1. After intraductal papilloma, unilateral bloody nipple discharge from one duct orifice is most commonly caused by which of the following pathologic conditions?
A. Paget's disease of the nipple.
B. Intraductal carcinoma.
C. Inflammatory carcinoma.
D. Subareolar mastitis.
DISCUSSION: Nipple discharge is surgically significant when it is grossly bloody and when it appears at a single duct orifice on one nipple. Bloody discharge is usually due to a benign intraductal papilloma; however, intraductal carcinoma in the large ducts under the nipple can be the cause of bloody discharge, and pathologically the lesion is frequently a large papillary tumor that has become malignant. Paget's disease of the nipple is also due to intraductal carcinoma arising in subareolar ducts, but it rarely is associated with nipple discharge. Subareolar mastitis may produce nipple discharge, but it is purulent and not bloody. Inflammatory carcinoma is not associated with nipple discharge.
2. Which of the following conditions is associated with increased risk of breast cancer?
A. Fibrocystic mastopathy.
B. Severe hyperplasia.
C. Atypical hyperplasia.
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.
3. 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.
DISCUSSION: 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.
4. 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.
DISCUSSION: 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.
5. Which of the following pathologic findings is the strongest contraindication to breast preservation (lumpectomy with breast radiation) as primary treatment for a newly diagnosed breast cancer?
A. Grade 3, poorly differentiated, infiltrating ductal carcinoma.
B. Extensive intraductal cancer around the invasive lesion.
C. Tumor size greater than 3 cm.
D. Positive surgical margin for invasive cancer.
DISCUSSION: The only firm contraindication to wide excision and radiation (breast preservation, lumpectomy) as the primary surgical treatment for a newly discovered breast cancer is the inability to achieve an uninvolved surgical margin after excision of the tumor. A positive surgical margin requires, at least, reoperation with an attempt at re-excision of the cancer. If the margin of removal is positive after attempts at re-excision, this is a strong reason to recommend mastectomy in preference to breast conservation. Tumor size is a relative contraindication when the cancer is so large in relation to the breast that excision to a clean surgical margin seems unreasonable. Other histologic findings, such as tumor grade or vascular invasion, are not strong reasons to recommend mastectomy if the patient would prefer breast conservation.
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.
DISCUSSION: 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.
7. 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.
DISCUSSION: 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.
8. Which of the following treatments should never be recommended to a patient with purely intraductal carcinoma?
A. Modified radical mastectomy.
B. Lumpectomy to clear surgical margins, followed by observation.
C. Incisional biopsy with an involved margin, followed by radiation.
D. Excisional biopsy to clear margins, followed by radiation.
DISCUSSION: The treatment approach to intraductal carcinoma depends on the extent of the disease, its multifocality, and the involvement of the surgical margin. For extensive disease, modified radical mastectomy is appropriate, particularly if there is a great likelihood of occult invasive disease, making axillary dissection logical. For small foci of disease excised to clear surgical margins, observation is an acceptable recommendation to a well-informed patient. Several noncontrolled reviews and the National Surgical Adjuvant Breast and Bowel Project (NSABP) trial for intraductal disease would indicate a greater chance of ipsilateral breast recurrence for lumpectomy only; however, the magnitude of the risk is small, and survival is excellent and unaffected. The only mode of treatment that cannot be recommended for routine management is leaving residual disease in the breast and treating only with radiation.
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.
DISCUSSION: 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.
10. Which of the following statements most accurately reflects the findings of large overview analyses of clinical trials in which adjuvant chemotherapy for early-stage breast cancer was compared to a control group treated only with surgery?
A. The benefit of adjuvant therapy is confined to young patients.
B. Adjuvant therapy benefits all patients and is independent of age or node status.
C. Adjuvant therapy does not work in estrogen-positive patients.
D. The magnitude of benefit is very large.
DISCUSSION: An overview analysis (meta-analysis) examined nearly all randomized clinical trials in which chemotherapy after surgery was compared to surgery alone for treatment of early-stage breast cancer. This examination of the world's published literature revealed that the magnitude of benefit (the reduction in the odds of recurrence) from chemotherapy was relatively small and in the range of a 20% reduction in the chance of recurrence or death; however, this benefit extended to patients of all ages (young and older) and to both node-positive and node-negative patients. The value of adjuvant chemotherapy does not depend on the hormone receptor content of the cancer. It is useful to remember that a constant reduction in the odds of recurrence results in a higher absolute benefit as the prognosis worsens. If the chance of recurrence is 50% (for node-positive groups) the absolute reduction will be in the range of 10% or 15%. In contrast, if the recurrence rate is 10%, the absolute difference between treated and control groups will be less than 5%. This means that many patients need to be exposed to the risks and side effects of chemotherapy to benefit a very small number. This kind of thinking is currently used to decide who should receive adjuvant chemotherapy after primary treatment (mastectomy or lumpectomy).
11. Which of the following statements are true about reconstruction of the breast following mastectomy?
A. A permanent prosthesis or tissue expander may be inserted at the time of the ablative surgery.
B. If the patient requires adjuvant chemotherapy or radiation therapy, reconstruction of the breast is delayed until completion of the treatment.
C. Extensive postmastectomy defects require the use of a flap.
DISCUSSION: Reconstruction can be initiated at the time of the ablative surgery, using a 6-cm. slightly curved incision at the level of the sixth rib through the serratus muscle. A pocket is created beneath the serratus and pectoralis major muscles, extending medially to the perforating internal mammary vessels and inferiorly beneath the fascial insertion of the rectus abdominis muscle. A tissue expander prosthesis is inserted into the pocket. If the patient requires adjuvant chemotherapy or radiation therapy, reconstruction of the breast is delayed until treatment is completed and an adequate recovery period has passed. If the quantity or quality of the chest skin or the pectoralis major muscle is insufficient, tissue must be brought in from adjacent areas. A latissimus dorsi musculocutaneous flap may be transferred on its blood supply via the thoracodorsal artery and vein. Extensive postmastectomy defects necessitate the use of the larger rectus abdominis musculocutaneous flap, which is based on the superior epigastric vessels. A “free” microvascular rectus abdominis or other myocutaneous flaps may be used. The thoracodorsal or anterior serratus vessels can usually be anastomosed to the inferior epigastric vessels of the rectus abdominis flap.
12. Which of the following statements are true about the management of mammary hyperplasia?
A. Reduction mammaplasty can be performed only on women younger than 40 years.
B. Removal of breast tissue to reduce size of the breast is usually predicated on the use of a nipple, areola, and dermal pedicle flap.
C. If removal of 2000 gm. of breast tissue is needed, breast amputation with immediate free nipple-areola grafting is performed.
DISCUSSION: Reduction mammaplasty can be performed at any age. Because of the increased weight of the breast considerable shoulder and back pain, accompanied by excoriation of the skin in the inframammary area and the shoulders, can occur. Older women frequently seek relief from these problems, which can be resolved by a reduction mammaplasty. The reduction in breast volume is usually accomplished by moving the nipple and areola on a dermal pedicle flap. The flap can be based inferiorly, medially, superiorly, laterally, vertically, or horizontally. It is possible to remove up to 3000 gm. of breast tissue utilizing a pyramidal-based breast flap with an inferior dermal nipple-areola pedicle since the blood supply to the tissues is preserved by this technique. Breast reduction involving removal of more than 3000 gm. requires a breast amputation technique with immediate free nipple grafting.
13. Which of the following statement(s) is/are true concerning the anatomy of the breast?
a. About 25% of the lymphatic drainage of the breast courses to the internal mammary nodes
b. Nerves within the axillary fat pad include the intercostal brachial nerve, the long thoracic nerve, and thoracodorsal nerve
c. Fascial bands projecting through the breast to the skin form a supporting framework known as Cooper’s ligaments
d. 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).
14. Which of the following statement (s) is/are true concerning the recurrence of breast cancer?
a. The majority of patients recur within five years of diagnosis
b. More than 70% of breast cancer recurrence involve distant metastases
c. Pulmonary metastases are the most common initial site of distant recurrence
d. The local recurrence rate following breast-conserving procedures varies from 10% to 40% whether or not radiation was used
e. 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.
15. Which of the following statement(s) is/are true concerning mammography?
a. Up to 50% of cancers detected mammographically are not palpable
b. One third of palpable breast cancers are not detected by mammography
c. The sensitivity of mammography increases with age
d. The American Cancer Society currently recommends routine screening mammography beginning at age 40
e. 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.
16. Which of the following statement(s) is/are true concerning radiation therapy after lumpectomy?
a. The total dose given to the breast is usually in the range of 2500 to 3000 cGy
b. Radiation to the axillary nodal bed is normally part of the procedure in most patients
c. Long-term complications of radiation therapy include rib fractures and arm edema
d. Breast edema and skin erythema usually resolves within a few weeks
e. None of the above
Breast conservation usually involves the use of lumpectomy and radiation therapy to achieve local control of breast cancer. Any technique used for post-lumpectomy radiation of the breast must adequately cover the volume at risk, deliver a homogenous dose throughout the target tissues, avoid overlapping or inadequate apposition of fields, and minimize the dose reaching the heart and lung. The entire breast should be treated with a total dose of 4500 to 5000 cGy. There is no good evidence to support a radiation boost to the site of the primary tumor. Complications from breast radiation are uncommon if performed correctly. Acute complications of radiotherapy include fatigue, breast edema, and skin erythema; these are almost always self-limited and resolve over weeks (fatigue) 2 months (erythema) or years (edema). The most common long-term problems are rib fractures and minor arm edema, each of which occur about 5% of the time.
17. 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?
a. The most common organism which would expect to be cultured is Staphylococcus aureus
b. Open surgical drainage is likely indicated
c. Breast-feeding absolutely should be discontinued
d. 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.
18. Which of the following statement(s) is/are true concerning the surgical staging of breast cancer?
a. All biopsy specimens should be transported to pathology in formalin within 24 hours of the procedure
b. Removal of only level I axillary lymph nodes may understage breast cancer in up to one-fourth of patients
c. Level III axillary lymph nodes should be removed in all axillary lymph node dissections
d. 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.
19. Which of the following statement(s) is/are true concerning the effect of various hormones on breast physiology?
a. Estrogen receptors are present only in breast cancer cells
b. Mammary ductal dilatation and differentiation of alveolar epithelial cells and secretory cells are the result of rising progesterone levels
c. The early first trimester breast changes are primarily due to the increased progesterone effects of pregnancy
d. Milk production and secretion after childbirth are maintained by ongoing secretion of prolactin by the anterior pituitary gland
Answer: b, d
Breast growth, development, and function are orchestrated by a variety of hormones and growth factors. Estrogen plays a central role in breast development, growth, and differentiation. Lipid-soluble estrogens gain entry to the normal and malignant breast cell by diffusing to the cell membrane. Once within the cell, estrogens bind with the estrogen receptor. Both normal and malignant breast cells contain estrogen receptors, but the low levels of receptors in normal breast tissue and in some breast cancers result in their testing negative in clinical assays. Cyclic changes associated with the menstrual cycle have a profound influence on breast morphology and physiology. During the period of relative quiescence, increasing Graafian follicle secretion of estrogen stimulates breast epithelial proliferation. As the luteal phase of the cycle is entered, progesterone levels rise. Mammary ductal dilatation and differentiation of alveolus epithelial cells into secretory cells result. At the onset of menstruation, the rapid decline of circulating sex-hormone levels leads to breast involution and the cycle begins anew. During pregnancy, marked ductular, lobular, and alveolar growth occur under the influence of estrogen, progesterone, placental lactogen, prolactin, and chorionic gonadotropin. These changes prepare the breasts for milk production at parturition. Early in the first trimester, ductal sprouting and lobular formation proceed under estrogenic influence. During the second trimester, lobular events predominate under the influence of progestins. Abrupt withdrawal of placental lactogen and sex-hormones that occurs with delivery, leaves the breast predominately under the influence of pituitary-derived prolactin. Milk production and secretion are maintained during lactation by ongoing secretion of prolactin by the anterior pituitary.
20. 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?
a. If the patient has received adjuvant therapy, her response is likely to be better
b. If the patient is ER-positive, hormonal therapy should be the first line of treatment
c. The response to chemotherapy will likely be dose-dependent
d. 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.
21. Which of the following statement(s) is/are true concerning intraductal papilloma?
a. This lesion is the most common cause of bloody nipple discharge
b. Serous non-bloody discharge is unlikely to be due to an intraductal papilloma
c. A nonpalpable lesion can often be diagnosed with ductography
d. An isolated lesion is considered premalignant
Answer: a, c
Intraductal papilloma represents the most common cause of bloody nipple discharge, although in half of the cases, the discharge is serous. Since the average size of an intraductal papilloma is 3–4 mm., they are rarely palpable. Ductography may demonstrate the lesion, or it may be found after subareolar duct excision performed to treat the discharge. An isolated intraductal papilloma is not considered premalignant nor does it place the patient at increased risk for breast cancer. Unlike isolated papillomas, diffuse papillomatosis is associated with an increased risk of breast cancer, perhaps as high as in 40% of women.
22. 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?
a. Mammography will play an important role in diagnosing the lesion
b. Ultrasonography is often useful in the differential diagnosis of this lesion
c. The mass should always be excised
d. The lesion should be considered pre-malignant
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.
23. Which of the following are factors associated with an increased risk for developing breast cancer?
b. Oophorectomy before age 35
c. Use of oral contraceptives
d. High-fat, high-caloric diet
e. Post-menopausal use of conjugated estrogens
Answer: a, d
Women who undergo oophorectomy before age 35 and do not take replacement estrogens have a two-thirds reduction in their breast cancer risk. Replacement estrogen therapy eliminates the beneficial effect of oophorectomy. Most investigations of oral contraceptive use do not demonstrate an associated increased risk of breast cancer development. Studies of estrogen replacement therapy for post-menopausal women have yielded equivocal results. Most contemporary studies fail to demonstrate an association between breast cancer risk and post-menopausal use of conjugated estrogens.
BREAST CANCER RISK FACTORS
Age more than 30 y
Female gender (130:1 female/male ratio)
GREATLY INCREASED RISK
Known carrier of breast cancer susceptibility gene
Strong family history—two or more first-degree relatives with
bilateral or premenopausal breast cancer
Atypical ductal or lobular hyperplasia or lobular carcinoma in situ
Ductal carcinoma in situ, risk limited to ipsilateral breast
MODERATELY INCREASED RISK
Family history—one or more relatives with breast cancer, not
bilateral or premenopausal
Menstrual history—menarche before age 12 y, menopause after
age 55 y
Parity—nulliparity or first live birth after age 30 y
Radiation—exposure to low-dose ionizing radiation in childhood or
Previous breast cancer—low-grade, node-negative, or receptor-
positive; lobular histology
Other cancers—colon or endometrial cancer
Diet—high-fat or high-calorie diet
24. Which of the following chromosomal and/or genetic abnormalities is/are associated with the development of breast cancer?
a. Mutations in the p53 tumor suppressor gene
b. A mutation in the short arm of chromosome 2
c. The presence of a BRCA 1 gene on chromosome 17
d. The presence of the BRCA 2 gene on chromosome 13
Answer: a, b, c, d
There are four inherited syndromes associated with the development of breast cancer. The Li-Fraumeni syndrome has an autosomal dominant mode of inheritance. The syndrome is attributed to mutations in the p53 tumor suppressor gene, a gene that codes for a protein that serves as a G1-S checkpoint regulator of the cell cycle. More recently, a mutation has been characterized on the short arm of chromosome 2 in a gene associated with DNA repair. Predisposition to a wide range of malignancies, including breast and colon cancer is associated with abnormalities at this locus. The most exciting development in inherited susceptibility to breast cancer relate to the identification and cloning of the BRCA 1 gene, which was initially localized on the long arm of chromosome 17 by linkage analysis. Germline abnormalities in BRCA a may be responsible for as many as 5% of all breast cancers in the United States. The gene is characterized by autosomal dominant inheritance with a high degree of penetrance. Almost 60% of women inheriting the gene will develop breast cancer by age 50, and a lifelong risk approaches 85%. Another breast cancer susceptibility gene, dubbed BRCA 2, has been localized by linkage analysis to a small region of chromosome 13q12-13. BRCA 2 apparently confers the high-risk of early onset female breast cancer. Similar to BRCA 1, the lifetime breast cancer risk approaches 90% in carriers of this gene.
25. 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 antibiotics
b. Biopsy of the nipple revealing malignant cells within the milk ducts is invariably associated with an underlying invasive carcinoma
c. The appropriate treatment is mastectomy
d. The lesion always represents a high-risk disease with a significant risk of subsequent metastatic disease
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.
26. Which of the following treatment(s) is/are of proven benefit in the treatment of mastodynia associated with fibrocystic breast disease?
a. Avoidance of methylxanthine compounds, particularly caffeine
b. Cessation of smoking
c. Vitamin E
Answer: a, b, d
The relationship of methylxanthines, particularly caffeine, to mastodynia and breast nodularity remains controversial. Most women do, however, experience diminution of their symptoms and are subject to improvement in breast nodularity by limiting or eliminating caffeine intake. Mastodynia patients should be advised to eliminate caffeine beverages for a period of 2 to 3 months to determine if there has been improvement in their symptoms. In addition to caffeine abstention, patients should be urged to stop smoking because nicotine is purported to worsen mastodynia. A number of medications have been advocated for the treatment of mastodynia. Unfortunately, because of the subjective nature of the disease and its propensity to be better tolerated by patients with reassurance, the exact method of most of these interventions is unclear. Vitamin E has been touted as beneficial, however, clinical data do not support the use of this or other vitamins for this condition. The use of hormonal agents to treat mastodynia has been more extensively treated. Danazol, a weak antigen, is the most effective drug available for treatment of mastodynia related to fibrocystic disease. Unfortunately, Danazol’s androgenic side effects are troublesome enough to restrict its use to the most problematic cases of mastodynia. Other hormonal agents have been investigated for the management of mastodynia. In young women, oral contraceptives have a variable effect on mastodynia. A trial and error search for optimal preparations may be necessary as the effect of oral contraceptives is dependent on the formulation of the pill.
27. Which of the following statement(s) is/are true concerning breast reconstruction?
a. The timing of breast reconstruction is of no oncologic significance
b. Breast reconstruction may interfere with detection of local recurrence of breast cancer
c. Maintenance of an effective subpectoral pocket for a breast implant requires preservation of the pectoralis fascia
d. Because of its complexity, the TRAM flap is seldom used for primary breast reconstruction
Answer: a, c
Breast reconstruction is suitable for any woman who has undergone mastectomy who desires reconstruction. Breast reconstruction may be performed at the time of mastectomy (immediate) or sometime subsequently (delayed) Because the presence of reconstruction may interfere with the accurate planning and administration of radiation therapy, reconstruction is generally delayed if the use of local or regional radiation therapy is anticipated. Otherwise, timing of breast reconstruction is of no oncologic significance. Because most local recurrences occur in the skin’s subcutaneous tissues, the presence of a reconstruction will not interfere with detection. Similarly, a reconstruction does not complicate the administration of chemotherapy.
Breast reconstruction techniques utilize either autogenous tissue or synthetic prostheses to recreate a breast mound. Prosthetic reconstruction is usually accomplished by sub-pectoral placement of a saline-or silicone gel-filled implant. Maintenance of an effective sub-pectoral pocket for an implant requires preservation of the pectoralis fascia and the medial pectoral nerve during mastectomy. The transferase rectus abdominous myocutaneous (TRAM) flap is the autogenous reconstruction of choice. The TRAM operation is complex and time consuming. Despite the magnitude of the procedure, it is still commonly used for immediate reconstruction.
28. Which of the following statement(s) is/are true concerning the histologic variants of invasive breast carcinoma?
a. The presence of an in situ component with invasive ductal carcinoma adversely affects prognosis
b. Medullary carcinomas, although often of large size, are associated with a better overall prognosis than common invasive ductal cancers
c. Mucinous or colloid carcinoma is one of the more common variants of invasive ductal cancer
d. Invasive lobular carcinoma is associated with a higher incidence of bilateral breast cancer
Answer: b, d
Although the breast is composed of both lobular and ductal elements, most breast cancer arises in the ductal elements. Invasive ductal carcinoma accounts for 70% to 80% of all cases of breast cancer. Although there is no single microscopic feature specific for infiltrating ductal carcinoma, it can be recognized histologically as an invasive adenocarcinoma involving ductal elements. The malignant ductal cells are often dispersed within the fibrous stroma, leading to the appellation of scirrhous carcinoma. A number of less common types of breast cancer arise from the ductal epithelium and are hence classified as variants of invasive ductal carcinoma. There are distinct histologic criteria for classifying these lesions; these criteria must be met throughout the entire tumor. Prognostically, histologically pure examples of these variant tumors are associated with a better long-term survival than ordinary type invasive ductal carcinoma. When mixed histologies are encountered, the clinical behavior parallels that of the invasive ductal element, not the other sub-type. Hence, these mixed tumors are considered together with pure invasive ductal carcinoma for prognostic purposes. In many cases, when areas of in situ ductal carcinoma are seen, the presence of an in situ component does not adversely affect prognosis, although it jeopardizes the attempts at breast conservation. Medullary carcinoma is one of the more common variants, accounting for approximately 6% of all invasive breast cancers. These tumors may grow to be a rather large size within the breast (5 to 10 cm) and are characteristically well-circumscribed. Mucinous carcinoma, also referred as colloid carcinoma, is encountered in 1% to 2% of breast cancer cases. Invasive lobular carcinoma arises from the lobular component of the breast and in most series accounts for approximately 10% of breast cancers. Almost every series has stressed the higher incidence of bilateral cancer in patients with invasive lobular carcinoma. The contralateral breast is involved either synchronously (3% of patients) or metachronously in up to 30% of patients.
29. Which of the following statement(s) is/are correct concerning cystosarcoma phyllodes?
a. The tumor is most commonly seen in post-menopausal women
b. Total mastectomy is necessary for all patients with this diagnosis
c. Axillary lymph node dissection is not necessary for malignant cystosarcoma phyllodes
d. Most patients with the malignant variant of cystosarcoma phyllodes die of metastatic disease
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.
30. Which of the following statement(s) is/are true concerning local recurrence of breast cancer?
a. The percentage of patients with chest wall recurrence as their initial site of failure following mastectomy is similar for node-negative and node-positive patients
b. Most patients with local-regional recurrence of their disease will eventually die of metastatic disease
c. The treatment of local recurrence following mastectomy includes local radiation therapy and systemic chemotherapy
d. In-breast recurrence following breast conserving surgery is not a negative prognostic factor
e. Regional lymph node recurrence following axillary node dissection is rare
Answer: a, b, c, e
Recurrence in the chest wall after mastectomy is ominous. In a large series of patients treated with mastectomy, 6.5% of node-negative and 8.8% of node-positive women had chest wall recurrence as their initial site of failure. By ten years after local-regional recurrence, about 60% of initially node-negative and almost all (> 90%) of initially node-positive patients had evidence of metastatic disease. Patients with local recurrence, who have not had prior chest wall radiation, should receive radiation therapy. A full course of at least 4500 to 5000 cGy should be delivered to the entire chest wall, with consideration given to a boost dose at any sites of gross tumor. Because post-mastectomy recurrence is often rapidly followed by metastatic disease, it is logical to postulate a role for adjuvant systemic therapy once local measures have achieved control of chest wall disease.
Recent data suggests that in-breast recurrence following breast conservation is a prognostic factor. Women who develop an in-breast recurrence have a higher likelihood of developing systemic disease than do women who remain disease-free in their breast. Fewer than 3% of patients develop recurrence of disease in the axilla after axillary node dissection.
31. Which of the following statement(s) is/are correct concerning prognostic factors for breast carcinoma?
a. Prognosis is improved with estrogen or progesterone receptor positivity
b. Increased thymidine labeling index, a measure of the proportion of cells in the DNA synthetic phase (S-phase), is associated with improved survival
c. High tumor levels of cathepsin D are associated with an improved prognosis
d. Immunohistochemical demonstration of active angiogenesis correlates with increased metastatic potential and poor prognosis
Answer: a, d
32. Which of the following statement(s) is/are true concerning adjuvant systemic therapy?
a. Adjuvant tamoxifen in post-menopausal, node-positive, ER-positive women is equivalent to cytotoxic chemotherapy
b. Tamoxifen clearly improves survival in all hormonal receptor-positive patients
c. CMF is associated with improved overall survival in both pre-menopausal and post-menopausal node-positive patients
d. There is no evidence to suggest a role for chemotherapy in node-negative patients
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.
33. Which of the following statement(s) is/are true concerning tissue sampling techniques for breast masses?
a. The sensitivity of fine needle aspiration biopsy is such that mastectomy can be performed in the case of malignant diagnosis
b. The accuracy of mammographic-directed fine needle aspiration biopsy is comparable to that achieved for that of palpable lesions
c. Core-needle biopsy showing normal breast tissue is an acceptable diagnosis
d. The technique of core-needle biopsy is not applicable to radiographically detected lesions
Whatever tissue sampling method is chosen, only biopsy (examination of cells or tissue) and not physical examination or mammography can establish a definitive diagnosis and avoid delay in treatment. Fine needle aspiration biopsy (FNAB) permits rapid, minimally invasive diagnosis of many palpable and some non-palpable, radiologically detected breast masses. The technique is both reliable and accurate. The incidence of false-positive findings is generally less than 0.5%. FNAB is not, however, so highly specific that definitive surgery (particularly mastectomy) should be performed without prior intraoperative frozen-section confirmation of the presence of cancer. Reported sensitivity of FNAB ranges from 7% to 99%; with 85% a good estimate of the true sensitivity in clinically relevant settings. Recently, x-ray-guided FNAB has been used to offer minimally invasive diagnosis in nonpalpable breast lesions detected mammographically. The technique is quite effective, especially for mass lesions. Accuracy is comparable to that achieved with FNAB of palpable lesions. Core-needle biopsy is a helpful tissue sampling method for palpable masses. The tissue obtained is useful for histologic analysis although inadequate for cytosol hormone receptor determination. The technique is also applicable by using mammographic guidance for nonpalpable lesions.
34. A 42-year-old woman undergoes her first mammogram. Clustered microcalcifications are seen but there is no mass palpable. Which of the following statement(s) is/are true concerning this patient’s diagnosis and management?
a. A needle localization and excision of the mass is necessary to establish the diagnosis
b. Frozen-section examination is particularly useful in the diagnosis of this lesion
c. Intense interlobular fibrosis and proliferation of small ductules with loss of orientation of lobules and epithelial cells may suggest carcinoma
d. This finding is associated with an increased risk of cancer
Answer: a, c
Sclerosing adenosis is a histologic subtype of fibrocystic change that is not associated with an increased risk of cancer development. It is, however, one of the benign breast processes most likely to be confused radiologically and histologically with cancer. Most commonly, it is detected on routine mammography as cluster microcalcifications without an associated palpable mass. In these cases, needle localization and excision are required to establish a diagnosis. Sclerosing adenosis microscopically is characterized by interlobular fibrosis and proliferation of small ductules. If the fibrous component is particularly intense, the orientation of lobules and epithelial cells may be lost, mimicking carcinoma. Differentiating sclerosing adenosis from cancer on frozen-section examination can be particularly difficult and should not be attempted.
35. Which of the following conclusion(s) can be drawn from the results of the NSABP prospective randomized trials completed in the 1970’s and 1980’s?
a. Delay of axillary node dissection until there is clinical evidence of disease does not influence overall survival
b. Removal of clinically negative nodes has no therapeutic benefit
c. Breast irradiation reduces both local recurrence and overall survival
d. Modified radical mastectomy offers no advantage of lumpectomy with axillary node dissection
Answer: a, b, d
The scientific basis of local-regional treatment strategies for stage I and stage II breast cancer was established by a series of studies conducted during the 1970’s and 1980’s by the NSABP. In the first of these protocols, total mastectomy with delayed node dissection only for nodes that subsequently turned positive, total mastectomy with local-regional radiation therapy, and radical mastectomy were clinically equivalent. Furthermore, the finding that delay of axillary node dissection until there is clinical evidence of disease does not influence survival emphasizes that the role of axillary dissection in clinically node negative patients is solely for staging. The removal of clinically negative nodes has no therapeutic benefit if regional recurrences are detected and treated promptly. In the second of these protocols, modified radical mastectomy, lumpectomy with axillary node dissection, and lumpectomy, axillary node dissection, and breast or irradiation were compared in small breast cancers. Modified radical mastectomy offered no advantage over other treatments when analyzed by disease-free or overall survival in either node-negative or node-positive patients. Breast irradiation after lumpectomy reduced the likelihood of in-breast tumor recurrence from 39% to 10% but did not affect overall survival when compared with lumpectomy alone.
36. Which of the following statement(s) is/are true concerning non-invasive breast carcinoma?
a. Ductal carcinoma in situ (DCIS) is associated with a significant risk of development of invasive ductal carcinoma in the same quadrant of the same breast as the initial lesion
b. DCIS should not be treated with breast conservation therapy
c. Lobular carcinoma in situ (LCIS) is the most common form of non-invasive breast cancer
d. When LCIS is found, there is an up to 50% chance of lobular carcinoma in situ of the contralateral breast
e. About one-third of patients with biopsy-proven LCIS develop invasive cancer, always of the same breast
Answer: a, d
Non-invasive (in situ) cancer is defined as a neoplastic entity within the epithelium of origin and without invasion to the basement membrane. Ductal carcinoma in situ (DCIS) arises from the ductular elements. The age distribution of DCIS does not differ significantly from that of invasive ductal carcinoma. Not every woman who undergoes complete excision of a focus DCIS develops invasive ductal cancer. Various studies suggest half or more patients develop invasive breast cancer after excisional biopsy alone. When a subsequent invasive cancer does occur, it is almost always of the invasive ductal type and located in the same quadrant of the breast as the initial DCIS. The latent period before the development of invasive cancer usually exceeds five years. Total mastectomy is usually associated with a nearly 100% cure rate for this condition. Although total mastectomy remains the gold-standard for treatment of DCIS, there is increasing experience with breast-conserving therapy. Breast conservation may be offered to DCIS patients in whom the entire tumor can be surgically removed with negative histologic margins and in whom the remaining breast tissue can be reliably assessed clinically and radiographically. It would appear that the disease-free survival following lumpectomy and radiation therapy is worse than that achievable with simple mastectomy. Therefore, breast conservation for DCIS commits patients to more careful long-term follow-up and will likely subject them to additional subsequent treatment to deal with the recurrences. Lobular carcinoma in situ (LCIS) accounts for one-third of the non-invasive breast cancers. LCIS patients are significantly younger than patients with invasive breast cancer. Three-fourths of affected women are pre-menopausal. LCIS is an infrequent finding in women over 75. When the opposite breast is sampled at the time of diagnosis, contralateral LCIS is found in 30–50% of cases. The prognosis of LCIS is solely related to the subsequent development of invasive carcinoma. About one-third of patients with biopsy-demonstrated LCIS develop invasive cancer; half occur in the index breast and half in the contralateral breast. The subsequent breast cancers can be either lobular or ductal in histology.
37. A 33-year-old woman is referred with nipple discharge. Which of the following statement(s) is/are true concerning her diagnosis and management?
a. Bilateral galactorrhea is suggestive of an underlying endocrinopathy
b. Brownish discharge is usually suggestive of old blood and is worrisome for an underlying breast cancer
c. Expressible bloody nipple discharge should be evaluated with a ductogram
d. 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.
38. Clinical features of breast cancer which are associated with a particularly poor prognosis include:
a. Edema of the skin of the breast
b. Skin ulceration
c. Lateral arm edema
d. Dermal lymphatic invasion
Answer: a, b, c, d
The histologic hallmark of inflammatory breast cancer is dermal lymphatic invasion demonstrable on skin biopsy. The stigmata of this clinical syndrome include breast warmth, tenderness, erythema, and edema.
39. Which of the following statement(s) is/are associated with gynecomastia?
a. If the disease is unilateral, it is unlikely drug-related
b. The standard surgical treatment is subcutaneous mastectomy
c. The presence of gynecomastia is often associated with the subsequent development of breast cancer
d. A formal endocrine evaluation is indicated in most patients with gynecomastia
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.