Chapter 23

Breast

Karen A. Chojnacki Diane R. Gillum Kandace Peterson

Francis E. Rosato

I Introduction

A Anatomy

(Tear-drop shape)

Four quadrants

Upper inner quadrant

Upper outer quadrant (includes the axillary tail of Spence), most common site for breast cancer Lower inner quadrant

Lower outer quadrant

Parenchyma

Alveoli (10–100) form each lobule.

Lobules (20–40) form each lobe.

Lobes (15–20) are radially arranged segments that are each drained by a duct; all lobes converge at the nipple.

B Vasculature

Arterial supply

Internal mammary artery (60%)

Lateral thoracic artery (30%)

Venous return

Axillary vein (primary)

Intercostal vein

Internal mammary veins

Lymphatic drainage follows venous drainage.

The axillary chain is important drainage for neoplastic disease and is divided into three levels (Fig. 23 -1).

The axilla and supraclavicular region should be examined for adenopathy.

C Radiologic exam

Mammogram

A baseline mammogram is advised when the woman is 40 years of age and then yearly as long as the patient is in good health.

The mammogram is done sooner if the patient has a family history of early breast cancer. For these patients, the first mammogram should be done 5 years earlier than the age of the family member when diagnosed with breast cancer. For example, a patient whose sister developed breast cancer at age 39 should have her first mammogram at age 34.

Mammography can reveal the following: breast architecture, asymmetry, skin thickening, irregular masses, and microcalcifications.

Ultrasound

Ultrasound is not recommended for routine screening.

It is useful as a targeted exam for a symptomatic patient.

It can further characterize abnormalities seen on mammogram or found on physical exam (i.e., cyst vs. solid mass).

Magnetic resonance imaging (MRI)

Also not used for routine screening

Very sensitive but not specific evaluation of the breast

Especially useful in the evaluation of patients with mammographically dense breasts, patients with axillary disease, and negative mammogram

MRI can detect the extent of tumor within the breast and residual tumor within the breast after lumpectomy and can differentiate between tumor and postsurgical scar.

D

Biopsy is necessary to make a diagnosis.

Fine-needle aspiration (FNA) is useful in the evaluation of palpable lesions.

Cyst aspiration is both diagnostic and therapeutic.

Cyst must be drained completely.

Cyst fluid must be nonbloody. If fluid is bloody, excision is recommended to rule out malignancy.

If the lesion is solid , a fine -needle aspirate can extract cells, which can be examined cytologically. If cytology reveals atypia, excisional biopsy is recommended. If cytology reveals malignancy, further surgery is necessary.

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Core -needle biopsy is used to evaluate palpable solid lesions.

Incisional biopsy may be useful for diagnosis of inflammatory breast cancer.

Excisional biopsy

Completely removes the lesion

It may be the only surgical treatment of breast tissue if the margins are adequate.

It can be done using a local anesthetic with mild sedation.

Nonpalpable radiographic abnormalities

A needle -guided biopsy is performed by excising the lesion after the radiologist places a localizing wire in the breast to identify the site. The lesion must be visible on two mammographic views to allow accurate needle placement.

A stereotactic or mammotome biopsy uses computed mammographic equipment to deploy a core needle into mammographic abnormalities. This biopsy accurately samples nonpalpable lesions. This less invasive biopsy technique is indicated for patients with small nonpalpable radiodensities, single or multiple foci of calcifications, lesions seen on only one mammographic view, and lesions adjacent to breast implants.

III Benign Breast Disease

A Infectious and inflammatory breast diseases

Cellulitis, mastitis

Infection of the breast is usually associated with lactation.

Bacteria enter through the nipple (Staphylococcus or Streptococcus ). Treatment is a 10 - to 14 -day course of antibiotics to cover Staphylococcus and Streptococcus.

Patient can continue to breast feed during treatment. If breast feeding is too painful, a breast pump should be used.

Abscess is a collection of purulent fluid within breast parenchyma. It is treated by surgical drainage.

A chronic subareolar abscess occurs at the base of the lactiferous duct. Squamous metaplasia of the duct may occur.

A sinus tract to the areola develops.

Treatment requires complete excision of the sinus tract.

Recurrences are common, especially if the entire tract is not excised.

Mondor's disease is phlebitis of the thoracoepigastric vein.

A palpable, visible, tender cord runs along the upper quadrants of the breast along the course of the

vein.

Disease is self-limited, but anti -inflammatory agents and warm compresses improve patient comfort and shorten disease course.

B Benign lesions of the breast

Fibrocystic change (chronic cystic mastitis). This term is used for a broad spectrum of benign breast changes. It is characterized by nodularity with or without pain. Any dominant masses must be biopsied.

Fibroadenoma

Fibroadenoma is a well-defined tumor of the breast.

It consists of fibrous stromal tissue with an epithelial component.

Fibroadenoma is most common in younger women.

It is mobile and well circumscribed.

Usually, it is well visualized by ultrasound.

FNA, core biopsy, or excision is used to establish diagnosis.

Phyllodes tumors were previously referred to as cystosarcoma phyllodes.

These tumors are giant fibroadenomas that are rarely malignant.

They consist more of a cellular stroma than a fibroadenoma.

Malignancy is determined in part by an increased number of mitoses per high-power field compared with benign phyllodes tumors.

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Treatment is with a wide local excision. Inadequate local excision is associated with higher rates of local recurrence.

Sclerosing adenosis is a proliferation of acini in the lobules, which may appear to have invaded the surrounding breast stroma.

Atypical hyperplasia has three to six times higher the risk of breast cancer.

Fat necrosis is associated with trauma or radiation therapy to the breast but may simulate cancer with a mass or skin retraction. (The biopsy is diagnostic.)

Mammary duct ectasia

It can be found in older women.

Dilatation of the subareolar ducts can occur.

A palpable retroareolar mass, nipple discharge, or retraction can be present.

Family history for breast carcinoma produces a two to three times higher risk.

First -degree relatives (i.e., mother, daughter, sister) are affected. Risk is higher if the relative is premenopausal.

Hereditary breast cancer (HBC). The breast cancer gene (BRCA) has two forms:

BRCA-1: 60%–80% lifetime risk of developing breast cancer

BRCA-2: 30%–80% lifetime risk

Prior contralateral breast cancer doubles the patient's risk.

TABLE 23-1 Risk Factors for Breast Cancer

One to Two Times Relative Risk

Adapted with permission from Kelsey JL, Gannon MD. The epidemiology of breast cancer. CA Cancer J Clin 1991;41(3):157.

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High socioeconomic status

A nulliparous woman's risk is increased two to three times.

The risk is lowest in women who become pregnant before 23 years of age.

Exogenous estrogen has been shown to increase the risk of breast cancer in postmenopausal women.

C Symptoms

Masses are the presenting symptom in 85% of patients with carcinoma. Approximately 60% of breast masses are discovered by patients on SBE.

Pain is rarely a symptom but should be completely evaluated to eliminate the possibility of a malignancy.

Metastatic disease may also be the initial symptom.

Axillary nodes. Two percent of patients with breast cancer present with axillary node enlargement but no palpable primary breast tumor.

Hodgkin's disease; lung, ovarian, or pancreatic cancer; and squamous cell carcinoma of the skin must be ruled out.

If the results of all studies (including MRI) are negative, a blind mastectomy (i.e., removal of the breast without evidence of malignancy) is indicated.

Distant organ

Asymptomatic patients. High-risk patients (i.e., family or personal history of breast cancer) should be followed closely with mammography and physical examination. They should also be advised to practice

SBE.

D

Noninvasive breast cancers constitute 10% of all types of breast cancer. The diagnosis has increased with early detection through mammography. The prognosis is good. Treatment is aimed at preventing the development of an invasive breast cancer.

Ductal carcinoma in situ (DCIS)

DCIS is confined to ductal cells.

No invasion of the underlying basement membrane occurs. Risk of axillary metastasis is <1%.

Treatment options

Excision with clear margins

Twenty-five percent risk of recurrence within 5 years

Recurrence may be invasive (50%) or DCIS (50%)

Excision with clear margins and radiation

Reduces risk of recurrence to 8%

Total (simple) mastectomy

Removal of breast tissue and areolar/nipple complex

No need to sample axillary nodes

Less than 1% chance of recurrence

Reconstruction can be done at the time of mastectomy.

Lobular carcinoma in situ (LCIS)

This type is most commonly found incidentally.

The risk of invasive cancer within 20 years is 15%–20% bilaterally.

Treatment involves careful follow-up, because the lesion is considered to be a marker for increased future risk of invasive cancer in both breasts. Bilateral total mastectomy may be considered if other risk factors are present (i.e., family history, other hormone -sensitive tumor, prior breast cancer).

Paget's disease

This uncommon lesion involves the nipple.

Histologically vacuolated cells (Paget's cells) are seen in the epidermis of the nipple and result in an eczematous dermatitis of the nipple.

Tubular carcinoma (grade 1 intraductal)

Colloid or mucinous carcinoma

Papillary carcinoma

Less favorable lesions

Medullary cancer. This type involves lymphocytic infiltration and a well-circumscribed lesion.

Invasive lobular cancer. Small cells infiltrate around benign ducts.

The prognosis is slightly better than for invasive ductal cancer.

There is a higher incidence of bilaterality.

Least favorable histologic type

Inflammatory breast cancer. The histology involves tumor-plugged subdermal lymphatics. The prognosis is a 5-year survival rate in approximately 30% of patients. Inflammatory signs are seen (e.g., warmth, swelling and pain).

F Staging and prognosis of breast cancer

After the diagnosis of breast cancer is made, the next step is to determine the extent of disease. This process of staging guides treatment and also predicts survival.

Clinical staging. Based on physical exam and mammogram. Distant disease is evaluated with chest x-ray, bone scan, liver function tests (LFT).

A mammogram is useful to determine both additional foci in the involved breast and the presence of metastatic or synchronous disease.

A chest radiograph detects pulmonary parenchymal or bone metastasis.

A computed tomography (CT) scan of the chest should be obtained for stage III patients to evaluate the supraclavicular area and mediastinum or if the chest radiograph is abnormal.

LFTs

Alkaline phosphatase is the most sensitive in detecting hepatic metastasis.

TABLE 23-3 Breast Cancer Prognosis Based on Stage

An ultrasound or a CT scan of the liver should be performed if the alkaline phosphatase level is abnormal or if other evidence of distant metastasis is present.

A bone scan should be performed if nodes are clinically positive or if nodes are clinically negative but the patient has symptoms of bone pain (patients in stages II, III, and IV).

A CT scan of the head should be done if neurologic signs or symptoms are present.

Clinical/pathologic staging

Tumor (T)

Tis = carcinoma in situ

T1 = Tumor 2 cm or less in greatest dimension

T2 = Tumor greater than 2 cm but no more than 5 cm

T3 = Tumor greater than 5 cm in greatest dimension

T4 = Tumor of any size with direct extension to chest wall (not pectoralis major) or skin

(1) Poor prognostic features include:

Edema or ulceration of the surrounding skin.

Tumor fixed to the chest wall or overlying skin.

Satellite skin nodules

Dermal lymphatic invasion. Peau d'orange is an orange -peel consistency of breast skin. Skin retraction and dimpling (shortening of tumor-involved Cooper's ligaments) occur.

Axillary node status (N) remains the best source of predicting survival or outcome.

N0 = No axillary metastasis

N1 = Metastases to movable axillary nodes

N2 = Metastases to fixed, matted axillary nodes

N3 = Metastases to ipsilateral internal mammary nodes

(1) Poor prognostic features include:

Capsular invasion

Extranodal spread

Edema of the arm

Distant disease/metastasis (M)

M0 = No distant metastases

M1 = Distant metastases, including ipsilateral supraclavicular nodes

(1) Sites of metastasis

Lung

Liver

Bone

Brain

Adrenal

G Treatment of breast cancer

Multimodality therapy that can include surgery, chemotherapy, radiation and/or hormonal therapy

Surgery

Most women are candidates for breast conservation or mastectomy. Much of the decision making, when medically appropriate, involves patient preference.

Breast Conservation. There is no survival difference between breast conservation (with or without radiation) and mastectomy. There is an increase in recurrence with breast conservation.

Lumpectomy with negative margins

Lumpectomy alone: 25% rate of recurrence

Lumpectomy with radiation: 8% rate of recurrence

Must include axillary sampling to accurately stage patient

Axillary lymphadenectomy (Fig. 23 -1)

Level I and II nodes are removed in relation to the axillary vein (Fig. 23 -2).

Skip metastasis (i.e., involved level III nodes with negative level I and II nodes) occurs in fewer than 5% of cases.

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FIGURE 23-2 The lymphatic drainage of the breast, showing lymph node groups and levels. Level I lymph nodes, lateral to lateral border of the pectoralis minor muscle; level II lymph nodes, behind the pectoralis minor muscle; level III lymph nodes, the medial to medial border of the pectoralis minor muscle.

Sentinel node biopsy

This biopsy allows minimal dissection with a substantial decrease in morbidity (lymphedema).

Nuclear scanning or vital blue dye is used to identify the first node drained by the breast.

This node is then examined for the presence of axillary disease. If the sentinel node is negative for metastatic disease, no further lymphadenectomy is performed. If the sentinel node is positive for metastatic disease, a standard lymphadenectomy is performed to stage the axilla.

The long thoracic nerve should be carefully preserved to prevent denervation of the serratus anterior muscle, which results in a winged scapula. The thoracodorsal nerve and blood supply to the latissimus muscle are also preserved.

Patients who choose breast conservation therapy should also undergo radiation therapy to decrease the risk of recurrence. Breast conservation cannot be performed for patients who have undergone chest radiation, have diffuse multicentric disease, collagen vascular disease, or persistent positive margins after lumpectomy. These patients are more effectively treated by mastectomy. Patients with a large tumor in relation to breast size may have superior cosmetic result with mastectomy.

Mastectomy is removal of the breast tissue and nipple/areolar complex.

Modified radical mastectomy includes axillary dissection/sentinel lymph node biopsy (Fig. 23 - 3).

Skin -sparing mastectomy (nonareolar breast skin is preserved) with immediate reconstruction

provides more cosmetic result and does not increase the risk of recurrence.

Radical mastectomy includes the pectoralis major muscle. It is used in the therapy of tumors invading that muscle.

Patients who are not candidates for surgery include those with:

Extensive edema of the breast

Satellite nodules of carcinoma

Inflammatory carcinoma

A parasternal tumor, indicating spread to the internal mammary nodes

Supraclavicular metastasis

Edema of the arm

Distant metastasis

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FIGURE 23-3 The borders of a mastectomy. Superior, clavicle; lateral, lateral border of the pectoralis major muscle; inferior, the inframammary fold (fifth to sixth rib); medial, the sternum.

Radiation

Whole breast radiation involves 4,500 rads. A boost of 2,000 rads is given to the tumor site.

Radiation therapy can be useful as adjuvant therapy after mastectomy in high-risk patients or in those with chest wall involvement.

Chemotherapy

Candidates for chemotherapy include node-positive patients, patients with tumor >1 cm, and estrogen receptor/progresterone receptor (ER/PR)-negative patients

Common chemotherapy drugs include cyclophosphamide (C), methotrexate (M), fluorouracil (F), and adriamycin (A)

Different combination drug regimens, given together for 3 to 6 months, include CMF, CAF, AC, and AC followed by paclitaxel (Taxol).

The results show improvement in both the diseasefree interval and the overall survival of premenopausal women.

Side effects

Myelosuppression requires monitoring of bone marrow function.

Alopecia

Cardiomyopathy (with adriamycin only)

Chemotherapy and hormone therapy are also used to treat recurrent and metastatic disease.

Neoadjuvant therapy is chemotherapy given before surgical therapy of local disease.

Inflammatory breast cancer. Diffuse intraductal invasive breast cancer requires chemotherapy treatment immediately.

Large fixed tumors or fixed nodal disease

Can downstage disease and enable resectability

Can also decrease tumor size and allow breast conservation

Can increase overall survival

Hormonal therapy –for ER/PR-positive patients. ER/PR-positive patients in general have better prognosis.

Tamoxifen or raloxifene (antiestrogens) or anastrozole (Arimidex) (aromatase inhibitor) are taken for 5 years.

Hormonal therapy is as effective as chemotherapy in postmenopausal patients.

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This therapy is an excellent choice of treatment in elderly persons who cannot tolerate chemotherapy. Adding tamoxifen decreases recurrence rates by 47% and death rates by 20%.

Side effects can include vaginal bleeding, hot flashes, thromboembolic events, and increased risk of endometrial cancer.

H Follow-up

(ipsilateral and contralateral breast)

Observation is made for tumor recurrence and complications.

Monthly SBE

Annual breast examination by a physician

Annual mammogram

Chest radiographs, CT scans, and tumor markers are not needed unless clinical suspicion arises.

Edema of the arm

Ten percent of women who have had axillary lymphadenectomy or modified radical mastectomy develop edema of the arm (acute or chronic).

Edema is worsened by radiation therapy to the axilla.

All minor trauma to the affected arm must be avoided.

Treatment

Because each infection increases lymphatic obstruction by obliterating the remaining open channels with fibrosis in reaction to the bacteria, even minor skin infections should receive early treatment with antibiotics.

Chronic edema can be treated with an elastic sleeve or a pneumatic compression device.

Complications. Chronic edema lasting 10 years or longer can lead (although rarely) to the development of lymphangiosarcoma in the affected arm.

I Recurrent disease

Patients with a recurrence in the first 2 years after treatment have a worse prognosis than do patients who have a recurrence after 5 years.

Most recurrences occur in the same quadrant as the original lesion.

Metastatic disease is present in 10% of patients with recurrence.

The treatment of an isolated breast recurrence after primary radiation therapy is mastectomy.

Radiation therapy can be a very effective form of palliative therapy in patients with bone or central nervous system metastases, resulting in relief of pain and control of local disease.

A local or regional recurrence can involve the operative field of a mastectomy, the breast after primary radiation therapy, or the axilla. Larger tumor size, receptor -negative status, and involved axillary nodes are all risk factors for the development of local or regional recurrences.

Chest wall recurrences

After mastectomy, chest wall recurrences are treated with radiation therapy.

Breast recurrences after radiation are treated with mastectomy.

Systemic therapy may also have a role in some cases.

Distant metastasis

Hormone therapy. Patients who respond to one hormone treatment modality generally continue to respond to sequential hormone therapy, whereas nonresponders do not. Few patients are cured once metastasis occurs, but hormone therapy is very effective in prolonging survival and in reducing the size of the tumor.

Chemotherapy is used for patients with recurrent disease who are estrogen-receptor negative or who do not respond to hormone therapy. Combinations of cyclophosphamide, methotrexate, fluorouracil, and doxorubicin are usually used in these cases. Temporary favorable responses, which are determined by a measurable decrease in tumor size or the relief of pain, are obtained in 60%–80% of patients with stage IV disease when this therapy is initiated.

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J Special cases

Breast cancer in pregnancy

Breast cancer occurs in 1.5% of women during their childbearing years.

Diagnosis is usually delayed secondary to normal nodularity that forms in breasts during pregnancy.

A suspicious mass should be evaluated with mammogram and ultrasound.

Core or excisional biopsy should be performed for any suspicious mass.

Excisional biopsy can be performed safely under sedation with local anesthesia.

The male breast

Gynecomastia

Prepubertal gynecomastia is rare and is caused by adrenal and testicular carcinoma.

Pubertal gynecomastia occurs in 60%–70% of prepubertal boys (12–15 years of age). Breast enlargement in the healthy male adolescent does not require treatment. In nearly all cases, the enlargement will regress with age. If enlargement is significant, unilateral, or distressing the patient, treatment is simple mastectomy.

Senescent gynecomastia

Forty percent of aging men have decreased testosterone, increased estradiol, and increased luteinizing hormone.

Unilateral or bilateral enlargement of the breast tissue directly behind the nipple

Causes of gynecomastia

Idiopathic

Drug therapies such as thiazide diuretics, digoxin, theophylline, antidepressants, and hormones

Alcohol and marijuana abuse

Disease conditions such as cirrhosis, renal failure, and malnutrition

Treatment

Evaluate for mass with mammography and physical exam

If a dominant mass is present, a biopsy must be performed to rule out cancer. Then, if no cancer is present, withdraw the offending agent, treat the underlying medical condition, perform a hormonal workup, and provide reassurance.

Cancer of the male breast

This type occurs in 0.7% of all breast cancers and in less than 1% of male cancers.

The average age is 63–70 years, which is older than in women.

Klinefelter's syndrome has been associated with male breast cancer (testicular hormone factors).

Many risk factors associated with male breast cancer can be linked to elevated estrogen levels.

Most patients present with a painless unilateral mass that is usually subareolar with skin fixation, chest wall fixation, and ulceration.

The workup is identical to that used for a woman. Gynecomastia is the primary differential diagnosis. Bilaterality and tenderness favor gynecomastia.

A thorough history of drug and hormone use along with alcohol intake is necessary.

Mammography may distinguish between the two.

This type originates as a ductal cancer.

Treatment is similar to that for carcinoma of the female breast.

Radical mastectomy has been the standard treatment.

Modified radical mastectomy is done if the pectoralis major muscle is not involved.

Breast conservation is done with radiation therapy if the primary tumor is small and does not involve the nipple -areola complex.

Hormonal manipulation involves castration or tamoxifen therapy.