BASIC SCIENCE QUESTIONS
1. How many lactiferous ducts drain into the nipple of the mature female breast?
The breast is composed of 15 to 20 lobes, which are each composed of several lobules.
Each lobe of the breast terminates in a major (lactiferous) duct (2 to 4 mm in diameter), which opens through a constricted orifice (0.4 to 0.7 mm in diameter) into the ampulla of the nipple. (See Schwartz 9th ed., p 426.)
2. During pregnancy, alveolar epithelium develops in the breast which is responsible after delivery for the production of milk. Which portion of the alveolar epithelial cell is responsible for production of the fat present in human milk?
A. Endoplasmic reticulum
C. Cell membrane
With pregnancy, the breast undergoes proliferative and developmental maturation. As the breast enlarges in response to hormonal stimulation, lymphocytes, plasma cells, and eosinophils accumulate within the connective tissues. The minor ducts branch and alveoli develop. Development of the alveoli is asymmetric, and variations in the degree of development may occur within a single lobule. With parturition, enlargement of the breasts occurs via hypertrophy of alveolar epithelium and accumulation of secretory products in the lumina of the minor ducts.
Two distinct substances are produced by the alveolar epithelium: (a) the protein component of milk, which is synthesized in the endoplasmic reticulum (merocrine secretion); and (b) the lipid component of milk (apocrine secretion), which forms as free lipid droplets in the cytoplasm. (See Schwartz 9th ed., p 427.)
3. The medial mammary artery is a tributary of the
A. 2nd, 3rd, and 4th intercostal arteries
B. Internal mammary artery
C. Thoracoacromial artery
D. Posterior intercostal arteries
The breast receives its principal blood supply from (a) perforating branches of the internal mammary artery; (b) lateral branches of the posterior intercostal arteries; and (c) branches from the axillary artery, including the highest thoracic, lateral thoracic, and pectoral branches of the thoracoacromial artery. The second, third, and fourth anterior intercostal perforators and branches of the internal mammary artery arborize in the breast as the medial mammary arteries. The lateral thoracic artery gives off branches to the serratus anterior, pectoralis major and pectoralis minor, and subscapularis muscles. It also gives rise to lateral mammary branches. (See Schwartz 9th ed., p 428.)
4. Which of the following hormones is primarily responsible for differentiation of the breast ductal epithelium?
Estrogen initiates ductal development, whereas progesterone is responsible for differentiation of epithelium and for lobular development. Prolactin is the primary hormonal stimulus for lactogenesis in late pregnancy and the postpartum period. It upregulates hormone receptors and stimulates epithelial development. (See Schwartz 9th ed., p 429.)
1. Absence of the breast (amastia) is associated with
A. Turner’s syndrome
B. Kleinfelter’s syndrome
C. Poland syndrome
D. Fleischer’s syndrome
Absence of the breast (amastia) is rare and results from an arrest in mammary ridge development that occurs during the sixth fetal week. Poland’s syndrome consists of hypoplasia or complete absence of the breast, costal cartilage and rib defects, hypoplasia of the subcutaneous tissues of the chest wall, and brachysyndactyly. (See Schwartz 9th ed., p 426.)
Turner’s syndrome (ovarian agenesis and dysgenesis) and Fleischer’s syndrome (displacement of the nipples and bilateral renal hypoplasia) may have polymastia as a component.
Klinefelter’s syndrome (XXY) is manifested by gynecomastia, hypergonadotropic hypogonadism, and azoospermia. This is an increased risk of breast cancer in men with Klinefelter’s syndrome. (See Schwartz 9th ed., p 431.)
2. The treatment of choice for Zuska’s disease is
A. Observation and nonsteroidal anti-inflammatory drugs (NSAIDs)
B. Antibiotics, incision, and drainage
C. Wide resection of the affected area
Zuska’s disease, also called recurrent periductal mastitis, is a condition of recurrent retroareolar infections and abscesses. This syndrome is managed symptomatically, by antibiotics coupled with incision and drainage as necessary. Attempts to obtain durable long-term control by wide débridement of chronically infected tissue and/or terminal duct resection are frequently frustrated by postoperative infections. Smoking has been implicated as a risk factor for this condition. (See Schwartz 9th ed., p 433.)
3. A clinically positive subclavicular lymph node is a
A. Level I node
B. Level II node
C. Level III node
D. Level IV node
The lymph node groups are assigned levels according to their anatomic relationship to the pectoralis minor muscle. Lymph nodes located lateral to or below the lower border of the pectoralis minor muscle are referred to as level I lymph nodes, which include the axillary vein, external mammary, and scapular groups. Lymph nodes located superficial or deep to the pectoralis minor muscle are referred to as level II lymph nodes, which include the central and interpectoral groups. Lymph nodes located medial to or above the upper border of the pectoralis minor muscle are referred to as level III lymph nodes, which consist of the subclavicular group. (See Schwartz 9th ed., p 429, and Fig. 17-1.)
FIG. 17-1. Axillary lymph node groups. Level I includes lymph nodes located lateral to the pectoralis minor muscle (PM); level II includes lymph nodes located deep to the PM; and level III includes lymph nodes located medial to the PM. Arrows indicate the direction of lymph flow. The axillary vein with its major tributaries and the supraclavicular lymph node group are also illustrated. (Reproduced with permission from Romrell LJ, Bland kI: Anatomy of the breast, axilla, chest wall, and related metastatic sites, in Bland kI, copeland eM III (eds): The Breast: Comprehensive Management of Benign and Malignant Diseases. Philadelphia: W.B. Saunders, 1998, p 32. copyright © elsevier.)
4. Which of the following conditions leads to gynecomastia due to an increased production of estrogen?
A. Klinefelter’s syndrome
B. Hepatocellular carcinoma
C. Aging (senescence)
D. Renal failure
Estrogen excess results from an increase in the secretion of estradiol by the testicles or by nontesticular tumors, nutritional alterations such as protein and fat deprivation, endocrine disorders (hyperthyroidism, hypothyroidism), and hepatic disease (nonalcoholic and alcoholic cirrhosis). (See Schwartz 9th ed., p 431, and Table 17-1.)
Klinefelter’s syndrome, aging, and renal failure all cause gynecomastia by a decrease in testosterone production.
TABLE 17-1 Pathophysiologic mechanisms of gynecomastia
5. The treatment of choice for Mondor’s disease is
A. Observation and nonsteroidal anti-inflammatory drugs (NSAIDs)
B. Antibiotics, incision, and drainage
C. Wide resection of the affected area
Mondor’s disease is a variant of thrombophlebitis that involves the superficial veins of the anterior chest wall and breast. In 1939, Mondor described the condition as “string phlebitis,” a thrombosed vein presenting as a tender, cord-like structure. Frequently involved veins include the lateral thoracic vein, the thoracoepigastric vein, and, less commonly, the superficial epigastric vein. Typically, a woman presents with acute pain in the lateral aspect of the breast or the anterior chest wall. A tender, firm cord is found to follow the distribution of one of the major superficial veins. Rarely, the presentation is bilateral, and most women have no evidence of thrombophlebitis in other anatomic sites. This benign, self-limited disorder is not indicative of a cancer. When the diagnosis is uncertain, or when a mass is present near the tender cord, biopsy is indicated. Therapy for Mondor’s disease includes the liberal use of anti-inflammatory medications and application of warm compresses along the symptomatic vein. Restriction of motion of the ipsilateral extremity and shoulder as well as brassiere support of the breast are important. The process usually resolves within 4 to 6 weeks. When symptoms persist or are refractory to therapy, excision of the involved vein segment is appropriate. (See Schwartz 9th ed., p 433.)
6. The appropriate therapy for Paget’s disease of the nipple is
A. Topical steroid cream
B. Topical antifungal medication
C. Intralesional steroid injection
Paget’s disease of the nipple was described in 1874. It frequently presents as a chronic, eczematous eruption of the nipple, which may be subtle but may progress to an ulcerated, weeping lesion. Paget’s disease usually is associated with extensive DCIS and may be associated with an invasive cancer. A palpable mass may or may not be present. A nipple biopsy specimen will show a population of cells that are identical to the underlying DCIS cells (pagetoid features or pagetoid change). Pathognomonic of this cancer is the presence of large, pale, vacuolated cells (Paget cells) in the rete pegs of the epithelium. Paget’s disease may be confused with superficial spreading melanoma. Differentiation from pagetoid intraepithelial melanoma is based on the presence of S-100 antigen immunostaining in melanoma and carcinoembryonic antigen immunostaining in Paget’s disease. Surgical therapy for Paget’s disease may involve lumpectomy, mastectomy, or modified radical mastectomy, depending on the extent of involvement and the presence of invasive cancer. (See Schwartz 9th ed., pp 444-445.)
7. In the ANDI (aberrations of normal development and involution) classification, a 2-cm fibroadenoma is considered
B. A disorder
C. A disease
D. A premalignant disease
The basic principles underlying the aberrations of normal development and involution (ANDI) classification of benign breast conditions are the following: (a) benign breast disorders and diseases are related to the normal processes of reproductive life and to involution; (b) there is a spectrum of breast conditions that ranges from normal to disorder to disease; and (c) the ANDI classification encompasses all aspects of the breast condition, including pathogenesis and the degree of abnormality. The horizontal component of Table 17-2 defines ANDI along a spectrum from normal, to mild abnormality (disorder), to severe abnormality (disease). The vertical component indicates the period during which the condition develops. (See Schwartz 9th ed., p 433.)
Fibroadenomas are seen predominantly in younger women aged 15 to 25 years. Fibroadenomas usually grow to 1 or 2 cm in diameter and then are stable but may grow to a larger size. Small fibroadenomas (≤1 cm in size) are considered normal, whereas larger fibroadenomas (≤3 cm) are disorders and giant fibroadenomas (>3 cm) are disease. Similarly, multiple fibroadenomas (more than five lesions in one breast) are very uncommon and are considered disease. (See Schwartz 9th ed., p 434.)
TABLE 17-2 ANDI classification of benign breast disorders
8. Which of the following conditions increases a woman’s risk of breast cancer?
A. Sclerosing adenosis
C. Atypical lobular hyperplasia
D. Intraductal papilloma
Atypical proliferative diseases include ductal and lobular hyperplasia, both of which display some features of carcinoma in situ. Women with atypical ductal or lobular hyperplasia have a fourfold increase in breast cancer risk. (See Schwartz 9th ed., p 434, and Table 17-3.)
TABLE 17-3 Cancer risk associated with benign breast disorders and in situ carcinoma of the breast
9. A 35-year-old woman with a BRAC1 gene mutation seeks your advice about her known increased risk of breast cancer. You should recommend
A. Mammograms and physical examination every 6 months until she is 50, then bilateral prophylactic mastectomy
B. Mammograms and physical examination every 6 months + tamoxifen
C. Prophylactic bilateral mastectomy and, if she has completed childbearing, prophylactic bilateral oophorectomy
D. None of the above
Present screening recommendations for BRCA mutation carriers who do not undergo prophylactic mastectomy include clinical breast examination every 6 months and mammography every 12 months beginning at age 25 years, because the risk of breast cancer in BRCA mutation carriers increases after age 30 years.
Despite a 49% reduction in the incidence of breast cancer in high-risk women taking tamoxifen, it is too early to recommend the use of tamoxifen uniformly for BRCA mutation carriers. Cancers arising in BRCA1 mutation carriers are usually high grade and are most often hormone receptor negative. Approximately 66% of BRCA1-associated DCIS lesions are estrogen receptor negative, which suggests early acquisition of the hormone-independent phenotype. Tamoxifen appears to be more effective at preventing estrogen receptor–positive breast cancers.
The risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers ranges from 20 to 40%, which is 10 times higher than that in the general population. Prophylactic oophorectomy is a reasonable prevention option in mutation carriers. The American College of Obstetrics and Gynecology recommends that women with a documented BRCA1 or BRCA2 mutation consider prophylactic oophorectomy at the completion of childbearing or at the time of menopause. Hormone replacement therapy is discussed with the patient at the time of oophorectomy. (See Schwartz 9th ed., pp 439-440.)
10. Which of the following statements about lobular carcinoma in situ (LCIS) is true?
A. In general, LCIS occurs at an older age than ductal carcinoma in situ (DCIS)
B. The majority of women with LCIS are premenopausal
C. LCIS is bilateral in 10 to 20% of women
D. Invasive ductal carcinoma can be expected to occur an average of 5 to 10 years later in approximately 75% of women with LCIS
LCIS tends to occur at a younger age than DCIS and the majority (approximately two thirds) of women with LCIS are premenopausal. LCIS is bilateral in 50 to 70% of women. Approximately 25 to 35% of women with LCIS can be expected to develop invasive ductal carcinoma an average of 15 to 20 years after diagnosis. (See Schwartz 9th ed., p 444, and Table 17-4.)
TABLE 17-4 Salient characteristics of in situ ductal (DCIS) and lobular (LCIS) carcinoma of the breast
11. Moderate ductal hyperplasia of the breast is characterized by the microscopic finding of
A. 3 to 4 cell layers above the basement membrane
B. 5 or more cell layers above the basement membrane
C. Obstruction of >50% of the ductal lumen by hyper-plastic cells
D. Obstruction of >70% of the ductal lumen by hyper-plastic cells
Mild ductal hyperplasia is characterized by the presence of three or four cell layers above the basement membrane. Moderate ductal hyperplasia is characterized by the presence of five or more cell layers above the basement membrane. Florid ductal epithelial hyperplasia occupies at least 70% of a minor duct lumen. It is found in >20% of breast tissue specimens, is either solid or papillary, and is associated with an increased cancer risk. (See Schwartz 9th ed., p 435, and Table 17-5.)
TABLE 17-5 Cancer risk associated with benign breast disorders and in situ carcinoma of the breast
12. Which of the following is appropriate treatment for a 3-cm fibroadenoma?
D. All of the above
Removal of all fibroadenomas has been advocated irrespective of patient age or other considerations, and solitary fibroadenomas in young women are frequently removed to alleviate patient concern. Yet most fibroadenomas are self-limiting and many go undiagnosed, so a more conservative approach is reasonable. Careful ultrasound examination with core-needle biopsy will provide for an accurate diagnosis. Ultrasonography may reveal specific features that are pathognomonic for fibroadenoma. In this situation a core-needle biopsy may not be necessary. Subsequently, the patient is counseled concerning the ultrasound and biopsy results, and excision of the fibroadenoma may be avoided. Cryoablation is an approved treatment for fibroadenomas of the breast. With short-term follow-up a significant percentage of fibroadenomas will decrease in size and will no longer be palpable. However, many will remain palpable, especially those larger than 2 cm. Therefore, women should be counseled that the options for treatment include surgical removal, cryoablation, or observation. (See Schwartz 9th ed., p 436.)
13. Which of the following women with recurrent subareolar infection should undergo a total duct excision (rather than a fistulotomy)?
A. 55-year-old with nipple inversion
B. 55-year-old without nipple inversion
C. 35-year-old with nipple inversion
D. 35-year-old without nipple inversion
In general, the criteria for performing a total duct excision in a woman with recurrent subareolar abscess are: older age, large or diffuse infection, and nipple inversion. (See Schwartz 9th ed., p 436, andTable 17-6.)
TABLE 17-6 Treatment of recurrent subareolar sepsis
14. The average lifetime risk for a woman to develop breast cancer is approximately
The average lifetime risk of breast cancer for newborn U.S. females is 12%. The longer a woman lives without cancer, the lower her risk of developing breast cancer. Thus, a woman aged 50 years has an 11% lifetime risk of developing breast cancer, and a woman aged 70 years has a 7% lifetime risk of developing breast cancer. (See Schwartz 9th ed., p 437.)
15. Routine mammography in women over 50 years of age decreases mortality from breast cancer by approximately
Routine use of screening mammography in women ≥50 years of age reduces mortality from breast cancer by 33%. This reduction comes without substantial risks and at an acceptable economic cost. However, the use of screening mammography in women 50 years of age is more controversial for several reasons: (a) breast density is greater and screening mammography is less likely to detect early breast cancer; (b) screening mammography results in more false-positive test findings, which results in unnecessary biopsies; and (c) younger women are less likely to have breast cancer, so fewer young women will benefit from screening. On a population basis, however, the benefits of screening mammography in women between the ages of 40 and 49 years still appear to outweigh the risks.
Current recommendations are that women undergo baseline mammography at age 35 and then have annual mammographic screening beginning at age 40. (See Schwartz 9th ed., pp 437-438.)
16. The most common genetic cause of breast cancer is a mutation in
A. PTEN (Cowden syndrome)
C. P53 (Li-Fraumeni syndrome)
D. MSH2 (Muir-Torre syndrome)
Mutations in BRAC1 and BRAC2 are the most common mutations associated with breast cancer (see Table 17-7).
Both BRCA1 and BRCA2 function as tumor-suppressor genes, and for each gene, loss of both alleles is required for the initiation of cancer.
The breast cancer risk for BRCA2 mutation carriers is close to 85%, and the lifetime ovarian cancer risk, while lower than for BRCA1, is still estimated to be close to 20%…. Unlike male carriers ofBRCA1 mutations, men with germline mutations in BRCA2 have an estimated breast cancer risk of 6%, which represents a 100-fold increase over the risk in the general male population.
Other hereditary syndromes associated with an increased risk of breast cancer include Cowden disease (PTEN mutations, in which cancers of the thyroid, GI tract, and benign skin and subcutaneous nodules are also seen), Li-Fraumeni syndrome (p53 mutations, also associated with sarcomas, lymphomas, and adrenocortical tumors), and syndromes of breast and melanoma. (See Schwartz 9th ed., p 438.)
TABLE 17-7 Incidence of sporadic, familial, and hereditary breast cancer