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77 Cards in this Set

  • Front
  • Back
Breast Anatomy
Breast tissue is located between the subcutaneous fat and the fascia of the pectoralis major and serratus anterior muscles. Posterior to the breast and anterior to the pectoralis fascia is the retromammary space, which contains small lymphatics and vessels. Breast tissue can extend to the clavicle, into the axilla (axillary tail of Spence), to the latissimus dorsi, and to the top of the rectus muscle. Running through the breasts from the deep fascia to the skin are suspensory ligaments (Cooper's ligaments)
Breast Vasculature
The arterial supply is from the internal thoracic artery, via perforating branches, and the axillary artery, via the long thoracic and thoracoacromial branches. Venous drainage is mainly to the axillary vein, as well as the internal thoracic, lateral thoracic, and intercostals veins
Breast Lymphatics
Lymphatic drainage of the breasts occurs via interlobular lymphatic vessels into a subareolar plexus (Sappey's plexus). From this plexus, the majority (75%) of the lymph drains into the axillary lymph nodes. Lymph from the medial breast may drain into the internal mammary nodes or the axillary nodes
Breast Innervation
Lateral and anterior cutaneous branches of the second to sixth intercostals nerves innervate the breasts
Axillary Anatomy
The borders of the axilla are defined as the axillary vein superiorly, latissimus dorsi laterally, and the serratus anterior muscle medially
Axillary Lymph Nodes
Level I nodes. Lateral to the pectoralis minor muscle
Level II nodes. Posterior to the pectoralis minor muscle
Level III nodes. Medial to the pectoralis minor muscle and most accessible with division of the muscle
Rotter's nodes. Between the pectoralis major and the minor muscles
Axillary Nerves
Long thoracic nerve: travels from superiorly to inferiorly along the chest wall at the medial aspect of the axilla and innervates the serratus anterior muscle. Injury to this nerve causes a “winged” scapula in which the medial and inferior angle of the scapula abduct away from the chest wall with arm extension.
Thoracodorsal nerve: courses along the posterior border of the axilla from superiorly to inferiorly on the subscapularis muscle and innervates the latissimus dorsi. Injury to this nerve causes weakness in arm abduction and external rotation.
Medial pectoral nerve: travels from the posterior aspect of the pectoralis minor muscle around the lateral border of the pectoralis minor to the posterior aspect of the pectoralis major muscle. It innervates the lateral third of the pectoralis major
History
Patients seek medical attention most commonly for an abnormal mammogram, a breast mass, breast pain, nipple discharge, or skin changes. History should include the following:
Duration of symptoms, change over time, associated pain or skin changes, relationship to pregnancy or the menstrual cycle, previous trauma.
Date of last menstrual period and regularity of the menstrual cycle.
Age of menarche.
Number of pregnancies and age at first full-term pregnancy.
Lactational history.
Age at menopause or surgical menopause (i.e., oophorectomy).
Prior history of breast biopsies or breast cancer.
Mammogram history.
Oral contraceptive and hormonal replacement therapy.
Family history of breast and gynecologic cancer, including the age at diagnosis. This should include at least two generations as well as any associated cancers, such as ovary, colon, prostate, gastric, or pancreatic
Assessment of Cancer Risks
Hormonal, environmental exposure, and genetics
BRCA1 and BRCA2
Prior Breast Bx Histologies
Models for breast cancer risk
Hormonal, environmental exposire, & genetic risk factors
Hormonal, environmental exposure, and genetics are correlated to an increased risk for breast cancer. A family history of breast cancer in a first-degree relative is associated with a doubling of risk. If two first-degree relatives (e.g., a mother and a sister) have breast cancer, the risk is further elevated. These familial effects are enhanced if the relative had either early-onset cancer or bilateral disease. Breast-feeding may exert a protective effect against the development of breast cancer. Overall, factors that increase a patient's risk by 1.5- to 4-fold include the following:
Increased estrogen or progesterone exposure due to early menarche (before age 12 years) or late menopause (age >55 years).
Late age at first full-term pregnancy: Women with a first birth after age 30 years have twice the risk of those with a first birth before age 18 years.
High body-mass index after menopause.
Exposure to ionizing radiation
BRCA1 & BRCA2
BRCA1 and BRCA2 are breast cancer susceptibility genes associated with 80% of hereditary breast cancers but account for only 5% of all breast cancers. Women with BRCA1 mutations have an estimated risk of 85% for breast cancer by age 70 years, a 50% chance of developing a second primary breast cancer, and a 20% chance of developing ovarian cancer. BRCA2 mutations carry a lower risk for breast cancer and account for 4% to 6% of all male breast cancers. Screening for BRCA gene mutations should be reserved for women who have a strong family history of breast or ovarian cancer
Prior Breast Bx Histologies
No increased risk is associated with adenosis, cysts, duct ectasia, or apocrine metaplasia.
There is a slightly increased risk with moderate or florid hyperplasia, papillomatosis, and complex fibroadenomas.
Atypical ductal (ADH) or lobular hyperplasia (ALH) carries a 4- to 5-fold increased risk of developing cancer
Models for breast cancer risk
he original Gail model estimates the absolute risk (probability) that a woman in a program of annual screening will develop breast cancer over a defined age interval. The risk factors in this model include current age, age at menarche, age at first full-term pregnancy, previous breast
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biopsies, presence of ADH on prior biopsy, and number of affected first-degree relatives. The National Surgical Adjuvant Breast and Bowel Project (NSABP) modified this model to project the absolute risk of developing only invasive breast cancer. This modified Gail model has been used to define eligibility criteria for entry into chemoprevention trials. The NSABP and the National Cancer Institute offer an interactive online risk assessment tool, which is available at http://www. cancer.gov/bcrisktool
Physical Exam
1. Inspection: sitting & lying with arms above head
2. Palpation breast
3. Axillary, Supraclavicular, Infraclavicular, & Cervical Nodes
Screening Mammogram
Screening for breast cancer. Screening mammogram lowers mortality from breast cancer. It is performed in the asymptomatic patient and consists of two standard views, mediolateral oblique (MLO) and craniocaudal (CC). The current recommendation from the National Cancer Institute and American College of Surgeons is annual screening mammography for women aged 40 years and older. Breast lesions on mammograms are classified according to the American College of Radiology by BI-RADS (Breast Imaging Reporting and Database System) scores
BI-RADS Scores
0 = Needs further imaging
Malignant mammographic findings
a. New or spiculated masses.
b. Clustered microcalcifications in linear or branching array.
c. Architectural distortion
Benign mammographic findings
i. Radial scar.
ii. Fat necrosis.
iii. Milk of calcium.
iv. Cysts
Benign mammographic findings: Radial scar.
• Generally due to fibrocystic breast condition (FBC)
Benign mammographic findings: Fat necrosis.
• Results from local trauma to the breast. It may resemble carcinoma on palpation and on mammography. The fat may liquefy instead of scarring, which results in a characteristic oil cyst. A biopsy may be needed to rule out malignancy
Benign mammographic findings: Milk of calcium.
• Associated with FBC
Benign mammographic findings: Cysts
• cannot be distinguished from solid masses by mammography
Screening in high-risk patients
For patients with known BRCA mutations, annual mammograms and semiannual physical examinations should begin at age 25 to 30 years. In patients with a strong family history of breast cancer but undocumented genetic mutation, annual mammograms and semiannual physical examinations should begin 10 years earlier than the age of the youngest affected relative and no later than age 40 years
Screening MRI
selected high-risk patients with:
i. A lifetime risk of breast cancer greater than 20% as defined by available risk assessment tools (e.g., BRCAPRO, Gail, Claus, and Tyrer-Cuskick models).
ii. BRCA mutations.
iii. A first-degree relative (parent, sibling, child) with a BRCA1 or BRCA2 mutation.
iv. History of radiation to the chest wall between the ages of 10 to 30 years (e.g., Hodgkin lymphoma patients).
v. Li-Fraumeni, Cowden, or Bannayan-Riley-Ruvalcaba syndromes
Diagnostic mammograms
symptomatic patient or to follow up on an abnormality noted on a screening mammogram. Additional views (spot-compression views or magnification views) may be used to further characterize any lesion. The false-negative and false-positive rates are both approximately 10%. A normal mammogram in the presence of a palpable mass does not exclude malignancy and further workup should be performed with an ultrasound, MRI, and/or biopsy
Diagnostic Ultrasonography
to further characterize a lesion identified by physical examination or mammography. It can determine whether a lesion is solid or cystic and can define the size, contour, or internal texture of the lesion. Although not a useful screening modality by itself due to significant false-positive rates, when used as an adjunct with mammography, ultrasonography may improve diagnostic sensitivity of benign findings to greater than 90%, especially among younger patients for whom mammographic sensitivity is lower due to denser breast tissue. In those patients with a known cancer, ultrasound is sometimes used to detect additional suspicious lesions and/or to map the extent of disease
Diagnostic MRI
adjunct to mammography to determine extent of disease, to detect multicentric disease in the dense breast, to assess the contralateral breast, to evaluate patients with axillary metastases and an unknown primary, and in patients in whom mammogram, ultrasound, and clinical findings are inconclusive. It is also useful for assessing chest wall involvement
Palpable mass workup
1. FNAB
2. Core Bx
3. Excisional Bx
4. Incisional Bx
FNAB for palpable mass?
reliable and accurate, with sensitivity greater than 90%. FNAB can determine the presence of malignant cells and estrogen and progesterone receptor status but does not give information on tumor grade or the presence of invasion. Nondiagnostic aspirates require an additional biopsy, either surgical or core needle biopsy (Am J Surg 1997
Core Bx for palpable mass?
preferred over FNAB. It can distinguish between invasive and noninvasive cancer and provides information on tumor grade as well as receptor status. For indeterminate specimens, a surgical biopsy is necessary
Excisional Bx for palpable mass?
primarily be used when a core biopsy cannot be done. It is performed in the operating room
Incisional Bx for palpable mass?
indicated for the evaluation of a large breast mass suspicious for malignancy but for which a definitive diagnosis cannot be made by FNAB or core biopsy. For inflammatory breast cancer with skin involvement, an incisional biopsy can consist of a skin punch biopsy
Non-Palpable mass workup
1. Stereotactic Core Bx
2. Vacuum-Assisted Bx
3. Ultrasound Guided Bx
4. Needle Localization Bx (NLB)

Minimally invasive breast biopsy is the optimal initial tissue acquisition method and procedure of choice for obtaining a pathologic diagnosis of image-detected abnormalities. Correlation between pathology results and imaging findings is mandatory. Patients with histologically benign findings on percutaneous biopsy do not require open biopsy if imaging and pathological findings are concordant. Patients with high-risk lesions on image-guided biopsy (ADH, ALH, lobular carcinoma in situ, radial scar) may have malignancy at the same site and should undergo a surgical biopsy
Stereotactic Core for non-palpable mass
for nonpalpable mammographically detected lesions, such as microcalcifications, which cannot be seen with ultrasonography. Tissue can be collected from several foci in disparate quadrants of the breast. Using a computer-driven stereotactic unit, two mammographic images are taken to triangulate the lesion in three-dimensional space. A computer determines the depth of the lesion and the alignment of the needle, which can be positioned within 1 mm of the intended target. Biopsies are taken, and postfire images are obtained of the breast and specimen. Contraindications include lesions close to the chest wall or in the axillary tail and thin breasts that may allow needle strikethrough. Superficial lesions and lesions directly beneath the nipple-areola complex are also often not approachable with stereotactic techniques. Nondiagnostic and insufficient specimens should undergo needle-localized excisional biopsy (NLB, see later discussion), as should discordant pathologic findings on core needle stereotactic biopsy
Vacuum Assisted Bx for non-palpable mass?
used during stereotactic core biopsies and ultrasound-guided core biopsies. These devices employ large needles (9 to 14 gauge) to contiguously acquire tissue, which is pulled into the bore of the needle by vacuum suction. Multiple contiguous samples of tissue are collected while the probe remains in the breast. Volumes up to 1 mL can be collected during a single insertion. A metallic marking clip is usually placed through the probe after sampling is complete to allow for identification of the biopsy site should excisional biopsy or partial mastectomy be necessary. This is the preferred approach for lesions presenting with microcalcifications without a visible or palpable mass
Ultrasound Guided Bx for non-palpable mass?
preferred method if a lesion can be visualized with ultrasound because it is generally easier to perform than a stereotactic core biopsy. Lesions with a cystic component are better visualized with ultrasound, and ultrasound-guided biopsy can be used to aspirate the cyst as well as to provide core biopsy specimens
Needle Localization Bx for non-palpable mass?
an excisional biopsy. Using localization mammograms as a map, the whole hookwire, breast lesion, and a rim of normal breast tissue are removed en bloc. The specimen is oriented, and a radiograph is performed to confirm the presence of the lesion within the specimen
Benign Breast Conditions?
1. Fibrocystic Breast Change
2. Breast Cysts
3. Fibroadenoma
4. Mastalgia
5. Nipple Discharge
6. Breast Infections
7. Gynecomastia
Fibrocystic Breast Change
encompasses several of the following pathologic features: stromal fibrosis, macro- and microcysts, apocrine metaplasia, hyperplasia, and adenosis (which may be sclerosing, blunt-duct, or florid).

a. FBC is common and may present as breast pain, a breast mass, nipple discharge, or abnormalities on mammography.
b. The patient presenting with a breast mass or thickening and suspected FBC should be re-examined in a short interval, preferably on day 10 of the menstrual cycle, when hormonal influence is lowest. Often, the mass will have diminished in size.
c. A persistent dominant mass must undergo further radiographic evaluation, biopsy, or both to exclude cancer
Breast Cysts
frequently present as tender masses or as smooth, mobile, well-defined masses on palpation. If tense with fluid, its texture may be firm, resembling a solid mass. Aspiration can determine the nature of the mass (solid vs. cystic) but is not routinely necessary. Cyst fluid color varies and can be clear, straw-colored, or even dark green.

a. Cysts discovered by mammography and confirmed as simple cysts by ultrasound are usually observed if asymptomatic.
b. Symptomatic simple cysts should be aspirated. If no palpable mass is present after drainage, the patient should be evaluated in 3 to 4 weeks. If the cyst recurs, does not resolve completely with aspiration, or yields bloody fluid with aspiration, then mammography or ultrasonography should be performed to exclude intracystic tumor. Nonbloody clear fluid does not need to be sent for cytology
Fibroadenoma
most common discrete mass in women younger than 30 years of age. They typically present as smooth, firm, mobile masses.
a. They enlarge during pregnancy and involute after menopause.
b. They have well-circumscribed borders on mammography and ultrasound.
c. They may be managed conservatively if clinical and radiographic appearance is consistent with a fibroadenoma and is less than 2 cm. If the mass is symptomatic, greater than 2 cm, or enlarges, it should be excised
Mastalgia
Most women (70%) experience some form of breast pain or discomfort during their lifetime. The pain may be cyclic (worse before a menstrual cycle) or noncyclical, focal or diffuse. Benign disease is the etiology in the majority of cases. However, pain may be associated with cancer in up to 10% of patients. Features that raise the suspicion of cancer are noncyclic pain in a focal area and pain associated with a mass or bloody nipple discharge. Once cancer has been excluded, most patients can be managed successfully with symptomatic therapy and reassurance
Nipple Discharge
A. Lactation
Lactation is the most common physiologic cause of nipple discharge and may continue for up to 2 years after cessation of breast-feeding. In parous nonlactating women, a small amount of milk may be expressed from multiple ducts. This requires no treatment.
B. Galactorrhea
• Galactorrhea is milky discharge unrelated to breast-feeding. Physiologic galactorrhea is the continued production of milk after lactation has ceased and menses resumed and is often caused by continued mechanical stimulation of the nipples.
a. Drug-related galactorrhea is caused by medications that affect the hypothalamic-pituitary axis by depleting dopamine (tricyclic antidepressants, reserpine, methyldopa, cimetidine, and benzodiazepines), blocking the dopamine receptor (phenothiazine, metoclopramide, and haloperidol), or having an estrogenic effect (digitalis). Discharge is generally bilateral and nonbloody.
b. Spontaneous galactorrhea in a nonlactating patient may be due to a pituitary prolactinoma. Amenorrhea may be associated. The diagnosis is established by measuring the serum prolactin level and performing a computed tomography (CT) or MRI scan of the pituitary gland. Treatment is bromocriptine or resection of the prolactinoma.
C. Pathologic nipple discharge
Pathologic nipple discharge is either (1) bloody or (2) spontaneous, unilateral, and originates from a single duct. Normal physiologic discharge is usually nonbloody, from multiple ducts, can be a variety of colors (clear to yellow to green), and requires breast manipulation to produce.
a. Pathologic discharge is serous, serosanguineous, bloody, or watery. The presence of blood can be confirmed with a guaiac test.
b. Cytologic evaluation of the discharge is not generally useful.
c. Malignancy is the underlying cause in 10% of patients.
d. If physical examination and mammography are negative for an associated mass, the most likely etiologies are benign intraductal papilloma, duct ectasia, or fibrocystic changes. In lactating women, serosanguinous or bloody discharge can be associated with duct trauma, infection, or epithelial proliferation associated with breast enlargement.
e. A solitary papilloma with a fibrovascular core places the patient at marginally increased risk for the development of breast cancer. Patients with persistent spontaneous discharge from a single duct require a surgical microdochectomy, ductoscopy, or major duct excision.
i. Microdochectomy: Excision of the involved duct and associated lobule. Immediately before surgery, the involved duct is cannulated, and radiopaque contrast is injected to obtain a ductogram, which identifies lesions as filling defects. The patient is then taken to the operating room, and the pathologic duct is identified and excised, along with the associated lobule.
ii. Ductoscopy utilizes a 1-mm rigid videoscope to perform an internal exploration of the major ducts of the breast. Once a ductal lesion is identified, this single associated duct with the lesion is excised.
iii. Major duct excision may be used for women with bloody nipple discharge from multiple ducts or in postmenopausal women with bloody nipple discharge. It is performed through a circumareolar incision, and all of the retroareolar ducts are transected and excised, along with a cone of tissue extending up to several centimeters posterior to the nipple
Breast Infections
A. Lactational Mastitis
B. Nonpuerperal Abscesses

A. Lactational mastitis
Lactational mastitis may occur either sporadically or in epidemics.
a. The most common causative organism is Staphylococcus aureus.
b. It presents as a swollen, erythematous, and tender breast
Gynecomastia
a. Pubertal hypertrophy occurs in adolescent boys, is usually bilateral, and resolves spontaneously in 6 to 12 months.
b. Senescent gynecomastia is commonly seen after age 70 years, as testosterone levels decrease.
c. Drugs associated with this are similar to those that cause galactorrhea in women, for example, digoxin, spironolactone, methyldopa, cimetidine, tricyclic antidepressants, phenothiazine, reserpine, and marijuana.
d. Tumors can cause gynecomastia secondary to excess secretion of estrogens: testicular teratomas and seminomas, bronchogenic carcinomas, adrenal tumors, and tumors of the pituitary and hypothalamus.
e. Gynecomastia may be a manifestation of systemic diseases such as hepatic cirrhosis, renal failure, and malnutrition.
f. During the workup of gynecomastia, cancer should be excluded by mammography and subsequently by biopsy if a mass is found. The cause of gynecomastia should be identified and corrected if possible. If workup fails to reveal a medically treatable cause or if the enlargement fails to regress, excision of breast tissue via a periareolar incision can be performed
Malignancy of Breast Epidemiology
most common cancer in women, with a lifetime risk of 1 in 8 women. In 2007, approximately 178,000 new cases of invasive breast cancer and 62,000 new cases of noninvasive in situ carcinoma of the breast will be diagnosed (CA Cancer J Clin 2007
TNM Staging
T0 No evidence of primary tumor
Tis Carcinoma in situ
T1 Tumor ≤2 cm in greatest dimension
T1 mic Microinvasion ≤0.1 cm in greatest dimension
T1a Tumor >0.1 cm but not >0.5 cm
T1b Tumor >0.5 cm but not >1 cm
T1c Tumor >1 cm but not >2 cm
T2 Tumor >2 cm but <5 cm in greatest dimension
T3 Tumor >5 cm in greatest dimension
T4 Tumor of any size with direct extension into the chest wall or skin
T4a Extension to chest wall (ribs, intercostals, or serratus anterior)
T4b Peau d'orange, ulceration, or satellite skin nodules
T4c T4a + b
T4d Inflammatory breast cancer
Regional lymph nodes
NX Regional lymph nodes not assessable
N0 No regional lymph node involvement
N1 Metastasis to movable ipsilateral axillary lymph nodes
N2 Metastases to ipsilateral axillary lymph nodes fixed to one anotheror to other structures
N3 Metastases to ipsilateral internal mammary lymph node with or without axillary lymph node involvement, or in clinically apparent clavicular lymph node.
Distant metastases
MX Presence of distant metastases not assessable
M0 No distant metastases
M1 Existent distant metastases (including ipsilateral supraclavicular nodes)

0 Tis N0 M0
I T1 N0 M0
IIA T0, 1 N1 M0
T2 N0 M0
IIB T2 N1 M0
T3 N0 M0
IIIA T0, 1, 2 N2 M0
T3 N1, 2 M0
IIIB T4 Any N M0
Any T N3 M0
IV Any T Any N M1
Preop Staging/Metastatic Workup
a. Complete blood cell count, complete metabolic panel, and chest x-ray.
b. A bone scan if the alkaline phosphatase or calcium level is elevated.
c. CT scan of the liver if liver function panel is abnormal.
d. Patients with clinical stage III disease should undergo bone scan and CT scan due to a high probability of distant metastases
Noninvasive Breast Cancer
1. DCIS
2. LCIS
DCIS
a. It is usually detected by mammography as clustered pleomorphic calcifications.
b. Physical examination is normal in the majority of patients.
c. It may advance in a segmental manner, with gaps between disease areas.
d. It can be multifocal (two or more lesions >5 mm apart within the same index quadrant) or multicentric (in different quadrants)
DCIS: Histology
a. There are five architectural subtypes: papillary, micropapillary, solid, cribriform, and comedo. Specimens are also grouped as comedo versus noncomedo.
b. The high-grade subtype is often associated with microinvasion, a higher proliferation rate, aneuploidy, gene amplification, and a higher local recurrence rate.
c. ER and PR expression levels should be obtained if hormone therapy is being considered
DCIS: Treatment
Surgical Excision, Assessment of Axillary Lymph Nodes, Adjuvant Therapy

i. Surgical excision alone (via partial mastectomy) with margins greater than 10 mm is associated with a local recurrence rate of 14% at 12 years (Am J Surg 2006
DCIS: Surgical Excision
i. Surgical excision alone (via partial mastectomy) with margins greater than 10 mm is associated with a local recurrence rate of 14% at 12 years (Am J Surg 2006
DCIS: Assessment of Axillary Lymph Nodes
Axillary dissection is not performed for pure DCIS.
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1. Sentinel lymph node biopsy (SNLB, see later discussion) may be considered when there is a reasonable probability of finding invasive cancer on final pathologic examination (e.g., >4 cm, palpable, or high grade).
2. Some surgeons perform SLNB in all patients with DCIS undergoing mastectomy because SLNB cannot be performed postmastectomy if an occult invasive cancer is found. This is an area of ongoing controversy and research.
3. A positive sentinel node indicates invasive breast cancer and changes the stage of the disease
DCIS: Adjuvant Therapy
1. For pure DCIS, there is no added benefit from systemic chemotherapy because the disease is confined to the ducts of the breast. However, in those patients with ER-positive DCIS, adjuvant tamoxifen can reduce the risk of breast cancer recurrence by 37% over 5 years and the risk of developing a new contralateral breast cancer (NSABP B-24 trial). However, there is no survival benefit. Aromatase inhibitors (e.g., anastrazole, exemestane, letrozole), which block the peripheral conversion of androgens into estrogens by inhibiting the enzyme aromatase but does not affect estrogen produced by the ovaries, are sometimes used as an alternative in postmenopausal patients.
2. Adjuvant radiation should be given to patients with DCIS treated with partial mastectomy to decrease the local recurrence rate (NSABP B-17 trial). This is especially true for younger women with close margins or large tumors. However, there is no survival benefit. For older patients with smaller, widely excised DCIS of low or intermediate grade, the benefit of radiation therapy is so small that adjuvant radiation is not recommended
Van Nuys Prognostic Index ?
a numerical algorithm (based on lesion size, margin, tumor grade, presence of necrosis, and age) used to stratify patients with DCIS into three groups to determine which patient is at greatest risk of recurrence and would therefore benefit the most from a more aggressive treatment approach. The low-scoring group may be treated with partial mastectomy alone. The intermediate-scoring group has been shown to benefit from adjuvant radiation therapy, and the high-scoring group should undergo mastectomy because the risk of recurrence with partial mastectomy with or without radiation is high (Adv Surg 2000
LCIS (characteristics, treatment)
not considered a preinvasive lesion but rather an indicator for increased breast cancer risk of approximately 1% per year (~20% to 30% at 15 years) (JNCCN 2006
Invasive Breast Cancer: Histology
five different subtypes: infiltrating ductal (75% to 80%), infiltrating lobular (5% to 10%), medullary (5% to 7%), mucinous (3%), and tubular (1% to 2%)
Invasice Cancer: Surgical Options for Stage I & II
(a) Mastectomy v. BCT
(b) SLNB v. ALND
Invasive Cancer: Modified Radical Mastectomy
a. Modified radical mastectomy (MRM) involves total (simple) mastectomy and axillary lymph node dissection. It is indicated for patients with clinically positive lymph nodes or a positive axillary node based on previous SLNB or FNAB.
i. Total (simple) mastectomy with SLNB is for patients with a clinically negative axilla. A skin-sparing mastectomy (preserves skin envelope and inframammary ridge) may be performed with immediate reconstruction, resulting in improved cosmesis: The nipple-areolar complex, a rim of periareolar breast skin, and any previous excisional biopsy or partial mastectomy scars are excised.
ii. Immediate reconstruction at the time of mastectomy should be offered to eligible patients. Options include latissimus dorsi myocutaneous flaps, transverse rectus abdominis myocutaneous flaps, and inflatable tissue expanders followed by exchange for saline or silicone implants. Immediate reconstruction has been shown not to affect patient outcome adversely. The detection of recurrence is not delayed, and the onset of chemotherapy is not changed.
iii. Follow-up after mastectomy: physical examination every 3 to 6 months for 3 years, then every 6 to 12 months for the next 2 years, and then annually (J Clin Oncol 2006
Invasive Cancer: BCT
partial mastectomy and SLNB (or axillary lymph node dissection
Invasive Cancer: Management of Axilla
Approximately 30% of patients with clinically negative exams will have positive lymph nodes in an axillary lymph node dissection (ALND) specimen. The presence and number of lymph nodes involved affect staging and thus prognosis. However, complications are not infrequent (see later discussion). Thus, sentinel lymph node biopsy was developed to provide sampling of the lymph nodes without needing an ALND
Invasive Cancer: SLNB
established as a standard of care for predicting axillary involvement in most patients with breast cancer. The procedure requires a multidisciplinary approach, including nuclear medicine, pathology, and radiology.
1. It involves injection of blue dye (either Lymphazurin or methylene blue) in the operating room and/or technetium-labeled sulfur colloid (in the nuclear medicine department, radiology suite, or sometimes by the surgeon). The combination of blue dye and radioisotope provides higher node identification rates and increases the sensitivity of the procedure. The goal is to identify the primary draining lymph node(s) in the axillary nodal basin.
2. A variety of injection techniques are used: intraparenchymal versus intradermal (intradermal methylene blue will cause skin necrosis at the injection site)
Invasive Cancer: ALND
clinically positive lymph nodes, with positive SLN, or with positive should undergo ALND for local control. ALND involves the following:
1. Removal of level I and level II nodes and, if grossly involved, possibly level III nodes. Motor and sensory nerves are preserved unless there is direct tumor involvement.
2. An ALND should remove 10 or more nodes. The number of nodes identified is often pathologist dependent.
3. Patients with 4 or more positive lymph nodes should undergo adjuvant radiation to the axilla. Selective patients with 1 to 3 positive nodes may also benefit from radiation therapy to the axilla.
4. Intraoperative complications: potential injury to the axillary vessels and neuropathy secondary to injury to the motor nerves of the axilla (the long thoracic, thoracodorsal, and medial pectoral nerves).
5. Most frequent postoperative complications: wound infections and seromas. Persistent seroma may be treated with repeated aspirations or reinsertion of a drain. Other complications include pain and numbness in the axilla and upper arm, impaired shoulder mobility, and lymphedema.
Lymphedema occurs in approximately 10% to 40% of women undergoing axillary dissection
Invasive Cancer: Adjuvant Chemotherapy
Node (Positive v. Negative) Disease

a. All node-positive patients should receive adjuvant chemotherapy.
i. Regimens are guided by the tumor biomarkers. Typical regimens comprise four to eight cycles of a combination of cyclophosphamide and an anthracycline, followed by a taxane administered every 2 to 3 weeks.
ii. Patients with ER-positive tumors receive adjuvant hormonal therapy for 5 years. Tamoxifen is given to premenopausal women, and aromatase inhibitors are given to postmenopausal women (aromatase inhibitors are not used in premenopausal women).
iii. In postmenopausal women older than 70 years, chemotherapy is performed less frequently. In postmenopausal women with tumors with ER or PR positivity, tamoxifen or an aromatase inhibitor is frequently the sole adjuvant medical therapy.
iv. In patients with Her2/neu-positive tumors, polychemotherapy is combined with biological therapy targeting the Her2/neu protein: Trastuzumab is a recombinant monoclonal antibody that binds to Her2/neu receptor to prevent cell proliferation. The NSABP trial B-31 and the North Central Cancer Treatment Group trial N9831 showed that adding trastuzumab to a chemotherapy regiment of doxorubicin, cyclophosphamide, and paclitaxel was associated with an increase in the disease-free survival by 12% and a 33% reduction in the risk of death at 3 years. It is usually administered intravenously monthly for 12 months. The most serious toxicity with the regiment was cardiac failure (N Engl J Med 2005
Invasive Cancer: Adjuvant Radiation
a. Indications for adjuvant radiation to the chest wall and axilla after mastectomy include T3 and T4 tumors, attachment to the pectoral fascia, positive surgical margins, skin involvement, involved internal mammary nodes, inadequate or no axillary dissection, four or more positive lymph nodes, and residual tumor on the axillary vein. Presence of one to three positive axillary nodes is a relative indication.
b. Randomized, prospective trials have shown a significantly decreased recurrence and improved survival in premenopausal women with these indications treated with chemotherapy and radiation therapy (N Engl J Med 1997
Locally Advanced Breast Cancer (LABC) Definition
comprises T3 or T4, N1 or greater, and M0 cancers (stages IIIA and IIIB).

Inflammatory v. Non-Inflammatory
Non-Inflammatory LABC
(chest wall or skin involvement, skin satellites, ulceration, fixed axillary nodes)
1. Patients should receive neoadjuvant chemotherapy (often cyclophosphamide combined with an anthracycline and taxane), followed by surgery and radiation. The high response rates seen with this regimen for stage IIIB allow modified radical mastectomy to be carried out, with primary skin closure. Adjuvant radiation to the chest wall and regional nodes and adjuvant chemotherapy follow surgery. SLNB may be used in selected patients with clinically negative axilla.
2. Patients with stage IIIA disease receiving neoadjuvant chemotherapy who can be converted to BCT candidates have no difference in overall survival outcome.
3. Approximately 20% of patients with stage III disease present with distant metastases after appropriate staging has been performed.
4. Follow-up. Due to higher risk for local and distant recurrence, patients should be examined every 3 months by all specialists involved in their care
Inflammatory LABC
T4d. edema (peau d'orange).
2. It represents 1% to 6% of all breast cancers.
3. An underlying mass is present in 70% of cases. Associated axillary adenopathy occurs in 50% of cases.
4. It is often misdiagnosed initially as mastitis.
5. Skin punch biopsy confirms the diagnosis: In two thirds of cases, tumor emboli are seen in dermal lymphatics.
6. Approximately 30% of patients have distant metastasis at the time of diagnosis.
7. Inflammatory breast cancer requires aggressive multimodal therapy because median survival is approximately 2 years, with a 5-year survival of only 5%.
8. Follow-up. Due to higher risk for local and distant recurrence, patients should be examined every 3 months by all specialists involved in their care
Locoregional Recurrence
Patients with locoregional recurrence should have a metastatic workup to exclude visceral or bony disease and should be considered for systemic chemotherapy or hormonal therapy.

i. Recurrence in the breast after BCT requires total (simple) mastectomy. Provided margins are negative, survival is similar to that for patients who received mastectomy initially.
ii. Recurrence in the axilla requires surgical resection followed by radiation to the axilla and systemic therapy.
iii. Recurrence in the chest wall after mastectomy occurs in 4% to 5% of patients. One third of these patients have distant metastases at the time of recurrence, and greater than 50% will have distant disease within 2 years. Multimodal therapy is essential. For an isolated local recurrence, excision followed by radiotherapy results in excellent local control. Rarely, patients require radical chest resection with myocutaneous flap closure
Chemoprevention in breast cancer
1. NSABP P-1:
a. Women taking tamoxifen achieved an overall reduction in the risk of developing invasive breast carcinoma of 49% and a reduction in the risk of developing noninvasive breast cancer of 50%.
b. In subgroups of women with a history of LCIS and with a history of ADH, tamoxifen reduced the risk of developing invasive breast cancer by 65% and 86%, respectively.

2. NSABP B-24: tamoxifen provided a 37% overall risk reduction for all breast cancers (invasive and noninvasive) in women with DCIS treated with lumpectomy and radiation.
a. The toxicities of the drug include an increased risk of endometrial cancer, thrombotic vascular events, and cataract development. Women on tamoxifen also reported increased vasomotor symptoms (hot flashes) and vaginal discharge.
b. Tamoxifen also provided a significant reduction in hip fractures in women older than 50 years of age. There was no difference noted in the incidence of ischemic heart disease for women taking tamoxifen.
c. Tamoxifen has been approved by the Food and Drug Administration (FDA) for (1) the treatment of metastatic breast cancer, (2) adjuvant treatment of breast cancer, and (3) chemoprevention of invasive or contralateral breast cancer in high-risk women.
d. The dosage for chemoprevention is 20 mg/day for 5 years. It is estimated that chemoprevention could prevent as many as 500,000 invasive and 200,000 noninvasive breast cancers over 5 years in the United States alone.

3. STAR: Raloxifene has not been FDA approved for chemoprevention, but was shown to provide equal risk reduction for the development of invasive breast cancers as tamoxifen. It was not as effective at reducing the risk of developing noninvasive breast cancer. Its side effect profile is somewhat different than that of tamoxifen, so it can be considered in patients with relative contraindications to tamoxifen
Pregnancy: Bloody Nipple Discharge
may occur in the second or third trimester. It results from epithelial proliferation under hormonal influences and usually resolves by 2 months postpartum. If it does not resolve by then, standard evaluation of pathologic nipple discharge should be performed
Pregnancy: Breast Masses
Breast masses occurring during pregnancy include galactoceles, lactating adenoma, simple cysts, breast infarcts, fibroadenomas, and carcinoma. Fibroadenomas may grow during pregnancy due to hormonal stimulation.

a. Masses should be evaluated by ultrasound, and a core needle biopsy should be performed for any suspicious lesion.
b. Mammography can be performed with uterine shielding but is rarely helpful due to increased breast density.
c. If a breast lesion is diagnosed as malignant, the patient should be given the same surgical treatment options, stage for stage, as a nonpregnant woman, and the treatment should not be delayed because of the pregnancy
Pregnancy: Invasive Cancer
a. It occurs in approximately 1 in 5,000 gestations and accounts for almost 3% of all breast cancers.
b. Workup is the same as in a nonpregnant woman. The standard preoperative staging workup is performed. Laboratory values such as alkaline phosphatase may be elevated during pregnancy. For advanced-stage disease, MR scan or ultrasound may be used in lieu of CT scan for staging. Excisional biopsy can be safely performed under local anesthesia if there is some contraindication to the preferred core needle biopsy.
c. Therapeutic decisions are influenced by the clinical cancer stage and the trimester of pregnancy and must be individualized. MRM has been the standard surgical modality for pregnant patients with breast cancer, but BCT can be offered to selected patients. The radiation component of BCT cannot be applied during pregnancy, and delaying radiation therapy is not ideal. For these reasons, BCT is usually not recommended to patients in their first or second trimester. For patients in the third trimester, radiation can begin after delivery. SLNB is starting to be used more frequently
Padget Disease of the Nipple
eczematoid changes of the nipple, which may involve the surrounding areola.
a. Burning, pruritus, and hypersensitivity may be prominent symptoms.
b. Paget disease is almost always accompanied by an underlying malignancy, either invasive ductal carcinoma or DCIS.
c. Palpable masses are present in approximately 60% of patients.
d. Mammography should be performed to identify other areas of involvement. If clinical suspicion is high, a pathologic diagnosis should be obtained by wedge biopsy of the nipple and underlying breast tissue.
e. Treatment is mastectomy or BCT with excision of the nipple-areolar complex (sometimes called a central lumpectomy), followed by radiation therapy. The prognosis is related to tumor stage
Breast Cancer in Men
less than 1% of male cancers and less than 1% of all breast cancers. BRCA2 mutations are associated with approximately 4% to 6% of these cancers.
a. Patients generally present with a nontender hard mass. This contrasts with unilateral gynecomastia, which is usually firm, central, and tender.
b. Mammography can be helpful in distinguishing gynecomastia from malignancy. Malignant lesions are more likely to be eccentric, with irregular margins, and are often associated with nipple retraction and microcalcifications. Biopsy of suspicious lesions is essential, and core needle biopsy is preferred.
c. Modified radical mastectomy was traditionally the surgical procedure of choice
Phyllodes Tumors
1% of breast neoplasms.
a. They present as a large, smooth, lobulated mass and may be difficult to distinguish from fibroadenoma on physical exam.
b. They can occur in women of any age, but most frequently between ages 35 and 55 years.
c. Skin ulcerations may occur secondary to pressure of the underlying mass.
d. FNAB cannot reliably diagnose these tumors