Monday, 3 February 2020

BREAST

ANATOMY

- Blood supply (arterial)

• perforating branches of the internal mammary artery

• lateral branches of the posterior intercostal arteries

• branches from the axillary artery, including the highest thoracic, lateral thoracic,
and pectoral branches of the thoracoacromial artery

- Blood supply (venous)

• perforating branches of the internal thoracic vein

• perforating branches of the posterior intercostal veins

• tributaries of the axillary vein

- intercostobrachial nerve = loss of sensation over the
medial aspect of the upper arm

- interpectoral group (Rotter’s lymph nodes)

- Level 1: lateral to or below the lower border of the

pectoralis minor

- Level 2: superficial or deep to the pectoralis minor

muscle

- Level 3: medial to or above the upper border of the

pectoralis minor muscle

PHYSIOLOGY

- Estrogen

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• ductal development
- progesterone

• differentiation of epithelium and for lobular development

- Prolactin

• lactogenesis in late pregnancy and the postpartum period

• stimulates epithelial development

- Gynecomastia

• at least 2 cm in diameter

• neonatal period, adolescence, and senescence

• Grade I—mild breast enlargement without skin redundancy

• Grade IIa—moderate breast enlargement without skin redundancy

• Grade IIb—moderate breast enlargement with skin redundancy

• Grade III—marked breast enlargement with skin redundancy and ptosis

BACTERIAL INFECTION

- Staphylococcus aureus

• more localized and may be situated deep

- Streptococcus

• diffuse superficial involvement

- Epidemic puerperal mastitis

• by highly virulent strains of methicillin-resistant S aureus that are transmitted via

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the suckling neonate

- Nonepidemic (sporadic) puerperal mastitis

• interlobular connective tissue of the breast by an infectious process.

• nipple fissuring and milk stasis —> retrograde bacterial infection.

- recurrent periductal mastitis

• Zuska’s disease

• recurrent retroareolar infections and abscesses

MYCOTIC INFECTIONS

- Candida albicans

• erythematous, scaly lesions of the inframammary or axillary folds

• Tx: Nystatin

MONDOR’S DISEASE

- thrombophlebitis that involves the superficial veins of the anterior chest wall and
breast.

- “string phlebitis,”

- Frequently involved veins include the lateral thoracic vein, the thoracoepigastric vein,
and, less commonly, the superficial epigastric vein

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- resolves within 4 to 6 weeks.

BENIGN DISORDERS

- Atypical ductal hyperplasia (ADH)

• monotonous round, cuboidal, or polygonal cells enclosed by basement membrane

with rare mitoses.

• 2 or 3 mm
- DCIS if it is larger than 3 mm

- In lobular neoplasias, such as ALH and LCIS, there is a lack of E-cadherin vs ductal

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neoplasia would present with
E-cadherin

- Periductal mastitis

• preferred initial surgical

treatment is by fistulectomy and
primary closure with antibiotic
coverage

• 2- to 4-week course is
recommended before total duct
excision

CANCER SCREENING

- Women age 45 to 54 years should be screened annually, and those 55 years and
older should transition to biennial screening

- average-risk women begin annual screening mammograms at ≥40 years of age,

along with annual clinical breast exams and breast awareness

- Tamoxifen

• chemoprevention

• selective estrogen receptor modulator,

• decrease was evident only in ER-positive

• for age 35 to 59, women over the age of 60, or women with a diagnosis of LCIS or
atypical ductal or lobular hyperplasia

• deep vein thrombosis occurs 1.6 times as often, pulmonary emboli 3.0 times as
often, and endometrial cancer 2.5 times as often

- aromatase-inhibitors

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• exemestane was shown to reduce invasive breast cancer incidence by 65%
- higher arthritis and hot flashes

• anastrozole reduced the incidence of invasive breast cancer by about 50%

- risk reducing surgery

• risk-reducing mastectomy was highly effective at preventing breast cancer in both

BRCA1 and 2

• Risk-reducing salpingo-oophorectomy was highly effective at reducing the

incidence of ovarian cancer and breast cancer in BRCA

BRCA MUTATIONS

- BRCA1

• tumor- suppressor genes

• 45% of hereditary breast cancers and in at least 80% of hereditary ovarian cancers

• autosomal dominant

• invasive ductal carcinomas, are poorly differentiated, hormone receptor negative,

and have a triple receptor negative

• early age of onset; a higher prevalence of bilateral breast cancer; and the presence
of associated cancers specifically ovarian cancer and possibly colon and prostate
cancers.

• Ashkenazi Jewish population

- BRCA2

• higher risk for male breast cancer

• invasive ductal carcinomas, well differentiated and to express hormone receptors

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• early age of onset, a higher prevalence of bilateral breast cancer, and the presence
of associated cancers specifically ovarian, colon, prostate, pancreatic, gallbladder,
bile duct, and stomach, as well as melanoma

- Candidates for gene testing

• Ashkenazi Jewish heritage; a 1st-degree relative with breast cancer <50yo; a

history of ovarian cancer at any age in the patient or 1st- or 2nd-degree relative with
ovarian cancer; breast and ovarian cancer in the same individual; two or more 1st-
or 2nd-degree relatives with breast cancer at any age; patient or relative with
bilateral breast cancer; and male breast cancer in a relative at any age

- for MRI imaging

• with a known BRCA1 or BRCA2 mutation, those who have a first-degree relative
with a BRCA1 or BRCA2 mutation, women who were treated with radiation therapy
to the chest between the ages of 10 and 30 years, and those who have Li-Fraumeni
syndrome, Cowden syndrome, or Bannayan-Riley-Ruvalcaba syndrome, or a
first-degree relative with one of these syndromes

- for BRCA1 and 2: consideration for bilateral risk-reducing salpingo-oophorectomy

should be between the ages of 35 and 40
years at the completion of childbearing

- site of metastasis

• bone, lung, pleura, soft tissues, and liver

CARCINOMA IN SITU

- Multicentricity = occurrence of a second

breast cancer outside the breast quadrant
of the primary cancer (or at least 4 cm
away)

- multifocality refers to the occurrence of a

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second cancer within the same breast quadrant as the primary cancer (or within 4 cm
of it)

- LCIS

• distention and distortion of the terminal duct lobular units by cells that are large
but maintain a normal nuclear to cytoplasmic ratio

• calcifications associated with LCIS typically occur in adjacent tissues.

- DCIS

• intraductal carcinoma

• proliferation of the epithelium that

lines the minor ducts, resulting in
papillary growths within the duct
lumina

• cribriform = hyperchromasia and

loss of polarity

• solid = pleomorphic cancer cells

with frequent mitotic figures
obliterate the lumina and distend
the ducts

• comedo = cells outstrip their blood supply and become necrotic

- Invasive

• Paget’s disease of the nipple

- chronic, eczematous eruption of the nipple

- with extensive DCIS and may be associated with an invasive cancer

- large, pale, vacuolated cells (Paget cells) in the rete pegs of the epithelium

• Invasive ductal carcinoma

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- poorly defined margins

- central stellate configuration with chalky white or yellow streaks extending into
surrounding breast tissues

- usually ER +

• Medullary carcinoma
- BRCA1

- cancer is soft and hemorrhagic

- rapid increase in size may occur secondary to necrosis and hemorrhage

- dense lymphoreticular infiltrate composed predominantly of lymphocytes and

plasma cells

- large pleomorphic nuclei that are poorly differentiated and show active mitosis

- sheet-like growth pattern with minimal or absent ductal or alveolar

differentiation

- usually with DCIS

• Mucinous carcinoma (colloid carcinoma),

- older population as a bulky tumor

- extracellular pools of mucin which surround aggregates of low-grade cancer

cells

- cancer is glistening and gelatinous

- hormone receptor positive

• Papillary carcinoma
- small and rarely attain a size of 3 cm

- papillae with fibrovascular stalks and multilayered epithelium

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- low frequency of axillary lymph node metastases

• Tubular carcinoma
- perimenopausal or early menopausal

- haphazard array of small, randomly arranged tubular elements

- ER +

• Invasive lobular carcinoma

- small cells with rounded nuclei, inconspicuous nucleoli, and scant cytoplasm

- multifocal, multicentric, and bilateral

- ER +

TREATMENT OPTIONS

- LCIS

• Tamoxifen

• Bilateral total mastectomy

- DCIS

• BCS + RT

• Total mastectomy

• Tamoxifen

• 2mm margin
- Early invasive cancer (St1, 2A and 2B)

• lumpectomy and radiation therapy

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• RT can be avoided in select older patients with ER-positive, early-stage breast
cancer

• mastectomy with axillary staging and breast conserving surgery with axillary
staging and radiation therapy are considered equivalent

• BCS is not for (a) prior RT to the breast or chest wall, (b) persistently positive
surgical margins after re-excision, (c) multicentric disease, and (d) scleroderma or
lupus erythematosus.

• Removal of the tissue expander and definitive reconstruction, usually with

autologous tissue, can proceed 6 months to 1 year after RT

• ACOSOG Z0011 trial

- tumors <5 cm, clinically negative axillary nodes, and 1-2 positive sentinel nodes
who are treated with lumpectomy and whole-breast radiation

- Advance locoregional breast cancer (St3A and 3B)

• Neoadjuvant therapy

• ipsilateral breast tumor recurrence

- had clinical N2 or N3 disease, >2 cm of residual, multifocal, and lymphovascular
space invasion

- Distant metastasis (St4)

• chemotherapy indication
- hormone receptor-negative cancers, “visceral crisis,” and hormone-refractory
metastases

SLNB

- not recommended with inflammatory breast cancers, those with biopsy proven
metastasis, DCIS without mastectomy, or prior axillary surgery

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- 10% reading of the axillary bed

- 4 SLNs

BCS

- “no tumor on ink” for St1 and 2

- Oncoplastic surgery

• significant area of breast skin will

need to be resected with the
specimen to achieve negative
margins

• large volume of breast parenchyma

will be resected resulting in a
significant defect

• the tumor is located between the nipple and the inframammary fold, an area often
associated with unfavorable cosmetic outcomes

• excision of the tumor and closure of the breast may result in malpositioning of the
nipple.

Nipple sparing mastectomy

- tumor located more than 2 to 3 cm from the border of the areola, smaller breast size,
minimal ptosis, no prior breast surgeries with periareolar incisions, body mass index
less than 40 kg/m2, no active tobacco use, no prior breast irradiation, and no evidence
of collagen vascular disease.

Chemotherapy

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- blood vessel or lymph vessel invasion, high nuclear grade, high histologic grade,
HER2/ neu overexpression, and negative hormone receptor status, positive LNs,
>1cm, special-type cancer that is >3 cm

Tamoxifen

- side effects: bone pain, hot flashes, nausea, vomiting, and fluid retention

- with DCIS that is found to be ER-positive.

Aromatase inhibitors

- in post menopausal (1st line)

- anastrozole and letrozole and exemestane

- risk of osteoporosis can be averted by treatment with bisphosphonates

Ablative endocrine therapy

- premenopausal

• oophorectomy or ovarian radiation

• gonadotrophin-hormone releasing hormone agonists, such as goserelin or

leuprolide

• with an aromatase inhibitor can be considered in select premenopausal women

with high-risk features (age <40 years, positive lymph nodes) who warranted
adjuvant chemotherapy.

Anti-Her2neu

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- with HER2-positive tumors benefit if trastuzumab is added to taxane chemotherapy

- 1 year

- Pertuzumab

• in combination with trastuzumab and docetaxel for patients with metastatic

HER2-positive breast cancer who have not received prior HER2-targeted therapy or
chemotherapy for metastatic disease

• neoadjuvant setting, it is approved in combination with trastuzumab and docetaxel

in HER2-positive, early stage breast cancers that are greater than 2 cm or
node-positive

Nipple discharge

- Unilateral

• high risk for cancer if spontaneous, unilateral, localized to a single duct, present in
women ≥40 years of age, bloody, or associated with a mass

- Bilateral

• benign condition if it is bilateral and multiductal in origin, occurs in women ≤39

years of age, or is milky or blue-green.

• Prolactin-secreting pituitary adenomas

Axillary metastasis with unknown primary

- 90% from breast CA

Pregnancy

- CBC, LFTs and CXR

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- MRM during 2nd and 3rd trimester

- 1st trimester chemo have a 12% risk of teratogenicity

Male breast cancer

- preceded by gynecomastia in 20%

- present at an advanced stage

- hormone receptor–positive —> adjuvant tamoxifen

Phyllodes

- classical leaf-like (phyllodes) appearance

- malignant type has liposarcomatous or rhabdomyosarcomatous elements

- 1-cm margin

- Axillary dissection is not recommended

Inflammatory breast CA

- Stage 3B

- brawny induration, erythema

with a raised edge, and edema
(peau d’orange)

- palpable axillary
lymphadenopathy

- distant metastases

- PET-CT scan should be

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considered at the time of diagnosis

- neoadjuvant chemotherapy with an anthracycline-containing regimen

- MRM

- need adjuvant RT

RARE BREAST CA

- Squamous cell (epidermoid) carcinoma

• metaplasia within the duct system

• devoid of distinctive clinical or radiographic characteristics

• distant mets are rare

- Adenoid cystic carcinoma

• indistinguishable from adenoid cystic carcinoma arising in salivary tissues

• 1 to 3 cm in diameter at presentation and are well circumscribed

- Apocrine carcinomas

• well- differentiated cancers that have rounded vesicular nuclei and prominent
nucleoli

• very low mitotic rate

• aggressive growth pattern

- Sarcomas

• large, painless breast mass with rapid growth

• Axillary dissection is not indicated

- Lymphoma

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• palpable axillary lymphadenopathy

• association with breast implants for cosmetic or reconstructive purposes

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