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Which of the following conditions is associated with increased risk of breast cancer?

A. Fibrocystic mastopathy.B. Severe hyperplasia.C. Atypical hyperplasia.D. Papillomatosis

Answer: C

DISCUSSION: Fibrocystic mastopathy, or fibrocystic disease, was once thought to increase the risk of breast cancer; however, later studies of the pathologic findings in fibrocystic complex found an increased cancer risk only for patients whose biopsies showed atypical hyperplasia. “Severe hyperplasia” is a pathologic term that refers to the amount of hyperplasia and is frequently seen in the biopsy specimens of young women; it is a misleading term and is not associated with a disease risk. Papillomatosis is also part of the fibrocystic complex and is a frequent finding in benign breast biopsies; it does not confer an increased risk of cancer.

Which of the following breast lesions are noninvasive malignancies?

A. Intraductal carcinoma of the comedo type.B. Tubular carcinoma and mucinous carcinoma.C. Infiltrating ductal carcinoma and lobular carcinoma.D. Medullary carcinoma, including atypical medullary lesions.Answer:

Answer: ADISCUSSION: Tubular, mucinous, and medullary carcinomas are histologic variants of infiltrating ductal cancer and are all invasive malignancies. Infiltrating lobular cancer is a particular histologic variant of invasive breast cancer characterized by permeation of the stroma with small cells that resemble those found in the breast lobule or acinus. Intraductal carcinoma refers to a malignancy of ductal origin that remains enclosed within duct structures. This noninvasive proliferation can undergo central necrosis, which frequently calcifies to form the microcalcifications seen on mammography. The central necrosis within enlarged and back-to-back ductal structures resembles comedoes and gives rise to the term “comedocarcinoma,” now reserved for this histologic variety of intraductal carcinoma.

Which of the following are the most important and clinically useful risk factors for breast cancer?

A. Fibrocystic disease, age, and gender.B. Cysts, family history in immediate relatives, and gender.

C. Age, gender, and family history in immediate relatives.D. Obesity, nulliparity, and alcohol use.

Answer: CDISCUSSION: The most important risk factors for breast cancer are the patient's age, gender, and a family history of breast cancer in immediate relatives (sisters, mother, daughter). The age-adjusted incidence of breast cancer increases with age. Breast cancer does occur in males, but the disease is far more common in women. Family history is important when breast cancer occurs within the immediate family; history of breast cancer in more distant relatives (grandmothers, cousins, aunts) is less important. In addition, age factors into the risk associated with family history. An affected young primary relative is far more significant as a risk factor than an older relative with breast cancer. The other important risk factor not listed here is a history of breast cancer, either within the conserved ipsilateral breast or in the contralateral breast. Again, age plays an important modifying role; as the age at which breast cancer was first diagnosed increases, the risk of a subsequent second cancer decreases. Although patients with fibrocystic disease are at increased risk for breast cancer, risk concentrates in those patients with fibrocystic disease who show atypical epithelial hyperplasia within breast ducts. Obesity, nulliparity, and alcohol all appear to increase risk slightly and are important to the epidemiologic study of breast cancer; however, the effect of these factors is not sufficient to warrant their use in common clinical practice.

9. The proper treatment for lobular carcinoma in situ (LCIS) includes which of the following components?

A. Close follow-up.B. Radiation after excision.

C. Mirror-image biopsy of the opposite breast.D. Mastectomy and regional node dissection.

Answer: ADISCUSSION: LCIS is best thought of as a precursor lesion that confers increased risk for eventual cancer. The magnitude of this risk appears to be in the range of seven- to ninefold over baseline risk. The chance of breast cancer is equal in both breasts, not just in the biopsied breast, and the type of cancer is not confined to a lobular histology. After a diagnosis of LCIS, patients are at increased risk for invasive and noninvasive ductal carcinoma in both breasts. Therefore, mirror-image biopsy as practiced in the past has little to offer. Since LCIS is purely noninvasive, nodal dissection is not required if mastectomy is chosen. There are no data on the use of breast radiation therapy for LCIS. Most surgical oncologists recommend close follow-up for patients who have LCIS only; the alternative surgical treatment that makes most sense is bilateral simple mastectomies, with or without reconstruction.

•Which of the following statement(s) is/are true concerning the anatomy of the breast?

1.About 25% of the lymphatic drainage of the breast courses to the internal mammary nodes2.Nerves within the axillary fat pad include the intercostal brachial nerve, the long thoracic nerve, and thoracodorsal nerve

3.Fascial bands projecting through the breast to the skin form a supporting framework known as Cooper’s ligaments4.The ductal system of the breast from the alveoli to the skin are lined with columnar epithelium

Answer: b, c

The breast abuts against the fascia of the pectoralis major and serratus anterior muscles. Projections of the fascia course through the breast to the

skin, forming a supporting framework of the breast parenchyma. These fascial bands, called suspensory ligaments of Cooper, are better developed in

the upper breast. The structure of the breast can be divided into lobular and ductal elements. The lobule is the functional unit of the breast. Within a

lobule, the terminal elongated tubular ducts are referred to as alveoli. Ten to one hundred alveoli coalesce to form a larger duct which defines a lobular

unit. The lobular ducts join to form progressively larger ducts and ultimately an excretory duct. The alveolar ducts, lobular ducts, and excretory ducts are

all lined with either cuboidal or columnar epithelium. Eventually, 10-20 excretory ducts, each dilate into a short excretory sinus (lined with squamous

epithelium) just beneath the areola. Excretory ducts then course perpendicular to exit through the nipple.

The lymphatic anatomy of the breast is of interest to the surgeon because of the tendency of breast cancer to involve the regional lymph nodes. Studies using radioactive tracers demonstrate at least 97% of lymphatic flow

from the breast is into the axilla; the remainder courses into the internal mammary nodes. These studies also show that lymph flowing into the internal mammary gland chain is not restricted in origin to the medial half and sub-areolar region of the breast, as was thought, but can originate in any quadrant of the breast. In the axilla,

lymphatic vessels terminate in the lymph nodes embedded within the axillary fat pad. Also within the axillary fat pad are the intercostal brachial nerves (a sensory nerve supply in the under arm), the long thoracic nerve (a

motor nerve to the serratus anterior and subscapularis muscles) and the thoracodorsal nerve (a motor nerve to the latissimus dorsi adjacent to its accompanying arteries and veins).

•Which of the following statement (s) is/are true concerning the recurrence of breast cancer?

1.The majority of patients recur within five years of diagnosis2.More than 70% of breast cancer recurrence involve distant metastases

3.Pulmonary metastases are the most common initial site of distant recurrence4.The local recurrence rate following breast-conserving procedures varies from 10% to 40% whether or not radiation was used

5.Recurrent disease will be seen in at least 35% of node-negative patients undergoing appropriate primary breast therapy

Answer: a, b, d Metastatic disease following primary therapy for breast cancer can recur at any time. However, of those who relapse, 50% to 70% do within two years and over 85% relapse within five years. More than 70% of recurrences are distant, but anywhere from 10% to 30% of recurrences are local. Bone and lung are the most common initial sites of distant relapse (50% and 25%), respectively. A breast-conserving procedure can be associated with a local tumor recurrence rate. The rate of local recurrence falls from 40% to 10% if postoperative radiation therapy is given to the entire breast. Despite potentially curative resection, at least 20% of node-negative and 60% of node-positive breast cancer patients have recurrence of their disease at some time after surgery.

•Which of the following statement(s) is/are true concerning mammography?

1.Up to 50% of cancers detected mammographically are not palpable2.One third of palpable breast cancers are not detected by mammography3.The sensitivity of mammography increases with age4.The American Cancer Society currently recommends routine screening mammography beginning at age 40

Only about 10% of nonpalpable lesions detection mammographically are found to be malignant at biopsy

Answer: a, c, d Although mammography has been available for years, it did not become widely used until the findings of the Health Insurance Plan of New York and the Breast Cancer Detection Demonstration project studies of screening mammography were disseminated. These and other investigators demonstrated that 10%–50% of cancers detected mammographically are not palpable. Conversely, palpation recognizes 10%–20% of tumors not detectable mammographically. The incidence of breast cancer begins to rise sharply at age 40, and the sensitivity of mammograms increases with age as the dense parenchymal tissue of young women is progressively replaced by fatty tissue. Routine screening mammography has been shown to decrease breast cancer-related mortality in asymptomatic women over the age of 50. Controversy exists concerning the role of screening in younger woman. However, currently the American Cancer Society recommends that mammographic screening begin at age 40. Although sensitive, mammography is not specific. Only about 25% of nonpalpable lesions detected mammographically are found to be malignant at biopsy. A spiculated density with ill-defined margins on mammogram is almost certainly malignant. Most commonly, features are seen that are suggestive but not diagnostic of cancer. These include clustered microcalcifications, asymmetric density, ductal asymmetry, and distortion of normal breast architecture and/or skin or nipple distortion.

•A 35-year-old woman, who is currently breast-feeding her firstborn child, develops an erythematous and inflamed fluctuant area on breast examination. Which of the following statement(s)

is/are true concerning her diagnosis and management?

1.The most common organism which would expect to be cultured is Staphylococcus aureus

2.Open surgical drainage is likely indicated3.Breast-feeding absolutely should be discontinued

4.If the inflammatory process does not completely respond, a biopsy may be indicated

Answer: a, b, d

Infection complicates breast-feeding in fewer than 1:100 women, but these lactational infections still account for 80% of all breast infections. Presumably, gaining access via

the skin of the irritated nipple of the nursing woman, Staphylococcus aureus is by far the most common pathogen in this setting. Many breast infections begin as cellulitis, without abscess formation. When an actual abscess is suspected, percutaneous aspiration can

establish the diagnosis and allow for bacterial culture and sensitivity testing. Open surgical drainage is the most prudent and effective treatment. Although women may

choose to cease breast feeding, there is no absolute indication for this. When mastitis or breast infection is suspected clinically, the possibility of an inflammatory carcinoma must

also be entertained. Any inflammatory process that does not respond completely and promptly to antibiotics or drainage should be subjected to biopsy to rule out cancer.

•Which of the following statement(s) is/are true concerning the surgical staging of breast cancer?

1.All biopsy specimens should be transported to pathology in formalin within 24 hours of the procedure2.Removal of only level I axillary lymph nodes may understage breast cancer in up to one-fourth of patients

3.Level III axillary lymph nodes should be removed in all axillary lymph node dissections4.A clinically negative axilla will be found to have histologically positive metastasis in approximately one-

third of patients

Answer: b, d Pathologic staging begins with the initial biopsy. Unless previously secured, fresh tumor needs to be obtained for hormone receptor analysis prior to placement into formalin solution. A period of warm ischemia as short as 30 minutes may cause underestimation of estrogen receptor levels. The need to remove axillary nodes must be determined preoperatively. Axillary lymph node metastasis will be found in approximately one-third of clinically negative axillae, but only if proper axillary dissection is performed. Removal of only level I nodes or “sampling” of axillary lymph nodes in a haphazard fashion increases the risk of injury to major axillary neurovascular structures and may understage up to 25% of women. Proper staging of axillary lymph nodes should include en bloc removal and examination of level I and level II nodes. When conducted for staging, axillary lymph node dissection should not include removal of level III axillary nodes; in fewer than 2% are metastases present in level III nodes when level I and level II nodes are negative. Removal of level III nodes, however, does increase the incidence of postoperative arm lymph edema almost fivefold. Therapeutic axillary lymph node dissection performed for palpable disease in the axilla should include removal of all levels to clear gross disease.

•A pre-menopausal woman three years after mastectomy for breast cancer presents with pulmonary metastases. Which of the following statement(s) is/are true concerning her

management?

1.If the patient has received adjuvant therapy, her response is likely to be better2.If the patient is ER-positive, hormonal therapy should be the first line of treatment

3.The response to chemotherapy will likely be dose-dependent4.Combination chemotherapy will likely work better in this patient than a woman who is post-

menopausal

Answer: b, c, d Chemotherapy for metastatic breast cancer is more likely to be employed for young women, those with ER-negative tumors, those with visceral organ involvement and those with rapidly advancing or life-threatening disease. Generally, combinations of agents are used in treating metastatic breast cancer with the response rate usually dose-dependent. All regimens are slightly less active in post-menopausal women. Response rates are highest in women who have not received prior treatment for metastatic disease. Prior adjuvant therapy is not consistently associated with a poorer response to therapy, particularly if a long interval has lapsed between adjuvant therapy and the development of metastases. Endocrine therapy is appropriate as the first-line treatment for nearly all women with ER-positive metastatic breast disease. Tamoxifen is the agent of choice for first-line hormonal therapy for metastatic breast cancer. Both pre-menopausal and post-menopausal patients can receive this agent and side effects are minimal.

•A 21-year-old woman presents with an asymptomatic breast mass. Which of the following statement(s) is/are true concerning her diagnosis and treatment?

1.Mammography will play an important role in diagnosing the lesion2.Ultrasonography is often useful in the differential diagnosis of this lesion3.The mass should always be excised

The lesion should be considered pre-malignant

Answer: b Fibroadenoma represents the most common tumor in adolescents and young woman, but if also frequently encountered in older women. It generally presents as a palpable breast mass and must be differentiated from cancer. Typically, fibroadenoma presents as a painless, slow-growing mass found incidentally on breast self examination. Palpation of a mass usually reveals a well-circumscribed, oval or round, mobile mass with a firm, rubbery texture. Because the mammographic appearance of a fibroadenoma is rarely characteristic, mammography plays little role in diagnosing this lesion. Ultrasonography can differentiate a solid mass from a cyst. Additionally, the ultrasonic appearance of a well-marginated, homogenous mass may be sufficiently characteristic to permit diagnosis of fibroadenoma. Excisional biopsy is not necessary for every fibroadenoma. Women under 30 years of age with characteristic physical examination and sonographic appearance of the fibroadenoma may be given the option of observation. Generally, fibroadenomas are not felt to be pre-malignant lesions, nor to indicate any increased risk for the development of breast cancer.

A 45-year-old woman presents with a weeping eczematoid lesion of her nipple. Which of the following statement(s) is/are true concerning her diagnosis and management?

a.Treatment is with warm compresses and oral antibioticsb.Biopsy of the nipple revealing malignant cells within the milk ducts is invariably associated with an underlying invasive carcinomac.The appropriate treatment is mastectomyd.The lesion always represents a high-risk disease with a significant risk of subsequent metastatic disease

Answer: c Paget’s disease is characterized by weeping, eczematoid lesion of the nipple. There is often accompanying edema and inflammation. Biopsy of the nipple reveals malignant cells within the milk ducts. The lesion is invariably associated with an underlying invasive or in situ ductal carcinoma. The prognosis of Paget’s disease is that of the underlying cancer. Standard treatment is mastectomy with axillary lymph node dissection only if invasive cancer is present.

•Which of the following statement(s) is/are correct concerning cystosarcoma phyllodes?

1.The tumor is most commonly seen in post-menopausal women2.Total mastectomy is necessary for all patients with this diagnosis3.Axillary lymph node dissection is not necessary for malignant cystosarcoma phyllodes

4.Most patients with the malignant variant of cystosarcoma phyllodes die of metastatic disease

Answer: c Cystosarcoma phyllodes is a tumor arising in the mesenchymal tissue of the breast. The tumors usually present as a painless breast mass. Phyllodes tumor is most commonly encountered in women age 30–40 years of age but can occur at any age, even before puberty. The differentiation of a benign from a malignant phyllodes tumor may be difficult. About one-fourth of all phyllodes tumors are histologically malignant, but only a fraction of these patients actually develop metastatic disease. The optimum treatment for benign or malignant phyllodes tumor is wide excision with a margin of normal breast tissue. The margin must be histologically free of involvement because even benign lesions can recur after incomplete excision. If this can be done leaving an adequate cosmetic appearance, mastectomy is not necessary. Total mastectomy is reserved for large lesions in small-breasted women or recurrences after previous local excision that is not amenable to repeat local excision. Axillary lymph node dissection is not performed in the absence of biopsy-proven nodal involvement, even for malignant phyllodes tumors, because axillary metastases are uncommon.

•Which of the following statement(s) is/are true concerning adjuvant systemic therapy?

1.Adjuvant tamoxifen in post-menopausal, node-positive, ER-positive women is equivalent to cytotoxic chemotherapy

2.Tamoxifen clearly improves survival in all hormonal receptor-positive patients3.CMF is associated with improved overall survival in both pre-menopausal and post-

menopausal node-positive patients4.There is no evidence to suggest a role for chemotherapy in node-negative patients

Answer: a

Adjuvant tamoxifen leads to a prolonged disease-free interval in post-menopausal ER-positive women with histologically positive nodes and in pre-menopausal and post-menopausal ER-positive women with negative

nodes. Because of similar results and, because tamoxifen is generally less toxic than chemotherapy, this treatment is the treatment of choice for post-menopausal, node-positive, ER-positive women. CMF

(cyclophosphamide, methotrexate, and 5-fluorouracil) is associated with both a longer disease-free survival and overall survival time in pre-menopausal patients with positive lymph nodes. In post-menopausal women with

positive nodes, there is an improved disease-free survival, but there is no significant difference in overall survival. Several trials of adjuvant chemotherapy with CMF or related regimens have been conducted in node-negative

patients. The early results of all of these trials have been similar: disease-free survival is definitely improved with adjuvant chemotherapy. These studies are definitely not mature enough to draw definitive conclusions regarding

overall survival. Therefore, the National Cancer Institute has recommended the use of adjuvant chemotherapy for all patients with tumors large enough to have hormonal receptor levels measured.

•A 33-year-old woman is referred with nipple discharge. Which of the following statement(s) is/are true concerning her diagnosis and management?

1.Bilateral galactorrhea is suggestive of an underlying endocrinopathy

2.Brownish discharge is usually suggestive of old blood and is worrisome for an underlying breast cancer3.Expressible bloody nipple discharge should be evaluated with a ductogram

4.Milky breast discharge would not be expected one year after discontinuation of breast feeding

Answer: a, c At one time or another, many women notice a nipple discharge. The most common physiologic basis for nipple discharge is lactation. Milk may continue to be secreted intermittently for as long as two years after breast feeding has stopped, particularly with breast stimulation. A milky whitish discharge, usually bilateral, that is not related to lactation or breast stimulation is termed “galactorrhea.” The presence of bilateral galactorrhea should prompt an evaluation for underlying endocrinopathy causing increased prolactin secretion by the pituitary. Classically, this is associated with amenorrhea, but galactorrhea may be the only sign of hypoprolactinemia. Nipple discharges associated with fibrocystic disease are generally, green, yellow, or brown, Intraductal papillomas and cancer lead to a bloody or blood-tinged serous discharge. The brownish discharge of fibrocystic disease can easily be confused with old blood. A guaiac test or simply dabbing the discharge with a gauze pad and examining the stain can usually differentiate the two. A bloody or blood-tinged discharge must be promptly evaluated to exclude carcinoma. If the discharge is expressible at the time the patient is seen, a contrast ductogram may be obtained.

•Which of the following statement(s) is/are associated with gynecomastia? •If the disease is unilateral, it is unlikely drug-related•The standard surgical treatment is subcutaneous mastectomy•The presence of gynecomastia is often associated with the subsequent development of breast cancerA formal endocrine evaluation is indicated in most patients with gynecomastia

Answer: b Gynecomastia is defined as palpable enlargement of the male breast. Pathologic causes of estrogen excess or testosterone deficiency are associated with

gynecomastia. In many cases, no cause is found. Clinically significant gynecomastia has been associated with the use of a number or drugs including cimetidine, digoxin, spironolactone and tricyclic antidepressants. The use of marijuana has also been associated with gynecomastia. Drug-related gynecomastia is often unilateral or unequal between the two breasts, and discontinuation of the offending drug does not always lead to resolution of the condition. A formal endocrine evaluation is not indicated for gynecomastia unless some other sign of hormonal imbalance is found on routine evaluation. The standard surgical treatment of gynecomastia consists of subcutaneous mastectomy performed under local anesthesia. The presence of gynecomastia is not associated with the subsequent development of cancer, yet protracted hyperestrogenemic states, which are associated with gynecomastia are linked to breast cancer development. 

6. Axillary lymph node dissection is routinely used for all of the following conditions except:A. 2-cm. pure comedo-type intraductal carcinoma.

B. 1-cm. infiltrating lobular carcinoma.C. 8-mm. infiltrating ductal carcinoma.

D. A pure medullary cancer in the upper inner quadrant .

Answer: ADISCUSSION: Intraductal carcinoma is carcinoma in situ and does not metastasize to regional or distant sites. Lymph node dissection is not routinely required for a pure in situ cancer of the breast. In contrast, all of the other cancers listed above (infiltrating lobular, infiltrating ductal, and medullary carcinoma) are invasive malignancies that are capable of nodal and distant metastasis. Lymph node dissection is commonly recommended for these invasive malignancies. Intraductal lesions that have grown larger than 5 cm. are more apt to have become focally invasive. Since this invasive component might be missed histologically, many surgeons advocate selective use of axillary node dissection for large intraductal lesions, particularly high-grade tumors such as the comedo variant. However, a purely intraductal 2-cm. cancer would most likely be treated without performing node dissection.

Failure to perform radiation after wide excision of an invasive cancer risks which of the following outcomes?

A. Recurrence of cancer in the ipsilateral breast.B. Shorter survival time.

C. Regional nodal recurrence.D. Greater chance of breast cancer mortality.

Answer: ADISCUSSION: Retrospective reviews and prospective surgical trials agree that omission of breast radiation after wide excision leads to a higher rate of ipsilateral breast recurrence. However, survival and the risk of distant disease are not altered in patients treated by excision alone, within the follow-up time of the studies and given their inherent power to detect differences in outcome. Regional node metastasis is not affected by the choice of mastectomy versus wide excision and radiation

•Which of the following statement(s) is/are true concerning the surgical staging of breast cancer?

1.All biopsy specimens should be transported to pathology in formalin within 24 hours of the procedure2.Removal of only level I axillary lymph nodes may understage breast cancer in up to one-fourth of patients3.Level III axillary lymph nodes should be removed in all axillary lymph node dissections

A clinically negative axilla will be found to have histologically positive metastasis in approximately one-third of patients

Answer: b, d Pathologic staging begins with the initial biopsy. Unless previously secured, fresh tumor needs to be obtained for hormone receptor analysis prior to placement into formalin solution. A period of warm ischemia as short as 30 minutes may cause underestimation of estrogen receptor levels. The need to remove axillary nodes must be determined preoperatively. Axillary lymph node metastasis will be found in approximately one-third of clinically negative axillae, but only if proper axillary dissection is performed.

. Removal of only level I nodes or “sampling” of axillary lymph nodes in a haphazard fashion increases the risk of injury to major axillary neurovascular structures and may understage up to

25% of women. Proper staging of axillary lymph nodes should include en bloc removal and examination of level I and level II nodes. When conducted for staging, axillary lymph node

dissection should not include removal of level III axillary nodes; in fewer than 2% are metastases present in level III nodes when level I and level II nodes are negative. Removal of level III nodes,

however, does increase the incidence of postoperative arm lymph edema almost fivefold. Therapeutic axillary lymph node dissection performed for palpable disease in the axilla should

include removal of all levels to clear gross disease.