and is more likely to occur in older patients.
• For selected cases of pure tubular carcinoma removed with an adequate negative
margin, mastectomy, radiation therapy, or even axillary lymph node staging may be
unnecessary.

Breast Infections: Principles, Pathology and Management

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Breast Infections: Principles, Pathology and Management

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Breast Infections

Principles, Pathology and management

Dr. Mahmoud W. Qandeel

Dr. Mahmoud W. Qandeel

• Uncommon outside of the postpartum period

• Classified as lactating or nonlactating infections

• Staphylococcus aureus and Streptococcus species are the organisms most

Dr. Mahmoud W. Qandeel

• In the initial stages of infection, a mastitis or cellulitis is typically found,

Dr. Mahmoud W. Qandeel

1. Pain management (acetaminophen, NSAIDs)

• Improves within 24-48 hours after initiation of antibiotics.

Dr. Mahmoud W. Qandeel

• Delay or inadequate management may lead to tissue destruction,

Dr. Mahmoud W. Qandeel

• Can present as mastitis , peri-areolar abscesses or less commonly as

• An underlying clinical condition should always be sought and treated.

• Indeed, in addition to cultures, radiological modalities such as

Dr. Mahmoud W. Qandeel

Dr. Mahmoud W. Qandeel

• For larger and/or deeper abscesses, incision and drainage may be

• I&D can be performed under local anesthesia if small and superficial,

Dr. Mahmoud W. Qandeel

• Biopsy of the cavity should always be considered, as breast infection may be

Dr. Mahmoud W. Qandeel

Dr. Mahmoud W. Qandeel

• Also called recurrent periductal mastitis,

• Smoking has been implicated as a risk

• This syndrome is managed

• Also called “string phlebitis,” a thrombosed vein

• Frequently involved veins include the lateral thoracic

• Typically, a woman presents with acute pain in the

• A tender, firm cord is found to follow the distribution

• Therapy for Mondor’s disease includes the liberal use

• The process usually resolves within 4 to 6 weeks.

• When symptoms persist or are refractory to therapy, excision of the

Dr. Mahmoud W. Qandeel

Dr. Mahmoud W. Qandeel

Dr. Mahmoud W. Qandeel

Dr. Mahmoud W. Qandeel

• Peak between 35- 50 years of age

Dr. Mahmoud W. Qandeel

• By definition benign and do not require further intervention

• A follow-up CBE with or without ultrasound can be performed in 3 to 6 months to

Dr. Mahmoud W. Qandeel

• On ultrasound, complicated cysts appear as

Dr. Mahmoud W. Qandeel

Dr. Mahmoud W. Qandeel

Dr. Mahmoud W. Qandeel

• Cryoablation and ultrasound-guided vacuum assisted biopsy are approved treatments

Dr. Mahmoud W. Qandeel

Dr. Mahmoud W. Qandeel

- These calcifications fill the acini.

Dr. Mahmoud W. Qandeel

Skin Calcification (Tattoo sign) Vascular Calcification

Coarse or (Popcorn-like) Round and punctate calcifications

Eggshell Calcification (Fat Necrosis, oil cyst)

Dystrophic calcifications (lava like) (Fat Necrosis)

Fine Linear Branching (DCIS)

Dr. Mahmoud W. Qandeel

• Can harbor areas of atypia or DCIS

• Often an incidental finding on biopsy

• Not associated with a significant risk for breast cancer