General Surgery (Board Review Series) 1st Edition

18

Breast

Laurence H. Brinckerhoff

Craig L. Slingluff Jr.

1. Overview of Breast Development and Function
2. Embryology
3. Normal female breast development

• depends on estrogenand progesterone.

2. Milk line regression
3. Failure of regressionresults in accessory breast tissue.

• This is most commonly found in the axilla.
• The most common congenital breast anomaly is accessory nipple(s), or polythelia.

1. Abnormal regressionmay lead to underdevelopment of the breast, or amastia.

• The Poland syndromeis amastia associated with hypoplasia of the chest wall and pectoralis muscles.

1. Anatomy
2. The normal breast

• has a “teardrop” shape resulting from the extension of the breast tissue into the axilla, the “axillary tail,” or the “tail of Spence.”

2. Breast asymmetry

• is common.
• usually represents a normal variation.

3. Vascular supply
4. The medial and central portions are supplied by

• perforating branches from the internal mammary artery.

1. Laterally, the breast is supplied by

• the lateral thoracic.

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• the thoracodorsal and suprascapular and perforating branches of the intercostal arteries.

4. The venous drainage

• runs in parallel to the arterial supply.
• includes a venous plexus in the subareolar region.

5. The lymphatic drainage

• plays an important role in the spread of breast cancer.

1. Of the entire breast lymphatic drainage, 97% flows into the axilla. The remainder flows to the internal mammary nodes.
2. Any quadrant of the breast can drain to the internal mammary nodes.
3. Regional breast nodes

• are important in the evaluation of breast cancer.

1. The three different levels of axillary nodes

• are defined by their relation to the pectoralis minor muscle (Figure 18-1).

2. Level I nodesare lateral to the pectoralis muscle, within the axillary fat pad.
3. Level II nodesare beneath or inferior to the pectoralis minor muscle.
4. Level III nodesare medial to the pectoralis muscle.
5. Rotter's nodes(see Figure 18-1)

Figure 18-1. Lymphatic drainage of the breast. (Adapted with permission from Lawrence P. Essentials of General Surgery, 2nd ed. Baltimore, Williams & Wilkins, 1994, p 275.)

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• are usually too small to be visualized.
• are located between the pectoralis major and pectoralis minor muscles.

1. Internal mammary lymph nodes

• directly drain a small portion of breast tissue.

1. Supraclavicular nodes

• also need to be assessed in patients with breast cancer.

7. Fascial elements of the breast

• There are two distinct but connected fascial elements of the breast.

1. The fascial envelope

• surrounds the breast tissue.
• extends to the pectoralis major and serratus anterior muscle fascia.

1. Suspensory ligaments of Cooper

• are fascial strands extending from the facial envelope through the breast tissue to the skin (Figure 18-2).

1. These subdivide the breast into segments.
2. Breast cancers involving these strands may cause skin dimpling.
3. Histology
4. Breast tissue

• has two histologically distinct tissues: lobularand ductal.

1. Both tissues have associated stroma comprised of

• connective tissue.
• nerves.
• blood vessels.
• lymphatics (see Figure 18-2).

Figure 18-2. A tangential and sagittal view of the breast. (Adapted with permission from O'Leary P. The Physiologic Basis of Surgery, 2nd ed. Baltimore, Williams & Wilkins, 1996, p 287.)

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4. The lobule

• is the functional unit of the breast.

2. Alveoliare terminal elongated tubular ducts.
3. Around 10–100 alveoli coalesce to form larger lobular ductal units.
4. Twenty to 40 coalesce to form an excretory duct.
5. The ductal tissue

• is a double layer of cuboidal and columnar cells.

1. These ducts form the channels for milk flow during lactation.
2. These ducts define the lobes of the breast.
3. Physiology
4. Estrogen

• stimulates epithelial proliferation and blood flow to the breast.

2. Progesterone

• induces the cellular differentiation of alveolar cells into secretory cells.

3. Prolactin

• is produced from the anterior pituitary.
• stimulates alveolar milk secretion.

1. Nipple stimulation

• during breast feeding promotes secretion of prolactin.

1. Cortisol and insulin

• play a permissive role for prolactin function.

4. Oxytocin

• is produced from the posterior pituitary.
• stimulates contraction of breast myoepithelia.
• Nipple stimulation during breast feeding induces milk ejection.

5. At menopausethe lack of estrogen and progesterone results in atrophy of the breast glandular tissue.
6. Basic Surgical Terminology
7. A lumpectomy

• refers to the removal of a lesion with a small rim of normal tissue.

1. Axillary lymph node dissection

• is the removal of the level I and level II axillary lymph nodes for staging purposes.
• current data shows no survival advantage to axillary node dissection versus observation for clinically palpable nodes.

1. Subcutaneous mastectomy

• is the removal of the bulk of the breast tissue, with preservation of the nipple-areolar complex.

1. A total mastectomy

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• is the removal of all the breast tissue, including the nipple-areolar complex.

1. Radical mastectomy

is the en bloc excision of

• the breast.
• the overlying skin.
• pectoralis major and minor muscles.
• level I, II, and III lymph nodes.

1. Modified radical mastectomy

• is a total mastectomycombined with an axillary node dissection.

III. Evaluation of Breast Abnormalities

1. Breast imaging
2. Mammography

• can detect a large proportion of nonpalpable breast cancers.

1. Palpation

• detects 10%–20% of bilateral mammogram (MMG)-negative cancers.

1. The sensitivity of an MMG increases with age

• due to replacement of dense parenchymal tissues by fatty tissues.

1. Of MMG-positive, nonpalpable lesions

• only 15%–25% are cancerous.

1. A spiculated, dense lesion

• with ill-defined margins is likely to be cancer (Figure 18-3A)

1. Other lesionssuggestive of cancer on MMG include

• clusters of microcalcifications (Fig 18-3B).
• asymmetric densities.
• ductal asymmetry.
• distortion of normal breast architecture.
• skin or nipple distortion.

2. The American Cancer Society's recommendations for a screening MMG

. Age 35–39: a baseline MMG.

1. Age 40–49:an MMG every 1–2 years.
2. Over age 50:an MMG yearly.
3. All women undergoing breast biopsy

• should have an MMG for evaluation of synchronous ipsilateral or contralateral disease.

1. An MMG should be considered for all symptomatic women.
2. If there is a family history of breast cancer

• screening should start 5 years before the age of the youngest affected relative.

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1. General approach to suspicious nonpalpable mammographic lesions

Figure 18-3. Mammograms demonstrating characteristic findings of breast carcinoma. (A) Note spiculated irregular margins of breast lesion. (B) Note clustered microcalcifications. (Reprinted with permission from Daffner RH: Clinical Radiology: The Essentials, 2nd ed. Baltimore, Williams & Wilkins, 1999, pp 245 and 247.)

1. Only about 15%–25% of these lesions will be malignant.
2. Independent of a woman's age these lesions require a tissue biopsy.
3. General approach to the palpable breast mass (Figure 18-4)
4. Many breast cancers present as a palpable mass.Thus self breast examination is a primary method for diagnosis.
5. Women over age 30 and postmenopausal women
6. Obtain an MMG

• to screen for occult concurrent disease.

1. Regardless of the MMG results

• biopsyof any and all suspicious lesions is mandatory.

2. Fine needle aspiration (FNA)

• for palpable lesions provides cells for analysis.
• provides a rapid, minimally invasive cellular diagnosis.
• The accuracy of FNA depends on the cytologist.

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3. Needle localized excisional biopsy

• provides intact tissue sections for analysis.

1. Incisional biopsyis indicated for masses larger than 3 cm.
2. Excisional biopsyis the gold standard for lesions smaller than 3 cm.
3. Core needle biopsy

• may be substituted for needle localization because it also provides intact tissue sections for analysis.
• may be comparable to surgical excisional biopsy in accuracy.
• is considered to be a minimally invasive procedure.
• There have been reports of a higher level of false-negatives.
• This procedure is considered better than FNA because it allows for histologic analysis.

Figure 18-4. Approach to a new breast mass or thickening. MMG = mammogram; FNA = fine needle aspiration.

3. Women under the age of 30
4. Most of these patients have a low risk of cancer, unless there is a family history of breast cancer at a young age.
5. Fibroadenomas (see IV B)

• Ultrasoundmay be used to help diagnose fibroadenomas.

1. For a presumptive diagnosisof fibroadenoma, it is reasonable to follow the breast mass over several months.
2. A definitive diagnosiscan be obtained using FNA.
3. If a presumed fibroadenoma enlarges, surgical excisionis indicated.
4. Cysts

• Ultrasoundmay also be used to help diagnose cysts.

1. Cysts may be aspiratedand followed with serial ultrasounds.

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2. If the cyst is complexor returns after aspiration, surgical excision is indicated.
3. If it becomes symptomaticor painful, it may be appropriate to remove the cyst.
4. Benign Breast Disorders (Table 18-1)

Table 18-1. Benign Breast Disease

1. Fibrocystic changes or fibrocystic disease

• refer to a continuum of a disease state in response to cyclical hormones.

1. Bothare characterized by nodular, lumpy breast tissue, which varies with the hormone cycle.
2. Neither diagnosis carries an increased risk of cancer.

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3. Fibrocystic change

• refers to patients without significant symptoms.

4. Fibrocystic disease

• refers to women with severely symptomatic breasts.

1. Signs and symptoms include

• mastodynia (i.e., breast pain) (see IV C 9).
• breast masses.
• nipple discharge (see IV C 8).

1. Care must be taken to rule outother causes of pain such as infection and cancer.
2. Some of the risk factorsdiffer from those of breast cancer, and include

• early menarche.
• late menopause.
• irregular menses.
• small breast size.
• normal or low body weight.
• history of cyclic breast mass.
• history of spontaneous abortions.

6. The classic histologic changesare microscopic and macroscopic cysts.

. Fibrosis and adenosis with lymphocytic infiltration is characteristic.

1. Mild to moderate ductal or lobular hyperplasiamay be present with no atypia.
2. Many of these findingscan be found in normal breast tissue.
3. Sclerosing adenosisis a histologic subtype of fibrocystic change.
4. Most commonly it presents asa cluster of microcalcifications on MMG without an associated palpable mass or pain
5. It is easily confused with breast cancerhistologically and radiographically.
6. Wire localizationand surgical excision may be required for diagnosis.
7. It is distinguished from cancerby the regularity of nuclei and absence of mitoses.
8. Primary treatments are reassuranceand symptomatic relief.
9. Fibroadenoma (see Table 18-1)
10. Overview

• It is the most common breast tumorin adolescents and young women.
• Patients will have multiple fibroadenomasin 10%–15% of cases.

2. Characteristics of a fibroadenomainclude

• a painless, slow growing massfound on self-breast examination.

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• growth to several centimeters in size, and then no further progression.
• changes in size and symptoms with menstrual cycle.
• well-circumscribed, oval or round, mobile masses.
• firm rubbery texture(may become rock hard with degeneration).
• Fibroadenomas may enlarge quickly during pregnancy.

3. Diagnosis
4. On MMGfibroadenomas rarely have a characteristic nature.

• However, with degeneration, they will appear as classic “popcorn calcifications.”

1. Ultrasound evaluationis seldom definitive, but may substantiate the diagnosis.
2. Treatment

• is based on the probability of missing a primary breast cancer.

1. Women under age 30with a confirmed diagnosis may be observed and followed up.

• Removal is indicated only if the mass enlarges or changes in character.

1. Women 30 and overrequire an FNA for a definitive diagnosis.

• If FNA is nondiagnostic, or if any changes occur, surgery is indicated.

5. Giant fibroadenomas(larger than 5 cm)

• are a subclass of the simple adenoma.
• usually occur immediately after menarche or menopause.
• Recurrence is rare if excision is complete.

1. Other benign breast diseases
2. Radial scar(radial sclerosing lesions) (see Table 18-1)
3. The classic MMG showsa stellate, irregular, spiculated mass lesion.
4. Though hard to differentiate from cancerthere is no increased risk.

• A tissue diagnosisis required to differentiate from cancer.

2. Fat necrosis
3. Pathophysiology and presentation

• The pathophysiology is thought to be inflammatory necrosisfrequently related to trauma. Only about 50% of cases, however, are associated with known trauma.
• The attendant fibrosismay cause skin dimpling and a mass effect.

1. Diagnosis

• Microscopically, macrophagesladen with fat lobules, or foreign body giant cells are diagnostic.

1. Treatment

• involves reassurance without excision.

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3. Periductal mastitis

• (i.e, mammary duct ectasia, plasma cell mastitis) is an uncommon disease.

1. Pathological characteristics

• are dilated mammary ducts with inspissated secretions and marked periductal inflammation.

1. Signs and symptoms

• include noncyclical mastodynia; nipple retraction; thick, white creamy nipple discharge; and sterile subareolar abscesses.

1. History

• Most patients will give a history of difficulty with breast-feeding.

1. Diagnosis and treatment

• depend on the involved symptoms.

2. If there is the typical discharge, then only reassurance is indicated.
3. If an abscesshas formed, surgical incision and drainage is indicated.
4. Infectious mastitis

. When a primary infection of the breast is suspected clinically, care must be taken to rule out inflammatory breast cancer.

1. Although uncommon, 80% of infectionsare associated with breast-feeding.
2. The most common pathogenis Staphylococcus aureus.
3. In nonlactating women, mastitis may also be caused by

• chronic infections(e.g., actinomycosis, tuberculosis, syphilis).
• autoimmune diseases(e.g., lupus erythematosus).

1. Most infections

• begin as skin cellulitis.
• may be treated with antibiotics safe for feeding the infant.

5. Galactoceles

• are breast cysts that are filled with milk.

1. It is almost exclusively seenafter breast-feeding and represents dilated obstructed breast ducts.
2. Treatment

• ranges from simple aspiration to surgical incision and drainage.

6. Mondor's disease

• is thrombophlebitisof superficial veins of the breast.

1. This inflammation typically

• affectsthe lower outer quadrant.
• presents asa palpable, cord-like mass with associated burning pain.

1. The etiology is unknown

• but it is associated with trauma and strenuous exercise.

1. Treatment

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• with nonsteroidal anti-inflammatory drugs (NSAIDs) is indicated if pain is severe.

7. Intraductal papilloma(see Table 18-1)

• is the most common cause of bloody nipple discharge, although half the time the discharge is serous.

1. These lesions are usually

• small.
• nonpalpable.
• close to the nipple.

1. Diagnosis

• can be made by ductography.

1. Treatment

• with subareolar excision is generally curative.

1. Diffuse papillomatosis

• affects multiple ducts and both breasts.

1. The papillomas are larger than when papillomas occur as a single lesion.
2. The discharge is serous, not bloody.
3. There is an increased risk of breast cancer(40% develop breast cancer).
4. Nipple discharge

. Most causes of nipple discharge are benign.

1. Intraductal papillomas and breast cancercan produce a bloody or blood-tinged serous discharge.
2. Subareolar infections

• produce purulent discharge with tender areola.

1. Galactorrhea

• is defined as a milky white discharge.
• is usually bilateral, and not related to lactation or breast stimulation.

2. It may signify an increase in prolactin secretion.
3. The most common cause is pituitary microadenoma.
4. Drugshave also been shown to increase prolactin levels, including phenothiazines, metoclopramide, birth control pills (BCPs), α-methyldopa, reserpine, and tricyclic antidepressants (TCAs).
5. Hypothyroidism as well as hyperthyroidism has also been associated.
6. It is usually associated with amenorrhea.
7. Fibrocystic disease

• uncommonly produces green/yellow or brown discharges.

9. Mastodynia(i.e., breast pain) (see Table 18-1)

. Malignancy is rarely associated with mastodynia.

1. It needs to be distinguished from Tietze syndrome, which is costochondritis of the upper ribs with referred pain to the breast.

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1. There are two distinct typesof mastodynia: cyclic and continuous.
2. Cyclic mastodynia

• is characterized by pain before the menstrual period.

1. The pain may be referred to the axilla or to the underside of upper arm.
2. It is most commonly associated with fibrocysticdisease.
3. Continuous mastodynia

• is characterized by continual pain unrelated to the menstrual cycle.
• often represents an acute or subacute infection.
• most commonly presents as a single large cyst.

1. Treatment
2. Progressing from cyclic to continuous, mastodynia is usually refractoryto treatment.
3. Most patients can be treated with reassurance.
4. Treatment for persistent painincludes using NSAIDs or acetaminophen, eliminating methylxanthines and caffeine, smoking cessation, danazol (a weak androgen), BCPs, vitamin E, and tamoxifen.
5. Noninvasive Breast Cancer/Premalignant Breast Cancer

(Table 18-2)

1. Ductal carcinoma in situ (DCIS)
2. This lesion contains malignant cells

• from the ductal epithelium without microinvasion(invasion through the basement membrane).

2. The median age of diagnosis

• is between 50–60, but it is also found in young women.

3. Based on histologic findings, there are four major distinct forms of DCIS:
4. Comedo DCIS

• is the most aggressive form, with the highest microinvasion rate.
• can display multicentricity (simultaneous occurrence in different breast quadrants).

1. Solid DCIS

• is identified by malignant cells completely filling the ducts.

1. Cribriform DCIS

• has small, uniform cells in a fenestrated pattern.

1. Micropapillary DCIS

• tends to be multicentric.

4. Microinvasion is rare

• in lesions smaller than 2.5 cm.

5. Classic MMG findings

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• are clustered microcalcifications(see Figure 18-3B).

1. Between 25%–35%of untreated DCIS will develop into invasive cancer.
2. Approximately 10%of women will develop DCIS in the contralateral breast.

Table 18-2. Premalignant and Malignant Breast Cancer

Breast Pathology Histology Presentation Treatment Comments Premalignant Breast Cancer Ductal carcinoma in situ (DCIS) Noninvasive adeno-carcinoma cells (five subtypes) Clustered micro-calcifications on MMG Segmental mastectomy or lumpectomy with post-operative radiation; axillary node dissection for lesion > 3 cm Comedo is the mostaggressive subtype Lobular carcinoma in situ (LCIS) Multicentric and multi-focal lesions are common Pathologic examination Close observation Risk factor for ductal carcinoma Invasive Breast Cancer Infiltrating ductal carcinoma Medullary Tubular Mucinous (colloid) Secretory (juvenile) Invasive adenocar-cinoma cells in a fibrous stroma Mass on self-breast exam Lumpectomy + axillary node dissection + radiation therapy or modified radical mastectomy Juvenile carcinoma may present before age 30 Infiltrating lobular carcinoma Multicentric and multi-focal Pathologic examination; mass effect on MMG Lumpectomy + axillary node dissection + radiation therapy or modified radical mastectomy MMG = mammogram.

6. Treatment optionsfor DCIS may include

. Total mastectomy, with or without reconstruction.

• This option is usually considered too aggressive for DCIS lesions.
• It may be indicated if the majority of the breast has DCIS changes.

1. Segmental mastectomy(lumpectomy), with or without postoperative radiation.

• Postoperative radiation therapy may reduce the local recurrence rate to 10%.

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• Patients with a small, low grade DCIS may not need postoperative therapy.

1. An axillary node dissectionor sentinel node biopsy

• may be considered for a DCIS lesion larger than 3 cm.

7. Close follow-up

• with physical examination and MMG is essential.

1. Lobular carcinoma in situ (LCIS)
2. Lesionsare

• defined histologically by terminal lobule intra-epithelial proliferation.
• generally nonpalpableand diagnosed by pathologic evaluation.
• primarily found in premenopausal women.

2. LCIS is a risk factorfor developing bilateral breast cancer.

• Bilateral disease occurs in 30%–50% of patients.

3. A diagnosis of LCISconfers a 5% chance of having a synchronous invasive lesion.

• Sixty to seventy percent of invasive lesions associated with LCIS are ductalcarcinomas.

4. Multifocal disease

• (i.e., simultaneously occurring lesions within the same breast quadrant) and multicentricdisease is common.

5. Although controversial, treatment optionsfor LCIS may include close observation or bilateral prophylactic mastectomy without axillary node dissection.
6. Invasive Breast Cancer

(see Table 18-2)

1. Overview
2. Incidence

• There are approximately 150,000 new cases of female breast cancer and 44,000 deaths per year secondary to breast cancer.
• The incidence of breast cancer has increased 150% since 1970.

2. It has been estimated that 7% (1/14) of women who reach age 70 will develop breast cancer.
3. Risks factors for breast cancer

are covered in Table 18-3.

1. Adenocarcinoma of the breast
2. Invasive ductal carcinoma/infiltrating ductal carcinoma

• represents 70%–80%of all breast cancer.

1. Invasive adenocarcinoma cellsin a fibrous stroma, sometimes with associated microcalcifications, are typically observed microscopically.
2. Ductal cancers typically metastasizeto axillary lymph nodes and may spread to bone, lung, liver, and brain.

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1. When mixed in histologythe clinical behavior is like that of ductal cancer.

Table 18-3. Risk Factors for Developing Breast Cancer

Greatly Increased Risk Moderately Increased Risk Increasing age Nulliparity or first birth after age of 30 Female gender Menarche before age 12, menopause after age 55 Strong family history: two or more first degree relatives with bilateral, premenopausal breast cancer Moderate family history: one or more relatives with breast cancer, not bilateral or premenopausal DCIS, LCIS, atypical ductal or lobular hyperplasia Low-dose ionizing radiation in childhood or adolescence History of contralateral breast cancer Other cancers: colon, endometrial BRCA-1, BRCA-2 (genetic tumor markers) Diet: high-fat or high-calorie diets Oral contraceptives and the use of postmenopausal conjugated estrogens have not been shown to increase the long-term risk of breast cancer. Many women diagnosed with breast cancer do not have a risk factor other than gender. DCIS = ductal carcinoma in situ; LCIS = lobular carcinoma in situ.

2. Variants of invasive ductal carcinoma

. Medullary carcinoma

• represents about 6% of all the breast cancers.
• tumors are typically larger than ductal carcinomas.

3. Typically, marked lymphocytic infiltration and large pleomorphic nuclei are observed microscopically.
4. Ninety plus percent are estrogen- and progesterone-positive.
5. This variant carries a better prognosisthan other invasive ductal carcinomas.
6. Tubular carcinoma

• represents about 2% of all the breast cancers.

1. These tumors are typically smaller, being identified on screening MMG.
2. Small tubule formation of over 75% of the tumor with stroma and elastic tissue is observed microscopically.
3. This variant carries a better prognosisthan other invasive ductal carcinoma.
4. Mucinous (colloid) carcinoma

• represents about 2% of breast cancers.

1. Microscopically, there is an abundance of extracellular mucin.
2. This variant may confer a better prognosis.
3. Secretory carcinoma (juvenile carcinoma)

• is a very rare variant.

1. The mean age of diagnosis is 25, but ranges from 11–75.
2. These slow growing, mobile tumors are commonly mistaken for fibroadenomas.
3. Small, secretion filled, glandular cells in a lobulated pattern can be seen microscopically.

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3. Invasive lobular carcinoma/infiltrating lobular carcinoma

• represents about 5%–10% of invasive breast cancers.

1. These tumors differ from ductal cancer.

• Microcalcifications are rarely seen on MMG.
• They are usually extensively infiltrating, often with no distinct tumor mass.
• Multicentricity and multifocality are much more common.

1. A single-file arrangementof adenocarcinoma cells is observed microscopically.

• If larger signet-ring cellscan be seen, there is a poorer prognosis.

1. These tumors metastasizeto axillary lymph nodes, bone, lung, liver and brain. They may also metastasize to the meninges and serosal surfaces.
2. Treatment guidelines

• for infiltrating ductal or lobular carcinoma are covered in Table 18-2.

1. Other histologic types of breast cancer
2. Metaplastic adenocarcinoma

• takes the appearance of nonglandular tumors.

1. The most common types of metaplasiaare squamous and pseudosarcomatous.
2. The prognosisis the same as that of the tumor from which it was derived.

• Although uncommon, squamous carcinomahas a worse prognosis than ductal cancer.

2. Adenoid cystic carcinomas

• are large, well circumscribed lesions.
• have a better prognosisthan ductal cancers.
• can be thought of as a large cyst containing DCIS.

1. Factors that influence prognosis
2. The most important prognostic factor

• for patients without clinically advanced disease is the number of lymph nodes positivefor cancer.

2. Other factors, in order of importance, include

• tumor size.
• histologic grade.
• estrogen receptor and progesterone receptor status.
• the histologic type.

VII. Management of Breast Cancer

1. Assessment of breast cancer
2. Diagnoseall evident local and systemic disease (Table 18-4).
3. Assessfor the extent of regional and systemic disease.

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• If there is evidence of lymphatic microinvasion, there is a 30% chance of either regional or systemic disease.

Table 18-4. Indications and Staging Studies After the Diagnosis of Breast Cancer

Study Indication Complete blood count, liver function tests Routine Chest radiograph Routine Bilateral mammogram Routine Computed tomography scan of the liver Symptoms, abnormal liver function test Bone scan Suggestive symptoms, locally advanced primary, abnormal alkaline phosphatase

1. Treatment for breast cancer
2. Treatmentis based on the stage of the disease.

• The American Joint Committee on Cancer tumor-node-metastasis (TNM) staging is outlined in Table 18-5.

2. The approach for breast cancer managementis based on disease location.
3. Local control:lumpectomy with irradiation or mastectomy.
4. Regional control:axillary lymph node dissection, irradiation to localized disease.
5. Systemic disease:chemotherapy.
6. Micrometastatic disease:hormonal therapy, chemotherapy, or both.
7. Adjuvant therapyincludes chemotherapy and hormonal therapy.

• Decisionsabout adjuvant therapies are affected by factors such as age and receptor status (Table 18-6).

4. Even women withoutevidence of lymphatic microinvasive breast cancer may benefit from antiestrogen therapies and/or chemotherapy.
5. Microinvasive breast cancer

• is DCIS with a focus (<10%) of microinvasion in biopsy.

1. The incidence

• of axillary node metastasis is 0%–10%.

2. Axillary node dissection

• is not felt to be warranted in these patients.

3. Treatment

• is similar to the treatment for DCIS: lumpectomy with postoperative radiation therapy.

1. Early-stage breast cancer (T1–T2, N0–N1)

• represents 75% of patients who present with breast cancer.

1. There are three standard treatment optionswith equivalent survival rates:
2. Lumpectomy, axillary node dissection, followed by postoperative radiation.

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1. Modified radical mastectomy alone.
2. Modified radical mastectomy with reconstruction.

Table 18-5. The American Joint Committee on Cancer Tumor-Node-Metastasis (TNM) Staging

Tumor (T) Tx —Primary tumor cannot be assessed T0 —No evidence of primary tumor Tis —Carcinoma in situ: intraductal or loblar carcinoma in situ, or Paget's disease of the nipple with no tumor T1 —Tumor mass < 2 cm in diameter T2 —Tumor > 2 cm and < 5 cm in diameter T3 —Tumor > 5 cm in diameter T4 —Tumor of any size with direct extension to chest wall or skin Nodes (N) Nx —Regional nodes cannot be assessed—previously removed N0 —No regional lymph node metastasis N1 —Metastasis to movable ipsilateral axillary lymph nodes N2 —Metastasis to ipsilateral axillary nodes that are fixed, nonmobile N3 —Metastasis to ipsilateral internal mammary lymph nodes Distant Metastasis (M) Mx —Presence of disease cannot be assessed M0 —No evidence of distant metastasis M1 —Distant metastasis Stage T N M Stage 0 Tis N0 M0 Stage I T1 N0 M0 Stage IIA T0 T1 T2 N1 N1 N0 M0 M0 M0 Stage IIB T2 T3 N1 N0 M0 M0 Stage IIIA T0 T1 T2 T3 T3 N2 N2 N2 N1 N2 M0 M0 M0 M0 M0 Stage IIIB T4 Any T Any N N3 M0 M0 Stage IV any T Any N M1

2. Determining which treatment optionto use depends on multiple variables:
3. If the breast is small, then lumpectomy may yield a poor cosmetic result.
4. If there is aggressive histology, a more aggressive treatment may be advocated.
5. Patient's desires, age, and reliability for follow-up are all considered.
6. Axillary node dissectionis important for staging, even with nonpalpable nodes.
7. Axillary node status is a major predictor of 5-year survival.
8. No positive axillary nodes:confers a 75% five-year survival.

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2. With 1–3 nodes positive:60%.
3. With 4–10 nodes positive:40%.
4. Among early breast cancers with nonpalpable axillary nodes, 20%–30% will have nodal disease identified with surgery.
5. The nodal status

• also helps to direct adjuvant chemotherapy (see VII B 3).

1. Minimally invasive techniques

• like sentinel node biopsy may allow for an accurate assessment of the nodal status of patients with little pain and risk.

Table 18-6. Indications for Adjuvant Chemotherapy

Tumor Size ER/PR Status Nodal Status Recommendations Premenopausal Postmenopausal < 1 cm + - No adjuvant therapy No adjuvant therapy > 1 cm + - Chemotherapy plus tamoxifen Tamoxifen - - Chemotherapy Chemotherapy Any size + + Chemotherapy plus tamoxifen Chemotherapy plus tamoxifen - + Chemotherapy Chemotherapy ER = estrogen receptor; PR = progesterone receptor.

1. Locally advanced breast cancer
2. This cancer is comprised of large (T3) tumorsor extensive regional disease without distant metastasis.
3. About 10%–20% of patientspresent with this stage of breast cancer.

• About 75%will have clinically palpable axillary or supraclavicular nodes.

1. About 20% of patients who appear to be stage III on examination will be stage IV after complete staging.
2. Inflammatory breast cancer

• is a rare, virulent form of breast cancer.

1. It usually presentsas an erythematous, warm breast, with edema and pain (peau d'orange).
2. Tumor emboliin dermal lymphatics can be seen in skin biopsies for diagnosis.
3. Locally recurrent breast cancer

• is usually only focal disease.
• may be controlled with a salvage mastectomy.
• Postmastectomy recurrence typically occurs within 2 years and is associated with distant disease and a median survival of 2–3 years.

4. Paget's disease of the nipple

• is a sometimes weeping, eczematous lesion of the nipple.

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• may be associated with edema and inflammation.
• usually represents malignant cells within the milk ducts.

5. Metastatic breast cancer

• generally cannot be cured.

1. The median survival is about 2 years.
2. Treatmentwith surgery and chemotherapy is generally palliative.

VIII. Atypical Breast Cancer

1. Cystosarcoma phylloides

• are rare tumors, representing about 0.5%–1.0% of breast tumors.

1. The median ageat presentation is 50.
2. Microscopically there are stromal and epithelial elements.
3. These are usually larger tumors, and can be benign or malignant.
4. These tumors rarely metastasize.

• If they do, they can metastasize to the lung, bone and mediastinum (note notaxilla).

5. Treatmentis local excision without axillary node dissection.
6. Occult breast cancer

• is breast cancer presenting as axillary metastaseswith an unknown primary.

1. Fifty-five to seventy-five percent of these patients are found to have cancer after mastectomy.
2. Radiation therapymay be an option for patients who desire breast conservation.
3. Treatmentis usually modified radical mastectomy.
4. Male breast cancer
5. Overview
6. There are approximately 900 new cases of male breast cancer per year, about 1% of breast cancer cases.
7. Mean age of presentation is 60–65.
8. Risk factorsinclude

• previous radiation.
• family history.
• Klinefelter's syndrome.
• protracted hyperestrogenemic state.

3. These tumors are

• ductal in origin, and 80% are estrogen receptor-positive.
• tend to metastasizeearly in the course of the disease.

4. Treatmentis a modified radical mastectomy.

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Review Test

Directions: Each of the numbered items or incomplete statements in this section is followed by answers or by completions of the statement. Select the ONE lettered answer or completion that is BEST in each case.

1. A newborn is found to have an additional nipple in the right axilla. Which of the following characteristics are most likely to be associated with this condition?

(A) Amastia

(B) Hypoplasia of the ipsilateral chest

(C) Hypoplasia of the ipsilateral breast

(D) Normal development

(E) Bilateral breast hyperplasia

1–D. The failure of the regression of the milk line results in accessory breast tissue. The most common congenital breast anomaly is accessory nipple(s), or polythelia, and is associated with normal breast development. Accessory breast tissue, separate from the main breast mound, is most commonly found in the axilla. A complete accessory breast, possessing both breast tissue and nipple, is rare. Abnormal or total regression of the milk line may lead to underdevelopment of the breast, or amastia, and is usually associated with hypoplasia of the ipsilateral chest wall and pectoralis muscles, or Poland syndrome.

2. A newborn is examined immediately after birth and is found to have bilateral breast hyperplasia with an associated creamy-white discharge. What is the most appropriate evaluation for this patient?

(A) Immediate computed tomography (CT) scan of the brain to evaluate for a microadenoma and possible surgery

(B) Observation with reassurance to the parents that this is a known normal phenomenon

(C) Bilateral ductography and simple mastectomy to remove diffuse papillomas

(D) Close observation of the newborn and thyroid supplementation

(E) Close observation and a toxin scan of both mother and infant

2–B. The epithelial bud differentiates from the retained thoracic portion of the milk line, developing from the seventh week of gestation to birth. This bud forms into the nipple and functional breast tissues. Thus, these tissues may respond to in utero maternal hormone stimulation by hypertrophy and the postbirth production of colostrum. Therefore, although a microadenoma causing an increase in prolactin levels is the most common cause of bilateral nipple discharge in adults, in the newborn population this is a known normal phenomenon and requires only observation and reassurance of the parents. Diffuse papillomatosis is primarily seen in an older population and produces a serous discharge. Both hyperthyroidism and hypothyroidism have been associated with a bilateral discharge, but this is rare and is usually seen in adults. There are a few toxins that can cause developmental abnormalities in the newborn, however these usually cause extensive global abnormalities.

3. A 45-year-old, premenopausal woman presents to her doctor with a new breast mass discovered on self-breast examination. It is a small, firm, mobile mass in the left lower outer quadrant of her breast. There are no skin changes or dimpling and no lymph nodes palpable in her axilla. Which of the following histories would confer the greatest concern that this mass represents an invasive ductal carcinoma?

(A) Her sister had postmenopausal breast cancer

(B) She had her menarche before age 12

(C) She had never been pregnant

(D) She had a history of atypical lobular hyperplasia

(E) She had been on birth control pills (BCPs) for 5 years when in her 20s

3–D. The risk of breast cancer increases with age, and the majority of invasive ductal carcinomas present as a new mass on physical examination. All of the histories described are considered risk factors for the development of breast cancer. However, having never been pregnant, having an early menarche before age 12, or having a sister who had postmenopausal breast cancer all confer a lower risk than having the premalignant changes of atypical lobular hyperplasia, estimated to be four to five times the risk. In addition, both lobular carcinoma in situ (LCIS) and lobular hyperplasia are strong risk factors for the development of invasive ductal carcinoma. Birth control pills (BCPs) have not been shown to confer an increased long-term risk for breast cancer.

4. A 48-year-old, premenopausal woman presents to her doctor for routine health maintenance. She is found to have a small, firm palpable breast mass in her left breast. The patient undergoes a bilateral mammogram (MMG) to evaluate for concurrent disease, subclinical breast disease presenting simultaneously with the mass. The MMG shows no abnormalities, including no microcalcifications or mass effect near the area of the palpable breast mass. Which of the following is the most appropriate next step in the evaluation of this patient?

(A) Close observation to evaluate for increases in size or decreased mobility

(B) Ultrasound evaluation in 1 year

(C) Fine needle aspiration (FNA) for cellular evaluation

(D) Excisional biopsy and axillary node dissection

(E) Core needle biopsy and axillary node dissection

4–C. There are a large number of women without risk factors who develop breast cancer each year. The most common presentation for breast cancer is a new mass on physical examination. Therefore, great care must be taken to rule out breast cancer in any women who present with a new breast mass; observation is inadequate in this patient. Even though the sensitivity of a mammogram (MMG) increases with age due to replacement of dense parenchymal tissues by fatty tissues, palpation detects 10%–20% of MMG-negative cancers. Most women over the age of 30 presenting with a new mass on physical examination require a definitive, cell-based, diagnosis. If a cyst was found on an ultrasound study, suggesting a benign process, close follow-up and serial exams may be indicated rather than immediate biopsy. A fine needle aspiration (FNA) would be the most appropriate next step in this patient owing to the pretest's likelihood that this lesion is malignant. However, if the FNA was nondiagnostic, excisional biopsy or a core needle biopsy would be indicated. Axillary node dissection would be premature at this point.

5. A 54-year-old woman presents with a clinically node-positive, 3-cm infiltrating ductal carcinoma in her left breast. She has no other symptoms. Which of the following would be appropriate for the initial evaluation of this patient?

(A) Chest radiograph, bone scan, complete blood count with liver function tests, bilateral mammogram (MMG), and a computed tomography (CT) scan of the liver

(B) Chest radiograph, bone scan, bilateral MMG, and a CT scan of the liver

(C) Chest radiograph, complete blood count with liver function tests, and a bilateral MMG

(D) Chest radiograph, bone scan, and a complete blood count with liver function tests

(E) Chest radiograph, bone scan, bilateral MMG, and a CT scan of the liver

5–C. This patient is presenting with a locally advanced tumor and therefore has a relatively high risk for metastatic disease. Infiltrating ductal carcinoma usually spreads to regional lymph nodes first, then can metastasize to the lungs, liver, and bone. Therefore, a chest radiograph and liver function tests are indicated. Bone metastases will either be painful or cause an increase in alkaline phosphatase. If the patient does not have either of these, then a bone scan is not indicated. A bilateral mammogram (MMG) is indicated in all patients presenting with recurrent disease to evaluate for concurrent disease. A computed tomography (CT) scan of the liver is not as sensitive for small liver metastases, and therefore would only be obtained if the liver function tests were abnormal.

6. A 34-year-old woman underwent a wide local excision, axillary node dissection, and postoperative radiation to her left breast for a node-positive, 2-cm, infiltrating ductal carcinoma 3 years ago. She received adjuvant chemotherapy at that time. She now presents with a new 2-cm mass in the same breast, and it shows infiltrating ductal carcinoma. She has no other symptoms and has no palpable lymph nodes. Which of the following is the most appropriate treatment for this patient?

(A) Re-excision to free margins, second axillary node dissection, and radiation therapy

(B) Combination chemotherapy alone

(C) Left total mastectomy

(D) Left modified mastectomy

(E) Combination chemotherapy and radiation therapy

6–C. Local recurrence in the breast occurs in approximately 10% of patients who are treated with wide local excision, axillary node dissection, and radiation therapy. “Salvage” total mastectomy is usually required and survival rates approach those obtained when a modified radical mastectomy is performed originally. In the absence of palpable lymph nodes, a second lymph node dissection is unnecessary. The effect of radiation on tissues is cumulative and does not diminish with time. Therefore, use of more radiation therapy in this patient increases the risk of toxicity to normal tissues and thus is usually not considered appropriate. Chemotherapy alone would be inappropriate because of a lower long-term survival with this approach.

Questions 7-8

7. A 43-year-old professional woman presents to your office with questions about breast cancer screening. She has never had a mammogram previously, but does monthly self-breast examinations and has not noted any masses. Her mother was diagnosed with breast cancer at age 65, but she has no other relatives with cancer. She has had 3 children and her menarche was at age 13. The best screening routine for this patient is to obtain a baseline mammogram

(A) At age 45, then every 2 years after age 50

(B) Now, then every 2 years thereafter

(C) Now, then every 2 years until age 50, then yearly thereafter

(D) Now, and then every 6 months thereafter

(E) Now, and then every 5 years thereafter

7–C. This woman has only one risk factor for developing breast cancer; her mother was diagnosed with postmenopausal disease. All women, however, should obtain a baseline mammogram (MMG) between the ages of 35 and 39. Then, if there are no abnormalities, a screen MMG should be obtained every 1–2 years between the ages of 40 and 49, and yearly thereafter. An MMG should be obtained in all women over the age of 30 that present with breast symptoms even when there are no palpable lesions. Mammography can detect 90% of nonpalpable breast lesions.

8. This patient undergoes a bilateral mammogram (MMG) and is discovered to have an area of microcalcifications in her right breast. She then undergoes a needle localized excisional biopsy that demonstrates a cellular, monomorphic pattern, with poorly cohesive intact cells, nuclear crowding, and a variation in nuclear size, prominent nucleoli, and clumping of the chromatin. There is no evidence of microinvasion and the largest diameter is 1 cm. The margins are negative. Which of the following management options is most appropriate?

(A) Modified radical mastectomy

(B) Reassuring the patient that the process is benign

(C) Axillary node dissection with postoperative breast radiation therapy

(D) Breast radiation therapy alone

(E) Axillary node dissection alone

8–D. This patient's lesion is most consistent with ductal carcinoma in situ (DCIS), therefore simple reassurance is inappropriate. Other findings on mammogram (MMG) that are suggestive of DCIS include asymmetric densities, ductal asymmetry, and distortion of normal breast architecture and skin or nipple distortion. Once a diagnosis of DCIS has been made, there are multiple factors that help determine the most appropriate treatment. Patient's preference and reliability for close follow-up, breast size, and family history are all taken into account. In this patient, local control of her DCIS was obtained with the lumpectomy. If this lesion had been observed, there would be approximately a 30% chance that it would develop into an invasive carcinoma. Because the lesion was small (< 3 cm in diameter) and there was no evidence of microinvasion, an axillary node dissection is not indicated. Although some may advocate the use of a modified radical mastectomy for such lesions, most people would agree that this is too aggressive for DCIS. Postoperative radiation therapy has been shown to be beneficial in reducing the local recurrence rate for small DCIS lesions.

9. A 55-year-old woman status post-breast conservation therapy for ductal carcinoma in situ (DCIS) develops a large, fixed node in her right axilla. There are no breast masses on physical examination, and a bilateral mammogram (MMG) demonstrates no abnormalities. You obtain a fine needle aspiration (FNA) from the axillary mass, which shows adenocarcinoma cells. Which of the following is the most appropriate next step in the management of this patient?

(A) Axillary node dissection for staging, and radiation therapy to the breast

(B) Axillary node dissection for staging alone

(C) Radical mastectomy

(D) Modified radical mastectomy

(E) Radiation to the axillary mass without surgery

9–D. In any patient with ductal carcinoma in situ (DCIS), close follow-up with breast examination and mammogram is essential. This patient now has evidence of regional metastatic disease with an unknown primary. In this case, axillary node dissection is not only used for staging, but is also considered therapeutic because of the overall reduction in tumor mass. However, axillary node dissection alone does not adequately treat the unknown primary, and thus a mastectomy is indicated. Radiation of the axilla may also treat the regional disease, but this is inadequate and does not address the unknown primary breast lesion. Most people would agree that a radical mastectomy is too aggressive for such a patient. A modified radical mastectomy, the removal of all the breast tissue combined with an axillary node dissection, is the most appropriate therapy for this patient because it provides treatment for the regional disease as well as for the unknown primary. Approximately 55%–75% of patients with occult breast cancer are found to have lesion on mastectomy.

10. A 28-year-old woman presents to your office with painful breasts. She states that she used to suffer from pain in her breasts only before her period, but the pain now never goes away and she can no longer function normally. She does take birth control pills (BCPs), but does not smoke and does not drink coffee. On physical examination, you find no dominant masses and no nodes positive in her axilla. No nipple discharge is expressible. Over the next few months you try to treat her pain conservatively, but without success. Which of the following is the best approach to the treatment of this patient?

(A) Continue with observation alone because the process is self-limiting

(B) Prescribe more potent pain relieving drugs such as narcotics

(C) Launch an extensive work-up for invasive ductal carcinoma

(D) Prescribe danazol, with follow-up to evaluate for side effects

(E) Obtain bilateral ultrasounds to localize the fibroadenomatous disease

10–D. The patient is suffering from mastodynia, which is rarely associated with malignancy, or fibroadenomas. She has progressed from cyclic to continuous mastodynia and thus represents a population of patients who are usually refractory to conservative therapy. However, in this situation, treatment with reassurance alone is inappropriate because of the disabling nature of her disease. Narcotics do not provide good pain relief for such a disease. Danazol has been shown to be very effective for such patients, as well as low-dose tamoxifen. Danazol is usually well tolerated, but may cause amenorrhea, body fat redistribution, hirsutism, acne, weight gain, and deepening of the voice. Long-term use has been associated with liver function abnormalities.

11. A 37-year-old woman presents to the clinic with a history of left-sided bloody nipple discharge. She denies any pain or any changes on self-breast examination. She has no other complaints. She is very concerned because her sister died at the age of 42 of breast cancer. On physical examination, you cannot appreciate any dominant masses. There is a small amount of blood-tinged nipple discharge. On mammogram (MMG), there are no abnormalities seen. Which of the following is the most appropriate next step in the evaluation and treatment of this patient?

(A) Observation with strict instructions to return when and if the bloody discharge occurs again

(B) Ultrasound to evaluate for any cystic masses

(C) Re-examination in 6 months with bilateral mammogram (MMG)

(D) Simple mastectomy and close follow-up

(E) Ductography and potential subareolar excision

11–E. Most causes of nipple discharge are benign, however, spontaneous nipple discharge that is bloody tinged may represent cancer. Therefore, in low risk patients, observation combined with serial examinations is probably sufficient. However, in the high-risk patient, great care is required to confirm the diagnosis of an intraductal papilloma and observation is inadequate. Intraductal papillomas are the most common cause of bloody nipple discharge, although half the time the discharge is serous. These are usually small, nonpalpable lesions close to the nipple that are usually not seen on mammogram (MMG) or ultrasound, so evaluation in 6 months with MMG or ultrasound would usually miss the papilloma. Diagnosis is generally made by ductography and curative treatment consists of subareolar excision. There is no increased risk of cancer, so simple mastectomy may be too aggressive for the treatment of this disease. Diffuse papillomatosis affects multiple ducts and both breasts. The papillomas are larger and the discharge is serous, not bloody. With this diagnosis, there is an increased risk of breast cancer (40%), therefore simple mastectomy may be indicated.

12. A 66-year-old woman returns to your office 10 years after being treated for advanced left breast cancer. At that time, she had a radical mastectomy and radiation therapy to her axilla for regional control. She states that for the last 4 years, she has noticed swelling in her left hand and now is somewhat distressed because there seems to be a rash progressing up her arm. On physical examination, she does have 4+ pitting edema in her hand as well as multiple painless purplish red nodules that seem to be spreading up her arm. Which of the following is the most likely diagnosis for this mass?

(A) Bacterial cellulitis

(B) Paraneoplastic coagulopathy

(C) Post-traumatic hematoma

(D) Lymphangiosarcoma

(E) Lymphoma

12–D. Long-standing lymphedema of any kind predisposes to the development of lymphangiosarcoma. Most of these tumors develop in patients with massive lymphedema, usually as a result of the combination of a complete axillary node dissection (including the level III nodes) and axillary radiation. A single discrete tumor is rarely encountered. Rather, purplish red nodules are usually seen and are easily mistaken for bacterial cellulitis. These tumors are almost always high-grade and spread rapidly to involve most of the arm as well as the shoulder and chest wall. Pulmonary metastases are also commonly found at the time of diagnosis. Most patients die within 2 years of presentation. If these lesions represented a post-traumatic hematoma or the manifestations of a paraneoplastic coagulopathy, they would probably be painful. Lymphomas are typically solitary masses.

Directions: Each set of matching questions in this section consists of a list of four to twenty-six lettered options followed by several numbered items. For each numbered item, select the appropriate lettered option(s). Each lettered option may be selected once, more than once, or not at all.

Questions 13-17

1. Infiltrating ductal carcinoma
2. Comedo intraductal carcinoma
3. Lobular carcinoma in situ
4. Medullary carcinoma
5. Inflammatory carcinoma

Match each histologic type of breast cancer with the most likely associated description.

13. Associated with lymphocytic infiltration and a good prognosis. (SELECT 1 TYPE)

13–D. Medullary carcinoma usually presents as a palpable mass with smooth borders on mammogram (MMG) that mimic a benign condition. However, histologic examination reveals its malignant nature and typically has marked lymphocytic infiltration. Overall, it carries a relatively good prognosis.

14. Significant likelihood of multicentric ipsilateral disease. (SELECT 2 TYPES)

14–B, C. The comedo form of ductal carcinoma in situ (DCIS) has the highest microinvasive rate and multicentric rate of these lesions. It is best treated with lumpectomy and postoperative radiation therapy. Lobular carcinoma in situ (LCIS) is also characterized by a high rate of multicentricity.

15. Highest likelihood of bilateral disease. (SELECT 1 TYPE)

15–C. Lobular carcinoma in situ (LCIS) is usually considered a major risk factor for ductal carcinoma and usually presents as an incidental finding on breast biopsy of another lesion in postmenopausal women. Approximately 20%–25% of women who are found to have LCIS will develop breast cancer within 15 years of the diagnosis, with both breasts being at equal risk.

16. Dermal lymphatic invasion. (SELECT 1 TYPE)

16–E. Inflammatory carcinoma, a variant of infiltrating ductal carcinoma, is characterized by the clinical appearance of inflammation (peau d'orange, warmth, edema, and pain) secondary to dermal lymphatic invasion. Its prognosis is poor.

17. Most common carcinoma presenting as a breast mass. (SELECT 1 TYPE)

17–A. Although there are variants of infiltrating ductal carcinoma, overall this lesion is the most common malignancy presenting as a breast mass.